Knockdown of RFC4 inhibits the cell proliferation of nasopharyngeal carcinoma in vitro and in vivo / 医学前沿

Nasopharyngeal carcinoma (NPC) is a malignant tumor that mainly occurs in East and Southeast Asia. Although patients benefit from the main NPC treatments (e.g., radiotherapy and concurrent chemotherapy), persistent and recurrent diseases still occur in some NPC patients. Therefore, investigating the pathogenesis of NPC is of great clinical significance. In the present study, replication factor c subunit 4 (RFC4) is a key potential target involved in NPC progression via bioinformatics analysis. Furthermore, the expression and mechanism of RFC4 in NPC were investigated in vitro and in vivo. Our results revealed that RFC4 was more elevated in NPC tumor tissues than in normal tissues. RFC4 knockdown induced G2/M cell cycle arrest and inhibited NPC cell proliferation in vitro and in vivo. Interestingly, HOXA10 was confirmed as a downstream target of RFC4, and the overexpression of HOXA10 attenuated the silencing of RFC4-induced cell proliferation, colony formation inhibition, and cell cycle arrest. For the first time, this study reveals that RFC4 is required for NPC cell proliferation and may play a pivotal role in NPC tumorigenesis.

Current status of prevention and treatment of esophagogastric variceal bleeding in cirrhotic portal hypertension patients in Ningxia region: a multicenter study / 中华消化外科杂志

Objective:To investigate the current status of prevention and treatment of esophagogastric variceal bleeding (EVB) in cirrhotic portal hypertension patients in Ningxia region.Methods:The retrospective and descriptive study was conducted. The clinical data of 820 cirrhotic portal hypertension patients who were admitted to 21 medical centers in Niangxia region from January 2018 to December 2020 were collected, including 85 cases in Ningxia Hui Autonomous Region People′s Hospital, 73 cases in the Fifth People′s Hospital of Ningxia Hui Autonomous Region, 59 cases in the Wuzhong People′s Hospital, 52 cases in the Qingtongxia People′s Hospital, 50 cases in the Guyuan People′s Hospital, 47 cases in the Yuanzhou District People′s Hospital of Guyuan City, 47 cases in the Yinchuan Second People′s Hospital, 40 cases in the General Hospital of Ningxia Medical University, 40 cases in the Tongxin People′s Hospital, 35 cases in the Yinchuan First People′s Hospital, 34 cases in the Third People′s Hospital of Ningxia Hui Autonomous Region, 32 cases in the Zhongwei People′s Hospital, 30 cases in the Lingwu People′s Hospital, 30 cases in the Wuzhong New District Hospital, 30 cases in the Yanchi People′s Hospital, 29 cases in the Ningxia Hui Autonomous Region Academy of Traditional Chinese Medicine, 28 cases in the Shizuishan Second People′s Hospital, 25 cases in the Shizuishan First People′s Hospital, 21 cases in the Haiyuan People′s Hospital, 20 cases in the Pengyang People′s Hospital, 13 cases in the Longde People′s Hospital. There were 538 males and 282 females, aged (56±13)years. Observation indicators: (1) clinical charac-teristics of cirrhotic portal hypertension patients; (2) overall prevention and treatment of EVB in cirrhotic portal hypertension patients; (3) prevention and treatment of EVB in cirrhotic portal hypertension patients from different grade hospitals. Measurement data with normal distribution were represented as Mean± SD. Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test. Results:(1) Clinical characteristics of cirrhotic portal hypertension patients: of 820 cirrhotic portal hypertension patients, 271 cases were in compensated stage and 549 cases were in decompensated stage. Of the 271 cases in compensated stage, there were 183 maels and 88 females, aged (53±12)years. There were 185 Han people, 85 Hui people and 1 case of other ethic group. The etiological data of liver cirrhosis showed 211 cases of viral hepatitis B, 4 cases of alcoholic liver disease, 8 cases of viral hepatitis C, and 48 cases of other etiology. There were 235 cases of Child-Pugh grade A and 36 cases lack of data. Of the 549 cases in decompensated stage, there were 355 males and 194 females, aged (57±14) years. There were 373 Han people, 174 Hui people and 2 cases of other ethic group. The etiological data of liver cirrhosis showed 392 cases of viral hepatitis B, 33 cases of alcoholic liver disease, 10 cases of viral hepatitis C, and 114 cases of other etiology. There were 80 cases of Child-Pugh grade A, 289 cases of grade B, 170 cases of grade C and 10 cases lack of data. (2) Overall prevention and treatment of EVB in cirrhotic portal hypertension patients: of 271 patients in compensated stage, 38 cases received non-selective β-blocker (NSBB) therapy, 16 cases received endoscopic treatment, 6 cases received interventional therapy. Of 549 patients in decompensated stage, 68 cases received NSBB therapy, 46 cases received endoscopic treatment, 28 cases received interventional therapy. (3) Prevention and treatment of EVB in cirrhotic portal hypertension patients from different grade hospitals: of 271 patients in compensated stage, 181 cases came from tertiary hospitals, of which 28 cases received NSBB therapy, 15 cases received endoscopic treatment, 6 cases received interventional therapy. Ninety cases came from secondary hospitals, of which 10 cases received NSBB therapy, 1 cases received endoscopic treatment. There was no significant difference in NSBB for prevention of EVB between tertiary and secondary hospitals ( χ2=0.947, P>0.05), while there was a significant difference in endoscopic treatment for prevention of EVB between tertiary and secondary hospitals ( χ2=5.572, P<0.05). Of 549 patients in decompensated stage, 309 cases came from tertiary hospitals, of which 22 cases received NSBB therapy, 29 cases received endoscopic treatment, 22 cases received interventional therapy. Two hundreds and fourty cases came from secondary hospitals, of which 46 cases received NSBB therapy, 17 cases received endoscopic treatment, 6 cases received interven-tional therapy. There were significant differences in NSBB and interventional therapy for prevention of EVB between tertiary and secondary hospitals ( χ2=18.065, 5.956, P<0.05). Conclusions:The proportion of receiving EUB prevention in cirrhotic portal hypertension in Ningxia is relatively low. For patients with compensated liver cirrhosis, the proportion of NSBB therapy and endoscopic treatment in the secondary hospitals was lower than that in tertiary hospitals. For patients with decompensated liver cirrhosis, the proportion of interventional treatment in secondary hospitals is lower than that of tertiary hospitals, but the proportion of NSBB in secondary hospitals taking is higher than that of tertiary hospitals.

