Objective To investigate the expression of arginase Ⅱ(ArgⅡ)in kidney tissue of rats with diabetic nephropathy(DN)and its significance in the development of DN.Methods A total of 10 male SD rats were randomly divided into the control group and the model group,with 5 rats in each group.An rat model of DN was developed by feeding with high-sugar and high-fat diet combined with intra-peritoneal injection of low-dose streptozotocin(45 mg/kg),and they were sacrificed after 11 weeks of continued feeding.The body weight,and biochemical indexes of blood and urine of rats were determined.The right kidney was weighed and histopathological examination was performed.The pathological changes of kidney tissues and protein expression of ArgⅡ and CD68+were observed,and the immunofluores-cence double staining was used to observe the distribution and expression of ArgⅡand a marker of renal macrophage activation CD68+;the protein expression of ArgⅡ,NF-κB,TNF-α and IL-6 in kidney tissues was determined by Western blot.Results Compared with the control group,the ratio of kidney weight to body weight,24-hour urine volume,24-hour urine protein,fasting blood glucose,urea nitrogen and insulin level in the model group were significantly increased(P<0.05).The renal histopathology showed that the mesangial cells of the renal glomerular were necrotic with vascular dilatation,and the renal tubular epithelial cells were steatosis and congestion.Compared with the control group,the protein expression of ArgⅡ,CD68+,NF-κB,TNF-α and IL-6 in the kidney tissues of the model group were significantly increased(P<0.05).Immunofluorescence double staining demonstrated the co-expression of ArgⅡ and CD68+in renal tissue,and the fluorescence intensities of both ArgⅡ and CD68+in the model group were significantly stronger than those in the control group(P<0.01).Conclusion The expression of ArgⅡ is increased in DN,which may be participated in the occurrence of inflammatory lesions in DN.

Objective To investigate the expression of arginase Ⅱ(ArgⅡ)in kidney tissue of rats with diabetic nephropathy(DN)and its significance in the development of DN.Methods A total of 10 male SD rats were randomly divided into the control group and the model group,with 5 rats in each group.An rat model of DN was developed by feeding with high-sugar and high-fat diet combined with intra-peritoneal injection of low-dose streptozotocin(45 mg/kg),and they were sacrificed after 11 weeks of continued feeding.The body weight,and biochemical indexes of blood and urine of rats were determined.The right kidney was weighed and histopathological examination was performed.The pathological changes of kidney tissues and protein expression of ArgⅡ and CD68+were observed,and the immunofluores-cence double staining was used to observe the distribution and expression of ArgⅡand a marker of renal macrophage activation CD68+;the protein expression of ArgⅡ,NF-κB,TNF-α and IL-6 in kidney tissues was determined by Western blot.Results Compared with the control group,the ratio of kidney weight to body weight,24-hour urine volume,24-hour urine protein,fasting blood glucose,urea nitrogen and insulin level in the model group were significantly increased(P<0.05).The renal histopathology showed that the mesangial cells of the renal glomerular were necrotic with vascular dilatation,and the renal tubular epithelial cells were steatosis and congestion.Compared with the control group,the protein expression of ArgⅡ,CD68+,NF-κB,TNF-α and IL-6 in the kidney tissues of the model group were significantly increased(P<0.05).Immunofluorescence double staining demonstrated the co-expression of ArgⅡ and CD68+in renal tissue,and the fluorescence intensities of both ArgⅡ and CD68+in the model group were significantly stronger than those in the control group(P<0.01).Conclusion The expression of ArgⅡ is increased in DN,which may be participated in the occurrence of inflammatory lesions in DN.

