OBJECTIVE To formulate Guidelines for the standardized implementation of pharmacist-managed clinics （ 2026 edition ） in response to the challenges faced by such clinics in China， including uneven development， large discrepancies in service specifications， insufficient patient awareness， and limited medical insurance coverage. METHODS Led by the Pharmaceutical Affairs Professional Committee of the Chinese Hospital Association， the Evidence-based Pharmacy Professional Committee of the Chinese Pharmaceutical Association， and the Hospital Pharmacy Professional Committee of the Cross-strait Medical and Health Exchange Association， a total of 19 domestic hospital pharmacy experts were organized. Through a systematic review of national policies and literature research， current practical experience was summarized. Consensus on the contents of the guidelines was reached after in-depth discussions. RESULTS &CONCLUSIONS The guidelines covered five sections： definition and connotation of pharmacist-managed clinics， establishment requirements， implementation and management， post competency， and practical research. Firstly， the definition and connotation included three operational forms of pharmacist-managed clinics （independent mode， physician-pharmacist joint mode， and online pharmacist-managed clinic mode） and classified service modes （specialty-specific， drug-specific， and disease-specific pharmacist-managed clinics）. The establishment requirements were further refined， covering system construction （pharmaceutical service management system， quality control and assessment mechanism）， personnel qualifications （professional credentials， continuing education and professional training， etc）， service recipients， as well as service venues and facilities. Subsequently， the implementation and management of pharmacist-managed clinics were proposed， involving service procedures， intervention measures， documentation and records， patient education and follow-up， humanistic care， as well as risk management and quality control. Finally， post competency encompassed the competency requirements for pharmacists providing services in pharmacist-managed clinics， as well as the suggestions on teaching methods； practical research encouraged the conduct of high-quality pharmaceutical practice in the setting of pharmacist-managed clinics. The guidelines provide valuable guidance for the standardized implementation of pharmacist-managed clinics in China in terms of establishment， management， teaching， and research， fill the guideline gap in this field， and can promote the high-quality development of pharmacist-managed clinics.

Objective To investigate the role and regulatory mechanism of LINC00657 in the progression of cervical cancer. Methods Bioinformatics analysis predicted potential binding sites between LINC00657 and miR-30a-5p and between miR-30a-5p and Skp2. These sites were verified by using RNA immunoprecipitation and dual-luciferase reporter experiments. LINC00657, miR-30a-5p, and Skp2 mRNA expression levels in cervical cancer tissues and cell lines were assessed by utilizing RT-qPCR. Western blot analysis was employed to examine the protein levels of Skp2 in cells and subcutaneous xenograft tumor models in nude mice. Immunohistochemistry was applied to analyze Skp2 expression in animal tissues. The cellular processes of cervical cancer cell lines were evaluated through CCK-8, scratch, and Transwell assays. Results LINC00657 and Skp2 presented binding sites for miR-30a-5p. In cervical cancer, LINC00657 and Skp2 showed high expression levels (P<0.05), whereas miR-30a-5p displayed low expression (P<0.05). Functional experiments demonstrated that linc00657 upregulates Skp2 expression, a process that is dependent on its sequestration of miR-30a-5p. Conclusion LINC00657 promoted the malignant progression of cervical cancer by upregulating Skp2 expression through specifically sequestering miR-30a-5p, thereby relieving its inhibitory effect on the target gene Skp2.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Objective:To investigate the mechanism of LncRNA XIST on proliferation,apoptosis and invasion of tongue squamous cell carcinoma(TSCC)cells by regulating miR-337/ADAM28.Methods:qRT-PCR was used to detect the expression of XIST,miR-337,ADAM28 mRNA in TSCC tissues and cells.The expression of ADAM28,CyclinD1,MMP-9,MMP-14,Caspase-3 and Bax proteins was detected by Western blot.MTT assay was applied to detect cell activity.Transwell method was applied to detect the invasion ability of cells.Cell apoptosis was detected by flow cytometry.The double luciferase reporter gene experiment was applied to verify the targeting relationship between miR-337 and LncRNA XIST,miR-337 and ADAM28.Results:Compared with the adja-cent tissues,the expression of XIST and ADAM28 mRNA in TSCC increased,the expression of miR-337 decreased(P＜0.05).Compared with human normal oral mucosa cell HOK,the expression of XIST and ADAM28 in human TSCC cell lines increased,the expression of miR-337 decreased(P＜0.05).Silencing XIST reduced the expression of CyclinD1,MMP-9 and MMP-14,up-regula-ted the expression of Caspase-3 and Bax proteins,restrained the proliferation and invasion of CAL27 cells,and induced apoptosis.Inhibition of miR-337 expression reversed the silencing XIST on the proliferation and invasion of CAL27 cells,as well as the promo-ting effect on apoptosis.The double luciferase reporter gene experiment showed that XIST targeted down-regulation of miR-337,and miR-337 targeted negative regulation of ADAM28 expression.Conclusion:LncRNA XIST down-regulates miR-337 expression,up-regulates the expression of ADAM28,induces the proliferation and invasion of TSCC cells,and inhibits cell apoptosis.

