Objective To explore the effect of sorafenib on HeLa cell proliferation by inducing cell apoptosis and autophagy and its impact on drug resistance.Methods The drug-resistant cell strains were constructed through in-termittent induction method,with concentrations of 0,2.5,5.0,7.5,10.0,15.0,20.0 μmol/L.HeLa cells were incubated with increasing concentrations of sorafenib with each concentration for 1 week.The drug-resistant cell strains with stable passages were collected.MTT assay was used to detect the effect of sorafenib on cell prolifer-ation.Cell cycle distribution was analyzed by flow cytometry.The change in the expression of drug-resistant and ap-optotic genes in the parents and drug-resistant cell strains under different drug concentrations was examined by semi-quantitative PCR.The changes of apoptotic related marker proteins LC3-Ⅰ and LC3-Ⅱ were detected by Westernblot.Results Stable drug-resistant strains were successfully obtained;Drug-treated cells were more blocked in the G1 phase.In drug-resistant cells,the expression of apoptosis suppressor gene Bcl-2 was significantly decreased and the apoptotic gene Bax as well as the drug-resistant genes were all significantly increased(P＜0.05).The LC3-Ⅱ/LC3-Ⅰ ratio of drug-resistant cells was significantly higher than that of parent cells(P＜0.05).Conclusions Sorafenib may block the cell cycle,suppress malignant cell proliferation and promote autophage.On one hand,autophagy participates in the development of cell drug resistance and promotes cell survival.On the other hand,drug-induced autophagy may activate some of apoptotic signaling pathway in drug-resistant cells and promote the reversal of cell drug resistance.

Objective:To evaluate the development of fetal cerebral sulci and gyrus and the blood perfusion in pregnant women with gestational diabetes mellitus(GDM) by ultrasound.Methods:A total of 1 540 pregnant women with 28-34 weeks of pregnancy who underwent systematic screening in Henan Provincial People′s Hospital from January 2022 to October 2022 were prospectively selected, 100 pregnant women with GDM were selected as the GDM group. According to the effect of blood glucose control, the GDM group was divided into 2 groups: the satisfied control group (GDM group 1), and the dissatisfied control group (GDM group 2), with 50 cases in each group. At the same period, 50 healthy pregnant women at 28-34 weeks of gestation were enrolled as the control group. The differences of the sylvian fissure, parietooccipital sulci, calcarine sulci and cinguli sulci among the 3 groups were statistically analyzed. And the correlations between the deep of the brain cerebral sulci and gyrus and controlled blood glucose levels were evaluated. The umbilical artery pulsation index(UAPI), middle cerebral artery pulsation index(MCAPI) and ductus venosus pulsation index(DVPI) among the 3 groups were compared, and the differences in fetal blood perfusion among the 3 groups were evaluated.Results:There were no significant differences in the depths of the sylvian fissure, parietooccipital sulci, calcarine sulci and cinguli sulci between the control group and the GDM group 1 (all P>0.05), and they were larger than those of the GDM group 2 (all P<0.05). The depths of lateral fissure, parieto-occipital sulcus, cingulate sulcus and calcarine sulcus were negatively correlated with fasting blood glucose, 1 h and 2 h postprandial blood glucose (all P<0.05). There were no significant differences in MCAPI, UAPI and DVPI between the control group and GDM1 group (all P>0.05). The MCAPI in GDM 2 group was lower than that in the control group and GDM 1 group, and the UAPI and DVPI values were higher than those in the control group and GDM1 group(all P<0.05). Conclusions:The maturity of fetal cerebral sulci and gyrus in GDM pregnant women is related to the blood glucose control of pregnant women. The change of blood perfusion caused by persistent hyperglycemia in pregnant women and intrauterine hypoxia may cause the development retardation of cerebral sulci and gyrus.

