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.

ObjectiveTo evaluate the clinical efficacy and safety of Wenshen Yangxue decoction combined with endometrial microstimulation in the treatment of infertile patients with polycystic ovary syndrome （PCOS， syndrome of kidney-Yang deficiency and blood stasis）. MethodsA randomized， positive-drug parallel-controlled， open-label clinical study was conducted. A total of 240 infertile PCOS patients with the syndrome of kidney-Yang deficiency and blood stasis who met the inclusion and exclusion criteria were randomly assigned into 4 groups， with 60 patients in each group. The control group was treated with clomiphene citrate （50-100 mg·d^-¹， orally for 5-10 consecutive days） for ovulation induction. On the basis of the therapy in the control group， the Wenshen group was additionally treated with Wenshen Yangxue decoction （250 mL， warm oral administration， twice daily， in the morning and evening）， and the stimulation group received endometrial microstimulation during the early follicular phase. The combined group was treated with clomiphene citrate plus Wenshen Yangxue decoction （at the same dosages as aforementioned） and endometrial microstimulation. The course of treatment for all the groups was 3 menstrual cycles. The pregnancy rate， ovulation status， sex hormone levels， glucose metabolism indicators， coagulation function， endometrial thickness， traditional Chinese medicine （TCM） symptom scores， and adverse reactions were observed in each group. ResultsA total of 239 patients were included in the final analysis， with 59 patients in the Wenshen group and 60 patients in each of the other three groups. The pregnancy rates were 43.3%（26/60） in the combined group and 32.2%（19/60） in the Wenshen group， both significantly higher than that （10%） in the control group （χ²=17.56，P<0.01）. Compared with the control group， the combined and Wenshen groups had increased mature follicle rates （P<0.01）， while the Wenshen group showed a decreased luteinization rate （P<0.05）. All the groups exhibited significant reductions in TCM symptom scores after treatment， and the Wenshen and combined groups had lower scores than the control group （P<0.01）. No statistically significant difference was found in the incidence of adverse events among the four groups， and all the adverse events were mild. ConclusionWenshen Yangxue decoction combined with endometrial microstimulation can alleviate the TCM symptoms of infertile PCOS patients with the syndrome of kidney-Yang deficiency and blood stasis， promote follicular maturation and ovulation， increase the cumulative pregnancy rate， and has good safety. It can provide new clinical evidence for the integrated traditional Chinese and Western medicine treatment of PCOS infertility.

ObjectiveTo evaluate the clinical efficacy and safety of Wenshen Yangxue decoction combined with endometrial microstimulation in the treatment of infertile patients with polycystic ovary syndrome （PCOS， syndrome of kidney-Yang deficiency and blood stasis）. MethodsA randomized， positive-drug parallel-controlled， open-label clinical study was conducted. A total of 240 infertile PCOS patients with the syndrome of kidney-Yang deficiency and blood stasis who met the inclusion and exclusion criteria were randomly assigned into 4 groups， with 60 patients in each group. The control group was treated with clomiphene citrate （50-100 mg·d^-¹， orally for 5-10 consecutive days） for ovulation induction. On the basis of the therapy in the control group， the Wenshen group was additionally treated with Wenshen Yangxue decoction （250 mL， warm oral administration， twice daily， in the morning and evening）， and the stimulation group received endometrial microstimulation during the early follicular phase. The combined group was treated with clomiphene citrate plus Wenshen Yangxue decoction （at the same dosages as aforementioned） and endometrial microstimulation. The course of treatment for all the groups was 3 menstrual cycles. The pregnancy rate， ovulation status， sex hormone levels， glucose metabolism indicators， coagulation function， endometrial thickness， traditional Chinese medicine （TCM） symptom scores， and adverse reactions were observed in each group. ResultsA total of 239 patients were included in the final analysis， with 59 patients in the Wenshen group and 60 patients in each of the other three groups. The pregnancy rates were 43.3%（26/60） in the combined group and 32.2%（19/60） in the Wenshen group， both significantly higher than that （10%） in the control group （χ²=17.56，P<0.01）. Compared with the control group， the combined and Wenshen groups had increased mature follicle rates （P<0.01）， while the Wenshen group showed a decreased luteinization rate （P<0.05）. All the groups exhibited significant reductions in TCM symptom scores after treatment， and the Wenshen and combined groups had lower scores than the control group （P<0.01）. No statistically significant difference was found in the incidence of adverse events among the four groups， and all the adverse events were mild. ConclusionWenshen Yangxue decoction combined with endometrial microstimulation can alleviate the TCM symptoms of infertile PCOS patients with the syndrome of kidney-Yang deficiency and blood stasis， promote follicular maturation and ovulation， increase the cumulative pregnancy rate， and has good safety. It can provide new clinical evidence for the integrated traditional Chinese and Western medicine treatment of PCOS infertility.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

