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 investigate the mechanism of Qinggan Jianpi Houxue prescription against hepatic fibrosis in mice using metabolomics. MethodsA hepatic fibrosis mouse model was established by intraperitoneal injection of 20% carbon tetrachloride （CCl₄， diluted with olive oil at a ratio of 4∶1） at a dose of 2.5 mL·kg^-1 for 4 weeks. A total of 54 C57BL/6J mice were randomly divided into the blank control group， model group， Qinggan Jianpi Houxue prescription high-dose group （47.32 g·kg^-1）， medium-dose group （23.66 g·kg^-1）， low-dose group （11.83 g·kg^-1）， and Biejiajian pill group （1.365 g·kg^-1）， with 9 mice in each group. Concurrently with modeling， each administration group received the corresponding dose continuously for 4 weeks， once daily. After 4 weeks， liver tissues and blood samples were collected for liver function and hepatic pathological examinations. Non-targeted metabolomics was employed to detect hepatic metabolites. Principal component analysis （PCA）， partial least squares discriminant analysis （PLS-DA） and orthogonal partial least squares discriminant analysis （OPLS-DA） were performed to explore the metabolites and their involved metabolic pathways in the liver tissues of mice in the blank control group， model group and Qinggan Jianpi Houxue prescription high-dose group. Western blot validation was conducted at both the cellular and animal levels. ResultsCompared with the blank control group， the model group showed significantly increased levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） （P<0.01）， along with increased inflammatory cell infiltration， and formation of fibrous septa. The predominantly enriched pathway was the forkhead box O （FoxO） signaling pathway. Compared with the model group， the Qinggan Jianpi Huoxue prescription high-dose group exhibited significantly decreased ALT and AST levels （P<0.01）. In all administration groups of Qinggan Jianpi Huoxue prescription， inflammatory cell infiltration was reduced， fibrous septa were narrowed and diminished， collagen fibers were reduced， and the collagen area was significantly decreased. Non-targeted metabolomics identified 79 differential metabolites， among which 49 were up-regulated and 30 down-regulated， primarily enriched in the tricarboxylic acid （TCA） cycle and pyruvate metabolism pathways. Western blot results demonstrated that， compared with the blank control group， the model group exhibited significantly upregulated protein expressions of α-smooth muscle actin （α-SMA）， lactate dehydrogenase A （LDHA）， FoxO1， pyruvate kinase M2 （PKM2）， hexokinase 2 （HK2）， and phosphofructokinase 1 （PFK1） in liver tissues （P<0.05， P<0.01）. In hepatic stellate cells， the glucose concentration increased， and the protein expression of α-SMA， LDHA， FoxO1， PKM2， glucose transporter 1 （GLUT1）， and PFK1 were significantly up-regulated （P<0.05， P<0.01）. Conversely， compared with the model group， the Qinggan Jianpi Huoxue prescription high-dose group showed significantly downregulated protein expression of α-SMA， LDHA， FoxO1， PKM2， HK2， and PFK1 in liver tissues （P<0.05， P<0.01）. In hepatic stellate cells， the glucose concentration decreased， and the protein expression of α-SMA， LDHA， FoxO1， PKM2， GLUT1， and PFK1 were significantly down-regulated （P<0.05， P<0.01）. ConclusionQinggan Jianpi Huoxue prescription can alleviate the pathological progression of hepatic fibrosis in mice， potentially by regulating the TCA cycle and pyruvate metabolism through FoxO1， and by modulating glycolytic metabolic reprogramming in hepatic stellate cells， thereby promoting liver tissue repair.