Objective:To investigate the effects of continuous renal replacement therapy (CRRT) on plasma concentration, clinical efficacy and safety of colistin sulfate.Methods:Clinical data of patients received with colistin sulfate were retrospectively analyzed from our group's previous clinical registration study, which was a prospective, multicenter observation study on the efficacy and pharmacokinetic characteristics of colistin sulfate in patients with severe infection in intensive care unit (ICU). According to whether patients received blood purification treatment, they were divided into CRRT group and non-CRRT group. Baseline data (gender, age, whether complicated with diabetes, chronic nervous system disease, etc), general data (infection of pathogens and sites, steady-state trough concentration, steady-state peak concentration, clinical efficacy, 28-day all-cause mortality, etc) and adverse event (renal injury, nervous system, skin pigmentation, etc) were collected from the two groups.Results:A total of 90 patients were enrolled, including 22 patients in the CRRT group and 68 patients in the non-CRRT group. ① There was no significant difference in gender, age, basic diseases, liver function, infection of pathogens and sites, colistin sulfate dose between the two groups. Compared with the non-CRRT group, the acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) were higher in the CRRT group [APACHE Ⅱ: 21.77±8.26 vs. 18.01±6.34, P < 0.05; SOFA: 8.5 (7.8, 11.0) vs. 6.0 (4.0, 9.0), P < 0.01], serum creatinine level was higher [μmol/L: 162.0 (119.5, 210.5) vs. 72.0 (52.0, 117.0), P < 0.01]. ② Plasma concentration: there was no significant difference in steady-state trough concentration between CRRT group and non-CRRT group (mg/L: 0.58±0.30 vs. 0.64±0.25, P = 0.328), nor was there significant difference in steady-state peak concentration (mg/L: 1.02±0.37 vs. 1.18±0.45, P = 0.133). ③ Clinical efficacy: there was no significant difference in clinical response rate between CRRT group and non-CRRT group [68.2% (15/22) vs. 80.9% (55/68), P = 0.213]. ④ Safety: acute kidney injury occurred in 2 patients (2.9%) in the non-CRRT group. No obvious neurological symptoms and skin pigmentation were found in the two groups. Conclusions:CRRT had little effect on the elimination of colistin sulfate. Routine blood concentration monitoring (TDM) is warranted in patients received with CRRT.

Background::Transplant renal artery stenosis (TRAS) is a vascular complication after kidney transplantation associated with poor outcomes. This study aimed to analyze the efficacy and safety of low-dose aspirin for preventing TRAS.Methods::After kidney transplantation, patients were enrolled from January 2018 to December 2020 in Henan Provincial People’s Hospital. A total of 351 enrolled recipients were randomized to an aspirin group with low-dose intake of aspirin in addition to standard treatment ( n = 178), or a control group with only standard treatment ( n = 173). The patients was initially diagnosed as TRAS (id-TRAS) by Doppler ultrasound, and confirmed cases were diagnosed by DSA (c-TRAS). Results::In the aspirin and control groups, 15.7% (28/178) and 22.0% (38/173) of the recipients developed id-TRAS, respectively, with no statistical difference. However, for c-TRAS, the difference of incidence and cumulative incidence was statistically significant. The incidence of c-TRAS was lower in the aspirin group compared with the control group (2.8% [5/178] vs. 11.6% [20/173], P = 0.001). Kaplan–Meier estimates and Cox regression model identified the cumulative incidence and hazard ratio (HR) of TRAS over time in two groups, showing that recipients treated with aspirin had a significantly lower risk of c-TRAS than those who were not treated (log-rank P = 0.001, HR = 0.23, 95% confidence interval [CI]: 0.09–0.62). The levels of platelet aggregation rate ( P < 0.001), cholesterol ( P = 0.028), and low-density lipoprotein cholesterol ( P = 0.003) in the aspirin group were decreased compared with the control group in the third-month post-transplantation. For the incidence of adverse events, there was no statistical difference. Conclusion::Clinical application of low-dose aspirin after renal transplant could prevent the development of TRAS with no significant increase in adverse effects.Trial Registration::Clinicaltrials.gov, NCT04260828.

Mitophagy is the process of selective clearance of damaged mitochondria by autophagy. There are several regulatory mechanisms for mitophagy, and the PINK1/Parkin pathway is considered the main pathway for mitophagy. Recent studies have shown that PINK1/Parkin-mediated mitophagy plays an important role in the pathogenesis of various diseases including Parkinson’s disease. This article introduces the mechanism of PINK1/Parkin-mediated mitophagy and its role in various liver diseases including nonalcoholic fatty liver disease, liver fibrosis, and hepatocellular carcinoma, in order to provide new clues and ideas for the treatment of diseases.

