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.

Sishen Pills and its separated prescriptions are classic prescriptions of traditional Chinese medicine to treat intestinal diseases. In this study, a high-performance liquid chromatography-electrospray ionization tandem mass spectrometry(HPLC-ESI-MS/MS) technology was used to identify the components of Sishen Pills, Ershen Pills, and Wuweizi Powder. The positive and negative ion sources of electrospray ionization were simultaneously collected by mass spectrometry. A total of 11 effective components were detected in Sishen Pills, with four effective components detected in Ershen Pills and eight effective components detected in Wuweizi Powder, respectively. To explore the effects of Sishen Pills and its separated prescriptions on the human intestinal flora, an in vitro anaerobic fermentation model was established, and the human intestinal flora was incubated with Sishen Pills, Ershen Pills, and Wuweizi Powder in vitro. The 16S rDNA sequencing technology was used to analyze the changes in the intestinal flora. The results showed that compared with the control group, Sishen Pills, and its separated prescriptions could decrease the intestinal flora abundance and increase the Shannon index after fermentation. The abundance of Bifidobacterium was significantly increased in the Sishen Pills and Ershen Pills groups. However, the abundance of Lactobacillus, Weissella, and Pediococcus was significantly increased in the Wuweizi Powder group. After fermentation for 12 h, the pH of the fermentation solution of three kinds of liquids with feces gradually decreased and was lower than that of the control group. The decreasing amplitude in the Wuweizi Powder group was the most obvious. The single-bacteria fermentation experiments further confirmed that Sishen Pills and Wuweizi Powder had inhibitory effects on Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis, and the antibacterial activity of Wuweizi Powder was stronger than that of Sishen Pills. Both Sishen Pills and Ershen Pills could promote the growth of Lactobacillus brevis, and Ershen Pills could promote the growth of Bifidobacterium adolescentis. This study provided a more sufficient theoretical basis for the clinical application of Sishen Pills and its separated prescriptions.
Humans ; Gastrointestinal Microbiome/drug effects* ; Drugs, Chinese Herbal/chemistry* ; Fermentation/drug effects* ; Bacteria/drug effects* ; Chromatography, High Pressure Liquid ; Tandem Mass Spectrometry ; Intestines/microbiology*

OBJECTIVES: To evaluate the photothermal and antibacterial activities of polydopamine-modified phycocyanin nanoparticles (PDA@PC NPs) and their capacity for promoting wound healing. METHODS: PDA@PC NPs were synthesized from phycocyanin (C-PC) and dopamine hydrochloride using a one-pot method. The photothermal activity of the nanoparticles was assessed in vitro by 808 nm laser irradiation, their biocompatibility was evaluated using CCK-8 assay, and their photothermal antibacterial activity by plate colony counting. In adult male BALB/c mice, two symmetrical full-thickness skin wounds (1.0 cm ×1.0 cm) were created on both sides of the spine, and 200 μL of Staphylococcus aureus suspension was inoculated into the wounds. The mice were divided into control group, PDA@PC NPs group, and PDA@PC NPs with laser irradiation group, and wound healing rates and histomorphological changes in the wound tissues were evaluated on days 0, 7 and 14 after modeling. RESULTS: The synthesized PDA@PC NPs exhibited no obvious cytotoxicity up to a concentration of 500 μg/mL and showed strong photothermal and antibacterial activities in response to 808 nm laser irradiation. In the mouse models, the size of the infected skin wounds showed substantial reduction at 7 and 14 days in PDA@PC NPs group and PDA@PC NPs with laser irradiation group, and the mean wound healing rate was faster in the latter group. HE staining and Masson's trichrome staining revealed extensive granulation tissue formation and collagen deposition on the wound surfaces in both of the treatment groups, and these changes were more obvious in the PDA@PC NPs with laser irradiation group. CONCLUSIONS PDA@PC NPs possess excellent photothermal and antibacterial activities and can effectively promote wound healing in mice.
Animals ; Indoles/chemistry* ; Wound Healing/drug effects* ; Mice ; Mice, Inbred BALB C ; Male ; Nanoparticles ; Polymers/chemistry* ; Phycocyanin/chemistry* ; Skin/injuries* ; Staphylococcus aureus/drug effects* ; Anti-Bacterial Agents/pharmacology*

