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.

Objective To understand the current status of low-density lipoprotein cholesterol (LDL-C) control in patients after coronary artery bypass grafting (CABG). Methods Clinical data of patients who underwent isolated CABG in Beijing Anzhen Hospital in 2023 were collected. All patients returned to our hospital approximately one year after surgery (10-13 months) for a lipid level recheck. We analyzed their LDL-C attainment status and influencing factors. Patients were categorized into two groups based on whether their LDL-C met the target: a LDL-C attainment group and a LDL-C non-attainment group. Results This study included 1456 patients who underwent CABG, including 320 females and 1136 males, with an average age of (61.41±9.12) years. One year post-surgery, 234 patients achieved the LDL-C target, with an attainment rate of 16.07%. The proportion of patients in the LDL-C attainment group who were ultra-high risk (77.35% vs. 92.06%, P＜0.001), female (16.24% vs. 23.08%, P=0.021), and those with comorbid hypertension (55.98% vs. 63.18%, P=0.038) was significantly lower than those in the LDL-C non-attainment group. Additionally, the baseline body mass index (BMI) [(25.37±3.24) kg/m2 vs. (26.03±3.56) kg/m2, P=0.017], total cholesterol levels [(3.30±0.84) mmol/L vs. (4.01±1.03) mmol/L, P＜0.001], LDL-C [(1.62±0.63) mmol/L vs. (2.25±0.85) mmol/L, P＜0.001], and high-density lipoprotein cholesterol [(0.98±0.26) mmol/L vs. (1.02±0.24) mmol/L, P=0.049] upon admission in the attainment group were all lower than those in the non-attainment group. Moreover, the lipid-lowering drug usage rate in the attainment group (100.00% vs. 96.24%, P=0.003) and the proportion using two types of drugs together (25.21% vs. 10.72%, P＜0.001) were both higher than those in the non-attainment group, while the statin monotherapy rate was lower than that in the non-attainment group (74.79% vs. 85.19%, P＜0.001). Logistic regression analysis showed that baseline BMI (OR=0.928, P=0.012) and baseline LDL-C levels (OR=0.207, P<0.001), patient cardiovascular risk stratification (OR=0.155, P<0.001) and lipid-lowering drug treatment regimen (OR=3.758, P<0.001) are significant factors affecting the LDL-C control status. Conclusion The LDL-C compliance rate of patients undergoing CABG is at a relatively low level 1 year after surgery. Patients with very high risk of atherosclerotic cardiovascular disease, high baseline LDL-C levels, and overweight or obesity should be strengthened lipid management. For these patients, the intensity of lipid-lowering drug use or combination medication should be increased upon discharge.

Objective To compare the clinical characteristics of pneumococcal meningitis in different age groups, and to provide a basis for early diagnosis of pneumococcal meningitis. Methods Cerebrospinal fluid and/or serum samples were collected from 1742 suspected cases of meningitis in Baoji, Shaanxi Province from August 2013 to July 2019. Streptococcus pneumoniae was detected by isolation culture and real-time fluorescence quantitative polymerase chain reaction. Retrospective analysis of clinical manifestations, biochemical indicators and other information of laboratory confirmed cases was conducted by χ² test or Fisher's exact test. Results A total of 1742 samples of encephalitis or meningitis cases were detected, and 41 cases were confirmed as laboratory-confirmed Streptococcus pneumoniae infection. Among them, there were 12 cases (29.27%) in the infant group, 14 cases (34.15%) in the child group, and 15 cases (36.59%) in the adult group. The proportion of the adults with headache was significantly higher than that of the infants (χ²=11.408，P＜0.017). The proportion of the adults with consciousness disorder, elevated white blood cells and elevated neutrophils were significantly higher than those in the infant and the child groups（Fisher's exact test, P＜0.017；χ² =6.428，P＜0.017；χ² =10.898，P＜0.017；χ² =6.421，P＜0.017；χ² =9.758，P＜0.017；χ² =7.744，P＜0.017). The proportion of the infants with cerebrospinal fluid turbidity was significantly higher than that of the children (Fisher's exact test，P＜0.017). The proportion of the infants with decreased white blood cells and reduced glucose in cerebrospinal fluid was significantly higher than that of the children group and the adult group（Fisher's exact test, P＜0.001；Fisher's exact test, P＜0.001；Fisher's exact test, P＜0.017; Fisher's exact test, P＜0.017). Conclusion Most adult patients with pneumococcal meningitis have headache and consciousness disorders, with significantly increased proportion of white blood cells and neutrophils. Infant patients tend to have cloudy appearance of cerebrospinal fluid, leukopenia in blood, and decreased glucose in cerebrospinal fluid.

The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has posed a global challenge to the control of the coronavirus disease 2019 (COVID-19) pandemic. Therefore, developing countermeasures that broadly protect against SARS-CoV-2 and related sarbecoviruses is essential. Herein, we have developed a lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) encoding the full-length Spike (S) glycoprotein of SARS-CoV-2 (termed RG001), which confers complete protection in a non-human primate model. Intramuscular immunization of two doses of RG001 in Rhesus monkey elicited robust neutralizing antibodies and cellular response against SARS-CoV-2 variants, resulting in significantly protected SARS-CoV-2-infected animals from acute lung lesions and complete inhibition of viral replication in all animals immunized with low or high doses of RG001. More importantly, the third dose of RG001 vaccination elicited effective neutralizing antibodies against current epidemic XBB and JN.1 strains and similar cellular response against SARS-CoV-2 Omicron variants (BA.1, XBB.1.16, and JN.1) were observed in immunized mice. All these results together strongly support the great potential of RG001 in preventing the infection of SARS-CoV-2 variants of concern (VOCs).