Objective To explore the value of MR diffusion tensor imaging(DTI)in evaluating the effect of march training on the thigh muscles of recruits.Methods DTI scans of the right thigh were performed three times in forty recruits:before and after the march training and one month after the rest.Fractional anisotropy(FA)was measured on the cross-sectional images of the thigh muscles,including rectus femoris(RF),vastus medialis(VM),vastus lateralis(VL),vastus intermedius(VI),gracilis muscle(GM),sartorius muscle(SM),semitendinosus muscle(STM),semimembranosus muscle(SMM),long head of biceps femoris(LHBF)and short head of biceps femoris(SHBF).The percentage changes in FA values of each muscle after the training and rest were calculated.Paired samplet-tests were used to analyze the differences in FA among the thigh muscles at different time points,and one-way ANOVA was used to analyze the differences in the percentage changes of FA among the thigh muscles after the training and rest.Results Compared to pre-training,the FA values of all thigh muscles significantly decreased after the training,with statistical differences(P＜0.05).After the rest,the FA values of all thigh muscles recovered,but statistical differences remained in RF(P＜0.001),VM(P＜0.001),VL(P=0.001),STM(P=0.046),and LHBF(P=0.013).After the training and rest,the FA values of the recruits'thigh muscles showed a"decreasing first and then increasing"trend.There were statistical differences in the percentage changes of FA after the training and the recovery percentages of FA after the rest among the thigh muscles(P＜0.001,P＜0.001).Conclusion DTI may reflect the ultra-structure changes in the thigh muscles of recruits after the march training and provide a quantitative and noninvasive assessment of muscle micro-injuries.

Objective To investigate the safety and efficacy of novel bioabsorbable vascular scaffold(BVS)in the treatment of patients with complex coronary artery disease.Methods This was a retrospective,matched,single-center observational study.45 patients with coronary atherosclerotic cardiopathy received BVS treatment in the cardiovascular medicine department Department of the Affiliated Hospital of Guangdong Medical University from June 2020 to June 2021(BVS),and 45 patients treated with drug-eluting stents(DES)group were selected according to matching study requirements during the same period.Baseline,surgical,and follow-up data were compared between the two groups to evaluate safety and efficacy.The main measures of safety were:surgical time,intraoperative adverse events,etc.,and the end point of efficacy was target lesion failure(TLF),including cardiac death,target vessel myocardial infarction,and ischa-driven target lesion revascularization.Results A total of 90 patients were enrolled in this study,all of whom were followed up for at least 3 years.There were 20 cases of bifurcation lesions and 25 cases of diffuse long lesions in the two groups,and 50 cases of imaging were reviewed among the 90 patients.The proportion of stable coronary heart disease,history of diabetes,history of hypertension,history of smoking,pre-dilated balloon pressure and postoperative diastolic blood pressure in BVS group was higher than that in DES group,and the proportion of family history was lower than that in DES group(all P＜0.05).There were no statistically significant differences in the rates of cardiac death,target vessel myocardial infarction,and ischemia-driven revascularization of target lesions between the two groups(all P＞0.05).Binary Logistic regression model analysis showed that the diameter stenosis ratio of target lesions was an independent risk factor for intrastent restenosis(OR 2.786,95％CI 1.096-7.081,P=0.031).Conclusions Compared with traditional DES,BVS implantation has consistent safety and efficacy in the treatment of complex coronary artery disease within 3 years.The diameter stenosis ratio of target lesions was an independent risk factor for intrastent restenosis.

OBJECTIVE: To investigate a family with congenital dysfibrinogenemia, and analyze the risk of hemorrhage and thrombosis and blood transfusion strategies. METHODS: Prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) of the proband and her family members were detected by automatic coagulometer, fibrinogen (Fg) activity and antigen were detected by Clauss method and PT algorithm respectively. Meanwhile, thromboelastometry was analyzed for proband and her family members. Then, peripheral blood samples of the proband and her family members were collected, and all exons of FGA, FGB and FGG and their flanks were amplified by PCR and sequenced to search for gene mutations. RESULTS: The proband had normal APTT and PT, slightly prolonged TT, reduced level of Fg activity (Clauss method). The Fg of the proband's aunt, son and daughter all decreased to varying degrees. The results of thromboelastogram indicated that Fg function of the proband and her family members (except her son) was basically normal. Gene analysis showed that there were 6233 G/A (p.AαArg35His) heterozygous mutations in exon 2 of FGA gene in the proband, her children and aunt. In addition, 2 polymorphic loci were found in the family, they were FGA gene g.9308A/G (p.AαThr331Ala) and FGB gene g.12628G/A (p.BβArg478Iys) polymorphism, respectively. The proband was injected with 10 units of cryoprecipitate 2 hours before delivery to prevent bleeding, and no obvious bleeding occurred during and after delivery. CONCLUSION Heterozygous mutation of 6233G/A (p.AαArg35His) of FGA gene is the biogenetic basis of the disease in this family with congenital dysfibrinogenemia.
Humans ; Child ; Female ; Fibrinogen/genetics* ; Pedigree ; Afibrinogenemia/genetics* ; Mutation ; Blood Transfusion