The prelimbic cortex (PL) plays a critical role in processing both the sensory and affective components of pain. However, the underlying molecular mechanisms remain poorly understood. In this study, we observed a reduction in hyperpolarization-activated cation current (I_h) in layer V pyramidal neurons of the contralateral PL in a mouse model of spared nerve injury (SNI). The expression of hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) channels was also decreased in the contralateral PL. Conversely, microinjection of fisetin, a partial agonist of HCN2, produced both analgesic and anxiolytic effects. Additionally, we found that cyclin-dependent kinase 5 (CDK5) was activated in the contralateral PL, where it formed a complex with HCN2 and phosphorylated its C-terminus. Knockdown of CDK5 restored HCN2 expression and alleviated both pain hypersensitivity and anxiety-like behaviors. Collectively, these results indicate that CDK5-mediated dysfunction of HCN2 in the PL underlies nerve injury-induced mechanical hypersensitivity and anxiety.
Animals ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/metabolism* ; Hyperalgesia/metabolism* ; Cyclin-Dependent Kinase 5/metabolism* ; Neuralgia/metabolism* ; Male ; Anxiety/metabolism* ; Mice ; Potassium Channels/metabolism* ; Mice, Inbred C57BL ; Disease Models, Animal ; Pyramidal Cells/metabolism*

Objective:To explore the clinicopathological features of rectal neuroendocrine tumor (R-NET) G2, identify prognostic factors, and summarize treatment experience.Methods:The clinical data of patients diagnosed with R-NET G2 by pathological diagnosis admitted to Cancer Hospital of the Chinese Academy of Medical Sciences from January 2003 to September 2023 were retrospectively analyzed. The Fisher's exact test and Kaplan-Meier curves were performed to analyze the association between pathological features and prognosis.Results:A total of 22 patients were enrolled in this study and 21 patients were followed up for a period of 6-98 months with a median follow-up time of 42 months. 5 patients died due to tumor progression during the follow-up period. The 1-, 3-, and 5-year cancer-specific survival (CSS) of the whole group were 100.0%, 92.9%, and 69.6%, respectively. Of the 22 patients, 20 underwent surgical treatment, of which 15 underwent postoperative adjuvant therapy; 2 underwent medical treatment for liver and bone multiple metastases. The 5-year survival rates of patients with tumours ≥2 cm in length, T2-3 stage, lymph node metastasis, and distant metastasis (57.1%, 68.8%, 66.7%, and 63.6%, respectively) were shorter than those of patients with tumours <2 cm in length, T1 stage, no lymph node metastasis, and no distant metastasis (all 100.0%, P＜0.001). In addition, patients with liver metastases had larger primary tumor diameters and higher T-stages compared with those without distant metastasis ( P＜0.05). Conclusions:R-NET G2 has a high degree of malignancy compared with G1 and a high propensity for metastasis. Clinicians should formulate appropriate diagnostic and treatment strategies based on factors such as tumor size, depth of invasion, lymph node status, presence of distant metastasis, and the location and extent of distant metastasis.

Objective To investigate the relationship between the appearance of ligand 1 in inflammatory fibroblasts,primary tumor-ous cells,tumor Impregna-ted immune-free cellulars and clinical pathologic signs in colorectal carcinoma.Methods The group meth-od of immunization was used,and PDGFRa and RGS5 were used to mark iCAF.The levels of PDGFRa,RGS5(mesenchyma,mesenchy-ma prior to tumor infiltration)and PD-L1 in TC and TIIC were detected in 120 CRC patients in our hospital from 2019 to 2021.To ana-lyze the relationship between the appearance of iCAF and PD-L1 in cancer tissues and clinical pathologic signs and overall survival(OS).Results The high rate of PDGFRa and RGS5 was 56.7％(68/120)and 47.5％(57/120)in the mesenchyma of 120 patients with colorectal carcinoma.The high detection rate of PDGFRa and RGS5 was 39.2％(47/120).The high surface level of PDGFRa and RGS5 is related to the emergence of neoplastic buds and the metastasis of luoba nodules in the region.The high surface reach rate of PDG-FRa was 71.7％(86/120)and that of RGS5 was 57.5％(69/120).The high detection rate of PDGFRa and RGS5 was 47.5％(57/120).The high surface level of PDGFRa and RGS5 is related to the emergence of tumor buds,the metastasis of lubaria in the region,and the phase of T.The positive rate of TC PD-L1 was 5.8％(7/120)and that of TIIC PD-L1 was 48.3％(58/120).The surface reach of TC PD-L1 is related to the regional luoba nodal transfer.Kaplan-Meier and Log-rank results were shown.The patient's OS was associated with histological grading,neoplasmic metastasis,neoplasmic budding,TIIC PD-L1,PDGFRa,and RGS5(mesenchyma,mesenchyma prior to neoplasmic infiltration).COX monofactor and polyfactor regression analysis showed:Histologic grading,luba metasta-sis,TIIC PD-L1,RGS5(mesenchyma,mesenchyma prelimbic)and PDGFRa(mesenchyma prelimbic)are independent of OS in pa-tients with CRCCreate a preemptive factor.The surface reach of PDGFRa(mesenchymal)was negatively correlated with that of TC PD-L1(r=-0.213,P=0.020).The surface reach of RGS5(mesenchymal)was negatively correlated with that of TC PD-L1(r=-0.183,P=0.046).Conclusion In CRC,iCAF has a negative correlation with TC PD-L1.Targeting the treatment of iCAF in CRC may benefit it,and the detection of TC PD-L1 and TIIC PD-L1 may provide reference for the therapeutic effect of clinical anti-epidem-ic therapy and the prediction of CRC.

