Objective:To evaluate the role of nuclear factor E2-related factor 2 (Nrf2)/heme oxidase-1 (HO-1) in reduction of renal ischemia-reperfusion (I/R) injury by the human umbilical cord mesenchymal stem cells (hucMSCs)-derived exosomes (hucMSCs-exo) in mice.Methods:The hucMSCs were cultured, and exosomes were extracted and identified by transmission electron microscopy, nanoparticle tracking analysis and Western blot. Thirty-six male SPF-grade C57BL/6 mice, weighing 20-25 g, were used. Thirty mice were selected and divided into 5 groups ( n=6 each) by a random number table method: sham operation group (Sham group), sham operation + Nrf2 inhibitor ML385 group (Sham + ML385 group), renal I/R group (I/R group), renal I/R + exosome group (I/R+ EXO group), and renal I/R + exosome + Nrf2 inhibitor ML385 group (I/R+ EXO+ ML385 group). A model of renal I/R injury was prepared by clamping the bilateral renal pedicles for 45 min followed by perfusion in anesthetized animals. ML385 30 mg/kg was intraperitoneally injected at 45 min before preparing the model in Sham+ ML385 group and I/R+ EXO+ ML385 group, and hucMSCs-exo 100 μg was injected via the tail vein at 15 min before reperfusion in I/R+ EXO group and I/R+ EXO+ ML385 group. Serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations were detected at 24 h of reperfusion. The renal tissues were obtained for examination of the pathological changes and for determination of contents of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA), superoxide dismutase (SOD) activity and reactive oxygen species (ROS) levels and expression of Nrf2 and HO-1 protein and mRNA (by Western blot and quantitative real-time polymerase chain reaction). The left 6 mice were allocated to sham operation group (Sham-IM group, n=3) and renal I/R group (I/R-IM group, n=3) by a random number table method for VISQUE in living imaging observation. Results:The exosomes showed a typical cup-shaped morphology with a transmission electron microscope, the nanoparticles tracked and analyzed the average diameter of the exosome, with an average diameter of 96.7 nm, and the positive expression of surface markers CD9, CD63 and TSG101 was detected using Western blot. The renal fluorescence intensity value was significantly increased in I/R-IM group as compared with Sham-IM group ( P<0.05). Compared with Sham group, the serum BUN and Cr concentrations were significantly increased, the contents of IL-6, TNF-α and MDA and ROS levels were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 protein and mRNA was down-regulated ( P<0.05), and the pathological changes of renal tissues were aggravated in I/R group, and no significant change was found in serum BUN and Cr concentrations in Sham+ ML385 group ( P>0.05). Compared with I/R group, the serum BUN and Cr concentrations were significantly decreased, the contents of IL-6, TNF-α and MDA and ROS levels were decreased, the activity of SOD was increased, the expression of Nrf2 and HO-1 protein and mRNA was up-regulated ( P<0.05), and the pathological changes of renal tissues were significantly attenuated in I/R+ EXO group. Compared with I/R+ EXO group, the serum BUN and Cr concentrations were significantly increased, the contents of IL-6, TNF-α and MDA and ROS levels were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 protein and mRNA was down-regulated ( P<0.05), and the pathological changes of renal tissues were aggravated in I/R+ EXO+ ML385 group. Conclusions:The mechanism by which hucMSCs-exo reduces renal I/R injury may be related to activation of the Nrf2/HO-1 signaling pathway in mice.

Objective To investigate the efficacy and safety of intravenous thrombolysis with low-dose and standard-dose recombinant tissue plasminogen activator(rt-PA)in the elderly patients(aged over 80 years)with acute ischemic stroke(AIS).Methods A total of 201 elderly patients with AIS treated at Tianjin Fourth Central Hospital from February 2019 to February 2023 were prospectively included and randomly assigned to the rt-PA low-dose group(n=93,0.6 mg/kg)and rt-PA standard-dose group(n=108,0.9 mg/kg).The incidence of intra-cranial hemorrhage,symptomatic intracranial hemorrhage,fatal intracranial hemorrhage,neurologic deterioration within 7 days and mortality within 90 days were observed to evaluate the safety.The neurologic improvement rate and good prognosis rate at 90 days were used to evaluate the effectiveness.A stratified analysis of 90-day outcomes was performed based on stroke severity and age.Results The incidence of intracranial hemorrhage,symptomatic intracranial hemorrhage and fatal intracranial hemorrhage within 7 days in rt-PA low-dose group was lower than that in rt-PA standard-dose group(P＜0.05).There were no statistically significant differences between the two groups concerning the residual safety index and the effectiveness index.The 90-day good prognosis rate of moderate stroke sub-group and of≥90 years of age sub-group in rt-PA low-dose group were both higher than that of rt-PA standard-dose group(P＜0.05).Conclusions For AIS patients with moderate stroke and aged over 90 years,intravenous thrombolytic therapy with rt-PA 0.6 mg/kg is recommended.

