BACKGROUND:Inherited heart disease has a high prevalence and mortality rate,but its pathogenesis has not yet been clarified.Although relevant animal models have been established to provide a foundation for the pathogenesis research of inherited heart disease,the value of these research results has been significantly reduced due to differences among species.Therefore,a new model is needed to explore its occurrence and development. OBJECTIVE:To review the current role of induced pluripotent stem cells in disease modeling and potential application prospects in various inherited heart diseases. METHODS:The first author searched the relevant articles published nearly 13 years in PubMed from January to March 2023.The search terms were"induced pluripotent stem cell,inherited heart disease,congenital heart disease".Finally,76 articles were included for analysis. RESULTS AND CONCLUSION:Since 2007,when induced pluripotent stem cells were induced from human somatic cells,many studies have been reported on disease-specific induced pluripotent stem cells.Due to the ability of disease-specific induced pluripotent stem cells to reproduce disease phenotypes,they are expected to become a new research tool for in vitro disease modeling,used to analyze pathogenesis and develop auxiliary drugs.In the research of cardiovascular genetic diseases,cardiomyocytes derived from patient-specific induced pluripotent stem cells contain gene mutations that are involved in cardiac dysplasia.Therefore,it can be used as a new tool to study the potential mechanisms of inherited heart disease.Up to now,induced pluripotent stem cells-derived cardiomyocytes have been widely used to study the molecular mechanisms of various genetic heart diseases,such as cardiac electrophysiological diseases,cardiomyopathy,and some syndromic inherited heart diseases.

Objective:To investigate the effect of nuclear factor-erythroid 2-related factor 2 (Nrf2) gene on the proliferation and apoptosis of colorectal adenocarcinoma cells in vitro, and the role of Nrf2 gene in regulation of epithelial-mesenchymal transition (EMT) pathway.Methods:Three Nrf2 small interfering RNA (siRNA) sequences were designed and synthesized, namely siRNA-223, siRNA-538 and siRNA-756, and the unrelated sequences were designed and synthesized. The plasmids carrying various siRNA sequences of Nrf2 were constructed, and the plasmids carrying siRNA sequences and the plasmids carrying unrelated sequences were transfected into human colorectal adenocarcinoma Caco-2 cells, namely interference group and empty vector group, respectively. Additionally, Caco-2 cells without any treatment were used as the control group. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blotting (WB) methods were used to detect the relative expression of Nrf2 gene in transcription and translation levels in each group of cells, in order to verify the interference effect of Nrf2; the siRNA with the best interference effect was selected for subsequent experiments. CCK-8 method was used to detect the proliferation ability of each group of cells (expressed as absorbance value); RT-qPCR was used to detect the relative expression of EMT pathway-related factors [vimentin (Vim), N-cadherin (N-cad) and E-cadherin (E-cad)] in transcription level in each group of cells; WB method was used to detect the expression of pro-apoptotic protein Bax in each group of cells.Results:The results of RT-qPCR and WB methods showed that compared with the control group and the empty group, the relative expression of Nrf2 gene in transcription and translation levels in Caco-2 cells of the siRNA-756 interference group were the lowest, and the differences were statistically significant (all P < 0.05). The CCK-8 results showed that the absorbance values of Caco-2 cells in the control group, empty group and siRNA-756 interference group after 48 hours of culture were (100±5)%, (94±4)% and (82±5)%, respectively; compared with the control group and the empty group, the siRNA-756 interference group had lower absorbance value, and the differences were statistically significant (all P < 0.05). The results of RT-qPCR method showed that the relative expression of Vim and N-cad in transcription level in the siRNA-756 interference group were higher than those in the control group and the empty vector group, and the differences were statistically significant (all P < 0.05); the relative expression of E-cad in transcription level was lower than those in the control group and the empty vector group, and the differences were statistically significant (both P < 0.05). The results of WB method showed that the relative expression of Bax protein in the siRNA-756 interference group was higher than that in the control group, and the difference was statistically significant ( P < 0.05). Conclusions:Interference with Nrf2 expression in vitro can weaken the proliferation and anti-apoptotic abilities of human colorectal adenocarcinoma Caco-2 cells. The mechanism may be that Nrf2 regulates the expression of Vim, N-cad and E-Cad in the EMT pathway to enhance the EMT ability of tumor cells.

