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.

ObjectiveTo investigate the differences in clinical features and outcomes between patients with hepatic Wilson's disease （WD） presenting with the syndrome of combined phlegm and stasis and the syndrome of dampness-heat internal accumulation. MethodsA retrospective cohort study was conducted by consecutively recruiting patients with hepatic WD from the Encephalopathy Center of the First Affiliated Hospital of Anhui University of Chinese Medicine between January 2022 and August 2025. According to traditional Chinese medicine （TCM） syndrome differentiation， the patients were assigned into a combined phlegm and stasis group and a dampness-heat internal accumulation group. All the patients received standard treatment. Baseline data， laboratory indicators， complications， Model for End-Stage Liver Disease （MELD） score， Child-Turcotte-Pugh （CTP） score， and Chronic Liver Failure-Sequential Organ Failure Assessment （CLIF-SOFA） score were recorded. The clinical features and outcomes of the two groups of patients were compared by t-test， U-test and multivariate logistic regression. ResultsA total of 141 patients with hepatic WD were included. The combined phlegm and stasis group comprised 68 patients with an average age of （28.22±10.47） years， including 43 males and 25 females. The dampness-heat internal accumulation group comprised 73 patients with an average age of （30.22±8.79） years， including 44 males and 29 females. Univariate analysis showed no statistically significant differences in age or gender between the two groups. The combined phlegm and stasis group had lower platelet （PLT）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， creatine （CRE）， total cholesterol （TC）， and triglycerides （TG） levels （P<0.05 or P<0.01） and higher total bilirubin （TBIL） and prothrombin time （PT） （P<0.05） than the dampness-heat internal accumulation group. There were no statistically significant differences in the incidence of hepatic encephalopathy， infection， spontaneous bacterial peritonitis， ascites， or gastrointestinal bleeding between the two groups. The incidence of splenomegaly and the MELD score were higher in the combined phlegm and stasis group （P<0.05）. The CTP and CLIF-SOFA scores were also higher in the combined phlegm and stasis group， while these differences were not statistically significant. Eleven patients in the combined phlegm and stasis group and 9 patients in the dampness-heat internal accumulation group developed liver failure. Multivariate logistic regression analysis showed that PT （OR=1.794， 95%CI 1.249-2.576）， TBIL （OR=1.111， 95%CI 1.026-1.203）， ALT （OR=1.053， 95%CI 1.004-1.105）， and TCM syndrome （OR=5.420， 95%CI 1.384-21.227） were independent risk factors for the development of liver failure in hepatic WD. ConclusionCompared with the hepatic WD patients with the syndrome of dampness-heat internal accumulation， those with the syndrome of combined phlegm and stasis exhibit severe liver function impairment and disease conditions. Furthermore， TCM syndrome serves as an independent predictive factor for the occurrence of liver failure in patients with hepatic WD.

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.

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.

ObjectiveTo optimize the flow cytometric sorting workflow for myeloid-derived suppressor cells （MDSCs） from murine Lewis lung carcinoma （LLC） subcutaneous tumor tissues， improving single-cell suspension preparation efficiency and sorting purity， thereby providing high-quality cells for subsequent functional studies. MethodsSubcutaneous LLC tumor tissues were harvested from C57BL/6 mice， and two enzymatic digestion protocols were first compared to evaluate their effects on single-cell suspension preparation. After staining with a viability dye （Live/Dead） and fluorochrome-conjugated anti-mouse antibodies against CD45， CD11b， and Gr-1， cells were loaded onto a Beckman CytoFLEX cell sorter. Next， conventional and optimized gating strategies were applied. In the optimized strategy， the CD45⁺ population was used as the initial gate to directly define an MDSC-enriched region， followed by selection of CD11b⁺Gr-1⁺ cells. Finally， purity was assessed by flow cytometry， viability was determined by trypan blue staining， and RT-qPCR was performed to measure the expression of MDSC signature genes， including Arg1， Nos2， IL-10， and S100A8/A9. ResultsThe optimized enzymatic digestion protocol significantly increased the yield and viability of single cells. After optimization of the gating strategy， the post-sort positivity rate （purity） was markedly improved. Arg1， Nos2， IL-10 and S100A8/A9 were highly expressed in the sorted cells， indicating that the isolated cells retained characteristic MDSC features and functional signatures. ConclusionBy optimizing both the tissue digestion protocol and the flow cytometric gating strategy， we establish an efficient workflow for isolating MDSCs from tumor tissues. This method improves the yield and purity of single-cell preparations while preserving antigen integrity， providing a reliable methodological foundation for subsequent studies on MDSC function and metabolism.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Intervention in chronically activated microglia-mediated neuroinflammation is a novel approach to treat Alzheimer's disease (AD). The low permeability of the blood‒brain barrier (BBB) and non-selective distribution in the brain severely restrict AD drugs' disease-modifying efficacy. Here, an immunosuppressant TREM2-lowing antisense oligonucleotides (ASOs) and resveratrol co-loaded cationic liposome is developed as an immune reprogramming nanomodulator modified by acid-cleavable BBB-targeting peptide and microglia-targeting peptide (Res@TcMNP/ASO) for AD management. Res@TcMNP/ASO can enter brain endothelial cells via D-T7 peptides. Then D-T7 undergoes an acid-responsive cleavage, facilitating the escape of Res@MNP/ASO from endo/lysosomes to cross the BBB. The detached Res@MNP/ASO specifically targets M1-phenotype microglia via exposed MG1 peptides to prompt the simultaneous delivery of two drugs into activated microglia. This nanomodulator can not only restore the immune function of microglia through TREM2-lowing ASO but also mitigate the immune stimulation to microglia caused by reactive oxygen species (ROS) through resveratrol, thereby synergistically inhibiting the chronic activation of microglia to alleviate neuroinflammation in AD. Our results indicate that this combination treatment can achieve significant behavioral and cognitive improvements in late APP/PS1 mice.