OBJECTIVE: To study epidemiological characteristics and hospitalization costs of female inpatients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Beijing. METHODS: A retrospective study was conducted to analyze electronic hospitalization summary reports of female inpatients with AECOPD in Beijing from 2013 to 2020. Clinical characteristics (age distribution and comorbidities), epidemiological characteristics (temporal and spatial distribution characteristics), hospi-talization times and costs of patients were described. RESULTS: A total of 57 911 subjects in 166 hospitals were included in this study, with a mean age of (78.84±8.59) years and the highest number of patients aged 80-89 years (49.06%), followed by patients aged 70-79 years (31.08%), and the lowest number of patients under 50 years (0.41%). The proportions of patients with coronary heart disease, hypertension and heart failure were 30.60%, 30.52% and 26.54% respectively. The median number of daily hospitalizations during the study period was 18 (IQR: 16). The number of daily hospitalizations for AECOPD showed an overall growth trend over the eight years from 2013 to 2020, starting to increase significantly in 2015 and continuing to increase until 2019, then followed by a decline in 2020. The proportion of inpatient admissions was higher in winter and spring (54.09%) than that in summer and autumn (45.91%). The top three districts in terms of the proportion of total inpatient admissions were Xicheng district (14.18%), Chaoyang district (14.12%) and Fengtai district (13.47%). The density of inpatients was relatively high in the western regions, central urban areas and northeastern regions of the city, while the density of inpatients was relatively low in the near suburbs. The median number of hospital days for female patients with AECOPD was 12 days, and the median hospital costs was CNY 20 648.37. Patients from urban areas had longer hospitalization times and higher hospitalization costs than those from suburban areas (P < 0.001). Western medicine expenses accounted for the largest proportion of total hospital expenses (33.32%). During the study period, hospitalization costs exhibited an overall pattern of initial growth, followed by subsequent decline, eventually stabilizing. The differences in hospitalization costs among the patients with different comorbidities were significant. CONCLUSION Female hospitalized patients with AECOPD in Beijing were older than 70 years, often complicated by cardiovascular disease. AECOPD occurred mainly in winter and spring, with regional differences. The hospitalization costs were closely associated with the patients' age, comorbidities, and the geographicical region.
Humans ; Female ; Aged ; Aged, 80 and over ; Inpatients ; Beijing ; Retrospective Studies ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Hospitalization

Objective: To investigate the characteristics of non-alcoholic fatty liver disease (NAFLD) and its associated factors in rheumatoid arthritis (RA) patients. Methods: This cross-sectional study recruited 385 RA patients [including 72 (18.7%) male and 313 (81.3%) female] who received abdominal sonographic examination from August 2015 to May 2021 at Department of Rheumatology, Sun Yat-Sen Memorial Hospital. There were 28 RA patients at 16-29 years old and 32, 80, 121, 99, 25 at 30-39, 40-49, 50-59, 60-69, ≥ 70 years old, respectively. Demographic and clinical data were collected including age, gender, history of alcohol consumption, disease duration, body mass index (BMI), waist circumference, blood pressure, RA disease activity indicators and previous medications. Logistic regression analyses were used to identify the associated factors of NAFLD in RA patients. Results: The prevalence of NAFLD was 24.2% (93/385) in RA patients, 26.3% (21/80) in 40-49 age group and 33.1% (40/121) in 50-59 age group. There were 22.1% (85/385) and 3.6% (14/385) RA patients with overweight and obese, in which the prevalence of NAFLD was 45.9% (39/85) and 78.6% (11/14) respectively, which was 2.6 folds and 4.5 folds that of RA patients with normal BMI. Although there was no significant difference of age, gender and RA disease activity indicators between RA patients with or without NAFLD, those with NAFLD had higher proportions of metabolic diseases including obese (11.8% vs. 1.0%), central obesity (47.3% vs. 16.8%), hypertension (45.2% vs. 29.8%) and type 2 diabetes mellitus (24.7% vs. 12.0%), consistent with higher levels of total cholesterol [(5.33±1.31) mmol/L vs. (4.73±1.12) mmol/L], triglyceride [(1.51±1.08) mmol/L vs. (0.98±0.54) mmol/L] and low-density lipoprotein cholesterol [(3.37±0.97) mmol/L vs. (2.97±0.78) mmol/L, all P<0.05]. Multivariate logistic regression analysis showed that BMI (OR=1.314) and triglyceride (OR=1.809) were the independent factors positively associated with NAFLD in RA patients. Conclusion: NAFLD is a common comorbidity in RA patients, especially in those with middle-aged, overweight or obese, which is associated with high BMI or high triglyceride. Screening and management of NAFLD in RA patients especially those with overweight, obese or dyslipidemia should be emphasized.
Adolescent ; Adult ; Aged ; Arthritis, Rheumatoid/epidemiology* ; Cholesterol, LDL ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease/epidemiology* ; Obesity/epidemiology* ; Overweight/epidemiology* ; Triglycerides ; Young Adult