Objective: To investigate the difference of clinical characteristics of recurrent spontaneous abortion (RSA) in patients with losses after spontaneous gestation and after in vitro fertilization and embryo transfer ( IVFET) ． Methods : 237 patients diagnosed with RSA were divided into spontaneous gestation group ( n = 185) and IVF group (n = 52) according to their previous modes of fertilization．The clinical characteristics of the two groups were analyzed. Results: Compared with the spontaneous gestation group，the age of the first pregnancy and the age at the time of RSA in the IVF group were statistically greater than those in the natural pregnancy group ( P < 0. 05 ) ．The number of biochemical pregnancies in IVF group was statistically higher than that in spontaneous gestation group，and the number of spontaneous abortions in IVF group was statistically lower than that in spontaneous gestation group (P＜0. 001) ．The proportion of patients with irregular menstruation in IVF group was statistically higher than that in spontaneous gestation group ( P ＜ 0. 05 ) ． The serum activated partial prothrombin time (APTT) ，R , K，high density lipoprotein cholesterol (HDL-C) ，thyrotropin (TSH) and homocysteine ( HCY) in IVF group were statistically lower than those in spontaneous gestation group，and the Angel，Ma，low density lipoprotein cholesterol (LDL-C) and body mass index (BMI) in IVF group were statistically higher than those in spontaneous gestation group (P＜0. 05) ．In the comparison of etiological composition between the two groups，the proportion of anatomical factors in IVF group was statistically higher than that in spontaneous gestation group (P < 0. 05) ． Conclusion The abortion risk factors in RSA patients after IVF-ET is more serious than that in RSA patients after natural pregnancy．It is suggested to further improve and implement the pre-pregnancy examination and education of infertile patients during IVF-ET treatment，so as to reduce the risk of RSA and obtain a better pregnancy outcome.

Objective : To analyze the metabolism of blood glucose，blood lipid and insulin in patients with recur- rent pregnancy loss (RPL) ，and to compare the predictive efficacy of triglyceride glycemic index (TyG) ，triglycer- ide glycemic body mass index (TyG-BMI) and homeostatic model assessment of insulin resistance( HOMA-IR) for RPL． Methods : A total of 573 patients with RPL were selected as the RPL group，and 652 women who received as- sisted reproductive technology for male infertility were selected as the control group．The general data of the two groups were retrospectively analyzed．The levels of body mass index(BMI) ，fasting blood glucose (FPG) ，fasting triglyceride (FTG) ，fasting insulin ( FINS) ，TyG index，TyG-BMI index and HOMA-IR were compared between the two groups．Spearman correlation analysis was used to verify the correlation between TyG index，TyG-BMI in- dex and HOMA-IR. Receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of TyG index，TyG-BMI index and HOMA-IR for RPL occurrence，and the optimal predictive cut-off point was calculated. Results : The BMI，FPG，FTG，TyG index，TyG-BMI index and HOMA-IR in the RPL group were significantly higher than those in the control group (P＜0. 05) ．TyG index and TyG-BMI index were positively correlated with HOMA-IR , and the correlation coefficients were 0. 442 and 0. 505，respectively (P＜0. 001) . ROC curve a- nalysis showed that the area under the curve of TyG-BMI index predicting RPL was 0. 579 (95% CI : 0. 551 - 0. 607，P＜0. 001) ，which was greater than that of TyG index of 0. 557 (95% CI : 0. 529－0. 585，P＜0. 001) and HOMA-IR of 0. 535 (95% CI : 0. 507 －0. 563，P ＜0. 05) ，among which the difference between TyG-BMI index and HOMA-IR index area under the curve was statistically significant (P ＜0. 05 ) ．The optimal cut-off points of TyG-BMI index ，TyG index and HOMA-IR for predicting RPL were 172. 3 ( sensitivity 75. 7% ，specificity 37. 06% ) ，8. 32 ( sensitivity 59. 44% ， specificity 51. 61% ) and 3. 58 ( sensitivity 25. 87% ， specificity 81. 62% ) ，respectively． Conclusion The incidence of overweight，abnormal blood glucose，lipid and insulin me- tabolism in RPL patients is higher than that in normal women．TyG index and TyG-BMI index can be used as indi- cators of insulin metabolic status in RPL population besides HOMA-IR , and TyG-BMI index has a higher efficacy in predicting the occurrence of RPL compared to HOMA-IR.

