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Prognostic Significance of STK11/LKB1 Expression and Its Role in the Tumor Microenvironment of Colorectal Adenocarcinoma.
IF 1.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-03-01 DOI: 10.21873/invivo.13873
Yung-Heng Lee, Chun-Fan Yang, Yih-Farng Liou, Kevin Chih-Yang Huang, K S Clifford Chao, Shu-Fen Chiang

Background/aim: The loss or mutation of serine-threonine kinase 11/liver kinase B1 (STK11/LKB1) is known to negatively impact prognosis and immunotherapy outcomes in non-small cell lung cancer (NSCLC), and germline mutations in this gene cause gastrointestinal adenocarcinomas in patients with Peutz-Jeghers syndrome (PJS). Although STK11/LKB1 mutations are rare in colorectal cancer, the down-regulation of STK11/LKB1 has been implicated in its tumorigenesis. However, the relationship between STK11/LKB1 expression and the immunosuppressive tumor microenvironment in colorectal cancer remains unclear.

Materials and methods: In this study, we collected tissues from patients with colorectal adenocarcinoma (COAD) and constructed tissue microarrays (TMAs). STK11/LKB1 expression was assessed by immunohistochemistry and quantified by calculating H-scores. We also examined subsets of intratumoral tumor-infiltrating lymphocytes (TILs), including CD45+, CD8+, PD-1+, and CD45RO+ TILs, in these TMAs.

Results: STK11/LKB1 expression was significantly correlated with nodal metastasis. Kaplan-Meier survival analysis demonstrated that low STK11 expression was associated with significantly poorer overall survival (OS), particularly in COAD patients with KRAS mutations. However, STK11/LKB1 expression was not correlated with the presence of intratumoral CD45+, CD8+, PD-1+, or CD45RO+ TILs. Finally, multivariate Cox proportional regression analysis identified STK11/LKB1 expression as an independent prognostic factor in COAD patients.

Conclusion: While STK11/LKB1 expression is associated with tumor progression and survival outcomes, there is no evidence that STK11/LKB1 expression influences the infiltration of lymphocytes into the tumor microenvironment.

{"title":"Prognostic Significance of STK11/LKB1 Expression and Its Role in the Tumor Microenvironment of Colorectal Adenocarcinoma.","authors":"Yung-Heng Lee, Chun-Fan Yang, Yih-Farng Liou, Kevin Chih-Yang Huang, K S Clifford Chao, Shu-Fen Chiang","doi":"10.21873/invivo.13873","DOIUrl":"https://doi.org/10.21873/invivo.13873","url":null,"abstract":"<p><strong>Background/aim: </strong>The loss or mutation of serine-threonine kinase 11/liver kinase B1 (STK11/LKB1) is known to negatively impact prognosis and immunotherapy outcomes in non-small cell lung cancer (NSCLC), and germline mutations in this gene cause gastrointestinal adenocarcinomas in patients with Peutz-Jeghers syndrome (PJS). Although STK11/LKB1 mutations are rare in colorectal cancer, the down-regulation of STK11/LKB1 has been implicated in its tumorigenesis. However, the relationship between STK11/LKB1 expression and the immunosuppressive tumor microenvironment in colorectal cancer remains unclear.</p><p><strong>Materials and methods: </strong>In this study, we collected tissues from patients with colorectal adenocarcinoma (COAD) and constructed tissue microarrays (TMAs). STK11/LKB1 expression was assessed by immunohistochemistry and quantified by calculating H-scores. We also examined subsets of intratumoral tumor-infiltrating lymphocytes (TILs), including CD45+, CD8+, PD-1+, and CD45RO+ TILs, in these TMAs.</p><p><strong>Results: </strong>STK11/LKB1 expression was significantly correlated with nodal metastasis. Kaplan-Meier survival analysis demonstrated that low STK11 expression was associated with significantly poorer overall survival (OS), particularly in COAD patients with KRAS mutations. However, STK11/LKB1 expression was not correlated with the presence of intratumoral CD45+, CD8+, PD-1+, or CD45RO+ TILs. Finally, multivariate Cox proportional regression analysis identified STK11/LKB1 expression as an independent prognostic factor in COAD patients.</p><p><strong>Conclusion: </strong>While STK11/LKB1 expression is associated with tumor progression and survival outcomes, there is no evidence that STK11/LKB1 expression influences the infiltration of lymphocytes into the tumor microenvironment.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 2","pages":"691-701"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515549","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}
引用次数: 0
Chronic Kidney Disease Following Cardiac Arrest Manifesting as Dyspnoea and Peripheral Oedema in Cardiovascular Multimorbidity: Case Analysis and Brief Literature Review.
IF 1.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-03-01 DOI: 10.21873/invivo.13922
Kira Harding, Kate Emblin, Anca Ichim, Daniel Adlington, Rob Daniels, Kinan Mokbel

Background/aim: Chronic kidney disease (CKD) contributes significantly to morbidity, mortality, and healthcare costs. CKD is not only an independent risk factor for cardiovascular disease (CVD) but also a severe complication for patients with CVD, impacting substantially their prognosis and quality of life.

Case report: A 79-year-old male with a complex medical history, including asthma, hypertension, myocardial infarction, ischaemic heart disease, and recent atrial fibrillation, presented with new-onset exertional breathlessness and peripheral oedema following cardiac arrest and pacemaker insertion. Investigations, including medication reviews conducted shortly after in an outpatient setting, revealed severe renal impairment with creatinine levels at 250 μmol/l (reference range for adult males: 59-104), representing an initial acute kidney injury (AKI) that did not resolve and resulted in the diagnosis of stage 4 CKD (eGFR 25 ml/min/1.73 m2). The patient was treated with furosemide, dapagliflozin, and adjusted doses of ramipril and edoxaban. Following treatment, the patient's symptoms ameliorated and renal function slightly improved (eGFR 27 ml/min/1.73 m2).

