Diabetic retinopathy(DR)remains the leading cause of vision loss in patients with diabetes. Current anti-vascular endothelial growth factor(VEGF)therapies are limited by inadequate response in some patients and the necessity for repeated intravitreal injections, underscoring the urgent need for novel therapeutic targets. Angiopoietin-like protein 4(ANGPTL4), a multifunctional secreted protein, has emerged as a critical regulator in the pathogenesis and progression of DR, positioning it as a promising interventional target. This review systematically elaborates the biological characteristics of ANGPTL4, with a focus on its expression dynamics, molecular mechanisms, and regulatory networks rolesin the development of DR. Furthermore, the prospects of ANGPTL4-targeted therapeutic strategies are discussed, aiming to offer new insights and directions for understanding DR pathogenesis, advancing multi-target drug development, and improving clinical management.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Objective To explore the association between dynamic indexes of maternal progesterone in early pregnancy and the average level and growth rate of fetal head circumference(HC)in mid-and late pregnancy.Methods This study adopted a retrospective cohort design and included 255 singleton pregnant women in the maternal and infant cohort of The First Affiliated Hospital of Xi'an Jiaotong University from January 2015 to December 2024.The progesterone levels of their early venous blood were detected and divided into two groups of progesterone trajectories,namely,fluctuating type and increasing type,by morphology.The dynamic indicators of progesterone in early pregnancy were constructed:cumulative dynamic deviation index in the first trimester(CDDI-P1T),gestational age at progesterone peak(GA-PP),and maximal relative progesterone decline in the first trimester(MRD-P1T).The average head circumference level and linear growth rate of the fetuses in the middle and late pregnancy were calculated.Generalized linear regression(GLM)was used to analyze the linear association between progesterone dynamic indicators and head circumference development.The key gestational weeks of progesterone affecting fetal head development were explored by linear regression of gestational weeks.Ordinary least squares(OLS)regression and restricted cubic spline(RCS)plots were used to draw the nonlinear association between progesterone dynamic indicators and head circumference.Results Among the 255 pregnant women included,92.5％of the progesterone trajectories in early pregnancy were fluctuating,and 7.5％were increasing.The growth rates of the increasing progesterone trajectory group were higher in the second and third trimesters than in the fluctuating group,but the differences were not statistically significant(all P＞0.05).GLM analysis showed that for every 1 unit increase in CDDI-P1T,the head circumference in the middle and late pregnancy increased significantly by 1.574 cm and 1.193 cm(Z=3.714,2.885,P＜0.01).The delay of GA-PP was negatively correlated with the head circumference in the middle pregnancy(β=-0.190 cm,95％CI:-0.339--0.041,P=0.010)but positively correlated with the head circumference growth rate in the late pregnancy(β=0.022 cm/week,95％CI:0.003-0.041,P=0.025).A 10％decrease in the decline of CDDI-P1T increased the head circumference in the middle pregnancy by 0.200 cm(95％CI:0.016-0.384,P=0.033),and a 100％decrease in the decline increased the head circumference growth rate in the late pregnancy by 0.201 cm/week(95％CI:0.002-0.399,P=0.048).The analysis of the key time window showed that for every 20 nmol/L increase in progesterone during 9.5-13 weeks of pregnancy,the mid-term head circumference increased by 0.035-0.166 cm(Z=2.452-3.517,allP＜0.05),and the late-term head circumference increased by 0.767 cm during 9-13 weeks of pregnancy(Z=2.452-3.517,all P＜0.05).When progesterone increased during 9.5-10.5 weeks of pregnancy,the growth rate of mid-term head circumference increased by 0.013-0.023 cm/week(Z=2.074-2.243,all P＜0.01).When progesterone increased during 8.5-10.5 weeks of pregnancy,the growth rate of late-term head circumference increased by 0.010-0.026 cm/week(Z=2.061-3.137,all P＜0.05).Conclusion Progesterone dynamic index is a new sensitive tool for evaluating fetal head circumference development.There is a stage-specific window period for progesterone regulation.9.5-13 weeks of pregnancy is the critical period for progesterone to affect head circumference growth,and 9.5-10.5 weeks of pregnancy is the core window for regulating the growth rate of head circumference.Therefore,it is necessary to combine progesterone dynamic index and time window for individualized intervention to promote the transformation of prenatal care from pregnancy maintenance to eugenics intervention.

