Pub Date : 2025-12-12DOI: 10.1016/j.jve.2025.100620
Ourlad Alzeus G. Tantengco , Ian Kim B. Tabios , Abialbon G. Francisco , Clarissa L. Velayo , Ryan C.V. Lintao , Fresthel Monica M. Climacosa , Leslie Michelle M. Dalmacio , Leslie Faye T. Cando , Glenmarie Angelica S. Perias , Ronniel Alfred N. Acebes , Sheriah Laine M. de Paz-Silava
Persistent infection with high-risk human papillomavirus (HR HPV) is the necessary cause of cervical cancer. In the Philippines, available data on the prevalence and genotype distribution of HPV infections are limited and largely derived from earlier hospital-based studies. The present study determined the overall and type-specific prevalence of HR HPV infection among women in selected communities in the Philippines, along with the associated sociodemographic and behavioral factors. A total of 1,194 women from two communities were examined. Cervical swabs were collected, and the extracted DNA were analyzed for HPV genotyping through a commercial multiplex real-time PCR assay kit. Sociodemographic information, clinical history, and sexual and reproductive behavior were obtained through an interviewer-administered semi-structured questionnaire. The overall prevalence of HR HPV infection was 11.22 % (95 % CI: 9.56–13.14 %). Women residing in urban areas had 1.62 times higher odds (95 % CI: 1.08–2.42) of HR HPV infection than those in rural areas. Moreover, for every year of delaying vaginal sexual debut, there was a 7 % decrease in the odds of HR HPV infection. HPV 52 was the most prevalent genotype (2.59 %), followed by HPV 16 (1.84 %) and HPV 68 (1.09 %). Multiple HR HPV genotypes were recorded in 23 % of HR HPV-infected women. The most frequent co-infections are HPV 16 + HPV 18, HPV 16 + HPV 52, and HPV 39 + HPV 52. These findings highlight the need for updated surveillance and consideration of local genotype distribution in cervical cancer prevention strategies, such as in HPV DNA testing and HPV vaccination programs.
{"title":"Prevalence and genotype distribution of high-risk human papillomavirus infections among women in selected communities in the Philippines: Results of the defeat HPV study","authors":"Ourlad Alzeus G. Tantengco , Ian Kim B. Tabios , Abialbon G. Francisco , Clarissa L. Velayo , Ryan C.V. Lintao , Fresthel Monica M. Climacosa , Leslie Michelle M. Dalmacio , Leslie Faye T. Cando , Glenmarie Angelica S. Perias , Ronniel Alfred N. Acebes , Sheriah Laine M. de Paz-Silava","doi":"10.1016/j.jve.2025.100620","DOIUrl":"10.1016/j.jve.2025.100620","url":null,"abstract":"<div><div>Persistent infection with high-risk human papillomavirus (HR HPV) is the necessary cause of cervical cancer. In the Philippines, available data on the prevalence and genotype distribution of HPV infections are limited and largely derived from earlier hospital-based studies. The present study determined the overall and type-specific prevalence of HR HPV infection among women in selected communities in the Philippines, along with the associated sociodemographic and behavioral factors. A total of 1,194 women from two communities were examined. Cervical swabs were collected, and the extracted DNA were analyzed for HPV genotyping through a commercial multiplex real-time PCR assay kit. Sociodemographic information, clinical history, and sexual and reproductive behavior were obtained through an interviewer-administered semi-structured questionnaire. The overall prevalence of HR HPV infection was 11.22 % (95 % CI: 9.56–13.14 %). Women residing in urban areas had 1.62 times higher odds (95 % CI: 1.08–2.42) of HR HPV infection than those in rural areas. Moreover, for every year of delaying vaginal sexual debut, there was a 7 % decrease in the odds of HR HPV infection. HPV 52 was the most prevalent genotype (2.59 %), followed by HPV 16 (1.84 %) and HPV 68 (1.09 %). Multiple HR HPV genotypes were recorded in 23 % of HR HPV-infected women. The most frequent co-infections are HPV 16 + HPV 18, HPV 16 + HPV 52, and HPV 39 + HPV 52. These findings highlight the need for updated surveillance and consideration of local genotype distribution in cervical cancer prevention strategies, such as in HPV DNA testing and HPV vaccination programs.</div></div>","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"12 1","pages":"Article 100620"},"PeriodicalIF":2.0,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145765890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hepatitis B virus (HBV) infection is a major risk factor for liver fibrosis, cirrhosis, and hepatocellular carcinoma. Whether patients with chronic hepatitis B (CHB) receiving oral nucleos(t)ide analogue (NA) therapy can safely discontinue treatment after HBsAg seroclearance is attracting clinical attention.This study aimed to explore the maintenance rate of HBsAg-negative status and the predictors of HBsAg repositivity after drug withdrawal in non-cirrhotic CHB patients who had achieved HBsAg seroclearance following long-term NAs therapy.
Methods
This is a single center retrospective study focusing on non-cirrhotic CHB patients who received NAs treatment and achieved HBsAg seroclearance.These patients were treated in the hepatitis clinic of West China Hospital of Sichuan University and followed up for a long time. CHB patients were required to have complete demographic and clinical data. Additionally, serum levels of HBV RNA and HBcrAg were measured in all patients at the time of NAs cessation.