Aim To explore the mechanism of action of Guizhi Jia Gegen decoction(GGD)in treating pneu-monia-enteritis induced by H1N1 influenza virus infec-tion in a mouse model,using network pharmacology and molecular docking techniques,followed by in vivo verification.Methods A pneumonia-enteritis mouse model was established,and the intervention effects of GGD on the model mice were evaluated using indica-tors such as body weight,rectal temperature,lung in-dex,colon length,H1N1 M gene expression,relative mRNA expression levels of inflammatory cytokines,and pathological sections of the lung and intestine.The targets of the blood-absorbed components of GGD were identified using the Swiss Target Prediction platform,and the disease targets were retrieved from the Gene-Cards platform.The intersecting targets were analyzed through PPI network analysis using the STRING data-base to identify core targets.GO analysis and KEGG pathway enrichment analysis were performed using the Metascape database.RT-qPCR was employed to vali-date the core targets and pathways.Molecular docking was conducted using AutoDock Tools software to verify the interactions between blood-absorbed components and key targets.Results GGD demonstrated signifi-cant therapeutic effects on the pneumonia-enteritis mouse model.The results of network pharmacology in-dicated that the therapeutic effects of GGD were strong-ly associated with targets such as TNF,ALB,PTGS2,MMP9,EGFR,ESR1,SRC,HSP90AA1,PPARG and MMP2.RT-qPCR results indicated that GGD could intervene in pneumonia-enteritis by regulating the targets TNF,ALB,EGFR and the related targets of the NF-κB pathway.Molecular docking results re-vealed that blood-absorbed components such as puerar-in and liquiritin could stably bind to TNF,ALB and EGFR.Conclusion Components such as puerarin and liquiritin in GGD may exert therapeutic effects on pneumonia-enteritis induced by H1N1 influenza virus infection by acting on targets such as TNF,ALB and EGFR.