Objective: To investigate the association between high sensitivity C-reactive protein (hsCRP) level and new-onset hypertension in different age groups. Methods: This was a prospective cohort study involving non-hypertensive population in Kailuan Group community who participated in health examination between 2006 and 2007.Follow-up was conducted every 2 years, and the time of new onset of hypertension was used as the endpoint of follow-up. The endtime of follow-up for patients without hypertension was the time of death or the last follow-up (December 31, 2017).According to the baseline hsCRP level, the participants were divided into low-risk group (hsCRP<1.0 mg/L), medium-risk group (hsCRP ≥1.0 and ≤3.0 mg/L), and high-risk group (hsCRP>3.0 mg/L), and further stratified by age. Kaplan-Meier method was used to calculate the cumulative incidence of hypertension in each group. Multivariate Cox regression model was used to analyze the association between hsCRP level and new-onset hypertension. Results: A total of 51 179 participants were included in this study, including 38 606 males (75.43%) with an average age of (48.1±12.2) years. The baseline hsCRP was 0.64 (0.25, 1.60) mg/L. The baseline hsCRP was 0.30 (0.16, 0.59), 1.57 (1.20, 2.10), 5.17 (3.80, 7.10) mg/L respectively in low-, medium- and high-risk groups. During the follow-up of (8.1±2.2) years, a total of 9 523 (18.60%) patients developed hypertension, and the cumulative incidence rates of low-, medium- and high-risk groups were 17.41%, 20.48% and 20.73%, respectively. The cumulative incidence of hypertension in low-, medium- and high-risk groups of<45, 45-54, 55-64, ≥65 years old were 13.53%, 15.82%, 16.76%; 19.27%, 22.84%, 21.62%; 21.55%, 24.19%, 24.88%;20.20%, 22.35%, 19.11%, respectively. Except for people aged ≥65 years, there were significant differences in the cumulative incidence of hypertension in low-, medium- and high-risk groups (all P<0.05).Multivariate Cox regression analysis showed that the risk of new-onset hypertension in the high risk group was 1.11 times higher than that in the low risk group (HR=1.11, 95%CI 1.05-1.18). The risk of new-onset hypertension in the high-risk group was 1.22 times (HR=1.22, 95%CI 1.08-1.38), 1.14 times (HR=1.14, 95%CI 1.04-1.26), 1.16 times (HR=1.16, 95%CI 1.04-1.30), and 1.02 times (HR=1.02, 95%CI 0.86-1.20) of the low-risk group, in the<45, 45-54, 55-64, and ≥65 years old groups, respectively. Conclusion: Higher hsCRP level is a risk factor for new-onset hypertension, and the risk of developing hypertension caused by elevated hsCRP is age-dependent.
Male ; Humans ; Adult ; Middle Aged ; Aged ; C-Reactive Protein ; Prospective Studies ; Hypertension/diagnosis* ; Risk Factors ; Incidence

