Objective To investigate the effect and its mechnism of ubiquitin ligase cullin3 (CUL3) on the proliferation, migration and invasion of gastric cancer cells. Methods The expression of CUL3 in gastric cancer and adjacent tissues and its relationship with clinical prognosis were analyzed based on TCGA database. HGC-27 and BGC-823 cells were transfected with CUL3 shRNA and empty lentivirus to construct a CUL3 knockdown gastric cancer cell line group (shCUL3 group) and an empty lentivirus transfection group (Vector group). CCK-8 assay, clone formation assay, EdU staining, scratch assay and Transwell assay were used to detect the changes of proliferation, migration and invasion ability of the two groups; Western blotting was used to detect the expression of epithelial-mesenchymal transition (EMT)-related proteins and PI3K/Akt/GSK3β pathway proteins in two groups;The changes of migration and invasion ability of shCUL3 group were detected after application of PI3K agonist 740 Y-P. Results In the TCGA database, CUL3 was highly expressed in gastric cancer, and was significantly associated with poor prognosis of gastric cancer patients. Compared with Vector group, CCK-8, clone formation assay and EdU staining showed that the proliferation of gastric cancer cells in shCUL3 group was inhibited (P<0.05), and CUL3 shRNA could significantly inhibit cell migration and invasion (P<0.05); In addition, compared with Vector group, the expression of E-cadherin protein in shCUL3 group increased, and the protein levels of vimentin, β-catenin, p-PI3K, p-Akt and p-GSK-3β significantly decreased (P<0.05); In contrast, application of the PI3K agonist 740 Y-P could partially reverse the inhibitory effect of CUL3 shRNA on gastric cancer cell migration and invasion. Conclusions Knockdown of CUL3 can inhibit the proliferation, migration and invasion of gastric cancer cells, and the mechanism of action of CUL3 in gastric cancer may be related to the activation of PI3K/Akt/GSK3β signaling pathway.

Chronic obstructive pulmonary disease (COPD) is one of the most common comorbidities in patients with atrial fibrillation, and the both diseases share a series of common risk factors. COPD promotes the occurrence and development of atrial fibrillation by variety of pathophysiological mechanisms, is the important factor affecting the prognosis of patient with atrial fibrillation, and results in an elevation of clinical adverse and cardiovascular death events. Atrial fibrillation also affects the treatment strategy and prognosis of COPD patients. Treatment plan for patients with both atrial fibrillation and COPD faced huge challenging.The research findings of home and abroad related to atrial fibrillation complicated with COPD were summarized in present paper from the aspects of epidemiology, pathophysiology mechanism, patient management, outcome and prognosis, in order to provide help for the integrated multidisciplinary management and individualized treatment for these patients.

Liver transplantation is currently an effective treatment for end-stage liver disease. Postoperative infection is the main important cause of death in patients after liver transplantation. Due to the lack of specificity of clinical symptoms of postoperative infections, further insight is needed into the incidence, risk factors, diagnosis and treatment of different infections, including bacterial, fungal and viral. In addition, it could reduce the perioperative mortality that understanding the characteristics of changes in immune function after liver transplantation and timely prevention and treatment of post-transplant complications of infection, which would ultimately improve the outcome of patients. Nowadays, the use of immune-supporting drugs such as thymosin α₁, intravenous immunoglobulin and ulinastatin have also shown some efficacy in patients with post-transplant infections.This article reviews the characteristics of infection, the changes of immune function and the feasibility of immunosupportive therapy after liver transplantation.

Objective To evaluate the application value of extended non-invasive prenatal genetic testing (NIPT-plus) in prenatal screening. Methods All the NIPT-plus data were collected from Zhujiang Hospital of Southern Medical University and the Seventh Affiliated Hospital of Southern Medical University from January 2018 to June 2021. The abnormal results of NIPT-plus were validated by fetal chromosome examination through amniocentesis. The positive predictive value and negative predictive value of NIPT-plus were analyzed, and the fetal prognosis was followed up. Results A total of 2191 cases were detected, and 38 cases were abnormal (positive rate was 1.7%), among which 6 cases were chromosomal copy number variation. A total of 31 cases were confirmed by amniocentesis, of which 18 cases were consistent with the results of NIPT-plus. The total positive predictive value of NIPT-plus was 58.1%, and the negative predictive value was 100.0%. There were 5 cases of chromosome copy number variation for prenatal diagnosis, of which 3 cases were consistent with the results of NIPT-plus test and the positive predictive value was 60.0%. Conclusion The use of NIPT-plus in prenatal screening has a certain warning value for pregnant women with risk of fetal chromosomal abnormalities.