Conclusion: This case highlights the importance of individualised treatment for patients with CKD alongside complex cardiovascular multi-morbidity. The administration of dapagliflozin and furosemide, together with careful adjustments to ramipril, were instrumental in stabilising the patient's renal function and alleviating symptoms. This case demonstrates how a multifaceted approach, continuous monitoring, and patient education are essential for achieving optimal outcomes in patients with CKD and cardiovascular comorbidities.

{"title":"Chronic Kidney Disease Following Cardiac Arrest Manifesting as Dyspnoea and Peripheral Oedema in Cardiovascular Multimorbidity: Case Analysis and Brief Literature Review.","authors":"Kira Harding, Kate Emblin, Anca Ichim, Daniel Adlington, Rob Daniels, Kinan Mokbel","doi":"10.21873/invivo.13922","DOIUrl":"https://doi.org/10.21873/invivo.13922","url":null,"abstract":"<p><strong>Background/aim: </strong>Chronic kidney disease (CKD) contributes significantly to morbidity, mortality, and healthcare costs. CKD is not only an independent risk factor for cardiovascular disease (CVD) but also a severe complication for patients with CVD, impacting substantially their prognosis and quality of life.</p><p><strong>Case report: </strong>A 79-year-old male with a complex medical history, including asthma, hypertension, myocardial infarction, ischaemic heart disease, and recent atrial fibrillation, presented with new-onset exertional breathlessness and peripheral oedema following cardiac arrest and pacemaker insertion. Investigations, including medication reviews conducted shortly after in an outpatient setting, revealed severe renal impairment with creatinine levels at 250 μmol/l (reference range for adult males: 59-104), representing an initial acute kidney injury (AKI) that did not resolve and resulted in the diagnosis of stage 4 CKD (eGFR 25 ml/min/1.73 m<sup>2</sup>). The patient was treated with furosemide, dapagliflozin, and adjusted doses of ramipril and edoxaban. Following treatment, the patient's symptoms ameliorated and renal function slightly improved (eGFR 27 ml/min/1.73 m<sup>2</sup>).</p><p><strong>Conclusion: </strong>This case highlights the importance of individualised treatment for patients with CKD alongside complex cardiovascular multi-morbidity. The administration of dapagliflozin and furosemide, together with careful adjustments to ramipril, were instrumental in stabilising the patient's renal function and alleviating symptoms. This case demonstrates how a multifaceted approach, continuous monitoring, and patient education are essential for achieving optimal outcomes in patients with CKD and cardiovascular comorbidities.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 2","pages":"1182-1189"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515589","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}
引用次数: 0
A Survey on the Prescribing Orientation Towards Complementary Therapies Among Oncologists in Italy: Symptoms and Unmet Patient Needs.
IF 1.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-03-01 DOI: 10.21873/invivo.13905
Maria Rosaria Valerio, Giuseppa Scandurra, Martina Greco, Vittorio Gebbia, Dario Piazza, Daniela Sambataro

Background/aim: A high percentage of cancer patients use complementary therapies (CM) during their disease journey. Several barriers for CM prescription still exist among oncologists. This study explored oncologists' attitudes toward prescribing CM with oral supplements or confirming prescriptions made by others.

Materials and methods: The study employed a mixed semi-quantitative and qualitative research strategy via a web-based platform interview as a preliminary step for a program of observational studies on the oncologist's prescriptions of oral supplements in cancer management, in Italy.

Results: Out of 95 invited oncologists, 40 participated in the study, mainly working in a general hospital or a cancer center. The deep knowledge of guidelines on integrative medicine was generally poor. The symptoms driving oncologists to initiate discussions on CM with patients were fatigue, anorexia/poor appetite, weight loss, insomnia, distress, neuropathy, or pain. The presence of reliable data in the medical literature on prescribing CM was a significant factor in choosing a supplement.

Conclusion: This study reveals that oncologists' limited knowledge and lack of standardized guidelines hinder the prescription of CM, despite recognizing its potential benefits. CM discussions are primarily patient-driven, with prescriptions influenced by reliable scientific data and symptom management. Expanding integrative medicine services and research on CM efficacy could enhance oncologists' confidence, improve patient care, and address unmet needs in oncology.

