Background Arsenic is an environmentally harmful substance that causes hepatic insulin resistance and liver damage, increasing the risk of type 2 diabetes mellitus. Objective To explore whether the insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) is involved in insulin resistance in HepG2 cells after arsenic exposure through the peroxisome-proliferator-activated receptor γ (PPAR-γ) / glucose transporter 4 (GLUT4) pathway. Methods Cell viability was determined using cell counting kit 8 (CCK8) and an appropriate NaAsO₂ infection dose was determined. A cellular arsenic exposure model of HepG2 cells was established by four concentrations of NaAsO₂ solution for 24 h (the experiment was divided into four groups: 0, 2, 4, and 8 μmol·L⁻¹); HepG2 cells were firstly treated with pcDNA3.1-IGF2BP2 and pcDNA3.1-NC respectively for 6 h, then with 8 μmol·L⁻¹ NaAsO₂ for 24 h to establish a IGF2BP2 overexpression cell model (the experiment was divided into 4 groups: control, NaAsO₂, NaAsO₂+pcDNA3.1-IGF2BP2, and NaAsO₂+pcDNA3.1-NC); finally the cells were subject to 100 nmol·L⁻¹ insulin stimulation for 30 min. Glycogen and glucose in HepG2 cells were determined by glycogen and glucose assay kits; mRNA expression levels of IGF2BP2 were measured by quantitative real-time PCR; protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in HepG2 were detected by Western blot (WB); and the binding of IGF2BP2 to PPAR-γ and PPAR-γ to GLUT4 was verified by co-immunoprecipitation (CO-IP) experiment. Results The results of CCK8 experiment showed a dose-effect relationship between NaAsO₂ concentration and cell viability. When the concentration of NaAsO₂ was ≥4 μmol·L⁻¹ , the cell viabilities were lower than that of the control group (P <0.05). With the increasing dose of NaAsO₂ infection, reduced glucose consumption and glycogen levels in HepG2 cells were found in the 2, 4, and 8 μmol·L⁻¹ NaAsO₂ treatment groups compared to the control group (P <0.05). The difference between the mRNA expression level of IGF2BP2 in the HepG2 cells treated with 4 or 8 μmol L⁻¹ NaAsO₂ and the control group was significant (P <0.05). In the IGF2BP2 overexpression cell model, compared with the control group, glucose consumption and glycogen levels were lowered in the NaAsO₂ group (P <0.05), the mRNA expression level of IGF2BP2 and the protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in the cell membrane were all decreased (P <0.05). Compared with the NaAsO₂ group, the glucose consumption and glycogen levels were increased in the NaAsO₂+pcDNA3.1-IGF2BP2 group (P <0.05), and the mRNA expression level of IGF2BP2 and the protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in the cell membrane were all increased (P <0.05). The results of CO-IP experiments showed that IGF2BP2 interacted with PPAR-γ as well as PPAR-γ with GLUT4 protein. Conclusion IGF2BP2 is involved in arsenic exposure-induced insulin resistance in HepG2 cells by acting on the PPAR-γ/GLUT4 pathway.

