OBJECTIVE To investigate a dynamic monitoring of drug consumption （DMDC） model based on the seasonal Mann-Kendall trend test， aiming to provide scientific evidence for the efficient and macroscopic monitoring of drug use. METHODS A monitoring list of key outpatient drugs was established based on the top 20% of drugs ranked by sales volume in the outpatient pharmacy in October 2024. A DMDC model based on the Mann-Kendall trend test was constructed using the monthly usage data of key outpatient drugs from November 2021 to October 2024， aiming to eliminate the impact of seasonal fluctuations and analyze the temporal trends in drug consumption. Taking mucolytic expectorants， triazole derivatives for dermatophytosis， and single-agent hydroxymethylglutaryl coenzyme A （HMG-CoA） reductase inhibitors as examples， the monitoring effectiveness of the DMDC model was demonstrated， and its performance was compared with that achieved by the traditional sequential growth rate ranking method. RESULTS A total of 215 drug varieties were included in the monitoring list， and DMDC models were successfully established for all of them. Among these， 119 showed a significant increasing trend （P＜0.05， S′＞0）. The model successfully monitored the monthly consumption of mucolytic expectorants， triazole derivatives for dermatophytosis， and single- agent HMG-CoA reductase inhibitors. The precision and recall rates of the DMDC model for identifying abnormal drug use were 60.7% and 85.0%， respectively， both significantly higher than those of the sequential growth rate ranking method （8.3% and 15.0%， respectively） （χ2＝20.114， P＜0.001； χ2＝19.600， P＜0.001）. CONCLUSIONS DMDC model based on the seasonal Mann-Kendall trend test can effectively identify long-term trends in drug consumption， eliminate seasonal interference， enhance monitoring accuracy and management efficiency， and is suitable for the dynamic monitoring of drug consumption.

Purpose: This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery. Materials and Methods: Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety. Results: From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events. Conclusion Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.

ObjectiveTo explore the function and related molecular mechanisms of magnoflorine against colon cancer via network pharmacology， molecular docking， and in vitro cell experiments. MethodsIn this study， the canonical SMILES of magnoflorine was obtained from the PubChem database， and the potential targets of magnoflorine were predicted by the Swiss Target Prediction database， while the disease targets of colon cancer were obtained from the DisGeNET， GeneCards and OMIM databases. The intersecting targets between magnoflorine's predicted targets and colon cancer disease targets were taken， and a protein-protein interaction （PPI） network was constructed and analyzed. The DAVID online database was employed to conduct Gene Ontology （GO） and KEGG pathway enrichment analyses on core targets. The top five key targets screened were docked with magnoflorine using AutoDock software. Finally， cellular experiments including CCK-8 assays， EdU experiments， cell scratch assays， and Transwell assays were conducted to validate the results from network pharmacology and molecular docking. Results44 key targets of magnoflorine in resisting colon cancer were acquired. The molecular docking results showed that magnoflorine had a strong binding activity with the core target signal transducer and activator of transcription 3 （STAT3） in the top five of the PPI network. Cellular experiments confirmed that magnoflorine could inhibit the proliferation and migration of colon cancer cells by suppressing the JAK/STAT3 signaling pathway. ConclusionMagnoflorine may inhibit the proliferation and migration of colon cancer cells by regulating the JAK/STAT3 signaling pathway.

