目的 探究急性脑梗死（ACI）患者血清碱性螺旋-环-螺旋转录因子40（BHLHE40）、丝氨酸蛋白酶抑制剂家族E成员1（SERPINE1）、胆绿素还原酶B（BLVRB）水平与其颈动脉粥样硬化（CAS）程度、近期预后的关系。方法 选择2023年4月—2024年8月邯郸市第一医院（以下简称“本院”）收治的112例ACI患者（研究组），另选取在本院通过健康体检的110例健康人为对照组。根据患者颈动脉内膜中层的厚度（IMT）结果，将研究组患者中的22例纳入正常组，38例纳入增厚组，52例纳入斑块组。以预后评估结果为基准，将研究组患者中的68例纳入预后良好组，44例纳入预后不良组。用ELISA法测定BHLHE40、SERPINE1、BLVRB在ACI患者血清中的表达水平；多因素Logistic回归分析ACI预后不良危险因素；ROC曲线分析BHLHE40、SERPINE1、BLVRB的预测价值。结果 与对照组比较，研究组患者血清BHLHE40、SERPINE1、BLVRB水平明显升高（P<0.05）；与正常组对比，增厚组、斑块组患者血清BHLHE40、SERPINE1、BLVRB水平明显升高，且斑块组显著高于增厚组（P<0.05）；与预后良好组比较，预后不良组血清BHLHE40、SERPINE1、BLVRB水平及NIHSS评分明显提高（P<0.05）；在ACI患者中，血清BHLHE40、SERPINE1、BLVRB水平升高，NIHSS评分提高是其预后不良的危险因素（P<0.05）；BHLHE40、SERPINE1、BLVRB联用，预测ACI预后不良的AUC为0.939；联合预测AUC优于单独预测（Z值分别为3.804、3.197、3.240，P<0.05）。结论 ACI患者血清BHLHE40、SERPINE1、BLVRB水平升高，三者不仅与病情进展相关，亦是预后的影响因素；联合检测可有效提升对ACI不良预后的预测效能。

A colon-specific drug delivery system has great potential for the oral administration of colorectal cancer. However, the uncontrollable in vivo fate of liposomes makes their effectiveness for colonic location, and intratumoral accumulation remains unsatisfactory. Here, an oral colon-specific drug delivery system (CBS-CS@Lipo/Oxp/MTZ) was constructed by covalently conjugating Clostridium butyricum spores (CBS) with drugs loaded chitosan (CS)-coated liposomes, where the model chemotherapy drug oxaliplatin (Oxp) and anti-anaerobic bacteria agent metronidazole (MTZ) were loaded. Following oral administration, CBS germinated into Clostridium butyricum (CB) and colonized in the colon. Combined with colonic specifically β-glucosidase responsive degrading of CS, dual colon-specific release of liposomes was achieved. And the accumulation of liposomes at the CRC site furtherly increased by 2.68-fold. Simultaneously, the released liposomes penetrated deep tumor tissue via the permeation enhancement effect of CS to kill localized intratumoral bacteria. Collaborating with blocking the translocation of intestinal pathogenic bacteria from lumen to tumor with the gut microbiota modulation of CB, the intratumoral pathogenic bacteria were eliminated fundamentally, blocking their recruitment to immunosuppressive cells. Furtherly, synchronized with lipopolysaccharide (LPS) released from MTZ-induced dead Fusobacterium nucleatum and the tumor-associated antigens produced by Oxp-caused immunogenic dead cells, they jointly enhanced tumor infiltration of CD8⁺ T cells and reactivated robust antitumor immunity.

Depression is a serious mental illness with a complex pathogenesis and a lack of ideal treatment methods.The crosstalk between neurons and microglia is not only crucial for brain development and maturation,but also for the learning and memory abilities of mature brains.The interaction disorder between neurons and microglia is a key factor leading to depression.In addition,neural stem cells and microglia also have complex interactions,and regulating the interaction between the two can promote the production of new neurons.Traditional Chinese medicine has a long history of preventing and treating depression.It can regulate the microglial state transition,protect neurons from damage,promote synaptic plasticity and neurogenesis.In this context,it is promising that clarifying the mechanism of neuronal-microglial crosstalk and the regulation of both by traditional Chinese medicine can yield new strategies for targeted therapeutics of depression.

Depression is a serious mental illness with a complex pathogenesis and a lack of ideal treatment methods.The crosstalk between neurons and microglia is not only crucial for brain development and maturation,but also for the learning and memory abilities of mature brains.The interaction disorder between neurons and microglia is a key factor leading to depression.In addition,neural stem cells and microglia also have complex interactions,and regulating the interaction between the two can promote the production of new neurons.Traditional Chinese medicine has a long history of preventing and treating depression.It can regulate the microglial state transition,protect neurons from damage,promote synaptic plasticity and neurogenesis.In this context,it is promising that clarifying the mechanism of neuronal-microglial crosstalk and the regulation of both by traditional Chinese medicine can yield new strategies for targeted therapeutics of depression.

