OBJECTIVE To investigate the improvement effect and mechanism of processed Oxytropis falcata on renal fibrosis （RF） in rats. METHODS RF model was induced by adenine. After modeling， the rats were divided into the model group， positive control group （colchicine， 0.45 mg/kg）， and processed O. falcata low-， medium- and high-dose groups （0.5， 1， 2 g/kg）， respectively. Additionally， a blank group without modeling was set up， with 8 rats in each group. The positive control group and the various dosage groups of processed O. falcata were given the corresponding medicinal solutions intragastrically， while the blank group and model group were given equal volume of normal saline intragastrically， once daily for 28 consecutive days. The appearance and histopathological morphology of the rats’ kidneys were observed. Serum levels of renal function indexes [bl ood urea nitrogen （BUN）， creatinine （Cr） ] and inflammatory factors [interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） ] in rats were detected. Protein expressions of fibronectin （FN）， α -smooth muscle actin （ α -SMA） and collagen type Ⅰ （Col-Ⅰ） in renal tissue of rats were determined. mRNA expressions of transforming growth factor-β 1 （TGF-β 1 ）， Smad3 and extracellular signal-regulated kinase 1/2 （ERK1/2） in renal tissues were measured. Protein expression of TGF-β 1 and phosphorylation levels of Smad3 and ERK1/2 in renal tissues were detected. RESULTS Compared with the blank group， the rats in the model group exhibited enlarged kidneys with pale color， rough and uneven surface. There was a significant infiltration of inflammatory cells and vacuolated cells in the renal tubules， along with marked proliferation of collagen fibers. Serum levels of BUN， Cr， IL-6 and TNF-α， protein expressions of α -SMA， Col-Ⅰ and FN in renal tissues， mRNA expressions of TGF-β 1 ， Smad3， ERK1 and ERK2 and protein expression of TGF-β 1 as well as phosphorylation levels of Smad3 and ERK1/2 in renal tissues were increased significantly （ P ＜0.05）. Compared with the model group， renal pathological changes of rats were alleviated in processed O. falcata groups， with reduced infiltration of inflammatory cells and proliferation of collagen fibers. The levels of the aforementioned quantitative indicators were all significantly reversed （ P ＜0.05）. CONCLUSIONS Processed O. falcata can improve renal function in RF rats， alleviate inflammatory responses， and reduce abnormal collagen fiber deposition. Its mechanism of action may be related to the inhibition of the activity of the TGF-β 1 /Smad signaling pathway.

Objective Cirrhotic cardiomyopathy(CCM)refers to cardiac dysfunction and electrophysiological disorder caused by liver cirrhosis and is closely associated with the prognosis of patients with liver cirrhosis.Endothelial cell-specific molecule 1(endocan)can be used as a diagnostic marker for cardiovascular diseases,and it remains unclear whether it is involved in the pathogenesis of CCM.The aim of this study is to investigate the expression of serum endocan in patients with CCM and its possible role in the development of CCM.Methods This cross-sectional study was conducted among the patients with liver cirrhosis who were consecutively admitted to Beijing YouAn Hospital,Capital Medical University,from January 2019 to January 2021,and according to the presence or absence of CCM,the patients were divided into CCM group with 19 patients and non-CCM group with 106 patients.ELISA was used to measure the serum level of endocan,and its correlation with liver function and cardiac function was analyzed.The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U rank sum test was used for comparison of continuous data with skewed distribution between two groups;the chi-square test was used for comparison of categorical data between groups.A Pearson or Spearman correlation analysis was used to investigate the correlation between indicators,and the receiver operating characteristic(ROC)curve was used to assess the CCM predictive model.Results The CCM group had a significantly higher expression level of serum Endocan than the non-CCM group(2.69±0.43 ng/mL vs 2.23±0.52 ng/mL,t=2.247,P=0.034).The patients with compensated cirrhosis had a significantly lower expression level of serum endocan than those with decompensated cirrhosis(2.41±0.37 ng/mL vs 2.72±0.49 ng/mL,t=3.214,P=0.02).In the CCM group,the serum level of endocan was positively correlated with Child-Pugh score(r=0.509,P=0.026)and MELD-Na score(r=0.484,P=0.036)and was negatively correlated with mean arterial pressure(r=-0.591,P=0.013)and mitral ratio of peak early to late diastolic filling velocity(r=-0.515,P=0.042).The serum endocan had an area under the ROC curve of 0.658(95%CI:0.522～0.781)in predicting CCM,when the cut-off value was 2.61 ng/mL,the sensitivity was 67.1%and the specificity was 73.7%.Conclusion There is a certain association between serum endocan and CCM,and serum endocan may be involved in the pathogenesis of CCM.

