BACKGROUND:Low temperatures have detrimental effects on the human cardiovascular system,with a higher prevalence of hypertension and related cardiovascular diseases,especially among people living in cold climates.Transient receptor potential M8(TRPM8)is often recognized as a physiological sensor of environmental cold,and glutamate receptor-3(GLR-3)/glutamate receptor ionotropic,kainate 2(GluK2)is also cold-sensitive.However,the specific molecular mechanisms of cold-associated TRPM8 and GLR-3/GluK2 in regulating hypertension remain puzzling.OBJECTIVE:Through a review of the literature in this field,to find out the general pattern of TRPM8 and GLR-3/GluK2 in regulating the body's cold response,as well as the specific mechanism of action in hypertension,thereby providing a theoretical basis for subsequent research on the treatment of hypertension based on cold-stimulation-related targets,and further expanding the new ideas and methods for the treatment of hypertension.METHODS:We searched,reviewed and screened the relevant literature on"cold stimulation,TRPM8,GLR-3/GluK2 and hypertension"to lay the theoretical foundation for the analysis of the whole article.Comparative analysis method,through reading and analyzing the obtained literature,comparing the similarities and differences between the literature,was performed to provide reasonable theoretical support for the argument.Through further comparative analysis of the literature,the relationship between the relevant indicators was clarified,and the ideas were clarified for the analysis of the full text.RESULTS AND CONCLUSION:(1)TRPM8 can be activated by cold and mainly mediates cool temperature perception in mammals.Its activation can trigger neurogenic inflammatory response and indirectly affect the inflammatory process.Abnormal TRPM8 signal can lead to excessive activation of immune cells,which is significantly associated with the occurrence and development of hypertension.(2)The activation threshold of GLR-3/GluK2 is lower than that of TRPM8,which may preferentially respond to noxious cold stimulation rather than ordinary cool temperature.In cold environment,GLR-3/GluK2 activation enhances sympathetic nerve excitability by regulating interneuron signal transduction and causes peripheral vascular constriction.Long-term effects can lead to increased peripheral vascular resistance.To conclude,TRPM8 and GLR-3/GluK2 are involved in the interaction of the nerve-immune-vascular system by sensing different cold stimuli.Abnormal TRPM8 signaling indirectly promotes the progression of hypertension through inflammation and immune dysregulation,while GLR-3/GluK2 directly exacerbates vascular constriction and resistance by enhancing sympathetic nerve activity.The combination of the two factors may constitute the key molecular mechanism of the occurrence and development of hypertension in cold environment,and provide a potential target for the intervention of cold-related cardiovascular diseases.

OBJECTIVE To explore the potential mechanism by which drug-containing serum of Dianxianqing granules （DXQ） inhibits microglial ferroptosis. METHODS Male SD rats were given normal saline and Dianxianqing granules solution via intragastric administration to prepare normal serum and DXQ， respectively. Mice microglia BV2 cells were collected and successfully transfected with a negative control small interfering RNA （si-NC）， and then they were included in the si-NC group and cultured under normal conditions. Cells successfully transfected with small interfering RNA targeting glutathione peroxidase 4 （GPX4） （si-GPX4） were divided into the si-GPX4 group， the CsA group （treated with 1 μmol/L cyclosporine A）， and the DXQ- L， DXQ-M and DXQ-H groups （treated with 5%， 7% and 10% DXQ， respectively）. These groups were subsequently treated with their corresponding drug solutions and ferroptosis inducer Erastin （10 μmol/L）. The intracellular levels of total iron ions， glutathione （GSH）， reactive oxygen species （ROS）， and the expression of mitochondrial superoxide were determined in each group after 48 h of treatment. Additionally， mitochondrial membrane potential， the opening degree of mitochondrial permeability transition pore （MPTP）， and mRNA expressions of GPX4 and cyclophilin D （CypD） were detected. Furthermore， the expressions of ferroptosis-related proteins[GPX4， transferrin receptor 1 （TfR1） and ferritin heavy chain 1 （FTH1）]， as well as MPTP-related proteins [adenine nucleotide translocator （ANT）， cytochrome C （CytC）， mitochondrial calcium uniporter （MCU） and CypD] were assessed. RESULTS Compared with si-NC group， the levels of total iron ions and ROS， the expression level of mitochondrial superoxide， the opening degree of MPTP， protein and its mRNA expressions of CypD as well as protein expressions of TfR1 and MCU were increased or up-regulated significantly （P＜0.01）； however， GSH content， mitochondrial membrane potential， protein and mRNA expressions of GPX4， and protein expressions of FTH1， ANT and CytC were decreased or down-regulated significantly （P＜0.01）. Compared with the si-GPX4 group， the cells in the DXQ-M， DXQ-H groups showed a general improvement in the above quantitative indicators （P＜0.01 or P＜0.05）. CONCLUSIONS DXQ can enhance antioxidant capacity by activating the GSH/GPX4 pathway， regulate the expressions of TfR1 and FTH1 protein to correct iron ion homeostasis， inhibit excessive opening of MPTP to improve mitochondrial function， and ultimately suppress microglial ferroptosis.

