OBJECTIVE To provide standardized guidance for the homogenization construction and management of pharmaceutical care in urban medical groups. METHODS This consensus was jointly initiated by the Therapeutic Drug Monitoring Professional Committee of the Chinese Pharmacological Society and the Expert Committee on Precision Clinical Medication of the Guangdong Pharmaceutical Association. Led by Guangzhou Red Cross Hospital， a drafting group of 7 members and an expert group of 36 members were organized. The outline of the Expert Consensus on Homogeneous Construction and Management of Pharmaceutical Care in Urban Medical Groups （hereinafter referred to as the “Consensus”） was discussed and finalized using the nominal group technique， and a preliminary draft was formed. The Delphi method was used for online c orrespondence review， and 12 external experts were invited for evaluation. After analyzing and revising expert opinions， the final Consensus was formed. RESULTS &CONCLUSIONS This Consensus defines the position setting and appointment procedures for the chief pharmacist， and establishes a three-tier professional guidance network of “chief pharmacist-regional/specialist pharmacist-pharmaceutical liaison of member institutions”. It formulates unified management standards for the drug supply catalog， establishes a full-process homogenization mechanism for prescription review， prescription commentation and comprehensive pharmaceutical care， and specifies the core functions and performance requirements of the prescription review system. It also supports by long-term mechanisms including cost allocation and performance assessment. This consensus can serve as a systematic reference for the homogeneous construction and management of pharmaceutical care systems in urban medical groups.

Exportin 1 (XPO1) is aberrantly overexpressed in various malignant tumors and can lead to the loss of anti-tumor effects of important tumor suppressor proteins such as p53, RB1, and FOXO by mediating their nuclear export. Although XPO1 inhibitor Selinexor has entered clinical application, its single-agent anti-tumor activity remains suboptimal, which is closely related to the compensatory activation of multiple signaling pathways in response to XPO1 inhibition. Focusing on the core regulatory role of XPO1 in tumor cells, this article systematically summarizes the current landscape of combination therapies involving XPO1 inhibitors and various targeted agents, including inhibitors of CDK4/6, FLT3, BET, ATR, and BCL2/MDM2, aiming to provide some reference for the development of XPO1-centered combination therapy strategies.

Objective To fabricate a large-diameter vascular graft with a pore size gradient structure mimicking that of natural blood vessels, using poly-L-lactic acid (PLLA) and polycaprolactone (PCL) as base materials through electrospinning and ultrasonic pore-forming techniques, and to evaluate its application potential. Methods A three-layered tubular graft was fabricated from a PCL/PLLA blend (mass ratio 6 : 4) via electrospinning, followed by an ultrasonic pore-forming process to create a gradient porosity. The resulting graft (diameter: 2 cm, length: 4 cm) was implanted into the descending thoracic aorta of an experimental pig using an end-to-end anastomosis. Graft patency and anastomotic sites were monitored by computed tomography angiography (CTA) at 1 and 6 weeks post-surgery. After 2 months, the graft was explanted for systematic evaluation of vascular regeneration and repair through gross examination, histopathology (H&E and elastic fiber staining), immunohistochemistry [for ETS-related gene (ERG), Actin, and Vimentin], and scanning electron microscopy (SEM). Results Postoperative CTA confirmed excellent graft patency at both 1 and 6 weeks, with no evidence of thrombosis or anastomotic stenosis. Gross examination of the 2-month explant revealed a smooth luminal surface covered by neotissue. Histopathological analysis demonstrated that the graft successfully induced the formation of a three-layered structure resembling a native vessel wall, comprising endothelial cells, smooth muscle cells, and fibroblasts. Immunohistochemistry further verified coverage of the luminal surface by endothelial cells (ERG-positive), along with the presence of neosmooth muscle (Actin-positive) and fibroblasts (Vimentin-positive). Endothelial cells were observed adhering to the inner surface of the artificial vessel under SEM. Conclusion The biomimetic, three-layered PLLA/PCL large-diameter vascular graft, constructed via electrospinning and ultrasonic pore-forming, exhibits excellent short-term patency and biocompatibility in a large animal model. More importantly, it demonstrates a significant potential to promote host cell infiltration and achieve in situ regeneration of a three-layered vascular wall structure, providing a promising experimental basis for the development of next-generation functional vascular substitutes.

