Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

To analyze the relationship between serum non-HDL-C levels and cardiovascular disease (CVD) mortality in community populations. A retrospective cohort study was conducted using the Yuecheng District Health Information Platform in Shaoxing City, Zhejiang Province. The study cohort included individuals aged 40 years or older with no prior history of CVD who underwent physical examinations at Yuecheng District healthcare institutions between January and December 2019. A total of 39 038 participants were included, including 19 085 males (48.9%) and 19 953 females (51.1%), with a mean age of (73.64±9.10) years. The mean follow-up duration was 52.3 months. During follow-up, 1 227 CVD death events occurred. The results indicated a significant overall association between non-HDL-C levels and the risk of CVD mortality, including coronary heart disease (CHD) and stroke. Cox models indicated that, using the ideal level of non-HDL-C as the reference, the hazard ratios (HRs) for risk of CVD death in the suitable level, borderline elevated level and elevated level groups were 1.24 (95% CI: 1.08-1.42), 1.57 (95% CI: 1.34-1.85) and 2.31 (95% CI: 1.87-2.86), respectively. The corresponding HRs for CHD death were 1.39 (95% CI: 1.10-1.76), 1.69 (95% CI: 1.28-2.12) and 2.53 (95% CI: 1.76-3.64), respectively. Subgroup analysis revealed significant interaction effects between non-HDL-C and sex, smoking, alcohol consumption, and diabetes (all P interaction<0.05). Sensitivity analyses confirmed that results were consistent with the primary findings regarding the association between non-HDL-C and CVD mortality risk. In conclusion, increasing non-HDL-C levels are associated with higher risks of death from cardiovascular diseases, including stroke and CHD. The risk of CVD death associated with elevated non-HDL-C is greater among males, individuals with a history of diabetes, smokers or drinkers. In the future, attention should be paid to the monitoring of non-HDL-C in community health management, and the intensive and personalized management of blood lipids in high-risk population should be strengthened.

Objective:To investigate variation and correlation of type 2 intrinsic lymphocyte(ILC2)and related factors in acute and chronic brucellosis,to identify immune role of ILC2 in chronic brucellosis.Methods:Forty-three patients with acute brucel-losis and 45 patients with chronic brucellosis were compared with 49 healthy controls.ILC2 level in each group was detected by flow cytometry.mRNA level of GATA3 in PBMC was detected by fluorescence quantitative PCR.Serum IL-33,ST2,IL-4 and IL-13 levels were detected by ELISA.ALT and AST levels were measured by fully automatic biochemical analyzer.Results:ILC2 level,GATA3 mRNA in PBMC,serum IL-33,IL-4 and IL-13 levels in chronic brucellosis group were significantly higher than healthy control group and acute brucellosis group(P<0.01).Correlation analysis showed that ILC2 level was positively correlated with GATA3 mRNA,IL-33,IL-4 and IL-13 levels,while negatively correlated with ST2 level.ROC curve suggested that ILC2,GATA3,IL-33 and ST2 had good predictive ability for severity of brucellosis patients(AUC>0.7).Conclusion:Increase of ILC2 and its related factors are closely related to chronic brucella infection,which may play an important immune role in pathogenesis of brucella infection.