背景/目的:很大比例的癌症患者在患病期间会使用辅助疗法(CM)。肿瘤学家在开具中医处方时仍存在一些障碍。本研究探讨了肿瘤学家对使用口服补充剂开具中药处方或确认他人处方的态度:本研究采用了半定量和定性相结合的研究策略,通过网络平台进行访谈,作为在意大利开展肿瘤学家在癌症治疗中开具口服补充剂处方的观察研究计划的第一步:在 95 位受邀的肿瘤学家中,有 40 位参与了研究,他们主要在综合医院或癌症中心工作。他们对综合医学指南的了解普遍较少。促使肿瘤学家开始与患者讨论中医治疗的症状包括疲劳、厌食/食欲不振、体重减轻、失眠、痛苦、神经病变或疼痛。医学文献中关于中药处方的可靠数据是选择补充剂的一个重要因素:本研究表明,尽管认识到中药的潜在益处,但肿瘤学家有限的知识和标准化指南的缺乏阻碍了中药处方的开具。中药讨论主要以患者为主导,处方受可靠的科学数据和症状管理的影响。扩大中西医结合服务和中药疗效研究可增强肿瘤学家的信心,改善患者护理,满足肿瘤学领域尚未满足的需求。
{"title":"A Survey on the Prescribing Orientation Towards Complementary Therapies Among Oncologists in Italy: Symptoms and Unmet Patient Needs.","authors":"Maria Rosaria Valerio, Giuseppa Scandurra, Martina Greco, Vittorio Gebbia, Dario Piazza, Daniela Sambataro","doi":"10.21873/invivo.13905","DOIUrl":"https://doi.org/10.21873/invivo.13905","url":null,"abstract":"<p><strong>Background/aim: </strong>A high percentage of cancer patients use complementary therapies (CM) during their disease journey. Several barriers for CM prescription still exist among oncologists. This study explored oncologists' attitudes toward prescribing CM with oral supplements or confirming prescriptions made by others.</p><p><strong>Materials and methods: </strong>The study employed a mixed semi-quantitative and qualitative research strategy via a web-based platform interview as a preliminary step for a program of observational studies on the oncologist's prescriptions of oral supplements in cancer management, in Italy.</p><p><strong>Results: </strong>Out of 95 invited oncologists, 40 participated in the study, mainly working in a general hospital or a cancer center. The deep knowledge of guidelines on integrative medicine was generally poor. The symptoms driving oncologists to initiate discussions on CM with patients were fatigue, anorexia/poor appetite, weight loss, insomnia, distress, neuropathy, or pain. The presence of reliable data in the medical literature on prescribing CM was a significant factor in choosing a supplement.</p><p><strong>Conclusion: </strong>This study reveals that oncologists' limited knowledge and lack of standardized guidelines hinder the prescription of CM, despite recognizing its potential benefits. CM discussions are primarily patient-driven, with prescriptions influenced by reliable scientific data and symptom management. Expanding integrative medicine services and research on CM efficacy could enhance oncologists' confidence, improve patient care, and address unmet needs in oncology.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 2","pages":"1000-1008"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515457","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}
引用次数: 0
Risk of Pneumocystis jirovecii Pneumonia in Patients With HIV in Taiwan: Evidence from a Cross-sectional Study.
IF 1.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-03-01 DOI: 10.21873/invivo.13910
Jiun-Yi Wang, Kuang-Hua Huang, Chih-Jaan Tai, Shuo-Yan Gau, Tung-Han Tsai, Chun-Nan Wu, Chien-Ying Lee

Background/aim: Studies have demonstrated that patients with HIV are at a higher risk of Pneumocystis jirovecii pneumonia (PJP). Epidemiological knowledge of the risk of PJP among patients with HIV infection is lacking. This study aimed to assess the risk of PJP among patients with HIV.

Patients and methods: This cross-sectional study was conducted using the National Health Insurance Research Database of Taiwan. The participants were 18,929 patients with new-onset HIV infection from 2002 to 2015. Each patient was matched with four HIV-negative patients for age, sex, insured salary, urbanization status, Charlson Comorbidity Index score, and year of enrollment. The logistic regression with adjustment for relevant variables was performed to analyze the risk of PJP among patients with HIV at the 3-year follow-up. Sensitivity analysis was performed to compare the risk of PJP among different cohorts (patients with chronic kidney disease) and at different follow-up periods (6-month, 1-year, and 2-year follow-up).

Results: Patients with HIV had a higher risk of PJP [adjusted odds ratio (aOR)=199.36; 95% confidence interval (CI)=119.47-332.66] than HIV-negative individuals at the 3-year follow-up. Male patients had a higher risk of PJP (aOR=1.62; 95%CI=1.18-2.24) than female patients. Patients with chronic obstructive pulmonary disease (COPD) had a higher risk of PJP (aOR=1.74; 95%CI=1.27-2.39) at the 3-year follow-up.

Conclusion: Patients with HIV had a higher risk of PJP. Male patients had a higher risk of PJP than female patients. The risk of PJP was higher among patients with COPD.

