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.

This study investigated the association between a proximal promoter polymorphism of IFNGR1 (interferon-γ receptor α chain, IFNGR-α) and breast cancer susceptibility, as well as the prognostic value of its expression variation in breast cancer patients. A case-control study was conducted at the Sixth Medical Center of PLA General Hospital from June 2020 to June 2022. The study included 182 pathologically confirmed breast cancer patients as the breast cancer group, 177 non-tumor patients with benign breast lesions as the benign breast lesions group, and 229 healthy individuals as the normal control group. 2-3 ml EDTA anticoagulant whole blood samples were collected from all participants, and genomic DNA was extracted and stored for further analysis. Basic patient information was retrieved from the hospital′s electronic medical records by patients′ ID number. The proximal promoter sequence of IFNGR1 was obtained from NCBI, and sequencing primers were designed using Primer Premier 6.0. Sanger sequencing was employed to analyze the IFNGR1 promoter sequence in the three groups, and the results were compared with the Eukaryotic Promoter Database (EPD) sequence using Bioedit software. Statistical analysis was performed on single nucleotide polymorphisms (SNPs) in the IFNGR1 promoter. The TCGA database was utilized to assess the relationship between IFNGR1 expression levels and breast cancer patient survival. The findings revealed that the -56 TG genotype of the IFNGR1 promoter was significantly associated with increased breast cancer risk ( Z=2.73, P<0.05). Notably, IFNGR1 expression was lower in breast cancer group compared to normal control group ( P<0.05). Analysis of the TCGA database indicated that patients with high IFNGR1 expression had longer survival times than those with low expression ( HR=0.87, 95% CI:0.77-0.98, P<0.05). In summary, the IFNGR1 -56 TG genotype is associated with an increased risk of breast cancer, and there is a positive correlation between IFNGR1 expression levels and the survival of breast cancer patients.

Objective To establish an animal model of hand,foot,and mouth disease(HFMD)in Syrian hamsters coinfected with coxsackievirus A6(CVA6)and coxsackievirus B1(CVB1).Methods 42 Syrian hamsters were divided into a CVA6 infection group,CVB1 infection group,CVA6 and CVB1 coinfection group and control group.A HFMD model was established by nasal instillation of virus solution and phosphate-buffered saline.Clinical and physiological indicators and detoxification status were monitored and recorded for 15 d,and animals were selected on day 7(D7)after infection for histopathology and viral antigen and nucleic acid testing.Results Hamsters in the single-infection and coinfection groups showed clinical symptoms similar to human HFMD.White blood cell,neutrophil,and lymphocyte result were characteristic of viral infection.Both viral nucleic acids were detected in throat swabs,feces,blood,and tissues and both viruses were isolated from fecal samples.Pathological damage and positive co-localization of CVA6 and CVB1 viral antigen proteins and nucleic acids were found in brain and other tissues.Conclusions Nasal instillation of a CVA6 and CVB1 mixture can successfully coinfect Syrian hamsters,replicate herpes infection similar to human HFMD,and cause pathological viral myocarditis and encephalitis damage.The result showed that the coinfection group was more seriously affected than the single-infection group,with worse clinical symptoms,increased viral replication,and obvious tissue pathological damage.This study provides a reference for further basic and clinical research into human enterovirus coinfection.

