Abstract:Due to the complexity of tumor microenvironment，traditional cancer therapies have serious limitations，such as poor drug responsiveness，toxic side effects，difficulty in reaching deeper tumors，and tumors prone to recurrence. In recent years，bacterial - mediated cancer immunotherapy is attracting attention with its unique advantages. These bacteria preferentially colonize the hypoxic zone of tumors and kill tumor cells through various mechanisms，such as reshaping the tumor immune microenvironment and activating anti-tumor immunity. Based on this，genetic engineering techniques to construct recombinant antitumor strains that target tumors and secrete therapeutic proteins or nucleic acid drugs in the tumor core or in combination with other anticancer therapies are promising as a new cancer treatment strategy. This paper introduces the research progress of different antitumor bacteria and their clinical application status，and provides new ideas for bacterial immunotherapy of tumors.

Abstract:Hepatocellular carcinoma(HCC)is the most common type of primary liver cancer. The boom in novel immunotherapies has topped the most remarkable progress in HCC treatment in the past decade. As members of the immune system，natural killer(NK) cells play a vital role in anti-tumor immunity. Chimeric antigen receptor(CAR)-NK cell therapy is a new type of tumor immunotherapy， in which NK cells are genetically engineered to specifically recognize tumor-associated antigens to produce more precise and efficient anti -tumor efficacy. Focusing on CAR targets and related immune checkpoints，this review summarizes the challenges and possible solutions for CAR-NK in HCC treatment. Furthermore，it discusses potential strategies for boosting the efficacy of CAR-NK.

Abstract:Objective：To explore the role of mTOR signaling pathway in CD4 ⁺ regulatory T cell(Treg)glucose metabolism in ovarian cancer patients. Methods：Flow cytometry was used to detect the percentage of mTOR⁺ CD4 ⁺ Treg in peripheral blood with ovarian cancer(OC)patients，benign ovarian tumor(BOT)patients and healthy controls(HC). We established a coculture system of human CD4⁺ Treg with ovarian cancer cell SKOV3，and detected the percentage of mTOR⁺ CD4⁺ Treg before and after co-culture. After mTOR signal was inhibited by rapamycin，the glucose uptake and glycolysis levels of CD4⁺ Treg were detected by colorimetry，and the expression levels of genes and proteins related to glucose metabolism in CD4 ⁺ Treg were detected by real-time quantitative PCR and Western blot. Results：The percentage of mTOR⁺ CD4⁺ Treg in peripheral blood of ovarian cancer patients was significantly higher than that of healthy controls[(77.4±8.12)% vs(. 64.19±9.7)%，P ＜ 0.01]. After co-culture with SKOV3，the percentage of mTOR⁺ CD4 ⁺ Treg were elevated(P ＜ 0.05)，and the levels of mTOR signaling pathway related genes and proteins also increased. After inhibition of mTOR signal of CD4 ⁺ Treg in SKOV3 growth environment，the glucose uptake(193.49 ± 13.28 vs. 174.05 ± 14.58，P ＜ 0.01)and glycolysis level(21.97±0.87 vs. 4.85±1.54，P ＜ 0.001)were decreased significantly. Glucose metabolism - related genes and proteins were also significantly reduced. Conclusion：mTOR and its downstream signaling pathway are significantly activated in peripheral blood CD4 ⁺ Treg of ovarian cancer patients，and mTOR signaling pathway can affect glucose metabolism of CD4 ⁺ Treg by regulating glucose metabolist-related genes and protein levels.

Abstract:Objective：To investigate the expression of lncRNA RP11-490M8.1 in patients with breast cancer and its roles in the proliferation of breast cancer cells. Methods：The Cancer Genome Atlas(TCGA)and the Kaplan -Meier plotter database were used to define the expression level and prognostic value of RP11-490M8.1 in breast cancer，respectively. qRT-PCR was performed to detect the expression level of RP11-490M8.1 in paired breast cancer tissues and adjacent normal tissues. CCK8 and clone formation assays were carried out to determine the effects of the overexpression or knockdown of RP11-490M8.1 on the proliferation of breast cancer cells. Results：Compared with adjacent normal tissues，RP11-490M8.1 was significantly downregulated in breast cancer tissues. Moreover， lower expression of RP11-490M8.1 was associated with the advanced clinical stage and worse overall survival(OS)(P=0.034). However，there was no correlation between RP11-490M8.1 level and the expression of estrogen receptor，progesterone receptor，human epidermal growth factor receptor-2 and age. Overexpression of RP11-490M8.1 markedly suppressed the proliferation of breast cancer cells，while knockdown of RP11-490M8.1 promoted its proliferation. Conclusion：RP11-490M8.1 acts as a tumor suppressor in breast cancer，which may serve as a potential prognostic molecule and therapeutic target for breast cancer