Objective:To evaluate the role of the Toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88)-tumor necrosis factor receptor-associated factor 6 (TRAF6) signaling pathway in the reduction of cerebral ischemia-reperfusion injury (CIRI) by trilobatin pretreatment in rats.Methods:Eighty clean-grade healthy male Sprague-Dawley rats, aged 8 weeks, weighing 250-300 g, were divided into 4 groups ( n=20 each) using a random number table method: sham operation group (group S), group CIRI, trilobatin+ CIRI group (group TC) and trilobatin+ CIRI+ AAV-TLR4 group (group TCA). The model of CIRI was established by middle cerebral artery occlusion in anesthetized animals in CIRI, TC and TCA groups. In group TCA, the adeno associated virus was injected into the cortical region to up-regulate the expression of TLR4 at 21 days before developing the model. Trilobatin 15 mg/kg was administered by gavage twice daily for 3 days prior to ischemia in TC and TCA groups. The cognitive function was assessed using the modified Longa score at 24 h of reperfusion. Then the rats were sacrificed and the whole brain tissues were isolated for determination of the cerebral infarct size (by TTC staining), expression of TLR4, MyD88 and TRAF6 (by Western blot), and contents of interleukin-1 beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α) (by enzyme-linked immunosorbent assay) and for microscopic examination of the neuronal ultrastructure in ischemic cerebral cortex tissues (with a transmission electron microscope). Results:Compared with group S, the Longa score and percentage of cerebral infarct size were significantly increased, the expression of TLR4, MyD88 and TRAF6 in cerebral cortex tissues of ischemic regions was up-regulated, the contents of IL-1β, IL-6 and TNF-α were increased ( P<0.05), and the pathological damage to cortical neurons was aggravated in CIRI group. Compared with group CIRI, the Longa score and percentage of cerebral infarct size were significantly decreased, the expression of TLR4, MyD88 and TRAF6 was down-regulated, the contents of IL-1β, IL-6 and TNF-α were decreased in cerebral cortex tissues of ischemic regions ( P<0.05), and the pathological damage to cortical neurons was significantly attenuated in group TC. Compared with group TC, the Longa score and percentage of cerebral infarct size were significantly increased, the expression of TLR4, MyD88 and TRAF6 was up-regulated, the contents of IL-1β, IL-6 and TNF-α were increased in cerebral cortex tissues of ischemic regions ( P<0.05), and the pathological damage to cortical neurons was aggravated in group TCA. Conclusions:The TLR4-MyD88-TRAF6 signaling pathway is involved in the reduction of cerebral I/R injury by trilobatin pretreatment in rats.

