The repair of the nervous system after hypoxic-ischemic brain damage (HIBD) in neonates lacks specific therapeutic approaches, posing a challenge and hot topic in the medical field. Autophagy, as a cellular self-repair mechanism, plays a role through different signaling pathways at different stages, yet its specific roles and mechanisms in different stages of HIBD remain unclear. This article reviews the recent research advancements on autophagy in different neonatal HIBD stages: heightened autophagic activity manifests during the acute hypoxic-ischemic phase, with its neuroprotective or deleterious impact subject to ongoing debate; during the subacute and chronic phases, autophagy exert dual effects on neuronal death and repair; in sequelae period, autophagy-related studies are still insufficient, but the expression levels of autophagy-related genes (ATG) in children with cerebral palsy suggest both positive and negative aspects of autophagy post-HIBD. Collectively, optimal autophagic flux facilitates the elimination of detrimental substrates and toxic proteins, thereby engendering neuroprotection. Further studies on the roles and mechanisms of autophagy in HIBD therapy holds promise for devising efficacious preventative and therapeutic strategies rooted in autophagy, and to improve the survival rate and quality of life of the children.

Objective     To analyze the clinical efficacy and survival outcome of totally thoracoscopic redo mitral valve replacement and evaluate its efficiency and safety. Methods     The clinical data of patients with totally thoracoscopic redo mitral valve replacement in Guangdong Provincial People’s Hospital between 2013 and 2019 were retrospectively analyzed. Survival analysis was performed using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were used to determine the risk factors for postoperative death. Results     There were 48 patients including 29 females and 19 males with a median age of 53 (44, 66) years. All the procedures were performed successfully with no conversion to median sternotomy. A total of 15, 10 and 23 patients received surgeries under non-beating heart, beating heart and ventricular fibrillation, respectively. The in-hospital mortality rate was 6.25% (3/48), and the incidence of early postoperative complications was 18.75% (9/48). Thirty-five (72.92%) patients had their tracheal intubation removed within 24 hours after the operation. The 1- and 6-year survival rates were 89.50% (95%CI 81.30%-98.70%) and 82.90%(95%CI 71.50%-96.20%), respectively. Age>65 years was an independent risk factor for postoperative death (P=0.04). Conclusion     Totally thoracoscopic redo mitral valve replacement is safe and reliable, with advantages of rapid recovery, reducing blood transfusion rate, reducing postoperative complications and acceptable long-term survival rate. It is worthy of being widely popularized in the clinic.

Objective:To compare and analyze the clinical curative effect and safety of chemoembolization with drug-loaded microspheres of different particle sizes (D-TACE) for the treatment of hepatocellular carcinoma.Methods:Clinical data of 281 cases with hepatocellular carcinoma treated with drug-loaded microspheres-transarterial chemoembolization (TACE) were retrospectively analyzed. According to the different particle sizes of drug-loaded microspheres, they were divided into 100~300 μm (small particle size) and 300~500 μm (large particle size) group. Tumor response rate and complication conditions at 1, 3, and 6 months after chemoembolization were compared. The overall survival time of the two groups were analyzed. Quantitative data conformed to normal distribution and homogeneity of variance were compared using t-test, while other with Wilcoxon signed rank-sum test. Qualitative data were compared using χ2 test. Kaplan-Meier method was used for survival analysis, and the differences in survival were analyzed using Log-rank test. P＜0.05 was considered as statistically significant. Survival curves and histograms were drawn using GraphPad Prism9.1 software. Results:The complete remission rates at 1, 3 and 6 months after surgery in the small and large particle size groups were 31.25%, 30.15%, and 42.45% and 18.25%, 15.79% and 24.74%, respectively, and the differences were statistically significant between groups (P 1 month=0.012, P 3 month=0.009, P 6 month=0.008, P＜0.05). The objective remission rates at 1, 3 and 6 months after surgery in the small and large particle size groups were 88.19%, 76.99%, and 70.75% and 81.02%, 72.81% and 53.60%, respectively. Six months after surgery, the small particle size group (objective response rate = 70.75%) was significantly higher than the large particle size group (objective response rate=53.6%, P=0.012). The disease control rates of the small particle size group were 95.14%, 83.33%, and 74.53%, while large particle size group were 91.24%, 81.58%, and 64.95%, respectively, with no statistically significant difference between the two groups. However, the incidence of postoperative biliary tumors (6.20%) was significantly higher in the small-size than large-size group (0.70%), and the difference was statistically significant ( P＜0.05, P=0.03). There were no statistically significant differences between other adverse events such as post-embolization syndrome, liver abscess, and myelosuppression. The median survival time of the small and large particle size groups was 31.8 months and 20.5 months, respectively, but the difference was not statistically significant ( P=0.182). Conclusions:In the treatment of hepatocellular carcinoma with D-TACE, the short-term curative effect of the small particle size group was better than large particle size group, but the incidence of biliary tumors was high, and D-TACE of different particle sizes had no significant effect on long-term survival.