Objective To compare the clinical efficacy and safety differences between the triple immunosuppressive regimen of mizoribine (MZR) or mycophenolate mofetil (MMF) combined with tacrolimus (Tac) and glucocorticoids of kidney transplant recipients in one year after transplantation. Methods A single-center retrospective cohort study design was adopted. The clinical data of 156 patients who underwent the first allogeneic kidney transplantation at the Third Hospital of Peking University from January 2022 to December 2024 were included. The patients were divided into the MZR group (78 cases) and the MMF group (78 cases) based on the initial immunosuppressive regimen after transplantation. The baseline data, medication use in one year after transplantation, blood routine indicators, adverse events and clinical outcomes were compared between the two groups. For the repeated-measurement longitudinal data, repeated-measurement analysis of variance was used to evaluate the main effects of the groups, time and their interaction effects. Results At the primary efficacy endpoint, there were no statistically significant differences in the one-year survival rate, graft survival rate and incidence of acute rejection between the two groups (all P > 0.05). In terms of medication patterns and laboratory test indicators, there were significant time main effects and "time × group" interaction effects for Tac dosage (all P < 0.05). The Tac dosage in the MZR group was lower than that in the MMF group from 2 to 3 months after transplantation, and it was higher in the MZR group than in the MMF group from 7 to 12 months and one year after transplantation. White blood cell count in the MZR group was higher at one month after transplantation, and the platelet count was higher one year after transplantation (all P < 0.05). In terms of infection, the incidence of novel coronavirus and Pneumocystis jirovecii pneumonia infections in the MZR group was lower (all P < 0.05). In terms of metabolic indicators, the post-transplantation uric acid level was better in the MZR group than in the MMF group, but the total cholesterol level was higher one year after transplantation (all P < 0.05). In terms of liver function, there was a brief and mild increase in transaminase in the early stage after transplantation in the MZR group. Conclusions During the one-year follow-up after transplantation, both the MZR and MMF regimens demonstrate comparable immunosuppressive efficacy and overall safety in Chinese kidney transplant recipients. The MZR regimen shows clear advantages in reducing specific infection risks, alleviating bone marrow suppression and improving uric acid metabolism, but its potential impact on blood lipids needs to be monitored. Therefore, the MZR regimen may be an effective and safe alternative immunosuppressive option for kidney transplant recipients, especially those with high infection risk, poor hematological tolerance, or comorbid hyperuricemia.

ObjectiveTo explore the mechanisms of Qingchang Wenzhong Decoction （清肠温中方， QWD） in treating ulcerative colitis （UC）. MethodsA total of 100 male C57BL/6J mice were assigned to a pseudo-germ-free group （n=45） and a conventional group （n=55） using a random number table. Pseudo-germ-free model was established by giving antibiotic treatment and subsequently subjected to acute UC induction. After the model was successfully established， the 45 pseudo-germ-free acute UC mice were randomly allocated to a pseudo-germ-free model group， a pseudo-germ-free QWD group， and a pseudo-germ-free mesalazine group， with 15 mice in each group. The 55 conventional mice were randomly divided into a normal control group （n=10）， as well as a conventional model group， a conventional QWD group， and a conventional mesalazine group， with 15 mice in each group. Except for the normal control group， acute UC models were established in all other groups. Mice in the control group received no intervention. From day 32 of the experiment， mice in the pseudo-germ-free QWD group and the conventional QWD group were administered with QWD granules at a dose of 9.71 g/（kg·d） by gavage with deionized water， while those in the pseudo-germ-free mesalazine group and the conventional mesalazine group were given mesalazine enteric-coated tablets at a dose of 151.67 mg/（kg·d） by gavage. Mice in the remaining groups received an equal volume of deionized water once daily for 7 consecutive days. On day 25 of the experiment， six mice were randomly selected from both the pseudo-germ-free group and the conventional group to measure body weight， and fecal samples were collected for 16S rDNA sequencing to compare differences in gut microbiota， including operational taxonomic units （OTUs）， Shannon index， Observed_species index， and phylogenetic diversity （PD whole tree）. On day 39， body weight was measured in all groups， and the disease activity index （DAI） was evaluated. Colon length and colon wet weight were recorded. Histopathological changes in colonic tissues were assessed by hematoxylin and eosin （HE） staining， and histological injury scores were determined. In addition， the expression levels of mucopolysaccharides and mucin 2 （MUC2） in colonic tissues were measured. ResultsOn day 25， there was no significant difference in body weight between the pseudo-germ-free group and the conventional microbiota group （P＞0.05）. Compared to the conventional microbiota group， the pseudo-germ-free group showed significantly reduced OTUs， Shannon index， Observed_species index， and PD whole tree （P＜0.01）. On day 39， compared to the normal control group， mice in the conventional model group showed a significant decrease in the body weight and an increase in DAI， along with increased colon wet weight， shortened colon length， markedly elevated histopathological scores， and reduced expression of mucopolysaccharides and MUC2 （P＜0.01）. In contrast， no significant differences were observed in these parameters in the pseudo-germ-free model group （P＞0.05）. Compared to the conventional model group， the conventional QWD group showed significant improvement in all measured parameters， whereas the conventional mesalazine group showed reductions only in DAI scores and colon wet weight （P＜0.01）. No statistically significant differences were observed among the pseudo-germ-free model group， the pseudo-germ-free QWD group， and the pseudo-germ-free mesalazine group （P＞0.05）. ConclusionQWD may promote the reconstruction of the intestinal mucus barrier by regulating the intestinal flora， thereby exerting a therapeutic effect on acute UC.