Stearoyl-coenzyme A desaturase 1 (SCD1) catalyzes the rate-limiting step of de novo lipogenesis and modulates lipid homeostasis. Although numerous SCD1 inhibitors were tested for treating metabolic disorders both in preclinical and clinic studies, the tissue-specific roles of SCD1 in modulating obesity-associated metabolic disorders and determining the pharmacological effect of chemical SCD1 inhibition remain unclear. Here a novel role for intestinal SCD1 in obesity-associated metabolic disorders was uncovered. Intestinal SCD1 was found to be induced during obesity progression both in humans and mice. Intestine-specific, but not liver-specific, SCD1 deficiency reduced obesity and hepatic steatosis. A939572, an SCD1-specific inhibitor, ameliorated obesity and hepatic steatosis dependent on intestinal, but not hepatic, SCD1. Mechanistically, intestinal SCD1 deficiency impeded obesity-induced oxidative stress through its novel function of inducing metallothionein 1 in intestinal epithelial cells. These results suggest that intestinal SCD1 could be a viable target that underlies the pharmacological effect of chemical SCD1 inhibition in the treatment of obesity-associated metabolic disorders.

Cancer immunotherapy has emerged as a promising strategy. However, low response rates and immune-related side effects have plagued immunotherapy. Metallic nanoparticles, utilizing metals as their framework, are gaining prominence in cancer immunotherapy. Metal ions have shown the ability to modulate immune status by activating the cGAS-STING pathway and inducing immunogenic cell death (ICD), thereby enabling multidimensional activation of immunotherapy. Metallic nanoparticles offer significant advantages in cancer immunotherapy, leading to their increasing use in enhancing therapeutic outcomes. In view of the ever-increasing research on metallic nanoparticles, this review presents the construction, characterization, and enhanced cancer immunotherapeutic effects of different types of metal nanosystems from the perspective of the immunoregulatory mechanisms of metal ions. We delve into the current limitations and future directions of metallic nanoparticles in this rapidly evolving field. To the best of our knowledge, this review offers the most up-to-date and systematic analysis of metallic nanoparticles in immunotherapeutic applications. It is anticipated that this review of metallic nanoparticles will inspire a more refined and intelligent design of metallic nanoparticles for future research, paving the way for advancing their clinical applications.

Objective:To investigate the role of Fem-1 homolog C(FEM1C)in breast cancer progression and elucidate its underlying regulat-ory mechanism.Methods:The expression of FEM1C in breast cancer tissues and cells were detected with qPCR.The binding of FEM1C to ELAVL1 protein was predicted with an online database and validated by CoIP analysis;and the binding of ELAVL1 protein to OPA1 mRNA was predicted by using the starBase database and validated by RIP analysis.Next,breast cancer cell MDA-MB-231 was transfected with FEM1C shRNA(sh-FEM1C)or overexpression vector(FEM1C)or/and ELAVL1 overexpression vector(ELAVL1)or/and OPA1 overexpression vector(OPA1),or treated with 100 μM Mdivi-1,an DRP1 inhibitor,or MYLS22,an OPA1 inhibitor.Finally,nude mice were injected with sh-FEM1C lentiviral vectors to construct xenograft tumor models,and tumor growth was monitored.Results:The expression of FEM1C was upregu-lated in breast cancer tissues(P<0.01).Silencing FEM1C inhibited the proliferation,induced apoptosis,promoted the expression of auto-phagy protein LC3 Ⅱ/Ⅰ,inhibited p62 protein expression,upregulated the protein level of PINK1 in mitochondrial,promoted the expres-sion of mitochondrial fission proteins DRP1 and MIEF2,and inhibited the expression of fusion proteins OPA1 and MFN1 in MDA-MB-231 cells(P<0.01).Mdivi-1 treatment inhibited DRP1 expression(P<0.01),but had no effect on cell viability(P>0.05);MYLS22 treatment inhibited OPA1 expression and counteracted the effect of FEM1C overexpression on MDA-MB-231 cells(P<0.01).Mechanistic studies revealed that FEM1C binds to ELAVL1 protein and promotes its expression(P<0.01);ELAVL1 protein stabilizes OPA1 mRNA by binding to it and upregu-lates OPA1 protein levels(P<0.01).Overexpression of OPA1 reversed the effect of FEM1C silencing on MDA-MB-231 cells(P<0.01).In vivo results showed that knockdown of FEM1C inhibited tumor growth in vivo(P<0.01).Conclusions:FEM1C promotes the stability of OPA1 mRNA by upregulation of ELAVL1 protein to promote mitochondrial fusion and inhibit autophagy,thereby promoting breast cancer progression.