背景/目的:研究表明,艾滋病病毒感染者患肺孢子虫肺炎(PJP)的风险较高。目前尚缺乏有关艾滋病病毒感染者患肺孢子虫肺炎风险的流行病学知识。本研究旨在评估艾滋病病毒感染者患 PJP 的风险:这项横断面研究使用了台湾国民健康保险研究数据库。研究对象为 2002 年至 2015 年间新发 HIV 感染的 18929 名患者。每名患者均与四名 HIV 阴性患者进行了年龄、性别、投保工资、城市化状况、Charlson 合并症指数评分和参保年份配对。在对相关变量进行调整后,进行了逻辑回归,以分析 HIV 感染者在 3 年随访期间罹患 PJP 的风险。为了比较不同组群(慢性肾病患者)和不同随访期(6 个月、1 年和 2 年随访)的 PJP 风险,进行了敏感性分析:结果:在 3 年随访期间,HIV 感染者比 HIV 阴性者患 PJP 的风险更高[调整赔率比 (aOR)=199.36; 95% 置信区间 (CI)=119.47-332.66] 。男性患者的 PJP 风险(aOR=1.62;95%CI=1.18-2.24)高于女性患者。慢性阻塞性肺病(COPD)患者在 3 年随访中患 PJP 的风险更高(aOR=1.74;95%CI=1.27-2.39):结论:HIV 感染者罹患 PJP 的风险更高。男性患者的 PJP 风险高于女性患者。慢性阻塞性肺病患者患 PJP 的风险更高。
{"title":"Risk of <i>Pneumocystis jirovecii</i> Pneumonia in Patients With HIV in Taiwan: Evidence from a Cross-sectional Study.","authors":"Jiun-Yi Wang, Kuang-Hua Huang, Chih-Jaan Tai, Shuo-Yan Gau, Tung-Han Tsai, Chun-Nan Wu, Chien-Ying Lee","doi":"10.21873/invivo.13910","DOIUrl":"https://doi.org/10.21873/invivo.13910","url":null,"abstract":"<p><strong>Background/aim: </strong>Studies have demonstrated that patients with HIV are at a higher risk of <i>Pneumocystis jirovecii</i> pneumonia (PJP). Epidemiological knowledge of the risk of PJP among patients with HIV infection is lacking. This study aimed to assess the risk of PJP among patients with HIV.</p><p><strong>Patients and methods: </strong>This cross-sectional study was conducted using the National Health Insurance Research Database of Taiwan. The participants were 18,929 patients with new-onset HIV infection from 2002 to 2015. Each patient was matched with four HIV-negative patients for age, sex, insured salary, urbanization status, Charlson Comorbidity Index score, and year of enrollment. The logistic regression with adjustment for relevant variables was performed to analyze the risk of PJP among patients with HIV at the 3-year follow-up. Sensitivity analysis was performed to compare the risk of PJP among different cohorts (patients with chronic kidney disease) and at different follow-up periods (6-month, 1-year, and 2-year follow-up).</p><p><strong>Results: </strong>Patients with HIV had a higher risk of PJP [adjusted odds ratio (aOR)=199.36; 95% confidence interval (CI)=119.47-332.66] than HIV-negative individuals at the 3-year follow-up. Male patients had a higher risk of PJP (aOR=1.62; 95%CI=1.18-2.24) than female patients. Patients with chronic obstructive pulmonary disease (COPD) had a higher risk of PJP (aOR=1.74; 95%CI=1.27-2.39) at the 3-year follow-up.</p><p><strong>Conclusion: </strong>Patients with HIV had a higher risk of PJP. Male patients had a higher risk of PJP than female patients. The risk of PJP was higher among patients with COPD.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 2","pages":"1054-1066"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515588","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}
引用次数: 0
Association of PTX3 Genetic Variants With Development of Diabetic Neuropathy.
IF 1.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-03-01 DOI: 10.21873/invivo.13874
Yung-Nan Hsu, Ying-Chi Fan, Shih-Chi Su, Lun-Ching Chang, Shun-Fa Yang

Background/aim: Pentraxin 3 (PTX3), initially discovered as a key player in the defense against infectious pathogens, is crucial for inflammation and tissue regeneration. This study aimed to explore the impact of PTX3 gene variants on the development and progression of diabetic neuropathy (DN).

Materials and methods: The potential impact of PTX3 gene variants on the susceptibility to DN was examined by genotyping four single-nucleotide polymorphisms (SNPs) of the PTX3 gene (rs1840680, rs2305619, rs3816527, and rs2120243) in a study involving 730 DN cases and 861 diabetic controls with normal neurologic function.

Results: We demonstrated that diabetic subjects homozygous for the minor allele at rs1840680 [AA; adjusted odds ratio (AOR)=1.486; 95% confidence interval (CI)=1.050-2.103; p=0.02] or rs2120243 (AA; AOR=1.483; 95%CI=1.051-2.091; p=0.025) were more likely to develop neurologic complications compared to those homozygous for the corresponding major allele. Further stratification revealed that this correlation with DN risk was observed specifically in males but not in females. In addition, another SNP of the PTX3 gene, rs2305619, was found to be associated with the risk for DN in males (AA vs. GG, AOR=1.686; 95%CI=1.086-2.617, p=0.020), indicating a sex-specific impact of PTX3 gene polymorphisms on damage to the nerves in diabetic patients. Furthermore, DN patients homozygous for the minor allele of rs1840680 (AA), particularly males, had higher levels of LDL-cholesterol than those homozygous for the reference allele (GG) (p=0.034).

Conclusion: PTX3 gene polymorphisms are associated with dyslipidemia and nerve damage in diabetic patients in a sex-specific manner.