OBJECTIVETo evaluate the feasibility of right neck anastomosis in thoracoscopic and laparoscopic esophagectomy.

METHODSThis study used a retrospective cohort study method. Clinical data of 169 patients with stage I-III esophageal squamous cell carcinoma undergoing neck anastomosis in thoracoscopic and laparoscopic esophagectomy at the Department 5 of Thoracic Surgery, the Fourth Hospital of Hebei Medical University from November 2013 to October 2016 were retrospectively analyzed. Eighty-two cases underwent right neck anastomosis (right neck anastomosis group) and 87 cases underwent left neck anastomosis(left neck anastomosis group). Both groups underwent routine thoracoscopic and laparoscopic radical resection of esophageal cancer. The entry of right and left neck anastomosis group was at the anterior edge of the right and left sternocleidomastoid muscle respectively. Anastomosis of the esophagogastric junction was performed and the drainage tube was placed in the neck incision. The operation time, intraoperative blood loss, lymph node dissection and morbidity of postoperative complications were compared between the two groups.

RESULTSThere were 101 males and 68 females among 169 patients with esophageal cancer. There were no significant differences in age, gender, tumor location, clinical stage between two groups(all P>0.05). The total operation time of left and right neck anastomosis groups was (278.3±39.4) minutes and (287.8±39.4) minutes, respectively (t=1.563, P=0.120). The intraoperative blood loss was (134.9±71.5) ml and(147.9±85.5) ml, respectively (t=1.074, P=0.284). The number of lymph node dissections was (17.45±5.68) and (16.47±4.98), respectively (t=1.190, P=0.236). Seventeen cases(20.7%) in the right neck anastomosis group developed postoperative complications, while 31 cases (35.6%) in the left neck anastomosis group developed postoperative complications (χ²=4.609,P=0.032). Compared with left neck anastomosis group, right neck anastomosis group had lower rate of gastric emptying disorder (0% vs. 6.9%, P=0.029), anastomotic fistula (7.3% vs. 18.4%, χ²=4.572, P=0.033), pneumonia (18.3% vs. 32.2%, χ²=4.294, P=0.038) and ICU management (4.9% vs. 16.1%, χ²=4.726, P=0.030).

CONCLUSIONThoracoscopic and laparoscopic esophagectomy with right neck anastomosis is safe and effective, can completely remove the tumor, at the same time, has less complications than left neck anastomosis, and improve the quality of life.

Anastomosis, Surgical ; Esophageal Neoplasms ; surgery ; Esophagectomy ; Female ; Humans ; Laparoscopy ; Lymph Node Excision ; Male ; Postoperative Complications ; Quality of Life ; Retrospective Studies ; Thoracoscopy

Objective To explore the causes and management of postoperative complications of laparoscopic Roux-en-Y gastric bypass (LRYGB).Methods The retrospective cross-sectional study was conducted.The clinical data of 450 patients with metabolic diseases who underwent LRYGB between June 2004 and November 2016 were collected,including 283 (58 in hospital consultation) in the First Affiliated Hospital of Jinan University,140 in the Jihua Hospital Affiliated to Jinan University and 27 in the Zhengzhou Hospital of Jinan University.Observation indicators:situations of surgical completion,follow-up situations,occurrence,treatment and prognosis of complications.Follow-up using outpatient examination and telephone interview was performed to detect postoperative complications once at month 1,3,6 and 12 within 1 year postoperatively and once every year after 1 year postoperatively up to March 2017.Measurement data with skewed distribution were described as M (range).Count data were evaluated by the ratio,and comparison between groups was analyzed using the chi-square test.Results All the 450 patients with metabolic diseases underwent successful LRYGB,including 50 receiving LRYGB during surgical internship period and 400 receiving LRYGB after surgical internship period,without conversion to open surgery.All the 450 patients were followed up for 70 months (range,1-153 months).Twenty-seven patients had postoperative complications,with an incidence of 6.00％ (27/450).The incidence of postoperative complications was 20.00％(10/50) in 50 patients receiving LRYGB during surgical internship period and 4.25％ (17/400) in 400 patients receiving LRYGB after surgical internship period,with a statistically significant difference (x2 =16.86,P＜ 0.05).Of 27 patients with postoperative complications,1 was complicated with fulminant acute pancreatitis and died from multiple organ failure at day 15 postoperatively,5 with intra-abdominal bleeding,2 with anastomotic leakage,3 with gastrojejunal anastomosis stenosis,2 with gastrojejunal anastomosis ulcer,1 with improper anastomosis,1 with respiratory failure,1 with umbilicus infection,3 with internal hernia,2 with dumping syndrome,6 with weight-loss failure (1 refused to undergo revision surgery),and patients with postoperative complications were improved or cured by surgery or conservative treatment except one death.Conclusions The incidence of complications in patients receiving LRYGB after surgical internship period is significantly reduced,and complications needs to make the individualized treatment plan.