Objective:To investigate the pain status in diabetic foot ulcer (DFU) patients and analyze its influencing factors.Methods:A single-center cross-sectional survey research method was used. From May 2021 to February 2022, DFU patients who were admitted to the Fourth Medical Center of PLA General Hospital and met the inclusion criteria were selected and investigated. The scores of the heaviest pain, the least pain, the average pain, and the current pain in pain degree and the total score and the scores of influence on patients' daily life, mood, walking ability, daily work, relationship with others, sleep, and life interest in pain-related effects and the total score of patients were evaluated by the brief pain inventory. A self-designed general data questionnaire was used to collect the data including patients' gender, age, education level, body mass index, self-care ability, diabetes course, wound Wagner grade, bacterial culture result of wound specimen, and the levels of glycated hemoglobin, albumin, prealbumin, hemoglobin, and leukocyte count. Patients were classified according to general data, and the total scores of pain degree and pain-related effects were counted. Data were statistically analyzed with Kruskal-Wallis test and Mann-Whitney U test. The indicators with statistically significant differences in univariate analysis were selected for generalized linear model analysis to screen the independent risk factors of pain severity and pain-related effects in DFU patients. Results:A total of 44 questionnaires were sent out, and 42 valid questionnaires were collected, with effective recovery of 95.45%. The scores of the heaviest pain, the least pain, the average pain, and the current pain in DFU patients were 5 (0, 10), 2 (0, 6), 3 (0, 8), and 2 (0, 8), respectively, and the total score of the pain severity was 11 (0, 24); the scores of pain-related effects on patients' daily life, mood, walking ability, daily work, relationship with others, sleep, and life interest were 4 (0, 10), 4 (0, 10), 5 (0, 10), 5 (0, 10), 3 (0, 10), 4 (0, 10), and 4 (0, 10), respectively, and the total score of pain-related effects was 30 (0, 63). In 42 DFU patients, most patients were male, aged 39-87 (67±10) years, most patients had education level of junior high school, most patients had diabetes for more than 20 years, half of patients' wounds were Wagner grade 4, most patients had body mass index and leukocyte count within normal limits, most patients had partial dependence on self-care ability, the bacterial culture results of wound specimen in the vast majority of patients were positive, about half of the patients had abnormal level of albumin, and most patients had abnormal levels of glycosylated hemoglobin, prealbumin, and hemoglobin. Univariate analysis of the above general data showed that total scores of pain severity among patients with different hemoglobin levels and leukocyte counts were statistically significant different (with Z values of -2.05 and -2.55, respectively, P<0.05), and the total scores of pain-related effects on patients with different hemoglobin levels, leukocyte counts, and bacterial culture results of wound specimen were statistically significant different (with Z values of -2.66, -2.02, and -2.12, respectively, P<0.05). Generalized linear model analysis showed that leukocyte count was an independent risk factor for pain severity and pain-related effects in 42 DFU patients (with 95% confidence intervals of 0.28-11.87 and 5.67-36.99, respectively, standardized regression coefficient values of 6.17 and 21.33, respectively, both P values <0.05). The bacterial culture result of wound specimen was an independent risk factor for pain-related effects in 42 DFU patients (with 95% confidence interval of 2.92-39.09, standardized regression coefficient value of 21.00, P<0.05). Conclusions:DFU patients often suffer pain, and the bacterial culture results of wound specimen and leukocyte count are the main factors affecting the pain of DFU patients.

Activating humoral and cellular immunity in lymph nodes (LNs) of nanoparticle-based vaccines is critical to controlling tumors. However, how the physical properties of nanovaccine carriers orchestrate antigen capture, lymphatic delivery, antigen presentation and immune response in LNs is largely unclear. Here, we manufactured gold nanoparticles (AuNPs) with the same size but different shapes (cages, rods, and stars), and loaded tumor antigen as nanovaccines to explore their disparate characters on above four areas. Results revealed that star-shaped AuNPs captured and retained more repetitive antigen epitopes. On lymphatic delivery, both rods and star-shaped nanovaccines mainly drain into the LN follicles region while cage-shaped showed stronger paracortex retention. A surprising finding is that the star-shaped nanovaccines elicited potent humoral immunity, which is mediated by CD4⁺ T helper cell and follicle B cell cooperation significantly preventing tumor growth in the prophylactic study. Interestingly, cage-shaped nanovaccines preferentially presented peptide-MHC I complexes to evoke robust CD8⁺ T cell immunity and showed the strongest therapeutic efficacy when combined with the PD-1 checkpoint inhibitor in established tumor study. These results highlight the importance of nanoparticle shape on antigen delivery and presentation for immune response in LNs, and our findings support the notion that different design strategies are required for prophylactic and therapeutic vaccines.

