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 understand the thyroid function of the physical examination population in Tangshan area, and analyze the effects of thyroid function on blood lipids, fasting blood glucose (FPG), and serum 25 hydroxyvitamin D [25(OH)D].Methods:A population from the Tangshan area who underwent physical examinations at the Kailuan General Hospital from June 2020 to June 2021 was selected as the study subjects and the levels of their thyroid serological indicators [thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), triiodothyronine (TT3), and thyroid hormone (TT4)] were tested. According to thyroid function, they were divided into normal group, hyperthyroidism group, hypothyroidism group, subclinical hyperthyroidism group, and subclinical hypothyroidism group. We compared the blood lipid indicators [triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)], FPG, and 25(OH)D levels in different subgroups, and the Pearson correlation analysis was used to investigate the correlation between TSH levels and blood lipids, FPG, and 25(OH)D levels.Results:In this study, 2 884 subjects were selected from the physical examination population in Tangshan area. The proportion of people with abnormal thyroid function was 12.03%(347/2 884), among which the proportion of subclinical thyroid function abnormal population in the total thyroid function abnormal population was 80.69%(280/347). As men age, the proportion of thyroid dysfunction in the age groups of 21-<30 years old, 30-<40 years old, 40-<50 years old, and ≥50 years old was 5.06%(4/79), 7.52%(33/439), 8.91%(53/595), and 9.95%(66/663), respectively. The proportion of thyroid dysfunction in the above age group of women was 14.02%(15/107), 15.06%(61/405), 15.47%(67/433), and 29.45%(48/163). The serum TG, TC, LDL-C, and 25(OH)D levels in the hyperthyroidism group were lower than those in the normal group, while HDL-C and FPG levels were higher than those in the normal group, with statistically significant differences (all P<0.05). The serum TG and TC in the hypothyroidism group were higher than those in the normal group, while FPG and 25(OH)D were lower than those in the normal group, with statistically significant differences (all P<0.05). TSH levels were positively correlated with TC and LDL-C, while negatively correlated with FPG and 25(OH)D (all P<0.05). Conclusions:Subclinical thyroid dysfunction is the main cause of thyroid dysfunction in the Tangshan area, and TSH levels are correlated with blood lipids, fasting blood glucose, and serum 25(OH)D levels.

Renal interstitial fibrosis （RIF） is the main pathological feature of chronic kidney disease caused by a variety of factors. "Kidney deficiency and blood stasis in collateral， miniature mass of renal collateral" is the main pathogenesis of RIF. The deficiency of healthy Qi will influence the kidney Qi， resulting in kidney deficiency and unsmooth qi transformation. As a result， phlegm， heat， stasis， toxin and other excess pathogens block the kidney collaterals， forming miniature masses. The masses accumulate in the renal collaterals， finally leading to RIF. Autophagy is a key process that keeps your body's cells in proper balance by taking aged or damaged components in a cell and recycling them. It is involved in the occurrence and development of RIF. The metabolism of excess pathogens such as phlegm， heat， stasis， and toxin in vivo is related to the degradation and reabsorption of autophagy. Autophagy is a way to eliminate phlegm， heat， stasis， toxin and other excess pathogens. Autophagy dysfunction will cause the accumulation of phlegm， heat， blood stasis， toxin and other excess pathogens， further the stasis of the kidney collaterals， miniature mass in kidney， and finally RIF. Kidney deficiency and blood stasis in collateral are the root cause of autophagy dysfunction， and the miniature mass of renal collateral is the manifestation of autophagy dysfunction. Autophagy dysfunction and miniature mass of renal collateral have the same pathological evolution. In this paper， based on the pathogenesis of "kidney deficiency and blood stasis in collateral， miniature mass of renal collateral" of RIF and RIF-autophagy relationship， this paper discusses the "kidney deficiency and blood stasis in collateral-autophagy dysfunction-miniature mass of renal collateral" relationship in RIF and comprehensively interprets the scientific connotation of the pathogenesis of "kidney deficiency and blood stasis in collateral， miniature mass of renal collateral"， which is expected to lay a basis for explaining the role of autophagy in TCM theory and for the treatment of RIF and research on the mechanism.

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 study the expression of Proline rich protein11 (PRR11) in breast cancer and its relationship with clinical biological behavior, prognosis and survival.Methods:A prospective analysis method was used to select 80 patients with breast cancer from Jan. 2018 to Jan. 2019. Immunohistochemical S-P method was used to detect the expression of PRR11 in cancer tissues. Patients with positive expression of PRR11 were set as the study group ( n=47) and the patients with negative expression of PRR11 were set as the control group ( n=33) . All patients were followed up for 3 years to analyze and compare the survival rates of patients with positive and negative expression of PRR11. The relationship between PRR11 expression and clinical biological behavior, prognosis and survival was analyzed by Cox risk ratio review model. Results:80 patients were followed up for 3 years. It was found that the prognosis of patients with negative PRR11 expression was significantly better than that of patients with positive PRR11 expression ( χ2=5.75, P<0.001) . Chi square test was used to analyze the correlation between the expression of PRR11 and tumor size, TNM stage, lymph node metastasis, distant metastasis, histological grade, Ki67 expression and hormone receptor status ( P<0.05) . The expression of PRR11 in breast cancer tissues with larger tumors, distant metastasis and later staging was relatively high ( P<0.05) . Univariate Cox regression analysis showed that histological grade, TNM stage and PRR11 were independent risk factors affecting the prognosis of breast cancer patients ( P<0.001) . The AUC of prognosis prediction in patients with breast cancer was 0.812, and the 95% CI was 0.635-0.796. When PRR11 expression was positive, the sensitivity was 81.47%, and the specificity was 85.57%. Conclusions:The expression of PRR11 is relatively high in the late stage breast cancer tissue. The expression of PRR11 is closely related to the clinical biological behavior of breast cancer size, TNM stage and lymph node metastasis. The survival rate of patients with high PRR11 expression is low, and the positive expression of PRR11 is an independent risk factor affecting the prognosis of breast cancer patients. PRR11 detection has preferable clinical application value in predicting the prognosis of breast cancer.