Objective To explore the applications effect of evidence-based nursing in the health education for patients with mixed vaginal infections.Methods One hundred and sixty-eight patients with mixed vaginal infection were divided into observation group(n=84) and control group(n=84).Based on the evidence-based nursing method,the observation group first raised questions,then sought evidence to determine the conclusion according to the literature search,and finally combined with clinical evidence to formulate a reasonable plan for health education and effectively implemented.The control group was given conventional nursing.The two groups were compared in terms of rate of disease-related awareness in return visit 1 month after discharge,behavior 2 months after discharge and disease relapse 6 months after discharge.Results The rate of disease-related awareness and behavior in the experiment group were better than those of the control group significantly(all P<0.05).The rate of disease relapse of the experiment group was lower than that of the control group(P<0.01).Conclusion Application of evidence-based nursing method for patients with vaginal infections in health education can guide the nurses' health education target,improve the patients' cognitive and behavior and reduce the rate of disease relapse.

Hyperhomocysteinemia, which is an independent risk factor for atherosclerosis, may cause aberrant methylation and dysregulation of gene expression, but the characteristics of the aberrant methylation and its key links involved in its pathogenic mechanisms are still poorly understood. The effect of hyperhomocysteine on DNA methylation in vascular smooth muscle cells, its characteristics and the underlying mechanism of Hcy-induced changing in DNA methylation patterns were investigated. Clinical relevant concentrations of homocysteine was added into the cultured vascular smooth muscle cells of the Homo sapien umbilical vein for 24 h. The level of SAM and SAH was detected by HPLC. The activity of SAH Hydrolase was detected by real-time quantitative reverse transcription-PCR and Western blotting analysis. The level and patterns of DNA methylation were measured by endogenous C-5 DNA methyltransferase(C-5 MT-ase) activity and capacity of genomic DNA to accept methyl groups and methylation-dependent restriction analysis. The results indicated that an increased Hcy concentration induced elevated SAH, declined SAM and the ratio of SAM/SAH, reduced expression of SAH Hydrolase, but increased activity of C-5MT-ase. The methylation status of gDNA analyzed by methyl-accepting capacity of gDNA uncovered a demethylation process in gDNA, or homocysteine-caused hypomethylation in gDNA.With different methylation-dependent restriction endonucleases, the aberrant demethylation was found to prefer C↓CGG sequences to CpG islands. The impacts of different dosage of Hcy showed that the varied detrimental effects of Hcy could be attributed to different concentrations via different mechanisms. In mild and moderate hyperhomocysteinemia, the Hcy may primarily influence the epigenetic regulation of gene expression through the interference of transferring methyl-group metabolism, while in more higher Hcy concentration, the notorious impacts may be more directly caused via oxidative stress, apoptosis, inflammation etc.

Objective To observe the effects of homocysteine on the expression of estrogen receptor alpha(ER?) mRNA and the CpG island methylation of ER? gene promotor region in rats.Methods The serum level of homocysteine in rats was measured by reversed-phase HPLC.RT-PCR and methylated specific PCR(MSP) were applied to assay mRNA expression and the methylation status in promoter CpG island of ER? gene in aorta and cultured rat aortic smooth muscle cells(RASMCs).Results The homocysteine level was increased in ove and ove+H groups(P