Objective To analyze the disease burden and trends of bladder cancer in China and globally from 1992 to 2021.  Methods Using the GBD 2021 database, the incidence, prevalence, mortality, and disability-adjusted life years (DALYs) rates of bladder cancer in China and globally from 1992–2021 were analyzed. Average annual percentage change (AAPC) was calculated using Joinpoint regression. Subgroup analyses by sex and age were conducted, and a Bayesian age-period-cohort (BAPC) model was used to predict trends in age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) for the next 15 years.  Results In 2021, China reported 106 000 new cases (ASIR: 5.14/100 000), 571 000 prevalent cases (age-standardized prevalence rate, ASPR: 26.61/100 000), 43 000 deaths (ASMR: 2.34/100 000), and a DALY rate of 45.31/100 000. From 1992–2021, China showed upward trends in ASIR and ASPR but declines in ASMR and DALYs, while global ASIR, ASMR, and DALYs decreased overall with slow ASPR growth. The peak cases in China and globally were both concentrated in the 65-79 age group, with a significantly higher burden on males than females. In China, smoking-related ASMR and ASDR exceeded global averages and rose, whereas high glucose-related indexes were lower and declined. Projections for 2021–2036 indicated that the global incidence and mortality rates would be rising, but ASIR/ASPR would be declining, while in China, the incidence rate would continue to rise, and the mortality rate will stabilize, with a significant increase in ASIR and a gradual decrease in ASPR.  Conclusion From 1992 to 2021, the incidence of bladder cancer in China has shown a continuous upward trend and is projected to persist in the future, with significant gender and age differences. Particular attention should be given to elderly males aged 85-89. The disease burden of bladder cancer attributable to smoking continues to rise, highlighting the urgent need to strengthen tobacco control policies.

ObjectiveUlcerative colitis is a prevalent immunoinflammatory disease. Th17/Treg cell imbalance and gut microbiota dysregulation are key factors in ulcerative colitis pathogenesis. The actin cytoskeleton contributes to regulating the proliferation, differentiation, and migration of Th17 and Treg cells. Wdr63, a gene containing the WD repeat domain, participates in the structure and functional modulation of actin cytoskeleton. Recent research indicates that WDR63 may serve as a regulator of cell migration and metastasis via actin polymerization inhibition. This article aims to explore the effect of Wdr63 deletion on Th17/Treg cells and ulcerative colitis. MethodsWe constructed Wdr63^-/- mice, induced colitis in mice using dextran sulfate sodium salt, collected colon tissue for histopathological staining, collected mesenteric lymph nodes for flow cytometry analysis, and collected healthy mouse feces for microbial diversity detection. ResultsCompared with wild-type colitis mice, Wdr63^-/- colitis mice had a more pronounced shortening of colonic tissue, higher scores on disease activity index and histological damage index, Treg cells decreased and Th17 cells increased in colonic tissue and mesenteric lymph nodes, a lower level of anti-inflammatory cytokine IL-10, and a higher level of pro-inflammatory cytokine IL-17A. In addition, WDR63 has shown positive effects on maintaining intestinal microbiota homeostasis. It maintains the balance of Bacteroidota and Firmicutes, promoting the formation of beneficial intestinal bacteria linked to immune inflammation. ConclusionWdr63 deletion aggravates ulcerative colitis in mice, WDR63 inhibits colonic inflammation likely by regulating Th17/Treg balance and maintains intestinal microbiota homeostasis.