Objective:Haracterization of follicular helper T cells(Tfh)cells and related molecules early onset in premature ovarian insufficiency(POI)based on a mouse model of POI.Methods:After acclimatization feeding of 30 BALB/c mice were selected,mice were subjected to vaginal exfoliative cytology from 08:00 onwards every day for 10 consecutive days under light microscope obser-vation,20 healthy female mice with regular estrous cycle were screened out and randomly divided into model(POI)group and healthy control(HC)group according to random number table method,different chemical interventions were given and processed and tissue sampling was done on the 21st day.Every morning from the beginning to the end of the modeling period,the mice were subjected to cell smears of vaginal secretions,which were stained with Giemsa's stain and then observed under a light microscope.After the mice were sacrificed,bilateral ovarian tissues were taken and ovarian paraffin sections were made,and the tissues were stained with HE to observe pathological changes in ovaries of mice.Immunohistochemistry was used to detect expressions of ovarian Tfh-related molecules CXCR5 and BCL-6;flow assay was used to detect frequency of CD4+CXCR5+Tfh cells and CD4+ICOS+Tfh cells in spleens of mice;ELISA was used to detect levels of IL-6 and IL-21 in splenic tissues of mice;qRT-PCR was used to detect mRNA levels of CXCR5 and BCL-6 in mice;correlation analysis was performed to correlate frequencies of CD4+CXCR5+Tfh and CD4+ICOS+Tfh cells with levels of IL-6 and IL-21 in spleens of mice in both groups.Results:Pathological changes in ovarian tissue of mice in POI group:primordial folli-cles and growing follicles decreased,while atretic follicles increased.BCL-6 and CXCR5 were highly expressed in ovarian tissue of mice in POI group.Frequency of CD4+CXCR5+Tfh and CD4+ICOS+Tfh cells in spleen of POI mice was higher than that in HC group.Levels of IL-6 and IL-21 in spleens of mice in POI group were significantly higher than those in HC group,and were positively correlated with the frequency of CD4+CXCR5+Tfh and CD4+ICOS+Tfh cells in spleen of mice.Conclusion:In POI mouse model,Tfh cells are highly expressed and the level of Tfh-related molecules changes,which provides basic reference for studying pathogenesis of POI.

Objective:Haracterization of follicular helper T cells(Tfh)cells and related molecules early onset in premature ovarian insufficiency(POI)based on a mouse model of POI.Methods:After acclimatization feeding of 30 BALB/c mice were selected,mice were subjected to vaginal exfoliative cytology from 08:00 onwards every day for 10 consecutive days under light microscope obser-vation,20 healthy female mice with regular estrous cycle were screened out and randomly divided into model(POI)group and healthy control(HC)group according to random number table method,different chemical interventions were given and processed and tissue sampling was done on the 21st day.Every morning from the beginning to the end of the modeling period,the mice were subjected to cell smears of vaginal secretions,which were stained with Giemsa's stain and then observed under a light microscope.After the mice were sacrificed,bilateral ovarian tissues were taken and ovarian paraffin sections were made,and the tissues were stained with HE to observe pathological changes in ovaries of mice.Immunohistochemistry was used to detect expressions of ovarian Tfh-related molecules CXCR5 and BCL-6;flow assay was used to detect frequency of CD4+CXCR5+Tfh cells and CD4+ICOS+Tfh cells in spleens of mice;ELISA was used to detect levels of IL-6 and IL-21 in splenic tissues of mice;qRT-PCR was used to detect mRNA levels of CXCR5 and BCL-6 in mice;correlation analysis was performed to correlate frequencies of CD4+CXCR5+Tfh and CD4+ICOS+Tfh cells with levels of IL-6 and IL-21 in spleens of mice in both groups.Results:Pathological changes in ovarian tissue of mice in POI group:primordial folli-cles and growing follicles decreased,while atretic follicles increased.BCL-6 and CXCR5 were highly expressed in ovarian tissue of mice in POI group.Frequency of CD4+CXCR5+Tfh and CD4+ICOS+Tfh cells in spleen of POI mice was higher than that in HC group.Levels of IL-6 and IL-21 in spleens of mice in POI group were significantly higher than those in HC group,and were positively correlated with the frequency of CD4+CXCR5+Tfh and CD4+ICOS+Tfh cells in spleen of mice.Conclusion:In POI mouse model,Tfh cells are highly expressed and the level of Tfh-related molecules changes,which provides basic reference for studying pathogenesis of POI.

