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Cisplatin is a platinum-based drug that is frequently used to treat multiple tumors. The anti-tumor effect of cisplatin is closely related to the tumor immune microenvironment (TIME), which includes several immune cell types, such as the tumor-associated macrophages (TAMs), cytotoxic T-lymphocytes (CTLs), dendritic cells (DCs), myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), and natural killer (NK) cells. The interaction between these immune cells can promote tumor survival and chemoresistance, and decrease the efficacy of cisplatin monotherapy. Therefore, various combination treatment strategies have been devised to enhance patient responsiveness to cisplatin therapy. Cisplatin can augment anti-tumor immune responses in combination with immune checkpoint blockers (such as PD-1/PD-L1 or CTLA4 inhibitors), lipid metabolism disruptors (like FASN inhibitors and SCD inhibitors) and nanoparticles (NPs), resulting in better outcomes. Exploring the interaction between cisplatin and the TIME will help identify potential therapeutic targets for improving the treatment outcomes in cancer patients.

Background: With the refinement of catheter technology, distal medium vessel occlusions (DMVOs) are now viewed as amenable to endovascular treatment (EVT) but its efficacy and safety remains unclear in AIS patients with DMVO.

Methods: We conducted a systematic search of PubMed, Embase databases and Cochrane Library up to December 2023 using keywords to identify studies comparing EVT versus BMT in AIS with DMVOs. The assessed clinical outcomes were excellent functional outcome, good functional outcome, 90-day mortality, symptomatic intracranial hemorrhage (sICH), and early neurological improvement (ENI) after treatment.

Results: Overall, 31 studies were included. There were no significant differences in excellent functional outcome (OR: 1.21, 95% CI: 0.99-1.47), good functional outcome (OR: 1.03, 95% CI: 0.82-1.30) and 90-day mortality (OR: 1.17, 95% CI: 0.84-1.62). Additionally, EVT led to higher sICH (OR: 1.64, 95% CI: 1.09-2.47) and better ENI (OR: 1.50, 95% CI: 1.02-2.19) compared to BMT. In individuals with M2 occlusion receiving EVT showed better excellent functional outcomes (OR: 1.48, 95% CI: 1.07-2.03). Those patients with PCA occlusion showed no significant difference in functional outcomes. In individuals with ACA occlusion, EVT resulted in reduced functional independence (OR: 0.55, 95% CI: 0.31-0.98). For NIHSS < 6, BMT achieved better functional independence compared to EVT (OR: 0.71, 95% CI: 0.51-0.98) and EVT showed higher sICH (OR: 3.44, 95% CI: 1.42-8.31).

Conclusion: For patients with AIS and DMVO occlusion, EVT fails to improve functional prognosis while increasing sICH incidence. More randomized controlled trials are needed in the future to confirm these results.

Objective: We attempted to evaluate the immediate high-grade squamous intraepithelial lesion-cervical intraepithelial neoplasia grade 2/3 or worse (HSIL-CIN2+/3+, hereafter referred to as CIN2+/3+) risk of specific human papillomavirus (HPV) genotype and form the precise risk-based triage strategy for atypical squamous cells of undetermined significance (ASC-US) women.

Methods: The clinical data of ASC-US women who underwent HPV genotyping testing and colposcopy were retrospectively reviewed. The distribution and CIN2+/3+ risks of specific HPV genotype were assessed by three approaches. The risk-based triage strategy was further established, and its efficacy in detecting CIN2+/3+ was estimated.

Results: Totally, 5553 ASC-US women including 3648 HPV-positive and 1905 HPV-negative were analysed. CIN2+/3+ were 662/319 cases, including 639/306 HPV-positive and 23/13 HPV-negative women. HPV16, HPV52, HPV58 and HPV18 were always among the top 5 ranking genotypes, no matter in HPV-positive women or in HPV-positive CIN2+/3+ cases. HPV16 and HPV33 carried the highest risk, while HPV73 and 26 carried the least risk for CIN2+/3+. Based on the immediate CIN2+/3+ risk of specific HPV genotype, 18 HPVs were divided into three risk-stratified groups. Only women infected with HPVs included in group A were necessary for immediate colposcopy. Compared with conventional strategy, this new risk-based strategy not only had higher specificity (CIN2+: p = .00; CIN3+: p = .01) and positive predictive value (CIN2+: p = .00; CIN3+: p = .03) for detecting CIN2+/3+, but also needed fewer colposcopies to identify each CIN2+/3+.

Conclusions: A new triage strategy for ASC-US women was successfully constructed based on CIN2+/3+ risks of 14 high-risk and 4 intermediate-risk HPVs, which could significantly reduce unnecessary colposcopies.

Background: Delayed gastric emptying (DGE) is a frequent complication of pancreatoduodenectomy (PD) and is associated with prolonged hospital stay, readmission, increased hospital costs and decreased quality of life. However, the pathophysiology of DGE remains unclear.