Results
A total of 137 non-cirrhotic CHB patients with HBsAg seroclearance were screened. Ultimately, 54 patients agreed to discontinue treatment, while 83 declined. Among the 54 patients who terminated treatment, 43 were male and 11 were female. Of these discontinued patients, 44 received continuous monotherapy, while 10 received combination therapy. All patients in this study received NAs antiviral treatment for more than 5 years. 79.6 % (43/54) of patients were found to be positive for HBsAb and 59.3 % (32/54) of patients had HBsAb≥200 IU/ml at the time of NAs discontinuation. Among the discontinued patients, all 54 patients were HBV RNA negative, and 87.0 % (47/54) were HBcrAg negative.The rates of HBsAg repositive were 3.7 % (95 % CI, 0.6 %–12.7 %) and 9.3 % (95 % CI, 3.8 %–19.7 %) at 24 and 48 weeks after drug withdrawal, respectively, and 3 of them were accompanied by HBV DNA relapse. All patients who regained HBsAg positivity after NAs discontinuation had serum HBcrAg levels greater than 3 log10 U/mL at the time of discontinuation.
Conclusion
In this single-center cohort, most non-cirrhotic patients who achieved HBsAg seroclearance on long-term NAs therapy maintained HBsAg loss over 48 weeks after discontinuation. HBcrAg positivity at end of treatment was observed in all cases of HBsAg reappearance, suggesting HBcrAg may help identify patients at higher short-term risk of seroreversion. Larger, longer-term studies are required to confirm these findings.
{"title":"Discontinuation of nucleos(t)ide analogues after NA-induced HBsAg seroclearance: a single-center 48-week retrospective study","authors":"Yong-Hong Wang, Ya-Chao Tao, Meng-Lan Wang, Cheng-Run Song, Jiang-Nan Peng, En-Qiang Chen","doi":"10.1016/j.jve.2025.100617","DOIUrl":"10.1016/j.jve.2025.100617","url":null,"abstract":"<div><h3>Background</h3><div>Hepatitis B virus (HBV) infection is a major risk factor for liver fibrosis, cirrhosis, and hepatocellular carcinoma. Whether patients with chronic hepatitis B (CHB) receiving oral nucleos(t)ide analogue (NA) therapy can safely discontinue treatment after HBsAg seroclearance is attracting clinical attention.This study aimed to explore the maintenance rate of HBsAg-negative status and the predictors of HBsAg repositivity after drug withdrawal in non-cirrhotic CHB patients who had achieved HBsAg seroclearance following long-term NAs therapy.</div></div><div><h3>Methods</h3><div>This is a single center retrospective study focusing on non-cirrhotic CHB patients who received NAs treatment and achieved HBsAg seroclearance.These patients were treated in the hepatitis clinic of West China Hospital of Sichuan University and followed up for a long time. CHB patients were required to have complete demographic and clinical data. Additionally, serum levels of HBV RNA and HBcrAg were measured in all patients at the time of NAs cessation.</div></div><div><h3>Results</h3><div>A total of 137 non-cirrhotic CHB patients with HBsAg seroclearance were screened. Ultimately, 54 patients agreed to discontinue treatment, while 83 declined. Among the 54 patients who terminated treatment, 43 were male and 11 were female. Of these discontinued patients, 44 received continuous monotherapy, while 10 received combination therapy. All patients in this study received NAs antiviral treatment for more than 5 years. 79.6 % (43/54) of patients were found to be positive for HBsAb and 59.3 % (32/54) of patients had HBsAb≥200 IU/ml at the time of NAs discontinuation. Among the discontinued patients, all 54 patients were HBV RNA negative, and 87.0 % (47/54) were HBcrAg negative.The rates of HBsAg repositive were 3.7 % (95 % CI, 0.6 %–12.7 %) and 9.3 % (95 % CI, 3.8 %–19.7 %) at 24 and 48 weeks after drug withdrawal, respectively, and 3 of them were accompanied by HBV DNA relapse. All patients who regained HBsAg positivity after NAs discontinuation had serum HBcrAg levels greater than 3 log<sub>10</sub> U/mL at the time of discontinuation.</div></div><div><h3>Conclusion</h3><div>In this single-center cohort, most non-cirrhotic patients who achieved HBsAg seroclearance on long-term NAs therapy maintained HBsAg loss over 48 weeks after discontinuation. HBcrAg positivity at end of treatment was observed in all cases of HBsAg reappearance, suggesting HBcrAg may help identify patients at higher short-term risk of seroreversion. Larger, longer-term studies are required to confirm these findings.</div></div>","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"11 4","pages":"Article 100617"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.jve.2025.100616
Chao Han , Linlin Jin , Mujia Zhu , Qiuying Qin , Guiping Li , Zhihong Liu , Xiaoyong Zhang
Background and objectives
Pegylated interferon (PegIFN) is one of the few strategies capable of achieving hepatitis B surface antigen (HBsAg) seroclearance in chronic hepatitis B (CHB) patients. However, its role in HBeAg-negative chronic HBV infection (also referred to as immune-inactive or “inactive carrier” phase) remains unclear. This study compared PegIFN efficacy between immune-inactive and immune-active patients and explored predictors of treatment response.
Research methods
We retrospectively analyzed 211 consecutive HBeAg-negative patients treated with PegIFN α-2b in our center from 2019 to 2023, including 139 with immune-inactive chronic HBV infection and 72 immune-active CHB patients. Effectiveness was assessed in the full analysis set (FAS) and efficacy in the per-protocol set (PPS). Predictors of HBsAg seroclearance were identified using Cox regression.
Results
At week 48, overall HBsAg seroclearance was 26.5 % (FAS), with comparable outcomes between immune-inactive and immune-active groups (26.6 % vs. 26.4 %, P > 0.05). Inactive patients receiving PegIFN + nucleos(t)ide analogues (NAs) showed no added benefit. In the PPS, clearance reached 69.1 %, but 40.3 % discontinued prematurely—mostly due to subjective intolerance—highlighting a major gap between real-world effectiveness and theoretical efficacy. Multivariate analysis identified two independent predictors: baseline HBsAg <100 IU/mL (HR 2.999, 95 % CI 1.625–5.536, P < 0.001) and on-treatment HBsAg decline ≥1 log10 IU/mL within any 12-week interval (HR 11.205, 95 % CI 4.379–28.674, P < 0.001).
