The prescription of Qidong Yixin oral liquid is derived from the experience of national medical master Ren Jixue in treating viral myocarditis （VMC）. It has the functions of tonifying Qi， nourishing the heart，calming the mind， and relieving palpitations. It is used to treat VMC and angina pectoris of coronary heart disease caused by deficiency of both Qi and Yin. However，the understanding of its efficacy evidence， advantageous aspects， dosage and administration， and medication safety remains insufficient in clinical practice. Therefore，the development of the Expert Consensus on the Clinical Application of Qidong Yixin Oral Liquid （hereinafter referred to as consensus） was initiated. Consensus strictly followed the process and methods of the expert consensus on the clinical application of Chinese patent medicines of the China Association of Chinese Medicine，successively completing multiple tasks such as the consensus project initiation，determination of clinical problems，evidence search and evaluation，formation of recommendation opinions and consensus suggestions，solicitation of opinions，peer review， submission for review and release， and so on. Consensus formed a total of 10 recommendation opinions and 12 consensus suggestions，clarifying the clinical positioning，efficacy advantages，syndrome differentiation，dosage and administration，combination therapy，timing of medication，adverse reactions，contraindications， and precautions of Qidong Yixin oral liquid，indicating that it has good clinical advantages and safety in the treatment of VMC and angina pectoris of coronary heart disease，providing norms and references for physicians to safely and rationally apply Qidong Yixin oral liquid. Consensus was reviewed and approved for release by the Standardization Office of the China Association of Chinese Medicine on December 23， 2024. Standard number：GSCACM-376-2024.

BACKGROUND: G protein-coupled receptor kinase 2 (GRK2) could participate in the regulation of diverse cells via interacting with non-G-protein-coupled receptors. In the present work, we explored how paroxetine, a GRK2 inhibitor, modulates the differentiation and activation of immune cells in rheumatoid arthritis (RA). METHODS: The blood samples of healthy individuals and RA patients were collected between July 2021 and March 2022 from the First Affiliated Hospital of Anhui Medical University. C57BL/6 mice were used to induce the collagen-induced arthritis (CIA) model. Flow cytometry analysis was used to characterize the differentiation and function of dendritic cells (DCs)/T cells. Co-immunoprecipitation was used to explore the specific molecular mechanism. RESULTS: In patients with RA, high expression of GRK2 in peripheral blood lymphocytes, accompanied by the increases of phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR). In animal model, a decrease in regulatory T cells (T regs ), an increase in the cluster of differentiation 8 positive (CD8 + ) T cells, and maturation of DCs were observed. Paroxetine, when used in vitro and in CIA mice, restrained the maturation of DCs and the differentiation of CD8 + T cells, and induced the proportion of T regs . Paroxetine inhibited the secretion of pro-inflammatory cytokines, the expression of C-C motif chemokine receptor 7 in DCs and T cells. Simultaneously, paroxetine upregulated the expression of programmed death ligand 1, and anti-inflammatory cytokines. Additionally, paroxetine inhibited the PI3K-AKT-mTOR metabolic pathway in both DCs and T cells. This was associated with a reduction in mitochondrial membrane potential and changes in the utilization of glucose and lipids, particularly in DCs. Paroxetine reversed PI3K-AKT pathway activation induced by 740 Y-P (a PI3K agonist) through inhibiting the interaction between GRK2 and PI3K in DCs and T cells. CONCLUSION Paroxetine exerts an immunosuppressive effect by targeting GRK2, which subsequently inhibits the metabolism-related PI3K-AKT-mTOR pathway of DCs and T cells in RA.
G-Protein-Coupled Receptor Kinase 2/metabolism* ; Arthritis, Rheumatoid/immunology* ; Animals ; Dendritic Cells/metabolism* ; Paroxetine/therapeutic use* ; Proto-Oncogene Proteins c-akt/metabolism* ; Mice ; Humans ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Male ; Phosphatidylinositol 3-Kinases/metabolism* ; Lymphocyte Activation/drug effects* ; Female ; T-Lymphocytes/metabolism* ; Middle Aged

Alzheimer's disease(AD)is a neurodegenerative disease with highly heterogeneous pathological and clinical manifesta-tions,and it is the most common cause of dementia.This heterogeneity poses challenges for diagnosis,treatment,and evaluating novel pharmacological efficacy.This review summarizes the latest progress in the major clinical subtypes of AD based on clinical manifesta-tions,genetic,and pathological features.Early-onset and late-onset AD clinical subtypes may share the same symptoms but differ in etiology,age of onset,mode of presentation,disease progression,and associated comorbidities.Typical and atypical AD differ signifi-cantly in clinical manifestations,pathological features,and diagnostic criteria.Research on AD subtypes based on imaging and omics data has also made considerable progress.This review also outlines the molecular pathological heterogeneity of AD.A deep understand-ing of these heterogeneities is crucial for diagnosis,the formulation of pharmacological treatment strategies,and clinical management.