Gastric cancer is the third leading cause of death from malignancy and the fifth most common malignancy in the world. The development and progression of intestinal-type gastric cancer is in accordance with the "Correa model", in which gastric mucosal intestinal metaplasia (GIM) is the key link in the transformation of the gastric mucosa from benign to malignant and is also one of the most common precancerous lesions of gastric cancer, therefore, it is the key to investigate the pathogenesis of GIM and intervene it at an early stage for the prevention and treatment of gastric cancer. Helicobacter pylori (HP) infection is considered as one of the recognized risk factors for GIM. However, GIM cannot be reversed by eradication of HP alone, considering that there may be other factors that continue to play a role in the development and progression of GIM. In recent years, it has been confirmed in several studies that bile reflux can induce GIM, but the specific molecular mechanism by which bile reflux induces GIM is not clear.The mechanism of bile reflux induced gastric mucosal injury, the relationship between GIM and gastric cancer, the research status of bile reflux induced GIM, and the molecular mechanisms of bile acid induced GIM are discussed in this article, aiming to improve clinicians' understanding of GIM induced by bile reflux and provide a basis for the early intervention of GIM and prevention of gastric cancer.

Objective To investigate the clinical application value of chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) in fetuses with increased nuchal translucency (NT). Methods From January 2020 to April 2022, clinical data of 1013 fetuses were collected who underwent invasive prenatal diagnosis due to NT thickening [defined as NT ≥95th centile for the crown-rump length (CRL)] in the Third Affiliated Hospital of Zhengzhou University. All fetuses were undergone CMA detection, 49 fetuses with negative CMA results underwent further prenatal WES. According to NT value, fetuses were divided into the following four groups: <3.5 mm group (529 cases, 21 cases underwent WES), 3.5-4.5 mm group (273 cases, 8 cases underwent WES), 4.5-5.5 mm group (98 cases, 7 cases underwent WES), and ≥5.5 mm group (113 cases, 13 cases underwent WES). According to the results of ultrasound examination, all fetuses were divided into structural malformation group (88 cases, 23 cases underwent WES) and isolated increased NT group (925 cases, 26 cases underwent WES). The possible chromosomal anomalies were analyzed by CMA first. Furthermore, 49 cases with increased NT but negative CMA results were investigated by WES, and the outcomes were followed up. Results CMA showed that, among the 1013 cases of NT thickened fetus, 224 cases (22.1%) of causative genetic defects were detected, including 182 (18.0%) cases with chromosomal aneuploidy and 42 (4.1%) cases with pathogenic copy number variation (pCNVs). Among different NT value groups, the positive rate of CMA in NT ≥5.5 mm group was the highest (47.8%). In addition, the positive rate of CMA in fetuses with increased NT and structural malformations was higher than in isolated increased NT (45.5% vs. 19.9%). WES detected monogenic disease in 5 of 49 fetuses (10.2%) with increased NT and negative CMA results, including 3 cases of autosomal dominant disease, 1 case of autosomal recessive hereditary disease and 1 case of X-linked recessive hereditary disease. All the five fetuses had structural malformations, two of them with increased NT <3.5 mm, and only one of them was born alive. Conclusion WES can detect out monogenic disease in fetuses with increased NT combined structural malformations with negative CMA results. Fetuses with increased NT should also be alert for the possibility of monogenic disease even if the NT value less than 3.5 mm.

