ObjectiveTo explore the possible mechanism of Tongbian Decoction （通便汤， TD） in treating slow transit constipation （STC）. MethodsTwenty-four SD rats were randomly divided into normal group， model group， TD group， and mosapride group， with 6 rats per group. Except for the normal group， STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment， rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage， while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride， and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration， fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension， the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin （GAS） and motilin （MTL） were measured by ELISA. Colonic histopathology was observed by HE staining， and mucus secretion by Alcian blue-periodic acid-Schiff （AB-PAS） staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit， stem cell factor （SCF）， autophagy-related protein 5 （ATG5）， Beclin1， vesicle-associated membrane protein B （VAPB）， and protein tyrosine phosphatase interacting protein 51 （VAPB-PTPIP51） were measured by Western Blot， and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF， C-kit， Beclin1， and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group， rats in the model group showed significantly reduced fecal pellet number， fecal water content， small intestinal transit rate， and serum GAS and MTL levels （P＜0.01）； the number of goblet cells decreased， and the mucosal and muscular layers of the colon became thinner； mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased， while calcium content decreased （P＜0.05 or P＜0.01）； and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group， both TD group and mosapride group showed increased fecal pellet number， fecal water content， small intestinal transit rate， serum GAS and MTL levels， and colonic calcium content， along with decreased Beclin1 and ATG5 protein levels （P＜0.05 or P＜0.01）； the mucosal thickness and goblet cell number increased significantly， and autophagosomes decreased； in the TD group， ATG5 and Beclin1 mRNA levels decreased； in the mosapride group， SCF， VAPB， and PTPIP51 mRNA levels increased， while Beclin1 mRNA decreased （P＜0.05 or P＜0.01）. Compared to the mosapride group， the TD group showed higher fecal pellet number， fecal water content， serum GAS levels， colonic calcium content， and C-kit expression， along with lower ATG5 and Beclin1 levels （P＜0.05 or P＜0.01）. ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions， reducing autophagy of interstitial cells of Cajal， and promoting intestinal motility.

ObjectiveTo explore the possible mechanism of Tongbian Decoction （通便汤， TD） in treating slow transit constipation （STC）. MethodsTwenty-four SD rats were randomly divided into normal group， model group， TD group， and mosapride group， with 6 rats per group. Except for the normal group， STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment， rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage， while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride， and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration， fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension， the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin （GAS） and motilin （MTL） were measured by ELISA. Colonic histopathology was observed by HE staining， and mucus secretion by Alcian blue-periodic acid-Schiff （AB-PAS） staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit， stem cell factor （SCF）， autophagy-related protein 5 （ATG5）， Beclin1， vesicle-associated membrane protein B （VAPB）， and protein tyrosine phosphatase interacting protein 51 （VAPB-PTPIP51） were measured by Western Blot， and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF， C-kit， Beclin1， and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group， rats in the model group showed significantly reduced fecal pellet number， fecal water content， small intestinal transit rate， and serum GAS and MTL levels （P＜0.01）； the number of goblet cells decreased， and the mucosal and muscular layers of the colon became thinner； mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased， while calcium content decreased （P＜0.05 or P＜0.01）； and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group， both TD group and mosapride group showed increased fecal pellet number， fecal water content， small intestinal transit rate， serum GAS and MTL levels， and colonic calcium content， along with decreased Beclin1 and ATG5 protein levels （P＜0.05 or P＜0.01）； the mucosal thickness and goblet cell number increased significantly， and autophagosomes decreased； in the TD group， ATG5 and Beclin1 mRNA levels decreased； in the mosapride group， SCF， VAPB， and PTPIP51 mRNA levels increased， while Beclin1 mRNA decreased （P＜0.05 or P＜0.01）. Compared to the mosapride group， the TD group showed higher fecal pellet number， fecal water content， serum GAS levels， colonic calcium content， and C-kit expression， along with lower ATG5 and Beclin1 levels （P＜0.05 or P＜0.01）. ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions， reducing autophagy of interstitial cells of Cajal， and promoting intestinal motility.

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.