背景/目的:五羟色胺 3(Pentraxin 3,PTX3)最初是作为抵御感染性病原体的关键角色被发现的,它对炎症和组织再生至关重要。本研究旨在探讨 PTX3 基因变异对糖尿病神经病变(DN)发生和发展的影响:通过对 PTX3 基因的四个单核苷酸多态性(SNPs)(rs1840680、rs2305619、rs3816527 和 rs2120243)进行基因分型,研究了 PTX3 基因变异对 DN 易感性的潜在影响:我们发现,与等位基因相同的糖尿病患者相比,等位基因为 rs1840680 的小等位基因[AA;调整赔率(AOR)=1.486;95% 置信区间(CI)=1.050-2.103;p=0.02]或 rs2120243(AA;AOR=1.483;95%CI=1.051-2.091;p=0.025)的糖尿病患者更容易出现神经系统并发症。进一步分层发现,这种与 DN 风险的相关性只在男性中观察到,而在女性中没有观察到。此外,还发现 PTX3 基因的另一个 SNP rs2305619 与男性的 DN 风险相关(AA 与 GG,AOR=1.686;95%CI=1.086-2.617,p=0.020),这表明 PTX3 基因多态性对糖尿病患者神经损伤的影响具有性别特异性。此外,rs1840680小等位基因(AA)的DN患者,尤其是男性,其低密度脂蛋白胆固醇水平高于参考等位基因(GG)的患者(P=0.034):结论:PTX3 基因多态性与糖尿病患者的血脂异常和神经损伤有关,且具有性别特异性。
{"title":"Association of PTX3 Genetic Variants With Development of Diabetic Neuropathy.","authors":"Yung-Nan Hsu, Ying-Chi Fan, Shih-Chi Su, Lun-Ching Chang, Shun-Fa Yang","doi":"10.21873/invivo.13874","DOIUrl":"https://doi.org/10.21873/invivo.13874","url":null,"abstract":"<p><strong>Background/aim: </strong>Pentraxin 3 (PTX3), initially discovered as a key player in the defense against infectious pathogens, is crucial for inflammation and tissue regeneration. This study aimed to explore the impact of <i>PTX3</i> gene variants on the development and progression of diabetic neuropathy (DN).</p><p><strong>Materials and methods: </strong>The potential impact of <i>PTX3</i> gene variants on the susceptibility to DN was examined by genotyping four single-nucleotide polymorphisms (SNPs) of the <i>PTX3</i> gene (rs1840680, rs2305619, rs3816527, and rs2120243) in a study involving 730 DN cases and 861 diabetic controls with normal neurologic function.</p><p><strong>Results: </strong>We demonstrated that diabetic subjects homozygous for the minor allele at rs1840680 [AA; adjusted odds ratio (AOR)=1.486; 95% confidence interval (CI)=1.050-2.103; <i>p</i>=0.02] or rs2120243 (AA; AOR=1.483; 95%CI=1.051-2.091; <i>p</i>=0.025) were more likely to develop neurologic complications compared to those homozygous for the corresponding major allele. Further stratification revealed that this correlation with DN risk was observed specifically in males but not in females. In addition, another SNP of the <i>PTX3</i> gene, rs2305619, was found to be associated with the risk for DN in males (AA <i>vs.</i> GG, AOR=1.686; 95%CI=1.086-2.617, <i>p</i>=0.020), indicating a sex-specific impact of <i>PTX3</i> gene polymorphisms on damage to the nerves in diabetic patients. Furthermore, DN patients homozygous for the minor allele of rs1840680 (AA), particularly males, had higher levels of LDL-cholesterol than those homozygous for the reference allele (GG) (<i>p</i>=0.034).</p><p><strong>Conclusion: </strong><i>PTX3</i> gene polymorphisms are associated with dyslipidemia and nerve damage in diabetic patients in a sex-specific manner.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 2","pages":"702-712"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515521","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}
引用次数: 0
Molecular Hydrogen as an Adjuvant Therapy in Severe Lupus Serositis With Heart Failure: A Case Report on Immune Modulation and Fatigue Reduction.
IF 1.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-03-01 DOI: 10.21873/invivo.13924
Yun-Ting Lin, Jeng-Wei Lu, Yi-Jung Ho, Shan-Wen Lui, Ting-Yu Hsieh, Hsiao-Chen Liu, Kuang-Yih Wang, Feng-Cheng Liu

Background/aim: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multi-organ inflammation and damage across multiple organs, typically managed with steroids and immunomodulators. However, prolonged use of these treatments is often associated with significant side effects, underscoring the need for adjunctive therapies that improve disease outcomes while minimizing adverse effects. Molecular hydrogen (H2) has demonstrated potential as an antioxidant and anti-inflammatory agent. This report discusses a case of SLE with cardiac complications, evaluating the therapeutic impact of molecular hydrogen therapy on fatigue, immune modulation, and cardiac function.

Case report: A 51-year-old female with SLE and acute decompensated heart failure initially received steroids and immunomodulators for disease management. Subsequently, molecular hydrogen therapy was introduced as an adjuvant treatment. Over several months, her cardiac function showed notable improvement, evidenced by reductions in anti-dsDNA and anti-Ro52 antibody levels, and Pro-BNP levels, as well as favorable shifts in T and B cell subsets. Additionally, the patient experienced a significant reduction in fatigue. She successfully tapered off steroids while maintaining disease stability with ongoing molecular hydrogen therapy.

Conclusion: This case highlights the potential of molecular hydrogen therapy as an adjuvant treatment in SLE, with observed benefits in immune modulation and fatigue reduction. Further studies are warranted to elucidate its therapeutic role and applicability in autoimmune diseases.