Abstract:Objective：The current study aims to explore the expression of hsa_circ_0001479 in gastric cancer(GC)tissues and its effect on biological behavior of GC cells. Methods：The method for detecting the expression of hsa_circ_0001479 with real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was established and evaluated. Expression level of hsa_circ_0001479 in 76 pairs of GC and para-cancerous tissues was measured by RT-qPCR and relationship between the expression level and clinicopathological factors was analyzed. Small interfering RNA(siRNA)and overexpression vector of hsa_circ_0001479 were constructed and transfected into GC cell lines. Cell proliferation was detected by CCK-8 assay and clone formation assay. Cell cycle distribution was detected by flow cytometry. Cell migration was detected by wound healing assay and Transwell assay. Cell invasion was detected by transwell assay. Results：Using RT-qPCR to detect the expression of hsa_circ_0001479 possessed good precision， accuracy and linear range. Hsa_circ_0001479 was upregulated in GC tissues and the expression level was related to tumor size，depth of invasion，lymph node metastasis，TNM stage and CA19-9. Silencing of hsa_circ_0001479 inhibited the proliferation，invasion and migration of GC cells while overexpression of hsa_circ_0001479 showed the opposite results. Conclusion：The carrent study found that hsa_circ_0001479 was upregulated in GC tissues and could promote GC cell proliferation，invasion and migration.

Abstract:Objective：To evaluate the diagnostic ability of dynamic-contrast enhanced magnetic resonance imaging(DCE-MRI)and apparent diffusion coefficient(ADC)in differentiating smooth muscle tumours of uncertain malignant potential(STUMP)or malignant uterine mesenchymal tumours from leiomyomas that manifests restricted diffusion on diffusion-weighted imaging(DWI). Methods：A total of 68 patients with pathologically confirmed uterine mesenchymal tumors that manifest restricted diffusion on DWI(b=800 s/mm2 ) were included between January 2016 and September 2021. We assessed conventional MR features of the lesions. Histogram analysis was performed based on ADC and DCE -MRI，and the derived quantitative parameters were compared between STUMP or malignant uterine mesenchymal tumours(n=23)and leiomyomas that manifest restricted diffusion on DWI(n=45). Receiver operating characteristic(ROC)curve was used for evaluating diagnostic performance. Results：The incidence of cystic necrosis in the STUMP or malignant group was higher than that in the non -malignant group(34.8% vs. 8.9%，P=0.016). ADC_median and V_{e median} of the STUMP or malignant group were significantly lower than nonmalignant group(P ＜ 0.001，P=0.012)，with the highest area under the curve(AUC) for distinguishing STUMP or malignant uterine mesenchymal tumours reaching 0.795 and 0.713. ADC_median+ V_{e median} improved AUC to 0.850. ADC_median+V_{e median}+with or without cystic necrosis yield the highest AUC(0.883). Conclusion：The combination of ADC，DCE-MRI parameters and conventional MR features may serve as sensitive indicators for differentiating malignant uterine mesenchymal tumours from leiomyomas showing restricted diffusion on DWI.

Abstract:Objective：The current machine learning was performed based on the radiomic features of contrast - enhanced T1 - weighted imaging(T1WI+C)of glioma，which was used to construct a prediction model of Ki67 index for predicting the proliferation activity of glioma cells. Methods：A retrospective analysis onsisted 113 patients with glioma，which were confirmed by the surgical and pathological results of our hospital and the Ki67 index defined by immunohistochemistry. The training set and the test set were divided into 8∶2. The glial region of interest(ROI)was hand-painted by MRIcroGL software，1 338 image features were obtained by using the pyradiomics module in Python，and the best image features were obtained through t-test and the least absolute shrinkage and selection operator(Lasso)regression algorithm. Furthermore，using the support vector machine classifier to build the Ki67 prediction model based on the best features，using the receiver operating characteristic(ROC)curve and the calibration curve to evaluate the predictive performance of the model. Results：A total of 1 338 radiomics features were extracted from T1WI+C images of each patient，and six features closely related to glioma ki67 index were screened out after dimensionality reduction. Based on the support vector machine algorithm model，the AUC in the training set of Ki67 index prediction was 0.82，and the accuracy rate was 0.72；in the test set of Ki67 index prediction，the AUC was 0.91，and the accuracy rate was 0.83. The results of the calibration curve of the model showed that the difference was not statistically significant(Brier score=0.175). Conclusion：The prediction model of support vector machine that established on the learning of the T1W1+C imaging omics characteristics may have a better predictive effert on the proliferation activity of glioma cells，and it may help the selection of individual diagnosis and treatment plans for patients and the development of precision medical care in the future.