To analyze the relationship between serum non-HDL-C levels and cardiovascular disease (CVD) mortality in community populations. A retrospective cohort study was conducted using the Yuecheng District Health Information Platform in Shaoxing City, Zhejiang Province. The study cohort included individuals aged 40 years or older with no prior history of CVD who underwent physical examinations at Yuecheng District healthcare institutions between January and December 2019. A total of 39 038 participants were included, including 19 085 males (48.9%) and 19 953 females (51.1%), with a mean age of (73.64±9.10) years. The mean follow-up duration was 52.3 months. During follow-up, 1 227 CVD death events occurred. The results indicated a significant overall association between non-HDL-C levels and the risk of CVD mortality, including coronary heart disease (CHD) and stroke. Cox models indicated that, using the ideal level of non-HDL-C as the reference, the hazard ratios (HRs) for risk of CVD death in the suitable level, borderline elevated level and elevated level groups were 1.24 (95% CI: 1.08-1.42), 1.57 (95% CI: 1.34-1.85) and 2.31 (95% CI: 1.87-2.86), respectively. The corresponding HRs for CHD death were 1.39 (95% CI: 1.10-1.76), 1.69 (95% CI: 1.28-2.12) and 2.53 (95% CI: 1.76-3.64), respectively. Subgroup analysis revealed significant interaction effects between non-HDL-C and sex, smoking, alcohol consumption, and diabetes (all P interaction<0.05). Sensitivity analyses confirmed that results were consistent with the primary findings regarding the association between non-HDL-C and CVD mortality risk. In conclusion, increasing non-HDL-C levels are associated with higher risks of death from cardiovascular diseases, including stroke and CHD. The risk of CVD death associated with elevated non-HDL-C is greater among males, individuals with a history of diabetes, smokers or drinkers. In the future, attention should be paid to the monitoring of non-HDL-C in community health management, and the intensive and personalized management of blood lipids in high-risk population should be strengthened.

Objective:To investigate variation and correlation of type 2 intrinsic lymphocyte(ILC2)and related factors in acute and chronic brucellosis,to identify immune role of ILC2 in chronic brucellosis.Methods:Forty-three patients with acute brucel-losis and 45 patients with chronic brucellosis were compared with 49 healthy controls.ILC2 level in each group was detected by flow cytometry.mRNA level of GATA3 in PBMC was detected by fluorescence quantitative PCR.Serum IL-33,ST2,IL-4 and IL-13 levels were detected by ELISA.ALT and AST levels were measured by fully automatic biochemical analyzer.Results:ILC2 level,GATA3 mRNA in PBMC,serum IL-33,IL-4 and IL-13 levels in chronic brucellosis group were significantly higher than healthy control group and acute brucellosis group(P<0.01).Correlation analysis showed that ILC2 level was positively correlated with GATA3 mRNA,IL-33,IL-4 and IL-13 levels,while negatively correlated with ST2 level.ROC curve suggested that ILC2,GATA3,IL-33 and ST2 had good predictive ability for severity of brucellosis patients(AUC>0.7).Conclusion:Increase of ILC2 and its related factors are closely related to chronic brucella infection,which may play an important immune role in pathogenesis of brucella infection.

Objective To assess the diagnostic efficacy of extracellular volume fraction(fECV)based on multi-slice spiral CT in evaluating lymph node metastasis of pancreatic ductal adenocarcinoma.Methods A total of 74 patients diagnosed as pancreatic ductal adenocarcinoma from March 2018 to March 2023 in the First Hospital of Jiaxing were retrospectively collected.All patients underwent enhanced multi-slice spiral CT examination.Hematocrit was collected before examination.CT values at the plain phase,portal phase,the equilibrium phase of the lesion and CT values of abdominal aorta at the same level were respectively measured after examination,and fECV was calculated.Using postoperative pathological results as the"gold standard",the efficacy of fECV in diagnosing lymph node metastases of pancreatic ductal adenocarcinoma was evaluated by receiver operating characteristic curve.Results There were 33 cases with lymph node metastasis in positive group and 41 cases in negative group.There was no statistically significant difference in fECV at the portal phase between lymph node metastasis positive group and negative group(t=0.80,P＞0.05).There was statistically significant difference in fECV at the equilibrium phase between positive and negative lymph node metastasis group(t=2.84,P＜0.001).The area under the curve of lymph node metastasis in portal phase and equilibrium phase were 0.517 and 0.870,respectively.Conclusion The fECV based on multi-slice spiral CT equilibrium phase can evaluate lymph node metastasis of pancreatic ductal adenocarcinoma.