ObjectiveTo explore the mechanisms of Qingchang Wenzhong Decoction （清肠温中方， QWD） in treating ulcerative colitis （UC）. MethodsA total of 100 male C57BL/6J mice were assigned to a pseudo-germ-free group （n=45） and a conventional group （n=55） using a random number table. Pseudo-germ-free model was established by giving antibiotic treatment and subsequently subjected to acute UC induction. After the model was successfully established， the 45 pseudo-germ-free acute UC mice were randomly allocated to a pseudo-germ-free model group， a pseudo-germ-free QWD group， and a pseudo-germ-free mesalazine group， with 15 mice in each group. The 55 conventional mice were randomly divided into a normal control group （n=10）， as well as a conventional model group， a conventional QWD group， and a conventional mesalazine group， with 15 mice in each group. Except for the normal control group， acute UC models were established in all other groups. Mice in the control group received no intervention. From day 32 of the experiment， mice in the pseudo-germ-free QWD group and the conventional QWD group were administered with QWD granules at a dose of 9.71 g/（kg·d） by gavage with deionized water， while those in the pseudo-germ-free mesalazine group and the conventional mesalazine group were given mesalazine enteric-coated tablets at a dose of 151.67 mg/（kg·d） by gavage. Mice in the remaining groups received an equal volume of deionized water once daily for 7 consecutive days. On day 25 of the experiment， six mice were randomly selected from both the pseudo-germ-free group and the conventional group to measure body weight， and fecal samples were collected for 16S rDNA sequencing to compare differences in gut microbiota， including operational taxonomic units （OTUs）， Shannon index， Observed_species index， and phylogenetic diversity （PD whole tree）. On day 39， body weight was measured in all groups， and the disease activity index （DAI） was evaluated. Colon length and colon wet weight were recorded. Histopathological changes in colonic tissues were assessed by hematoxylin and eosin （HE） staining， and histological injury scores were determined. In addition， the expression levels of mucopolysaccharides and mucin 2 （MUC2） in colonic tissues were measured. ResultsOn day 25， there was no significant difference in body weight between the pseudo-germ-free group and the conventional microbiota group （P＞0.05）. Compared to the conventional microbiota group， the pseudo-germ-free group showed significantly reduced OTUs， Shannon index， Observed_species index， and PD whole tree （P＜0.01）. On day 39， compared to the normal control group， mice in the conventional model group showed a significant decrease in the body weight and an increase in DAI， along with increased colon wet weight， shortened colon length， markedly elevated histopathological scores， and reduced expression of mucopolysaccharides and MUC2 （P＜0.01）. In contrast， no significant differences were observed in these parameters in the pseudo-germ-free model group （P＞0.05）. Compared to the conventional model group， the conventional QWD group showed significant improvement in all measured parameters， whereas the conventional mesalazine group showed reductions only in DAI scores and colon wet weight （P＜0.01）. No statistically significant differences were observed among the pseudo-germ-free model group， the pseudo-germ-free QWD group， and the pseudo-germ-free mesalazine group （P＞0.05）. ConclusionQWD may promote the reconstruction of the intestinal mucus barrier by regulating the intestinal flora， thereby exerting a therapeutic effect on acute UC.