Objective:To develop a risk prediction model for early cardiac arrest in emergency sepsis utilizing a machine learning algorithm to enhance the quality and efficiency of patient treatment.Methods:This study focused on patients with sepsis who received treatment at the emergency room of the First Medical Center of Chinese PLA General Hospital from January 1, 2020 to June 1, 2023. The basic clinical characteristics such as vital signs and laboratory results were collected. Patients who fulfilled the specified inclusion criteria were allocated randomly into a training group and a testing group with a ratio of 8:2. A CatBoost model was constructed using Python software, and the prediction efficiency of the model was assessed by calculating the area under the receiver operating characteristic curve (AUC). Furthermore, the performance of the model was compared to that of other widely employed clinical scores.Results:This study included a cohort of 2 131 patients diagnosed with sepsis, among whom 449 experienced cardiac arrest. The CatBoost model demonstrated an AUC of 0.760, surpassing other scores. Notably, the top 10 predictors in the model were identified as age, lactate, interleukin -6, oxygen saturation, albumin, N-terminal pro-B-type natriuretic peptide, potassium, sodium, creatinine, and platelets.Conclusions:The utilization of this machine learning algorithm-based prediction model offers a more precise basis for predicting cardiac arrest in emergency sepsis patients, thereby potentially improving the treatment efficacy for this disease.

Objective:To evaluate the effect of stratified management of cardiovascular diseases risk in community population based on China-PAR.Methods:It was a single arm study. Beijing Jiaotong University faculty and staff who participated in annual health check-up from 2019 to 2021 and met the inclusion/exclusion criteria were enrolled in the study. The general data, physical examination and laboratory test results, including age, residence region, waist circumference, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C),blood pressure (BP), taking antihypertensive drugs,diabetes, family history of cardiovascular diseases,were collected. Participants were stratified according to China-PAR assessment model and then stratified management was carried out. For low-risk populations, family doctors provided online guidance or outpatient follow-up if necessary after their first interview. For middle and high-risk groups, outpatient and telephone follow-up were arranged in addition to online guidance. Relevant examinations were completed and drug treatment or adjustment were given by doctors when necessary. Frequency of outpatient follow-up for middle and high-risk groups was different and patients in these two groups were scored again at the end of 2-year follow-up.Results:A total 284 participants were enrolled,197 participants (69.4%) were males with a age of (46.9±8.8) years. Among them, 205 participants (72.2%) were in low-risk group, including 136 males (66.3%), and their 10-year risk of cardiovascular diseases was (2.5±0.1)%; 59 participants (20.8%) were in middle-risk group, including 43 males (72.9%), and their 10-year risk of cardiovascular diseases was (7.1±0.2)%;20 participants (7.0%) were in high-risk group,including 18 males (90.0%) and their 10-year risk of cardiovascular diseases was (14.0±1.1)%. After 2 years follow-up, the proportion of dietary imbalances and alcohol drinking, waist circumference, blood pressure, fasting glucose levels and risk score decreased significantly in high risk group ( P<0.05). The proportion of dietary imbalances, waist circumference, blood pressure, total cholesterol, and LDL-C levels decreased significantly in medium risk group ( P<0.05). In high-risk group, 2 participants (10.0%) converted to low-risk, 8 participants (40.0%) converted to middle-risk. In middle-risk group, 5 participants (8.5%) converted to low-risk and 7 participants (11.9%) converted to high-risk. Conclusion:The risk factors and risk stratification of cardiovascular disease in community population can be improved by stratified management based on China-PAR risk assessment model.