Objective To investigate the effect of macrophage inflammatory protein-1α (MIP-1α) on proliferation, migration and osteo-differentiation of human periodontal stem cells (hPDLSCs) and its possible mechanism. Methods A total of 16 healthy teeth (orthodontic minus premolar or blocked third molar) extracted from patients aged 12 to 25 years attending the outpatient clinic of the Department of Stomatology, the Second Affiliated Hospital of Xinjiang Medical University from November 2020 to October 2021 were collected and primary stem cells were cultured by tissue block method combined with enzymatic digestion, and the cell phenotype was identified by flow cytometry. (1) Cell biological characteristics experiment: the 3rd generation hPDLSCs were divided into 0 (control group), 1 and 10 μg/ml MIP-1α groups, and each group was then added with α-MEM medium containing volume fraction of 10% fetal bovine serum, 100 U/ml penicillin, and 2 mmol/L glutamine, respectively, and the proliferation ability of each group was detected by CCK-8 method after 24, 48 and 72 h of intervention. The lateral migration ability of cells in each group was detected by scratch assay after 24 h of intervention. (2) Effect and possible mechanism of osteo-differentiation: 3rd generation hPDLSCs were divided into 0 (control group) 1 and 10 μg/ml MIP-1α groups, and osteogenic induction solution was added to each group, and osteogenic ability of cells was detected by alkaline phosphatase (ALP) staining and semi-quantitative analysis 7 d after intervention and by alizarin red staining and semi-quantitative analysis 14 d after intervention;osteogenic ability of cells was detected by qRT-PCR and Western blotting. The mRNA and protein expression of osteogenic genes Runt-related transcription factor 2 (Runx2), bone bridge protein (OPN) and transcription factor SP7 (Osterix) and Notch1 receptor,Jagged 1 ligand and downstream factor Hey1 were detected by qRT-PCR and Western blotting 7 d after intervention. Results Flow cytometry results showed that hPDLSCs STRO-1 and CD146 showed positive expression, and CD34 showed negative expression.(1) In the experiment of cell biological characteristics, the results of CCK-8 method showed that the differences in OD values of hPDLSCs were not statistically significant (P>0.05) in 1 μg/ml and 10 μg/ml MIP-1α groups at 24 h and 48 h compared with control group; at 72 h, the differences in OD values of hPDLSCs were not statistically significant (P>0.05) in 1 μg/ml MIP-1α group compared with control group, while the differences in OD values of hPDLSCs in 10 μg/ml MIP-1α group were significantly higher (P<0.05). The results of scratch assay showed that the difference of scratch healing rate of cells in 1 μg/ml MIP-1α group was not statistically significant compared with that in control group (P>0.05), while the scratch healing rate of 10 μg/ml MIP-1α group was significantly higher (P<0.05). (2) In the experiments of the effect of osteo-differentiation and possible mechanism, ALP staining and semi-quantitative results showed that the ALP activity was obviously lower in 1 μg/ml and 10 μg/ml MIP-1α groups than that in control group (P<0.05). The results of alizarin red staining and semi-quantification showed that the number of mineralized nodules in 1 μg/ml and 10 μg/ml MIP-1α groups were significantly less than that in control group (P<0.05). qRT-PCR and Western blotting results showed that the osteogenesis-related genes Runx2, OPN and Osterix mRNA and protein expression levels in 1 μg/ml MIP-1α group of hPDLSCs were not statistically significant compared with control group, while those in the 10 μg/ml MIP-1α group were significantly lower (P<0.05). Notch1 mRNA and protein expression levels in 1 μg/ml and 10 μg/ml MIP-1α groups were significantly lower than those in control group (P<0.05); Jagged1 and Hey1 mRNA and protein expression levels in 10 μg/ml MIP-1α group were lower than those in control group (P<0.05). while the differences were not statistically significant in the 1 μg/ml MIP-1α group (P>0.05). Conclusion MIP-1α can promote proliferation and inhibit the osteo-differentiation of hPDLSCs, and the mechanism may be related to the inhibition of Notch signaling pathway activation.

Objective To investigate the clinical application value of chromosome karyotype combined with chromosome microarray analysis (CMA) on genetic diagnosis of embryo termination in early pregnancy. Methods The clinical information and embryo termination tissues were collected of 194 patients treated in the Prenatal Diagnosis Center of the Fourth Hospital of Shijiazhuang due to early embryo abortion from June 2019 to June 2020. Traditional chromosome karyotype analysis and CMA analysis were used for chromosome analysis of the enrolled embryos, and carry out genetic traceability test, summarize and analyze chromosome karyotype/CMA results in combination with embryo chromosome test results. Results (1) The average age of all enrolled patients was 34.1 (22-45) years, of them 120 cases (61.9%) were older than 35 years; The average gestational age was 9.75(7-14) weeks, of which 144 cases (74.2%) were with gestational age less than 10 weeks. Among 101 pregnant women (52.1%, 101/194) with adverse pregnancy and childbirth history, 79 cases (78.2%) had a history of embryo termination, and 22 cases had a history of spontaneous abortion (21.8%). (2) Among 124 cases with abnormal karyotype (63.9%, 124/194), 89 cases (71.8%)had trisomy, 15 cases (12.1%) had monosomy, 11 cases (8.9%) had triploidy, 8 cases (6.4%) had chimera, and 1 case (0.8%) had abnormal structure. (3) Among 33 cases of CMA test results, 9 cases of pathogenic, 2 cases of suspected pathogenic, 1 case of benign, and 21 cases of unknown clinical significance (VUS). The combination of CMA increased the detection rate of chromosomal variants by 4.6%. Among 124 cases of abnormal karyotype, 17 cases were associated with abnormal chromosome microstructure (3 cases were pathogenic, 1 case might be benign, and 13 cases were VUS). (4) The results of parental chromosome test showed that 4 cases of polymorphic chromosome changes and 4 cases of abnormal karyotype; Verification and comparison results in 33 couples with chromosome microstructure variation displayed that 1 case of benign and 1 case of VUS were inherited from the mother, and no chromosomal microstructural variation was detected from the other cases. Conclusion Traditional chromosome karyotype technology combined with CMA can effectively improve the detection rate of chromosome variation, and has certain reference value for guiding the future pregnancy.