Objective:Using atenolol as a model drug,the aim of this study was to develop a sustained and controlled transdermal drug delivery system(TDDS)based on polyethyleneimine-modified MoS2 nanoparticles(PEI-MoS2 NPs)that were responsive to near infrared(NIR)laser irradiation.Methods:The three-dimensional flower-like PEI-MoS2 NPs were successfully synthesized and further characterized by attenuated total reflection Fourier transform infrared spectroscopy,X-ray diffraction measurements,scanning electron microscopy,and transmission electron microscopy.The controlled release capacity of PEI-MoS2 NPs was examined using in vitro drug release and skin penetration experiments.Results:The PEI-MoS2 NPs exhibited a drug loading efficiency of 53.86% and high photothermal conversion ability.Moreover,the release of atenolol was enhanced by NIR stimulation with an enhancement ratio of 1.56.Conclusion:NIR-controlled PEI-MoS2 NPs was essential for the control and sustained release of drugs in TDDS.

Objective:To investigate the epidemiological and genetic characteristics of human metapneumovirus (hMPV) in Tianjin during two influenza epidemic seasons from October 2020 to March 2021 and from October 2021 to March 2022, and enrich the whole genome database of hMPV in China.Methods:A total of 1 040 pharyngeal swab samples collected from patients with influenza-like illness (ILI) were analyzed using microfluidic chip fluorescence quantitative PCR. RT-PCR was used to amplify the whole genome in hMPV-positive samples, and the second-generation sequencing was performed for complete genome sequencing. Bioinformatics software including CLC, DNAStar, and MEGA was used for sequence assembly, nucleotide and amino acid homology analysis, and phylogenetic tree mapping.Results:Among the 1 040 samples, 25 were positive for hMPV with a positive rate of 2.40%. The highest positive rate was observed in the age group of 3 to 5 years, reaching 3.71% (16/431). During the influenza epidemic seasons, the detection rate of hMPV peaked in December, reaching 6.67% (12/180). Twelve strains were successfully sequenced, and there were seven of type B2, four of type A2b, and one of type B1. More variations were detected in the G gene, with 111nt-dup sequence repeats observed in the G gene of three A2b strains.Conclusions:The prevalence of hMPV peaks in December during the influenza epidemic seasons in Tianjin, with Type B2 being the predominant type. Except for the G gene with more mutations, other genes remain stable.

Objective:To summarize the best evidence for external auditory canal irrigation in patients with cerumen embolism.Methods:The clinical decisions, guidelines, systematic reviews, expert consensus, group standards, evidence summaries, and randomized controlled trials regarding external auditory canal irrigation in patients with cerumen embolism were retrieved from databases and websites such as BMJ Best Practice, UpToDate, Guidelines International Network, National Institute for Health and Clinical Excellence, Joanna Briggs Institute Evidence-Based Health Care Center Database, PubMed, Embase, China National Knowledge Infrastructure, WanFang data, and China Biology Medicine disc. The search period was from database establishment to February 15, 2023. Six researchers screened the literature, evaluated the methodological quality, and extracted and summarized the best evidence for external auditory canal irrigation in patients with cerumen embolism.Results:A total of nine articles were included, including one clinical decision, two guidelines, two systematic reviews, one group standard, and three randomized controlled trials. Sixteen pieces of evidence were summarized from six aspects of operators: pre-operation evaluation and preparation, operation process, post-operation handling, health education, and adverse reactions during operation.Conclusions:This paper summarizes the best evidence for external auditory canal irrigation in patients with cerumen embolism. Medical and nursing staff should carefully select and apply evidence based on clinical scenarios and patient's wishes.