Background During pregnancy, negative emotions such as anxiety and depression may induce cortisol disruption. Cortisol can be transmitted to the fetus through the placental barrier, thereby affecting the neurodevelopment of the offspring. Objective To investigate the relationship between placental cortisol, maternal depression during pregnancy, and neurodevelopment of 3-month-old infants. Methods From September 2022 to September 2023, 171 pregnant women ordered routine prenatal checks at the obstetrics outpatient department of a tertiary hospital in Ningxia were selected using a prospective cohort design. After providing informed consent, these women participated in a questionnaire survey that covered general individual characteristics, prenatal depression, and sleep quality. At birth, placental samples were collected to measure cortisol levels using ELISA kits. Follow-up assessments on the neurodevelopmental of 3-month-old infants were conducted using the Warning Sign for Children Mental and Behavioral Development. LASSO regression analysis was conducted to screen the influencing factors of depression during pregnancy. Huber regression analysis was then applied to assess potential linear relationship between depression during pregnancy and placental cortisol levels. Log-binomial regression was used to analyze the linear relationships between cortisol levels and neurodevelopmental delay in 3-month-old infants. Additionally, a mediation effect model was fitted using R 4.3.3 to assess possible mediating role of cortisol in the association between prenatal depression and neurodevelopmental delay in 3-month-old infants. Results The positive rate of prenatal depression was 33.33%. Nine factors affecting prenatal depression were identified by LASSO regression, including rural residence, high school education or above, extroverted personality characteristics, moderate early pregnancy reactions, baby sex expectation, prenatal anxiety, family dysfunction, exposure to stressful life events during pregnancy, and moderate prenatal sleep quality. The Huber regression model showed a positive linear correlation between prenatal depression and placental cortisol (P<0.05). With or without controlling confounding factors, the results of log-binomial regression modeling showed that cortisol levels were associated with a reduced risk of neurodevelopmental delay in 3-month-old infants (crude model: RR=0.988, 95%CI: 0.9768, 0.9996, P＜0.05; adjusted model: RR=0.988, 95%CI: 0.9764, 0.9993, P＜0.05). A mediating effect of placental cortisol between prenatal depression and the risk of neurodevelopmental delay in 3-month-old offspring was found statistically significant (P=0.045), accounting for 67.0% of the total effect. Conclusion Prenatal depression is associated with elevated placental cortisol levels, and higher cortisol levels are found to be related to a lower risk of neurodevelopmental delay in infants. Placental cortisol mediates the relationship between prenatal depression and infant neurodevelopment.

Objective To investigate the effect of secondary preventive scheme on recurrence rate of ce-rebrovascular event based on China ischemic stroke subclassification(CISS)of intracranial arterial stenosis is-chemic stroke(IS).Methods A total of 192 patients with intracranial arterial stenosis IS were prospectively included and the secondary preventive scheme was formulated according to whether or not based on the patho-genesis.Then the patients were divided into the personalized treatment group and conventional treatment group.The personalized group conducted the classification and was given different the secondary preventive schemes the artery-artery embolism group was given the active lipid-lowering scheme to make the low density lipoprotein(LDL)reaching the standard;the low hypoperfusion group was given the smooth pressure reduc-tion program;the carrier artery occlusion perforating artery group was given the routine secondary prevention program;the mixture mechanism group was given the corresponding schemes superposition according to dif-ferent mechanisms].The conventional treatment group was given the conventional secondary preventive scheme.The difference in the recurrence rate of cerebrovascular events on 90 d was compared between the two groups.Meanwhile the univariate and multivariate logistic regression were used to analyze the influencing fac-tors of recurrence of cerebrovascular events on 90 d in intracranial arterial stenosis IS.Results Among 192 study subjects,there were 90 cases in the personalized treatment group(20 cases of vector artery occlusion and perforator artery,44 cases of arterial-arterial embolization,6 cases of hypoperfusion and 20 cases of mixed mechanism).There were 102 cases in the conventional treatment group(16 cases of perforator artery occlu-sion of the vector artery,52 cases of arterial-arterial embolism,8 cases of hypoperfusion and 26 cases of mixed mechanism).The occurrence rate of cerebrovascular events on 90 d in the personalized treatment group was significantly decreased compared to the conventional treatment group(7.8%vs.17.6%,χ2=4.112,P=0.043).The Logistic regression analysis revealed that the active lipid-lowering scheme for LDL reaching the standard was the independent protective factor of the cerebrovascular event recurrence on 90 d(OR=0.128,95%CI:1.150-71.170).Conclusion The personalized secondary prevention scheme based on pathogenesis reduces the recurrence rate of cerebrovascular event in intracranial arterial stenosis IS,in which making the LDL reaching the standard by the active lipid-lowering scheme is the independent protective factor for cerebro-vascular event recurrence in intracranial arterial stenosis IS.