Conclusions
PegIFN α-2b achieved clinically meaningful HBsAg seroclearance in both immune-inactive and immune-active patients. Early discontinuation markedly reduced real-world effectiveness. Baseline low HBsAg and dynamic on-treatment decline are pragmatic predictors for optimizing patient selection and guiding interferon-based strategies.
背景和目的聚乙二醇化干扰素（PegIFN）是少数能够在慢性乙型肝炎（CHB）患者中实现乙型肝炎表面抗原（HBsAg）血清清除的策略之一。然而，其在hbeag阴性慢性HBV感染（也称为免疫失活或“非活性载体”期）中的作用尚不清楚。本研究比较了PegIFN在免疫不活跃和免疫活跃患者之间的疗效，并探讨了治疗反应的预测因素。研究方法回顾性分析2019年至2023年在我中心连续接受PegIFN α-2b治疗的211例hbeag阴性患者，其中免疫失活性慢性HBV感染139例，免疫活动性CHB患者72例。以全分析集（FAS）和按方案集（PPS）评估疗效。使用Cox回归确定HBsAg血清清除率的预测因素。结果在第48周，总体HBsAg血清清除率为26.5% (FAS)，免疫无活性组和免疫活跃组的结果相当（26.6% vs. 26.4%, P > 0.05）。接受PegIFN +核苷类似物（NAs）的非活性患者没有显示出额外的益处。在PPS中，清除率达到69.1%，但40.3%过早停用，主要是由于主观不耐受，这突出了实际疗效与理论疗效之间的主要差距。多因素分析确定了两个独立的预测因子：基线HBsAg和lt 100 IU/mL （HR 2.999, 95% CI 1.625-5.536, P < 0.001）和治疗期间HBsAg下降≥1 log10 IU/mL （HR 11.205, 95% CI 4.379-28.674, P < 0.001）。结论spegifn α-2b在免疫失活和免疫活跃患者中均实现了具有临床意义的HBsAg清除率。早期停药显著降低了实际疗效。基线低HBsAg和治疗后动态下降是优化患者选择和指导基于干扰素的策略的实用预测指标。
{"title":"Efficacy and predictors of pegylated-interferon in hepatitis B surface antigen seroclearance in immune active and inactive chronic hepatitis B patients","authors":"Chao Han , Linlin Jin , Mujia Zhu , Qiuying Qin , Guiping Li , Zhihong Liu , Xiaoyong Zhang","doi":"10.1016/j.jve.2025.100616","DOIUrl":"10.1016/j.jve.2025.100616","url":null,"abstract":"<div><h3>Background and objectives</h3><div>Pegylated interferon (PegIFN) is one of the few strategies capable of achieving hepatitis B surface antigen (HBsAg) seroclearance in chronic hepatitis B (CHB) patients. However, its role in HBeAg-negative chronic HBV infection (also referred to as immune-inactive or “inactive carrier” phase) remains unclear. This study compared PegIFN efficacy between immune-inactive and immune-active patients and explored predictors of treatment response.</div></div><div><h3>Research methods</h3><div>We retrospectively analyzed 211 consecutive HBeAg-negative patients treated with PegIFN α-2b in our center from 2019 to 2023, including 139 with immune-inactive chronic HBV infection and 72 immune-active CHB patients. Effectiveness was assessed in the full analysis set (FAS) and efficacy in the per-protocol set (PPS). Predictors of HBsAg seroclearance were identified using Cox regression.</div></div><div><h3>Results</h3><div>At week 48, overall HBsAg seroclearance was 26.5 % (FAS), with comparable outcomes between immune-inactive and immune-active groups (26.6 % <em>vs</em>. 26.4 %, P > 0.05). Inactive patients receiving PegIFN + nucleos(t)ide analogues (NAs) showed no added benefit. In the PPS, clearance reached 69.1 %, but 40.3 % discontinued prematurely—mostly due to subjective intolerance—highlighting a major gap between real-world effectiveness and theoretical efficacy. Multivariate analysis identified two independent predictors: baseline HBsAg <100 IU/mL (HR 2.999, 95 % CI 1.625–5.536, P < 0.001) and on-treatment HBsAg decline ≥1 log<sub>10</sub> IU/mL within any 12-week interval (HR 11.205, 95 % CI 4.379–28.674, P < 0.001).</div></div><div><h3>Conclusions</h3><div>PegIFN α-2b achieved clinically meaningful HBsAg seroclearance in both immune-inactive and immune-active patients. Early discontinuation markedly reduced real-world effectiveness. Baseline low HBsAg and dynamic on-treatment decline are pragmatic predictors for optimizing patient selection and guiding interferon-based strategies.</div></div>","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"11 4","pages":"Article 100616"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-29DOI: 10.1016/j.jve.2025.100615
Marycelin Mandu Baba , Aisha Abba Kawu , Sadiya Alhaji Bukar , Musa Sundu Melton , Abdulwahab Mala , Ibrahim Salisu , Bamidele Soji Oderinde
The presence of neutralizing antibodies is considered a surrogate marker of protection against the three serotypes of poliovirus. The need to use the Microneutralization test in assessing the neutralizing antibodies to the three serotypes of polioviruses among vaccinated children aged 1–15 years informed this study. Of 400 children tested, 309 (77.3 %), 253 (63.3 %), and 308 (77.0 %) had neutralizing antibodies against P1, P2, and P3, respectively. Only 191 (47.8 %) had neutralizing antibodies against P1P2P3 simultaneously, the global target. Whilst 91 (22.8 %) had no neutralizing antibodies against P1, these children were protected against P2 (23.0 %) and P3 (43.9 %). Similarly, 147 (36.8 %) children had no neutralizing antibodies against P2, but were protected against P1 (66.0 %) and P3 (65.3 %). Furthermore, 52(13 %), 51(12.8 %), and 52 (13.0 %) had no neutralizing antibodies against the combination of P1P3, P1P2, and P2P3, respectively. Only 34 (8.5 %) of the children had no nAb to any of the three serotypes. The optimal number of Polio vaccine doses for effective immunity varied depending on the serotype. Also, gender differences may favor the speed at which children achieve the target antibody titers. Higher antibody titers (1:1280) were observed for P2 and P3, with six of the children having a titer of 1:10240 for P3. The combination of supplementary immunization activities and routine immunization generated a robust immune response across all poliovirus serotypes, in contrast to each of the two. The administrative data and population immunity were not commensurate. New strategies to increase immunity against the P1P2P3 simultaneously in all age groups are urgently required.