OBJECTIVE To provide scientific evidence and practical references for refined antimicrobial stewardship in multi- branch medical institutions. METHODS Data of antibiotic use density （AUD） of inpatients as well as physician-level case mix index （CMI） were collected from the Liji Road main campus and Panlongcheng branch campus of our hospital from August 2023 to March 2026. The two-factor decomposition method was adopted to decompose total AUD variation into a level effect and structural effect. Grey relational analysis （GRA） was performed to quantify the correlation degree between ward CMI， physician CMI and physician AUD， so as to identify wards and physicians requiring targeted key intervention in different campuses. A refined antimicrobial management framework for multi-branch hospitals was constructed and implemented based on the above analytical results. An interrupted time series （ITS） model incorporating seasonal dummy variables was applied. The research period was divided into pre-intervention stage （August 2023 to March 2024） and post-intervention stage （April 2024 to March 2026）. The temporal changing trends of AUD in two campuses were compared to evaluate management efficacy. RESULTS Driving factors for AUD variation presented significant heterogeneity between the two campuses. AUD variation in the main campus was dominated by level effect， while AUD variation in the branch campus was jointly affected by structural effect and level effect. The grey relational degrees of ward CMI and physician CMI with physician AUD were 0.901 and 0.882， respectively. After refined management implementation， AUD decreased by 7.48 DDDs/（100 bed·days） and 20.54 DDDs/（100 bed·days） in the main campus and branch campus， respectively； the rising trends of AUD in both campuses reversed to declining trends after intervention. CONCLUSIONS Driving factors of AUD variation under the multi-branch hospital model show obvious inter-campus heterogeneity. CMI is highly correlated with AUD. The refined management system developed via AUD attribution decomposition and CMI correlation analysis matches the differentiated clinical characteristics of multi- branch hospitals and effectively improves the precision of antimicrobial stewardship.

Precancerous lesions of gastric cancer （PLGC） are a group of pathological changes caused by abnormalities in the structure， morphology， and differentiation of gastric mucosal epithelial cells. Since the early symptoms are hidden and non-specific， PLGC is not easy to be diagnosed and it has often developed into intermediate or advanced gastric cancer once being diagnosed and missed the best time for treatment. Accordingly， the incidence of this disease is increasing year by year， which lifts a heavy burden on the patients. The pathogenesis of PLGC is complex， involving inflammatory microenvironment， bile reflux， glycolysis， autophagy， and apoptosis. Currently， PLGC is mainly treated with anti-inflammatory and endoscopic therapies， which are difficult to curb the development of PLGC. Therefore， seeking a safe and effective therapy is an important topic of modern research. Traditional Chinese medicine （TCM）， characterized by treatment based on syndrome differentiation and a holistic view， exerts effects via multiple pathways， mechanisms， and targets. Recent studies have confirmed that TCM can regulate the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR）， Wnt/β-catenin， Sonic Hedgehog， nuclear factor-κB （NF-κB）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， hypoxia-inducible factor-1α （HIF-1α）， neurogenic locus notch homolog protein （Notch）， nuclear factor E₂-related factor 2 （Nrf2） and other signaling pathways. By targeting these pathways， TCM can inhibit aerobic glycolysis， reduce oxidative stress， repair the inflammatory microenvironment， regulate cellular autophagy， and promote vascular normalization， thereby delaying or reversing PLGC. However， few researchers have systematically summarized the TCM regulation of PLGC-associated pathways. By reviewing the relevant articles at home and abroad， this paper summarized the roles of the above signaling pathways in the development of PLGC and the research progress in the regulation of signaling pathways by TCM in the treatment of PLGC， with a view to providing a new theoretical basis for the clinical research on PLGC and the drug development for this disease.

Objective To explore the expression characteristics of BAIAP2L1 in cervical cancer (CC) and its regulatory role in tumor cell metastasis. Methods The correlation between BAIAP2L1 expression and clinical prognosis was analyzed by using a public database. GO pathway enrichment and clinicopathological correlation analyses were conducted by employing R language. The effect of BAIAP2L1 knockdown on CC cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) were further investigated through gene silencing approaches. Results BAIAP2L1 expression was significantly upregulated in CC tissues (P_adj <0.001) and it was identified as an independent risk factor for patient mortality (HR=2.808, P=0.03). Elevated BAIAP2L1 levels showed significant correlations with poor overall survival, advanced T/N stage, recurrence, and metastasis (all P<0.05). Functional enrichment analysis revealed its involvement in tumor metastasis-related pathways. The knockdown of BAIAP2L1 significantly attenuated CC cell proliferation, invasion, and migration and suppressed key EMT processes (all P<0.05). Conclusion BAIAP2L1 is overexpressed in CC tissues and associated with patient prognosis and metastasis. The targeted inhibition of BAIAP2L1 can effectively curb tumor progression.

