Abstract:Objective：To investigate the effects of doxycycline on in vitro osteogenic differentiation of pro - osteoblasts cell line MC3T3-E1 and the possible mechanisms. Methods：Alizarin red staining was employed to detect the osteogenic differentiation. Real- time PCR was used to detect the effect of DOX on the expression of OCN and Runx2 in MC3T3-E1 cells. MC3T3-E1 cells were treated with either DOX，MEK inhibitor U0126 alone or in combination，and the levels of N-cadherin，p-MEK and p-ERK were detected by Western blot. Results：When DOX was added during osteogenic induction，alizarin red staining positivity of the cultured MC3T3-E1 was significantly enhanced. DOX increased the expression of OCN and Runx2 in MC3T3-E1 cells. Besides，DOX decreased the levels of N - cadherin and increased the level of p -MEK and p - ERK in MC3T3 - E1(P ＜ 0.05). On the contrary，MEK antagonist U0126 significantly increased the expression of N-cadherin protein and decreased the levels of p-MEK and p-ERK(P ＜ 0.05). When MC3T3-E1 cells were treated with DOX in the presence of MEK inhibitor U0126，the changes in N-cadherin，p-MEK and p-ERK were showed to be reversed comparing with DOX alone. When both U0126 and DOX were present during in vitro osteogenic differentiation of MC3T3-E1， alizarin red staining positivity was less observed than that of DOX alone. Conclusion：In this study，DOX is showed to enhance the in vitro osteogenic differentiation of MC3T3-E1，which is probably associated with MEK/ERK signaling pathway.

Abstract:Objective：To investigate the mechanism of yes - associated protein(YAP)in promoting the migration and invasion of hepatocellular carcinoma cells through regulating the expression of eukaryotic translation elongation factor 1 alpha 2(EEF1A2). Methods：YAP and EEF1A2 were knockdown or overexpressed in human hepatocellular carcinoma(HCC)cell lines(SMMC-7721 and SK - HEP1)respectively. Transwell assays were performed to examine the changes of the migratory and invasive ability of the HCC cells. Reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR)and Western blot were conducted to evaluate the expression of the indicated genes in HCC cells. Cleavage under targets and release using nuclease(CUT&RUN)-qPCR assay was performed to evaluate whether YAP interacts with the promoter of EEF1A2. Results：Upregulation of EEF1A2 was shown in HCC tissues，and the expression of YAP and EEF1A2 was positively correlated with the spontaneous migratory potential of HCC cell lines. EEF1A2 facilitated the migration and invasion of the low migratory potential SMMC7721 cells and the high migratory potential SK-HEP1 cells and regulated the expression of Snail and E-cadherin，which are two well-characterized epithelial-mesenchymal transition(EMT) markers. The results further showed that YAP regulated HCC cell migration and invasion by up - regulating EEF1A2. In addition， CUT&RUN-qPCR analysis demonstrated YAP occupancy at the promoter of the EEF1A2 in HCC cells. Conclusion：YAP up-regulates the expression of EEF1A2 through interacting with the sequence on the promoter of the EEF1A2，and subsequently promotes HCC cell migration and invasion.

