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.

OBJECTIVE: To explore the therapeutic effects and underlying mechanisms of Dendrobium officinale (Tiepi Shihu) extract (DOE) on insomnia. METHODS: Forty-two male Sprague-Dawley rats were randomly divided into 6 groups (n=7 per group): normal control, model control, melatonin (MT, 40 mg/kg), and 3-dose DOE (0.25, 0.50, and 1.00 g/kg) groups. Rats were raised in a strong-light (10,000 LUX) and -noise (>80 db) environment (12 h/d) for 16 weeks to induce insomnia, and from week 10 to week 16, MT and DOE were correspondingly administered to rats. The behavior tests including sodium pentobarbital-induced sleep experiment, sucrose preference test, and autonomous activity test were used to evaluate changes in sleep and emotions of rats. The metabolic-related indicators such as blood pressure, blood viscosity, blood glucose, and uric acid in rats were measured. The pathological changes in the cornu ammonis 1 (CA1) region of rat brain were evaluated using hematoxylin and eosin staining and Nissl staining. Additionally, the sleep-related factors gamma-aminobutyric acid (GABA), glutamate (GA), 5-hydroxytryptamine (5-HT), and interleukin-6 (IL-6) were measured using enzyme linked immunosorbent assay. Finally, we screened potential sleep-improving receptors of DOE using polymerase chain reaction (PCR) array and validated the results with quantitative PCR and immunohistochemistry. RESULTS: DOE significantly improved rats' sleep and mood, increased the sodium pentobarbital-induced sleep time and sucrose preference index, and reduced autonomic activity times (P<0.05 or P<0.01). DOE also had a good effect on metabolic abnormalities, significantly reducing triglyceride, blood glucose, blood pressure, and blood viscosity indicators (P<0.05 or P<0.01). DOE significantly increased the GABA content in hippocampus and reduced the GA/GABA ratio and IL-6 level (P<0.05 or P<0.01). In addition, DOE improved the pathological changes such as the disorder of cell arrangement in the hippocampus and the decrease of Nissel bodies. Seven differential genes were screened by PCR array, and the GABA_A receptors (Gabra5, Gabra6, Gabrq) were selected for verification. The results showed that DOE could up-regulate their expressions (P<0.05 or P<0.01). CONCLUSION DOE demonstrated remarkable potential for improving insomnia, which may be through regulating GABA_A receptors expressions and GA/GABA ratio.
Animals ; Dendrobium/chemistry* ; Rats, Sprague-Dawley ; Male ; Sleep Initiation and Maintenance Disorders/blood* ; Plant Extracts/therapeutic use* ; Receptors, GABA-A/metabolism* ; Noise/adverse effects* ; Light/adverse effects* ; gamma-Aminobutyric Acid/metabolism* ; Sleep/drug effects* ; Rats ; Receptors, GABA/metabolism*

Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, we demonstrated that a GsMTx4-based 17-residue peptide, which we call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.