Objective To evaluate the anticoagulation efficacy of non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKAs) in patients with high-risk atrial fibrillation (AF) undergoing transcatheter aortic valve implantation (TAVI). Methods A computer-based search was conducted on PubMed, EMbase, The Cochrane Library, CNKI, SinoMed, and VIP databases to identify studies on the application of NOACs and VKAs in high-risk AF patients after TAVI. The search period was from database inception to January 2023. The quality of the included studies was assessed using the Cochrane risk assessment tool and the Newcastle-Ottawa Scale (NOS). Meta-analysis was performed using RevMan 5.4 software. Results A total of 7 studies involving 24 592 patients were included. The meta-analysis results showed that compared to patients using VKAs, those treated with NOACs had a significantly lower risk of all-cause mortality [RR=0.74, 95%CI (0.58, 0.94), P=0.01]. Subgroup analysis indicated that when the follow-up period was less than 1 year, there was no significant difference in all-cause mortality between the NOAC and VKA groups [RR=0.57, 95%CI (0.17, 1.88), P=0.35]; however, when the follow-up period was ≥1 year, the VKA group had a higher all-cause mortality rate than the NOAC group, with a statistically significant difference [RR=0.73, 95%CI (0.57, 0.95), P=0.02]. No significant differences were found between the two groups regarding early stroke [RR=0.50, 95%CI (0.19, 1.28), P=0.15], stroke during follow-up [RR=1.04, 95%CI (0.88, 1.22), P=0.64], bleeding [RR=0.94, 95%CI (0.73, 1.21), P=0.61], major or life-threatening bleeding [RR=0.80, 95%CI (0.49, 1.31), P=0.38], or acute kidney injury [RR=0.51, 95%CI (0.16, 1.59), P=0.24]. Conclusion Compared to VKAs, the use of NOACs in patients with high-risk AF undergoing TAVI may reduce the risk of all-cause mortality, especially during long-term anticoagulation therapy, potentially offering greater benefits. However, further evidence from randomized controlled trials is needed to confirm these findings.