Objective:To investigate the clinicopathological characteristics and differential diagnosis of DICER1-mutant primary intracranial sarcoma.Methods:Five cases of DICER1-mutant primary intracranial sarcoma at Sanbo Brain Hospital, Capital Medical University, Beijing, China during May 2013 to November 2024 were collected. The clinical and imaging data were retrieved. Histological evaluation, immunohistochemical staining and next generation sequencing were performed. Additionally, a literature review was conducted.Results:All five DICER1-mutant primary intracranial sarcomas were located in the supratentorial region, with one case involving the basal ganglia. There were two males and three females. The median age at diagnosis was 25 (14.0, 30.5) years. Morphologically, they were characterized by high-grade spindle cell sarcoma, with brisk mitotic activity and cytoplasmic eosinophilic globules. Myxoid degeneration, necrosis, and invasion into surrounding brain tissue were observed in some cases. The tumor cells showed diffuse staining of vimentin and variable expression of myogenic marker (desmin), with or without focal MyoD1 and/or Myogenin expression. Four tumors exhibited diffuse, strong expression of TLE1 and p53, while only three tumors showed loss of ATRX (nuclear) expression. Two cases showed mosaic loss of H3K27me3 expression in neoplastic cells. The Ki-67 proliferation index was high (40%-80%). Various neuronal markers, such as synaptophysin, NF, SOX2 and MAP2, were expressed in all tumor samples. Genetically, all tumors samples harbored biallelic abnormalities of DICER1. One was a hotspot missense mutation in the RNase Ⅲb domain within exon 25 on one allele (p.E1813 or p.D1810), while the other allele had mutations including a germline mutation in one case, a somatic mutation in two cases, and a copy number deletion in two cases. In addition, these sarcomas showed alterations in TP53 (4/5), ATRX (3/5), and the genes of the mitogen-activated protein kinase pathway (3/5). Finally, all five cases were diagnosed as DICER1-mutant primary intracranial sarcoma. All patients underwent craniotomy that led to complete tumor resection. Three patients received adjuvant radiotherapy and chemotherapy, with progression-free survival time of 28, 48, and 50 months, respectively. Patient 2 succumbed to the tumor after 3 months post-surgery due to rapid progression and tumor dissemination. Patient 5 was lost to follow-up 3 months after the surgery.Conclusions:DICER1-mutant primary intracranial sarcoma is a newly defined tumor entity in the fifth edition of the World Health Organization Classification of Central Nervous System Tumors, and commonly occurs in children and young adults. High-grade malignant spindle cells are their typical morphological feature. Eosinophilic cytoplasmic globules and myogenic differentiation can help establish the diagnosis. This study suggests that DICER1-mutant primary intracranial sarcomas exhibit immunophenotypic neuronal differentiation. Rendering the diagnosis of DICER1-mutant primary intracranial sarcoma largely relies on detecting DICER1 pathogenic alterations or DNA methylation profiling.

AIM:To explore the therapeutic effect of Tongfeng-Qingli mixture(TFQLM)and its mechanism in hyperuricemic(HUA)rats based on uric acid(UA)transporter and Janus kinase 2(JAK2)/signal transducer and acti-vator of transcription 3(STAT3)signaling pathway.METHODS:(1)In vivo experiment:36 male SD rats were random-ly divided into control(CON)group,model(MOD)group,benzbromarone(BEN)group,low-dose TFQLM(TFQLM-L)group,medium-dose TFQLM(TFQLM-M)group,and high-dose TFQLM(TFQLM-H)group,with 6 rats in each group.In all groups except CON group,HUA was induced in rats by giving hypoxanthine(HP)combined with potassium oxybate(OP)for 35 consecutive days.The rats in CON group were given sodium carboxymethyl cellulose solution by gavage.A fully automatic biochemistry analyzer was used to detecte serum UA,serum creatinine(SCr)and blood urea nitrogen(BUN)levels.The xanthine oxidase(XOD)and adenosine deaminase(ADA)levels in the liver were detected by ELISA kits.The histopathological changes of kidneys were observed by HE staining.Immunohistochemistry was performed to de-tect urate transporter 1(URAT1)and glucose transporter 9(GLUT9),organic anion transporter 1(OAT1)and OAT3 ex-pression in the kidney.Western blot was used to measure the protein levels of URAT1,GLUT9,OAT1,OAT3,interleu-kin-6(IL-6),tumor necrosis factor-α(TNF-α),JAK2,p-JAK2,STAT3,p-STAT3 and repressor of cytokine signaling 3(SOCS3)in the kidney.(2)In vitro experiments:HUA cellular model was established by UA stimulation in HK2 cells,and the protein levels of URAT1,GLUT9,OAT1,OAT3,IL-6,TNF-α,JAK2,p-JAK2,STAT3,p-STAT3,and SOCS3 were detected by Western blot.RESULTS:Compared with MOD group,serum UA,SCr and BUN levels of the rats in all TFQLM groups were reduced(P<0.05).The XOD and ADA levels in liver tissues were significantly reduced(P<0.05).The protein levels of URAT1,GLUT9,IL-6,TNF-α,JAK2,p-JAK2,STAT3,p-STAT3 and SOCS3 were decreased(P<0.05),and OAT1 and OAT3 protein expression was increased(P<0.05)in kidneys and HK2 cells.CONCLUSION:By establishing rat and HK2 cell HUA models,it is hypothesized that TFQLM may reduce UA levels and attenuate renal inflammation in HUA rats,and its mechanism may be related to the regulation of UA transport proteins and inhibition of the JAK2/STAT3 signaling pathway.