Cardiotoxicity of Anti-PD-L1 Antibody and the Effect of Levothyroxine in Attenuating the Related Mortality in Mice / 中国肺癌杂志

BACKGROUND@#Immune checkpoint inhibitors (ICIs) such as antibodies against programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1), have shown remarkable efficacies in many subtypes of cancers. However, ICIs may also cause severe immune-related adverse events in the recipient patients. Recently, ICI-associated myocarditis have been reported in hundreds of patients worldwide, with a mortality rate of approximately 50% in these cases. This study aims to recapitulate the cardiotoxicity and explore the detoxicifying approaches to attenuate mortality caused by PD-1/PD-L1 inhibitors in healthy mice.@*METHODS@#Six to eight-week-old C57BL/6 mice were inoculated with anti-PD-1 antibody (12.5 μg/g every 5 days for 6 injections), anti-PD-L1 antibody (10 μg/g once a week for 6 weeks), anti-PD-L1 antibody (with the same dosage described above) in combination with levothyroxine (0.25 μg/g, intraperitoneally injected half an hour before anti-PD-L1 antibody injection), or isotype control immunoglobulin IgG (10 μg/g once a week for 6 weeks). The ejection function of the hearts was detected by echocardiography, body temperature and blood pressure were detected by Mouse MonitorTM and non-invassive blood pressure minotor, and serum free thyroxine concentration was detected by The enzyme linked immunosorbent assay (ELISA).@*RESULTS@#PD-L1 was expressed at different levels by the cardiomyocytes of the mice. The isotype control immunoglobulin and anti-PD-1 antibody did not cause death of the mice. The 12 mice receiving 3-6 injections of anti-PD-L1 antibody showed a significant increase in the heart-to-tibial ratio and cardiomyoctye degeneration, hyalinization and extravascular inflammatory cell infiltration. In addition, the serum thyroxine was mardedly decreased to 1/3 of that in the control group mice, and the blood pressure and body temperature were abnormally decreased in mice upon treatment with PD-L1 blockade. Eight of the 12 (66.7%) mice died from multiple intravenous injection of anti-PD-L1 antibody.Intraperitoneal injection of levothyroxine 30 min before the injection of anti-PD-L1 antibody significantly attenuated the mortality rate of the anti-PD-L1 antibody-treated mice.@*CONCLUSIONS@#The anti-PD-L1 antibody is cardiotoxic and lethal, and levothyroxine is able to rescue the mice from this immune checkpoint inhibitor-caused mortality.

