Studies on specific transient receptor potential melastatin 2 (TRPM2) channel inhibitors can deepen our understanding of the pathological mechanism of related diseases, and allow discovery of novel, effective targets and drugs for therapy. The development of TRPM2 channel inhibitors can be broadly classified into four categories with distinct characteristics: reutilization and structural modification of homologous ion channel modulators to produce a diverse array of TRPM2 channel inhibitors with strong inhibitory effects; TRPM2 channel inhibitors based on channel gating mechanism with high specificity; inhibitors identified through high-throughput screening with novel chemical structures; inhibitors developed from natural antioxidants with higher safety. In recent years, the application of computer-aided drug design has significantly accelerated the development of TRPM2 channel inhibitors. Several promising compounds such as ZA18, A1 and D9 have been discovered, and it is expected that more potent and selective TRPM2 channel inhibitor scaffolds will be discovered in the future. This article reviews the advances on the studies of TRPM2 channel inhibitors, aiming to provide insights for further research and clinical application of TRPM2 channel inhibitors.
TRPM Cation Channels/antagonists & inhibitors* ; Humans ; Drug Design

Globally, over 300 million surgeries are performed each year, and more than 50% of surgeries involve patients aged 65 and older. Aging poses significant challenges to perioperative brain health, as the deterioration of brain structure and function increases susceptibility to postoperative neurological complications. Protecting perioperative brain health remains a worldwide clinical challenge. With senescence, the brain undergoes a progressive decline in homeostasis across various molecular, cellular, and regional functions. Anesthetics and surgical stimuli may accelerate the disruption of brain homeostasis and exacerbate age-related neurodegeneration. This review provides a framework for understanding how anesthesia and surgery can affect brain health in the aging population and contribute to postoperative neurological complications, with a particular focus on perioperative neurocognitive disorder.

Objective A randomized controlled trial was conducted on colonoscopy inpatient and outpatients to compare the efficacy and safety of water exchange(WE)colonoscopy and CO2 convention insufflation colonoscopy in elderly patients.Methods 340 patients underwent fully sedated colonoscopy were randomly divided into two groups according to colonoscopy with either WE colonoscopy group(WE group)and CO2 insufflation colonoscopy group(CO2 group).The two groups were compared in terms of Boston bowel preparation scale(BBPS),withdrawal time,cecal intubation time,cecal intubation success rate,abdominal compression,willingness to repeat,polypdetectionrate(PDR),adenoma detection rate(ADR),and safety.Results The cecal intubation success rate was significantly higher in WE group(100.0%)compared with CO2 group(96.5%),the difference was statistically significant(P=0.013).The average cecal intubation time of WE group was(10.50±1.79)min,which was longer than that of CO2 group(7.55±1.50)min,and the difference was statistically significant(P<0.01).Comparison of withdrawal time and BBPS between the two groups,the differences were not statistically significant(P>0.05).The abdominal pressure rate was lower in WE group(5.9%)compared with CO2 group(13.5%),the difference was statistically significant(P=0.017).The rate of willingness to re-examination in the WE group was 98.2%,which was significantly higher than the 93.5%in the CO2 group.The PDR in WE group(80.6%)was higher than that in CO2 group(70.6%),the ADR in WE group(67.1%)was higher than that in CO2 group(50.6%),the differences were statistically significant(P<0.05).Multivariate Logistic regression analysis showed that WE group was an effective factor in improving ADR(O＾R=2.027,P<0.01).The overall adverse events were less than 3%,with no difference between the two groups(P=1.000).Conclusion The use of WE colonoscopy has a better improved efficacy in elderly patients,and safety should be ensured by individualized assessment of the patient's co-morbidities,bowel preparation tolerance,and willingness prior to the procedure.

Diabetic foot ulcer(DFU)is one of the severe complications of diabetes mellitus,which often leads to amputation and seriously impairs patients' quality of life.It has complex etiology,involving vascular disease,neuropathy,and infection,etc.,and western medical treatment options are limited.In traditional Chinese medicine(TCM),DFU is classified as"tuoju"(gangrene of the extremities).Simiao Yong'an Decoction,a commonly used formula,has demonstrated clinical effects in improving blood flow,repairing nerves,controlling infection,and promoting wound healing.This article reviewed the TCM pathogenesis of DFU and the clinical and experimental research progress of Simiao Yong'an Decoction,aiming to provide a scientific basis for its treatment.