Objective:To investigate the effects of dexmedetomidine(DEX)on T cell subsets in rats with rheumatoid arthritis(RA)by regulating interleukin-10(IL-10)/signal transduction factor and transcriptional activator 3(STAT3)signaling pathways.Methods:SD rats were grouped into control group(NC group),Model group,DEX low-dose group(DEX-L group,5 μg/kg),DEX medium-dose group(DEX-M group,10 μg/kg),DEX high-dose group(DEX-H group,20 μg/kg),methotrexate group(MTX group,0.33 mg/kg),AS101 group(IL-10 inhibitor,1.5 mg/kg)and DEX-H+AS101 group(20 μg/kg+1.5 mg/kg),with 18 rats in each group.Except NC group,RA models were established in rats of other groups.The administration was started 24 hours after the second immunization,once a day for 3 weeks.The changes of foot swelling rate and joint index were measured;HE staining was applied to detect the pathological changes of spleen tissue;the levels of TNF-α and IL-1β in rat spleen were detected by ELISA;the percentages of CD3+CD4+T cells,CD3+CD8+T cells and the proportions of helper T cell 17(Th17)and regulatory T cell(Treg)in rat spleen were measured by flow cytometry;and Western blot was applied to detect the expressions of IL-10 and p-STAT3 protein in rat spleen.Results:Compared with NC group,the pathological damage of spleen tissue in Model group was serious,the feet swelling rate,joint index,the levels of TNF-α and IL-1β,the percentage of CD3+CD4+T cells,Th17 cells,Th17/Treg were increased,the percentage of CD3+CD8+T cells,Treg,and expression of IL-10 and p-STAT3 protein were decreased(P<0.05);compared with Model group,the pathological damage of spleen tissue in DEX-L group,DEX-M group,DEX-H group and MTX group were reduced,the feet swelling rate,joint index,the levels of TNF-α and IL-1β,the percentage of CD3+CD4+T cells,Th17 cells,Th17/Treg decreased,the percent-age of CD3+CD8+T cells,Treg,and expressions of IL-10 and p-STAT3 protein were increased(P<0.05);compared with Model group,the pathological damage of spleen tissue in AS101 group was aggravated,the feet swelling rate,joint index,the levels of TNF-α and IL-1β,the percentage of CD3+CD4+Tcells,Th17 cells,Th17/Treg were increased,the percentage of CD3+CD8+T cells,Treg cells,and expression of IL-10 and p-STAT3 protein were decreased(P<0.05);AS101 attenuated the promoting effect of high dose DEX on the proportion balance of T cell subsets in RA rats.Conclusion:DEX may promote the balance of T cell subsets in RA rats by activating IL-10/STAT3 pathway.

Objective:To investigate the effects of dexmedetomidine(DEX)on T cell subsets in rats with rheumatoid arthritis(RA)by regulating interleukin-10(IL-10)/signal transduction factor and transcriptional activator 3(STAT3)signaling pathways.Methods:SD rats were grouped into control group(NC group),Model group,DEX low-dose group(DEX-L group,5 μg/kg),DEX medium-dose group(DEX-M group,10 μg/kg),DEX high-dose group(DEX-H group,20 μg/kg),methotrexate group(MTX group,0.33 mg/kg),AS101 group(IL-10 inhibitor,1.5 mg/kg)and DEX-H+AS101 group(20 μg/kg+1.5 mg/kg),with 18 rats in each group.Except NC group,RA models were established in rats of other groups.The administration was started 24 hours after the second immunization,once a day for 3 weeks.The changes of foot swelling rate and joint index were measured;HE staining was applied to detect the pathological changes of spleen tissue;the levels of TNF-α and IL-1β in rat spleen were detected by ELISA;the percentages of CD3+CD4+T cells,CD3+CD8+T cells and the proportions of helper T cell 17(Th17)and regulatory T cell(Treg)in rat spleen were measured by flow cytometry;and Western blot was applied to detect the expressions of IL-10 and p-STAT3 protein in rat spleen.Results:Compared with NC group,the pathological damage of spleen tissue in Model group was serious,the feet swelling rate,joint index,the levels of TNF-α and IL-1β,the percentage of CD3+CD4+T cells,Th17 cells,Th17/Treg were increased,the percentage of CD3+CD8+T cells,Treg,and expression of IL-10 and p-STAT3 protein were decreased(P<0.05);compared with Model group,the pathological damage of spleen tissue in DEX-L group,DEX-M group,DEX-H group and MTX group were reduced,the feet swelling rate,joint index,the levels of TNF-α and IL-1β,the percentage of CD3+CD4+T cells,Th17 cells,Th17/Treg decreased,the percent-age of CD3+CD8+T cells,Treg,and expressions of IL-10 and p-STAT3 protein were increased(P<0.05);compared with Model group,the pathological damage of spleen tissue in AS101 group was aggravated,the feet swelling rate,joint index,the levels of TNF-α and IL-1β,the percentage of CD3+CD4+Tcells,Th17 cells,Th17/Treg were increased,the percentage of CD3+CD8+T cells,Treg cells,and expression of IL-10 and p-STAT3 protein were decreased(P<0.05);AS101 attenuated the promoting effect of high dose DEX on the proportion balance of T cell subsets in RA rats.Conclusion:DEX may promote the balance of T cell subsets in RA rats by activating IL-10/STAT3 pathway.