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

OBJECTIVES: We propose a low-dose CT image restoration method based on central guidance and alternating optimization (FedGP). METHODS: The FedGP framework revolutionizes the traditional federated learning model by adopting a structure without a fixed central server, where each institution alternatively serves as the central server. This method uses an institution-modulated CT image restoration network as the core of client-side local training. Through a federated learning approach of central guidance and alternating optimization, the central server leverages local labeled data to guide client-side network training to enhance the generalization capability of the CT imaging model across multiple institutions. RESULTS: In the low-dose and sparse-view CT image restoration tasks, the FedGP method showed significant advantages in both visual and quantitative evaluation and achieved the highest PSNR (40.25 and 38.84), the highest SSIM (0.95 and 0.92), and the lowest RMSE (2.39 and 2.56). Ablation study of FedGP demonstrated that compared with FedGP(w/o GP) without central guidance, the FedGP method better adapted to data heterogeneity across institutions, thus ensuring robustness and generalization capability of the model in different imaging conditions. CONCLUSIONS FedGP provides a more flexible FL framework to solve the problem of CT imaging heterogeneity and well adapts to multi-institutional data characteristics to improve generalization ability of the model under diverse imaging geometric configurations.
Tomography, X-Ray Computed/methods* ; Humans ; Radiation Dosage ; Image Processing, Computer-Assisted/methods* ; Algorithms

Periodontal disease is a risk factor for many systemic diseases such as Alzheimer's disease and adverse pregnancy outcomes. Cleft palate (CP), the most common congenital craniofacial defect, has a multifaceted etiology influenced by complex genetic and environmental risk factors such as maternal bacterial or virus infection. A prior case-control study revealed a surprisingly strong association between maternal periodontal disease and CP in offspring. However, the precise relationship remains unclear. In this study, the relationship between maternal oral pathogen and CP in offspring was studied by sonicated P. gingivalis injected intravenously and orally into pregnant mice. We investigated an obvious increasing CP (12.5%) in sonicated P. gingivalis group which had inhibited osteogenesis in mesenchyme and blocked efferocytosis in epithelium. Then glycolysis and H4K12 lactylation (H4K12la) were detected to elevate in both mouse embryonic palatal mesenchyme (MEPM) cells and macrophages under P. gingivalis exposure which further promoted the transcription of metallopeptidase domain17 (ADAM17), subsequently mediated the shedding of transforming growth factor-beta receptor 1 (TGFBR1) in MEPM cells and mer tyrosine kinase (MerTK) in macrophages and resulted in the suppression of efferocytosis and osteogenesis in palate, eventually caused abnormalities in palate fusion and ossification. The abnormal efferocytosis also led to a predominance of M1 macrophages, which indirectly inhibited palatal osteogenesis via extracellular vesicles. Furthermore, pharmacological ADAM17 inhibition could ameliorate the abnormality of P. gingivalis-induced abnormal palate development. Therefore, our study extends the knowledge of how maternal oral pathogen affects fetal palate development and provides a novel perspective to understand the pathogenesis of CP.
Animals ; Female ; Porphyromonas gingivalis ; Pregnancy ; Mice ; Cleft Palate/etiology* ; Glycolysis

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

In order to investigate the role of sRNA OxyS in the pathogenicity of Salmonella typhi-murium infection,the OxyS gene deletion strain ATCC25241 △OxyS and the back-complemented strain ATCC25241 △OxyS/OxyS of Salmonella typhimurium ATCC25241 were constructed by using λRed homologous recombination technique.We investigated the effect of OxyS deletion on the biological characteristics and pathogenicity of Salmonella typhimurium ATCC25241.The re-sults showed that the deletion of OxyS did not affect the growth rate,the ability of biofilm forma-tion,and the ability of adhesion,invasion and intracellular survival of Salmonella typhimurium,but significantly reduced the motility of Salmonella typhimurium as well as its ability to survive in alkaline and oxidative environments.The results of mouse infection test showed that OxyS dele-tion caused a significant decrease in the virulence of Salmonella typhimurium in mice,and toxicity is reduced obviously.The qPCR results also showed that OxyS deletion could lead to changes in the transcript levels of a number of virulence-related genes of Salmonella typhimurium such as pipB,orf245,csgA,invH,tatA,sipA,sipB,and so on.The above results indicate that OxyS gene affects the biological characteristics and pathogenicity of Salmonella typhimurium and is an important virulence regulator of Salmonella typhimurium.

Objective To develop a core outcome set(COS)for clinical effectiveness trials of heart failure with preserved ejection fraction(HFpEF).Methods Outcome measures were collected through database literatures search,clinical experts questionnaire survey and semi-structured patients interview.Then,the outcome measures pool was constructed and domains were divided.Candidate outcome measures of COS were screened through two rounds of Delphi survey.Finally,a consensus meeting was held to determine COS and reach a consensus.Results A total of 317 outcome measures which could be divided into 6 domains were collected through literature research,questionnaire survey and semi-structured interview.15 candidate outcome measures of COS were screened through two rounds of Delphi survey.Finally,the consensus meeting reached consensus on a COS with 6 entries.Conclusion In this study,a COS for clinical effectiveness trials of HFpEF was developed,which is conducive to the standardization of efficacy evaluation.