OBJECTIVE To explore the specific application and evaluation effect of objective structured clinical examination(OSCE)-guided scenario-based practical teaching mode in training clinical pharmacists. METHODS Fifty-six trainees who participated in the clinical pharmacist training program in the Second Xiangya Hospital of Central South University from October 2020 to September 2022 were selected as the research objects. OSCE-guided teaching was conducted, and the application effect of OSCE-guided teaching mode in clinical pharmacist training was explored and analyzed by using theoretical examination results and OSCE assessment results as evaluation indicators. RESULTS Through comparative analysis, it was found that the OSCE-guided teaching mode not only enabled students to better grasp the theoretical knowledge points required by the training outline, but also improved their clinical thinking ability, problem-solving ability, and communication and coordination skills to varying degrees. CONCLUSION For clinical pharmacist trainees, the OSCE teaching mode is conducive to the comprehensive improvement of clinical pharmacist skills and is suitable for cultivating clinical pharmacists who are capable of independently carrying out clinical pharmacy services in the new situation.

Objective: To investigate the factors affecting macular degeneration (MD) in middle-aged and elderly populations, so as to provide the reference for prevention and treatment of MD. Methods: People at ages of 50 years and older who were admitted to ophthalmology department of Hangzhou First People's Hospital and received MD screening were selected as the study subjects. General information including age, gender, eye-using habits and family history of MD were collected by questionnaire surveys. MD was diagnosed by ophthalmological examination, and the prevalence of MD in middle-aged and elderly people was analyzed. A multivariable logistic regression model was used to identify the influencing factors of MD. Results: A total of 2 832 people were investigated, including 1 527 males (53.92%) and 1 305 females (46.08%), and 1 878 people (66.31%) aged 70 years and older. There were 498 people (17.58%) with good eye-using habits, 1 180 (41.67%) with general eye-using habits and 1 154 (40.75%) with poor eye-using habits. There were 1 817 people with family history of MD (64.16%). Multivariable logistic regression analysis showed that people at ages of 70 years and older (OR=2.815, 95%CI: 1.350-5.871), with poor eye-using habits (OR=2.354, 95%CI: 1.373-4.035), with family history of MD (OR=2.782, 95%CI: 1.138-6.799), with cataract (OR=2.593, 95%CI: 1.157-5.815) and with visual central defect (OR=2.601, 95%CI: 1.252-5.404) had a higher risk of MD. Conclusion Age, eye-using habits, family history of MD, cataract and visual central defect are influencing factors for MD in middle-aged and elderly populations.

Objective:To explore the clinical manifestations,pathological features,immunophenotype,as well as diagnosis,treatment and prognosis of patients with CD4-CD56+blastic plasmacytoid dendritic cell neoplasm(BPDCN),in order to further understand the rare disease.Methods:The clinical data,laboratory examinations and treatment regimens of two patients with CD4-CD56+BPDCN in the First Affiliated Hospital of Wannan Medical College were retrospectively analyzed.Results:The two patients were both elderly males with tumor involved in skin,bone marrow,lymph nodes,etc.Immunohistochemical results of skin lesions showed that both CD56 and CD123 were positive,while CD4,CD34,TdT,CD3,CD20,MPO and EBER were negative.Flow cytometry of bone marrow demonstrated that CD56,CD123,and CD304 were all positive,while specific immune markers of myeloid and lymphoid were negative.Two patients were initially very sensitive to acute lymphoblastic leukemia or lymphomatoid chemotherapy regimens,but prone to rapid relapse.The overall survival of both patients was 36 months and 4 months,respectively.Conclusion:CD4-CD56+BPDCN is very rare and easily misdiagnosed as other hematological tumors with poor prognosis.Acute lymphoblastic leukemia or lymphomatoid therapy should be used first to improve the poor prognosis.