Objective: To explore the effect of primary and acquired resistance to anti-human epidermal growth factor receptor 2 (HER-2) on the overall survival of patients with HER-2 positive advanced breast cancer. Methods: The clinical characteristics of HER-2 positive patients with advanced breast cancer admitted to Cancer Hospital of Chinese Academy of Medical Sciences from January 1998 to December 2018 were collected, and their neoadjuvant/adjuvant and advanced three-line chemotherapy were summarized. Among them, targeted drugs for HER-2 included trastuzumab, pertuzumab, T-DM1, RC48-ADC, lapatinib, pyrotinib, allitinib, sipatinib, seratinib. Based on the duration of benefit from anti HER-2 treatment, the patients were divided into two groups: primary anti HER-2 resistance group and acquired anti HER-2 resistance group. In this study, the overall survival (OS) was used as the main end point. Kaplan-Meier analysis and Cox proportional risk regression model were used to analyze the effects of different drug resistance mechanisms on the overall survival. Results: The whole group of 284 patients were included. The median age of recurrence and metastasis was 48 years old, 155 (54.6%) were hormone receptor (HR) positive and 129 (45.4%) were HR negative, 128 cases (45.1%) were premenopausal and 156 cases (54.9%) were postmenopausal, 277 cases (97.5%) had a score of 0-1 in ECoG PS and 7 cases (2.5%) had a score of more than 2 in the first diagnosis of relapse and metastasis. There were 103 cases (36.3%) in the primary drug resistance group and 181 cases (63.7%) in the secondary drug resistance group. The median overall survival time of the two groups was 24.9 months and 40.4 months, respectively, with statistical significance (P<0.001). Conclusion: Primary resistance to HER-2 is one of the factors of poor prognosis in HER-2 positive breast cancer, and its mechanism needs to be further explored.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Breast Neoplasms/pathology* ; Drug Resistance ; Female ; Humans ; Middle Aged ; Neoadjuvant Therapy ; Prognosis ; Receptor, ErbB-2/metabolism* ; Trastuzumab/therapeutic use* ; Treatment Outcome

Objective To summarize clinical characteristics and investigate possible pathogenic gene of Klippel-Feil syndrome(KFS)by the self-designed multigene panel sequencing,so as to decipher the molecular basis for early diagnosis and targeted therapy.Methods From January 2015 to December 2018,we consecutively recruited 25 patients who were diagnosed with KFS in Peking Union Medical College Hospital.The demographic information,clinical manifestations,physical examination and radiological assessments were analyzed.Multigene panel sequencing was performed after DNA extraction from peripheral blood.The possible pathogenic mutations of KFS were explored on the basis of bioinformatics analysis.Results The KFS cohort consisted of 25 patients,including 15 males and 10 females,with a mean age of(12.9±7.3)years.Limited cervical range of motion was the most common clinical feature(12 cases,48%).Based on the Samartzis classification,the proportion of patients suffered from short neck(P=0.031)and limited cervical range of motion(P=0.026)in type Ⅲ KFS was significantly higher than that in type Ⅱ and type Ⅰ KFS.Panel sequencing detected a total of 11 pathogenic missense mutations in eight patients,including COL6A1,COL6A2,CDAN1,GLI3,FLNB,CHRNG,MYH3,POR,and TNXB.There was no pathogenic mutation found in five reported pathogenic genes(GDF6,MEOX1,GDF3,MYO18B and RIPPLY2)associated with KFS.Conclusions Our study has shown that patients with multiple contiguous cervical fusions are more likely to manifest short neck,limited cervical range of motion,and clinical triad.Therefore,these patients need additional attention and follow-up.Our analysis highlights novel KFS-related genetic variants,such as COL6A and CDAN1,extending the spectrum of known mutations contributing to this syndrome and providing a basis for elucidating the pathogenesis of KFS.
Cervical Vertebrae ; Child ; Cohort Studies ; Female ; Glycoproteins ; Humans ; Klippel-Feil Syndrome/genetics* ; Male ; Mutation ; Nuclear Proteins ; Radiography ; Transcription Factors/genetics*