Background Arsenic exposure is a common and important environmental and occupational hazardous factor in China, and arsenic-induced insulin resistance (IR) has attracted widespread attention as a negative health outcome to the population. Objective To explore part of the mechanism of hepatic IR induced by arsenic exposure based on the peroxisome proliferators-activated receptors γ (PPARγ)/ glucose transporter 4 (GLUT4) pathway, and to investigate potential effects of Ginkgo biloba extract (GBE) on hepatic IR induced by arsenic exposure and associated mechanism of action. Methods The target of drug action was predicted by network pharmacology and verified by in vivo and in vitro experiments. In vivo experiments: 48 SPF C57BL/6J male mice were divided into 4 groups, including control group, 50 mg·L⁻¹ NaAsO₂ model group (NaAsO₂), 50 mg·L⁻¹ NaAsO₂+10 mg·kg⁻¹ GBE intervene group (NaAsO₂+GBE), and 10 mg·kg⁻¹ GBE group (GBE), 12 mice in each group. The animals were given free access to purified water containing 50 mg·L⁻¹ NaAsO₂, or given intraperitoneal injection of normal saline containing 10 mg·kg⁻¹ GBE once per week. After 6 months of exposure, blood glucose detection, intraperitoneal glucose tolerance test (IPGTT), and insulin tolerance test (ITT) were performed. Serum and liver tissues were collected after the mice were neutralized, liver histopathological sections were obtained, serum insulin levels, liver tissue glycogen content, glucose content were detected by enzyme linked immunosorbent assay (ELISA), and the expression of PPARγ and GLUT4 proteins was detected by Western blot (WB). In vitro experiments: HepG2 cells were divided into 4 groups, including control group, 8 μmol·L⁻¹ NaAsO₂ group (NaAsO₂), 8 μmol·L⁻¹ NaAsO₂ + 200 mg·L⁻¹ GBE intervene group (NaAsO₂+GBE), and 200 mg·L⁻¹ GBE group (GBE). The levels of glycogen and glucose were detected by ELISA, and the expression of PPARγ and GLUT4 proteins was detected by WB. Results A strong binding effect between GBE and PPARγ was revealed by network pharmacology. In in vivo experiments, the NaAsO₂ group exhibited an elevated blood glucose compared to the control group, and the NaAsO₂+GBE group showed a decreased blood glucose compared to the NaAsO₂ group (P<0.01). The histopathological sections indicated severe liver structural damage in the arsenic exposure groups (NaAsO₂ group and NaAsO₂+GBE group), with varying staining intensity, partial liver cell necrosis, and diffuse red blood cell appearance. Both results of in vitro and in vivo experiments showed a decrease in glycogen synthesis and glucose uptake in the NaAsO₂ groups compared to the control groups, which was alleviated in the NaAsO₂+GBE group (P<0.01). The results of WB revealed inhibited PPARγ expression and reduced GLUT4 levels on the cell membrane, and all these changes were alleviated in the NaAsO₂+GBE group (P<0.01). Conclusion This study findings suggest that GBE antagonizes arsenic exposure-induced hepatic IR by regulating the PPARγ/GLUT4 pathway, indicating that GBE has a protective effect on arsenic exposure-induced hepatic IR, and PPARγ may be a potential therapeutic target for arsenic exposure-induced hepatic IR.

Objective:To investigate the effects of extracorporeal carbon dioxide removal (ECCO 2R) combined with continuous renal replacement therapy (CRRT) on respiratory efficiency and diaphragm function in patients with acute respiratory distress syndrome (ARDS) received mechanical ventilation. Methods:A prospective randomized controlled study was conducted. Sixty patients with mild to moderate ARDS admitted to the department of respiratory and critical care medicine of Henan Provincial People's Hospital from January 2019 to January 2021 were enrolled, and they were divided into observation group and control group according to the random number table method, with 30 cases in each group. All patients received antibiotics, anti-inflammatory, and mechanical ventilation therapy. On this basis, the observation group received ECCO 2R and CRRT, while the control group received bedside CRRT. Baseline data including gender, age, etiology, acute physiology and chronic health evaluationⅡ(APACHEⅡ), etc., were recorded. Arterial blood gas analysis [including arterial partial pressure of oxygen (PaO 2), arterial partial pressure of carbon dioxide (PaCO 2), and oxygenation index (PaO 2/FiO 2)] was performed at 12 hours and 24 hours during the treatment, and respiratory mechanics parameters [including tidal volume, respiratory rate, maximum expiratory pressure (MEP), and maximum inspiratory pressure (MIP)] were recorded, and rapid shallow breathing index (RSBI) was calculated. The levels of glutathione peroxidase (GSH-Px), malondialdehyde (MDA), and superoxide dismutase (SOD) in serum were detected by enzyme-linked immunosorbent assay (ELISA). Diaphragm thickness and diaphragm activity were measured by ultrasonography at 24 hours during the treatment. Results:There were no significantly differences in age, gender, etiology, and APACHEⅡ score between the two groups, indicating that the baseline data of the two groups were balanced and comparable. Compared with the 12 hours after treatment, the PaO 2 and PaO 2/FiO 2 in the observation group significantly increased, PaCO 2 significantly decreased, RSBI significantly decreased, MEP and MIP significantly increased, and serum GSH-Px and MDA significantly decreased, while SOD significantly increased at 24 hours during the treatment. In the control group, only PaCO 2 significantly decreased. Compared with the control group, the PaCO 2 significantly decreased in the observation group at 12 hours and 24 hours [mmHg (1 mmHg≈0.133 kPa): 55.05±7.57 vs. 59.49±6.95, 52.77±7.88 vs. 58.25±6.92, both P < 0.05], but no significantly differences in PaO 2 and PaO 2/FiO 2. Compared with the control group, the observation group showed significant decreases in RSBI at 12 hours and 24 hours (times·min -1·L -1: 85.92±8.83 vs. 90.38±3.78, 75.73±3.86 vs. 90.05±3.66, both P < 0.05), significant increases in MEP and MIP [MEP (mmH 2O, 1 mmH 2O≈0.01 kPa): 86.64±5.99 vs. 83.88±4.18, 93.70±5.59 vs. 85.04±3.73; MIP (mmH 2O): 44.19±6.66 vs. 41.17±3.13, 57.52±5.28 vs. 42.34±5.39, all P < 0.05], and significant decreases in serum GSH-Px and MDA [GSH-Px (mg/L): 78.52±8.72 vs. 82.10±3.37, 57.11±4.67 vs. 81.17±5.13; MDA (μmol/L): 7.84±1.97 vs. 8.71±0.83, 3.67±0.78 vs. 8.41±1.09, all P < 0.05], as well as a significant increase in SOD (U/L: 681.85±49.24 vs. 659.40±26.47, 782.32±40.56 vs. 676.65±51.97, both P < 0.05). Compared with the control group, the observation group showed significant increases in diaphragm thickness and diaphragm activity at 24 hours of treatment [diaphragm thickness (cm): 1.93±0.28 vs. 1.40±0.24, diaphragmatic thickening fraction: (0.22±0.04)% vs. (0.19±0.02)%, quiet breathing diaphragm displacement (cm): 1.42±0.13 vs. 1.36±0.06, deep breathing diaphragm displacement (cm): 5.11±0.75 vs. 2.64±0.59, all P < 0.05]. Conclusion:ECCO 2R combined with CRRT can reduce work of breathing and oxidative stress levels in ARDS patients receiving non-invasive ventilation, and protect diaphragm function.

Objective To explore the effect of physical exercise on semen quality in order to provide basic data and theoretical basis for the improvement of male reproductive health.Methods A cross-sectional study was conducted on 1 059 males who visited the Reproductive Medicine Center of Shandong Maternal and Child Health Hospital for medical treatment and physical examination during July 2022 and April 2023.Their demographic data and physical exercise data were surveyed with questionnaires.Total sperm count,sperm concentration,total sperm motility,forward movement and normal sperm morphology were analyzed with computer aided analysis.Logistic regression model and multiple linear regression model were applied to analyze the effects of physical exercise on semen quality.Results After adjustment for confounding factors such as age,body mass index,alcohol consumption and smoking,logistic regression analysis showed that the risk of abnormal semen quality was increased in patients with moderate and heavy exercise intensity(OR=2.103,OR=2.229).Compared with the participants with physical exercise ≤10 min per session,those with＞20 min per session had a lower risk of abnormal semen quality(OR=0.357,0.256,0.289 for exercise time for＞20～30,＞30～60,＞60 min,respectively).There was no statistical significance between physical exercise frequency and semen quality(P＞0.05).The participants having exercise well were at a lower risk for abnormal semen quality(OR=0.711).Multiple linear regression analysis revealed that the frequency of physical exercise was an influencing factor of sperm concentration(β=7.474,95％CI:4.800～10.149,P＜0.05);the time of physical exercise per session was an influencing factor for total sperm count(β=20.632,95％CI:7.634～33.629);the intensity of physical exercise(β=-1.461,95％CI:-2.392～-0.530)and time of physical exercise per session(β=2.608,95％CI:1.404～3.812,P＜0.05)were influencing factors for percentage of forward motility sperm(P＜0.05);and physical exercise intensity(β=-1.934,95％CI:-3.238～-0.630),time of physical exercise per session(β=4.211,95％CI:2.525～5.897)and frequency of physical exercise(β=-2.008,95％CI:-3.480～-0.536)were influencing factors of total sperm motility(P＜0.05).Conclusion Physical exercise may affect semen quality,greater intensity of physical exercise may be a risk factor for abnormal semen quality,and longer physical exercise time may be related to improving semen quality.Therefore,proper physical exercise can help improve semen quality.

Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

Objective To explore the role of Adra1a in regulating the LPS-induced inflammation response in primary hepatocytes of lipopolysaccharide-binding protein knockout(Lbp-/-)mice.Methods Primary hepatocytes were extracted from WT and Lbp-/-mice using a two-step perfusion method,and an inflammation model was established using LPS induction.Expression of Adra1a in primary hepatocytes of Lbp-/-mice was suppressed by administering the inhibitor prazosin and transfection with si-Adra1a.The cells were divided into three groups under inhibitor conditions:control group A,LPS group A,and prazosin group.For siRNA transfection,cells were also divided into groups:control group B,LPS group B,si-NC group,and si-Adra1a group.WT primary hepatocytes were divided into two groups:control group(blank)and LPS group(12 h stimulation).Changes in the Adra1a response to LPS stimulation were verified by Western blot.Other method ologies,such as CCK-8,qRT-PCR,and Western blot assays,were used to confirm improvements in cell inflammation and the survival rate by prazosin and si-Adra1a.Results Significant elevation in Adra1a protein expression in Lbp-/-primary hepatocytes was observed post-LPS stimulation(P＜0.01),whereas no notable change was found in the wildtype.A remarkable increase in the cell survival rate was noted in prazosin and si-Adra1a groups(P＜0.01,P＜0.05).Furthermore,prazosin and si-Adra1a groups exhibited significantly reduced expression of proinflammatory factors TNF-αand IL-1 β(P＜O.01),p-p38,p-ERK,and p-JNK(P＜0.01),which are associated with cell damage and inflammation.Conclusions Following LPS stimulation,upregulation of Adra1a and proinflammatory cytokine expression was observed in Lbp-/-primary hepatocytes.Specific downregulation of Adra1a expression using prazosin and si-Adra1a significantly decreased LPS-induced proinflammatory cytokines in Lbp-/-primary hepatocytes.Adra1a is implicated in the regulation of the LPS-induced inflammation response in primary hepatocytes of Lbp-/-mice.