Abstract:Objective：To study the gene expression characteristics of renal tubular epithelial cells under oxidative stress caused by caspase-3 inhibitors via screening the potential candidate genes，which will lay the foundation for revealing the mechanism of caspase-3 regulating ROS injury in renal tubular epithelial cells. Methods：The renal tubular epithelial cells HK-2 were treated with H₂O₂ at a final concentration of 300 μmol/L for 6 h，and then randomly divided into control group and caspase-3 inhibitor group(Ac-DEVD-CHO， 15 μmol/L). The sequencing was completed by using the Illumina Hiseq 2500 platform. Enrichment analysis and an interaction network were performed to screen differential genes. Quantitative PCR was used to verify the first 10 differentially expressed genes (DEGs). The HK-2 cells treated with H₂O₂ (300 μmol/L)for 6 h were then divided into control group，caspase-3 inhibitor group (Ac-DEVD-CHO，15 μmol/L)，CTNNB1 group(pcDNA3.1(+)-CTNNB1)，caspase-3 inhibitor+CTNNB1 group(Ac-DEVD-CHO， 15 μmol/L+pcDNA3.1(+)-CTNNB1)and caspase -3 inhibitor+CTNNB1 NC group(Ac -DEVD -CHO，15 μmol/L+pcDNA3.1(+)- CTNNB1 NC)randomly. MTT assay was used to detect cell proliferation，flow cytometry was used to detect cell apoptosis and ROS level，Western blot was used to detect apoptosis-related proteins. Results：A total of 185 DEGs were selected in the control group and the caspase-3 inhibitor group. Quantitative PCR showed FIS1，EZR，COL7A1，RPL5，MAP4，CEBPB and CTNNB1 mRNA were lowly expressed(all P ＜ 0.05)and SNRPB mRNA was highly expressed in caspase-3 inhibitor group(P ＜ 0.05). The proliferation was higher in the caspase -3 inhibitor group and was lower the CTNNB1 group compared to the control(both P ＜ 0.05). The proliferation of the caspase-3 inhibitor+CTNNB1 group was lower than that of the caspase-3 inhibitor group(P ＜ 0.05)，but still higher than the control (P ＜ 0.05). The apoptosis and the expression of cleaved-caspase-3 and cleaved-PARP were lower in caspase-3 inhibitor group and were higher in CTNNB1 group compared to the control(both P ＜ 0.05). The apoptosis and the expression of cleaved-caspase-3 and cleaved-PARP in caspase-3 inhibitor+CTNNB1 group were higher than those in the caspase-3 inhibitor group(P ＜ 0.05)，but were still lower than the control(P ＜ 0.05). The ROS in the caspase-3 inhibitor group was lower but was higher in CTNNB1 group compared to that of the control group(P ＜ 0.05). The ROS in the caspase-3 inhibitor+CTNNB1 group was higher than that of the caspase-3 inhibitor group(P ＜ 0.05)，but was still lower than the control(P ＜ 0.05). Conclusion：Aberrant gene expression induced by caspase-3 inhibitor is associated with renal injury under oxidative stress. The injury of oxidative stress on renal tubular epithelial cells is caspase - 3 dependent. Inhibition of caspase-3 has a protective effect on renal injury and CTNNB1 is involved in this process.

Abstract:Objective：We used enterotoxigeni Escherichia coli(ETEC)to build the diarrhea model induced by intestinal flora dysfunction. Then the probiotics Akkermansia muciniphila(A. muciniphila)was used to analyze the protective effect in the diarrhea. Methods：The diarrhea model of mice was induced by ETEC. The experimental mice were randomly divided into PBS group，ETEC model group and A. muciniphila treatment group. Each mouse of the A. muciniphila treatment group was treated with A. muciniphila solution(1×10⁹ CFU/mL)0.2 mL/d for 5 days，and the model group was gavaged with ETEC solution(concentration 1×10⁹ CFU/mL) 0.5 mL/d for 5 days. The changes of physical condition，body weight，diarrhea rate and mortality of mice were recorded；the pathological changes of colon tissue were observed using HE staining；the contents of serum interleukin(IL)-1β，IL-6 and tumor necrosis factor-α (TNF-α)were detected using ELISA method；the expression of IL-1，TNF-α and IL-6 mRNA in colon tissue were detected by RT-PCR； and the feces of mice were collected for 16S rRNA high-throughput sequencing and statistical analysis. Results：Compared with the ETEC model group，the physical condition of the A. muciniphila treatment group was significantly improved，the diarrhea rate was reduced by 66%，the mortality rate was reduced by 30%，and the contents of serum IL - 1β，IL - 6 and TNF - α were significantly decreased. The contents of IL-1 mRNA，IL-6 mRNA and TNF-α mRNA in colon tissue were significantly decreased. The pathological changes of colon tissue were significantly improved. 16S rRNA sequencing showed that the relative abundance of species increased significantly，the α diversity and the composition of intestinal microflora changed significantly in the A. muciniphila treatment group. In the A. muciniphila treatment group，the abundance of multiple probiotics increased. Conclusion：Probiotics A. muciniphila can relieve diarrhea caused by ETEC through increasing intestinal flora diversity，protecting colonic mucosa and reducing the expression of inflammatory factors.