Objective To investigate the effects of Gandou Fumu Decoction on liver fibrosis,iron metabolism,and ferroptosis in patients with hepatolenticular degeneration(Wilson disease,WD).Methods Seventy-eight hospitalized patients with WD characterized by kidney and liver deficiency,with phlegm and blood stasis,from the Department of Neurology,the First Affiliated Hospital of Anhui University of Chinese Medicine,were randomly assigned to two groups using a random number table method.The control group(n=39)received sodium dimercaptosulfonate in combination with a low-copper and high-protein diet.The observation group(n=39)received the same treatment as the control group,with the addition of Gandou Fumu Decoction(one dose per day,taken twice daily,in the morning and evening).Both groups underwent six treatment cycles,each lasting eight days.Ultrasonographic parameters,including portal vein main trunk diameter(PVMD),portal vein velocity(PVV),shear wave velocity(SWV),liver stiffness measurement(LSM),serum liver fibrosis markers(hyaluronic acid[HA],laminin[LN],procollagen typeⅢN-terminal peptide[PⅢNP],collagen type Ⅳ[CⅣ],aspartate aminotransferase to platelet ratio index[APRI],fibrosis-4 index[FIB-4]),and iron metabolism indicators(serum iron[SI],ferritin[FT])were compared before and after treatment.The relationship between baseline iron metabolism markers and ultrasonographic parameters,as well as serum liver fibrosis markers,was analyzed.Clinical efficacy,traditional Chinese medicine(TCM)syndrome scores,and adverse reactions were also compared between the groups.Additionally,bioinformatics analysis was performed to identify potential targets of Gandou Fumu Decoction for WD treatment.Peripheral blood mononuclear cells were collected from a normal group of 20 healthy individuals,as well as from both the control and observation groups before and after treatment.Real time fluorogenic quantitative PCR was performed to validate the expression changes of these targets across the groups.Results Compared with pre-treatment values,no significant changes were observed in PVMD levels in either group after treatment.No significant change in PVV was observed in the control group,whereas a significant decrease was noted in the observation group(P＜0.01).SWV,LSM,HA,LN,PⅢNP,CⅣ,APRI,FIB-4,and FT levels were significantly reduced compared to pre-treatment levels(P＜0.05,P＜0.01),whereas SI remained unchanged.Compared with the control group,the observation group had no significant difference in PVMD but had significantly lower PVV,SWV,LSM,HA,LN,PⅢNP,CⅣ,APRI,FIB-4,and FT levels(P＜0.05,P＜0.01),whereas SI remained unchanged.The total effective rate of treatment in the observation group was significantly higher than that in the control group(P＜0.05).Both groups showed a significant reduction in TCM syndrome scores after treatment(P＜0.01),with a significantly greater reduction observed in the observation group(P＜0.01).No significant adverse reactions were reported during treatment.Before treatment,there was no significant correlation between the SI of both groups and PVMD,PVV,SWV,LSM,HA,LN,PⅢNP,CⅣ,APRI,and FIB-4.In the observation group,FT showed a positive correlation with SWV,LSM,LN,PⅢNP,CⅣ,APRI,and FIB-4(P＜0.05,P＜0.01),while in the control group,FT showed a positive correlation with HA,LN,PⅢNP,CⅣ,APRI,and FIB-4(P＜0.01).After treatment,in the control group,SI showed a positive correlation with APRI and FIB-4(P＜0.05,P＜0.01),but there was no significant correlation between SI in the observation group and FT in both groups with the above-mentioned indicators.Bioinformatics analysis identified four potential targets of Gandou Fumu Decoction for treating WD,namely heme oxygenase 1(HMOX1),peroxisome proliferator-activated receptor alpha(PPARα),small heat shock protein B1(HSPB1),and mitogen-activated protein kinase 3(MAPK3).Compared to the normal group,both the control and observation groups had significantly lower PPARαand HSPB1 expression and significantly higher HMOX1 and MAPK3 expression before treatment(P＜0.01).Compared to before treatment within the same group,both groups showed significantly increased PPARα and HSPB1 expression and significantly decreased HMOX1 and MAPK3 expression after treatment(P＜0.05,P＜0.01).After treatment,the observation group had significantly higher PPARα and HSPB1 expression and lower HMOX1 and MAPK3 expression than the control group(P＜0.05,P＜0.01).Conclusion Gandou Fumu Decoction demonstrates remarkable advantages in improving clinical efficacy,Chinese medicine syndrome scores,iron metabolism,liver fibrosis progression,ultrasound imaging parameters,and ferroptosis-related biomarkers expression in patients with WD,with a favorable safety profile.

Objective To investigate the protective effect and mechanism of Polygonatum sibiricum polysaccharides(PSP)on diabetic cardiomyopathy(DCM).Methods Forty SPF-grade male Sprague-Dawley rats were divided randomly into Control,Model,PSP,and metformin groups.After 4 weeks of feeding a high-fat diet,streptozotocin was injected intraperitoneally to establish a rat model of diabetes mellitus.The drug was administered by gavage for 12 weeks,and body mass and blood glucose were recorded every 2 weeks.Cardiac function was detected by non-invasive echocardiography at week 16.Myocardial histopathological changes and the degree of myocardial fibrosis were assessed by hematoxylin and eosin and Masson staining.Serum interleukin(IL)-6,IL-1β,IL-18,tumor necrosis factor-α(TNF-α),triglycerides,total cholesterol,low-density lipoprotein,and high-density lipoprotein were detected by enzyme-linked immunosorbent assay.Expression levels of the fibrosis-related proteins transforming growth factor(TGF)-β1,Smad2,Collagen-Ⅰ,Collagen-Ⅲ,and the pyroptosis-related proteins NOD-like receptor thermal protein domain associated protein 3(NLRP3),apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),and Caspase-1 were detected in rat myocardial tissues by Western blot.Cellular experiments were performed by exposing H9c2 cells to high glucose(40 mmol/L)to mimic the in vitro DCM model,cell viability was detected by Cell Counting Kit-8 assay,and the apoptotic cell ratio was detected by flow cytometry.Results Rats in the treatment group had significantly lower blood glucose,lipid,and serum inflammatory factor levels compared with the model group(P＜0.05),significantly higher ejection fraction and fractional shortening values(P＜0.05),and improved cardiac function.Myocardial fibers were better aligned and collagen fiber accumulation was reduced,and myocardial tissue levels of NLRP3,ASC,Caspase-1,Collagen-Ⅰ,Collagen-Ⅲ,TGF-β1,and Smad2 were significantly reduced(P＜0.05).In the cellular assay,PSP increased the viability and decreased the proportion of apoptotic cells in high glucose-induced H9c2 cardiomyocytes.Conclusions PSP can improve glucose-lipid metabolism,protect cardiac function,and delay the occurrence of myocardial fibrosis in diabetic rats,and can also improve the viability of cardiomyocytes.Its mechanism of action may be related to the inhibition of cellular pyroptosis and delayed occurrence of ventricular remodeling.