Degradation of SARS-CoV-2 receptor ACE2 by the E3 ubiquitin ligase Skp2 in lung epithelial cells / 医学前沿

An unexpected observation among the COVID-19 pandemic is that smokers constituted only 1.4%-18.5% of hospitalized adults, calling for an urgent investigation to determine the role of smoking in SARS-CoV-2 infection. Here, we show that cigarette smoke extract (CSE) and carcinogen benzo(a)pyrene (BaP) increase ACE2 mRNA but trigger ACE2 protein catabolism. BaP induces an aryl hydrocarbon receptor (AhR)-dependent upregulation of the ubiquitin E3 ligase Skp2 for ACE2 ubiquitination. ACE2 in lung tissues of non-smokers is higher than in smokers, consistent with the findings that tobacco carcinogens downregulate ACE2 in mice. Tobacco carcinogens inhibit SARS-CoV-2 spike protein pseudovirions infection of the cells. Given that tobacco smoke accounts for 8 million deaths including 2.1 million cancer deaths annually and Skp2 is an oncoprotein, tobacco use should not be recommended and cessation plan should be prepared for smokers in COVID-19 pandemic.

Genomic variations in the counterpart normal controls of lung squamous cell carcinomas / 医学前沿

Lung squamous cell carcinoma (LUSC) causes approximately 400 000 deaths each year worldwide. The occurrence of LUSC is attributed to exposure to cigarette smoke, which induces the development of numerous genomic abnormalities. However, few studies have investigated the genomic variations that occur only in normal tissues that have been similarly exposed to tobacco smoke as tumor tissues. In this study, we sequenced the whole genomes of three normal lung tissue samples and their paired adjacent squamous cell carcinomas.We then called genomic variations specific to the normal lung tissues through filtering the genomic sequence of the normal lung tissues against that of the paired tumors, the reference human genome, the dbSNP138 common germline variants, and the variations derived from sequencing artifacts. To expand these observations, the whole exome sequences of 478 counterpart normal controls (CNCs) and paired LUSCs of The Cancer Genome Atlas (TCGA) dataset were analyzed. Sixteen genomic variations were called in the three normal lung tissues. These variations were confirmed by Sanger capillary sequencing. A mean of 0.5661 exonic variations/Mb and 7.7887 altered genes per sample were identified in the CNC genome sequences of TCGA. In these CNCs, C:G→T:A transitions, which are the genomic signatures of tobacco carcinogen N-methyl-N-nitro-N-nitrosoguanidine, were the predominant nucleotide changes. Twenty five genes in CNCs had a variation rate that exceeded 2%, including ARSD (18.62%), MUC4 (8.79%), and RBMX (7.11%). CNC variations in CTAGE5 and USP17L7 were associated with the poor prognosis of patients with LUSC. Our results uncovered previously unreported genomic variations in CNCs, rather than LUSCs, that may be involved in the development of LUSC.