Abstract:Objective：To investigate the adverse events，the immune aging and the immunotherapeutic toxicity of elderly cancer patients over 75 years old that received immune checkpoint inhibitors，and the management of related toxicity. Methods：The adverse event information of solid cancer patients who received PD - 1/PD - l1 immune checkpoint inhibitor treatment in the First Affiliated Hospital of Nanjing Medical University between January 1，2018 and December 31，2021 was collected and the retrospective analysis and correlation evaluation were performed. Pearson’s chi - square test was used for correlation analysis of influencing factors，and Kaplan-Meier method was used for survival analysis. Results：A total of 166 patients received 910 times of treatment，with an average of 5.48 times of immune checkpoint inhibitor treatment. A total of 146 cases had adverse events of different degrees，and a total of 462 adverse events were recorded，with an average of 2.78 times/case. The incidence of adverse events was 87.9%. The adverse events with a higher proportion anemia(78.9%)，leucopenia(28.9%)，neutropenia(18.7%)，thrombocytopenia(42.8%)，hyperglycemia(21.7%)， abnormal thyroid function(9.6%)，abnormal cortisol(9.6%)，etc. The positive and likely adverse events related to immune checkpoint inhibitors accounted for 11.9% of the total adverse events . There were 22 cases of grade 3 and above adverse events，accounting for 13.2% of the total number of patients. After analysis，whether there are complications of ≥ 3 systems and whether they are combined with other antitumor drugs have a significant impact on the incidence of adverse events. Conclusion：Based on the data of the current study，the adverse events of immune checkpoint inhibitors in patients over 75 years old are equivalent to those in patients under 75 years old，and there is no increase in the occurrence of serious adverse events.

Abstract:Objective：To explore the effect of oxysterol-binding protein-like 2(OSBPL2)on the actin cytoskeleton in auditory cells and its related molecular mechanisms. Methods：OSBPl2 knockout(Osbpl2-KO)HEI-OC1 cells were used to investigate the effect of OSBPL2 deficiency on the the actin cytoskeleton in auditory cells. The stereocilia onmouse hair cells were observed by scanning electron microscopy. Western blot was used to detect the expression of Rho - associated coiled - coil - containing protein kinase 2 (ROCK2)，Lim domain kinase 1(LIMK1)and actin depolymerizing factor 1(ADF/CFL - 1)in HEI -OC1 cells and mouse cochleae. Results：In Osbpl2-KO HEI-OC1 cells，the distribution of F-actin in the microfilament skeleton was down-regulated，the pericellular microspikes and filopodia were noticeably reduced，and the cell migration ability was significantly weakened. In vivo，OSBPL2 deficiency resulted in shortened and disordered stereocilia on mouse inner hair cells. Western blot assay showed that OSBPL2 deficiency led to the inhibition of RhoA/ROCK2 signaling pathway in HEI - OC1 cells and mouse cochleae. Conclusion：OSBPL2 mediats RhoA/ROCK2 signaling pathway in auditory cells and plays an important role in maintaining the morphology and function of actin cytoskeleton.