Objective:To evaluate the role of the Toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88)-tumor necrosis factor receptor-associated factor 6 (TRAF6) signaling pathway in the reduction of cerebral ischemia-reperfusion injury (CIRI) by trilobatin pretreatment in rats.Methods:Eighty clean-grade healthy male Sprague-Dawley rats, aged 8 weeks, weighing 250-300 g, were divided into 4 groups ( n=20 each) using a random number table method: sham operation group (group S), group CIRI, trilobatin+ CIRI group (group TC) and trilobatin+ CIRI+ AAV-TLR4 group (group TCA). The model of CIRI was established by middle cerebral artery occlusion in anesthetized animals in CIRI, TC and TCA groups. In group TCA, the adeno associated virus was injected into the cortical region to up-regulate the expression of TLR4 at 21 days before developing the model. Trilobatin 15 mg/kg was administered by gavage twice daily for 3 days prior to ischemia in TC and TCA groups. The cognitive function was assessed using the modified Longa score at 24 h of reperfusion. Then the rats were sacrificed and the whole brain tissues were isolated for determination of the cerebral infarct size (by TTC staining), expression of TLR4, MyD88 and TRAF6 (by Western blot), and contents of interleukin-1 beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α) (by enzyme-linked immunosorbent assay) and for microscopic examination of the neuronal ultrastructure in ischemic cerebral cortex tissues (with a transmission electron microscope). Results:Compared with group S, the Longa score and percentage of cerebral infarct size were significantly increased, the expression of TLR4, MyD88 and TRAF6 in cerebral cortex tissues of ischemic regions was up-regulated, the contents of IL-1β, IL-6 and TNF-α were increased ( P<0.05), and the pathological damage to cortical neurons was aggravated in CIRI group. Compared with group CIRI, the Longa score and percentage of cerebral infarct size were significantly decreased, the expression of TLR4, MyD88 and TRAF6 was down-regulated, the contents of IL-1β, IL-6 and TNF-α were decreased in cerebral cortex tissues of ischemic regions ( P<0.05), and the pathological damage to cortical neurons was significantly attenuated in group TC. Compared with group TC, the Longa score and percentage of cerebral infarct size were significantly increased, the expression of TLR4, MyD88 and TRAF6 was up-regulated, the contents of IL-1β, IL-6 and TNF-α were increased in cerebral cortex tissues of ischemic regions ( P<0.05), and the pathological damage to cortical neurons was aggravated in group TCA. Conclusions:The TLR4-MyD88-TRAF6 signaling pathway is involved in the reduction of cerebral I/R injury by trilobatin pretreatment in rats.

The drugs used to improve brain metabolism mainly include ergotamine derivatives,GABA derivatives,vitamin B6 derivatives,neuropeptides,morpholines,hormones and other.However,these drugs may have adverse reactions during clinical application.This article focuses on the adverse effects of commonly used drugs for brain metabolism,and reviews the studies on the new state of pharmaceutical substances,such as drug combination,chiral resolution of isomers,crystal form of dominant drugs,co-crystal drugs and nanodrugs,with the aim of reducing adverse reactions.By summarizing the research on modifying the solid state of drugs to mitigate adverse reactions,this article provides new research insights for obtaining new drug with less adverse reaction and greater clinical value.

Traditional Chinese medicine (TCM) has become an important treasure trove of natural resources for the development of new medicines due to their diverse compositions, significant therapeutic effects, and few side effects. The screening of active ingredients in TCM represents a crucial step in elucidating the material basis and mechanism of action of TCM. At present, efficient and precise molecular recognition techniques based on intermolecular interactions have been extensively employed for the identification of active ingredients in TCM. This paper presents a review of the fundamental principles underlying solution-phase/affinity ligand fishing, solid-phase/affinity ligand fishing, molecular imprinting and molecular docking techniques, with a particular focus on their applications in the screening of active ingredients in TCM. Furthermore, the paper compares the advantages and disadvantages of the various techniques and identifies the limitations of existing techniques. In conclusion, the paper identifies the prospective trajectory of molecular recognition techniques in the domain of TCM research. This paper not only provides theoretical references for the development of new methods of active ingredient screening but also helps to promote the modernization and internationalization of TCM.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.