Objective Establishment and evaluation of a mouse model of aldosterone-induced multi-organ damage.Methods Twenty mice were randomly divided into four groups,with five mice in each group:a blank control group(0 μg/(kg·d)),a low-dose aldosterone group(150 μg/(kg·d))),a medium-dose aldosterone group(300 μg/(kg d)),and a high-dose aldosterone group(450 pug/(kg·d)).Aldosterone-containing osmotic minipumps were surgically implanted under the skin,and aldosterone was infused for 4 weeks to establish the aldosterone-induced damage model.The body weight and blood pressure of the mice were recorded weekly.After the 4 week modeling period,the mice were euthanized,and their tissues were collected for observation and analysis of blood pressure and histological morphology of various organs.Results(1)After 4 weeks of aldosterone infusion,the serum aldosterone levels were significantly increased in the medium-dose and high-dose aldosterone groups,but not in the low-dose aldosterone group.(2)After the implantation of osmotic minipumps,the systolic blood pressure was significantly increased in the low-dose,medium-dose,and high-dose aldosterone groups during the second and third weeks,but decreased in all these groups during the fourth week.(3)The kidney and heart in the low-dose,medium-dose,and high-dose aldosterone groups showed varying degrees of damage,interstitial edema,collagen deposition,and fibrotic lesions.The liver in the low-dose aldosterone group showed a small amount of collagen deposition,while the medium-dose and high-dose aldosterone groups showed varying degrees of hepatocyte damage,collagen deposition,and fibrotic lesions.Conclusions Aldosterone can induce multi-organ damage in mice.Under this modeling method,organ damage is mainly manifested as edema,collagen deposition,and fibrotic lesions.

Objective: To investigate the association between maternal parenting styles and quality of life among preschools，to provide a scientific theoretical basis for interventions targeting at prmoting early life health. Methods: From May to July, 2021, a stratified cluster sampling method was used to enroll 4 233 child mother dyads from 14 preschools in Chengdu. An online questionnaire survey was administered to collect socio demographic information, maternal parenting styles, and children s quality of life. Results: The overall score of quality of life was (80.17±9.81) among preschool children in Chengdu. In the multivariate linear regression models, maternal emotional warmth were significantly associated with higher scores in emotional functioning, social functioning, school functioning, psychosocial health summary score, and total scores ( β coefficients in the high level group were 2.63 , 4.95 , 12.05, 6.54,4.88, P <0.05). In contrast, both maternal rejection and overprotection were significantly associated with lower scores in physical functioning, emotional functioning, social functioning, school functioning, psychosocial health summary score, and the total scores of children s quality of life (for rejection: β coefficients in the high level group were -9.39, -10.82, -7.12 , -6.04 , -8.00, and -8.35 , respectively; for overprotection: β coefficients in the high level group were -6.71, -5.85, -3.08 , -2.39 , -3.77, and - 4.51 , respectively， P <0.05). The associations between high level of maternal rejection and children s emotional functioning showed significant gender differences( β =-3.23, P <0.05). Conclusion Maternal parenting style has a significant impact on children s quality of life. Interventions targeting at maternal parenting styles may be beneficial to improve the quality of life in preschool children.

Objective:To evaluate the feasibility and safety of a novel transjugular intrahepatic portosystemic shunt (TIPS) puncture set for transjugular intrahepatic portal puncture in swine.Methods:Thirteen domestic swine were randomly divided into experimental group ( n=7) and control group ( n=6) and received transjugular intrahepatic portal puncture with the novel puncture set and the R?sch-Uchida Transjugular Liver Access Set (RUPS-100), respectively. Three swines in each group were randomly selected and sacrificed immediately after the procedure and the rest were sacrificed 1 week later. The intraoperative technical success rate, puncture attempts, procedure time, fluoroscopy time, vital signs and occurrence of complications related to the procedure as well as the changes of liver and kidney function before, immediately after and 1 week after the procedure were compared between two groups. Independent sample t test, paired t test, Mann-Whitney U test, chi-square test or Fisher′s exact test were performed to compare the differences between groups. Results:The technical success rate was 100% for both groups. No significant difference in portal puncture attempts [2.0 (1.0, 5.0) vs. 2.0(1.0, 5.5), P>0.999], procedure time [(47.7±20.6) vs. (52.5±28.0)min, P=0.729] and fluoroscopy time [(725.1±489.2) vs. (763.7±562.4)s, P=0.897] was observed between two groups. In addition, no significant difference of the major liver and kidney function between two groups before, immediately after and 1 week after procedure ( P>0.05 at all time points). No significant difference of the major liver and kidney function change in two groups during perioperative period was identified (all P>0.05). Furthermore, no significant difference of non-target puncture occurrence was observed between two groups ( P>0.999). In the meantime, no significant difference of occurrence of small hematomas around hepatic hilar was discovered among swine sacrificed immediately after procedure between two groups ( P>0.999). No other major complications were identified in either group. Conclusion:The novel TIPS puncture set is feasible and safe to perform transjugular intrahepatic portal puncture in swine.