OBJECTIVE To investigate the mechanism of Xibining Ⅱ formula in alleviating synovial inflammation and fibrosis in knee osteoarthritis （KOA） rats based on Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） pathway. METHODS Seventy-five male SD rats were randomly divided into sham operation group （Sham group）， KOA group， Xibining Ⅱ low-dose group （XBNⅡ-L group， 4 g/kg）， Xibining Ⅱ high-dose group （XBNⅡ-H group， 8 g/kg）， and Xibining Ⅱ high-dose combined with STAT3 activator Colivelin trifluoroacetate （C-TFA） group [C-TFA group， 8 g/kg Xibining Ⅱ+ 1.0 mg/（kg·d） C-TFA]， with 15 rats in each group. Except for the Sham group， the KOA model was established by anterior cruciate ligament transection in the other groups. After successful modeling， each group was given corresponding drugs by intragastric administration and （or） intraperitoneal injection once daily for 28 consecutive days. After the last medication， the pathological changes of synovial tissue of knee joint in each group were evaluated and the indicators were calculated. The levels of serum inflammatory factors were detected. The positive expressions of phosphorylated JAK2 （p-JAK2） and phosphorylated STAT3 （p-STAT3） in synovial tissue of the knee joint were detected. The expressions of JAK2/STAT3 pathway-related proteins and mRNAs in synovial tissue were detected. RESULTS Compared with the Sham group， the synovial lining cells in the KOA group showed significant proliferation and disordered arrangement； the Krenn score， fibrosis ratio， positive area percentage of p-JAK2 and p-STAT3， p-JAK2/JAK2 and p-STAT3/STAT3， protein expression of Collagen-Ⅰ and α -smooth muscle actin， the mRNA expression of JAK2， STAT3， Collagen-Ⅰ and α -smooth muscle actin， as well as serum levels of interleukin-1β and interleukin-18 were significantly increased （ P ＜0.05）. Compared with the KOA group， the above pathological changes were significantly improved in each dose group of Xibining Ⅱ formula， and all indicators were significantly decreased （ P ＜0.05）， with the XBNⅡ-H group showing better effects than the XBNⅡ-L group （ P ＜0.05）. Compared with the XBNⅡ-H group， the above pathological damages were aggravated in the C-TFA group， and all indicators were significantly worsened （ P ＜0.05）. CONCLUSIONS Xibining Ⅱ formula can alleviate synovial inflammation and fibrosis in KOA rats， and its mechanism may be related to inhibiting the activation of JAK2/STAT3 pathway.

OBJECTIVE To investigate the clinical characteristics of euglycemic diabetic ketoacidosis （euDKA） induced by empagliflozin， and provide references for safe medication. METHODS Case reports of euDKA induced by empagliflozin were retrieved and analyzed from PubMed， Web of Science， CNKI， and Wanfang Data. The Naranjo’s scale was adopted to assess the causal relationship between empagliflozin and euDKA. RESULTS A total of 29 patients were enrolled， including 16 males and 13 females，with a median age of 58 years. All patients were diagnosed with type 2 diabetes mellitus； 22 patients had at least one comorbidity. The median time to euDKA onset was 60 days after administration， and 7 cases occurred within 2 weeks of treatment. Perioperative periods，fasting，and low-carbohydrate or ketogenic diets were the main predisposing factors. Common presentations included nausea，vomiting， fatigue， tachypnea，and tachycardia. The causal relationship between empagliflozin and euDKA was assessed as “probable” in all cases. According to adverse reaction severity grading， 13 cases were grade 3 （severe） and 16 cases were grade 4 （life-threatening）. All patients discontinued empagliflozin and recovered after corresponding treatment. CONCLUSIONS euDKA is a serious adverse reaction to empagliflozin， which mostly occurs early in treatment. Perioperative periods， fasting， and ketogenic diets are prone to induce euDKA. Elderly patients and those with comorbidities are at higher risk. Risk assessment should be conducted before clinical administration； blood ketones and acid-base monitoring should be strengthened in the early medication period； withhold the drug before elective surgery， avoid prolonged fasting；upon diagnosis， discontinue empagliflozin and initiate intravenous insulin， provide fluid resuscitation promptly， and use other treatments to improve patient prognosis.