OBJECTIVE To explore the expression level of miR-196a in cervical cells infected with high-risk human papillomavirus(HPV)16 and 18.METHODS The Gene Expression Omnibus(GEO)was used to screen for dif-ferentially expressed miRNAs between HPV 16 or 18-positive cervical cancer cells and normal cervical cells.On-line biological software https://kmplot.com/analysis/was utilized to analyze the relationship between the most differentially expressed miRNA and the overall survival of cervical cancer patients.Cervical swab samples positive for HPV 16 or HPV 18,detected by real-time fluorescent quantitative polymerase chain reaction(qPCR)genoty-ping,were collected as the study subjects.Cervical swab samples from the same period of physical examination population that were negative for HPV 16 or HPV 18 by qPCR genotyping served as negative controls.The qRT-PCR method was employed to detect the level of miR-196a in cervical cells,with data processed via the 2-△△Ctmethod.RESULTS Differential analysis of the GSE86100 data revealed that miR-196a expression de-creased in HPV 16 or HPV 18-positive cervical cells(log2FC=-6.60,P＜0.001),while miR-3188 expression significantly increased(log2FC=6.22,P＜0.001).Using online analysis tools https://kmplot.com/analysis,it was found that cervical cancer patients with high miR-196a expression had a shorter overall survival compared to those with low m iR-196a expression(HR=1.87,95％CI:1.17-3.00,P=0.008).H owever,there was no cor-relation between miR-3188 and the overall survival of cervical cancer patients(HR=1.47,95％CI:0.92-2.37,P=0.110).The results of specific qRT-PCR testing showed that the expression levels of miR-196a in cervical cells positive for HPV 16 and HPV 18 were 0.93±0.09 and 0.51±0.07,respectively,which were lower than those in the normal control group(1.89±0.13)(P＜0.05),consistent with the sequencing analysis results CONCLUSIONS Infection of cervical cells with HPV 16 or HPV 18 can lead to decreased expression of miR-196a,and the expres-sion level of miR-196a is negatively correlated with the overall survival of cervical cancer patients.

This study investigated the association between a proximal promoter polymorphism of IFNGR1 (interferon-γ receptor α chain, IFNGR-α) and breast cancer susceptibility, as well as the prognostic value of its expression variation in breast cancer patients. A case-control study was conducted at the Sixth Medical Center of PLA General Hospital from June 2020 to June 2022. The study included 182 pathologically confirmed breast cancer patients as the breast cancer group, 177 non-tumor patients with benign breast lesions as the benign breast lesions group, and 229 healthy individuals as the normal control group. 2-3 ml EDTA anticoagulant whole blood samples were collected from all participants, and genomic DNA was extracted and stored for further analysis. Basic patient information was retrieved from the hospital′s electronic medical records by patients′ ID number. The proximal promoter sequence of IFNGR1 was obtained from NCBI, and sequencing primers were designed using Primer Premier 6.0. Sanger sequencing was employed to analyze the IFNGR1 promoter sequence in the three groups, and the results were compared with the Eukaryotic Promoter Database (EPD) sequence using Bioedit software. Statistical analysis was performed on single nucleotide polymorphisms (SNPs) in the IFNGR1 promoter. The TCGA database was utilized to assess the relationship between IFNGR1 expression levels and breast cancer patient survival. The findings revealed that the -56 TG genotype of the IFNGR1 promoter was significantly associated with increased breast cancer risk ( Z=2.73, P<0.05). Notably, IFNGR1 expression was lower in breast cancer group compared to normal control group ( P<0.05). Analysis of the TCGA database indicated that patients with high IFNGR1 expression had longer survival times than those with low expression ( HR=0.87, 95% CI:0.77-0.98, P<0.05). In summary, the IFNGR1 -56 TG genotype is associated with an increased risk of breast cancer, and there is a positive correlation between IFNGR1 expression levels and the survival of breast cancer patients.