Abstract:Objective：To investigate the expression and clinical significance of Casitas B-lineage lymphoma(Cbl)protein family in cervical squamous cell carcinoma(CSCC). Methods：Immunohistochemistry was used to detect the expression of c-Cbl，Cbl-b，and Cbl-c in 114 cases of CSCC. The correlations between c-Cbl，Cbl-b，and Cbl-c expression and clinicopathological characteristics，disease free survival(DFS)and overall survival(OS)were analyzed. Results：Of the 114 CSCC patients，87 had high c-Cbl expression and 27 had low c-Cbl expression；69 had high Cbl-b expression and 45 had low Cbl-b expression；55 had high Cbl-c expression and 59 had low Cbl-c expression. The histochemistry score(H - score)of c -Cbl in CSCC tissues and the adjacent normal tissues was 143.80 ± 8.76 and 95.13 ± 6.54，respectively. c-Cbl expression was increased in CSCC compared with the adjacent normal tissues(P ＜ 0.001). The H-score of Cbl-b in CSCC tissues and the adjacent normal tissues was 83.95 ± 5.28 and 93.54 ± 3.91，respectively. There was no significant difference in Cbl-b expression between CSCC tissues and the adjacent normal tissues(P=0.146). The H-score of Cbl-c in CSCC tissues and the adjacent normal tissues was 83.62 ± 6.34 and 36.54 ± 4.64，respectively. Cbl-c expression was increased in CSCC compared with the adjacent normal tissues(P ＜ 0.001). c-Cbl expression was higher in highly to moderately differentiated tumors and tumors with a maximum diameter less than 4 cm(both P ＜ 0.05)，but it was not related to the patient’s age，vascular invasion，depth of invasion， lymph node metastasis and FIGO stage(all P ＞0.05). Cbl - b expression was higher in patients with invasion depth ＞ 2/3 of fibromuscular layer(P=0.045)，but it was not related to patient’s age，vascular invasion，tumor differentiation，maximum tumor diameter，lymph node metastasis and FIGO stage(all P ＞ 0.05). Cbl-c expression was higher in poorly differentiated tumors(P=0.012)， but it was not related to patient’s age，vascular invasion，depth of invasion，maximum tumor diameter，lymph node metastasis and FIGO stage(all P ＞ 0.05). Kaplan - Meier survival analysis showed that patients with high c - Cbl expression had prolonged DFS and OS compared with those with low c-Cbl protein expression(both P ＜ 0.05). However，the expression levels of Cbl-b and Cbl-c were not related to DFS and OS(P ＞ 0.05). Cox univariate and multivariate analysis showed that c - Cbl expression was an independent prognostic factor for DFS(P=0.042). c -Cbl was a factor affecting OS，but not an independent prognostic factor for OS in CSCC(P= 0.096). Conclusion：Patients with high c -Cbl expression have prolonged DFS and OS compared with those with low c -Cbl protein expression. c-Cbl expression is an independent prognostic factor for DFS，but not an independent prognostic factor for OS in CSCC. The expression levels of Cbl-b and Cbl-c are not related to DFS and OS in CSCC. Detection of the expression status of c-Cbl may provide a reference for predicting the prognosis of CSCC patients.