{"title":"Population immunity to the three serotypes of poliovirus post-interruption of wild poliovirus transmission in Nigeria","authors":"Marycelin Mandu Baba , Aisha Abba Kawu , Sadiya Alhaji Bukar , Musa Sundu Melton , Abdulwahab Mala , Ibrahim Salisu , Bamidele Soji Oderinde","doi":"10.1016/j.jve.2025.100615","DOIUrl":"10.1016/j.jve.2025.100615","url":null,"abstract":"<div><div>The presence of neutralizing antibodies is considered a surrogate marker of protection against the three serotypes of poliovirus. The need to use the Microneutralization test in assessing the neutralizing antibodies to the three serotypes of polioviruses among vaccinated children aged 1–15 years informed this study. Of 400 children tested, 309 (77.3 %), 253 (63.3 %), and 308 (77.0 %) had neutralizing antibodies against P1, P2, and P3, respectively. Only 191 (47.8 %) had neutralizing antibodies against P1P2P3 simultaneously, the global target. Whilst 91 (22.8 %) had no neutralizing antibodies against P1, these children were protected against P2 (23.0 %) and P3 (43.9 %). Similarly, 147 (36.8 %) children had no neutralizing antibodies against P2, but were protected against P1 (66.0 %) and P3 (65.3 %). Furthermore, 52(13 %), 51(12.8 %), and 52 (13.0 %) had no neutralizing antibodies against the combination of P1P3, P1P2, and P2P3, respectively. Only 34 (8.5 %) of the children had no nAb to any of the three serotypes. The optimal number of Polio vaccine doses for effective immunity varied depending on the serotype. Also, gender differences may favor the speed at which children achieve the target antibody titers. Higher antibody titers (1:1280) were observed for P2 and P3, with six of the children having a titer of 1:10240 for P3. The combination of supplementary immunization activities and routine immunization generated a robust immune response across all poliovirus serotypes, in contrast to each of the two. The administrative data and population immunity were not commensurate. New strategies to increase immunity against the P1P2P3 simultaneously in all age groups are urgently required.</div></div>","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"11 4","pages":"Article 100615"},"PeriodicalIF":2.0,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145516812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-25DOI: 10.1016/j.jve.2025.100614
Ibrahim Khalil , Md Imran Hossain , Sakib Abrar , Mst Mahmuda Akter , Supoma Ghosh Ria , M Rafiqul Islam
<div><h3>Background</h3><div>The HIV/AIDS epidemic remains a critical public health challenge in Bangladesh, with complex epidemiological trends and sex-specific disparities requiring detailed investigation to guide effective interventions. This study comprehensively analyzes the temporal dynamics of HIV/AIDS burden from 1990 to 2021 and employs advanced statistical modeling to forecast future trends up to 2050, aiming to inform targeted public health strategies.</div></div><div><h3>Methods</h3><div>Data on Disability-Adjusted Life Years (DALYs), deaths, incidence, prevalence, Years Lived with Disability (YLDs), and Years of Life Lost (YLLs) were sourced from a robust epidemiological database for Bangladesh. Joinpoint regression analysis was utilized to detect significant trend changes, calculating the average annual percent change (AAPC) and annual percent change (APC) with 95 % confidence intervals (CIs). Sex-stratified analyses elucidated disparities between males and females. Autoregressive Integrated Moving Average (ARIMA) models were applied to project age-standardized rates (ASRs) for each metric through 2050, incorporating historical trends and variability to ensure robust predictions.</div></div><div><h3>Results</h3><div>From 1990 to 2021, the HIV/AIDS burden in Bangladesh increased significantly across all metrics, with distinct sex-specific patterns. The overall AAPC for DALYs was 19.0332 % (95 % CI: 15.8145, 23.0026, p < 0.000001), with females showing a higher AAPC (21.7252 %, 95 % CI: 18.2308, 25.7026) than males (18.4703 %, 95 % CI: 15.1896, 22.5646). Deaths exhibited a similar trend, with an overall AAPC of 18.9645 % (95 % CI: 15.7008, 23.2166), higher in females (21.8808 %, 95 % CI: 18.4195, 25.9932) than males (18.4655 %, 95 % CI: 15.1992, 22.6832). Incidence rose with an AAPC of 15.7929 % (95 % CI: 11.6467, 19.1922), slightly higher in females (16.2581 %, 95 % CI: 12.1795, 20.0487) than males (15.1639 %, 95 % CI: 11.2952, 18.4817). Prevalence increased markedly (AAPC: 18.2239 %, 95 % CI: 14.5688, 22.2078), with females at 20.2887 % (95 % CI: 16.6453, 24.3006) and males at 18.1837 % (95 % CI: 14.6734, 21.841). YLDs and YLLs followed similar patterns, with females consistently showing higher AAPCs. Joinpoint analysis identified peak APCs in the 1990s and early 2000s, followed by moderated growth and declines post-2016, particularly from 2019 to 2021, reflecting potential intervention impacts. ARIMA forecasts project a decline in DALYs, deaths, and YLLs ASRs to negligible levels by 2050 for both sexes, with wide CIs indicating substantial uncertainty (e.g., DALYs overall: negligible, 95 % CI: 0, 583.3697). Incidence ASRs are expected to stabilize (e.g., overall: 0.963899, 95 % CI: 0, 3.819279), while prevalence ASRs are projected to rise dramatically, particularly for males (614.7463, 95 % CI: 0, 695680.4), highlighting significant long-term challenges.</div></div><div><h3>Conclusions</h3><div>The HIV/AIDS burden in Bangladesh