Objective : To investigate the effect of platelet particles on the extent of intestinal inflammation and in⁃ testinal mucosal permeability in mice with dextran sodium sulfate induced colitis. Methods : The experiment was divided into four groups : normal control group ( n = 10 , drinking sterile distilled water + intraperitoneal injection of 0. 9% sodium chloride solution) , PMPs group ( n = 10 , drinking sterile distilled water + intraperitoneal injection of PMPs) , DSS model group ( n = 10 , drinking DSS solution + intraperitoneal injection of 0. 9% sodium chloride solution) , and experimental group ( n = 15 , drinking DSS solution + intraperitoneal injection of PMPs) . Peripheral blood⁃derived PMPs suspension was collected from inflammatory bowel disease ( IBD) patients. A colitis model was constructed in mice by allowing them to freely drink a 5% DSS solution for 1 week , followed by continuous intraperitoneal injection of PMPs for 7 days. Disease activity index (DAI) scores was recorded daily and the severity of intestinal inflammation with histopathological scores (HI) was assessed by HE staining of colon samples at the end of the experiment. Myeloperoxidase (MPO) , neutrophil elastase (NE) , citrullinated histone H3 (citH3) , and free DNA levels were measured in colon homogenate , observe intestinal mucosal structure by transmission electron microscopy , and intestinal permeability was tested using fluorescein isothiocyanate⁃dextran (FITC⁃D) . Results: Compared with the normal control group , the colonic mucosa of mice in the PMPs group showed edema , severe destruction of epithelial structure , extensive aggregation of inflammatory cells , and increased overall HI score (P < 0. 01) ; the levels of inflammatory factors such as IL⁃1β and TNF⁃α in colonic tissue homogenates of mice in the PMPs group increased (P < 0. 05) , and the expression of NETs increased (P < 0. 05) ; the plasma FITC⁃D level of mice in the PMPs group significantly increased (P < 0. 05) , and the permeability of intestinal mucosa increased. Compared with the DSS group , the experimental group mice had higher plasma FITC⁃D levels ( P < 0. 05 ) and more electron microscopic colonic epithelial damage. Conclusion PMPs induces NETs formation in mice , promotes colonic inflammation in mice , increases intestinal mucosal permeability and aggravates intestinal inflammation in mice with DSS colitis.

Objective : To explore the general information，clinical features，imaging findings and outcome of pa- tients with drug-induced cholestatic． Methods : The clinical data of patients diagnosed as cholestatic drug-induced liver injury in recent 5 years were analyzed retrospectively，and followed up for at least 6 months. Results : There were 105 patients with drug-induced cholestatic liver injury in the hospital，the median age was 55 years old (54. 3% male) ，most of them had no specific clinical symptoms ; there were nearly 80 kinds of drugs involved，the top three were traditional Chinese medicine (34. 3% ) ，antineoplastic drugs (22. 9% ) and antibiotics ( 10. 5% ) . Among the 49 patients with magnetic resonance cholangiopancreatography ( MRCP) ，7 ( 14. 3% ) had sclerosing cholangitis-like changes ; most of the patients were combined with multiple liver-protecting and enzyme-lowering drugs ; there were 53 cured (50. 5% ) ，41 improved (39. 0% ) ，7 uncured (6. 7% ) ，and 4 died (3. 8% ) among 105 patients，and the total effective rate was 89. 5%． Conclusion Drug-induced cholestatic liver injury mainly oc- curs in elderly patients，involving many kinds of drugs，mainly traditional Chinese medicine．Drugs can also cause changes similar to sclerosing cholangitis，so drug-induced liver injury (DILI) should be used as one of the differen- tial diagnosis of cholestasis and abnormal cholangiography．Liver disease and the number of drugs have no effect on the prognosis of the patients，while low Roussel Uclaf causality assessment method (RUCAM) score and hemoglobin count，short hospitalization time and high white blood cell count are poor prognostic factors.