Abstract:Objective：The present study aims to investigate the role of protease - activated receptor 2(PAR2)in the regulation of human endothelial progenitor cell(EPC)function. Methods：EPCs were stimulated with tryptase(a natural agonist of PAR2)，SLIGKV- NH2(a synthetic agonist of PAR2)and FSLLRY-NH2(an antagonist of PAR2). Cell proliferation and migration were evaluated by EdU incorporation and Transwell model. Expression of the cytokines and receptors were estimated by real - time quantitative PCR and ELISA. Level of intercellular Ras homolog family member A(RhoA)was assessed by Western blot analysis. And RhoA antagonist Y- 27632 was also applied to determine whether the effects of PAR2 activation can be abolished by RhoA inhibition. Results：The agonists of PAR2 dramatically inhibited EPCs proliferation and migration in a dose - dependent manner(P ＜ 0.05). PAR2 activation markedly suppressed the expression of vascular endothelial growth factor-A，vascular endothelial growth factor receptor-2，stromal cell- derived factor -1and C -X -C chemokine receptor type 4(P ＜ 0.05). All these effects can be abolished by the PAR2 antagonist(P ＜ 0.05). PAR2 activation increased the level of RhoA in EPCs，which was also repressed by FSLLRY-NH2(P ＜ 0.05). Y-27632 notably reversed the influence of PAR2 activation on EPCs proliferation and migration(P ＜ 0.05). Conclusion：The activation of PAR2 blunted EPCs proliferation and migration via RhoA signal，hinting a potential role of PAR2 as a novel target for the modulation of endothelial regeneration and vasculogenesis.

Abstract:Objective：To study the effects of high fat diet on the proliferation，differentiation and collagen synthesis of mouse cardiac fibroblasts through exosomes from small intestinal epithelium. Methods：Exosomes from small intestinal epithelium of normal/ high fat diet mice were extracted and co-cultured with primary mouse cardiac fibroblasts. Exosomes uptake of cardiac fibroblasts of the two groups was observed by PKH26 labeling，and the gene expressions of proliferation，differentiation，fibrosis and inflammation of cardiac fibroblasts were determined by PCR. Immunofluorescence staining was used to observe the expression of α-SMA，Col1a1 and Col3a1 in cardiac fibroblasts of the two groups. Results：The exosomes from small intestinal epithelium of normal/high -fat diet mice could be absorbed by cardiac fibroblasts，and there was no difference in uptake efficiency between them. Compared with the normal diet group，the small intestinal exosomes of mice fed with high fat diet could significantly increase the gene expression of cardiac fibroblasts，such as genes associated with proliferation，differentiation，extracellular matrix accumulation and inflammation，and enhance the ability to synthesize α - SMA，Col1a1 and Col3a1 protein. Conclusion：High fat diet can promote the proliferation， differentiation and collagen production of cardiac fibroblasts through exosomes from small intestinal epithelium.

Abstract:Objective：This study aims to explore the effect of Prussian blue nanozyme on osteogenic differentiation of MC3T3-E1 cells in an oxidative microenvironment. Methods：Biocompatibility of different concentrations of Prussian blue nanozymes was detected by CCK-8 assay and flow cytometry；mimetic enzyme activity of Prussian blue nanozymes at different concentrations was measured by xylenol orange assay and WST-8 assay，and intracellular reactive oxygen species scavenging activity of Prussian blue nanozymes was detected by DCFH - DA probe immunofluorescence assay；and the osteogenesis differentiation of MC3T3 - E1 cells under oxidative microenvironment was evaluated by alkaline phosphatase(ALP)staining and activity assay，alizarin red staining and real - time fluorescence quantitative reverse transcription PCR. Results：CCK-8 and flow cytometry showed good biocompatibility of Prussian blue nanozyme between 0-100 μg/mL concentrations；xylenol orange assay and WST -8 assay showed good mimetic enzymatic activity of Prussian blue nanozyme in a concentration and time-dependent manner；DCFH-DA probe immunofluorescence showed that Prussian blue nanozyme also had good ability to scavenge intracellular reactive oxygen species；ALP staining and activity assay，alizarin red staining and real - time fluorescence quantitative reverse transcription PCR showed that Prussian blue nanozyme can significantly enhance osteogenesis differentiation of MC3T3 - E1 cells in oxidative microenvironment. Conclusion：Prussian blue nanozyme can enhance the antioxidant activity of MC3T3-E1 cells and promotes the osteogenic differentiation of cells in an oxidative environment.