{"title":"Navigating the HIV/AIDS epidemic in Bangladesh: A comprehensive retrospective analysis of epidemiological trends and sex-specific disparities (1990–2021) with long-term ARIMA forecasting to 2050 for strategic public health planning","authors":"Ibrahim Khalil , Md Imran Hossain , Sakib Abrar , Mst Mahmuda Akter , Supoma Ghosh Ria , M Rafiqul Islam","doi":"10.1016/j.jve.2025.100614","DOIUrl":"10.1016/j.jve.2025.100614","url":null,"abstract":"<div><h3>Background</h3><div>The HIV/AIDS epidemic remains a critical public health challenge in Bangladesh, with complex epidemiological trends and sex-specific disparities requiring detailed investigation to guide effective interventions. This study comprehensively analyzes the temporal dynamics of HIV/AIDS burden from 1990 to 2021 and employs advanced statistical modeling to forecast future trends up to 2050, aiming to inform targeted public health strategies.</div></div><div><h3>Methods</h3><div>Data on Disability-Adjusted Life Years (DALYs), deaths, incidence, prevalence, Years Lived with Disability (YLDs), and Years of Life Lost (YLLs) were sourced from a robust epidemiological database for Bangladesh. Joinpoint regression analysis was utilized to detect significant trend changes, calculating the average annual percent change (AAPC) and annual percent change (APC) with 95 % confidence intervals (CIs). Sex-stratified analyses elucidated disparities between males and females. Autoregressive Integrated Moving Average (ARIMA) models were applied to project age-standardized rates (ASRs) for each metric through 2050, incorporating historical trends and variability to ensure robust predictions.</div></div><div><h3>Results</h3><div>From 1990 to 2021, the HIV/AIDS burden in Bangladesh increased significantly across all metrics, with distinct sex-specific patterns. The overall AAPC for DALYs was 19.0332 % (95 % CI: 15.8145, 23.0026, p < 0.000001), with females showing a higher AAPC (21.7252 %, 95 % CI: 18.2308, 25.7026) than males (18.4703 %, 95 % CI: 15.1896, 22.5646). Deaths exhibited a similar trend, with an overall AAPC of 18.9645 % (95 % CI: 15.7008, 23.2166), higher in females (21.8808 %, 95 % CI: 18.4195, 25.9932) than males (18.4655 %, 95 % CI: 15.1992, 22.6832). Incidence rose with an AAPC of 15.7929 % (95 % CI: 11.6467, 19.1922), slightly higher in females (16.2581 %, 95 % CI: 12.1795, 20.0487) than males (15.1639 %, 95 % CI: 11.2952, 18.4817). Prevalence increased markedly (AAPC: 18.2239 %, 95 % CI: 14.5688, 22.2078), with females at 20.2887 % (95 % CI: 16.6453, 24.3006) and males at 18.1837 % (95 % CI: 14.6734, 21.841). YLDs and YLLs followed similar patterns, with females consistently showing higher AAPCs. Joinpoint analysis identified peak APCs in the 1990s and early 2000s, followed by moderated growth and declines post-2016, particularly from 2019 to 2021, reflecting potential intervention impacts. ARIMA forecasts project a decline in DALYs, deaths, and YLLs ASRs to negligible levels by 2050 for both sexes, with wide CIs indicating substantial uncertainty (e.g., DALYs overall: negligible, 95 % CI: 0, 583.3697). Incidence ASRs are expected to stabilize (e.g., overall: 0.963899, 95 % CI: 0, 3.819279), while prevalence ASRs are projected to rise dramatically, particularly for males (614.7463, 95 % CI: 0, 695680.4), highlighting significant long-term challenges.</div></div><div><h3>Conclusions</h3><div>The HIV/AIDS burden in Bangladesh ","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"11 4","pages":"Article 100614"},"PeriodicalIF":2.0,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145466297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-10DOI: 10.1016/j.jve.2025.100613
Jared Stern , Michael Roche , Rory Shepherd , Wendy Hartogensis , Patricia Moran , Leslie Cockerham , Nadia Saraya , Ajantha Rhodes , Paul U. Cameron , Judy J. Chang , Nitasha Kumar , Wendy B. Mendes , Steven G. Deeks , Frederick M. Hecht , Sharon R. Lewin
The persistence of latently infected CD4+ T cells is the major barrier to cure of people with HIV (PWH) on antiretroviral therapy (ART). While most latently infected cells are transcriptionally silent, some express low levels of cell associated (CA) HIV RNA. In this prospective controlled interventional study, we tested the hypothesis that acute psychological stress could drive HIV transcription in PWH on ART. PWH on suppressive ART underwent the Trier Social Stress Test (TSST) and comparisons were made to a similar period of time without an intervention (control).