Objective:To investigate the effectiveness of methylene blue in pain management after costal cartilage removal.Methods:A prospective, randomized controlled trial was conducted from June 2023 to March 2024. Female patients undergoing rhinoplasty with autologous costal cartilage transplantation were randomly divided into a methylene blue group and a control group. Before costal cartilage harvesting, patients in the methylene blue group received a 5 ml injection of 0.1% methylene blue solution into the skin and subcutaneous tissue of the costal cartilage donor site at the lower edge of the seventh costal cartilage or below the breast contour. Patients in the control group received an equal volume of normal saline injected into the same area. Postoperative management included routine observation and pain control (using oral analgesics and topical analgesia). Pain scores were assessed 24 hours after surgery using a visual analog scale (VAS, 0-10 points, higher scores indicate more severe pain) and a numerical rating scale (NRS, 0-10 points, higher scores indicate more severe pain), as well as the frequency of oral analgesics. Patients were followed up for postoperative complications within one month after surgery, and patient satisfaction with pain control was assessed using a self-made 5-point questionnaire (higher scores indicate greater patient satisfaction). Quantitative data were compared between groups using the independent sample t-test; qualitative data were compared between groups using the chi-square test. P<0.05 was considered statistically significant. Results:A total of 112 female patients were enrolled. Fifty-six patients were in the methylene blue group, aged (35.4 ± 5.6) years (range, 18-55 years), and 56 patients were in the control group, aged (36.1 ± 6.0) years (range, 19-54 years). The methylene blue group had significantly lower oral analgesic use 24 hours after surgery than the control group [(1.5±0.5) times vs. (4.7±1.2) times], with statistically significant differences ( P<0.05). The methylene blue group also had significantly lower VAS scores (3.2±1.2 vs. 5.8±1.3) and NRS scores (3.5±1.0 vs. 6.2±1.1) 24 hours after surgery than the control group ( P<0.05). At one-month follow-up, the incidence of postoperative complications in the methylene blue group was significantly lower than that in the control group [10.7% (6/56) vs. 21.4% (12/56)]. Patient satisfaction in the methylene blue group was significantly higher than that in the control group [4.5 ± 0.6 vs. 3.2 ± 0.8]. The differences were statistically significant ( P< 0.05). No serious adverse reactions were observed in either group. Conclusion:Methylene blue has a good analgesic effect after costal cartilage transplantation, reducing the need for analgesics, and no significant adverse reactions were observed.

OBJECTIVE To improve the quality standard of Zhuang medicine Yingbupu （Aralia armata）. METHODS A total of 23 batches of Yingbupu （A. armata） were studied. Their macroscopic characteristics and powder microscopic features were observed. TLC was employed for the qualitative identification of oleanolic acid and araloside A. Items such as water content， total ash， acid-insoluble ash， and ethanol-soluble extract were determined according to the methods specified in the 2020 edition of the Chinese Pharmacopoeia （part Ⅳ）. UPLC fingerprint was established for 23 batches of samples by using Similarity Evaluation System for Chromatographic Fingerprints of Traditional Chinese Medicine （2012 edition）， and the contents of oleanolic acid and araloside A were determined. RESULTS The powder microscopic characteristics of the medicinal material were distinctive. Oleanolic acid and araloside A were detected by TLC in all 23 batches. Among the 23 batches of samples， the content ranges of moisture， total ash， acid-insoluble ash， and ethanol-soluble extract were 6.9% to 10.4%， 1.8% to 6.8%， 0.1% to 1.9%， and 2.8% to 8.4%， respectively. Based on the UPLC fingerprint， a total of 15 common peaks were obtained， and 9 of these common peaks were identified. The content ranges of oleanolic acid and araloside A in the 23 batches of samples were 0.86% to 2.69% and 0.16% to 1.10%， respectively. CONCLUSIONS This study has added items such as moisture and total ash content fingerprint， TLC identification. A preliminary quality standard has been established for the medicinal material of Yingbupu （A. armata）， stipulating that the moisture content should not exceed 11.0%， the total ash content should not exceed 5.0%， the acid-insoluble ash content should not exceed 2.5%， the ethanol-soluble extract（No. content should not be less than 4.0%， and the contents of zyyzdxk-2023165） oleanolic acid and araloside A should not be less than 1.00% and 0.45%（ calculated by a dried basis）， respectively.

Objective: To explore the relationship between visual acuity and physical fitness of university freshmen, so as to provide reference for myopia prevention and control for freshmen. Methods: From October to November 2022, 2 160 college freshman without majoring in public safety administration, selected from Guangxi Police College in 2022 by using the stratified cluster random sampling method, were reviewed for the results of visual acuity test and physical fitness scores. The physical fitness indices were evaluated by using the Z scores of physical fitness test scores, and the strength of association between the level of physical fitness index and myopia was analyzed by using Logistic regression model. Results: Among 2 160 college freshman without majoring in public safety administration, 917 (42.5%) students were diagnosed screening myopia, including 66 (3.1%) cases of high myopia, 383 (17.7%) cases of moderate myopia and 468 (21.7%) cases of mild myopia. The differences in the distribution of visual acuity tests among students with different physical fitness indices, body mass index, and gender were statistically significant ( Z/H=54.50, 49.53, 15.51, P <0.01). Low level and low middle level physical fitness indices were associated with screening myopia among freshmen[ OR (95% CI )=2.81(1.93-4.08),1.87(1.38-2.54)], and low level physical fitness indexes were associated with high myopia [ OR (95% CI )=7.22(2.33-22.32)] ( P <0.01). Conclusions Screening myopia among college freshman without majoring in public safety administration is related to physical fitness, and low level and low middle level physical fitness index are risk factors for myopia. Improving the level of physical fitness might be effective in preventing myopia.