ObjectiveThis study aimed to investigate the action mechanism by which Banxia Xiexintang （BXT） inhibits epithelial-mesenchymal transition （EMT） in chronic atrophic gastritis （CAG） rats by regulating the interleukin-17（IL-17）/extracellular regulated protein kinases（ERK）/CCAAT enhancer binding protein β（C/EBPβ）signaling pathway， thereby providing new theoretical evidence for the treatment of CAG with classic traditional Chinese medicine formulas. MethodsA CAG rat model was established by using the combined factor method. After successful modeling， the rats were randomly divided into the model group， low-， medium-， and high-dose groups （0.549， 1.098， 2.196 g·kg^-1， respectively） of BXT， and the positive drug group （vitacoenzyme， 0.3 g·kg^-1）. A normal control group was also set up. After 8 weeks of intervention， the pathological changes of gastric tissue were evaluated. The enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of IL-17， tumor necrosis factor-α （TNF-α）， cyclooxygenase-2 （COX-2）， and C/EBPβ in serum， as well as the contents of EMT markers in gastric mucosal tissue including E-cadherin， N-cadherin， and vimentin. The immunohistochemistry method was employed to determine the localization and protein expression levels of IL-17， p-ERK， and C/EBPβ in gastric mucosal tissue. Western blot was used to detect the protein expressions of C/EBPβ， ERK， and its phosphorylated form （p）-ERK in gastric mucosa. Real-time polymerase chain reaction （Real-time PCR） was applied to measure the mRNA expression levels of ERK， COX-2， and C/EBPβ in gastric mucosa. ResultsCompared with those in the normal control group， the rats in the model group showed gastric mucosal glandular atrophy and inflammatory cell infiltration. The protein and their related mRNA expressions of C/EBPβ， ERK， and p-ERK in gastric mucosa were significantly increased （P<0.05，P<0.01）. The levels of IL-17， TNF-α， COX-2， and C/EBPβ in serum were significantly increased （P<0.01）. The contents of N-cadherin and vimentin in gastric mucosal tissue were significantly increased， while the content of E-cadherin was significantly decreased （P<0.01）. Compared with the model group， after intervention with different doses of BXT， the pathological damage of the gastric mucosa was improved to varying degrees. The protein and mRNA expressions of C/EBPβ， ERK， and p-ERK in gastric mucosa were significantly reduced （P<0.05，P<0.01）. The levels of IL-17， TNF-α， COX-2， and C/EBP β in serum were significantly decreased （P<0.01）. The contents of N-cadherin and vimentin in gastric mucosa tissue were decreased， while the content of E-cadherin was increased （P<0.05，P<0.01）. ConclusionBXT can effectively improve the pathological damage of gastric mucosal tissue in CAG rats. Its action mechanism may be related to reducing the levels of IL-17 and TNF-α in serum， regulating the IL-17/ERK/C/EBPβ signaling pathway and inhibiting the EMT process.

ObjectiveA mouse model of vaccinia virus Tiantan strain (VTT)-induced encephalopathy was developed using AG6 mice. MethodsVTT was amplified by infecting Vero cells at a multiplicity of infection (MOI) of 0.01, followed by concentration and titration. After 72 h of incubation, virus-containing cells were collected and subjected to concentration. The concentrated viral suspension was serially diluted (10-fold dilutions) and added to 6-well plates containing confluent Vero cell monolayers for plaque assay. The number of plaques formed in each well was counted, and the virus titer was calculated based on the dilution factor. Fourteen 5-6-week-old AG6 mice (half male and half female, housed separately by sex) were randomly divided into a control group (n=3, PBS), a low-dose group (n=6, 1×10⁵ PFU), and a high-dose group (n=5, 5×10⁵ PFU). The mice were anesthetized by isoflurane inhalation and then infected via intranasal instillation. The mental state of the mice in each group was observed daily, and the body weight and mortality were recorded. On day 13 post-infection, 2% Evans Blue (4 mL/kg body weight) was administered via tail vein injection to assess blood-brain barrier (BBB) disruption. Subsequently, brain tissue samples were collected for immunofluorescence analysis to evaluate the activation of astrocytes and microglia. ResultsThe titer of purified VTT was 1×10⁷ PFU/mL. Compared with the control group, mice in the low-dose group showed no significant change in body weight, and no lethality was observed. In contrast, mice in the high-dose group exhibited significant weight loss starting on day 5 post-infection (P<0.05), accompanied by lethality. On day 13 post-infection, no Evans Blue extravasation was detected in the brain tissues of the low-dose group, while the olfactory bulb region of the high-dose group displayed distinct blue staining, indicating disruption of the BBB. Immunofluorescence analysis revealed no significant proliferation of astrocytes and microglia in the olfactory bulb region of the low-dose group on day 13 post-infection. In contrast, marked activation of glial cells was observable in the high-dose group. ConclusionAn animal model of VTT-induced encephalopathy in AG6 mice is successfully established, characterized by BBB disruption and reactive gliosis specifically localized to the olfactory bulb region, manifested as astrocytic and microglial proliferation.