Objective To investigate the role of Toll-like receptor 4 (TLR4) in cardiac function injury of rats with heat stroke disease by regulating myocardial ferroptosis. Methods (1) 24 SD rats were randomly divided into control group and heat stroke disease (HS) group (12 in each group). During heat attack, anal temperature of rats was measured by anal thermometer, heart rate and mean arterial pressure of rats were measured by BL-420F biological function experiment system. (2) 24 SD rats were randomly divided into control group, ferroptosis inhibitor (Liproxstatin-1) group, HS group and HS+Liproxstatin-1 group (6 in each group). Thirty minutes before modeling, rats in Liproxstatin-1 group and HS+Liproxstatin-1 group were intraperitoneally injected with Liproxstatin-1 (10 mg/kg). The expression of solute carrier family 7 member 11 (SLC7A11) in myocardial tissue was detected by immunofluorescence staining, and the expression levels of SLC7A11 and glutathione peroxidase 4 (GPX4) were detected by Western blotting. (3) 48 SD rats were randomly divided into control group, TLR4 inhibitor (TAK-242) group, HS group and HS+TAK-242 group (12 in each group). Thirty minutes before modeling, rats in TAK-242 group and HS+TAK-242 group were intraperitoneally injected with TAK-242 (3 mg/kg). The expression of TLR4 in myocardial tissue was detected by immunofluorescence staining, cardiac hemodynamic indexes [left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), maximum rate of increase (+dp/dt_max) and maximum rate of decrease (–dp/dt_max) of left ventricular pressure] were detected by BL-420F biological function experiment system, cardiac function indexes [cardiac output (CO), diastolic left ventricular posterior wall thickness (LVPWd) and systolic left ventricular posterior wall thickness (LVPWs)] were detected by cardiac ultrasound, the expression levels of TLR4/NF-κB-p53 signaling pathway protein [TLR4, nuclear factor kappa B (NF-κB), p53] and ferroptosis related protein (SLC7A11 and GPX4) were detected by Western blotting. Results Compared with control group, the core body temperature and heart rate of rats in HS group increased significantly after heat shock for 180 minutes (P<0.01), the mean arterial pressure decreased significantly (P<0.05). Immunofluorescence staining results showed that compared with control group, the expression of myocardial SLC7A11 in HS group significantly decreased (P<0.01); Compared with HS group, the expression of SLC7A11 in HS+TAK-242 group improved significantly (P<0.01). The results of Western blotting showed that compared with control group, the expression levels of SLC7A11 and GPX4 in myocardium of HS group decreased significantly (P<0.05); Compared with HS group, the expression levels of SLC7A11 and GPX4 in HS+Liproxstatin-1 group improved significantly (P<0.05). Immunofluorescence staining results showed that compared with control group, the expression level of myocardial TLR4 in HS group increased significantly (P<0.01); Compared with HS group, the expression level of TLR4 in HS+TAK-242 group improved significantly (P<0.01). The results of BL-420F biological function test system showed that compared with control group, LVEDP increased, LVSP decreased (P<0.01) in HS group. LVSP, LVEDP, +dp/dt_max and –dp/dt_max were improved in HS+TAK-242 group (P<0.05). Compared with control group, CO was significantly decreased, and LVPWd and LVPWs were increased in HS group (P<0.01). Compared with HS group, CO increased, and LVPWd and LVPWs decreased in HS+TAK-242 group (P<0.05). Western blotting results showed that compared with control group, the expression levels of TLR4, NF-κB and p53 in the HS group increased significantly (P<0.01), and of SLC7A11 and GPX4 decreased significantly (P<0.01); Compared with HS group, the expression levels of TLR4, NF-κB and p53 decreased significantly, and of SLC7A11 and GPX4 increased significantly (P<0.05) in HS+TAK-242 group. Conclusion Ferroptosis may exist in myocardial injury caused by heat stroke. Inhibition of TLR4 can improve cardiac function of rats with heatstroke, and the mechanism may be related to ferroptosis mediated by TLR4/NF-κB-p53/SLC7A11 signaling pathway.

Fecal microbiota transplantation (FMT) is becoming a new approach for dysbiosis conditions. It means that fecal microbiota from healthy donors could be transplanted into the recipient's digestive tract, to modulate their tissue and organ function and intestinal microecology, thus gaining a therapeutic effects for dysbiosis disorders. The FMT rescue program aims to provide standard FMT technology and products to military institutions for treating antibiotic-associated diarrhea like clostridium difficile infection (CDI) and other dysbiosis conditions with the FMT indication. The program contents include the purpose, the application scope, the process and technology for rescue use, the composition and responsibility of institutions, etc.