Expression and identification of recombinant chimeric CARDS of Mycoplasma pneumoniae / 中国人兽共患病学报

We expressed multi-epitope chimeric protein of CARDS toxin protein of Mycoplasma pneumonia (Mp) in prokaryotic cells,and purified and investigated its immunoreactivity.A recombinant multi-epitope chimeric gene including ten critical epitopes was connected by linker and cloned into prokaryotic expression vector pET-28a(+),and transformed into E.coli BL21(DE3) cells for expression under induction of IPTG.The antigenicity of expressed recombinant protein was identified with 6 × His monoclonal antibody and human positive serum by Western blot.The recombinant expression vector pET-CARDS was constructed and the about 30 kDa recombinant chimeric protein expressed in BL21(DE3) successfully.Western blot analysis showed that it can react respectively with 6 × His monoclonal antibodies and human positive serum.This study showed that the chimeric CARDS protein has an obvious immunoreactivity and a potential to be a new antigen for the diagnosis of Mp infection.

Factors influencing antiretroviral therapy adherence among HIV-infected people on antiretroviral therapy in Ili Kazakh Autonomous Prefecture / 中华预防医学杂志

Objective@#To analyze factors influencing antiretroviral therapy (ART) adherence among human immunodeficiency virus (HIV) patients receiving ART at the town level in Ili Kazakh Autonomous Prefecture (Ili) in May 2015 and to document enhanced ART for acquired immunodeficiency syndrome (AIDS) cases.@*Methods@#A cross-sectional survey was conducted using one-on-one interviews and data collection from the system of AIDS follow-up management in three ART services centers at the town level of Ili. The subjects were HIV-infected individuals, aged 18 years or older, who were receiving ART during the survey. The surveys collected demographic characteristics, information related to ART and status of engaging ART, smoking and drinking behavior, depression, and quality of life.@*Results@#A total of 412 participants completed the survey. The age was (41.1±8.0) years (range, 19-67 years). Approximately 60.9% (251) were male and 39.1% (161) were female. The survey showed that 75.0% (309) of participants were in good adherence and the P50 (P25, P75) of quality of life was 56.31 (50.55, 59.42). Females demonstrated better adherence to ART (82.6% (n=133)) than males (70.1% (n=76)) (χ2=8.16, P=0.005). The compliance rate of participants (78.0% (n=54)) with depression was higher than non-depressed participants (63.5% (n=255)) (χ2=7.52, P=0.008). Multivariate logistic regression analyses showed that the probability of good adherence to ART increased with increasing quality of life (OR=1.06, 95%CI:1.02-1.09). Moreover, participants who consumed alcohol or disclosed their HIV infection status to families were less likely to have good adherence to ART (OR=0.26, 95% CI:0.13-0.53 and OR=0.31, 95% CI:0.13-0.72, respectively). Additionally, employed participants were also less likely to have good adherence to ART compared with unemployed participants (OR=0.45, 95% CI:0.21-0.97).@*Conclusion@#HIV/AIDS patients primarily showed good adherence to ART. Factors related to ART adherence included alcohol consumption, informing family of infection, work status, and quality of life.

Influence of thoracic sympathetic block on patients with diabetes mellitus complicated heart failure / 心血管康复医学杂志

Objective: To observe curative effect of thoracic sympathetic block on patients with diabetes mellitus (DM) complicated cardiac chamber enlargement and heart failure (HF). Methods: A total of 76 DM patients with cardiac chamber enlargement and HF were randomly divided into routine treatment group (n=36) and epidural nerve block group (nerve block group, n=40, received thoracic epidural nerve block based on routine treatment), and four weeks were a course of treatment. Changes of left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDd), left atrial diameter (LAD), levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), brain natriuretic peptide (BNP) and glycosylated hemoglobin (HbA1c) were observed in two groups. Results: There were no significant difference in all indexes between two groups before treatment (P>0.05). After treatment, total effective rate of cardiac function improvement in nerve block group was significantly higher than that of routine treatment group (95% vs. 66.7%, P<0.05). Compared with before treatment, there were significant decrease in LVEDd [(71.63±9.26)mm vs. (65.4±8.12)mm] and LAD[(45.62±7.10)mm vs. (37.14 ±6.28)mm] (P<0.05 both), significant increase in LVEF [(31.3±11.46)% vs. (42.12± 10.42) % , P< 0.01], and significant decrease in levels of TNF-α [(73.55±16.36)ng/L vs. (28.35±10.08) ng/L], IL-6 [(17.62±5.47) ng/L vs. (7.88±2.29) ng/L], BNP[(13.49±2.94) ng/L vs. (6.28±2.28) ng/L] and HbA1c [(7.9±2.6) % vs. (6.8±1.9) %] in nerve block group after treatment, P<0.05 or <0.001; and levels of LVEF, TNF-α, IL-6 and BNP in nerve block group after treatment were significantly improved than those of routine treatment group, P<0.05 or <0.01. Conclusion: Thoracic sympathetic block can significantly decrease levels of neuroendocrine and inflammatory factors, improve cardiac function, and elevate quality of life in patients with diabetes mellitus complicated heart failure.