Renal interstitial fibrosis（RIF）is a common pathway for the progression of chronic kidney disease to renal failure，and its pathogenesis is mainly related to renal inflammatory damage，oxidative stress，apoptosis，and excessive extracellular matrix（ECM） deposition. Transforming growth factor-β₁（TGF-β₁） signaling pathway，mammalian target of rapamycin（mTOR） signaling pathway and other signaling pathways mediate the occurrence and development of RIF. Because of the complicated mechanism of RIF，there have been no specific prevention and treatment measures in clinical practice. Autophagy is a non-damaging response produced by eukaryotic cells. It maintains the balance of tissue homeostasis through degradation and reabsorption. At present， Chinese medicine has achieved desirable clinical effects with its unique advantages of multiple components，multiple effects，and multiple targets in the treatment of chronic kidney disease to delay the process of RIF. Scholars have found that autophagy is consistent with the Yin-Yang theory and the theory of abdominal mass in traditional Chinese medicine （TCM） to a certain extent，and it is involved in many aspects of RIF. The progression of RIF is closely related to autophagy. The targeted therapy of RIF by intervention in autophagy has become the frontier of research. However，little is known about the role of autophagy in RIF and the regulation of autophagy by Chinese medicine in the treatment of RIF. Therefore，it is necessary to further elucidate the relationship between autophagy and RIF in order to clarify the mechanism of autophagy in RIF and the mechanism of Chinese medicine regulating autophagy in targeted therapy of RIF. This article focused on the correlation between autophagy and RIF based on TCM theory，and systematically summarized the role of autophagy in RIF and the intervention of Chinese medicine by combining the effects of autophagy on inflammation damage，oxidative stress，apoptosis，and excessive ECM deposition in RIF， and the regulation mechanism of autophagy in TGF-β₁ and mTOR signaling pathways in RIF. This study was expected to provide a certain reference for the clinical treatment of RIF and the development of new drugs.

Chronic renal failure （CRF）， a common outcome of various chronic kidney diseases， is characterized by retention of metabolites and toxins， water-electrolyte imbalance， acid-base disturbance， and various symptoms in diverse systems. The incidence and progression of this disease are influenced by many factors， particularly the change of intestinal flora. Previous research shows that the intestinal flora interacts with CRF. For CRF patients， the metabolic waste fails to be cleared in time due to the gradual decline of renal function and thus accumulates in vivo. Moreover， CRF changes the composition of intestinal flora， damages intestinal barrier， and accelerates the synthesis of intestinal uremic toxins and the accumulation in blood. As a result， the renal injury is aggravated. The imbalance of intestinal flora can induce acute kidney injury， increase cardiovascular complications， stimulate immune inflammatory responses， and thus aggravate the progression of CRF. Microbiota-targeted therapy for CRF has become the research focus. According to traditional Chinese medicine， kidney disease is related to the intestine and kidney disease should be treated from the intestine. Spleen and kidney are in the closest relationship with the pathogenesis of CRF and the intestinal flora. Chinese medicine， which features multiple targets， multiple effects， and multiple components， acts on the "gut-kidney axis". It is thus superior in the clinical treatment of CRF and the regulation of intestinal flora. To be specific， it intervenes in intestinal flora to delay the process of CRF. In this paper， based on the correlation of traditional Chinese medicine theory with intestinal flora and CRF， this paper reviewed the interaction between intestinal flora and CRF and traditional Chinese medicine intervention in the intestinal flora for the treatment of CRF， which is expected to serve as a reference for the clinical treatment of this disease and the drug development.

Objective:To explore the effect of multiple intelligences theory combined with the analysis, design, development, implementation, and evaluation (ADDIE) model in surgical clinical practice teaching.Methods:A total of 100 residents trained in Department of Gastrointestinal Surgery of Heping Hospital Affiliated to Changzhi Medical College from July 2019 to April 2020 were randomly divided into the control group ( n=50) and the observation group ( n=50). The control group used the ADDIE model, and the observation group adopted the multiple intelligences theory combined with the ADDIE model. The teaching assessment of the two groups was compared, and the core competence, critical thinking ability, self-evaluation, and teaching satisfaction of the two groups were evaluated. SPSS 22.0 was used for Chi-square test and t-test. Results:The scores of basic knowledges of gastrointestinal surgery, surgical clinical thinking and case analysis, routine skills and operations, and the total scores in the observation group were higher than those in the control group ( P<0.05). The scores of professional knowledge and skills, patient safety and rights, scientific research and academic ability, professional ethics, teamwork, personal and professional development ability in the observation group were higher than those in the control group ( P<0.05). While, there was no significant difference in the mastering of knowledge between the two groups ( P>0.05). The four dimensions of learning interest, self-learning ability, innovation ability, and clinical thinking establishment in the observation group were higher than those in the control group ( P<0.05). Conclusion:Multiple intelligences theory combined with ADDIE model in surgical clinical practice teaching can improve the teaching assessment results, significantly enhance the core competence, stimulate the learning interest, cultivate the self-learning ability and innovation ability of residents, and help them to establish clinical thinking ability.