Stroke is one of the leading causes of disability and mortality worldwide. Research into its mechanisms and the development of therapeutic strategies heavily rely on animal models that accurately replicate the pathological features of human disease. An ideal animal model for stroke should not only reproduce the neurological deficits and pathological changes observed in clinical patients but also demonstrate good reproducibility and translational value. This review focuses on the preparation and evaluation methods of ischemic stroke animal models. Firstly, it elaborates on the selection criteria, advantages, and disadvantages of experimental animals, including rodents (rats, mice) and non-rodents (non-human primates, miniature pigs, rabbits, zebrafish). Secondly, it provides a detailed overview of the modeling principles, key procedures, and application scopes for ischemic stroke models and hemorrhagic stroke models. Furthermore, the review summarizes advances in the applications of emerging technologies—including gene editing [e.g., clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing], multimodal imaging (e.g., two-photon microscopy, photoacoustic imaging), artificial intelligence, optogenetics, 3D bioprinting, organoid models, and multi-omics–in model optimization, precise assessment, and mechanistic investigation. Finally, based on a systematic analysis of relevant domestic and international literature from 2019 to 2024, this review discusses model selection strategies based on research objectives, a multidimensional evaluation system encompassing behavioral, imaging, and molecular pathological assessments, and envisions future directions involving technological integration to achieve model precision and individualization. This article aims to provide a comprehensive methodological reference to help researchers select appropriate animal models of stroke according to specific scientific questions.

OBJECTIVE To compare the efficacy and safety of evolocumab and probucol in patients with ultra-high-risk atherosclerotic cardiovascular disease （ASCVD） following percutaneous coronary intervention （PCI）. METHODS A retrospective analysis was conducted on 156 ultra-high-risk ASCVD patients who underwent PCI in our institution between January 1， 2023 and December 31， 2024. According to the lipid-lowering regimen， the patients were categorized into evolocumab group （ n ＝86） and probucol group （ n ＝70）. Changes in lipid parameters [total cholesterol （TC）， low-density lipoprot ein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， triglycerides， lipoprotein （a）， and lipid goal achievement rate ] ， inflammatory markers [interleukin-6 （IL-6） and C-reactive protein （CRP） ] ， and cardiac function indices （left ventricular ejection fraction， left ventricular end-systolic diameter， left ventricular end-diastolic diameter， and N-terminal pro-B-type natriuretic peptide） were compared between two groups at baseline and after 6 months of treatment. The incidence of adverse clinical events during treatment， including acute myocardial infarction， in-stent restenosis， acute heart failure， cerebral hemorrhage， and stroke， was also evaluated. RESULTS No statistically significant differences were observed between the two groups at baseline （ P ＞0.05）. After 6 months of treatment， both groups demonstrated significant improvements in lipid profiles （except HDL-C） and inflammatory markers compared to those at baseline （ P ＜0.05）. The evolocumab group exhibited greater reductions in TC， LDL-C， IL-6， and CRP， along with a higher lipid target achievement rate， compared with the probucol group （ P ＜0.05）. There were no statistically significant differences in the cardiac function-related indicators before and after treatment between the two groups， nor in the incidence of adverse events during the treatment （ P ＞0.05）. CONCLUSIONS For ultra-high-risk ASCVD patients after PCI， both of the above treatment options are associated with improvements in blood lipid and inflammatory response， with good safety during short-term follow-up. Evolocumab shows superior efficacy in TC， LDL-C and inflammatory markers reduction and lipid target achievement， compared to probucol.

Objective: To explore the association of outdoor activity time and sleep duration with screening myopia in primary school students, so as to provide strategies for myopia prevention. Methods: Through a convenience sampling method, a survey was conducted among 4 248 primary school students aged 7-13 years from three primary schools in Xihu District, Nanchang City, Jiangxi Province from May to July, 2023. The average daily outdoor activity time and sleep duration on both weekdays and weekends were investigated in primary school students by using a self designed questionnaire. Uncorrected visual acuity tests and non cycloplegic autorefraction were measured by professional optometrists. Inter group comparisons were conducted using the Chi square test. Logistic regression model was used to analyze the association of outdoor activity time and sleep duration with screening myopia. Results: The detection rate of screening myopia in primary school students was 33.6%, with the rate in boys (32.0%) lower than that in girls (35.3%), and the difference was statistically significant ( χ 2=5.11, P =0.02). The analysis results of Logistic regression showed that after adjusting for factors such as gender, grade and parental education level, both average daily outdoor activity time ＜2 h on both weekdays and weekends ( OR =1.27, 95% CI =1.11-1.46) and sleep duration <10 h ( OR =1.17, 95% CI =1.01- 1.35 ), as well as their combined effect ( OR =1.57, 95% CI =1.25-1.98), were associated with an increased risk of screening myopia in primary school students(all P <0.05). Subgroup analysis results indicated that compared to boys ( OR =1.46, 95% CI = 1.07 -1.99), girls( OR =1.73, 95% CI =1.22-2.44) with insufficient outdoor activity time and sleep duration had a higher risk of screening myopia(both P <0.05). Conclusions There is a negative correlation of outdoor activity time and sleep duration with screening myopia in primary school students. Outdoor activity time and extending sleep duration should be increased to reduce the risk of myopia in primary school students.