During the test, physiological markers of acute psychological stress including pre-ejection period and cardiac output changed in all participants, as anticipated. Compared to the control day, the TSST led to a significant increase in CA HIV RNA with no change in the level of cell associated HIV DNA, indicating an increase in HIV transcription in response to stress. Change in HIV transcription was associated with physiological markers of stress but not with changes in immune cells. These data demonstrate that HIV transcription is increased following acute stress and have implications on the impact of stress on the HIV reservoir and the design of cure strategies for PWH.
潜伏感染的CD4+ T细胞的持续存在是通过抗逆转录病毒治疗（ART）治愈艾滋病毒感染者（PWH）的主要障碍。虽然大多数潜伏感染的细胞在转录上沉默，但一些细胞表达低水平的细胞相关（CA） HIV RNA。在这项前瞻性对照干预研究中，我们验证了急性心理压力可以驱动抗逆转录病毒治疗PWH中HIV转录的假设。对抑制性抗逆转录病毒治疗的PWH进行了Trier社会压力测试（TSST），并与没有干预的类似时期（对照组）进行了比较。在测试期间，所有参与者的急性心理应激生理指标，包括射血前期和心输出量，如预期的那样发生了变化。与对照日相比，TSST导致CA HIV RNA显著增加，而细胞相关HIV DNA水平没有变化，表明HIV转录在应激反应中增加。HIV转录的变化与应激的生理标记有关，但与免疫细胞的变化无关。这些数据表明，急性应激后HIV转录增加，这对应激对HIV库的影响和PWH治疗策略的设计具有重要意义。
{"title":"The impact of acute stress on the HIV reservoir: a prospective interventional trial","authors":"Jared Stern , Michael Roche , Rory Shepherd , Wendy Hartogensis , Patricia Moran , Leslie Cockerham , Nadia Saraya , Ajantha Rhodes , Paul U. Cameron , Judy J. Chang , Nitasha Kumar , Wendy B. Mendes , Steven G. Deeks , Frederick M. Hecht , Sharon R. Lewin","doi":"10.1016/j.jve.2025.100613","DOIUrl":"10.1016/j.jve.2025.100613","url":null,"abstract":"<div><div>The persistence of latently infected CD4<sup>+</sup> T cells is the major barrier to cure of people with HIV (PWH) on antiretroviral therapy (ART). While most latently infected cells are transcriptionally silent, some express low levels of cell associated (CA) HIV RNA. In this prospective controlled interventional study, we tested the hypothesis that acute psychological stress could drive HIV transcription in PWH on ART. PWH on suppressive ART underwent the Trier Social Stress Test (TSST) and comparisons were made to a similar period of time without an intervention (control).</div><div>During the test, physiological markers of acute psychological stress including pre-ejection period and cardiac output changed in all participants, as anticipated. Compared to the control day, the TSST led to a significant increase in CA HIV RNA with no change in the level of cell associated HIV DNA, indicating an increase in HIV transcription in response to stress. Change in HIV transcription was associated with physiological markers of stress but not with changes in immune cells. These data demonstrate that HIV transcription is increased following acute stress and have implications on the impact of stress on the HIV reservoir and the design of cure strategies for PWH.</div></div>","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"11 4","pages":"Article 100613"},"PeriodicalIF":2.0,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145321254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-02DOI: 10.1016/j.jve.2025.100611
Caroline Schwarz , Angelika Schütz , Maximilian Anibas , David JM. Bauer , Lukas Burghart , Michael Schwarz , Enisa Gutic , Thomas Reiberger , Michael Gschwantler
Introduction
Directly observed therapy (DOT) is an effective strategy to optimize hepatitis C virus (HCV) cure rates in people who inject drugs (PWID) on stable opioid agonist therapy (OAT). While adherence to daily DOT is excellent, it remains unclear if extended DOT distribution intervals result in similar sustained virologic response (SVR) rates.
Methods
PWID undergoing DOT with direct-acting antiviral agents (DAA) alongside OAT for HCV infection at a low-threshold institution were included. Social distancing requirements during the COVID19 pandemic led to an extension in DOT dispensation intervals; therefore, the study population was classified according to “tight period” (DAA start 2014–2020) and “liberal period” (DAA start 2020–2023) cohorts. Socioeconomic characteristics, DOT distribution schedules, and rates of SVR at week 12 after end of therapy (SVR12) were compared between groups.
Results
We included 719 consecutive PWID (male: 76.5 %; median age: 39 years), 441 (61.3 %) were treated in the ”tight period” and 278 (38.7 %) in the “liberal period”. Baseline characteristics were comparable between cohorts, however, socioeconomic features of the “liberal period” group showed more problematic features (unemployment: 83.1 % vs. 67.3 %; lack of housing: 38.5 % vs. 35.1 %; ongoing injection drug use: 64.0 % vs. 57.8 %; each p < 0.001).
While the “tight period” group had their DAA most commonly dispensed on a daily basis (78.9 %), the “liberal period” group received their DAA/OAT mostly once weekly (45.0 %) or 2-3x/week (24.1 %; p < 0.001). The number of missed DAA ingestions (0.3 % vs. 0.4 %; p = 0.239) and SVR12 rates by modified intention to treat analysis (exclusion of PWID who were lost to follow-up [FU] or died) were similar (401/404, 99.3 % vs. 194/195, 99.5 %; p = 1.000) between tight and liberal period, respectively.
Loss of FU after end of DAA treatment was more common during the "liberal period" (28.8 % vs. 7.9 %; p < 0.001), yet no treatment interruptions or early discontinuations occurred.