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

Mesangial cell proliferation is an early pathological indicator of diabetic nephropathy (DN). Growing evidence highlights the pivotal role of paired-related homeobox 1 (Prrx1), a key regulator of cellular proliferation and tissue differentiation, in various disease pathogenesis. Notably, Prrx1 is highly expressed in mesangial cells under DN conditions. Both in vitro and in vivo studies have demonstrated that Prrx1 overexpression promotes mesangial cell proliferation and contributes to renal fibrosis in db/m mice. Conversely, Prrx1 knockdown markedly suppresses hyperglycemia-induced mesangial cell proliferation and mitigates renal fibrosis in db/db mice. Mechanistically, Prrx1 directly interacts with the Yes-associated protein 1 (YAP) promoter, leading to the upregulation of YAP expression. This upregulation promotes mesangial cell proliferation and exacerbates renal fibrosis. These findings emphasize the crucial role of Prrx1 upregulation in high glucose-induced mesangial cell proliferation, ultimately leading to renal fibrosis in DN. Therefore, targeting Prrx1 to downregulate its expression presents a promising therapeutic strategy for treating renal fibrosis associated with DN.

Objective To investigate the direct stimulatory effects of calprotectin S100A8/A9 on hepatic stellate cells(HSCs)and underlying regulatory mechanisms.Methods Primary HSCs of mice were stimulated with S100A8/A9 heterodimer recombinant protein at 200 and 1000 ng/mL.Data on quantitative proteomics was obtained using the tandem mass tag(TMT)-labeled method before changes in the protein level of HSCs were analyzed.Differentially expressed proteins(DEPs)were screened using Significance B method and P＜0.05,followed by Reactome pathway enrichment analysis.Furthermore,protein-protein interactions between the DEPs enriched in the pathways were analyzed using the STRING database.Results The protein expression profile of HSCs was significantly altered after treatment with S100A8/A9 at 1000 ng/mL.Reactome pathway enrichment analysis revealed significant enrichment in such pathways as transforming growth factor-beta(TGF-β)signaling,nuclear factor kappa-B(NF-κB)signaling activation,cytokine-mediated immune regulation,and collagen biosynthesis.The analysis of protein-protein interactions identified NF-kappa-B transcription factor subunit(RELB),chemokine(C-X-C motif)ligand 10(CXCL10)and Notch receptor 1(NOTCH1)as key hub proteins in the regulatory network.Conclusion S100A8/A9 can directly stimulate the activation of HSCs,through NF-κB signaling,TGF-β signaling,and Notch signaling pathways potentially.This study sheds light on the mechanisms underlying the activation of HSCs stimulated by S100A8/A9.

Macrophages are the key cells in the process of hepatic fibrosis. Therefore, they promote the progression and regression of liver fibrosis by participating in all stages. The treatment of liver fibrosis is significantly identified by the main subtypes of intrahepatic macrophages. This article summarizes the types and functions of macrophages according to the inflammatory phenotype, origin, and surface markers and their effect on fibrosis; introduces the new subtypes and mode of action in the occurrence and development of hepatic fibrosis, as revealed by the single-cell sequencing technique; and analyzes the limitations of traditional antifibrotic therapy and the advantages of macrophage-targeting therapeutics, which could indicate the new direction for the study of new macrophage subtypes in hepatic fibrosis.