Methods: This is a retrospective study of patients who underwent PD for pancreatic or periampullary tumours. All these patients were operated between January 2012 and February 2023. The patients were divided into four groups according to the development of DGE after PD: No DGE, DGE grade A, DGE grade B and DGE grade C. The groups were compared in terms of outcomes and complications. We also analysed the preoperative and perioperative risk factors for DGE development.

Results: Between January 2012 and February 2023, a total of 250 patients underwent PD. These patients were divided into four groups: No DGE (n = 152); DGE grade A (n = 42); DGE grade B (n = 45); and DGE grade C (n = 11). The incidence of the postoperative pancreatic fistulas (POPFs) grade B/C was significantly higher in the DGE grade C group (p < .001), and the rates of post-pancreatectomy haemorrhage (p = .004) and reoperation (p < .001) were significantly higher in the DGE grade B/C groups. A significantly higher rate of grade III-IV Clavien-Dindo complications (p < .001), longer intensive care unit (p < .001) and longer hospital stays (p < .001) were observed in the DGE grade C group; and 90-day mortality (p < .001) and morbidity (p < .001) were significantly higher in the DGE grade B/C groups. Multivariate analysis demonstrated that the POPF grade B/C was a risk factor of DGE grade B/C (OR: 9.147; 95%CI: 4.125-20.281; p < .001).

Conclusions: POPF B/C is a risk factor for grade B/C DGE. Prevention of surgical complications and early treatment could contribute to the decreased incidence of DGE.

Aim: The primary objective of this study is to investigate the impact of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its functional receptor, fibroblast growth factor-inducible 14 (Fn14), on the process of vascular smooth muscle cell (VSMC) senescence.

Methods: Rat arterial VSMCs were cultured with angiotensin II to establish a model of premature senescence. The effects of TWEAK and Fn14 on senescent VSMCs were evaluated. Additionally, the role of p38 phosphorylation pathway in the effect of TWEAK on VSMCs senescence was assessed.

Results: Expressions of TWEAK and Fn14 were significantly elevated in senescent VSMCs. TWEAK activated the p38 phosphorylation pathway and promoted the SA-β-gal staining and P53 expression.

Conclusion: These preliminary findings suggest that the TWEAK/Fn14 axis may play a crucial role in promoting VSMC senescence.

The diagnoses of longitudinal melanonychia (LM) may be nail matrix nevus, etc. During excision, factors like small/pale lesions make it hard to define the boundary. Head - mounted magnifiers have limited magnification and intraoperative dermatoscopes are often unavailable. We used a DSLR camera to take and magnify pictures. First estimate the incision, then adjust. This method is recommended for doctors without intraoperative dermatoscopes.

Background: This study was aimed to explore the global burden and trends of Clostridioides difficile infections (CDI) associated diseases.

Methods: Data for this study were obtained from the Global Burden of Disease Study 2021. The burden of CDI was assessed using the age-standardized rates of disability-adjusted life years (ASR-DALYs) and deaths (ASDRs). Trends in the burden of CDI were presented using average annual percentage changes (AAPCs).

Results: The ASR-DALYs for CDI increased from 1.83 (95% UI: 1.53-2.18) per 100,000 in 1990 to 3.46 (95% UI: 3.04-3.96) per 100,000 in 2021, with an AAPC of 2.03% (95% CI: 1.67-2.4%). The ASDRs for CDI rose from 0.10 (95% UI: 0.08-0.11) per 100,000 in 1990 to 0.19 (95% UI: 0.16-0.23) per 100,000 in 2021, with an AAPC of 2.26% (95% CI: 1.74-2.79%). In 2021, higher burdens of ASR-DALYs (10.7 per 100,000) and ASDRs (0.53 per 100,000) were observed in high socio-demographic index (SDI) areas, and among age group over 70 years (31.62/100,000 for ASR-DALYs and 2.45/100,000 for ASDRs). During the COVID-19 pandemic, the global ASR-DALYs and ASDRs slightly decreased. However, in regions with low SDI, low-middle and middle SDI, those rates slightly increased.

Conclusion: The global burden of CDI has significantly increased, particularly in regions with high SDI and among individuals aged 70 years and above. During the COVID-19 pandemic period from 2020 to 2021, the burden of CDI further increased in regions with low, low-middle, and middle SDI. These findings underscore the need for increased attention and intervention, especially in specific countries and populations.

Objective: The prognosis for severe asthma is poor, and the current treatment options are limited. The methyl-CpG binding domain protein 2 (MBD2) participates in neutrophil-mediated severe asthma through epigenetic regulation. Neutrophil extracellular traps (NETs) play a critical role in the pathogenesis of severe asthma. This study aims to detect if MBD2 can reduce NETs formation and the potential mechanism in severe asthma.