ObjectiveTo observe the short-term and long-term efficacy of traditional Chinese medicine （TCM） surgical operations in treating mixed hemorrhoids. MethodsA multi-center retrospective cohort study was conducted， collecting clinical data from 17，831 mixed hemorrhoid surgery patients in 8 top-tier TCM hospitals in Jiangsu Province. Standardized and structured datasets were obtained through artificial intelligence models. Patients who underwent western surgical treatment were categorized into the western surgery group （11,646 cases）， and those receiving TCM surgical operations were categorized into the TCM surgery group （6185 cases）. Propensity score matching （1∶1 matching） was used to balance baseline data between groups. The primary outcome was the one-year recurrence rate， and secondary outcomes included the main symptoms （rectal bleeding， degree of prolapse） and secondary symptoms （anal distension， anal edema， wound secretion and exudation， anal stenosis， residual skin tags， perianal itching， and anal pain） measured on days 7， 28， and 60 after discharge. ResultsAfter matching， 2194 patients were included in each group. Symptom scores showed that at 28 days after discharge， the TCM surgical group had superior improvement in rectal bleeding ［OR=5.786， 95%CI （3.092，10.827）］， degree of prolapse ［OR=4.510， 95%CI （1.649，12.333）］， and anal edema ［OR=3.188， 95%CI （1.295，7.845）］ compared to the western surgical group. At 60 days post-discharge， the TCM group still showed advantages in improving rectal bleeding ［OR=5.237， 95%CI （1.077，25.464）］ and anal pain ［OR=11.697， 95%CI （1.186，115.336）］ （P＜0.05）. Long-term follow-up showed that the one-year recurrence rate in the TCM surgery group was 1.1% （8/726）， while that in the western surgery group was 2.3% （10/444）， with no statistically significant difference between the two groups （P＞0.05）. ConclusionBased on real-world data， TCM surgical treatment for mixed hemorrhoids shows significant short-term symptom improvement， particularly in terms of hemostasis， reducing swelling， and alleviating prolapse of anal masses.