Objective:To investigate the expression of heterogeneous nuclear ribonucleoprotein A2B1 (HNRNPA2B1) in human esophageal cancer tissues and its clinical significance.Methods:Single-cell data for esophageal cancer were downloaded from the Gene Expression Omnibus (GEO) database (GSE160269 dataset, last updated on November 29, 2020) to analyze the expression of HNRNPA2B1. Transcriptional sequencing data for esophageal cancer from The Cancer Genome Atlas (TCGA) database, including the fragments per kilobase of transcript per million mapped reads (FPKM) quantitative data (173 samples, consisting of 162 esophageal cancer tissues and 11 adjacent normal tissues), and survival data in the phenotype category were downloaded. Analysis of FPKM quantitative data from the TCGA database for esophageal cancer was performed. The top 250 genes most correlated with HNRNPA2B1 were selected and the R4.3.0 clusterProfiler package was used to conduct Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on the selected gene set. FPKM quantitative data from the TCGA database for esophageal cancer were imported into the CIBERSORTx website to obtain immune cell abundance scores, and the correlation between HNRNPA2B1 and the degree of immune cell infiltration was analyzed. The clinicopathological data of patients from esophageal cancer tissue microarrays including 114 cases of esophageal squamous cell carcinoma tissues and 66 cases of adjacent normal tissues were collected. The patients underwent surgery from January 2006 to December 2008, and the follow-up period extended until July 2015. Cytokeratin (CK) and HNRNPA2B1 expression in esophageal cancer tissue microarrays were detected by using multi-color immunohistochemical (mIHC) staining, and multispectral tissue imaging was conducted. The R4.3.0 survival package and survminer package in TCGA database were used to calculate the optimal cut-off value of HNRNPA2B1 expression and the proportion of CK + HNRNPA2B1 + cells in tissue microarrays was used to calculate the cut-off value of HNRNPA2B1 expression based on which patients were categorized into high and low expression groups. The overall survival (OS) of both groups was compared and the factors influencing OS were analyzed by using the Cox proportional hazards model. Results:In the GSE160269 dataset of single-cell data for esophageal cancer, the expression level of HNRNPA2B1 in tumor epithelial cells was higher than that in normal epithelial cells, and HNRNPA2B1 was highly expressed in various immune cell subtypes. The high expression level of HNRNPA2B1 was positively correlated with regulatory T cells, naive B cells and memory CD4 + T cells. GO enrichment analysis revealed that HNRNPA2B1 was primarily involved in the biological process of nuclear division, cellular components were mainly enriched in chromosomal regions, and molecular functions were mainly enriched in ATP hydrolysis activity. KEGG enrichment analysis indicated that HNRNPA2B1 was primarily involved in biological processes such as the cell cycle, spliceosome, and DNA replication. Results from mIHC and multispectral tissue imaging demonstrated that CK was predominantly expressed in the cell membranes of tumor cells and normal esophageal epithelial cells, while HNRNPA2B1 was primarily expressed in the nuclei of tumor cells and normal esophageal cells. The expression level of HNRNPA2B1 in esophageal cancer tissues was higher than that in the normal paracancerous tissues ( U = 2 984.00, P < 0.05). Results of tissue microarrays and the survival analysis on the data in the TCGA database indicated that esophageal cancer patients with low HNRNPA2B1 expression had a better OS compared to those with high expression (both P < 0.05). Cox multivariate regression analysis revealed that age ( HR = 1.919, 95% CI: 1.158-3.182, P = 0.011), TNM stage ( HR = 2.404, 95% CI: 1.374-4.207, P = 0.002), T stage ( HR = 2.349, 95% CI: 1.150-4.789, P = 0.019), and the expression of HNRNPA2B1 in tumor epithelial cells ( HR = 2.160, 95% CI: 1.280-3.647, P = 0.004) were independent factors influencing OS in esophageal cancer patients. Conclusions:The high expression of HNRNPA2B1 protein in esophageal cancer tissues may play a role in the developement and progression of esophageal cancer, serving as a crucial biological indicator for prognostic assessment of esophageal cancer.