Conclusion
DOT originally aimed to address non-adherence among PWID by strict control through daily supervised OAT and DAA ingestion. While this approach inherently manifests a position of advanced distrust towards PWID, our findings suggest that a strategy of advanced trust and liberalization of DOT alongside effective harm reduction measures yields excellent adherence and results in similarly high HCV cure rates.
直接观察治疗（DOT）是一种优化丙型肝炎病毒（HCV）治愈率的有效策略，用于注射药物（PWID）的稳定阿片类激动剂治疗（OAT）。虽然每日DOT的依从性很好，但延长DOT分布间隔是否会导致相似的持续病毒学反应（SVR）率仍不清楚。方法纳入在低阈值机构接受DOT联合直接作用抗病毒药物（DAA）和OAT治疗HCV感染的spwid。covid - 19大流行期间的社交距离要求导致DOT分配间隔延长；因此，研究人群被分为“紧张期”（DAA开始于2014-2020年）和“自由期”（DAA开始于2020-2023年）队列。比较两组患者治疗结束后第12周的社会经济特征、DOT分布表和SVR率（SVR12）。结果纳入连续PWID 719例（男性占76.5%，中位年龄39岁），“紧张期”441例（61.3%），“宽松期”278例（38.7%）。然而，“自由时期”组的基线特征在队列之间具有可比性，社会经济特征显示出更多的问题特征（失业率：83.1%对67.3%；缺乏住房：38.5%对35.1%；持续注射吸毒：64.0%对57.8%；各p <； 0.001）。“紧张期”组的DAA通常是每天一次（78.9%），而“自由期”组的DAA/OAT大多是每周一次（45.0%）或每周2-3次（24.1%;p < 0.001）。经改良意向治疗分析（排除失访[FU]或死亡的PWID），漏食DAA的数量（0.3%对0.4%,p = 0.239）和SVR12率在紧期和自由期分别相似（401/404,99.3%对194/195,99.5%,p = 1.000）。DAA治疗结束后FU的丧失在“自由期”更为常见（28.8% vs. 7.9%; p < 0.001），但没有出现治疗中断或早期停药的情况。结论dot最初旨在通过日常监督OAT和DAA摄入的严格控制来解决PWID患者的依从性问题。虽然这种方法固有地表现出对PWID的高度不信任，但我们的研究结果表明，高度信任和DOT自由化的策略以及有效的减少危害措施可以产生出色的依从性，并导致同样高的HCV治愈率。
{"title":"A liberalized approach to directly observed therapy for HCV retains excellent cure rates among PWID in Vienna","authors":"Caroline Schwarz , Angelika Schütz , Maximilian Anibas , David JM. Bauer , Lukas Burghart , Michael Schwarz , Enisa Gutic , Thomas Reiberger , Michael Gschwantler","doi":"10.1016/j.jve.2025.100611","DOIUrl":"10.1016/j.jve.2025.100611","url":null,"abstract":"<div><h3>Introduction</h3><div>Directly observed therapy (DOT) is an effective strategy to optimize hepatitis C virus (HCV) cure rates in people who inject drugs (PWID) on stable opioid agonist therapy (OAT). While adherence to daily DOT is excellent, it remains unclear if extended DOT distribution intervals result in similar sustained virologic response (SVR) rates.</div></div><div><h3>Methods</h3><div>PWID undergoing DOT with direct-acting antiviral agents (DAA) alongside OAT for HCV infection at a low-threshold institution were included. Social distancing requirements during the COVID19 pandemic led to an extension in DOT dispensation intervals; therefore, the study population was classified according to “tight period” (DAA start 2014–2020) and “liberal period” (DAA start 2020–2023) cohorts. Socioeconomic characteristics, DOT distribution schedules, and rates of SVR at week 12 after end of therapy (SVR12) were compared between groups.</div></div><div><h3>Results</h3><div>We included 719 consecutive PWID (male: 76.5 %; median age: 39 years), 441 (61.3 %) were treated in the ”tight period” and 278 (38.7 %) in the “liberal period”. Baseline characteristics were comparable between cohorts, however, socioeconomic features of the “liberal period” group showed more problematic features (unemployment: 83.1 % vs. 67.3 %; lack of housing: 38.5 % vs. 35.1 %; ongoing injection drug use: 64.0 % vs. 57.8 %; each p < 0.001).</div><div>While the “tight period” group had their DAA most commonly dispensed on a daily basis (78.9 %), the “liberal period” group received their DAA/OAT mostly once weekly (45.0 %) or 2-3x/week (24.1 %; p < 0.001). The number of missed DAA ingestions (0.3 % vs. 0.4 %; p = 0.239) and SVR12 rates by modified intention to treat analysis (exclusion of PWID who were lost to follow-up [FU] or died) were similar (401/404, 99.3 % vs. 194/195, 99.5 %; p = 1.000) between tight and liberal period, respectively.</div><div>Loss of FU after end of DAA treatment was more common during the \"liberal period\" (28.8 % vs. 7.9 %; p < 0.001), yet no treatment interruptions or early discontinuations occurred.</div></div><div><h3>Conclusion</h3><div>DOT originally aimed to address non-adherence among PWID by strict control through daily supervised OAT and DAA ingestion. While this approach inherently manifests a position of advanced distrust towards PWID, our findings suggest that a strategy of advanced trust and liberalization of DOT alongside effective harm reduction measures yields excellent adherence and results in similarly high HCV cure rates.</div></div>","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"11 4","pages":"Article 100611"},"PeriodicalIF":2.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145268783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-27DOI: 10.1016/j.jve.2025.100612
Yu Du , Wangsheng Zuo , Yiting Shao , Yanying Ji , Bojin Su , Sihong Liang , Deyu Wang , Bin Li , Yujie Feng , Liping Gong , Jianning Chen , Chunkui Shao
Epstein–Barr virus-associated gastric carcinoma (EBVaGC), a distinct subtype of gastric cancer, accounts for approximately 10 % of all gastric cancer cases. 2-deoxyglucose (2-DG), a glycolysis inhibitor, has emerged as a crucial tool in cancer therapy. However, the differential effects of 2-DG on EBVaGC and EBV-negative gastric carcinoma (EBVnGC) are not yet fully understood. In this study, we demonstrated that 2-DG inhibited the proliferation of both AGS and AGS-EBV cells, with AGS-EBV cells exhibiting greater sensitivity, particularly under hypoxic conditions. Furthermore, EBV infection was found to upregulate glycolytic gene expression in AGS-EBV cells, particularly under hypoxic conditions, through HIF-1α-dependent mechanisms. Notably, 2-DG also inhibited EBV lytic reactivation in AGS-EBV cells under hypoxic conditions. These findings provide valuable insights into the molecular mechanisms of EBV-mediated metabolic reprogramming and highlight the potential of 2-DG as a therapeutic agent for EBVaGC.