Objective To investigate the roles of glucose-regulated protein 75(GRP75)and voltage-dependent anion channel 1(VDAC1)in heroin-induced arrhythmia.Methods Based on transcriptomic data from primary myocardial cells treated with heroin and the GSE31821 dataset from the Gene Expression Omnibus(GEO),differentially expressed genes(DEGs)were identified using R software.Enrichment analysis of DEGs was performed.The protein-protein interaction(PPI)network was constructed using STRING database,and key genes were selected using Cytoscape.Molecular docking of key genes was performed using HDOCK,followed by in vivo valida-tion.A total of 60 SD rats were randomly divided into control,model,model+7 d,model+14 d,and model+21 d groups.A rat model of heroin addiction was established,and the expression levels of DEGs in myocardial tissue were assessed using immunohistochemical staining and quantitative real-time PCR.Results A total of 51 DEGs primarily enriched in muscle cell development,myofibrils,actin binding,arrhythmic right ventricular cardiomyopathy,calcium signaling,and apoptosis pathways were identified.Based on the PPI and Cytoscape analyses,GRP75 and VDAC1 were identified as key genes.Molecular docking indicated a strong interaction between GRP75 and VDAC1,which form a stable complex.The results of immunohistochemical staining and qRT-PCR showed that the expression levels of GRP75 and VDAC1 were significantly increased in the model group compared to those in the control group(P＜0.05),and their expres-sion increased(P＜0.05)with the intervention period of heroin in a time-dependent manner.Conclusion GRP75 and VDAC1 may con-tribute to heroin-induced arrhythmogenesis.

Objective : To explore the expression profile of core 1 β1,3-galactosyltransferase 1(C1GALT1) in glioblastoma(GBM) and to elucidate its impact on the initiation and progression of GBM. Methods : The expression levels and prognostic significance of C1GALT1 in GBM were analyzed using the GEPIA and CGGA databases. Two representative glioblastoma cells(U251 and LN18) were selected to construct C1GALT1-knockdown cell lines and performed in vitro experiments. The Cell Counting Kit-8(CCK-8) and Transwell assays were employed to evaluate the impact of C1GALT1 on proliferation, migration and invasion of GBM cells. Transcriptome data were analyzed to identify potential signaling pathways. Senescence β-Galactosidase Staining Kit was used to detect β-galactosidase activity. Results : nalysis of GEPIA and CGGA databases revealed that C1GALT1 was significantly upregulated in GBM tissues compared to adjacent non-cancerous tissues (P < 0. 05) , and its high expression was associated with poor prognosis of patients (P < 0. 000 1) . The CCK-8 experiment demonstrated a significant reduction in prolifera- tion rate following C1GALT1 knockdown (P < 0. 05) . Transwell assay showed that cell migration and invasion de- creased after C1GALT1 was knocked down ( P < 0. 001) . Transcriptome sequencing and senescence β-galactosi- dase staining showed that C1GALT1 was involved in the cellular senescence signaling pathway , and the activity of β-galactosidase associated with cellular senescence significantly increased after C1GALT1 was knocked down(P < 0. 05) . Conclusion C1GALT1 is overexpressed in GBM tissues and may promote the proliferation , migration and invasion of GBM cells by inhibiting cellular senescence .