Objective:To assess the effects of recognition function of four-lead electrocardiogram(ECG)synchronization technique and multi-parameter fusion technique in reducing the number of false alarms and improving the quality of alarms in intensive care units(ICU).Methods:Four-lead ECG synchronization technique and multi-parameter fusion technique were used to strengthen the monitoring and assessment for the alarm of clinical monitors,and reduce the false alarm rate of monitors.The clinical alarm data of bed units corresponding to 48 monitors in clinical use of ICU,cardiovascular intensive care unit(CCU)and neurosurgery intensive care unit(NICU)of Hainan General Hospital from October 14 to December 27,2024 were selected.According to the opening and close of the four-lead ECG synchronization and multi-parameter fusion technique algorithm of the monitors,they were divided into group A(opened four-lead ECG synchronization and multi-parameter fusion),group B(opened four-lead ECG synchronization,but closed multi-parameter fusion),group C(closed four-lead ECG synchronization,but opened multi-parameter fusion)and group D(closed four-lead ECG synchronization and multi-parameter fusion),with 12 units in each group.The numbers of total alarms and false alarms generated by monitor of each bed unit among different optimization strategies were compared.Results:The numbers of average daily alarm of the monitors in groups A,B and C were respectively(134.2±32.4)cases,(392.5±68.2)cases and(583.4±126.5)cases,which were lower than those in group D(1 073.2±168.6),with statistically significant differences(Z=3.45,2.94,2.52,P<0.05).The optimization rates of the alarm numbers in groups A,B and C were increased by 87.51%,63.47%and 45.67%,respectively.The rates of average false alarm of the monitors in groups A,B and C were respectively(1.04±0.15)%,(1.73±0.12)%and(2.07±0.08)%,which were lower than(3.76±0.2)%in group D,with statistically significant differences(Z=3.45,2.94,2.52,P<0.05).Conclusion:Four-lead ECG synchronization technique and multi-parameter fusion technique can effectively optimize the number of alarms in ICU,and reduce the proportion of false alarms of monitors in department,and decrease fatigue of medical staffs for alarm.

Objective:To investigate the neuro-electrophysiological characteristics of patients with primary brain stem hemorrhage (PBSH).Methods:This is a retrospective case series study. The clinical data of 17 PBSH patients with Glasgow coma score 3 to 8 points who were admitted to the Department of Neurosurgery, Xiangya Hospital of Central South University from January 2022 to December 2023 were retrospectively analyzed. There were 14 males and 3 females, with an age( M (IQR)) of 46.0(14.0) years (range: 18.0 to 70.0 years).All patients underwent electro-physiological monitoring within 28 days after the onset of the disease. According to Glasgow outcome scale(GOS) 6 months after onset, PBSH patients were divided into two groups: unregained consciousness group with (GOS 1 to 2 points, 13 cases) and regained consciousness group (GOS 3 to 5 points, 4 cases). The neuro-electrophysiological indicators involved in this study included short latency somosensory evoked potential (SLSEP) component N20, brainstem auditory evoked potential (BAEP), electroencephalogram (EEG) background activity, EEG reactivity (EEG-R), EEG sleep structure waves, absolute amplitude of N1 at electrode Fz (FzN1A) and Cz (CzN1A), respectively, absolute amplitude of mismatch negativity at electrode Fz (FzMMNA) and Cz (CzMMNA), respectively. Then, the Fisher exact probability test and Mann Whitney U test were used for counting data and measurement data, respectively, to analyze the differences of neuro-electrophysiological indicators between the two groups. Results:The EEG background activity of 17 PBSH patients was mainly α-mode, α-θ mode and θ mode. Four patients with α-mode, 3 of whom regained consciousness (all with EEG-R). There were 3 patients with α-θ pattern. And 5 patients with θ pattern, 2 of whom died. Five patients with background EEG activity of delta pattern had poor prognosis, of which 4 patients died and 1 patient survived but did not regain consciousness 6 months after onset. SLSEP component N20 were absent bilaterally in 12 cases and BAEP in 5 cases. FzN1A and CzN1A were not extracted in 4 cases, and FzMMNA and CzMMNA were not extracted in 6 cases. The study showed that BAEP, EEG background activity, EEG-R, FzN1A, CzN1A, FzMMNA and CzMMNA were different between the two groups (all P<0.05), while there was no difference between N20 and EEG sleep structure (all P>0.05). Conclusion:The neuro-electrophysiological indicators including BAEP, EEG background activity, EEG-R, FzN1A, CzN1A, FzMMNA, and CzMMNA may be related to whether PBSH patients can regain consciousness 6 months after onset, and it is best to combine multiple indicators for comprehensive analysis in clinical practice.