Abstract:Objective：To investigate the effect and mechanism of resveratrol on neural cell apoptosis induced by endoplasmic reticulum stress(ERS). Methods：PC12 cells were treated with ERS inducer thapsigargin(TG)to construct ERS model. The expression of GRP78 protein was detected by Western blotting，the cytoplasmic calcium concentration was detected by laser scanning confocal microscope(LSCM)and Fluo-3/AM，the activity of Caspase-3 was measured by colorimetry，and the apoptosis rate was detected by flow cytometry. Results：Resveratrol reduced the high expression of GRP 78 induced by ERS inducer TG，prevented calcium overload induced by ERS. Resveratrol and calcium chelator BAPTA inhibited the activation of Caspase-3 induced by ERS and inhibited ERS- induced neuronal apoptosis. Conclusion：Resveratrol may inhibit neural cell apoptosis induced by ERS through Ca2 + /Caspase - 3 pathway.

Abstract:Objective：The current study aims to determine the effects of sulforaphane(SFN)on oxidized low-density lipoprotein(ox- LDL)-induced platelet activation and its possible mechanism. Methods：Purified human platelets were treated with SFN(1.0，2.5，5.0 μmol/L)for 40 minutes in vitro，and then stimulated by ox-LDL for additional 20 minutes. The levels of platelet CD62P expression and intracellular PF4 and CCL5 release were measured to determine the effects of SFN on platelet activation. Moreover，the phosphorylation of sarcoma tyrosine kinase(Src)and its downstream spleen tyrosine kinase(Syk)were measured by Western blot. Reactive oxygen species(ROS)assay kit was used to measure the levels of total intracellular ROS generation. Results：The ox-LDL- increased platelet CD62P expression and PF4 and CCL5 release were significantly inhibited by SFN when compared with the control group(P ＜ 0.05). SFN treatment greatly down-regulated Src and Syk phosphorylation and ROS generation stimulated by ox-LDL(P ＜ 0.05). Furthermore，the ox-LDL-increased the expression of CD62P and release of PF4 and CCL5 were significantly abolished by PP2， a specific inhibitor of Src family kinases，which，nevertheless，showed no synergistic effects when combined with SFN(P ＞ 0.05). In addition，the inhibitory effects of SFN on platelet activation induced by ox-LDL were reversed by an activator of Src family kinases MLR-1023. Conclusions：SFN attenuates platelet activation induced by ox-LDL possibly by down-regulating Src/Syk/ROS pathway.

Abstract:Objective：The aimofthestudywasto explore the structure-activity relationship of PSD95-nNOS decoupling agent ZL006 (1)，and the mechanism of decoupling. Methods：Basedon the PSD95-nNOS protein-protein interaction inhibitor ZL006 reported by our group，four series of 21 novel ZL006 derivatives were designed andsynthesized by modifying its lipophilic part，linker and Salicylic acid structure. All the structures were confirmed by 1 H NMR，13C NMR and ESI-MS. The protective effect of the target compounds on glutamate-induced damage of human neuroblastoma cells(SH-SY5Y)was tested by LDH experiment，and the cytotoxicity of the target compounds was tested by CCK-8 staining. Results：Most of the compounds had protective activity against cells，among which compounds 5e and 27a were comparable to the neuroprotective activity of the positive control compound ZL006(51.24%，48.42% at 10 μmol/L)，and compound 23 showed better cytoprotective activity than ZL006(54.34% at 10 μmol/L，29.58% at 1 μmol/L)and showed lower cytotoxicity(2.85% at 25 μmol/L). Conclusion：This study not only enriches the diversity of chemical structures suitable for PSD95-nNOS protein-protein interaction but also provides a useful tool to further explore the neuroprotection therapeutic potential.