Systemic Inflammatory Response Syndrome Score Predicting Nosocomial Infection and Outcome in ICU Patients / 中华医院感染学杂志

OBJECTIVE To study relativity of systemic inflammatory response syndrome(SIRS) score and nosocomial infection(NI) and outcome in ICU patients.METHODS A total of 1897 ICU patients were enrolled in our study.The SIRS within 48 hours after admission was recorded.And the prospective evaluation in NI and prognosis was made.RESULTS The nosocomial infection rate was 10.1%,and the mortality was 9.9%.With SIRS score increasing,NI and mortality rates increased as well and the tendency presented a linear correlation.CONCLUSIONS As a simple system,SIRS score can initially predict the risk of NI and outcome in ICU patients.

Risk Factors of Hospital Acquired Urinary System Infection in Neurology ICU and Emergency ICU / 中华医院感染学杂志

OBJECTIVE To study the risk factors of hospital acquired urinary system infection in neurology ICU(NICU) and emergency ICU(EICU).METHODS The general character,score of APACHE Ⅱ and the time length of urethral catheterization of the 502 NICU and EICU patients were enrolled in our study.Then the relativity of the risk factors and hospital acquired urinary system infection were investigated.RESULTS Urethral catheterization increased the chances of hospital acquired urinary system infection and there were more chances with the long time.CONCLUSIONS In order to decrease the rate of hospital acquired urinary system infection we must strictly grasp the indication of urethral catheterization and pull out the urethral catheter as early as possible.

Evaluation System for Risk Factors of Nosocomial Infection in ICU / 中华医院感染学杂志

OBJECTIVE To evaluate the risk factors of nosocomial infection(NI),then establish the evaluation system for risk factors of NI in ICU.METHODS A total of 1897 ICU patients were enrolled in our study.The risk factors of NI were classified and quantified,then investigated the relativity of the risk factors and NI.RESULTS NI correlated with APACHEⅡscore,serum prealbumin level,blood products uese,incision of trachea,mechanical ventilation,central vein cannula and enteral nutrition.CONCLUSIONS The risk factors of NI evaluatied in ICU can to be used to lay the foundation for the model of NI early warning.

Significance of nosocomiology subject in higher medical education / 中华医学教育探索杂志

The medical student should learn the knowledge and skill for NI control.Nosocomiology subject should be set up in higher medical education as early as possible to meet the needs of medical science development.

Diagnosis,Treatment and Prevention of Central Venous Catheter-related Bloodstream Infections / 中华医院感染学杂志

OBJECTIVE To focus on the diagnosis,treatment and prevention of central venous catheter(CVC)-related bloodstream infections(CRBSI)in clinical practice.METHODS The related articles within the nearest 10 years were reviewed,which published in the domestiec and foreign academic journals,at the same time,the related monitoring data of the hospital were analyzed.RESULTS Highlights on the diagnosis,treatment and prevention of CRBSI:for the patients with CVC,the possibility of the CRBSI should be considered,as soon as a high fever was found,and it could not be explained with the non-infectious causes.Infection occurring time and pathogen were different between the general catheters and the anti-infective catheters.The effect of the anti-infective catheters was limited.To pull out the catheters was one of the most effective treatment measures.CONCLUSIONS Prevention of CRBSI:the indications of CVC intubation should be undisputed.Silicone catheter should be used.When the catheter is predicted to be indwelling more than 5 days,anti-infective catheters should be chosen.To insert CVC at the subclavian vein instead of the femoral vein.To care the hub and keep the puncture point dry and do disinfection well.The health care workers should be trained.