BACKGROUND: Weather conditions are a possible contributing factor to age-related macular degeneration (AMD), a leading cause of irreversible loss of vision. The present study evaluated the joint effects of meteorological factors and fine particulate matter (PM_2.5) on AMD. METHODS: Data was extracted from a national cross-sectional survey conducted across 10 provinces in rural China. A total of 36,081 participants aged 40 and older were recruited. AMD was diagnosed clinically by slit-lamp ophthalmoscopy, fundus photography, and spectral domain optical coherence tomography (OCT). Meteorological data were calculated by European Centre for Medium-Range Weather Forecasts (ECMWF) reanalysis and were matched to participants' home addresses by latitude and longitude. Participants' individual PM_2.5 exposure concentrations were calculated by a satellite-based model at a 1-km resolution level. Multivariable-adjusted logistic regression models paired with interaction analysis were performed to investigate the joint effects of meteorological factors and PM_2.5 on AMD. RESULTS: The prevalence of AMD in the study population was 2.6% (95% CI 2.42-2.76%). The average annual PM_2.5 level during the study period was 63.1 ± 15.3 µg/m³. A significant positive association was detected between AMD and PM_2.5 level, temperature (T), and relative humidity (RH), in both the independent and the combined effect models. For PM_2.5, compared with the lowest quartile, the odds ratios (ORs) with 95% confidence intervals (CIs) across increasing quartiles were 0.828 (0.674,1.018), 1.105 (0.799,1.528), and 2.602 (1.516,4.468). Positive associations were observed between AMD and temperature, with ORs (95% CI) of 1.625 (1.059,2.494), 1.619 (1.026,2.553), and 3.276 (1.841,5.830), across increasing quartiles. In the interaction analysis, the estimated relative excess risk due to interaction (RERI) and the attributable proportion (AP) for combined atmospheric pressure and PM_2.5 was 0.864 (0.586,1.141) and 1.180 (0.768,1.592), respectively, indicating a synergistic effect between PM_2.5 and atmospheric pressure. CONCLUSIONS This study is among the first to characterize the coordinated effects of meteorological factors and PM_2.5 on AMD. The findings warrant further investigation to elucidate the relationship between ambient environment and AMD.
Humans ; Adult ; Middle Aged ; Cross-Sectional Studies ; Air Pollutants/analysis* ; Particulate Matter/analysis* ; China/epidemiology* ; Macular Degeneration/etiology* ; Meteorological Concepts

ObjectiveTo explore the formulation rules for the treatment of heart pain in the Medical Heart Enlightenment （《医学心悟》） from the perspective of the "Tangye Jingfa Tu"， thereby providing a way of thinking about the treatment of heart pain in traditional Chinese medicine （TCM） and the study of the Medical Heart Enlightenment. MethodThe "Tangye Jingfa Tu" contained in the Secrets for Auxiliary Cultivation Life： The Essential Method of Using Herbal Medicine for the Differential Treatment of the Five Zang Organs （《辅行诀五脏用药法要》） was used to analyze the nine prescriptions for heart pain in Volume Ⅲ of the Medical Heart Enlightenment by CHENG Guopeng in the Qing dynasty. A "table for analyzing the formulation of the nine prescriptions for heart pain" was developed. The analysis diagrams for decoction and meridian rules in nine prescriptions for heart pain were plotted and the compatible structure of the medicinal flavors was analyzed. ResultThe composition of Chenxiang Jiangqisan for the treatment of Qi-induced heart pain is "five pungent， four bitter， and two sweet drugs"， the composition of Shouniansan for the treatment of blood-induced heart pain is "five bitter， four pungent， three sweet， and one salty drugs"， the composition of Qingzhongtang for the treatment of heat-induced heart pain is "six bitter， three pungent， and two sweet drugs”， the composition of Jiangfutang with Cinnamomi Cortex for cold-induced heart pain is "three pungent and two sweet drugs"， the composition of Xiaobanxia modified with Fuling Tang for treating fluid retention-induced heart pain is "two pungent and two sweet drugs"， the composition of Baohetang for treating heart pain due to dietary stagnation is "five sweet， four pungent， four bitter， and one sour drugs"， the composition of Guipitang for the treatment of deficiency-induced heart pain is "eight sweet， four bitter， three pungent， and one sour drugs"， the combination of Huachongwan for the treatment of worm-induced heart pain is "seven bitter， six pungent， and four sweet drugs"， the composition of Shenzhusan， Congbaijiu， and Shengjiangtang for the treatment of resistance-induced heart pain is "eight pungent， four bitter， and two sweet drugs". ConclusionFrom the perspective of the "Tangye Jingfa Tu"， the Medical Heart Enlightenment is based on the compatibility principle of "pungent-bitter-sweet drugs" in the treatment of heart pain， with heart deficiency treated with salty drugs for tonifying， or bitter-sweet-salty drugs， and heart excess treated with bitter drugs for purging， or sweet-pungent-bitter drugs， mostly applying the transformation rules of five medicinal flavors， i.e.， "sweet-pungent-bitter drugs" and promoting the action of the pungent and sweet drugs acting on the spleen into the heart to relieve and purge the heart. In most cases， the treatment focuses on harmonizing the heart， liver， spleen， and kidneys， with an emphasis on the mother-child relationship and the application of the principles of the five elements generating and controlling each other. If the progression of the disease involves both the mother and child organs， the formulation should adhere to the compatibility rule of "the child organ makes the mother organ excess and the mother organ makes the child organ deficient".