Aim To evaluate the ameliorative effects of different ratios of Renshen-Huangjing(RH) on SPS-induced PTSD-like behaviors in mice,and to investi-gate the action mechanism using bioinformatics analysis and experimental studies.Methods The aqueous ex-tract was extracted in four ratios of RH in a total weight of 60 g,i.e.1∶0(RH1),2∶1(RH2),1∶2(RH3),and 0∶1(RH4).The extraction rates of Rg1,Rb1,and polysaccharides from different ratios of RH were then detected using UPLC-UV method.The SPS model was established,and RH1,RH2,RH3 and RH4(400 mg·kg-1)were administered by intragas-tric gavage for 14 day,followed by behavioral tests to e-valuate the PTSD-like behaviors.The serum CORT,IL-1β and IL-10 were determined by ELISA.The possible targets of action were analyzed using bioinformatics.The expression levels of Calpain-1,PSD95,BDNF and GluN2B in the hippocampus were detected by Western blot.Results The SPS model induced PTSD-like be-haviors in mice.Serum levels of CORT and IL-1β in-creased and level of IL-10 decreased in SPS model.After treatment with different ratios of RHs,RH2 showed the best therapeutic effect,which was manifes-ted in the suppression of PTSD-like behaviors,the re-duction of CORT and IL-1β levels,and the promotion of IL-10 levels;160 overlapping targets might explain the therapeutic effects of RH on PTSD,and these tar-gets were enriched in inhibiting synaptic damage,exer-ting antioxidant properties and suppressing neuroin-flammation,respectively.RH2 prevented the SPS-in-duced decrease in the expression of Calpain-1,PSD95,BDNF and the elevation of GluN2B.Molecular docking showed strong binding of Rg1 and Rb1 to Calpain-1,PSD95,and BDNF,respectively.Conclusions The a-queous extract of RH in a 2∶1 ratio can more effec-tively prevent SPS-induced PTSD-like behaviors,and its effect may be related to targets such as Calpain-1,PSD95,BDNF and GluN2B.