Objective Idiopathic non-cirrhotic portal hypertension (INCPH) is a rare cause of portal hypertension, and this study aims to analyze the clinical features of patients with INCPH, and to assist in diagnosis and differential diagnosis. Methods A total of 74 patients who were hospitalized in Beijing YouAn Hospital from January 2019 to July 2022 and were diagnosed with INCPH were enrolled, and 332 patients with liver cirrhosis who were hospitalized during the same period of time were enrolled as control group. Demographic data, laboratory markers, gastroscopy, liver elasticity, pathological examination, and complications were recorded and compared between the two groups. The receiver operating characteristic (ROC) curve was used to investigate the ability of liver stiffness measurement (LSM), aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) in the differential diagnosis of INCPH, and the DeLong test was used to compare the area under the ROC curve (AUC). The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. Results Among the patients with INCPH, 46.55% had no obvious symptoms at disease onset and 43.24% were misdiagnosed with liver cirrhosis. Compared with the patients with liver cirrhosis, the patients with INCPH had a significantly higher proportion of patients with gastrointestinal bleeding (62.16% vs 41.27%, χ 2 =10.67, P < 0.01) and a significantly lower proportion of patients with moderate-to-severe ascites (16.21% vs 29.82%, χ 2 =34.98, P < 0.01), and there were few patients with hepatic encephalopathy. As for pathology, 89.19% (66/74) of the INCPH patients manifested as typical occlusive portal vein disease. The statistical analysis showed that compared with the patients with liver cirrhosis, the patients with INCPH had significantly better liver function parameters, MELD score, and Child-Pugh score and significantly lower LSM [9.05(7.18-12.33) vs 25.32(16.21-47.23), Z =-8.41, P < 0.01], APRI score [0.70(0.41-1.28) vs 1.35(0.80-2.39), Z =-6.21, P < 0.01], and FIB-4 index [2.99(1.62-4.81) vs 6.68(4.06-10.42), Z =-8.39, P < 0.01]. LSM, FIB-4, and APRI had a good ability in differentiating INCPH from liver cirrhosis, and in particular, LSM had an AUC of up to 0.92 (95% confidence interval: 0.87-0.96), with a sensitivity of 92.68% and a specificity of 81.60%. Conclusion INCPH patients tend to have an insidious onset, a relatively high incidence rate of portal hypertension-related complications, and relatively good liver function, especially the patients with LSM < 14.5 kPa. The possibility of INCPH should be considered for such patients in clinical practice.

Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.
Humans ; Benzydamine ; Esophageal Neoplasms/drug therapy* ; Esophageal Squamous Cell Carcinoma/drug therapy* ; Molecular Docking Simulation ; Phosphorylation ; Cell Proliferation ; Cell Line, Tumor ; Apoptosis ; Cyclin-Dependent Kinase 2