Objective To investigate the serum levels and clinical significances of microRNA-335 (miR-335) and microRNA-155 (miR-155) in patients with primary gallbladder cancer (PCG).Methods A total of 96 PCG patients (PCG group) and 50 healthy controls (control group) admitted to the Second People's Hospital of Hainan Province from January 2016 to October 2018 were selected.Real-time quantitative PCR (RT-PCR) was used to detect the serum levels of miR-335 and miR-155 in each group.The relationships between miR-335 and miR-155 levels and clinical pathological characteristics of PCG patients were analyzed.The diagnostic value of miR-335 and miR-155 in PCG was analyzed by ROC curve.Results The serum level of miR-335 in PCG group was significantly lower than that in the control group (1.50 ± 0.42 vs.3.65 ± 1.18,t =10.319,P ＜0.001).The serum level of miR-155 in PCG group was significantly higher than that in the control group (3.18 ±0.61 vs.0.74±0.12,t =13.627,P＜0.001).The serum levels ofmiR-335 and miR-155 in PCG patients were correlated with TNM stage (t =4.863,P =0.024;t =5.117,P =0.008) and lymph node metastasis (t =5.725,P ＜ 0.001;t =6.802,P ＜ 0.001).ROC curve analysis showed that the critical values of serum miR-335 and miR-155 for diagnosing PCG were 1.18 and 2.35,respectively.The area under the curve of the two combined diagnosis of PCG (0.920,95％ CI:0.863-0.977) was the largest,with sensitivity and specificity of 93.8％ and 85.7％.Conclusion The low serum level of miR-335 and high level of miR-155 are associated with the higher TNM stage and lymph node metastasis of PCG,and the combined detection of the two is helpful to improve the diagnostic rate of PCG.