背景/目的:系统性红斑狼疮(SLE)是一种慢性自身免疫性疾病,以多器官炎症和多器官损害为特征,通常使用类固醇和免疫调节剂进行治疗。然而,长期使用这些治疗方法往往会产生严重的副作用,因此需要既能改善疾病治疗效果,又能将不良反应降至最低的辅助疗法。分子氢(H2)已被证明具有抗氧化和抗炎的潜力。本报告讨论了一例伴有心脏并发症的系统性红斑狼疮患者,评估了分子氢疗法对疲劳、免疫调节和心脏功能的治疗效果:病例报告:一名患有系统性红斑狼疮和急性失代偿性心力衰竭的 51 岁女性患者最初接受了类固醇和免疫调节剂治疗。随后,她接受了分子氢疗法作为辅助治疗。几个月后,她的心功能明显改善,抗dsDNA和抗Ro52抗体水平以及前BNP水平均有所下降,T细胞和B细胞亚群也发生了有利的变化。此外,患者的疲劳感也明显减轻。她成功地停用了类固醇,同时通过持续的分子氢疗法保持了病情稳定:本病例凸显了分子氢疗法作为系统性红斑狼疮辅助治疗的潜力,在免疫调节和缓解疲劳方面都有明显的疗效。我们有必要开展进一步研究,以阐明分子氢疗法在自身免疫性疾病中的治疗作用和适用性。
{"title":"Molecular Hydrogen as an Adjuvant Therapy in Severe Lupus Serositis With Heart Failure: A Case Report on Immune Modulation and Fatigue Reduction.","authors":"Yun-Ting Lin, Jeng-Wei Lu, Yi-Jung Ho, Shan-Wen Lui, Ting-Yu Hsieh, Hsiao-Chen Liu, Kuang-Yih Wang, Feng-Cheng Liu","doi":"10.21873/invivo.13924","DOIUrl":"https://doi.org/10.21873/invivo.13924","url":null,"abstract":"<p><strong>Background/aim: </strong>Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multi-organ inflammation and damage across multiple organs, typically managed with steroids and immunomodulators. However, prolonged use of these treatments is often associated with significant side effects, underscoring the need for adjunctive therapies that improve disease outcomes while minimizing adverse effects. Molecular hydrogen (H<sub>2</sub>) has demonstrated potential as an antioxidant and anti-inflammatory agent. This report discusses a case of SLE with cardiac complications, evaluating the therapeutic impact of molecular hydrogen therapy on fatigue, immune modulation, and cardiac function.</p><p><strong>Case report: </strong>A 51-year-old female with SLE and acute decompensated heart failure initially received steroids and immunomodulators for disease management. Subsequently, molecular hydrogen therapy was introduced as an adjuvant treatment. Over several months, her cardiac function showed notable improvement, evidenced by reductions in anti-dsDNA and anti-Ro52 antibody levels, and Pro-BNP levels, as well as favorable shifts in T and B cell subsets. Additionally, the patient experienced a significant reduction in fatigue. She successfully tapered off steroids while maintaining disease stability with ongoing molecular hydrogen therapy.</p><p><strong>Conclusion: </strong>This case highlights the potential of molecular hydrogen therapy as an adjuvant treatment in SLE, with observed benefits in immune modulation and fatigue reduction. Further studies are warranted to elucidate its therapeutic role and applicability in autoimmune diseases.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 2","pages":"1200-1206"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515507","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}
引用次数: 0
Correlation of HLA-A and HLA-B/C Expression With PD-1 and PD-L1 Expression in Patients With Metastatic Breast Cancer as a Potential Prognosticator of Favorable Survival.
IF 1.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-03-01 DOI: 10.21873/invivo.13880
Lukas Goerdt, Aleksandra Stefanovic, Ralph Wirtz, Uros Karic, Maximilian Kohler, Thomas M Deutsch, Andreas Schneeweiss, Marc Sütterlin, Stefan Stefanovic, Jan Hofmann, Markus Wallwiener

Background/aim: Class 1 human leukocyte antigen (HLA) ensures that cytotoxic T lymphocytes (CTLs) attack tumor cells. As part of tumor de-differentiation, the expression of HLA on the tumor cell surface may decrease, which can facilitate tumor growth. Therefore, reduced expression of HLA is generally negatively associated with overall survival (OS). The reverse is true for programmed cell death protein (PD-1) and programmed death ligand 1 (PD-L1). The presence of PD-1 and PD-L1 on the surface of cancer cells inhibits immune defense mechanisms against cancer cells. Therefore, one would expect that increased PD-1/PDL-1 expression would result in decreased 5-year survival. The aim of this study was to correlate the expression levels of HLA-A and HLA-B/C with the expression levels of PD-1 and PDL-1 to evaluate the reliability of their prediction of 5-year OS.

Materials and methods: This study retrospectively examined patients upon the start of a new therapy line for metastatic breast cancer (MBC). The pilot cohort fulfilling very demanding inclusion criteria consisted of 34 patients. The diagnostics were primarily carried out using RT-qPCR.

Results: The expression of HLA-A, HLA-B/C, PD-1, and PD-L1 is not significantly associated with OS.

Conclusion: This pilot study found no significant association between HLA-A, HLA-B/C, PD-1, or PD-L1 expression and OS in MBC, indicating limited prognostic value for these biomarkers in this cohort.