Abstract:Objective: To explore the correlation between serum interleukin-32 (IL-32) level and the presence and severity of pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD). Methods: Eighty-five CHD patients were enrolled in the experimental group, and these patients were divided into the non-PAH group ( PAPm ≤slant 20 mmHg ), grey area group ( 20 mmHg ＜ PAPm ＜25 mmHg ), mild group (25 mmHg ≤slant PAPm ＜35 mmHg ), and moderate-severe group ( PAPm ≥slant 35 mmHg ) by mean pulmonary artery pressure ( PAPm) measured using right heart catheterization; the control group consisted of 30 healthy adults. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum IL-32 level in various groups, and chemiluminescent microparticle immunoassay (CMIA) was used to measure the plasma B-type natriuretic peptide (BNP) level in the experimental group. Results: Serum IL-32 levels in the moderate-severe, mild, and grey area groups were significantly higher than those in the non-PAH and control groups. The serum IL-32 level in CHD (Qp/Qs ≥slant 1.5 ) patients was significantly higher than that in CHD (Qp/Qs ＜1.5 ) patients. The serum IL-32 level was positively correlated with \operatorname{PAPm}(r=0.377, P＜0.05), pulmonary artery systolic pressure (r=0.286, P＜0.05), and Q p / Qs (r=0.266, P＜0.05). Receiver operating characteristic (ROC) curve analysis found that the performance of IL-32 in the diagnosis of PAH (PAPm ＞20 mmHg ) was non-inferior to BNP, and diagnosis using the combined IL-32 and BNP had higher sensitivity, positive predictive value, and negative predictive value. Conclusion: Serum IL-32 may be a biomarker for PAH associated with CHD.

Abstract:Objective：This study aimed to verify the application values of the Chinese Group on the Study of Severe Hepatitis B (COSSH)acute-on-chronic liver failure(ACLF)Ⅱ score in predicting short-term prognosis and stratifying disease severity in patients with hepatitis B virus - related ACLF(HBV -ACLF). Methods：Clinical data and survival information of 114 patients admitted with HBV-ACLF to the First Affiliated Hospital of Wannan Medical College from January 2017 to December 2021were retrospectively evaluated. Baseline characteristics were compared between the survival group(n=67)and the death group(n=47)at day 90 from inclusion. Prognostic accuracies between the COSSH ACLFⅡ score and the COSSH ACLF score，the Chronic Liver Failure-Consortium(CLIF-C) ACLF score，the CLIF -C organ failure(CLIF -C OF)score，the model of end - stage liver disease(MELD)score，the MELD - sodium (MELD-Na)score，and the Child-Turcotte-Pugh(CTP)score in 90-day mortality prediction were compared using the area under the receiver operating characteristic curve(AUC)method. All patients were divided into three groups according to COSSH ACLF grade (ACLF-1，n=83；ACLF-2，n=23；ACLF-3，n=8)or the risk strata of the COSSH ACLFⅡ score(＜ 7.4，n=82；7.4~ ＜ 8.4，n=21； and ≥8.4，n=11)，and the cumulative 90- day survival rates among them were compared using the Kaplan -Meier method. Results： Compared with the survival group，the death group had greater age，a higher incidence of hepatic encephalopathy or bacterial infection， higher values of white blood cell count，neutrophil count，international normalized ratio，total bilirubin，creatinine，urea，and the above-mentioned 7 scores(P ＜ 0.05). The incidence of coagulation failure or cerebral failure and the proportion of patients with ACLF-1 in the death group were also higher than those in the survival group(P ＜ 0.01). For 90-day mortality prediction，the AUC of COSSH ACLFⅡ score(0.892)was larger than that of the CLIF-C ACLF score(AUC=0.853，P=0.089)，the COSSH ACLF score(AUC=0.841， P ＜ 0.05)，the CLIF-C OF score(AUC=0.813，P ＜ 0.05)，the MELD-Na score(AUC=0.771，P ＜ 0.01)，the MELD score(AUC=0.792， P ＜ 0.01)，and the CTP score(AUC=0.655，P ＜ 0.001). The cumulative 90- day survival rates significantly decreased with COSSH ACLF grade and risk strata of the COSSH ACLFⅡ score ascending(73.5% vs. 26.1% vs. 0，P ＜ 0.001；72.0% vs. 38.1% vs. 0，P ＜ 0.01). Conclusion：The COSSH ACLFⅡ score showed excellent prognostic performance in predicting short-term prognosis in patients with HBV-ACLF. Using risk strata of the new score can simplify the severity stratification of HBV-ACLF.

