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.

OBJECTIVE To establish an ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） method for the simultaneous determination of the contents of six Aconitum alkaloids in Compound chondroitin sulfate tablets， and to perform quality evaluation of samples from different batches， thereby providing a reference for the quality control of this preparation.METHODS Chromatographic separation was performed on an Agilent SB-C 18 column using gradient elution with 0.2% formic acid （adjusted to pH 7.5 with ammonia） and acetonitrile as the mobile phases. The flow rate was 0.3 mL/min， the column temperature was 35 ℃， and the injection volume was 1 μL. Mass spectrometric analysis was performed using an AJS ESI + ion source in multiple reaction monitoring mode， with quantification by the external standard method. Method validation was performed. The established UPLC-MS/MS method was applied to determine the contents of the six Aconitum alkaloids in 64 batches of samples from three manufacturers， including three diester-type alkaloids （aconitine， hypaconitine， and mesaconitine） and three monoester-type alkaloids （benzoylaconine， benzoylhypaconine， and benzoylmesaconine）. Descriptive statistics， the Kruskal-Wallis H test， principal component analysis （PCA）， and Spearman’s rank correlation analysis were used to evaluate the content distribution of Aconitum alkaloids， differences among samples from different manufacturers， and correlations among the components.RESULTS Good linearity was observed for the six Aconitum alkaloids over their respective concentration ranges， with correlation coefficients （all r ＞0.99）. The relative standard deviations （RSDs） for precision， repeatability， and stability were all less than 5%. The limits of detection and quantification were no higher than 0.003 ng/mL and 0.01 ng/mL， respectively. The mean recoveries ranged from 96.43% to 102.30%， with RSDs ranging from 0.35% to 4.92%. Among the 64 batches of samples， the total content of monoester-type alkaloids （mean value of 0.034 9 mg/tablet） was markedly higher than that of diester-type alkaloids （mean value of 0.002 2 mg/tablet）. Benzoylmesaconine showed the highest content， with a mean value of 0.031 0 mg/tablet， whereas the other five components were present at relatively low levels and showed considerable inter-batch variation. No statistically significant differences were observed in the contents of the six components among samples from different manufacturers （ P ＞0.05）. PCA showed no obvious clustering trend， and significant correlations were observed among some components （ P ＜0.05）.CONCLUSIONS The established UPLC-MS/MS method enables the rapid and accurate simultaneous determination of the above-mentioned six Aconitum alkaloids in Compound chondroitin sulfate tablets. The quality evaluation of multiple batches of samples provides a reference for the quality control of this preparation.

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 investigate the therapeutic efficacy of Erchen Decoction plus Sanzi Yangqin Decoction in the treatment of elderly patients with acute exacerbation of chronic obstructive pulmonary disease(COPD)of phlegm-dampness accumulation in lung syndrome,and to explore its possible therapeutic mechanism through the interleukin 33/soluble growth stimulation expressed gene 2(IL-33/ST2)signaling pathway.Methods A prospective trial was conducted on 92 elderly patients with acute exacerbation of COPD of phlegm-dampness accumulation in lung syndrome who were treated in Haikou Hospital of Traditional Chinese Medicine from January 2021 to June 2023.The patients were randomly divided into the control group and the observation group according to the random number table method,with 46 cases in each group.The control group was treated with conventional western medicine,while the observation group was treated with Erchen Decoction plus Sanzi Yangqin Decoction on the basis of treatment for the control group,and the course of treatment covered two weeks.The changes of traditional Chinese medicine(TCM)syndrome scores,lung function indicators,white blood cell count(WBC),neutrophil percentage(Neut%),and serum IL-33,ST2,interleukin 6(IL-6)and interleukin 8(IL-8)levels of patients in the two groups before and after the treatment were observed,and the clinical efficacy and medication safety of the patients in the two groups were evaluated.Results(1)After two weeks of treatment,the total effective rate of the observation group was 86.96%(40/46)and that of the control group was 67.39%(31/46),and the intergroup comparison(tested by chi-square test)showed that the therapeutic effect of the observation group was significantly superior to that of the control group(P<0.05).(2)After treatment,the TCM syndrome scores such as dyspnea,suppression in the chest,cough and expectoration in the two groups were decreased compared with those before treatment(P<0.05),and the decrease in the observation group was significantly superior to that in the control group(P<0.01).(3)After treatment,the lung function indicators such as forced vital capacity(FVC),forced expiratory volume in one second(FEV1),and peak expiratory flow(PEF)of the two groups all improved compared with those before treatment(P<0.05),and the improvement in the observation group was significantly superior to that in the control group(P<0.01).(4)After treatment,the levels of inflammatory indicators such as WBC,Neut%,and serum IL-33,ST2,IL-6 and IL-8 in the two groups were all decreased compared with those before treatment(P<0.05),and the decrease in the observation group was significantly superior to that in the control group(P<0.01).(5)The total incidence of adverse reactions in both groups was all 8.70%(4/46),and the intergroup comparison showed that the difference was not statistically significant(P>0.05).Conclusion The clinical efficacy of Erchen Decoction plus Sanzi Yangqin Decoction in the treatment of elderly patients with acute exacerbation of COPD of phlegm-dampness accumulation in lung syndrome is remarkable,and it is effective on improving the TCM syndromes,related inflammatory indicators and lung function.Its mechanism may be related to the reduction of the patients'serum IL-33 level,the inhibition of IL-33/ST2 signaling pathway and the expression of related inflammatory factors,so as to inhibit inflammatory response and improve the progression of COPD.