Objective:To analyze the relationship between early-life famine exposure and the risk of metabolic syndrome in Chinese population.Methods:Relevant literature on the relationship between early-life famine exposure and the risk of metabolic syndrome in the Chinese population was retrieved from databases such as CNKI, Wanfang, VIP, CBM, Web of Science, and PubMed. The search was conducted from the inception of the databases up to October 2022. Two researchers independently extracted and systematically evaluated the data from the literature, and meta-analysis was performed using Stata 16.0 software. Results:A total of 12 publications met the inclusion criteria, including 71 470 study subjects. Meta-analysis results showed that early-life famine exposure increased the risk of metabolic syndrome in the Chinese population( OR=1.28, 95% CI 1.16-1.40). Subgroup analysis showed that both fetal famine exposure( OR=1.25, 95% CI 1.03-1.52) and childhood famine exposure( OR=1.29, 95% CI 1.15-1.45) increased the risk of developing metabolic syndrome compared to the non-exposed group, and this significant association was only found in the female population. Conclusion:Early-life exposure to famine may increase the risk of developing metabolic syndrome in adulthood in the Chinese population, particularly among females.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

OBJECTIVE: To explore the mechanisms of Buyang Huanwu Decoction (BYHWD) modulating the gut microbiome and trimethylamine oxide (TAMO) to exert cardioprotective effects. METHODS: Ligation of the left anterior descending coronary artery was performed in rats to induce heart failure (HF). Except for the sham-operation group (n=10), 36 operation-induced models were randomized into 3 groups using a random number table (n=12 in each group): the model group, the BYHWD group (15.02 g/kg BYHWD), and the positive group (4.99 g/kg metoprolol succinate). After 4-week treatment (once daily by gavage), echocardiography was applied to evaluate the cardiac function and the Tei index (the ratio of ventricular isovolumic contraction time (IVCT) and isovolumic diastolic time (IVRT) to ejection time (ET)) was calculated; hematoxylin-eosin (HE) staining was observed to characterize the pathology of the myocardium and small intestinal villi. D-lactic acid was detected by an enzyme-linked immunosorbent assay (ELISA). Expressions of occludin, claudin-1, and zonula occludens (ZO-1) were detected by Western blot. 16S ribosomal ribonucleic acid (16S rRNA) sequencing was used to explore the changes in the intestinal flora. TMAO was detected via liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: In the echocardiography, the Tei index was considerably lower in the positive and BYHWD groups compared with the model group (P<0.05). Besides, BYHWD improved the pathology of myocardium and small intestine of HF rats and lowered the D-lactic acid content in the serum, when compared with the model group (P<0.05). BYHWD also improved the expression of occludin and claudin-1 (P<0.05); in the gut microbiota analysis, BYHWD slowed down modifications in the structure distribution of gut microbiota and regulated the diversity of intestinal flora in HF rats. The content of TMAO in the serum was significantly lowered by BYWHT compared with the model group (P<0.05). CONCLUSION BYHWD may delay progression of HF by enhancing the intestinal barrier structure, and regulating intestinal flora and TAMO.
Rats ; Animals ; Rats, Sprague-Dawley ; Gastrointestinal Microbiome ; Chromatography, Liquid ; Claudin-1 ; Occludin ; RNA, Ribosomal, 16S ; Tandem Mass Spectrometry ; Drugs, Chinese Herbal/pharmacology* ; Heart Failure