Objective:To investigate the association between C-reactive protein (CRP)/albumin (ALB) ratio (CAR) and mortality in peritoneal dialysis (PD) patients.Methods:Clinical data of 791 PD patients in the Second Affiliated Hospital of Soochow University from January 1, 2004 to December 31, 2019 were retrospectively collected. According to the baseline quartiles of CAR, patients were divided into three groups: low-level CAR group (CAR≤0.161 mg/g, n=264), medium-level CAR group (CAR 0.162-0.214 mg/g, n=263) and high-level CAR group (CAR≥0.215 mg/g, n=264). The clinical data among the three groups were compared. Follow-up was ended on March 31, 2020, or when the patients stopped PD due to death, shift to hemodialysis, renal transplantation or recovery of renal function. Kaplan-Meier survival curve, multivariate Cox proportional hazard model and Fine-Gray competing risk model were used to assess the relationship between CAR and all-cause mortality and cardiovascular and cerebrovascular mortality. The association between CAR, CRP, ALB, neutrophil to lymphocyte ratio (NLR), or platelet to lymphocyte ratio (PLR) and mortality in PD patients was compared by receiver-operating characteristic curve (ROC curve) analysis. Results:The age of the patients was (59.8±15.7) years old, and 447(56.5%) patients were males. 714(90.3%) patients had hypertension. 233(29.5%) patients had diabetes. 182(23.0%) patients had cardiovascular diseases. The median follow-up time was 55(31, 88) months. By the end of the follow-up, 236 deaths (29.8%) happened, and 95 patients (12.0%) died from cardiovascular and cerebrovascular diseases. Kaplan-Meier survival analysis results showed that the overall survival rate of the high-level CAR group was lower than those of the low-level CAR group and medium-level CAR group (Log-rank test χ2=109.50, P<0.001). Multivariate Cox regression analysis and Fine-Gray competing risk model revealed that CAR was independently correlated with all-cause mortality and cardiovascular and cerebrovascular mortality after adjusting for confounding factors ( HR=2.891, 95% CI 1.921-4.351, P<0.001; SHR=1.297, 95% CI 1.128-1.490, P<0.001). ROC curve analysis results showed that the area under the curve ( AUC) of CAR for predicting the risk of all-cause mortality in PD patients was 0.737(95% CI 0.700-0.774), which was superior to those of CRP ( AUC=0.643, 95% CI 0.599-0.687), NLR( AUC=0.608, 95% CI 0.563-0.653) and PLR ( AUC=0.554, 95% CI 0.508-0.601), and slightly lower than ALB ( AUC=0.752, 95% CI 0.716-0.788). The optimal cutoff value of CAR for death was 0.19 mg/g, with the sensitivity and specificity of 70.8% and 68.3%, respectively. Conclusions:Increasing CAR level is an independent risk factor of all-cause mortality and cardiovascular and cerebrovascular mortality in PD patients, and its correlation with mortality is higher than those of inflammatory parameters such as CRP, NLR and PLR.

T he recent development of imaging and sequencing technologies enables systematic advances in the clinical study of lung cancer.Meanwhile,the human mind is limited in effectively handling and fully utilizing the accumulation of such enormous amounts of data.Machine learning-based approaches play a critical role in integrating and analyzing these large and complex datasets,which have extensively characterized lung cancer through the use of different perspectives from these accrued data.In this review,we provide an overview of machine learning-based approaches that strengthen the varying aspects of lung cancer diagnosis and therapy,including early detection,auxiliary diagnosis,prognosis prediction,and immunotherapy practice.Moreover,we highlight the challenges and opportunities for future applications of machine learning in lung cancer.