背景/目的:1类人类白细胞抗原(HLA)可确保细胞毒性T淋巴细胞(CTL)攻击肿瘤细胞。作为肿瘤去分化的一部分,HLA在肿瘤细胞表面的表达可能会减少,从而促进肿瘤生长。因此,HLA表达的减少通常与总生存期(OS)呈负相关。程序性细胞死亡蛋白(PD-1)和程序性死亡配体 1(PD-L1)的情况则相反。癌细胞表面存在的 PD-1 和 PD-L1 会抑制针对癌细胞的免疫防御机制。因此,人们预计PD-1/PDL-1表达增加会导致5年生存率下降。本研究旨在将HLA-A和HLA-B/C的表达水平与PD-1和PDL-1的表达水平相关联,以评估其预测5年OS的可靠性:本研究对开始接受新疗法的转移性乳腺癌(MBC)患者进行了回顾性研究。符合非常严格的纳入标准的试点队列由 34 名患者组成。诊断主要通过 RT-qPCR 进行:结果:HLA-A、HLA-B/C、PD-1和PD-L1的表达与OS无显著相关性:这项试验性研究发现,HLA-A、HLA-B/C、PD-1或PD-L1的表达与MBC的OS无明显相关性,这表明这些生物标志物在这一人群中的预后价值有限。
{"title":"Correlation of HLA-A and HLA-B/C Expression With PD-1 and PD-L1 Expression in Patients With Metastatic Breast Cancer as a Potential Prognosticator of Favorable Survival.","authors":"Lukas Goerdt, Aleksandra Stefanovic, Ralph Wirtz, Uros Karic, Maximilian Kohler, Thomas M Deutsch, Andreas Schneeweiss, Marc Sütterlin, Stefan Stefanovic, Jan Hofmann, Markus Wallwiener","doi":"10.21873/invivo.13880","DOIUrl":"https://doi.org/10.21873/invivo.13880","url":null,"abstract":"<p><strong>Background/aim: </strong>Class 1 human leukocyte antigen (HLA) ensures that cytotoxic T lymphocytes (CTLs) attack tumor cells. As part of tumor de-differentiation, the expression of HLA on the tumor cell surface may decrease, which can facilitate tumor growth. Therefore, reduced expression of HLA is generally negatively associated with overall survival (OS). The reverse is true for programmed cell death protein (PD-1) and programmed death ligand 1 (PD-L1). The presence of PD-1 and PD-L1 on the surface of cancer cells inhibits immune defense mechanisms against cancer cells. Therefore, one would expect that increased PD-1/PDL-1 expression would result in decreased 5-year survival. The aim of this study was to correlate the expression levels of HLA-A and HLA-B/C with the expression levels of PD-1 and PDL-1 to evaluate the reliability of their prediction of 5-year OS.</p><p><strong>Materials and methods: </strong>This study retrospectively examined patients upon the start of a new therapy line for metastatic breast cancer (MBC). The pilot cohort fulfilling very demanding inclusion criteria consisted of 34 patients. The diagnostics were primarily carried out using RT-qPCR.</p><p><strong>Results: </strong>The expression of HLA-A, HLA-B/C, PD-1, and PD-L1 is not significantly associated with OS.</p><p><strong>Conclusion: </strong>This pilot study found no significant association between HLA-A, HLA-B/C, PD-1, or PD-L1 expression and OS in MBC, indicating limited prognostic value for these biomarkers in this cohort.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 2","pages":"758-765"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515593","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}
引用次数: 0
Cutaneous Cryosurgery in Dermatology: Evolving Principles and Clinical Applications for Benign, Premalignant, and Malignant Lesions.
IF 1.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-03-01 DOI: 10.21873/invivo.13865
Ramia Mokbel, Alevtina Kodresko, Kefah Mokbel, Heba Ghazal, Jon Trembley, Hussam Jouhara

Skin and subcutaneous diseases represent a significant public health burden, profoundly impacting quality of life, social interactions, mental health, and daily activities-raising concerns worldwide. In modern cryogenics, cryosurgery is among the therapeutic approaches employed by healthcare professionals to address this broad and complex range of diseases. Over the past four decades, cryosurgery has evolved into a valuable treatment option, used alone or as an adjunct therapy, and is adaptable to the needs of various special populations. This approach offers distinct advantages over established treatments due to its safety, efficiency, feasibility, and cost-effectiveness. However, a comprehensive, up-to-date review of cryosurgery's applications is lacking, which limits research dissemination and recognition among dermatologists. This review aims to provide an overview of cryosurgery principles and its current clinical practice in dermatology, covering a broad range of benign, premalignant, and malignant cutaneous conditions, and highlighting its potential as an essential approach in global healthcare.

皮肤和皮下疾病是重大的公共卫生负担,严重影响生活质量、社会交往、心理健康和日常活动,引起了全世界的关注。在现代低温医学中,冷冻手术是医护人员用来治疗这种广泛而复杂的疾病的治疗方法之一。在过去的四十年中,冷冻手术已发展成为一种有价值的治疗方法,既可单独使用,也可作为辅助疗法,并能适应各种特殊人群的需要。由于其安全性、高效性、可行性和成本效益,这种方法与已有的治疗方法相比具有明显的优势。然而,关于冷冻手术应用的全面、最新综述尚缺,这限制了研究在皮肤科医生中的传播和认可。本综述旨在概述冷冻手术的原理及其目前在皮肤病学中的临床实践,涵盖范围广泛的良性、恶性和恶性皮肤病,并强调其作为全球医疗保健中一种重要方法的潜力。
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引用次数: 0
Fibroma of Tendon Sheath Revisited.
IF 1.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-03-01 DOI: 10.21873/invivo.13866
Yuki Shinohara, Jun Nishio, Shizuhide Nakayama, Mikoro Koga, Mikiko Aoki, Takamasa Koga

Fibroma of tendon sheath (FTS) is a benign fibroblastic/myofibroblastic neoplasm that primarily occurs in the fingers and hands of young and middle-aged adults. The lesion typically presents as a small, firm, slow-growing, painless nodule. Ultrasonography usually shows a focal nodular mass with homogeneous hypoechogenicity. Magnetic resonance imaging reveals a well-defined nodular mass with decreased signal on all pulse sequences. No or minimal peripheral enhancement is often seen after intravenous contrast. Histologically, the lesion is well circumscribed and consists of bland spindle cells in a dense collagenous stroma with slit-like thin-walled vessels at the periphery. A cellular variant of FTS has also been described and shows at least a focal morphological overlap with nodular fasciitis. Immunohistochemistry does not play a significant role in the diagnosis of FTS. Cytogenetic studies have demonstrated the presence of 11q rearrangements. A significant subset of cellular variants of FTS are characterized by ubiquitin specific peptidase 6 (USP6) rearrangements, with a variety of fusion partners. Complete surgical excision is the treatment of choice. This review provides an updated overview of the clinical, radiological, histological, cytogenetic and molecular genetic features of FTS and discusses the differential diagnosis of this uncommon entity.