Objective To explore the effect of sitagliptin and metformin combined with zoledronic acid in the treatment of type 2 diabetes mellitus(T2DM)complicated with osteoporosis(OP)on the levels of glucose and lipid metabolism and bone metabolism in patients.Methods Patients with T2DM combined with OP admitted to Nantong Second People's Hospital from January 2021 to January 2024 were selected as the research subjects and randomly divided into the combined group(sitagliptin and metformin combined with zoledronic acid)and the control group(zoledronic acid only).After 6 months of treatment,the clinical efficacy,glucose and lipid metabolism indicators[fasting blood glucose(FBG),2-hour postprandial blood glucose(2hPG),glycated hemoglobin(HbA1c),total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C)],bone metabolism indicators[osteoprotegerin(OPG),bone-specific alkaline phosphatase(BALP),osteocalcin(OC)]levels,changes in bone density,and incidence of adverse reactions were compared between the two groups before and after treatment.Results A total of 120 patients were included,with 60 patients in each group.After treatment,the total effective rate of the combination group was 93.33％,significantly higher than the control group's 73.33％(P＜0.05).The levels of FBG,2hPG,HbA1c,TC,TG,and LDL-C in two groups were significantly lower than those before treatment,while the levels of HDL-C,OPG,BALP,OC,and bone density in the femoral neck and lumbar spine were significantly higher than before treatment(P＜0.05);and all indicators of the combined group were better than those of the control group(P＜0.05).There was no statistically significant difference in the total incidence of adverse reactions between the two groups(P＞0.05).Conclusion Sitagliptin and metformin combined with zoledronic acid in the treatment of patients with T2DM complicated with OP is more effective in regulating their glycolipid metabolism and bone metabolism levels,increasing bone density,improving therapeutic effects,and it has better safety than zoledronic acid alone.

Objective To explore the effect of sitagliptin and metformin combined with zoledronic acid in the treatment of type 2 diabetes mellitus(T2DM)complicated with osteoporosis(OP)on the levels of glucose and lipid metabolism and bone metabolism in patients.Methods Patients with T2DM combined with OP admitted to Nantong Second People's Hospital from January 2021 to January 2024 were selected as the research subjects and randomly divided into the combined group(sitagliptin and metformin combined with zoledronic acid)and the control group(zoledronic acid only).After 6 months of treatment,the clinical efficacy,glucose and lipid metabolism indicators[fasting blood glucose(FBG),2-hour postprandial blood glucose(2hPG),glycated hemoglobin(HbA1c),total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C)],bone metabolism indicators[osteoprotegerin(OPG),bone-specific alkaline phosphatase(BALP),osteocalcin(OC)]levels,changes in bone density,and incidence of adverse reactions were compared between the two groups before and after treatment.Results A total of 120 patients were included,with 60 patients in each group.After treatment,the total effective rate of the combination group was 93.33％,significantly higher than the control group's 73.33％(P＜0.05).The levels of FBG,2hPG,HbA1c,TC,TG,and LDL-C in two groups were significantly lower than those before treatment,while the levels of HDL-C,OPG,BALP,OC,and bone density in the femoral neck and lumbar spine were significantly higher than before treatment(P＜0.05);and all indicators of the combined group were better than those of the control group(P＜0.05).There was no statistically significant difference in the total incidence of adverse reactions between the two groups(P＞0.05).Conclusion Sitagliptin and metformin combined with zoledronic acid in the treatment of patients with T2DM complicated with OP is more effective in regulating their glycolipid metabolism and bone metabolism levels,increasing bone density,improving therapeutic effects,and it has better safety than zoledronic acid alone.