OBJECTIVE To evaluate the efficacy,safety and economics of the centrally procured generic versus original esomeprazole in the treatment of acute non-variceal upper gastrointestinal bleeding(ANVUGIB).METHODS A retrospective collection of real-world clinical data was conducted for ANVUGIB patients who received treatment at Shenzhen People's Hospital and University of Hong Kong-Shenzhen Hospital from January 2018 to March 2024.Patients were divided into imported original drug group(original drug group,221 cases)and centrally procured generic drug group(generic drug group,75 cases)according to the types of drug used.Propensity score matching(PSM)was performed at a ratio of 3∶1 to compare the clinical efficacy,safety and economics between the two groups.RESULTS Totally 241 patients were included after PSM,with 170 in the original drug group and 71 in the generic drug group.There were no significant differences between the two groups in terms of rebleeding rate,rate of second endoscopic intervention,blood transfusion rate,length of hospital stay,mortality due to gastrointestinal bleeding,30-day readmission due to rebleeding,and overall survival rate(P＞0.05).The incidence of adverse events among all patients in both groups also showed no statistically significant difference(P＞0.05);furthermore,the adverse events reported by the respective hospitals to the National Center for ADR Monitoring were comparable between the two groups.After PSM,the median total drug cost and high-dose esomeprazole cost in the generic drug group were significantly lower than those in the original drug group,while the median nursing fee and bed fee were significantly higher than those in the original drug group(P＜0.05).There was no statistically significant difference between the two groups in terms of median total hospitalization expenses,total treatment costs,laboratory fees,examination fees,material costs,or consultation fees(P＞0.05).CONCLUSIONS The clinical efficacy and safety of centrally procured generic esomeprazole in the treatment of ANVUGIB are comparable to those of the original drug,and it is more economical.

Objective:To investigate the effectiveness of methylene blue in pain management after costal cartilage removal.Methods:A prospective, randomized controlled trial was conducted from June 2023 to March 2024. Female patients undergoing rhinoplasty with autologous costal cartilage transplantation were randomly divided into a methylene blue group and a control group. Before costal cartilage harvesting, patients in the methylene blue group received a 5 ml injection of 0.1% methylene blue solution into the skin and subcutaneous tissue of the costal cartilage donor site at the lower edge of the seventh costal cartilage or below the breast contour. Patients in the control group received an equal volume of normal saline injected into the same area. Postoperative management included routine observation and pain control (using oral analgesics and topical analgesia). Pain scores were assessed 24 hours after surgery using a visual analog scale (VAS, 0-10 points, higher scores indicate more severe pain) and a numerical rating scale (NRS, 0-10 points, higher scores indicate more severe pain), as well as the frequency of oral analgesics. Patients were followed up for postoperative complications within one month after surgery, and patient satisfaction with pain control was assessed using a self-made 5-point questionnaire (higher scores indicate greater patient satisfaction). Quantitative data were compared between groups using the independent sample t-test; qualitative data were compared between groups using the chi-square test. P<0.05 was considered statistically significant. Results:A total of 112 female patients were enrolled. Fifty-six patients were in the methylene blue group, aged (35.4 ± 5.6) years (range, 18-55 years), and 56 patients were in the control group, aged (36.1 ± 6.0) years (range, 19-54 years). The methylene blue group had significantly lower oral analgesic use 24 hours after surgery than the control group [(1.5±0.5) times vs. (4.7±1.2) times], with statistically significant differences ( P<0.05). The methylene blue group also had significantly lower VAS scores (3.2±1.2 vs. 5.8±1.3) and NRS scores (3.5±1.0 vs. 6.2±1.1) 24 hours after surgery than the control group ( P<0.05). At one-month follow-up, the incidence of postoperative complications in the methylene blue group was significantly lower than that in the control group [10.7% (6/56) vs. 21.4% (12/56)]. Patient satisfaction in the methylene blue group was significantly higher than that in the control group [4.5 ± 0.6 vs. 3.2 ± 0.8]. The differences were statistically significant ( P< 0.05). No serious adverse reactions were observed in either group. Conclusion:Methylene blue has a good analgesic effect after costal cartilage transplantation, reducing the need for analgesics, and no significant adverse reactions were observed.