OBJECTIVE To analyze the specific risks and long-term toxicities of four BCR-ABL1 tyrosine kinase inhibitors （TKIs）（imatinib， dasatinib， nilotinib， and bosutinib） in pediatric patients with hematological malignancies. METHODS Adverse drug event （ADE） reports submitted to the the United States FDA Adverse Event Reporting System （FAERS） from January 2012 to December 2024， with imatinib， dasatinib， nilotinib， and bosutinib as the primary suspect drugs， were collected. Data mining was performed using the reporting odds ratio method and proportional reporting ratio method. ADE terms were classified and summarized by system organ class （SOC） and preferred term （PT） according to the Medical Dictionary for Drug Regulatory Activities （MedDRA， version 26.0）. Meanwhile， the ADE reports were divided by age into the adult group （≥18 years） and the pediatric group （＜18 years） to compare the differences in ADE between the two groups. RESULTS A total of 1 512 pediatric ADE reports were included： 993 for imatinib， 391 for dasatinib， 112 for nilotinib， and 16 for bosutinib. Among the reported ADEs， the patients were mainly aged 12-＜18 years； the reports mainly originated from the United States， France， and Japan； and the primary indications were chronic myeloid leukemia and acute lymphoblastic leukemia. A total of 5 256 ADE signals were mined， among which 235 were positive signals， involving 1 103 PT across 27 SOC. The top five PT ranked by the number of positive signals were nausea， febrile neutropenia， abdominal pain， neutropenia， and anemia. The top two SOC were general disorders and administration site conditions， and gastrointestinal disorders. Compared with the adult group， the pediatric group had relatively higher proportions of events related to infections and infestations as well as blood and lymphatic system disorders. Pediatric long-term toxicity signals primarily included growth retardation， accompanied by signals related to endocrine system abnormalities and bone metabolism abnormalities. Specific signals included imatinib-associated septic shock， dasatinib-associated chylothorax， and nilotinib-associated electrocardiographic QT interval prolongation. CONCLUSIONS When pediatric patients use BCR-ABL1 TKIs， priority monitoring of infection risk and hematologic parameters is required， along with long-term follow-up of height， endocrine， and bone metabolism parameters. Targeted screening and management of drug-specific signals should be performed to ensure the long-term safety of pediatric medication.

BACKGROUND:Low temperatures have detrimental effects on the human cardiovascular system,with a higher prevalence of hypertension and related cardiovascular diseases,especially among people living in cold climates.Transient receptor potential M8(TRPM8)is often recognized as a physiological sensor of environmental cold,and glutamate receptor-3(GLR-3)/glutamate receptor ionotropic,kainate 2(GluK2)is also cold-sensitive.However,the specific molecular mechanisms of cold-associated TRPM8 and GLR-3/GluK2 in regulating hypertension remain puzzling.OBJECTIVE:Through a review of the literature in this field,to find out the general pattern of TRPM8 and GLR-3/GluK2 in regulating the body's cold response,as well as the specific mechanism of action in hypertension,thereby providing a theoretical basis for subsequent research on the treatment of hypertension based on cold-stimulation-related targets,and further expanding the new ideas and methods for the treatment of hypertension.METHODS:We searched,reviewed and screened the relevant literature on"cold stimulation,TRPM8,GLR-3/GluK2 and hypertension"to lay the theoretical foundation for the analysis of the whole article.Comparative analysis method,through reading and analyzing the obtained literature,comparing the similarities and differences between the literature,was performed to provide reasonable theoretical support for the argument.Through further comparative analysis of the literature,the relationship between the relevant indicators was clarified,and the ideas were clarified for the analysis of the full text.RESULTS AND CONCLUSION:(1)TRPM8 can be activated by cold and mainly mediates cool temperature perception in mammals.Its activation can trigger neurogenic inflammatory response and indirectly affect the inflammatory process.Abnormal TRPM8 signal can lead to excessive activation of immune cells,which is significantly associated with the occurrence and development of hypertension.(2)The activation threshold of GLR-3/GluK2 is lower than that of TRPM8,which may preferentially respond to noxious cold stimulation rather than ordinary cool temperature.In cold environment,GLR-3/GluK2 activation enhances sympathetic nerve excitability by regulating interneuron signal transduction and causes peripheral vascular constriction.Long-term effects can lead to increased peripheral vascular resistance.To conclude,TRPM8 and GLR-3/GluK2 are involved in the interaction of the nerve-immune-vascular system by sensing different cold stimuli.Abnormal TRPM8 signaling indirectly promotes the progression of hypertension through inflammation and immune dysregulation,while GLR-3/GluK2 directly exacerbates vascular constriction and resistance by enhancing sympathetic nerve activity.The combination of the two factors may constitute the key molecular mechanism of the occurrence and development of hypertension in cold environment,and provide a potential target for the intervention of cold-related cardiovascular diseases.