OBJECTIVE: To evaluate the long-term prognosis of patients with ST-segment elevation myocardial infarction (STEMI) treated with different reperfusion strategies in Chinese county-level hospitals. METHODS: A total of 2,514 patients with STEMI from 32 hospitals participated in the China Acute Myocardial Infarction registry between January 2013 and September 2014. The success of fibrinolysis was assessed according to indirect measures of vascular recanalization. The primary outcome was 2-year mortality. RESULTS: Reperfusion therapy was used in 1,080 patients (42.9%): fibrinolysis ( n= 664, 61.5%) and primary percutaneous coronary intervention (PCI) ( n= 416, 38.5%). The most common reason for missing reperfusion therapy was a prehospital delay > 12 h (43%). Fibrinolysis [14.5%, hazard ratio ( HR): 0.59, 95% confidence interval ( CI) 0.44-0.80] and primary PCI (6.8%, HR= 0.32, 95% CI: 0.22-0.48) were associated with lower 2-year mortality than those with no reperfusion (28.5%). Among fibrinolysis-treated patients, 510 (76.8%) achieved successful clinical reperfusion; only 17.0% of those with failed fibrinolysis underwent rescue PCI. There was no difference in 2-year mortality between successful fibrinolysis and primary PCI (8.8% vs. 6.8%, HR = 1.53, 95% CI: 0.85-2.73). Failed fibrinolysis predicted a similar mortality (33.1%) to no reperfusion (33.1% vs. 28.5%, HR= 1.30, 95% CI: 0.93-1.81). CONCLUSION In Chinese county-level hospitals, only approximately 2/5 of patients with STEMI underwent reperfusion therapy, largely due to prehospital delay. Approximately 30% of patients with failed fibrinolysis and no reperfusion therapy did not survive at 2 years. Quality improvement initiativesare warranted, especially in public health education and fast referral for mechanical revascularization in cases of failed fibrinolysis.
Humans ; ST Elevation Myocardial Infarction/therapy* ; Percutaneous Coronary Intervention ; East Asian People ; Treatment Outcome ; Myocardial Reperfusion ; Myocardial Infarction ; Registries ; Hospitals

Neuropathic pain(NP) has similar phenotypes but different sequential neuroinflammatory mechanisms in the pathological process. It is of great significance to inhibit the initiation of neuroinflammation, which has become a new direction of NP treatment and drug development in recent years. Mongolian drug Naru-3 is clinically effective in the treatment of trigeminal neuralgia, sciatica, and other NPs in a short time, but its pharmacodynamic characteristics and mechanism of analgesia are still unclear. In this study, a spinal nerve ligation(SNL) model simulating clinical peripheral nerve injury was established and the efficacy and mechanism of Naru-3 in the treatment of NPs was discussed by means of behavioral detection, side effect evaluation, network analysis, and experimental verification. Pharmacodynamic results showed that Naru-3 increased the basic pain sensitivity threshold(mechanical hyperalgesia and thermal radiation hyperalgesia) in the initiation of SNL in animals and relieved spontaneous pain, however, there was no significant effect on the basic pain sensitivity threshold and motor coordination function of normal animals under physiological and pathological conditions. Meanwhile, the results of primary screening of target tissues showed that Naru-3 inhibited the second phase of injury-induced nociceptive response of formalin test in mice and reduced the expression of inflammatory factors in the spinal cord. Network analysis discovered that Naru-3 had synergy in the treatment of NP, and its mechanism was associated with core targets such as matrix metalloproteinase-9(MMP9) and interleukin-1β(IL-1β). The experiment further took the dorsal root ganglion(DRG) and the stage of patho-logical spinal cord as the research objects, focusing on the core targets of inducing microglial neuroinflammation. By means of Western blot, immunofluorescence, agonists, antagonists, behavior, etc., the mechanism of Naru-3 in exerting NP analgesia may be related to the negative regulation of the MMP9/IL-1β signaling pathway-mediated microglia p38/IL-1β inflammatory loop in the activation phase. The relevant research enriches the biological connotation of Naru-3 in the treatment of NP and provides references for clinical rational drug use.
Rats ; Mice ; Animals ; Matrix Metalloproteinase 9/metabolism* ; Rats, Sprague-Dawley ; Neuroinflammatory Diseases ; Interleukin-1beta/metabolism* ; Spinal Cord/metabolism* ; Signal Transduction ; Hyperalgesia/metabolism* ; Neuralgia/metabolism*

The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.
Rats ; Mice ; Animals ; Chronic Pain/metabolism* ; Rats, Sprague-Dawley ; Ganglia, Spinal/metabolism* ; Ligands ; Signal Transduction ; Hyperalgesia/metabolism* ; Drugs, Chinese Herbal