Objective:To identify whether splenectomy for treatment of hypersplenism has any impact on development of hepatocellular carcinoma(HCC) among patients with liver cirrhosis and hepatitis.Methods:Patients who underwent splenectomy for hypersplenism secondary to liver cirrhosis and portal hypertension between January 2008 and December 2012 were included from seven hospitals in China, whereas patients receiving medication treatments for liver cirrhosis and portal hypertension (non-splenectomy) at the same time period among the seven hospitals were included as control groups. In the splenectomy group, all the patients received open or laparoscopic splenectomy with or without pericardial devascularization. In contrast, patients in the control group were treated conservatively for liver cirrhosis and portal hypertension with medicines (non-splenectomy) with no invasive treatments, such as transjugular intrahepatic portosystemic shunt, splenectomy or liver transplantation before HCC development. All the patients were routinely screened for HCC development with abdominal ultrasound, liver function and alpha-fetoprotein every 3 to 6 months. To minimize the selection bias, propensity score matching (PSM) was used to match the baseline data of patients among splenectomy versus non-splenectomy groups. The Kaplan-Meier method was used to calculate the overall survival and cumulative incidence of HCC development, and the Log-rank test was used to compare the survival or disease rates between the two groups. Univariate and Cox proportional hazard regression models were used to analyze the potential risk factors associated with development of HCC.Results:A total of 871 patients with liver cirrhosis and hypertension were included synchronously from 7 tertiary hospitals. Among them, 407 patients had a history of splenectomy for hypersplenism (splenectomy group), whereas 464 patients who received medical treatment but not splenectomy (non-splenectomy group). After PSM,233 pairs of patients were matched in adjusted cohorts. The cumulative incidence of HCC diagnosis at 1,3,5 and 7 years were 1%,6%,7% and 15% in the splenectomy group, which was significantly lower than 1%,6%,15% and 23% in the non-splenectomy group ( HR=0.53,95% CI:0.31 to 0.91, P=0.028). On multivariable analysis, splenectomy was independently associated with decreased risk of HCC development ( HR=0.55, 95%CI:0.32 to 0.95, P=0.031). The cumulative survival rates of all the patients at 1,3,5,and 7 years were 100%,97%,91%,86% in the splenectomy group,which was similar with that of 100%,97%,92%,84% in the non-splenectomy group ( P=0.899). In total,49 patients (12.0%) among splenectomy group and 75 patients (16.2%) in non-splenectomy group developed HCC during the study period, respectively. Compared to patients in non-splenectomy group, patients who developed HCC after splenectomy were unlikely to receive curative resection for HCC (12.2% vs. 33.3%,χ2=7.029, P=0.008). Conclusion:Splenectomy for treatment of hypersplenism may decrease the risk of HCC development among patients with liver cirrhosis and portal hypertension.

Objective:To identify whether splenectomy for treatment of hypersplenism has any impact on development of hepatocellular carcinoma(HCC) among patients with liver cirrhosis and hepatitis.Methods:Patients who underwent splenectomy for hypersplenism secondary to liver cirrhosis and portal hypertension between January 2008 and December 2012 were included from seven hospitals in China, whereas patients receiving medication treatments for liver cirrhosis and portal hypertension (non-splenectomy) at the same time period among the seven hospitals were included as control groups. In the splenectomy group, all the patients received open or laparoscopic splenectomy with or without pericardial devascularization. In contrast, patients in the control group were treated conservatively for liver cirrhosis and portal hypertension with medicines (non-splenectomy) with no invasive treatments, such as transjugular intrahepatic portosystemic shunt, splenectomy or liver transplantation before HCC development. All the patients were routinely screened for HCC development with abdominal ultrasound, liver function and alpha-fetoprotein every 3 to 6 months. To minimize the selection bias, propensity score matching (PSM) was used to match the baseline data of patients among splenectomy versus non-splenectomy groups. The Kaplan-Meier method was used to calculate the overall survival and cumulative incidence of HCC development, and the Log-rank test was used to compare the survival or disease rates between the two groups. Univariate and Cox proportional hazard regression models were used to analyze the potential risk factors associated with development of HCC.Results:A total of 871 patients with liver cirrhosis and hypertension were included synchronously from 7 tertiary hospitals. Among them, 407 patients had a history of splenectomy for hypersplenism (splenectomy group), whereas 464 patients who received medical treatment but not splenectomy (non-splenectomy group). After PSM,233 pairs of patients were matched in adjusted cohorts. The cumulative incidence of HCC diagnosis at 1,3,5 and 7 years were 1%,6%,7% and 15% in the splenectomy group, which was significantly lower than 1%,6%,15% and 23% in the non-splenectomy group ( HR=0.53,95% CI:0.31 to 0.91, P=0.028). On multivariable analysis, splenectomy was independently associated with decreased risk of HCC development ( HR=0.55, 95%CI:0.32 to 0.95, P=0.031). The cumulative survival rates of all the patients at 1,3,5,and 7 years were 100%,97%,91%,86% in the splenectomy group,which was similar with that of 100%,97%,92%,84% in the non-splenectomy group ( P=0.899). In total,49 patients (12.0%) among splenectomy group and 75 patients (16.2%) in non-splenectomy group developed HCC during the study period, respectively. Compared to patients in non-splenectomy group, patients who developed HCC after splenectomy were unlikely to receive curative resection for HCC (12.2% vs. 33.3%,χ2=7.029, P=0.008). Conclusion:Splenectomy for treatment of hypersplenism may decrease the risk of HCC development among patients with liver cirrhosis and portal hypertension.