Objective To compare the efficacy of low-frequency and high-frequency repetitive transcranial magnetic stimulation(rTMS)in patients with tremor-dominant Parkinson's disease.Methods A total of 88 tremor-dominant Parkinson's disease patients who visited Suqian Hospital of Nanjing Drum Tower Hospital Group from January 2021 to June 2024 were randomly assigned to low-frequency rTMS group(treated by 1 Hz stimulation)and high-frequency rTMS group(treated by 5 Hz stimulation),with 44 patients in each group.Treatment was administered once a day,five times a week,for 4 weeks.Another 50 patients were enrolled as the control group.During the rTMS treatment,regular medications were continuously administrated.Before and after treatment,the following assessments were conducted:unified parkinson's disease rating scale part Ⅲ(UPDRS-Ⅲ),Parkinson's disease questionnaire-39(PDQ-39),timed up and go(TUG)test,tremor amplitude,tremor peak frequency,and cortical excitability(resting motion threshold[rMT]and active motion threshold[aMT]).Results After treatment,there were significant differences in the UPDRS-Ⅲ score,TUG time,PDQ-39 score,rMT and aMT values,and tremor amplitude between the two groups(P<0.05),and the high-frequency rTMS group was lower/shorter than the other two group.There was no significant difference in tremor peak frequency between the two groups(P>0.05).Conclusion Both low-frequency and high-frequency rTMS can significantly improve motor function and quality of life in tremor-dominant Parkinson's disease patients.High-frequency rTMS demonstrates better efficacy in improving various symptoms and provides a more effective treatment option for tremor-dominant Parkinson's disease.

Objective To detect Serum metabolites with label-free surface-enhanced Raman spectroscopy(SERS)for quickly distinguishing the metabolic profiles of breast cancer patients and healthy subjects.Methods A kind of Plasma nano-material was synthesized as a probe for SERS,which has also been used to detect Raman reporter mol-ecules to assess its detection capability.Serum samples from breast cancer patients and healthy subjects were col-lected and the proteins were precipitated with methanol and removed to collect serum metabolites.Probe-based SERS was used to analyze the serum metabolites of patients and explore the changes in the metabolic profiles of breast cancer patients.Results The SERS probe was synthesized and validated.An analytical method based on SERS probe was established,which achieved a linear range(LR)of 4 orders of magnitude and a limit of detection(LOD)up to 10 nmol/L.Raman spectra of serum metabolites from 5 breast cancer patients and 5 healthy subjects were analyzed to study differences in metabolite changes.Conclusions In this study,the molecular spectrum differences of serum metabolites in breast cancer patients were screened by probe-based SERS method,which pro-vides a technology support research on the metabolic changes caused by breast cancer so potentially provide a new method for fast breast cancer screening.

Objective To compare the differences in clinical features and treatment choices between periph-eral spondyloarthritis(pSpA)and axial spondyloarthritis(axSpA),and better understand the clinical charac-teristics and medication needs of pSpA.Methods Our study is a retrospective cohort study.The patients who first visited the First Medical Center of Chinese PLA General Hospital between January 2016 and December 2022 and were diagnosed with axSpA or pSpA according to the classification criteria established by the Assess-ment of SpondyloArthritis International Society were selected as the study subjects.Demographic data,clinical characteristics,laboratory tests,and treatment information of these patients were obtained through the electronic medical records management system and the intelligent management system for spondyloarthritis.The research compared the distribution of swollen and tender joints between pSpA and axSpA patients,as well as that between pSpA1(excluding patients with psoriatic arthritis)and axSpA patients.Additionally,we analyzed differences in clinical features and treatment options among these groups.Results A total of 1639 pa-tients were included in the study,of which 184 had pSpA(including 97 with psoriatic arthritis),and 1455 had axSpA.Compared to axSpA patients,pSpA patients had fewer male patients(62.5％vs.79.7％,P＜0.001),later onset age(33.8 years vs.22.0 years,P＜0.001),shorter diagnostic delays(6.0 months vs.14.2 months,P=0.004),more associated peripheral arthritis(71.7％vs.9.3％,P＜0.001)and dac-tylitis(6.5％vs.0.3％,P＜0.001),more cases of psoriasis(52.7％vs.1.1％,P＜0.001)and a more common family history of psoriasis(11.4％vs.3.4％,P＜0.001).pSpA patients had higher levels of in-flammatory markers but a lower positive rate of human leukocyte antigen(HLA)-B27(43.5％vs.87.4％,P＜0.001).A positive HLA-B27 was associated with an earlier onset age,fewer cases of psoriasis,and a fami-ly history of ankylosing spondylitis.pSpA patients had a higher proportion of using conventional synthetic dis-ease-modifying antirheumatic drugs(csDMARDs),biologic disease-modifying antirheumatic drugs(bDMARDs),and oral glucocorticoids,and they also more frequently used a combination of bDMARDs and csDMARDs(19.0％vs.12.2％,P=0.009)or multiple csDMARDs(65.8％vs.12.5％,P＜0.001).Compared to axSpA patients,pSpA1 patients(excluding psoriatic arthritis)did not show significant differences in the prevalence of psoriasis,uveitis,family history of psoriasis,or the use of bDMARDs,but the subgroup analysis of other variables was consistent with the results of pSpA patients.Conclusions pSpA patients tend to have a later onset of disease,a lower proportion of male and HLA-B27 positivity,more associ-ated peripheral arthritis,dactylitis,psoriasis,and a more common family history of psoriasis.The disease bur-den in terms of treatment for pSpA is not lower than that for axSpA.Due to the presence of more peripheral symptoms,psoriasis,and higher levels of inflammation,they also require more medication.