OBJECTIVE To explore the expression level of miR-196a in cervical cells infected with high-risk human papillomavirus(HPV)16 and 18.METHODS The Gene Expression Omnibus(GEO)was used to screen for dif-ferentially expressed miRNAs between HPV 16 or 18-positive cervical cancer cells and normal cervical cells.On-line biological software https://kmplot.com/analysis/was utilized to analyze the relationship between the most differentially expressed miRNA and the overall survival of cervical cancer patients.Cervical swab samples positive for HPV 16 or HPV 18,detected by real-time fluorescent quantitative polymerase chain reaction(qPCR)genoty-ping,were collected as the study subjects.Cervical swab samples from the same period of physical examination population that were negative for HPV 16 or HPV 18 by qPCR genotyping served as negative controls.The qRT-PCR method was employed to detect the level of miR-196a in cervical cells,with data processed via the 2-△△Ctmethod.RESULTS Differential analysis of the GSE86100 data revealed that miR-196a expression de-creased in HPV 16 or HPV 18-positive cervical cells(log2FC=-6.60,P＜0.001),while miR-3188 expression significantly increased(log2FC=6.22,P＜0.001).Using online analysis tools https://kmplot.com/analysis,it was found that cervical cancer patients with high miR-196a expression had a shorter overall survival compared to those with low m iR-196a expression(HR=1.87,95％CI:1.17-3.00,P=0.008).H owever,there was no cor-relation between miR-3188 and the overall survival of cervical cancer patients(HR=1.47,95％CI:0.92-2.37,P=0.110).The results of specific qRT-PCR testing showed that the expression levels of miR-196a in cervical cells positive for HPV 16 and HPV 18 were 0.93±0.09 and 0.51±0.07,respectively,which were lower than those in the normal control group(1.89±0.13)(P＜0.05),consistent with the sequencing analysis results CONCLUSIONS Infection of cervical cells with HPV 16 or HPV 18 can lead to decreased expression of miR-196a,and the expres-sion level of miR-196a is negatively correlated with the overall survival of cervical cancer patients.

Objective To establish an animal model of hand,foot,and mouth disease(HFMD)in Syrian hamsters coinfected with coxsackievirus A6(CVA6)and coxsackievirus B1(CVB1).Methods 42 Syrian hamsters were divided into a CVA6 infection group,CVB1 infection group,CVA6 and CVB1 coinfection group and control group.A HFMD model was established by nasal instillation of virus solution and phosphate-buffered saline.Clinical and physiological indicators and detoxification status were monitored and recorded for 15 d,and animals were selected on day 7(D7)after infection for histopathology and viral antigen and nucleic acid testing.Results Hamsters in the single-infection and coinfection groups showed clinical symptoms similar to human HFMD.White blood cell,neutrophil,and lymphocyte result were characteristic of viral infection.Both viral nucleic acids were detected in throat swabs,feces,blood,and tissues and both viruses were isolated from fecal samples.Pathological damage and positive co-localization of CVA6 and CVB1 viral antigen proteins and nucleic acids were found in brain and other tissues.Conclusions Nasal instillation of a CVA6 and CVB1 mixture can successfully coinfect Syrian hamsters,replicate herpes infection similar to human HFMD,and cause pathological viral myocarditis and encephalitis damage.The result showed that the coinfection group was more seriously affected than the single-infection group,with worse clinical symptoms,increased viral replication,and obvious tissue pathological damage.This study provides a reference for further basic and clinical research into human enterovirus coinfection.

BACKGROUND:Artificially synthesized hydroxyapatite ceramic granules are widely used in clinical practice to repair large-volume bone defects.However,the osteogenic effect of hydroxyapatite ceramic granules prepared by high-temperature sintering is limited by their low degradability and bioactivity. OBJECTIVE:To prepare biomimetically precipitated nanocrystalline calcium phosphate granules by a novel low-temperature deposition technique,and to characterize their physicochemical properties and cytocompatibility. METHODS:Biomimetically precipitated nanocrystalline calcium phosphate granules were prepared using a modified supersaturated calcium phosphate mineralization solution and a repeated settling and decantation washing method.Hydroxyapatite bioceramic granules were used as the control.The morphology and phase composition of the granules were characterized by scanning electron microscopy,X-ray diffraction,and Fourier transform infrared spectroscopy.The specific surface area,porosity distribution,hardness and hydrophilicity of the granules were characterized by BET-N2 method,hardness test,and contact angle test.The adsorption properties of the granules for bovine serum albumin and fetal bovine serum protein were determined by bicinchoninic acid assay.The two kinds of granules or granule extracts were co-cultured with human umbilical cord mesenchymal stem cells,and the cell proliferation was detected by MTT assay. RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the surface of the two kinds of particles was slightly rough and accompanied by tiny particles,the surface of the hydroxyapatite bioceramic particles was dense and smooth,and the biomimetically precipitated nanocrystalline calcium phosphate granules were mainly composed of needle/plate crystals with non-uniform nanometer size,and formed a nanopore structure between the crystals.X-ray diffraction and Fourier transform infrared spectroscopy exhibited that compared with hydroxyapatite bioceramic granules,biomimetically precipitated nanocrystalline calcium phosphate granules had smaller crystalline particles,lower crystallinity,and more binding water and carbonic acid groups.Compared with hydroxyapatite bioceramic granules,biomimetically precipitated nanocrystalline calcium phosphate granules had higher specific surface area,better hydrophilicity,lower hardness,and higher protein adsorption capacity.(2)The results of MTT assay showed that the two kinds of granule extracts had no cytotoxicity,human umbilical cord mesenchymal stem cells survived well on the surface of the two kinds of granules,and the biomimetically precipitated nanocrystalline calcium phosphate granules had stronger cell proliferation activity.(3)These findings indicate that compared with hydroxyapatite bioceramic granules,biomimetically precipitated nanocrystalline calcium phosphate granules have better physicochemical properties and cytocompatibility.