Objective:To explore expression of Siglec-7 on monocytes in peripheral blood of patients with brucellosis and cor-relation between Siglec-7+monocytes and Th1/Th2 cells,and to analyze clinical significance of Siglec-7 molecule in patients with bru-cellosis.Methods:Fifty patients with newly diagnosed Brucella infection(BI group)and 46 healthy controls(control group)were in-cluded.Flow cytometry was used to detect expression of Siglec-7 on monocytes,and correlation between Siglec-7+monocytes and clini-cal indicators of patients with brucellosis were analyzed.Flow cytometry was used to detect Th1/Th2 cells levels,and CBA method was used to detect IFN-γ and IL-4 in peripheral serum.Correlation between Siglec-7+monocytes and Th1/Th2 cells,IFN-γ/IL-4 were ana-lyzed.Results:Siglec-7+monocytes level in BI group was significantly higher than that in control group(P<0.001);Siglec-7+mono-cytes level in patients with abnormal liver function and lung X-ray were higher than those in patients with normal liver function and lung X-ray(P<0.001,P<0.05);Compared with control group,Th2 cell and IL-4 levels were significantly increased(P<0.05),while Th1 cells and IFN-γ levels were significantly reduced(P<0.001);Th1/Th2 and IFN-γ/IL-4 were also significantly reduced(P<0.001).Siglec-7+monocyte level was negatively correlated with Th1 and IFN-γ(r=-0.651,r=-0.407),while was positively correlated with Th2 and IL-4(r=0.706,r=0.530).Conclusion:During Brucella infection,increased percentage of Siglec-7+monocytes may be involved in Th1/Th2 cell imbalance.

Objective:To investigate the expression of the novel immune checkpoint SIGLEC9 and SIGLEC9+T cells in cervical cancer and its clinical correlation.Methods:A total of 132 paraffin-embedded specimens of cervical tissue from patients with cervical cancer who under-went surgical treatment or pathological biopsy at The First Affiliated Hospital of Xinjiang Medical University from May 2022 to October 2023 were included for study.In addition,58 paraffin-embedded specimens of normal cervical tissue from patients with benign uterine leiomyomas who underwent total uterine excision during the same period were selected as normal controls.Furthermore,108 peripheral blood samples from patients with cervical cancer who underwent surgical treatment or pathological biopsy were collected for study,and 86 peripheral blood samples from healthy individuals during the same time period were selected as controls.Bioinformatics technology,im-munohistochemical(IHC)staining,flow cytometry,and double immunofluorescence(IF)staining were used to assess the expression of SIGLEC9 and SIGLEC9+T cells in cervical cancer,followed by correlation analysis with clinical indicators.Results:The bioinformatics,IHC,and double IF staining results showed that SIGLEC9 and SIGLEC9+T cells were highly expressed in cervical cancer tissues(P<0.05).The flow cyto-metry results showed that SIGLEC9+CD4+T and SIGLEC9+CD8+T cells were increased in the peripheral blood of patients with cervical cancer(P<0.05).SIGLEC9 expression correlated with tumor size,FIGO stage,lymph node metastasis,and human papillomavirus(HPV)infection(P<0.05).Conclusions:The novel immune checkpoint SIGLEC9 was highly expressed in cervical cancer tissues,and SIGLEC9+T cells infiltrated cervical cancer tissues.In vitro cell experiments showed that SIGLEC9 affects T cell function.In summary,SIGLEC9 provides a novel research direction for understanding the immune escape mechanism of cervical cancer and a novel therapeutic target for cervical cancer immuno-therapy.