Abstract:Objective：To investigate the relationship between vitamin D level and renal prognosis in patients with IgA nephropathy (IgAN). Methods：The general clinical data and pathological findings of IgAN patients diagnosed by renal biopsy in the First Affiliated Hospital of Nanjing Medical University from January 2014 to March 2019 were collected and analyzed retrospectively. The participants were divided into 25-(OH)D deficiency group and 25-(OH)D non-deficiency group. The end-point event was defined as progression of renal function，a doubling of serum creatinine or the onset of end-stage kidney disease(ESRD). The differences of renal function progression between 25-(OH)D deficiency group and 25-(OH)D non-deficiency group in IgAN patients were compared by Kaplan -Meier survival curve. Cox regression method was used to analyze the influencing factors of poor renal prognosis. Results：A total of 646 IgAN patients were enrolled in this study，there were 485 cases in 25-(OH)D deficiency group(75.08%)and 161 cases in 25-(OH)D non -deficiency group(24.92%). Compared with the 25-(OH)D non -deficiency group，the levels of hemoglobin，serum albumin，blood IgA and blood IgG were lower，and the levels of total cholesterol and urinary protein were higher in the 25-(OH)D deficiency group. The results of Kaplan-Meier survival curve analysis showed that the progressive rate of renal function in the 25(- OH)D deficiency group was higher than that in the non-deficiency group(log-rank test χ2 =4.217，P=0.040). The results of multivariate Cox regression analysis showed that 25-(OH)D deficiency was an independent factor affecting poor renal prognosis(HR=0.976，95%CI： 0.958~0.995，P=0.014). Conclusion：High level of 25-(OH)D has independent protective effect on renal prognosis in patients with IgAN. It implies that patients with low 25(- OH)D need supplementation of vitamin D.

Abstract:Objective：To evaluate the impact of transjugular intrahepatic portosystemic shunt(TIPS)on splenic volume and blood corpuscle. Methods：The general information，laboratory and CT imaging data of 120 patients with portal hypertension due to cirrhosis were retrospectively collected before and 1，3，6 and 12 months after TIPS from May 2015 to December 2020 in Department of Interventional Radiology，the First Affiliated Hospital of Nanjing Medical University. The changes of splenic volume，platelet count，hemoglobin，and leukocyte count before and after TIPS were evaluated by Friedman test and Spearman correlation analysis. Results：Changes of observed indexes of 120 patients from preoperation to postoperative 12 months：the splenic volume decreased from 749.3(479.0，1152.2)cm³ to 577.4(343.0，884.1)cm³ (P ＜ 0.001)，platelet(PLT)count increased from 50(40，80)×10⁹ /L to 86.5(60，124)×109 /L(P ＜ 0.001)，hemoglobin(Hb)increased from 81(70，94)g/L to 121(106，132)g/L(P ＜ 0.001)and the leukocyte (WBC)count increased from 4.1(2.5，6.6)×109 /L to 5.9(5.0，7.0)×10⁹ /L(P ＜ 0.001). The rate of change in splenic volume and corpuscle was the most obvious in the first month after TIPS and the spleen had shunk by 6.5%，and the PLT count，Hb，and WBC count increased by 15.1%，17.3% and 11.2% respectively. In addition，the rate of increase in PLT was significantly correlated with the rate of decrease in splenic volume. Conclusion：The splenic volume is decreased and PLT count，Hb and WBC count are increased after TIPS，and the improvement is the most obvious in the first month after TIPS. The rate of increase in PLT is significantly related to the rate of decrease in splenic vloume.

Abstract:Objective：The aim of this study was to investigate the associations between psychological factors(depression，anxiety， and stress)during pregnancy and non-indicated cesarean delivery. Methods：We conducted a prospective cohort study of 1 453 women who were enrolled between October 2016 and January 2019 in the Women’s Hospital of Nanjing Medical University. The self-rating anxiety scale，Centre for Epidemiologic Studies Depression scale，and perceived stress scale were used to assess the psychological status of pregnant women in the first，second and third trimesters. The generalized estimation equation(GEE)was performed to investigate the association between antepartum psychological status and cesarean delivery among pregnant women without medical indications for cesarean delivery. Results：Among the 1 453 participants in this study，516 had medical indications for cesarean delivery. The rest 937 women had no medical indications for cesarean delivery，among which 139 women had cesarean delivery. Any adverse psychological symptom(depression，anxiety，or stress)in late pregnancy was associated with increased risk of non -indicated cesarean delivery(OR=1.69，95%CI：1.04~2.73，P=0.034)after the adjustment for maternal age at delivery，pre-pregnancy body mass index(BMI)，diabetes during pregnancy，parity，and gestational age. Particularly，depressive symptom in pregnant women was significantly related to the risk of non-indicated cesarean delivery(OR=1.32，95%CI：1.03~1.69，P=0.028). No statistically significant association was observed between stress and press in women and the risk of non-indicated cesarean delivery. Conclusion：Depressive symptom in the third trimester increased the risk of non-indicated cesarean delivery. It is suggested that more attention should be paid to the psychological counseling of pregnant women，especially in late pregnancy.