Objective: To analyze the implementation status of the “Three-Exemptions” policy for voluntary blood donation in China by taking Shandong Province as a case study, explore the sociodemographic characteristics of policy beneficiaries and the distribution differences in blood donation frequencies, so as to provide practical references for improving the honor incentive system of voluntary blood donation and stabilizing the blood donation team. Methods: Excel was used to sort out and summarize the policy documents from 31 provincial-level administrative regions of China (excluding Hong Kong, Macao and Taiwan), and its implementation models, temporal characteristics and implementation basis were analyzed. Using 238 193 policy beneficiaries in Shandong Province as the research objects, Stata was adopted for descriptive statistical analysis of sociodemographic characteristics including gender, age, educational background and occupation. The Mann-Whitney U test and Kruskal-Wallis H test were performed to compare the distribution differences of blood donation frequencies among populations with different characteristics. Results: The “Three Exemption” policy has been implemented in 29 provinces nationwide, forming five differentiated implementation models. Specifically, 45.16% of the regions adopted province-wide unified implementation, 32.26% adopted partial prefecture-level city implementation, 12.90% adopted partial clause implementation, 3.23% adopted encouraging implementation, and 6.45% had not implemented the policy. The period from 2023 to 2026 witnessed the concentrated promotion of the policy. In Shandong Province, the beneficiaries were mainly males (82.08%), middle-aged individuals aged 40-60 years (71.78%), groups with junior and senior high school education (56.57%), and staff employees (30.60%). The distribution of blood donation frequencies showed that nearly 60% (56.95%) of the beneficiaries had donated blood 20 to 29 times. Statistically significant differences in donation frequency distributions were observed across genders, age groups, educational backgrounds, and occupations (all P<0.05). Further analysis revealed that the proportion of males with 40 or more blood donations was higher than that of females (24.32% vs 15.60%), while females had a higher proportion of 20-29 blood donations than males (65.98% vs 54.99%). With the increase of age, the proportion of those with 20-29 blood donations gradually decreased, whereas the proportion of those with≥40 blood donations gradually increased. Conclusion: The coverage of the “Three Exemptions” policy for voluntary blood donation in China continues to expand. However, there is still room for optimization in terms of policy implementation standards, population structure adaptation and incentive gradient design. Future efforts should strengthen national top-level design to balance regional development gaps. Moreover, hierarchical and targeted incentive and publicity strategies combined with population structural characteristics should be implemented to enhance public enthusiasm for voluntary blood donation.

OBJECTIVE To investigate the current status of informatization tools applied to antimicrobial stewardship in county hospitals in China， and to provide a reference for promoting the informatization development of antimicrobial stewardship in county hospitals.METHODS From August to September 2025， an online questionnaire survey was conducted among 1 007 county hospitals across 31 provinces（autonomous regions， and municipalities） in China. The survey focused on the application of four types of informatization tools：the real-time monitoring system for antimicrobial use， the pre-prescription review system， the irrational use warning system， and the electronic prescription evaluation system（hereinafter referred to as the “monitoring system”“review system”“warning system”“evaluation system”，respectively）. Correlation analysis and binary Logistic regression analysis were employed to explore the influencing factors.RESULTS Of the county hospitals， 80.83% were equipped with at least one type of informatization tool for antimicrobial stewardship， while 19.17% had no relevant tool. Only 18.87% of the hospitals were equipped with all four types of tools. The monitoring system exhibited the highest equipped rate （70.80%）， whereas the warning system was equipped in only 33.96% of the hospitals. Four types of tools are evenly and adequately deployed in the eastern region， the central and western regions have far lower deployment rates of intervention tools including review system and warning system， accompanied by prominent intra-provincial gaps. The total number of the health technicians， hospital grade， and prescription review rate of outpatient antibacterial drug were significantly and positively correlated with the deployment rates of the four informatization tools （ P ＜0.05）. The results of the Logistic regression model fitting indicated that the model of the review system was rated “excellent” [area under the receiver operating characteristic curve （AUC）＝0.81]， and the model of the warning system was rated “further improvement” （AUC＝0.67）. The total number of health technicians was significantly positively correlated with the deployment rates of all four types of informatization tools （all P ＜0.05）.CONCLUSIONS The informatization of antimicrobial stewardship in county hospitals in China remains in the initial stage of transitioning from “passive statistics” to “active prevention and control”， with challenges such as structural imbalance and regional disparities. In the future， differentiated support strategies should be implemented， the allocation of resources should be optimized， to enhance the level of refined antimicrobial stewardship.