Objective:To explore the association between the use of tetracyclines during pregnancy and congenital malformations, with the aim of providing evidence-based guidance for the rational use of antibiotics during pregnancy.Methods:Data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the Canada Vigilance Adverse Reaction (CVAR) database from January 2015 to September 2024 were collected. Five methods including Tree-based scan statistic (TreeScan), proportional reporting ratio (PRR), reporting odds ratio (ROR), the UK Medicines and Healthcare Products Regulatory Agency (MHRA) comprehensive standard, and the Bayesian confidence propagation neural network (BCPNN) were used to detect signals of risk for congenital malformations in offspring following maternal use of tetracyclines during pregnancy. A signal that met the threshold criteria of all above 5 methods was considered as a risk signal. Based on population-based cohort of the drug exposures and adverse pregnancy outcomes (DEEP) data from January 2013 to December 2021 in Xiamen City, propensity score matching (PSM)-based Poisson regression was applied to evaluate the association between the first-trimester tetracyclines exposure and congenital malformations in offspring. Adjusted relative risk (a RR) and its 95% confidence interval ( CI) were calculated. Sensitivity analysis was conducted to validate the reliability of the results. Results:A total of 304 098 reports of adverse events during pregnancy were obtained from the FAERS and CVAR databases. Among them, 5 028 reports were related to tetracyclines, including 1 026 reports of congenital malformations in offspring, involving congenital malformations of musculoskeletal system, other digestive system, and other congenital malformations. Signal detection results suggested that tetracyclines may be a risk signal for above congenital malformations in offspring. The DEEP data included 411 936 pregnant women. After PSM, 240 pregnant women exposed to tetracyclines were included. The results showed no significant association between the first-trimester tetracyclines exposure and congenital malformations in offspring (a RR=0.75, 95% CI: 0.26-2.17), sensitivity analysis also showed no correlation. Conclusions:Data mining from the FAERS and CVAR databases suggests a potential association between tetracyclines use during pregnancy and congenital malformations in offspring. However, the DEEP data study shows no significant correlation.

Objective:To evaluate the feasibility, safety, and clinical outcomes of full-time full-endoscopic lumbar interbody fusion (FELIF) using a bladed retractor fusion channel (BRFC) system with reversed-mounting designed instruments compared to a tubular fusion channel (TFC).Methods:This retrospective study analyzed 101 cases of uniportal coaxial endoscopic lumbar interbody fusion performed between June 2018 and April 2023. Based on the type of fusion channel utilized, patients were divided into the TFC group (59 cases) and the BRFC group (42 cases). The BRFC technique involved neurological decompression, endplate preparation, and interbody fusion performed under full-time endoscopic monitoring with reversed-mounting designed instruments. Key parameters, including surgery duration, intraoperative estimated blood loss (IEBL), complication incidence, and interbody fusion rate (assessed by Bridwell criteria), were compared between the two groups. Clinical outcomes, including visual analog scale (VAS) scores for back and leg pain, Japanese Orthopaedic Association (JOA) scores, and Oswestry Disability Index (ODI), were recorded preoperatively, postoperatively, and at the final follow-up. Additionally, disc height at the fusion level was measured at one week postoperatively.Results:The mean follow-up duration was 42.9±12.1 months in the TFC group and 20.9±4.9 months in the BRFC group. No statistically significant differences were observed between the two groups in terms of surgery duration, IEBL, complication incidence, or interbody fusion rate (Grade 1 or 2 by Bridwell criteria) ( P>0.05). For single-level cases, the TFC group showed significantly better short-term clinical outcomes than the BRFC group at one week postoperatively, with JOA scores of 23(20, 25) versus 20(18, 23) ( Z=3.020, P=0.003) and ODI scores of 16%(11%, 21%) versus 28%(21%, 41%) ( Z=4.740, P<0.001). For double-level cases, the JOA score in the TFC group [23(20, 25)] was also significantly better than that in the BRFC group [20(18, 21)] ( Z=2.054, P=0.040) at one week postoperatively. However, at the final follow-up, all clinical indicators showed no significant differences between the two groups ( P>0.05). The disc height at the fusion level significantly increased at one week postoperatively compared to preoperative measurements in both groups ( P<0.05). However, the BRFC group demonstrated a significantly more recovery of disc height at one week postoperatively [(1.46±0.28) cm] compared to the TFC group [(1.17±0.20) cm] ( t=5.947, P<0.001). Conclusion:Full-time FELIF using the BRFC system and reversed-mounting designed instruments is a feasible, safe, and effective approach. However, its short-term clinical outcomes appear inferior to traditional FELIF using the TFC system.