Abstract:Objective：To explore the therapeutic effect of expanded autologous peripheral blood mononuclear cells(PBMC)in vitro on patients with amyotrophic lateral sclerosis(ALS)，and the correlation between the peripheral blood lymphocyte subgroup classification and the improvement of symptoms. Methods：Between October 2019 and August 2021，a total of 65 ALS cases were enrolled from the Department of Neurology at Sir Run Run Hospital affiliated of Nanjing Medical University and Nanjing Hospital affiliated of Nanjing University of Traditional Chinese Medicine. The patients were randomly assigned to two groups：the PBMC group (33 cases)received a treatment of PBMCs(1×10⁶ /kg body weight)and 20% human albumin(100 mL)，while the control group(32cases)received only 20% human albumin(100 mL). The revised ALS Functional Rating Scale(ALSFRS-R)was scored before and on the day 5 and day 14 after the treatment. The number of CD4⁺ T cells，CD8⁺ T cells，CD4⁺ CD25⁺ Foxp3⁺ Treg cells，and CD16⁺ CD56⁺ NK cells in peripheral blood were measured. Results：①The ALSFRS-R scores in PBMC group were significantly higher on the 5th day (30.1 ± 3.4 points)and the 14th day(26.5 ± 2.0 points)after treatment than that before treatment(25.3 ± 1.4 points)(P ＜ 0.05). There was no significant difference in ALSFRS-R score before and after treatment in the control group(P ＞ 0.05)；②CD8+ T cells and CD4+ CD25⁺ Foxp3⁺ Treg cells in PBMC group were increased on the 5th and 14th day after treatment，which were significantly higher than those in control group and PBMC group before treatment(P ＜ 0.05). There was no statistical significance in CD4+ T cells and CD16⁺ CD56 ⁺ NK cells before and after treatment in PBMC group and compared with the control group(P ＞ 0.05). Also there was no statistical significance in all the changes of the above in control group before and after treatment(P ＞ 0.05)；③At the 5th and 14th day after PBMC treatment，the number of CD8⁺ T cells was negatively correlated with the ALSFRS-R score(P ＜ 0.05)；The number of CD4⁺ CD25 ⁺ Foxp3 ⁺ Treg cells was positively correlated with the ALSFRS-R score(P ＜ 0.05). Conclusion：The reinfusion therapy of autologous PBMC expanded in vitro can improve the clinical symptoms of ALS patients in a short time，and the changes in the number of CD8⁺ T cells and CD4⁺ CD25⁺ Foxp3⁺ Treg cells in peripheral blood are correlated to the clinical progression of the disease.

Abstract:Objective：To investigate the changes of platelet-lymphocyte ratio(PLR)in obstructive sleep apnea hypopnea syndrome (OSAHS)patients with acute ischemic stroke and the clinical value of PLR. Methods：The case data of 155 patients with OSAHS were retrospectively analyzed. According to the presence or absence of acute ischemic stroke，patients were divided into simple OSAHS group(group A，n=93)and OSAHS combined with acute ischemic stroke group(group B，n=62). According to apnea hypopnea index (AHI)，patients in group B were divided into three grades：mild，medium and severe. Clinical data of the two groups were collected and SPSS 25.0 software was used to analyze the correlation between the two groups and the efficacy of PLR in predicting acute ischemic stroke in OSAHS patients. Results：①There were significant differences in LYM，PLT，NEUT，neutrophil lymphocyte ratio(NLR)， PLR，TS90% and AHI between the two groups(P ＜ 0.05). ②PLR was positively correlated with AHI in group B(P=0.000). ③ Logistics analysis showed that PLR was an independent risk factor for acute ischemic stroke in OSAHS patients(P=0.000). ④ROC curve analysis showed that the best cut-off value of serum PLR for predicting acute ischemic stroke in OSAHS patients was 130.79，and the area under the curve was 0.888(95%CI：0.832-0.945). Conclusions：High serum PLR is positively correlated with AHI in OSAHS patients with acute ischemic stroke，and PLR may be an independent predictor of acute ischemic stroke in OSAHS.

Abstract:Objective：To observe the relationship between serum aPLA2Rab titer and the severity of renal disease and renal prognosis in patients with PLA2R-related membranous nephropathy. Methods：A total of 237 patients with PLA2R-related membranous nephropathy confirmed by renal biopsy in the Department of Nephrology of the First Affiliated Hospital of Soochow University were included and were followed up for ≥1 year. The end point was renal insufficiency，defined as a 40% decrease of eGFR from baseline. Clinical indicators of patients were collected for statistical analysis. Results：A total of 273 patients were included in the current study， of which serum aPLA2Rab titer ＜50 RU/mL group(low titer group)had 44 cases，50~＜150 RU/mL group(medium titer group)142 cases and ≥150 RU/mL group(high titer group)87 cases. Serum aPLA2Rab titers were significantly correlated with gender，baseline serum albumin，serum creatinine，total cholesterol，urinary NAG，urinary RBP，and glomerular C4 deposition. Multivariate Cox analysis showed that aPLA2Rab titer was still an independent risk factor for renal insufficiency after correction for clinicopathological parameters. The cutoff point of serum aPLA2Rab titers for predicting renal insufficiency was 135.66 RU/mL，with a sensitivity of 65.8% and a specificity of 63.8%. The renal survival rates without reaching renal insufficiency at 1，5 and 10 years were all 100% in the low titer group；100%， 87.0% and 75.5% in the medium titer group；95.4%，72.3% and 72.3% in the high titer group，respectively；there was a significant difference among the three groups. Conclusion：The current study further confirmed that the serum aPLA2Rab titer level in patients with PLA2R - related membranous nephropathy was related to disease severity and renal prognosis，providing theoretical support for the new concept of immunological remission as the therapeutic target.