This study was aimed at investigating infections with Giardia and Cryptosporidium in Ochotona curzoniae in Zoige County,Sichuan Province.O.curzoniae were captured in five townships of Zoige County(Dazhasi,Axi,Hongxing,Tangke,and Maixi)between March and December of 2023.DNA from the gastrointestinal contents was subjected to nested PCR to amplify Giardia bg,gdh,and tpi genes,and the Cryptosporidium SSU rRNA gene.The sequences of PCR-PCR products were analyzed and compared.Phylogenetic trees were constructed to determine the protozoa species and genotypes.A total of 114 O.curzoniae animals were captured,among which 44 samples showed bg gene positivity,and 14 samples showed gdh gene positivity for Giardia.The total detection rate was 43.9％(50/114),and two assemblages were detected(assem-blage E and a new assemblage tentatively termed assemblage OC1);the positivity rate for Cryptosporidium was 7.0％(8/114),and three new genotypes were observed.Mixed infection with Cryptosporidium and Giardia was present in some sam-ples,with a detection rate of 3.5％(4/114).Giardia lamblia and Giardia sp.(REG-1,REG-2)were prevalent in O.curzoni-ae in Zoige County in Sichuan province;assemblage E was the dominant assemblage,and the new assemblage OC1 was pres-ent;and Cryptosporidium sp.(REG-1,REG-2,and REG-3)were identified.In summary,future monitoring of Giardia and Cryptosporidium should be further strengthened in Zoige to provide detailed data for promoting local public health.

Objective:the subclavian approach without insufflation, the ability of assistants to master the technique of holding the endoscope plays a crucial role in the thoroughness and smoothness of the surgery. The author has summarized the "six-marker method", which adjusts the mirror holding technique based on surgical steps and surgical operation goals, so that assistants can quickly grasp the essentials of mirror holding and assist the chief surgeon in completing the surgery smoothly. This method has wide applicability and feasibility, which can achieve good coordination between the surgeon and the mirror holder, shorten the surgical time and break in period. It is worth promoting and applying in clinical practice.

Objective:To evaluate the efficacy and safety of baricitinib combined with ruxolitinib cream in the treatment of progressive nonsegmental vitiligo.Methods:Clinical data were retrospectively collected from patients with progressive nonsegmental vitiligo in Boao Super Hospital. All the patients were treated with oral baricitinib daily (2 mg/day for patients weighing ≤ 50 kg; 4 mg/day for those > 50 kg) in combination with topical application of ruxolitinib cream twice daily for 24 consecutive weeks. Disease severity was assessed using the facial vitiligo area scoring index (F-VASI) and total body VASI (T-VASI) at baseline, week 12, and week 24. Adverse reactions were monitored throughout the treatment course.Results:Six patients with progressive nonsegmental vitiligo were collected, including 3 males and 3 females, aged 26 - 42 years, with the disease duration ranging from 0.5 to 25 years. At week 12, 3 patients achieved a 50% ~ < 75% improvement in facial vitiligo lesions (F-VASI 50), 1 patient achieved F-VASI 75 (75% ~ < 90% improvement), and 1 patient achieved T-VASI 50; at week 24, 4 patients achieved F-VASI 50, 1 patient achieved F-VASI 75, 1 patient achieved F-VASI 90 (≥ 90% improvement), and 3 patients achieved T-VASI 50. During the treatment, upper respiratory infection occurred in 1 patient, acne in 1 patient, pruritus in 2 patients, elevation of total cholesterol levels in 2 patients, and increase of high-density lipoprotein levels in 2 patients. No severe adverse events were observed during the treatment.Conclusion:The combination therapy with baricitinib and ruxolitinib cream may have potential efficacy and safety in the treatment of progressive nonsegmental vitiligo.

Objective:To investigate the prevalence of sexual drug use in men who have sex with men (MSM) in Chengdu and analyze the relationship between depression and sexual drug use.Methods:A total of 1 277 MSM were recruited between November 2021 and May 2022. Questionnaire was used to collect information about their demographic characteristics, depression status and sexual drug use behavior. Univariate and multivariate logistic regression models were used to analyze the relationship between depression and sexual drug use.Results:In the 1 277 MSM, assessment identified 503 mild depression cases (39.4%), 196 moderate depression cases (15.3%) and 171 severe depression cases (13.4%) and 444 MSM (34.8%) reported sexual drug use in the past 6 months. Multivariate logistic regression models showed that compared with non-depression, mild depression (a OR=1.67,95% CI:1.24-2.23), moderate depression (a OR=1.50,95% CI: 1.02-2.19) and severe depression (a OR=1.56,95% CI:1.04-2.32) were positively associated with sexual drug use. Conclusions:The prevalence of depression and sexual drug use were high in MSM in Chengdu. There was a positive correlation between depression and sexual drug use. It is necessary to pay close attention to depression and sexual drug use and conduct targeted intervention in MSM.