[摘 要] 目的：探究β-半乳糖苷α2,6-唾液酸转移酶1（ST6GAL1）和双特异性磷酸酶26（DUSP26）在结直肠癌（CRC）中的表达及其对巨噬细胞极化和肿瘤进展的影响。方法：选取CRC患者126例，采用免疫组织化学染色法检测肿瘤组织和癌旁组织中ST6GAL1、DUSP26蛋白表达。采用Western blotting、免疫共沉淀、外泌体鉴定、流式细胞术、ELISA、免疫荧光等方法，分析ST6GAL1、DUSP26及其相关信号通路对CRC细胞外泌体介导的M2型巨噬细胞极化、线粒体功能和内质网应激的影响。CRISPR/Cas9和慢病毒系统构建ST6GAL1敲除（ST6GAL1-KO）和DUSP26过表达（DUSP26-OE）细胞模型，并采用小鼠肿瘤模型评估ST6GAL1-KO + DUSP26-OE联合干预对肿瘤生长、细胞增殖及凋亡的影响。结果：CRC患者肿瘤组织中ST6GAL1蛋白阳性率显著高于癌旁正常组织，而DUSP26蛋白阳性率显著低于癌旁正常组织（均P < 0.001）；CRC细胞中ST6GAL1蛋白表达显著高于正常结肠上皮细胞，而DUSP26蛋白表达及p-JNK/JNK、p-c-JUN/c-JUN水平均显著低于正常结肠上皮细胞（均P < 0.05）。CRC细胞来源的外泌体显著促进M2巨噬细胞极化，并上调下游蛋白p-Syk、p-PI3K、p-AKT、线粒体功能障碍蛋白DRP1和内质网应激蛋白CHOP、GRP78蛋白表达（均P < 0.01）。DUSP26-OE组或ST6GAL1-KO组CRC细胞来源的外泌体可抑制上述效应（P < 0.05或P < 0.01）。动物实验显示，ST6GAL1-KO组和DUSP26-OE组肿瘤体积均明显小于Vector组，联合干预组抑瘤效果最为显著（均P < 0.001）；联合干预组细胞增殖标志物PCNA阳性率降低，TUNEL阳性细胞显著增加（P < 0.05或P < 0.001）。ST6GAL1-KO和DUSP26-OE可显著降低小鼠肿瘤组织GRP78和DRP1阳性比例及小鼠体内M2巨噬细胞比例。结论：CRC中ST6GAL1高表达可能通过影响外泌体唾液酸化水平，参与M2型巨噬细胞极化及应激相关蛋白表达调控，DUSP26低表达可能削弱JNK相关通路对ST6GAL1表达的负向调控；两者联合干预对移植瘤生长的抑制作用更明显。

Autosomal dominant polycystic kidney disease （ADPKD） is a systemic hereditary renal disorder and can affect multiple organs， and congenital hepatic fibrosis is one of the manifestations of liver involvement and is an important complication of ADPKD. Symptomatic management is currently the main treatment method for this disease， and disease-specific drugs such as tolvaptan have limited indications and cannot correct the underlying genetic defect. This article reports a case of ADPKD with congenital hepatic fibrosis， and sirolimus was identified as the individualized treatment regimen based on peripheral blood functional genomic analysis and drug sensitivity prediction platform. The patient achieved significant improvements in symptoms and quality of life after treatment， with a stable kidney volume. This case shows that functional genomics has a potential value in guiding individualized treatment of rare genetic disorders， which provides new treatment ideas and practice paths for similar patients.