Autophagy is an important mechanism to maintain cellular function and metabolism,whereas ab-normal autophagy can cause the advent and worsening of various diseases.N6-Methyladenosine(m6A)RNA methylation is a reversible RNA modification,which is regulated by m6A methyltransferase,m6A demethylase and m6A-binding protein.Studies have shown that autophagy-related genes promote or attenuate autophagy level dependent on the regulation of m6A,and then participate in the process of diseases.This paper reviews the progress of m6A modification regulatory enzymes and their binding proteins in regulating cell autophagy to provide reference for future researches.

Objective To investigate the effects and mechanism of Zhachong Shisanwei Pills on rats with cerebral ischemia.Methods Totally 75 rats were randomly divided into sham-operation group,model group,positive drug group(Ginaton,21.6 mg/kg),and Zhachong Shisanwei Pills low-,medium-,and high-dosage groups(81,162,324 mg/kg).Each treatment group was given the corresponding drug by gavage for 5 days.On the 6th day,a cerebral ischemia rat model was prepared by suture method.After 24 hours of modeling,the drugs were given in the same manner for 2 days.Neurological function scoring,horizontal beam walking scoring,and grip strength testing were performed on rats.TTC staining was used to detect the cerebral infarction rate,HE staining and Nissl staining were used to observe the morphology of brain tissue.TUNEL staining was used to detect the apoptosis rate of brain tissue cells.Differential genes in the treatment of cerebral ischemia using Zhachong Shisanwei Pills were screened by transcriptomics,and RT-qPCR,immunohistochemistry and Western blot were used to detect differential gene mRNA and protein expression.Results Compared with the sham-operation group,the model group rats showed a decrease in neurological function scores,horizontal beam walking scores,grip strength,an increase in cerebral infarction rate,neuronal nucleus condensation,vacuolar changes,widened intercellular spaces,the number of Nissl bodies reduced,and the apoptosis rate increased(P<0.01,P<0.001);compared with the model group,the Zhachong Shisanwei Pills medium-dosage group showed an increase in neurological function score,horizontal beam walking score,and grip strength in rats,a decrease in cerebral infarction rate,a lower degree of neuronal damage,an increase in the number of Nissl bodies,and a decrease in cell apoptosis rate(P<0.05,P<0.01).Transcriptome and bioinformatics analysis screened the Hippo signaling pathway related to the anti-cerebral ischemia effect of Zhachong Shisanwei Pills.The key genes of this pathway,mammalian sterile line 20 like kinase(MST1)1,Yes related protein(YAP)1,large tumor suppressor kinase(LATS)1,and TEA domain family member(TEAD)1 were detected.The results showed that the expression of MST1 mRNA and protein in brain tissue of model rats significantly increased,while the expressions of YAP1,LATS1,TEAD1 mRNA and protein significantly decreased;Zhachong Shisanwei Pills could down-regulate the expression of MST1 in brain tissue of model rats,and up-regulate the expressions of YAP1,LATS1 and TEAD1.Conclusion Zhachong Shisanwei Pills may exert anti-cerebral ischemia effects through the Hippo signaling pathway.