We retrieved the PDTC patient medical record in our center who have received multi-disciplinary comprehensive treatment in March 2019. By reviewing his treatment process, we hope to improve the recognition of this disease and provide reference for individualized programs.

Objective:To investigate the antibacterial effect of iodophor on Staphylococcus aureus biofilm (BBF).Methods:Staphylococcus aureus were cultured in vitro and 480 pieces of titanium alloy plates were selected. On the surface of titanium plates, in vitro models of Staphylococcus aureus biofilms were established at days 7, 14, 21 and 28 respectively with 120 pieces of titanium plates at each time points. The biofilms at each time point were assigned to no iodophor immersion (PBS group), 5 g/L iodophor immersion for 5 minutes (5-min group) and 5 g/L iodophor immersion for 10 minutes (10-min group), according to the random number table method. FITC-ConA, propidium iodide (PI) and SYT09 were used to dye Staphylococcus aureus in PBS group. After dyeing, confocal laser scanning microscopy and scanning electron microscopy were used to observe the morphological structure of bacterial biofilms, and the Colony forming unit (CFU) was counted by the viable count method. In the other two groups, PI and SYT09 were applied to dye Staphylococcus aureus, and then confocal laser scanning microscopy and scanning electron microscopy were used to observe the changes of biofilms and bacterial viability after iodophor immersion. The antibacterial effect of iodophor was evaluated by the viable count method.Results:After dyeing Staphylococcus aureus with FITC-ConA and PI in PBS group, confocal laser scanning microscopy showed that the extracellular polymers of the bacteria increased gradually with the extension of culture time. The space structure of biofilm was gradually mature, changed significantly at day 21 and became mature at day 28. After staining Staphylococcus aureus with PI and SYT09 in PBS group, confocal laser scanning microscopy showed that the number of bacteria increased, and had a mountain-like shape. Scanning electron microscopy showed that the number of bacterial extracellular polymers increased gradually with the extension of culture time and a structured microenvironment was formed and gradually matured. In 5-min and 10-min groups, all bacteria were killed at days 7 and 14 [0(0, 0)CFU/ml], the antibacterial effect was weakened at 21 days, but the antibacterial effect of iodophor immersion in 10-min group [100 (100, 125)CFU/ml] was better than that in 5-min group [300 (275, 425)CFU/ml] ( P<0.05). There was no significant difference in iodophor immersion in 5-min group [500 (375, 700)CFU/ml] and 10-min group [250 (175, 400)CFU/ml] at 28 days ( P>0.05). Conclusions:The maturation of biofilm is the overall maturation of bacteria and bacterial extracellular polymers and the formation of a spatialized microenvironment. Bounded by the 21st day, biofilms are divided into young biofilms and mature biofilms. The main difference between them lies in the maturation of extracellular polymers and microenvironment. For the bacterial biofilm with culture time less than 21 days, the antibacterial effect of the iodophor immersion for 10 min is better than that of 5 min. However, for the bacterial biofilm with culture time greater than 21 days, there is no significant difference in the antibacterial effect of the bacterial biofilm of prolonged iodophor immersion time.