Objective To explore the association between dynamic indexes of maternal progesterone in early pregnancy and the average level and growth rate of fetal head circumference(HC)in mid-and late pregnancy.Methods This study adopted a retrospective cohort design and included 255 singleton pregnant women in the maternal and infant cohort of The First Affiliated Hospital of Xi'an Jiaotong University from January 2015 to December 2024.The progesterone levels of their early venous blood were detected and divided into two groups of progesterone trajectories,namely,fluctuating type and increasing type,by morphology.The dynamic indicators of progesterone in early pregnancy were constructed:cumulative dynamic deviation index in the first trimester(CDDI-P1T),gestational age at progesterone peak(GA-PP),and maximal relative progesterone decline in the first trimester(MRD-P1T).The average head circumference level and linear growth rate of the fetuses in the middle and late pregnancy were calculated.Generalized linear regression(GLM)was used to analyze the linear association between progesterone dynamic indicators and head circumference development.The key gestational weeks of progesterone affecting fetal head development were explored by linear regression of gestational weeks.Ordinary least squares(OLS)regression and restricted cubic spline(RCS)plots were used to draw the nonlinear association between progesterone dynamic indicators and head circumference.Results Among the 255 pregnant women included,92.5％of the progesterone trajectories in early pregnancy were fluctuating,and 7.5％were increasing.The growth rates of the increasing progesterone trajectory group were higher in the second and third trimesters than in the fluctuating group,but the differences were not statistically significant(all P＞0.05).GLM analysis showed that for every 1 unit increase in CDDI-P1T,the head circumference in the middle and late pregnancy increased significantly by 1.574 cm and 1.193 cm(Z=3.714,2.885,P＜0.01).The delay of GA-PP was negatively correlated with the head circumference in the middle pregnancy(β=-0.190 cm,95％CI:-0.339--0.041,P=0.010)but positively correlated with the head circumference growth rate in the late pregnancy(β=0.022 cm/week,95％CI:0.003-0.041,P=0.025).A 10％decrease in the decline of CDDI-P1T increased the head circumference in the middle pregnancy by 0.200 cm(95％CI:0.016-0.384,P=0.033),and a 100％decrease in the decline increased the head circumference growth rate in the late pregnancy by 0.201 cm/week(95％CI:0.002-0.399,P=0.048).The analysis of the key time window showed that for every 20 nmol/L increase in progesterone during 9.5-13 weeks of pregnancy,the mid-term head circumference increased by 0.035-0.166 cm(Z=2.452-3.517,allP＜0.05),and the late-term head circumference increased by 0.767 cm during 9-13 weeks of pregnancy(Z=2.452-3.517,all P＜0.05).When progesterone increased during 9.5-10.5 weeks of pregnancy,the growth rate of mid-term head circumference increased by 0.013-0.023 cm/week(Z=2.074-2.243,all P＜0.01).When progesterone increased during 8.5-10.5 weeks of pregnancy,the growth rate of late-term head circumference increased by 0.010-0.026 cm/week(Z=2.061-3.137,all P＜0.05).Conclusion Progesterone dynamic index is a new sensitive tool for evaluating fetal head circumference development.There is a stage-specific window period for progesterone regulation.9.5-13 weeks of pregnancy is the critical period for progesterone to affect head circumference growth,and 9.5-10.5 weeks of pregnancy is the core window for regulating the growth rate of head circumference.Therefore,it is necessary to combine progesterone dynamic index and time window for individualized intervention to promote the transformation of prenatal care from pregnancy maintenance to eugenics intervention.