ObjectiveTo investigate the effect of Gelian Tiaotang pills on renal fibrosis in db/db mice based on the nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3）/cysteinyl aspartate-specific proteinase （Caspase）-1/gasdermin D （GSDMD） signaling pathway. MethodsForty db/db mice were randomly assigned into model， positive control （0.001 3 g·kg·d^-1 dapagliflozin suspension）， and high-， medium-， and low-dose Gelian Tiaotang pills （3.12， 1.56， and 0.78 g·kg·d^-1 suspension of Gelian Tiaotang pills， respectively） groups， with 8 mice in each group. Eight db/m mice were selected as the normal group. The normal group and model group were given equal volumes of pure water， while the drug interventions groups were administrated with corresponding agents by gavage once a day for 12 consecutive weeks. The general conditions of mice were observed daily. The fasting blood glucose （FBG） and body mass were measured every 4 weeks. Kidneys were weighed after sampling， and the kidney index was calculated. An automatic biochemical analyzer was used to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， serum creatinine （SCr）， and blood urea nitrogen （BUN）. The pathological changes， extracellular matrix deposition， and renal fibrosis degree were examined by hematoxylin-eosin， periodic acid-schiff （PAS）， and Masson staining， respectively. Enzyme-linked immunosorbent assay was employed to measure the levels of interleukin （IL）-1β and IL-18 in the renal tissue. Immunohistochemistry （IHC） was used to detect the localization and expression of fibronectin and collagen Ⅰ in the renal tissue. Western blot was employed to determine the protein levels of NLRP3， Caspase-1， cleaved Caspase-1， GSDMD， and GSDMD-N in the renal tissue. ResultsCompared with the normal group， the model group generally had poor general states and increases in the body mass， kidney weight， kidney index， and levels of FBG， TG， TC， SCr， and BUN （P<0.01）. In addition， glomerular pyknosis， increased matrix， vacuolar degeneration of renal tubular epithelial cells， and interstitial infiltration of inflammatory cells were observed in the model group （P<0.01）， together with rises in the levels of IL-1β and IL-18 in the renal tissue （P<0.01） and up-regulated protein levels of NLRP3， Caspase-1， cleaved Caspase-1， GSDMD， GSDMD-N， fibronectin， and collagen Ⅰ in the renal tissue （P<0.01）. Compared with the model group， 12 weeks of drug interventions reduced the body mass， kidney weight， and kidney index and lowered the levels of FBG， TG， TC， SCr， and BUN in the serum and IL-1β and IL-18 in the renal tissue （P<0.05， P<0.01）. Furthermore， drug interventions ameliorated the renal lesions and down-regulated the protein levels of NLRP3， Caspase-1， cleaved Caspase-1， GSDMD， GSDMD-N， fibronectin， and collagen Ⅰ in the renal tissue （P<0.05， P<0.01）. The high-dose group of Gelian Tiaotang pills had the best effects. ConclusionGelian Tiaotang pills may inhibit pyroptosis and reduce inflammatory responses by regulating the NLRP3/Caspase-1/GSDMD signaling pathway， thus delaying the process of renal fibrosis in diabetes.