{"title":"Fibroma of Tendon Sheath Revisited.","authors":"Yuki Shinohara, Jun Nishio, Shizuhide Nakayama, Mikoro Koga, Mikiko Aoki, Takamasa Koga","doi":"10.21873/invivo.13866","DOIUrl":"https://doi.org/10.21873/invivo.13866","url":null,"abstract":"<p><p>Fibroma of tendon sheath (FTS) is a benign fibroblastic/myofibroblastic neoplasm that primarily occurs in the fingers and hands of young and middle-aged adults. The lesion typically presents as a small, firm, slow-growing, painless nodule. Ultrasonography usually shows a focal nodular mass with homogeneous hypoechogenicity. Magnetic resonance imaging reveals a well-defined nodular mass with decreased signal on all pulse sequences. No or minimal peripheral enhancement is often seen after intravenous contrast. Histologically, the lesion is well circumscribed and consists of bland spindle cells in a dense collagenous stroma with slit-like thin-walled vessels at the periphery. A cellular variant of FTS has also been described and shows at least a focal morphological overlap with nodular fasciitis. Immunohistochemistry does not play a significant role in the diagnosis of FTS. Cytogenetic studies have demonstrated the presence of 11q rearrangements. A significant subset of cellular variants of FTS are characterized by ubiquitin specific peptidase 6 (USP6) rearrangements, with a variety of fusion partners. Complete surgical excision is the treatment of choice. This review provides an updated overview of the clinical, radiological, histological, cytogenetic and molecular genetic features of FTS and discusses the differential diagnosis of this uncommon entity.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 2","pages":"613-620"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515371","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}
引用次数: 0
Global, Regional and National Burden of Edentulism and Periodontal Diseases from 1990 to 2021: Analysis of Risk Factors and Prediction of Trends in 2050.
IF 1.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-03-01 DOI: 10.21873/invivo.13919
Yong Feng, Liyuan Xiao, Ling-Ling Fu, Martin Gosau, Tobias Vollkommer, Ulrike Speth, Ralf Smeets, Rico Rutkowski, Reinhard E Friedrich, Ming Yan

Background/aim: Periodontal diseases and edentulism remain a prevalent and disabling oral health condition worldwide, with significant regional disparities. This study systematically evaluated the burden of periodontal disease and edentulism at global, regional, and national levels from 1990 to 2021, using the Global Burden of Disease (GBD) 2021 framework.

Patients and methods: We analyzed trends in incidence, prevalence, and years lived with disability (YLD), exploring their associations with the socio-demographic index (SDI) and other risk factors.

Results: The findings reveal considerable variations across SDI regions, with low and low-middle SDI regions experiencing the highest burden. In 2021, the global prevalence of periodontal diseases reached approximately 1.07 billion cases, and the age-standardized incidence and prevalence rates varied significantly by SDI levels. The burden of periodontal disease showed an increasing trend among middle-aged and elderly populations. While sex differences were present in both edentulism and periodontal diseases, they were relatively minor. ARIMA model projections indicate that the burden of edentulism will fluctuate by 2050, while the burden of periodontal diseases will remain stable.

Conclusion: This study underscores the need for targeted public health interventions, particularly in resource-limited regions, to improve access to oral healthcare and integrate preventive strategies into broader health initiatives.

{"title":"Global, Regional and National Burden of Edentulism and Periodontal Diseases from 1990 to 2021: Analysis of Risk Factors and Prediction of Trends in 2050.","authors":"Yong Feng, Liyuan Xiao, Ling-Ling Fu, Martin Gosau, Tobias Vollkommer, Ulrike Speth, Ralf Smeets, Rico Rutkowski, Reinhard E Friedrich, Ming Yan","doi":"10.21873/invivo.13919","DOIUrl":"https://doi.org/10.21873/invivo.13919","url":null,"abstract":"<p><strong>Background/aim: </strong>Periodontal diseases and edentulism remain a prevalent and disabling oral health condition worldwide, with significant regional disparities. This study systematically evaluated the burden of periodontal disease and edentulism at global, regional, and national levels from 1990 to 2021, using the Global Burden of Disease (GBD) 2021 framework.</p><p><strong>Patients and methods: </strong>We analyzed trends in incidence, prevalence, and years lived with disability (YLD), exploring their associations with the socio-demographic index (SDI) and other risk factors.</p><p><strong>Results: </strong>The findings reveal considerable variations across SDI regions, with low and low-middle SDI regions experiencing the highest burden. In 2021, the global prevalence of periodontal diseases reached approximately 1.07 billion cases, and the age-standardized incidence and prevalence rates varied significantly by SDI levels. The burden of periodontal disease showed an increasing trend among middle-aged and elderly populations. While sex differences were present in both edentulism and periodontal diseases, they were relatively minor. ARIMA model projections indicate that the burden of edentulism will fluctuate by 2050, while the burden of periodontal diseases will remain stable.</p><p><strong>Conclusion: </strong>This study underscores the need for targeted public health interventions, particularly in resource-limited regions, to improve access to oral healthcare and integrate preventive strategies into broader health initiatives.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 2","pages":"1148-1161"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515492","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}
引用次数: 0
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