Objectives:To investigate the association between normal-weight central obesity with new-onset cardiovascular disease and all-cause mortality risk. Methods:A prospective cohort study was conducted,selecting a total of 93885 participants from the Kailuan Study who had their first physical examination in 2006-2007.According to waist circumference (central obesity:male waist circumference ≥90 cm,female waist circumference ≥85 cm;no central obesity:male waist circumference<90 cm,female waist circumference<85 cm) and body mass index (BMI,normal weight:18.5 kg/m2≤BMI<24.0 kg/m2;overweight/obesity:BMI ≥24.0 kg/m2),the participants were divided into 4 groups:normal weight no central obesity group (G1 group),normal weight central obesity group (G2 group),overweight/obesity no central obesity group (G3 group) and overweight/central obesity group (G4 group);Using the Kaplan-Meier method,the cumulative incidence of new-onset cardiovascular diseases (including hemorrhagic stroke,ischemic stroke and myocardial infarction) and all-cause mortality in different groups was calculated,and the Log-rank test was used for intergroup comparisons.Furthermore,the associations between the different groups and the risk of new-onset cardiovascular diseases and all-cause mortality were analyzed using the multivariate Cox proportional hazard regression model. Results:After a median follow-up of 14.97 (14.55,15.17) years,the cumulative incidence of new-onset cardiovascular diseases in G1 group,G2 group,G3 group and G4 group was 7.62％,10.84％,8.67％,12.91％ respectively (log-rank P<0.05) and the cumulative incidence of all-cause mortality was 12.83％,19.72％,10.65％,16.33％ respectively (log-rank P<0.01).After adjusting for confounding factors,Cox regression analysis showed that the HR (95％CI) of new-onset cardiovascular diseases in G2 group,G3 group and G4 group were 1.14 (1.04-1.25),1.07 (1.01-1.14),1.27 (1.21-1.34),respectively compared with G1 group (all P<0.05).The HR (95％CI) of all-cause mortality were 1.06 (1.00-1.14),0.90 (0.85-0.95),0.97 (0.93-1.01) compared with G1 group,and P values were 0.07,<0.01,0.15,respectively.The results of sensitivity analysis were consistent with the above major studies after excluding overweight/obesity and cancer participants during follow-up. Conclusions:Normal-weight central obesity increases the risk of new-onset cardiovascular diseases and all-cause mortality.

ObjectiveTo systematically evaluate the safety of Tianzhi granules used in the treatment of mild-to-moderate vascular dementia. MethodA randomized， double-blind， double-simulated， positive drug/placebo parallel controlled multi-center phase Ⅳ clinical trial and an open multi-center phase Ⅳ clinical trial of Tianzhi granules in the treatment of mild-to-moderate vascular dementia were conducted. Safety data of 1 492 patients were included and analyzed according to inclusion and exclusion criteria. The main evaluation measures were the incidence rate of adverse events/adverse reactions， laboratory indicators， vital signs， and electrocardiogram （ECG） results. ResultA total of six adverse events possibly related to the test drug occurred in 520 patients of the double-blind trial， and the symptoms were all mild and recovered. The incidence of adverse events was not statistically different among Tianzhi granules， donepezil， and placebo groups. Nine adverse events possibly related to the test drug were observed in 972 patients of the open trial， and the symptoms were mild and recovered. Laboratory tests （blood routine， urine routine， liver function， kidney function， and coagulation） and vital signs were compared before treatment （baseline） and after treatment of 12 and 24 weeks， respectively. There was no statistical significance in the main indicators before and after treatment. In the double-blinded trial， there was no significant difference in safety indicators between different groups before and after treatment. The most frequent adverse reaction was gastrointestinal discomfort， with an incidence rate of 6.64‰. ConclusionAdverse reactions occasionally occur in patients using Tianzhi granules， and it is safe to use Tianzhi granules to treat mild-to-moderate vascular dementia clinically.

Objective To investigate the characteristics of menopause-related symptoms and cognition status of menopausal hormone therapy(MHT)among menopausal women.Methods A total of 619 menopausal women with menopause-related symptoms who were admitted to The First Affiliated Hospital of Xi'an Jiaotong University were selected as the study subjects.Data were collected by questionnaire to analyze the characteristics of menopause-related symptoms,and the menopausal women's cognitive status of MHT and therapeutic effects were explored.Results Among 371 perimenopausal women,the menopause-related symptoms with the top three rates were fatigue(69.81％),insomnia(66.85％),and hot flush-sweating(58.22％).Among 248 postmenopausal women,the menopause-related symptoms with the top three rates were hot flashes and sweating(64.11％),bone and joint pain(60.89％),and fatigue(56.85％).The incidence of insomnia and fatigue in postmenopausal women was significantly lower than that in perimenopausal women(P＜0.01),while the incidence of bone and arthralgia,urinary system infection,vaginal dryness and painful intercourse was significantly higher than that in perimenopausal women(P＜0.01).There was no significant difference in Kupperman score between perimenopausal and postmenopausal women(P＞0.05),but score degree distribution differed significantly(P＜0.05).Perimenopausal women had the highest proportion of mild score while postmenopausal women had the highest proportion of moderate score.There were significant differences in Kupperman score among postmenopausal women with different menopause ages,menopause years and menopause mode(P＜0.05).The earlier menopause age and shorter menopause years,the higher Kupperman score was;the Kupperman score was significantly higher in surgical menopause than in natural menopause(P＜0.05).Multivariate Logistic regression analysis showed that age of 45-54 years old,retirement or unemployment,spouse's disease or death,abnormal sexual life,and high education level were the risk factors for the occurrence of menopausal symptoms(P＜0.05);high family income and＞3 times/week exercise were the protective factors for the occurrence of menopausal symptoms(P＜0.05).The Internet was the way that accounted for the highest proportion of menopausal women's understanding of MHT(39.92％),and the tumor accounted for the highest proportion of menopausal women's concern about MHT(33.67％).There were 465 menopausal women without MHT contraindications(89.77％)who used MHT under the guidance of professional doctors,and their symptoms improved significantly after treatment(P＜0.05).Conclusion Menopausal women have obvious menopause-related symptoms,and the earlier the age,the shorter the menopause years and the more severe symptoms in the surgical menopause.Therefore,it is necessary to pay attention to the impact of menopause on the health of menopausal women and increase the use rate of MHT to improve the quality of life of menopausal women.