Objective To explore the protective effect of hydroalcoholic extract of Portulaca oleracea L.(POHA)on ulcerative colitis(UC)and bone loss in mice.Methods The C57BL/6 mice were treated with dextran sulfate sodium(DSS)to establish UC model.A total of 50 mice were randomly assigned to including control group,DSS group,mesalazine(MS)group,low dose of POHA(POHAL)group,or high dose of POHA(POHAH)group.The control group freely drank drinking water,while the DSS,MS,POHAL and POHAH groups drank drinking water containing DSS for 8 weeks.Since the 2nd week,the control group and DSS group were given normal saline by gavage.The MS group was given MS(100 mg/kg)by gavage.The POHAL group and POHAH group were given POHA(1 000 mg/kg and 2 000 mg/kg)by gavage,respectively.Body weight and disease activity index(DAI)were recorded and calculated every 2 d.On the 56th day,the colon weight index,liver index,and spleen index were calculated,and the histological changes of colon were observed.Serum levels of bone metabolism markers and microstructure parameters of femur were detected.Results Compared with the control group,the DSS group showed significantly increased DAI score,colon weight index,liver index,and spleen index(all P＜0.01).The DSS group exhibited significant pathological damage in colon tissues and significantly increased serum levels of osteocalcin,C-terminal peptide of collagen type Ⅰ,and tartrate-resistant acid phosphatase 5b(P＜0.01).The bone loss was significant in the DSS group,manifested by markedly decreased bone mineral density(BMD),bone tissue volume to tissue volume ratio(BV/TV),trabecular bone number(Tb.N),and trabecular bone thickness(Tb.Th),and markedly increased bone surface to bone volume ratio(BS/BV)and trabecular bone separation(Tb.Sp)(P＜0.05 or P＜0.01).Compared with the DSS group,the BMD,BV/TV,Tb.N and Tb.Th of the femur in the MS group and POHAH group of mice were all increased(P＜0.05 or P＜0.01),the BS/BV all decreased(P＜0.05 or P＜0.01),and the Tb.Sp all decreased without significant differences(all P＞0.05).The above bone microstructure parameters in the POHAL group showed no significant differences compared with those in the DSS group(all P＞0.05).Conclusion POHA has protective effect on DSS-induced UC and bone loss,and the mechanism may be related to the inhibition of hyperactive bone metabolism.

Objective:To assess the safety,effectiveness and economy of some brands and models of domestic and imported anesthesia machine in clinical application,so as to provide reference for improving the competitiveness of anesthesia machine of domestic brands.Methods:A total of 195 patients who underwent general anesthesia in surgery through used respectively domestic Mindray WATO-EX-55Pro anesthesia machine,and imported GE CS620 and GE Aelite NXT anesthesia machines at Inner Mongolia People's Hospital from January 2021 to January 2023 were selected.According to the different brands of the used anesthesia machine by the patients,they were divided into domestic Mindray WATO-EX-55Pro anesthesia machine group(Domestic group),imported GE Aelite NXT anesthesia machine group(Import group of NXT)and imported GE CS620 anesthesia machine group(Import group of 620),with 65 cases in each group.Based on the clinical application data of anesthesia machines in real-world,the actual application effects of anesthesia machines of different brands were assessed in terms of 3 aspects included effectiveness,safety and economy.Results:In the indicators about effectiveness,there was statistically significant difference in postoperative blood oxygen saturation among the Domestic group[100%(99%,100%)],Import group of NXT[99%(98%,100%)]and Import group of 620[99%(99%,100%)](Z=14.723,P<0.05).There was statistically significant difference in the different value of blood oxygen saturation between before and after surgery among three groups(Z=-1.681,P<0.05),and there was significant difference in the postoperative partial pressure of carbon dioxide(PCO2)among three groups(Z=5.574,P<0.05).There was no statistically significant difference in the other indicators of effectiveness among three groups(P>0.05).In the indicators about safety,there was no statistically significant difference in the incidence of adverse events among the three groups(P>0.05).In the indicators about economy,the total costs of anesthesia for patients were respectively 1190.00 CNY(870.00,1582.50),2650.00 CNY(2357.50,2928.75)and 2462.00 CNY(1657.50,2847.50)in the Domestic group,Import group of NXT and Import group of 620,and the difference of that among three groups was statistically significant(Z=88.825,P<0.05).Conclusion:There are not significant differences in the analyzed effectiveness and safety among the domestic anesthesia machine and the imported anesthesia machines,and domestic anesthesia machine is more economical than imported anesthesia machines,which can reduce the cost of anesthesia in surgery,and alleviate the financial burden of patients in medical expenses.