Objective:the subclavian approach without insufflation, the ability of assistants to master the technique of holding the endoscope plays a crucial role in the thoroughness and smoothness of the surgery. The author has summarized the "six-marker method", which adjusts the mirror holding technique based on surgical steps and surgical operation goals, so that assistants can quickly grasp the essentials of mirror holding and assist the chief surgeon in completing the surgery smoothly. This method has wide applicability and feasibility, which can achieve good coordination between the surgeon and the mirror holder, shorten the surgical time and break in period. It is worth promoting and applying in clinical practice.

This research aims to construct a stable epithelial cell senescence model for screening and e-valuation of senolytics.We explored the optimal conditions for doxorubicin-induced senescence of non-transformed epithelial cells MCF 10A,including the optimal induction concentration,the optimal inter-vention time,and the optimal senescence duration,and confirmed the feasibility of MCF 10A as an epi-thelial senescence model by multiple ways.The optimal condition for Doxorubicin-induced senescence of MCF 10A cells was treatment with 0.6 μmol/L Doxorubicin for 16 h to achieve the best senescence state on the 8th day.Under the optimal induction conditions,the positive rate of senescence-associated β-gal-actosidase(SA-β-gal)staining in the treated group reached 97％.At the same time,biochemical results of detecting the expression of mRNA,proteins,and immunofluorescence demonstrated that the expression levels of senescence-associated secretory phenotype(SASP),p16,p21 and p53 in the treated group were significantly higher than those in the control cells,and Lamin B1 was significantly decreased(P＜0.001),which were consistent with the specific characteristics of senescence.In summary,an epithelial senescence model was successfully induced in MCF 10A cells by Doxorubicin in this study,which will promote the screening of senolytics for senescent epithelial cells.

BACKGROUND: Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke. METHODS: This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes. RESULTS: Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1-Q3: 20-88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12-0.49, P  <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11-0.41, P  <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08-0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06-0.50, P  <0.01). CONCLUSIONS: Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes. REGISTRATION ClinicalTrials.gov , NCT03222024.
Humans ; Male ; Female ; Prospective Studies ; Ischemic Stroke/mortality* ; Aged ; Middle Aged ; Aged, 80 and over ; Stroke ; Brain Ischemia

Hematologic malignancies, including leukemia, lymphoma, and multiple myeloma, are hazardous diseases characterized by the uncontrolled proliferation of cancer cells. Dysregulated cell cycle resulting from genetic and epigenetic abnormalities constitutes one of the central events. Importantly, cyclin-dependent kinases (CDKs), complexed with their functional partner cyclins, play dominating roles in cell cycle control. Yet, efforts in translating CDK inhibitors into clinical benefits have demonstrated disappointing outcomes. Recently, mounting evidence highlights the emerging significance of WEE1 G2 checkpoint kinase (WEE1) to modulate CDK activity, and correspondingly, a variety of therapeutic inhibitors have been developed to achieve clinical benefits. Thus, WEE1 may become a promising target to modulate the abnormal cell cycle. However, its function in hematologic diseases remains poorly elucidated. In this review, focusing on hematologic malignancies, we describe the biological structure of WEE1, emphasize the latest reported function of WEE1 in the carcinogenesis, progression, as well as prognosis, and finally summarize the therapeutic strategies by targeting WEE1.
Humans ; Protein-Tyrosine Kinases/physiology* ; Hematologic Neoplasms/drug therapy* ; Cell Cycle Proteins/antagonists & inhibitors* ; Nuclear Proteins/antagonists & inhibitors* ; Cyclin-Dependent Kinases ; Molecular Targeted Therapy ; Animals