To explore the immunomodulatory effects of interleukin-17 (IL-17) on acute lung injury (ALI) induced by lipopolysaccharide (LPS). Methods Thirty-six SPF-class C57BL/6 mice were divided into normal saline control group (NS group) and LPS-induced ALI model group (LPS group, LPS 5 mg/kg intratracheal drip) according to random number table method, with 18 mice in each group. Six mice were sacrificed at 2, 6 and 24 hours after model reproduction, and peripheral blood, lung and spleen tissues were harvested. After staining with hematoxylin-eosin (HE), the pathological changes of lung tissue were observed under microscope and the infiltration level of lymphocytes, neutrophils and macrophages in the alveolar wall and tracheal wall were detected. Immunohistochemistry was used to detect the protein expression of IL-17 in alveolar wall and tracheal wall, and the correlation between IL-17 expression and lymphocytes, neutrophils and macrophages infiltration in alveolar wall and tracheal wall were analyzed. The level of IL-17 in lung tissue homogenate was determined by enzyme linked immunosorbent assay (ELISA). Flow cytometry was used to detect the proportion of CD4+IL-17+ helper T cells (Th17 cells) in CD4+ T cells in peripheral blood, lung tissue and spleen tissue. Results ① Microscopy showed that the lung tissue structure of NS group was basically normal at each time after model reproduction, and there was no obvious inflammatory cell infiltration, while the lung tissue edema and inflammatory reaction were gradually aggravated in the LPS group, and the lung injury score was significantly higher than that in NS group at each time (2 hours: 4.47±1.42 vs. 1.10±0.55, 6 hours: 7.93±2.14 vs. 1.23±0.50, 24 hours:12.67±2.67 vs. 1.20±0.61, all P < 0.01). ② Immunohistochemistry showed that the protein expression of IL-17 in alveolar wall and tracheal wall of LPS group increased gradually with time, while that in NS group was negative or weak positive. Quantitative analysis showed that the immunohistochemical staining score of IL-17 protein in alveolar wall and tracheal wall of LPS group were higher than those of NS group (alveolar wall: 2.70±1.40 vs. 0.90±0.37 at 2 hours, 5.10±1.76 vs. 1.17±0.59 at 6 hours, 9.67±1.32 vs. 1.10±0.45 at 24 hours; tracheal wall: 2.87±0.89 vs. 0.90±0.39 at 2 hours, 4.97±1.48 vs. 1.10±0.41 at 6 hours, 8.67±1.54 vs. 1.03±0.29 at 24 hours; all P < 0.05). ③ Correlation analysis showed that the protein expression of IL-17 in alveolar wall and tracheal wall were positively correlated with the degree of lymphocyte, neutrophil and macrophage infiltration (alveolar wall: r value was 0.632, 0.550, 0.466; tracheal wall: r value was 0.695, 0.662, 0.575, respectively; all P < 0.01). ④ IL-17 content (μg/L) in lung tissue homogenate was significantly higher than that in NS group at each time after model reproduction (2 hours: 1.37±0.14 vs. 1.01±0.18, 6 hours: 1.65±0.19 vs. 1.11±0.18, 24 hours: 1.92±0.36 vs. 1.17±0.24, all P < 0.01). ⑤ The proportion of Th17 cells in the peripheral blood, lung tissue and spleen tissue of the LPS group were higher than those of the NS group at each time after model reproduction [peripheral blood: (2.62±0.62)% vs. (1.42±0.40)% at 2 hours, (3.74±0.43)% vs. (1.27±0.32)% at 6 hours, (4.44±0.65)% vs. (1.59±0.45)% at 24 hours; lung tissue: (2.32±0.44)% vs. (1.50±0.25)% at 2 hours, (3.66±0.36)% vs. (1.33±0.24)% at 6 hours, (4.60±0.54)% vs. (1.60±0.27)% at 24 hours; spleen tissue: (1.49±0.36)% vs. (0.69±0.21)% at 2 hours, (2.58±0.55)% vs. (0.59±0.18)% at 6 hours, (3.76±0.57)% vs. (0.65±0.26)% at 24 hours; all P < 0.01]. Conclusion IL-17 is involved in the inflammatory immune regulation of ALI mice.

Objective To investigate the effects of parenteral nutrition with ω-3 fatty acids on nutrition,inflammatory response,immunity and prognosis in criticallyill cancer patients.Methods 60 critically ill cancer patients were randomly divided into study group and the control group,30 cases each.All Patients were given isonitrogen and isocalorie enteral and parenteral nutrition for 2 weeks,which added ω-3 fatty acids in the study group by parenteral nutrition.The indicators of nutrition,inflammation,immune function were detected weekly.prognostic indicators (mortality,intensive care unit [ICU] length of stay,infectious complications) were compared.Results The indicators of nutrition,inflammatory reaction and immune function of study group were significantly improved than control group,and length of stay in ICU of study group was shorter than control group.There were less mortality and morbidity of infection complications in the study group compared with control group,but difference were not significant (P =0.13 and P=0.165).Conclusion ω-3 fatty acids supplementation of parenteral nutrition in critically ill cancer patients can improve nutritional status and immune function,reduce inflammatory response,shorten ICU length of stay,but not significantly improve ICU mortality and reduce infectious complications.