BACKGROUND:Eupatilin,a flavonoid active component derived from Artemisia sinensis,has been reported to relieve inflammation and improve neurological scores in rats with subarachnoid hemorrhage,but its role and mechanism in learning and memory remain unclear.OBJECTIVE:To investigate the effects of eupatilin on learning and memory abilities and P38 mitogen activated protein kinase(p38 MAPK)/signal transducer and activator of transcription-3(STAT3)pathway proteins in rats with subarachnoid hemorrhage.METHODS:A total of 50 Sprague-Dawley rats were randomly divided into sham surgery group,model group,eupatilin group,hesperetin group,eupatilin+hesperetin group,with 10 rats in each group.Except for the sham surgery group,the rats in the other groups were used to construct a subarachnoid hemorrhage model through intravascular perforation.Two hours after successful modeling,the eupatilin group was injected with 10 mg/kg eupatilin via the tail vein,the hesperetin group was injected with 50 mg/kg hesperetin(p38 MAPK/STAT3 signaling pathway activator)via the tail vein,the eupatilin+hesperetin group was injected with 10 mg/kg eupatilin and 50 mg/kg hesperetin via the tail vein,and the sham surgery group and the model group were injected with 10 mL/kg saline via the tail vein.The drug treatment lasted for 24 hours.The neurologic deficit score and Morris water maze experiment were applied to detect the neurological function and learning and memory abilities of rats.Hematoxylin-eosin staining was performed to detect the histopathological changes of the hippocampus.TUNEL method was used to detect neuronal apoptosis.Immunohistochemical staining was conducted to detect the number of doublecortin-positive cells in hippocampal tissue.Western blot was applied to detect the expression of p38 MAPK/STAT3 protein in hippocampal tissue.RESULTS AND CONCLUSION:Compared with the sham surgery group,rats in the model group had lower neurological deficit scores,learning and memory abilities,and number of doublecortin-positive cells(P<0.05),and higher neuronal apoptosis rate and protein expression of p-p38 MAPK/p38 MAPK and p-STAT3/STAT3(P<0.05).Compared with the model group,rats in the eupatilin group showed higher neurological deficit scores,learning and memory abilities,and number of doublecortin-positive cells(P<0.05),and lower neuronal apoptosis rate and protein expression of p-p38 MAPK/p38 MAPK and p-STAT3/STAT3(P<0.05),while those in the nerolone group showed lower neurological deficit scores,learning and memory abilities,and number of doublecortin-positive cells(P<0.05),and higher neuronal apoptosis rate and protein expression of p-p38 MAPK/p38 MAPK and p-STAT3/STAT3(P<0.05).Compared with the eupatilin group,rats in the eupatilin+hesperetin group had lower neurological deficit scores,learning memory abilities,and number of doublecortin-positive cells(P<0.05),and higher neuronal apoptosis rate and protein expression of p-p38 MAPK/p38 MAPK and p-STAT3/STAT3(P<0.05).Hematoxylin-eosin staining showed that compared with the model group,the nerve cells were more neatly arranged in the eupatilin group,disorganized in the hesperetin group,and arranged in a similar way to the model group in the eupatilin+hesperetin group.To conclude,eupatilin may improve learning and memory abilities of rats with subarachnoid hemorrhage by inhibiting the p38 MAPK/STAT3 signaling pathway.