Methods: A severe asthma model was established in C57BL/6 wild-type mice exposure to house dust mite (HDM), ovalbumin (OVA), and lipopolysaccharide (LPS). Enzyme-linked immunosorbent assay was used to measure the concentrations of IL-4, IL-17A, and IFN-γ in lung tissues. Flow cytometry was employed to determine the percentages of Th2, Th17, and Treg cells in lung tissues. Quantitative real-time polymerase chain reaction was utilized to assess the mRNA expression levels of MBD2, JAK2, and PAD4. Western blotting and immunofluorescence were conducted to detect the protein of MBD2, JAK2, PAD4, and CitH3. HL-60 cells were differentiated into neutrophil-like cells by culturing in a medium containing dimethyl sulfoxide and then stimulated with LPS. KCC-07, Ruxolitinib, and Cl-amidine were used to inhibit the expressions of MBD2, JAK2, and PAD4, respectively.

Results: Severe asthma mice were characterized by pulmonary neutrophilic inflammation and increased formation of neutrophil extracellular traps (NETs). The expression of MBD2, JAK2, and PAD4 was elevated in severe asthma mice. Inhibiting the expression of MBD2, JAK2, and PAD4 reduced NETs formation and decreased airway inflammation scores, total cell counts and neutrophil counts in BALF, and percentage of Th2 and Th17 cell in lung tissues, whereas increasing Treg cell counts. In both severe asthma mice and HL-60-differentiated neutrophil-like cells in vitro, inhibiting MBD2 reduced the mRNA and protein expression of JAK2 and PAD4, and inhibiting JAK2 reduced the expression of PAD4 mRNA and protein.

Conclusion: MBD2 regulates PAD4 expression through the JAK2 signaling pathway to promote NETs formation in mice with severe asthma. Further bench-based and bedside-based studies targeting the MBD2, PAD4, and JAK2 signaling pathways will help open new avenues for drug development of severe asthma.

Objective: Primary care general practitioners (GPs) play a crucial role in common skin diseases (CSDs) diagnosis and treatment for community residents. This study investigates their clinical diagnostic ability for CSDs and influencing factors among GPs in Shanghai.

Methods: In 2023, we recruited 5745 GPs in Shanghai, and online survey was conducted among 5745 GPs with written informed consents. Images of ten CSDs was used to evaluate the diagnostic ability among GPs, logistic regression (LR) analysis was applied to explore influencing factors in GPs with a good skin diseases diagnostic ability.

Results: The 5745 GPs included 1740 male (30.3%), the age ranged from 25 to 60 years with an average of age of 40.8 years. The total score for GSDs diagnostic ability ranged from 2 to 10, with a median of 7.5. In this study, GPs who have achieved ≥ 9 scores were identified as GPs with good diagnostic ability, with a prevalence of 26.7%. LR analysis indicated that GPs with 11 to 15 and over 15 years of work experience had a higher prevalence of good diagnostic ability compared with those with <5 years, the OR was 1.23 (95% CI: 1.02-1.48) and 1.25 (95% CI: 1.05-1.49) respectively. GPs with advanced studies [OR = 1.61, 95% CI:1.33-1.95] and work experience [OR = 1.39, 95% CI:1.20-1.61] in dermatology had a higher prevalence of good diagnostic ability.

Conclusion: The diagnostic ability for CSDs was good among GPs in Shanghai. GPs with more years of work, advanced studies and work experience in dermatology have better diagnostic abilities CSDs.

Background: Accumulating evidence has demonstrated that the long non-coding RNA (lncRNA) lymphocytic leukaemia deletion gene 1 (DLEU1) is abnormally overexpressed in many cancer types, including cervical cancer (CC). However, the potential clinical significance of DLEU1 in serum exosomes of patients with CC remains unclear.

Methods: The expression of serum exosomal DLEU1 was detected by quantitative real-time polymerase chain reaction (qRT-PCR). A receiver operating characteristic (ROC) curve was plotted to evaluate the clinical diagnostic efficacy of DLEU1. The Kaplan-Meier survival curve and Cox proportional hazards model were used to assess the effect of DLEU1 on postoperative recurrence, metastasis and prognosis among patients with CC.

Results: Our research showed that DLEU1 expression in the serum exosomes of patients with CC was significantly upregulated compared to that in patients with cervical intraepithelial neoplasia (CIN) and healthy controls (HCs) (both p < .001). DLEU1 relative expression was significantly correlated with tumour size, cervical invasion depth, pathological grade, International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node metastasis among patients with CC (p < .01 all). The combined detection of DLEU1, carbohydrate antigen 125 (CA-125) and squamous cell carcinoma (SCC) exhibited significantly higher diagnostic efficiency (p < .01). Furthermore, the overall survival (OS) and disease-free survival (DFS) of CC patients in the high DLEU1 expression group were markedly lower than those in the low DLEU1 expression group (both p < .01). Cox univariate and multivariate regression analyses indicated that DLEU1 was an independent risk factor for postoperative recurrence and metastasis in CC patients.

Conclusions: Our findings suggest that serum exosome DLEU1 has certain clinical value for diagnosing, monitoring recurrence and metastasis, and evaluating CC prognosis.