Objective To evaluate the effectiveness and safety of multimodal postoperative analgesia of thoracotomy for malignant tumor excision.Method Sixty patients undergoing thoracotomy for malignant tumor excision were recuited.They were randomized into four groups:group A receiving single flurbiprofen axetil injection,group B using electronic analgesia pump for sufentanil PCIA,group C using electronic analgesia pump for dezocine PCIA and group D receiving sufentanil controlled by PCA-TCI system.Vital signs,artery lood gas analysis,PrinceHenry score,Ramsay score,remedial measure and untoward reactions were recorded.Results The falling down degree of Prince-Henry score of Group D was higher than those of Groups A,B and C (P ＜ 0.05).Reduction of Ramsay score of Group D was higher than those of Groups A,B and C (P ＜ 0.05).The number of the patients in Group D not undergoing Bolus remedial measure was larger than that of those in Groups B and C (P ＜ 0.05).Conclusion When referring to the effectiveness and safety of the models administrated the thoracotomy for malignant tumors excision,the analgesia model of PC A-TCI sufentanil (plasma target concentration:0.12～ 0.14 ng/ mL) used in Group D is superior to other models used in Groups A,B and C.Moreover,individual analgesia can be reached by the PCA-TCI sufentanil model.

Chlorella is nutritious and has been used as a functional food much earlier than the other microalgae. C. pyrenoidosa, the potential microalgae which is currently cultured and developed for the new strategic industry of biofuels production and biological CO2 fixation, is a new resource food announced by the Ministry of Health of the People's Republic of China late 2012. Accumulation of high value-added substances in C. pyrenoidosa during the cultivation for lipid makes it possible to reduce the costs for C. pyrenoidosa-based biofuels production. Among these potential substances, hot water extract of Chlorella (CE), commercially known as "Chlorella growth factor", is the unique one that makes Chlorella more precious than the other algae, and the market price of CE is high. It is believed that CE is effective in growth promotion and immunoregulation. However, there is no systematic analysis on the research status of CE and its bioactivity. The present report summarized recent research progress of CE and its bioactivity. Generally, besides the main effect on immunoregulation and tumor inhibition, CE was efficient in improving metabolic syndrome, scavenging for free radicals, protecting against ultraviolet damage, chelating heavy metals, and protecting liver and bowel. Several major challenges in CE research as well as its prospects were also analysed in the present report.
Biofuels ; Chlorella ; chemistry ; Humans ; Lipids ; chemistry ; Plant Extracts ; chemistry ; pharmacology ; Water

Objective To observed the expression of serum TNF-α and IL-10 in rats with severe acute pancreatitis (SAP) at different altitudes,and to explore the relationships between TNF-α and IL-10,the pathological changes of the pancreas,and the experimental basis for clinical diagnosis and treatment of SAP.Methods 72 specific pathogen free (SPF) Wistar male rats were divided randomly into three groups:1 500 meters altitude (group L),3 300 meters altitude (group M),and 4 300 meters altitude (group H).These three groups were then each divided randomly into four subgroups:control (group n),6 hours after pancreatitis (group p 6 h),12 hours after pancreatitis (group p 12 h),and 24 hours after pancreatitis (group p 24 h).Pancreatitis was induced by intraductal administration of 5％ sodium taurocholate hydrate (NaTc).The rats were killed at 6,12,and 24 hours after NaTc injection in groups p.The group n rats were killed after 6 hours of pancreas observation.Blood samples and pancreatic tissues were collected post mortem and enzyme-linked immunosorbent assay (ELISA) measured serum TNF-α and IL-10.Results Compared with the control (group n),histopathological scores,IL-10,and TNF-α in the same altitude had a significant difference (P ＜ 0.05) in group p at each time point.In the same altitude of group p,histopathological scores and IL-10 were increased with time elapsed (P ＜ 0.05),while TNF-α was decreased with time elapsed (P ＜ 0.05).There was a significant difference between group Mp and Lp in histopathological scores,IL-10,and TNF-α (P ＜ 0.05),and the same result between group Hp and Lp (P ＜ 0.05),but there was no significant difference between group Hp and Mp (P ＜ 0.05).Meanwhile,IL-10 had a positive relationship with histopathological score,but TNF-α had a negative relationship with histopathological score.Conclusions The level of TNF-α increased with increasing altitude but significantly reduced with elapsed time.The level of IL-10 increased with both increasing altitude elapsed time.These results suggested that TNF-o and IL-10 might play a important role at different times in severe acute pancreatitis.