OBJECTIVE: To study the effects of myo-inositol and luteolin on human lung cancer A549 cells and explore the possible mechanisms. METHODS: A549 cells were treated with different concentrations of myo-inositol and luteolin, either alone or in combination, and the cell viability was examined using MTT assay. A549 cells and human bronchial epithelial Beas-2B cells were treated for 48 h with 10 mmol/L myo-inositol and 20 μmol/L luteolin, alone or in combination, and the cell proliferation was detected using MTT assay; the colony formation and migration of the cells were examined with colony formation assay and wound healing assay, respectively. The protein expression levels in A549 cells were detected using Western blotting. RESULTS: Both myo-inositol and luteolin could dose-dependently inhibit the viability of A549 cells. Treatments with 10 mmol/L myo-inositol, 20 μmol/L luteolin, and both for 48 h caused significant reduction in the cell viability (92%, 83% and 70% of the control level, respectively) and colony number (79%, 73% and 43%, respectively), and significantly lowered the wound closure rate (24.61%, 13.08% and 8.65%, respectively, as compared with 29.99% in the control group). Similar treatments with myoinositol and luteolin alone or in combination produced no significant inhibitory effect on the growth, colony formation or migration of Beas-2B cells. The expressions of p-PDK1 and p-Akt in myo-inositol-treated A549 cells and the expression of pPDK1 in luteolin-treated cells were significantly decreased ( < 0.05), and the decrements were more obvious in the combined treatment group ( < 0.05). CONCLUSIONS Luteolin combined with myo-inositol can selectively inhibit the proliferation and migration of A549 cells, and these effects are probably mediated, at least in part, by suppressing the activation of PDK1 and Akt.
A549 Cells ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Humans ; Inositol ; administration & dosage ; therapeutic use ; Lung Neoplasms ; drug therapy ; metabolism ; Luteolin ; administration & dosage ; therapeutic use ; Protein-Serine-Threonine Kinases ; drug effects ; metabolism ; Proto-Oncogene Proteins c-akt ; drug effects ; metabolism ; Vitamin B Complex

Objective To analyze the effects of alprostadil combined with benazepril in the treatment of diabetes and the effect on blood glucose fluctuation.MethodsEighty cases with diabetes were randomly divided into the control group and the observation group with 40 cases in each group.The control group was treated with benazepril while the observation group was additionally treated with alprostadil.The treatment effects, the changes of blood glucose, blood lipids and renal function were compared between the two groups, and the incidence of adverse reactions was recorded.ResultsThe total effective rate in the observation group was higher than that in the control group (P<0.05).After treatment, the fasting plasma glucose (FPG), postprandial 2h plasma glucose (2hPG) and glycosylated hemoglobin (HbA1c) were reduced to the normal level but the volatility differences of FPG and 2hPG in the observation group were lower than those in the control group (P<0.05).After 4 weeks of treatment, the total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) decreased while high-density lipoprotein cholesterol (HDL-C) increased (P<0.05) but the differences between the two groups showed no statistical significance.After treatment, the improvement of renal function indexes in the observation group was better than that in the control group (P<0.05), and the incidence of adverse reactions showed no significant difference between the two groups.ConclusionThe application of alprostadil combined with benazepril in the treatment of diabetes can reduce blood glucose fluctuation, improve renal function, and reduce the risk of diabetic nephropathy.

Objective To explore the potential correlation between fluoride levels of urine and influencing factors in water-high-fluoride areas.Methods In 2010,based on plain area,mountainous area and mixed area (altitudes were 898,2 200,1 460 m,respectively),3 villages of water-high-fluoride areas were selected by purpose sampling;pupils' family members were selected as survey population by cluster sampling.Questionnaire was conducted to collect general information;fluoride contents in urine and drinking water were measured using ionselective electrode.A linear multiple regression was used to examine which factors affected urinary fluoride.Results Totally there were 968 people distributed in plain area (444),mixed area (368) and mountainous area (156),medians of urinary fluoride level were 0.71,1.59 and 1.67 mg/L,respectively,the difference was significant (F =203.90,P ＜0.01);medians of water fluoride level in the three different habitats were 0.50,1.00 and 3.50 mg/L,respectively,the difference was significant (F =331.98,P ＜ 0.01).Age,gender,fluoride contents in drinking waters and habitat explained 33.1％ of urinary fluoride variation.Male had higher urine fluoride than female,older age and higher level fluoride in drinking water contributed to higher fluoride level in urine,higher altitude contributed to higher urinary fluoride.Conclusion Once fluoride content in urine is used to estimate fluoride exposure level among people in high fluoride area,gender and age must be taken in consideration.