Objective    To evaluate the effect of smoking and drinking status on the prognosis of patients with esophageal squamous cell carcinoma (ESCC). Methods    The clinical data of 483 patients with ESCC who underwent surgical treatment in Shannxi Provincial People's Hospital from 2007 to 2016 were retrospectively analyzed. Among them, 352 patients were male and 131 were female, with a median age of 64 (37-80) years. There were 311 smokers and 172 drinkers. The relationship between preoperative drinking or smoking status and the clinicopathological characteristics of patients with ESCC was analyzed. Log-rank method and Cox risk regression were used to conduct univariate and multivariate survival analysis, respectively. Results    The preoperative smoking status was related to the patient's tumor location (P=0.030). Drinking status was associated with tumor location (P=0.001), degree of differentiation (P=0.030), pathological T stage (P=0.024) and pathological N stage (P=0.029). Univariate survival analysis showed that smoking status did not affect the disease-free survival (DFS) (P=0.188) and overall survival (OS) (P=0.127) of patients with ESCC. However, patients who drank alcohol had worse PFS than non-drinking patients (29.37 months vs. 42.87 months, P=0.009). It was further proved that alcohol consumption was an independent risk factor affecting patients' recurrence and metastasis by using multivariate analysis (RR=1.28, P=0.040). Alcohol consumption also reduced the OS of patients by 21.47 months (P=0.014), however, multivariate analysis did not yield significant results. Conclusion    Preoperative drinking status is related to the stage and differentiation of patients with ESCC. It is an independent risk factor affecting the recurrence and metastasis of ESCC.

ObjectiveTo systematically evaluate the value of contrast-enhanced computed tomography (CECT) and contrast-enhanced magnetic resonance imaging (CEMRI) in the diagnosis of residual or recurrent lesion after transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC). MethodsPubMed, Embase, Cochrane Library, Web of Science, CNKI, and Wanfang Data were searched for studies on CECT and/or CEMRI in the diagnosis of residual or recurrent lesion after TACE published up to April 2019. After two reviewers independently performed literature screening, data extraction, and assessment of the risk of bias using the QUADAS-2 tool, Stata 12.0 and RevMan 5.3 were used to analyze pooled sensitivity, specificity, and area under the receiver operator characteristic curve (AUC). ResultsA total of 13 studies on CECT and 13 studies on CEMRI in the diagnosis of residual or recurrent HCC lesion after TACE were included, with 934 lesions from 748 patients and 847 lesions from 557 patients, respectively. High heterogeneity was observed in the 13 studies on CECT in the diagnosis of residual or recurrent HCC lesion after TACE (P=0.001, Q=12.56, I2=84.08%), while no significant heterogeneity was observed in the 13 studies on CEMRI (P=0.473, Q=0.11, I2=0). In the diagnosis of residual or recurrent HCC lesion after TACE, CECT had a sensitivity of 72% (95% confidence interval ［CI］: 66%-78%), a specificity of 99% (95% CI: 93%-100%), and an AUC of 0.87 (95% CI: 0.83-0.89), and CEMRI had a sensitivity of 88% (95% CI: 82%-93%), a specificity of 96% (95% CI: 91%-98%), and an AUC of 0.98 (95% CI: 0.96-0.99). CECT had a significantly lower sensitivity than CEMRI in the diagnosis of residual or recurrent HCC lesion after TACE (Z=2.12, P=0.03). ConclusionIn comparison with CECT, CEMRI has an extremely higher diagnostic efficiency in the diagnosis of residual or recurrent HCC lesion after TACE and is thus an effective method for diagnosis.

Objective In order to understand the chondrogenesis differentiation of mesenchymal stem cells in either hydrogel or pellet culture,we applied the two methods and reveal the possible mechanism and for further investigation.Methods In C3H10T1/2 chondrogenic differentiation,we apply extracellular matrix hydrogel mixed the cell suspensions of freshly prepared (including scaling chondroitin sulfate,sodium hyaluronate synthesis and cross-linking agent) co-culture system and high cell density pellet formed by centrifugation.Chondrogenic differentiation of C3H10T1/2 was induced by treatment with TGF-β3 (10 ng/ml),dexamethasone (100 nmol/L),ascorbic acid (50 ug/ml),1 ∶ 100 dilution ITS+Premix and high glucose-DMEM medium with 0.2 volume fraction fetal bovine serum.And high glucose-DMEM medium with 0.2 volume fraction fetal bovine serum is for control group.Histochemistry staining was utilized to identify extracellular proteoglycan and real-time PCR was performed to assess gene expression of SOX9,collagen Ⅱa1/Ⅹa1 and aggrecan for the 1st,2nd and 3rd week respectively.Results In the hydrogel model for 3 weeks chondrogenic differentiation,the expression of master transcription factor SOX9 was upregulated in both culture models.While the marker genes of collagen Ⅱa1 and collagen Ⅹa1 were all promoted in hydrogel culture,the aggrecan gene expression was peaked in pellet culture.In addition,immunocytochemistry analysis of the hydrogel and pellet for 3 week illustrated the expression of extracellular matrix and more obviously in the hydrogel model.Conclusion In compared with pellet culture,the MSCs in the hydrogel were more likely promoted chondrogenesis leading to the eventual expression of marker genes.And the hydrogel would be applied in regeneration of cartilage injury.