Objective:To investigate the status quo of subclinical thyroid diseases in the faculty and staff of a university and to explore their affecting factors.Methods:A total of 4 219 faculty and staff members who met the exclusion criteria and underwent the health examination in the Community Health Service Center of Beijing Jiaotong University in 2021 were enrolled in the study. General clinical data and laboratory findings of the enrolled subjects were collected. According to the upper and low reference range of thyroid stimulating hormone (TSH) in our laboratory (0.35-5.5 μIU/ml), subjects were classified into subclinical hyperthyroidism group, subclinical hypothyroidism group and normal thyroidism group. The association of gender, age and body mass index (BMI), as well as the metabolic indices with the prevalence of subclinical thyroid disease was analyzed.Results:The prevalence rates of subclinical hypothyroidism and subclinical hyperthyroidism were 4.10% (173/4 219) and 0.69% (29/4 219), respectively. The prevalence of subclinical thyroid diseases in females was higher than that in males(5.90% (77/2 101) vs. 3.66%(125/2 018),χ 2=11.58, P<0.05); there was a significant difference in prevalence among different age groups(χ 2=39.49, P<0.05)and the prevalence increased with the age. There were significant differences in levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), diastolic blood pressure(DBP), fasting blood glucose (FBG), free triiodothyronine (FT 3), free thyroxine (FT 4), thyroglobulin antibody (TGAb) and thyroid peroxidase antibody (TPOAb) among three groups ( P<0.05). TSH levels were positively correlated with the age ( r=0.58, P<0.001), and levels of TG ( r=0.66, P<0.001), TC ( r=0.67, P<0.001), LDL-C ( r=0.62, P<0.001), TPOAb ( r=0.78, P<0.001), TGAb ( r=0.77, P<0.001); was negatively correlated with FBG ( r=-0.50, P<0.001). Conclusion:The prevalence of subclinical thyroid diseases among faculty and staff of the studied university is relatively high, and it is related to gender, age, thyroid antibodies, blood glucose and lipid levels.

Objective To examine the association between caregiver burden and comorbidity in elderly patients with cognitive impairment.Methods The study was conducted in 212 patients at the Memory Clinic and the Departments of Geriatrics and Neurology of Fuxing Hospital from September 2014 to September 2016.Recruited patients were assigned into a dementia group and a non-dementia group according to their cognitive status and were examined using mini mental state examination (MMSE),auditory verbal learning test (AVLT),activity of daily living (ADL),neuropsychiatric inventory(NPI),and Charlson comorbidity index(CCI).Their caregivers were surveyed with Zarit burden inventory (ZBI).Results The ZBI score was significantly correlated with patients' age,gender,CCI,MMSE,NPI,and ADL.The ZBI score was higher in male patients(21.21 ± 11.24)than in female patients(18.33±10.38).Age(r=0.10,P＜0.001),NPI(r=0.32,P＜0.001),ADL(r=0.29,P ＜0.001),and CCI(r =0.38,P ＜0.001) were positively correlated with caregiver burden,while MMSE(r =-0.28,P ＜ 0.001) was negatively correlated with it.Multiple linear regression model analysis indicated that MMSE,NPI,ADL,and CCI were influencing factors for caregiver burden.When CCI was stratified into CCIno dementia and CCIdementi8,influencing factors for caregiver burden were identified as MMSE,NPI,ADL,and CCIdementia.Conclusions Cognitive deterioration,decrease in ADL,and neuropsychiatric symptoms in elderly patients are the major causes of increased caregiver burden.Besides,the number and severity of comorbidity are independent factors for caregiver burden.

Objective To analyze the pathogenesis and clinical characteristics of drug-induced liver injury (DILI) and to explore the corresponding nursing interventions. Methods From January 2011 to December 2013, a total of 84 patients with chronic drug-induced liver injury in Beijing You'an Hospital were recruited by convenience sampling method according to the diagnostic criteria of Guidelines for the Management of Drug-Induced Liver Injury. The demographic characteristics, the possible drugs and clinical characteristics were inputted into Epidata management database and were analyzed using SPSS 16.0. Results In the study, there were 132 kinds of drugs which induced chronic liver injury. Thirty-three of all the recruited patients were using over 2 kinds of medications, among which traditional Chinese medicine accounted for 47.0%, which were mainly used for dermatopathy, rheumatosis and healthcare. The second were non-steroidal anti-inflammatory drugs and antituberculosis drugs. Fifty-six patients had underlying diseases, accounting for 66.7%, of which 16 patients had more than 2 underlying diseases. The main clinical manifestations were fatigue, anorexia and jaundice. 14.3% of the patients showed complications. Conclusions The incidence of drug-induced liver injury was increasing with years. It's important to conduct the health education of drug-using safety, especially to the elderly women and the ones with underlying diseases. The course of chronic liver injury was long and tends to relapse, so it's essential to observe the reaction to drugs and take correspondent measures during the nursing work. Besides, we need to pay much attention to psychological counseling of the patients.