Objective:To investigate the efficacy and safety of endoscopic ligation and injection sclerotherapy for internal hemorrhoids.Methods:From April 2020 to October 2023, 106 patients with grade Ⅰ to Ⅲ internal hemorrhoids who underwent endoscopic ligation or injection sclerotherapy in the First Affiliated Hospital with Nanjing Medical University (Jiangsu Province People's Hospital) were consecutively enrolled in the retrospective cohort study. Patients were divided into the ligation group ( n=70) and the injection sclerotherapy group ( n=36) according to the endoscopic treatment methods. The effective rate, hospital stay, postoperative pain, the incidence of complications, patient satisfaction and the recurrence rate of the two groups were assessed. Results:The effective rate was 95.7% (67/70) and 100.0% (36/36) respectively in the ligation group and the injection sclerotherapy group without significant difference ( P=0.549). The hospital stay was 6.0 (4.0, 7.3) days and 3.0 (2.0, 4.0) days respectively in the ligation group and the injection sclerotherapy group with significant difference ( Z=4.305, P<0.001). The incidence of 24-hour postoperative pain was 58.6% (41/70) and 11.1% (4/36) in the two groups respectively and the difference was statistically significant ( χ2=20.020, P<0.001). There were no serious postoperative adverse events such as anal stenosis or thrombotic external hemorrhoids in the two groups. Only the incidence of anal distension was significantly different between the ligation group and the injection sclerotherapy group [38.6% (27/70) VS 5.6% (2/36), χ2=11.431, P<0.001]. The patient satisfaction rate of the two groups showed no significant difference [87.1% (61/70) VS 86.1% (31/36), P=1.000]. There was 1 patient and 15 patients lost to follow-up respectively in the ligation group and the injection sclerotherapy group, and the recurrence rate of the two groups showed no significant difference [14.5% (10/69) VS 33.3% (7/21), P=0.064]. Subgroup analysis of grade Ⅰ-Ⅱ internal hemorrhoids: there were 43 patients and 29 patients in the ligation group and the injection sclerotherapy group, respectively. No significant difference was found between the two groups in terms of the effective rate, incidence of postoperative hemorrhage, incidence of uroschesis, or patient satisfaction rate ( P>0.05). The incidences of postoperative pain [65.1% (28/43) VS 10.3% (3/29), χ 2=19.016, P<0.001] and anal distension [41.9% (18/43) VS 3.4% (1/29), χ 2=11.252, P<0.001] of the ligation group were significantly higher than those of the injection sclerotherapy group. Forty-three patients in the ligation group and 17 patients in the injection sclerotherapy group completed follow-up, and the recurrence rate was 11.6% (5/43) and 23.5% (4/17), respectively, without significant difference ( P=0.256). Subgroup analysis of grade Ⅲ internal hemorrhoids: there were 27 patients in the ligation group and 7 patients in the injection sclerotherapy group, and 26 and 4 patients completed follow-up, with a recurrence rate of 19.2% (5/26) and 75.0% (3/4), respectively. Conclusion:Endoscopic ligation and injection sclerotherapy are both safe and effective for grade Ⅰ-Ⅲ internal hemorrhoids. Injection sclerotherapy demonstrates shorter hospital stays and lower incidences of postoperative pain and anal distension. For grade Ⅰ-Ⅱ internal hemorrhoids, injection sclerotherapy is recommended due to its efficacy and fewer complications. Conversely, for grade Ⅲ internal hemorrhoids, ligation is suggested to reduce recurrence rates.