Objective A randomized controlled trial was conducted on colonoscopy inpatient and outpatients to compare the efficacy and safety of water exchange(WE)colonoscopy and CO2 convention insufflation colonoscopy in elderly patients.Methods 340 patients underwent fully sedated colonoscopy were randomly divided into two groups according to colonoscopy with either WE colonoscopy group(WE group)and CO2 insufflation colonoscopy group(CO2 group).The two groups were compared in terms of Boston bowel preparation scale(BBPS),withdrawal time,cecal intubation time,cecal intubation success rate,abdominal compression,willingness to repeat,polypdetectionrate(PDR),adenoma detection rate(ADR),and safety.Results The cecal intubation success rate was significantly higher in WE group(100.0%)compared with CO2 group(96.5%),the difference was statistically significant(P=0.013).The average cecal intubation time of WE group was(10.50±1.79)min,which was longer than that of CO2 group(7.55±1.50)min,and the difference was statistically significant(P<0.01).Comparison of withdrawal time and BBPS between the two groups,the differences were not statistically significant(P>0.05).The abdominal pressure rate was lower in WE group(5.9%)compared with CO2 group(13.5%),the difference was statistically significant(P=0.017).The rate of willingness to re-examination in the WE group was 98.2%,which was significantly higher than the 93.5%in the CO2 group.The PDR in WE group(80.6%)was higher than that in CO2 group(70.6%),the ADR in WE group(67.1%)was higher than that in CO2 group(50.6%),the differences were statistically significant(P<0.05).Multivariate Logistic regression analysis showed that WE group was an effective factor in improving ADR(O＾R=2.027,P<0.01).The overall adverse events were less than 3%,with no difference between the two groups(P=1.000).Conclusion The use of WE colonoscopy has a better improved efficacy in elderly patients,and safety should be ensured by individualized assessment of the patient's co-morbidities,bowel preparation tolerance,and willingness prior to the procedure.

Objective To investigate the correlation between neuropeptide S receptor(NPSR)single nucleotide polymorphism(SNP)(rs323917,rs323920,rs323922,rs2530547,rs324957)and primary insomnia(PI).Methods A total of 157 patients diagnosed with PI in the outpatient department of Center of Sleep Medicine,Gansu Provincial People's Hospital from December 2016 to May 2019 were selected as PI group,and 133 healthy physical examination subjects during the same period were selected as control group.Venous blood samples were collected and DNA,polymerase chain reaction(PCR)amplification and agarose gel electrophoresis were extracted.rs323917,rs323920,rs323922,rs2530547,rs324957 single nucleotide loci were genotypized by target site sequencing.Meanwhile,standard polysomnosis monitoring was performed to analyze the correlation between gene polymorphism and PI.Results There were no significant differences in the genotype distribution of NPSR SNP sites(rs323917,rs323920,rs323922,rs2530547)and allele frequency and rs324957 allele frequency between two groups(P＞0.05).There was significant difference in genotype distribution of rs324957(P=0.034).There was no significant difference in the frequency of different haplotypes between two groups(P＞0.05).Conclusion The expression of rs324957 SNP genotypes in NPSR may be related to PI,and AG genotype is dominant.

An improved U-Net model(channel attention module U-Net,CAMU-Net)is proposed to achieve precise segmentation of retinal vessels.CAMU-Net model enhances its understanding of regional features by employing residual enhancement convolution to extract important information from the regions,improves the global feature acquisition capability by introducing feature refinement module to promote feature extraction,realizes precise segmentation by adding channel attention module to capture image features accurately,and enhances its capability to perceive target boundaries and details through a multi-scale feature fusion structure.The ablation study on the DRIVE dataset validates the role of each module in retinal vessel segmentation.The comparison with other mainstream network models on DRIVE and STARE datasets verify that CAMU-Net model is superior to other models.

Objective This study aimed to investigate the factors influencing the personal burden rate incerebral ische-mic patients,compare the difference in the burden rate among the patients with varying degrees of cerebral ischemia,provide a reference for establishing a personal burden rate evaluation,and propose suggestions for control its increase.Methods The medi-cal insurance data were collected from 8164 discharged patients in a tertiary hospital in Tianjin between January and December 2022.With the data,the Generalized Linear Model was utilized to analyze the factors affecting the personal burden rate across different Diagnosis Related Groups(DRGs).Results Statistically significant differences were observed in the cost structure a-mong different DRGs.Age,length of hospital stays,total hospitalization cost,hospital admission mode,number of hospitaliza-tions,and type of medical insurance significantly impacted the personal burden rate.The personal burden rate was inversely cor-related with age and length of hospital stays,but directly correlated with the total hospitalization cost.The patients admitted from emergency,first-time hospitalization,and those covered by the basic medical insurance program for urban employees had a lower personal burden rate.Conclusion Hospitals should establish diverse personal burden rate performance evaluation standards for patients with different types of medical insurance,incorporating factors such as average length of hospital stays and average hospi-talization cost.A more equitable hospital internal assessment plan should be developed by considering patients admitted to differ-ent departments and aligning with the characteristics of clinical pathways.Medical institutions should minimize self-funded pro-jects under declared medical insurance,increase the enrollment of cases in DRGs,and promote tiered diagnosis and treatment to reduce the personal burden rate for patients.