Abstract:Objective：To study the precise timing of labor induction in GDM women with term premature rupture of membranes and its infuence on maternal and neonatal outcomes. Methods：A retrospective analysis was performed on 585 pregnant women with premature rupture of membranes at term without other comorbidities and complications except GDM in Nanjing Maternal and Child Health Hospital between June 2017 and July 2021，which were divided into three groups according to the interval time(P-O)between preterm rupture of membranes and initiation of oxytocin induction：group A(2~6 h)，group B(6~9 h)，group C(9~12 h). The general clinical data，maternal and neonatal outcomes of the cases in the three groups were statistically analyzed. Results：①The time from premature rupture of membranes to delivery(P-D)increased with the delay of induction of labor initiation(P-O)(P_trend ＜ 0.05)，with the shortest P-D time in group A(P ＜ 0.05). ②The incidence of cesarean delivery，interpartum fever，chorioamnionitis，and intrauterine distress increased with the prolongation of P-O(P_trend ＜ 0.05)，of which the incidence was the lowest in group A(P ＜ 0.05)；no statistical difference was found in the incidence of uterine contraction weakness，postpartum hemorrhage，and puerperal disease in the three groups. ③The incidence of cesarean delivery due to uterine atony increased with the delay of P-O in the three groups(P_trend ＜ 0.05). ④ The incidence of neonatal sepsis and neonatal intracranial hemorrhage in group A was significantly lower than that in group C(P _trend＜0.05)，incidence were significantly lower than those in group C(P ＜ 0.05). Conclusion：In pregnant women with GDM and PROM at term，to exclude other complications and contraindications to vaginal delivery，the choice of oxytocin induction of labor within 2~6 h can both reduce the use of clinical antimicrobials and significantly reduce the incidence of adverse maternal and neonatal outcomes.

Abstract:For the past few years，a unique type of adipose tissue，surrounding our cardiovascular system but cerebrovascular， known as perivascular adipose tissue(PVAT)，has been seen as a new kind of adipose tissue different from the classic visceral fat due to its unusual anatomic location and function. PVAT exerts a bidirectional effect on the cardiovascular system，including the protectional role under physiological state and the deleterious influence under pathological state，through the release of vasoconstrictive/ relaxant adipokine in a paracrine/endocrine manner，the induction of inflammation and phenotypic transformation of adipocytes. PVAT also shows a potential role in the diagnosis and treatment of cardiovascular disease(CVD)as a new parameter and intervention. In this review，we will discuss the characteristics of PVAT to distinguish from classic adipose tissue and its effect on CVD under physiology/ pathology conditions，also，its application in CVD diagnosis and treatment.

Abstract:The self-renewal，proliferation and differentiation of spermatogonial stem cells are critical for maintaining spermatogenesis. However，the molecular mechanism mediating this process remains largely unclear. Spermatogonial stem cells include different cell subtypes which play different roles in spermatogenesis. Single-cell RNA sequencing technology provides an effective method to reveal different subtypes of spermatogonia and their changes in transcriptome levels and biological functions，which could provide new perspectives for investigaing further molecular mechanisms of spermatogonial stem cells.

Abstract:Gestational diabetes mellitus(GDM)is a common obstetric complication that can easily lead to the occurrence of serious adverse pregnancy outcomes，including preterm birth，high risk of poor outcomes in newborns and seriously threatening the health of newborns. Early screening and diagnosis are critical for preterm birth in GDM pregnant women. In this review，the screening and prediction methods for preterm birth in GDM pregnant women at home and abroad in recent years are briefly summarized，and the predictive values of routine and novel biomarkers in preterm birth of GDM pregnant women is systematically summarized，in order to provide a basis for establishing a reasonable prediction model for preterm birth of GDM pregnant women，so as to achieve early diagnosis and intervention，as well as improve maternal and infant outcomes