{"title":"2-Deoxyglucose as a therapeutic strategy for EBV-associated gastric carcinoma: Glycolytic and lytic reactivation inhibition under hypoxic conditions","authors":"Yu Du , Wangsheng Zuo , Yiting Shao , Yanying Ji , Bojin Su , Sihong Liang , Deyu Wang , Bin Li , Yujie Feng , Liping Gong , Jianning Chen , Chunkui Shao","doi":"10.1016/j.jve.2025.100612","DOIUrl":"10.1016/j.jve.2025.100612","url":null,"abstract":"<div><div>Epstein–Barr virus-associated gastric carcinoma (EBVaGC), a distinct subtype of gastric cancer, accounts for approximately 10 % of all gastric cancer cases. 2-deoxyglucose (2-DG), a glycolysis inhibitor, has emerged as a crucial tool in cancer therapy. However, the differential effects of 2-DG on EBVaGC and EBV-negative gastric carcinoma (EBVnGC) are not yet fully understood. In this study, we demonstrated that 2-DG inhibited the proliferation of both AGS and AGS-EBV cells, with AGS-EBV cells exhibiting greater sensitivity, particularly under hypoxic conditions. Furthermore, EBV infection was found to upregulate glycolytic gene expression in AGS-EBV cells, particularly under hypoxic conditions, through HIF-1α-dependent mechanisms. Notably, 2-DG also inhibited EBV lytic reactivation in AGS-EBV cells under hypoxic conditions. These findings provide valuable insights into the molecular mechanisms of EBV-mediated metabolic reprogramming and highlight the potential of 2-DG as a therapeutic agent for EBVaGC.</div></div>","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"11 4","pages":"Article 100612"},"PeriodicalIF":2.0,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145222029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-23DOI: 10.1016/j.jve.2025.100610
Kai Zhou , Yingshou Lei , Yaoqi Zhou , Jian Zhan
The persistent challenge posed by viruses such as HIV, HBV, and SARS-CoV-2 necessitates the continuous evolution of molecular tools for their study and for advancing therapeutic research. Split-protein complementation assays (PCAs), where a reporter protein is divided into two inactive fragments, have evolved from simple reporters of biological events into an increasingly important tool in modern virology. This review traces the evolutionary trajectory of split-protein systems. We begin with their foundational use in mechanistic discovery, where they first visualized viral-host interactions in living cells. We then explore their translation into practical applications, such as high-throughput drug screening and rapid point-of-care diagnostics. A step in this evolution was the development of systematic engineering platforms, dramatically accelerating the creation of novel biosensors. Finally, we discuss the latest frontier: engineering therapeutically active "split effectors." By integrating principles from synthetic biology, these advanced systems can function as programmable logic gates that respond to specific viral signatures. While therapeutic translation remains preclinical, split-protein platforms are emerging as tangible tools for advanced research and potential therapeutic development.
{"title":"Evolution of split-protein technologies in virology: From mechanistic discovery and diagnostics to therapeutic promise","authors":"Kai Zhou , Yingshou Lei , Yaoqi Zhou , Jian Zhan","doi":"10.1016/j.jve.2025.100610","DOIUrl":"10.1016/j.jve.2025.100610","url":null,"abstract":"<div><div>The persistent challenge posed by viruses such as HIV, HBV, and SARS-CoV-2 necessitates the continuous evolution of molecular tools for their study and for advancing therapeutic research. Split-protein complementation assays (PCAs), where a reporter protein is divided into two inactive fragments, have evolved from simple reporters of biological events into an increasingly important tool in modern virology. This review traces the evolutionary trajectory of split-protein systems. We begin with their foundational use in mechanistic discovery, where they first visualized viral-host interactions in living cells. We then explore their translation into practical applications, such as high-throughput drug screening and rapid point-of-care diagnostics. A step in this evolution was the development of systematic engineering platforms, dramatically accelerating the creation of novel biosensors. Finally, we discuss the latest frontier: engineering therapeutically active \"split effectors.\" By integrating principles from synthetic biology, these advanced systems can function as programmable logic gates that respond to specific viral signatures. While therapeutic translation remains preclinical, split-protein platforms are emerging as tangible tools for advanced research and potential therapeutic development.</div></div>","PeriodicalId":17552,"journal":{"name":"Journal of Virus Eradication","volume":"11 4","pages":"Article 100610"},"PeriodicalIF":2.0,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145222053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号