Objective:To investigate the mechanism of LncRNA XIST on proliferation,apoptosis and invasion of tongue squamous cell carcinoma(TSCC)cells by regulating miR-337/ADAM28.Methods:qRT-PCR was used to detect the expression of XIST,miR-337,ADAM28 mRNA in TSCC tissues and cells.The expression of ADAM28,CyclinD1,MMP-9,MMP-14,Caspase-3 and Bax proteins was detected by Western blot.MTT assay was applied to detect cell activity.Transwell method was applied to detect the invasion ability of cells.Cell apoptosis was detected by flow cytometry.The double luciferase reporter gene experiment was applied to verify the targeting relationship between miR-337 and LncRNA XIST,miR-337 and ADAM28.Results:Compared with the adja-cent tissues,the expression of XIST and ADAM28 mRNA in TSCC increased,the expression of miR-337 decreased(P＜0.05).Compared with human normal oral mucosa cell HOK,the expression of XIST and ADAM28 in human TSCC cell lines increased,the expression of miR-337 decreased(P＜0.05).Silencing XIST reduced the expression of CyclinD1,MMP-9 and MMP-14,up-regula-ted the expression of Caspase-3 and Bax proteins,restrained the proliferation and invasion of CAL27 cells,and induced apoptosis.Inhibition of miR-337 expression reversed the silencing XIST on the proliferation and invasion of CAL27 cells,as well as the promo-ting effect on apoptosis.The double luciferase reporter gene experiment showed that XIST targeted down-regulation of miR-337,and miR-337 targeted negative regulation of ADAM28 expression.Conclusion:LncRNA XIST down-regulates miR-337 expression,up-regulates the expression of ADAM28,induces the proliferation and invasion of TSCC cells,and inhibits cell apoptosis.

Objective To explore the clinical efficacy of Liuwei Dihuang Capsules for type 2 diabetes mellitus(T2DM)with yin deficiency syndrome and the effects on intestinal flora and inflammatory factors.Methods Totally 60 patients of T2DM with yin deficiency syndrome in Dongzhimen Hospital of Beijing University of Chinese Medicine from September 2022 to June 2023 were selected as the study objects,and were divided into control group and observation group according to the method of block randomization,with 30 cases in each group.Both groups received basic treatment.The control group was given a simulated agent of Liuwei Dihuang Capsules,while the observation group was given Liuwei Dihuang Capsules.The treatment course for both groups was 4 weeks.Clinical efficacy,blood glucose levels[fasting plasma glucose(FPG),2-hour postprandial plasma glucose(2 hPG),glycated albumin(GA)],serum insulin levels[fasting insulin(FINS)and insulin resistance index(HOMA-IR)],changes in gut microbiota,and serum inflammatory cytokine levels[interleukin(IL)-6,tumor necrosis factor(TNF)-α]of both groups were compared.Results The total effective rate of the observation group(76.67%)was better than that of the control group(50.00%)(P<0.05).Compared with before treatment,the FPG,2 hPG,GA,FINS and HOMA-IR decreased in the observation group,while the FPG,2 hPG and FINS decreased in the control group(P<0.05);after treatment,the Shannon index of the observation group increased after treatment(P<0.05),and the diversity of the microbiota increased;the abundance of the microbial communities such as Coprococcus 3,Cutibacterium,Pseudomonas,Faecalibaculum,Dubosiella and Mucispirillum significantly increased(P<0.05);the abundance of Sphingomonas,Corynebacterium 1,Ileibacterium,Ruminiclostridium and other microbiota communities significantly decreased(P<0.05).Compared with before treatment,the levels of IL-6 and TNF-α in both groups were significantly reduced after treatment(P<0.01,P<0.05).After treatment,the levels of IL-6 and TNF-α in the observation group were significantly lower than those in the control group(P<0.05).Conclusion Liuwei Dihuang Capsules can effectively reduce blood glucose levels in patients of T2DM with yin deficiency syndrome,improve insulin resistance,increase gut microbiota diversity,increase beneficial bacterial abundance,reduce harmful bacterial abundance,and alleviate inflammatory cytokine levels.