Objective: To determine the association between exposure to entertainment screen content on mobile phones and symptoms of anxiety-depression co-morbidity among college students,so as to provide evidence for mental health interventions. Methods: A baseline survey was conducted from April to May 2019. A total of 1 135 college students were selected from one university each in Shangrao City, Jiangxi Province and Hefei City, Anhui Province using cluster random sampling method. A follow up study was conducted in November 2019, resulting in 1 110 matched valid responses. Self rating questionnaires were used to assess the exposure of entertainment screen content. The Depression Anxiety Stress Scale-21(DASS-21) and the Patient Health Questionnaire-9 (PHQ-9) were used to evaluate the anxiety symptoms, depressive symptoms, and symptoms of anxiety-depression co-morbidity among college students. A multivariate binary Logistic regression model was constructed following initial intergroup comparisons with Chi-square test to determine the association between baseline exposure to mobile entertainment screen content and the risk of symptoms of anxiety depression co-morbidity at baseline and the 6 month follow up. Results: The prevalence rates of symptoms of anxiety-depression co-morbidity among college students were 25.4% and 20.6% at baseline and follow up, respectively.After adjusting for confounding factors such as gender, self rated family economic status and self rated health status, the results of multivariate binary Logistic regression analysis showed that compared with the appropriate exposure level group, the exposure of entertainment screen content on mobile phones at baseline, including frequent exposure to reading( OR =1.65,95% CI =1.14-2.39), occasional exposure to other entertainment screen content ( OR =1.46,95% CI =1.01-2.10)and frequent exposure to other entertainment screen content( OR =1.76,95% CI =1.20-2.60), increased the co-occurrence risk of symptoms of anxiety-depression co-morbidity among college students during the follow up period (all P <0.05). Conclusion Occasional or frequert exposure to mobile entertainment screen content can increase the risk of symptoms of anxiety depression co-morbidity among college students.

ObjectiveTo investigate the mechanisms of Tongnao decoction （TND） in mice with acute ischemic stroke （AIS）. MethodsFifty male C57BL/6J mice were randomly divided into a sham operation group， model group， TND low-dose group （1.86 g·kg^-1）， TND high-dose group （3.72 g·kg^-1）， and butylphthalide （NBP） group （10 mg·kg^-1）， with 10 mice in each group. A mouse model of cerebral ischemic injury was established using photochemical thrombosis （PT）. The sham operation group and model group were administered an equal volume of normal saline by gavage. All five groups were treated once daily for 14 consecutive days. Behavioral tests were performed before modeling and at the end of administration. T₂-weighted imaging （T₂WI） was performed 3 days after modeling to evaluate the extent of injury. Hematoxylin-eosin （HE） staining was used to observe histological changes in the cerebral cortex， and Nissl staining was used to observe neuronal morphology. Cerebral blood flow in mice was detected using a laser speckle contrast imaging （LSCI） system. Immunofluorescence staining was used to detect the cell proliferation marker bromodeoxyuridine （BrdU） and the highly glycosylated type I transmembrane glycoprotein CD34. Western blot analysis was used to detect the expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， glycogen synthase kinase-3β （GSK-3β）， and their phosphorylation levels， as well as tight junction-related proteins zonula occludens-1 （ZO-1）， Occludin， and Claudin-5 in the peri-infarct tissue. Thirty-five zebrafish were randomly divided into normal control group， model group， TND low and high dose groups （0.16， 0.32 g·L^-1） and NBP group （10 μmol·L^-1）， with 7 in each group. A stereoscopic fluorescence microscope was used to observe vascular growth in zebrafish. ResultsImaging showed that PT caused ischemia in the right cortical region. Behavioral tests indicated that， compared with the model group， the drug-treated groups reduced the error rate of irregular balance ladder climbing on the affected side and shortened the tape removal time （P<0.05）. HE staining and Nissl staining showed that， compared with the model group， the drug-treated groups exhibited reduced brain tissue damage， fewer scars， and improved neuronal morphology. LSCI results showed that the drug-treated groups partially restored cerebral blood perfusion and promoted the establishment of collateral circulation compared with the model group. Immunofluorescence staining indicated that the drug-treated groups increased the positive rates of BrdU and CD34 compared with the model group （P<0.01）， promoting angiogenesis. Meanwhile， compared with the model group， the drug-treated groups upregulated the expression levels of p-PI3K， p-Akt， p-GSK-3β， and tight junction proteins ZO-1， Occludin， and Claudin-5 （P<0.05，P<0.01）， and increased the number of intersegmental vessels in zebrafish （P<0.05，P<0.01）. ConclusionTND can promote angiogenesis around the infarct in PT model mice by regulating the PI3K/Akt/GSK-3β signaling pathway， thereby improving cerebral ischemic injury.