Abstract:Objective：To investigate the time and influencing factors for patients suffering from osteoporosis after stroke. Methods： The medical records of 685 patients diagnosed as stroke in the Rehabilitation Department of Liyang People’s Hospital from January 2010 to January 2017 were screened using retrospective cohort study methods. One hundred and five cases，complying with the standards，were included. According to whether being diagnosed as osteoporosis within 5 years after stroke，they were divided into osteoporosis group and non-osteoporosis group，with 46 and 59 cases in each group. Logistic regression analysis was used to analyze the factors affecting the occurrence of osteoporosis in stroke patients with the outcome of whether osteoporosis occurs within 5 years. Kaplan- Meier survival analysis was applied to calculate the media time of osteoporosis occurrence and 95% confidence interval. Multivariate Cox regression was used to analyze the factors affecting the rate of osteoporosis in stroke patients after stroke. Results：Gender(female) (OR=8.145，95%CI：1.361~48.735，P=0.022)and age(OR=1.263，95%CI：1.135~1.406，P ＜ 0.001)had an effect on the incidence of poststroke osteoporosis. The media time of osteoporosis occurrence was 3.42 years. Age influenced the onset time of poststroke osteoporosis(HR=1.162，95%CI：1.029~1.313，P=0.016). Compared with manual labor，mental labor has an effect on the occurrence time of osteoporosis after stroke(HR=4.256，95% CI：1.447~12.519，P=0.008). Compared with hyperbaric oxygen therapy after stroke，the occurrence time of osteoporosis after stroke is affected by the absence of hyperbaric oxygen therapy(HR=4.418，95%CI： 1.868~10.450，P=0.001). Compared with 0 times of rehabilitation therapy per year，1-2 times of rehabilitation therapy per year has an impact on the occurrence time of poststroke osteoporosis(HR=14.002，95%CI：2.641~74.450，P=0.002). Compared with anti-osteoporosis therapy, the absence of anti-osteoporosis therapy had an impact on the onset time of poststroke osteoporosis(HR=2.306，95%CI：1.088~ 4.889，P=0.029). Conclusion：Female and old age are independent risk factors for osteoporosis in stroke patients. Young age，physical work，hyperbaric oxygen therapy and anti-osteoporosis therapy are beneficial to slow the development of osteoporosis.

Abstract:Objective：To analyze the clinical characteristics of patients with pulmonary hypertension(PH)according to neutrophil/ lymphocyte ratio(NLR)and red cell distribution width(RDW)combined with multislice spiral CT(MSCT)，and to explore the correlation between the clinical characteristics and the severity of disease. Methods：The clinical data of 124 patients with PH assessed by transthoracic echocardiography(TTE)in the First Affiliated Hospital of Nanjing Medical University from August 2018 to February 2022 were collected as PH group，and data of 120 healthy patients in our hospital during the same period were collected as control group. MSCT，TTE，blood routine examination and other related results were included to comprehensively evaluate the severity of the disease. Results：①Compared with normal control group，NLR，RDW and diameters of the main pulmonary artery(dMPA)，ratio of main pulmonary artery to ascending aorta diameter(rPA) and ascending aortic diameter(AOD) measured by MSCT were significantly increased in PH group，and the differences were statistically significant(P ＜ 0.05). ②Compared with the mild PH group， the NLR，RDW，dMPA and rPA were significantly higher in the moderate and severe PH group，and the differences were statistically significant(P ＜ 0.05). ③The NLR，RDW，dMPA and rPA were positively correlated with systolic pulmonary artery pressure(PASP)， while AOD had no correlation with PASP. ④The NLR，RDW，dMPA and rPA measured by MSCT had better predictive value for the severity of PH. ⑤RDW，dMPA were the risk factors for elevated PASP. Conclusion：For the assessment of the severity of PH，NLR， RDW，dMPA and rPA all have high predictive value，these indicators can be used as common indicators to evaluate the severity of patients’disease. RDW，dMPA are confirmed to be independent predictors of the exacerbation of PH patients.