Objective To explore the role of σ1 receptor (σ1R) in the clinical prognosis of cervical cancer,and provide a theoretical basis for σ1R targeted molecular therapy through observing the inhibition of synthetic σ1R-specific ligand compounds on the growth of cervical cancer cells. Methods (1) Immunohistochemical or immunocytochemistry staining were respectively used to detect the expression and localization of σ1R protein.(2)The Cancer Genome Atlas (TCGA) data set was used to validate our results. (3)Two series of 4 novel σ1R ligand compounds were synthesized by altering the N-terminal substituents on the piperidine ring of the prezamicol analogue, named as 14a, 14e, 15c and 15f. Methyl thiazolyl-tetrazolium (MTT) assay was detect the anti-proliferative effect of the four compounds on HeLa and SiHa cells. Compound 14a with potent inhibitory activity and the highest specificity of σ1R was selected for further experiments. Scratch test was observed the migration effect of compound 14a on HeLa and SiHa cells. Flow cytometry was determined cell cycles and apoptosis. Results (1) Immunostaining of σ1R protein was located in the cytoplasm and nucleus of cervical epithelium. The expression of cervical squamous cell carcinoma (SCC) was significantly higher than those of high-grade squamous intraepithelial lesion (HSIL) or normal cervical tissues. There was no significant difference in the expression of σ1R between HSIL and normal cervical tissues. σ1R expression in cervical adenocarcinoma (AC) was higher than that in SCC (P=0.020). The nuclear expression rate of σ1R in AC (10/18) was higher than that of SCC (27.1%, 19/70; P=0.024). The median overall survival (MOS) of σ1R-positive SCC patients was lower than that of σ1R-negative patients [(45.8±3.1) vs (51.7±2.9) months, P=0.045]. MOS of the patients with σ1R nuclear positive SCC was lower than that of non-nuclear staining [(38.9±3.8) vs (48.7±2.1) months, P=0.022]. MOS of the patients with σ1R nuclear positive AC was lower than that of non-nuclear staining [(35.0± 6.3) vs (44.2±4.2) months, P=0.034]. (2) Analysis of TCGA data showed that σ1R expression of in SCC was correlated with age (P=0.005). σ1R expression in AC was significantly associated with advanced stage, lymphnode metastasis and vascular invasion (all P<0.05). MOS of AC patients with σ1R overexpression was significantly lower than that of the patients with low expression (P=0.034). There was no significant difference in the MOS of different expression of σ1R mRNA in SCC patients(P=0.930). (3) MTT assay showed that these four compounds could suppressed the growth of HeLa and SiHa cells in time- and dose-dependent manner. The growth inhibition rates of HeLa and SiHa cells at 48 hours treated by combination of different concentrations of nedaplatin (NDP) with compound 14a (6 μmol/L) were significantly higher than those treated by NDP alone. Compound 14a (30 μmol/L) significantly inhibited the migration (both P<0.01) and induced the apoptosis of HeLa or SiHa cells (both P<0.01). Conclusions σ1R is over-expressed in cervical cancer and HSIL. σ1R nuclear expression is an important marker of AC. σ1R over-expression, especially σ1R nuclear expression is associated with the poor prognosis of cervical cancer. Our study is mostly consistent with cervical cancer data of TCGA. These results suggest that the novel synthetic prezamicol analogues 14a for σ1R could inhibit the growth of cervical cancer cells and cell migration through inducing apoptosis and arresting cell cycle in G0/G1 period, enhance NDP-induced cytotoxicity.