BACKGROUND:Previous studies have verified that mesenchymal stem cells could be transplanted into inflammatory bowel mucosa to repair inflammatory bowel tissue. OBJECTIVE:To observe the differential gene expression in large intestine before and after mesenchymal stem celltransplantation in repair of inflammatory bowel tissue of rats using microarray technology, and to primarily discover the main genes during mesenchymal stem celltransplantation, differentiation, and reparation in inflammatory colorectal tissue region. METHODS:Healthy Sprague-Dawley rats were randomly divided into two groups. Experimental rat models of inflammatory bowel disease were established using trinitrobenzene sulfonic acid via enema. At 24 hours after model establishment, green fluorescent protein-labeled mesenchymal stem cells were infused via the caudal vein. The control group was treated with physiological saline by enema, instead of trinitrobenzene sulfonic acid. At 28 days, large intestine was obtained from the experimental group and control group. Differential y expressed genes were screened in the experimental and control groups using microarray technique. RESULTS AND CONCLUSION:The microarray analysis results showed that there were 388 differential genes in the control and experimental groups (P<0.05, FC>2), in which 191 were up-expressed, and 197 were down-expressed. Al of these genes were mainly involved in inflammatory reaction, immune reaction and celldifferentiation. In the top 10 up-regulation and down-regulation differential genes (total y 20 genes), 3 genes were involved in inflammation, 3 genes were involved in immune reaction, and 2 genes were related to stem celldifferentiation. In the 388 genes, 33 were related to signaling pathways (P<0.05), 6 related to inflammation, 8 related to immunity, and 5 related to stem celldifferentiation. Results suggested that the main genes involved in mesenchymal stem cells in repair of inflammatory bowel tissue were primarily screened using gene expression microarray technique.

BACKGROUND:β-catenin is the most critical signaling molecule in the Wnt/β-catenin signaling pathway, which is involved in the regulation of cellproliferation, differentiation and tissue self-healing balance.
OBJECTIVE:To construct a stableβ-catenin over-expression lentivirus-mediated vector and to transfect mesenchymal stem cells line for investigating its effects on proliferation and migration of mesenchymal stem cells.
METHODS:Over-expression vector, PLV-EF1A-catenin-RFP, was constructed and transfected the 293T cellto infect mesenchymal stem cells, and positive cells were selected with puromycin. The up-regulated efficiency of targetingβ-catenin gene at mRNA level was detected by real-time quantitative PCR, the effect on proliferation of mesenchmal stem cellwas assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and growth curve, and the migration ability was detected by Transwel motility assay.
RESULTS AND CONCLUSION:The lentiviral vector targetingβ-catenin gene was constructed successful y, and a stable mesenchymal stem cellline that up-regulatedβ-catenin was established. Real-time quantitative PCR results showed that the expression ofβ-catenin gene was efficiently up-regulated by infecting PLV-EF1A-catenin-RFP (P<0.05). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and growth curve showed that celldoubling time was shortened after infected with pLV-EF1A-catenin-RFP (P<0.05), indicating that the over-expression of theβ-catenin gene successful y increased the proliferative capability of mesenchymal stem cells. The Transwel assay also showed similar increasing results on the migration ability (P<0.01). The lenvivirus-mediated over-expression of theβ-catenin gene can be used to increase the proliferation and migration abilities of the mesenchymal stem cells.

Objective To construct a lentiviral vector over-expressing β-catenin gene by multisite Gateway technology and confirm its effect.Methods By using multisite Gateway clone technique,the entry clone of pDown-Ctnnb1 was constructed using BP recombination reaction.Then,LR recombination reaction was performed among pUp-EF1A,pDown-Ctnnb1,pTail-IRES/DsRed-Express2 and pLV.Des3d.P/puro to generate an expression clone of pLV.EX3d.P/puro-EF1A＞Ctnnb1 ＞IRES/DsRed-Express2.In each step,PCR and sequencing analysis were used to verify the constructions.When it was verified that plasmids were transfected into 293T cells,PT-PCR was performed to determine the mRNA level of β-catenin gene.Results Both PCR and sequencing analysis revealed that β-catenin over-expression gene was inserted into the target site and the insertion sequence was perfectly corrected.The RT-PCR results showed that the expression of β-catenin gene was significantly upregulated.Conclusion The lenvivirus-mediate β-catenin over-expression gene was successfully constructed..

Objective To explore the factors influencing the recovery of ability in the activities of daily living (ADL) after intracerebral hemorrhage. Methods A total of 108 patients with intracerebral hemorrhage admitted for rehabilitation to the rehabilitation medicine department of Huashan Hospital between January 2007 and June 2011 were studied.Twelve items of clinical data were collected with regard to the patients' medical history,physical status,modified Barthel index (MBI) score and Brunnstrom stage at admission.Functional status was classified according to the MBI scores and Brunnstrom stages assessed at admission and before discharge.Linear regression analysis was used to relate the variables. Results After rehabilitation,the MBI scores and Brunnstrom stages had improved relative to the scores at admission.Factors influencing the MBI improvements included the intervention timing of rehabilitation and the course of therapy employed. Conclusions It is very important to comprehend the factors influencing the recovery of ADL ability after cerebral hemorrhage in order to design effective rehabilitation strategies,better predict functional outcomes and improve patients' ADL ability effectively.