Abstract:The tumor necrosis factor receptor superfamily(TNFRSF) interacts with members of the tumor necrosis factor superfamily(TNFSF)to play fundermental roles in regulating immune responses，cell survival，proliferation and differentiation. TNFRSF19 is a new member of the TNFRSF family，mainly expressed in epithelial cells，hair follicles and brain tissue cells. In recent years，studies have shown that TNFRSF19 plays an important physiological function in regulating the development of the nervous system and maintaining the stemness of stem cells. TNFRSF19 plays diametrically opposite functions of tumor - promoting or tumor - suppressing in different tumors，and its functions are closely related to the tissue origin of tumors. This article briefly reviews the physiological function of TNFRSF19 and its latest research progress in cancer.

Abstract:Vasculogenic mimicry(VM)is a vascular network -like pipeline structure formed by tumor cells through deformation， migration，and matrix remodeling. Glioma is the most common primary malignant tumor in the brain，which is characterized by high vascularization. However，antiangiogenic therapy has not achieved the expected results in the clinical application of glioma，which may be caused by VM. Although its detailed molecular mechanism is unclear，accumulating evidences showed that the tumor microenvironment plays an important role in the development of glioma VM. Here，we reviewed the recent progresses in the influence of tumor microenvironment on VM formation and its pharmacological significance in the treatment of glioma. We also raise some issues that should be focused on in future research.

Abstract:p53 binding protein 1(53BP1)plays a crucial role in coordinating the selection of DNA double - strand break(DSB) repair pathway. Underlying molecular mechanisms of 53BP1 recruitment to damaged chromatin and the function of histone modifications in that process have been reported in extensive literature. H4K20me2 and H2AK15ub are the key factors that determine whether 53BP1 can bind to damaged chromatin. Recent evidence suggests that the acetylation of H3K18 and H3K56，as well as the acetylation/methylation of H4K16，have a certain effect on 53BP1 recruitment. This article reviews the structure of 53BP1，the molecular mechanism of 53BP1 recruitment，and the role of histone modifications in regulating 53BP1 recruitment，and provides new ideas for cancer therapy.

Abstract:COVID-19，caused by the severe acute respiratory syndrome coronavirus 2(SARS-COV-2)in 2019，resulted in a global pandemic and had impacts on human lives，public healthcare system，and the global economy. Vaccination is the most important intervention to protect the population from coronavirus disease 2019(COVID-19). The period before and during pregnancy and during lactation is of widespread interest and attention，to study the impact of COVID-19 vaccination on them and their offspring is of great significance. In this review，we aimed to collect relevant reports so far on the impact of COVID - 19 vaccination on male and female reproductive system as well as the effects during pregnancy and lactation，and summarize the clinical data about the safety of COVID- 19 vaccine on males and females before and during pregnancy and during lactation，and on their offspring，in the hope of providing useful information for future systematic evaluation the safety and use of COVID-19 vaccine in this population

Abstract:Noninvasive neuromodulation techniques are bioengineering technologies that use non-implantable technology(non-invasive) to physically or pharmacologically stimulate nerve fibers to regulate neuronal activity and achieve a certain therapeutic effect. In recent years，noninvasive neuromodulation technology has developed rapidly. The neuromodulation technology represented by transcranial magnetic stimulation and transcranial DC/AC electrical stimulation has been widely used in the field of rehabilitation medicine and has become an effective“weapon”for clinical treatment. The application，safety and possible development trend of noninvasive neuromodulation techniques in children’s rehabilitation are reviewed.