Clinical study of 2473 cases with peptic ulcer / 中华消化内镜杂志

Objective To study the clinical characteristics in patients with peptic ulcer (PU) in different nationalities and regions. Methods Retrospective analysis on the clinical data of 2473 cases of PU encountered in our hospital within past 15 years. Results The detecting rate of PU is 12.53％ ; whith the ratio of males and females 3.67:1 inwhich the detecting rates of Han and Hui nationalities are 13.42％ and 10.66％ respectively, Among them 44.4％ were duodenal ulcer,50.63％ were gastric ulcer, the ratio being 0.88:1. Conclusion The detecting rate of peptic ulcer in Han nationality is hihger than in Hui nationality , gastric ulcer occurs more often than duodenal ulcer. Episodic attacks occur mostly in spring and autumn . As to the location of ulcer in duodenal ulcer they are most on anterior wall and greater curvature of bulb; in gastric ulcer they are most on gastric angul and antrum , the peak age of incidence is 21 to 50. Bleeding is the most common complication in peptic ulcer patients.

Study on Endonuclease Map of P1 Protein Gene of Mycoplasma Pneumoniae Isolated Strain in Shenyang / 中国医科大学学报

Objective: Our aims were to classify mycoplasma pneumoniae (MP) clinical isolated strain according to endonuclease map of the PCR-products of the MP P1 protein gene and to investigate MP epidemic state in Shenyang.Methods:The P1 protein gene fragment of MP isolated strain was amplified by using PCR method ,and its products were digested with Hea III, 1.5 % argarose gel electrophoresis.Results:Isolated strain showed the same map as MP FH standard strain.Conclusion: Clinical isolated strain of mycoplasma pneumoniae in Shenyang belongs to groupⅡ.

Nosocomial Infection Point-prevalence Survey:Results and Analysis of Three Consecutive Years / 中华医院感染学杂志

OBJECTIVE To estimate the prevalence of nosocomial infections(NI) of our hospital.METHODS With a method of transversal sectional investigation,choosing one day each year during from 2004 to 2006,we investigated all these days′ hospitalized patients,using the same criteria,collected the questionnaires,sorted out and anayzed the nosocomial infection cases.RESULTS Among 2738 investigated patients,the prevalence rate of nosocomial infection was 6.49%,5.70% and 4.47% respective.CONCLUSIONS The respective prevalence rate of NI are consistent with the month and the year survey results.

Rational Use of Antibiotics:Comparative Study Before and after Intervention / 中华医院感染学杂志

OBJECTIVE To survey the effect of the intervention measures according to the guiding principle of antibiotics rational use. METHODS The data of medication of two groups of patients in Mar 2004 and Mar 2005 were collected respectively,and the condition of antibiotics use was compared. RESULTS In comparison with that in Mar 2004 the average in-hospital days and antibiotics costs in Mar 2005 were reduced remarkably;the percentage of antibiotics use was much lower;the ratio of the rational use of antibiotics increased notably(P

A STUDY OF THE DOSAGE AND VOLUME OF LOCAL ANESTHETICS FOR ESWL UNDER EXTRADURAL ANESTHESIA / 重庆医科大学学报

Both dosage and volume of local anesthetics taken for extradural anesthesia in ESWL were studied in 112 cases. The results showed that small dose of coxylacaine (1.33% of xylocaine and 0.16% Bupivacaine in 3-5ml) given extradurally is not only safe but also suitable for ESWL without obvious side effect

Effects of pulse pressure on coronary artery disease / 西安交通大学学报(医学版)

Objective To study the effects of pulse pressure (PP) on coronary artery disease. Methods High and low systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP) were measured in 221 cases with coronary heart disease diagnosed by coronary artery radiography, and the differences of coronary artery count, score, and clinic features were analyzed. Results ① Compared with low SBP group \[81mmHg)) were older in age, with higher percentage of females and lower incidence of unstable angina pectoris(UA) and acute myocardial infarction(AMI). ② Compared with low PP group(