The continuing challenges that limit effectiveness of tumor therapeutic vaccines were high heterogeneity of tumor immunogenicity, low bioactivity of antigens, as well as insufficient lymph nodes (LNs) drainage of antigens and adjuvants. Transportation of in situ neoantigens and adjuvants to LNs may be an effective approach to solve the abovementioned problems. Therefore, an FA-TSL/AuNCs/SV nanoplatform was constructed by integrating simvastatin (SV) adjuvant loaded Au nanocages (AuNCs) as cores (AuNCs/SV) and folic acid modified thermal-sensitive liposomes (FA-TSL) as shells to enhance de novo antitumor immunity. After accumulation in tumor guided by FA, AuNCs mediated photothermal therapy (PTT) induced the release of tumor-derived protein antigens (TDPAs) and the shedding of FA-TSL. Exposed AuNCs/SV soon captured TDPAs to form in situ recombinant vaccine (AuNCs/SV/TDPAs). Subsequently, AuNCs/SV/TDPAs could efficiently transport to draining LNs owing to the hyperthermia induced vasodilation effect and small particle size, achieving co-delivery of antigens and adjuvant for initiation of specific T cell response. In melanoma bearing mice, FA-TSL/AuNCs/SV and laser irradiation effectively ablated primary tumor, against metastatic tumors and induced immunological memory. This approach served a hyperthermia enhanced platform drainage to enable robust personalized cancer vaccination.

Objective: To investigate the prevalence of dyslipidemia among adult professional athletes in Guangdong Province, so as to provide insights into dyslipidemia screening and health management among professional athletes. Methods: In 2019, active athletes at ages of 18 to 30 years were recruited from 12 provincial sports teams in Guangdong Province using a cluster sampling method. A self-designed questionnaire survey was conducted to collect gender, age and sport items, and the levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were detected. The non-HDL-C level was calculated, and the gender- and sport item-specific prevalence of dyslipidemia was estimated. Results: Totally 460 athletes were investigated, including 245 males (53.26%) and 215 females (46.74%), with a mean age of (21.91±2.77) years. The overall detection of dyslipidemia was 25.87%, and the detection rates of high TG, high TC, high LDL-C, low-HDL-C and high non-HDL-C were 20.22%, 5.87%, 13.04%, 3.26% and 9.57%, respectively. The detection rates of high TG (9.39% vs. 1.86%; χ2=11.743, P<0.05), low HDL-C (5.31% vs. 0.93%; χ2=6.951, P<0.05) and high non-HDL-C (12.24% vs. 6.51%; χ2=4.351, P<0.05) were significantly greater in men than in women, and the detection of high TC was lower in men than in women (17.96% vs. 22.79%; χ2=8.627, P<0.05). There was a significant difference in the detection of dyslipidemia among athletes engaging in different sport items (χ2=47.552, P<0.05), and a high detection rate of dyslipidemia was seen in baseball athletes (34.29%), softball athletes (37.04%), shooting/archery athletes (52.73%). Conclusion The prevalence of dyslipidemia was 25.87% among adult professional athletes in Guangdong Province, and high TC in combination with high LDL-C were the predominant type of dyslipidemia. The management of blood lipids should be given a high priority to male athletes and baseball, softball and shooting/archery athletes.

Objective:To explore the effects of interpregnancy interval (IPI) on pregnancy outcomes of subsequent pregnancy.Methods:A multicenter retrospective study was conducted in 21 hospitals in China. Information of age, height, pre-pregnancy weight, IPI, history of diseases, complications of pregnancy, gestational age of delivery, delivery mode, and pregnancy outcomes of the participants were collected by consulting medical records of pregnant women who had two consecutive deliveries in the same hospital during 2011 to 2018. The participants were divided into 4 groups according to IPI:<18 months, 18-23 months, 24-59 months and ≥60 months. According to the WHO′s recommendation, with the IPI of 24-59 months group as a reference, to the effects of IPI on pregnancy outcomes of subsequent pregnancy were analyzed. Stratified analysis was further carried out based on age, history of gestational diabetes mellitus (GDM), macrosomia, and premature delivery, to explore the differences in the effects of IPI on pregnancy outcomes among women with different characteristics.Results:A total of 8 026 women were included in this study. There were 423, 623, 5 512 and 1 468 participants in <18 months group, 18-23 months group, 24-59 months group and ≥60 months group, respectively. (1) The age, pre-pregnancy body mass index (BMI), history of cesarean section, GDM, gestational hypertension and cesarean section delivery rate of <18 months group, 18-23 months group, 24-59 months group and ≥60 months group were gradually increased, and the differences were statistically significant ( P<0.05). (2) After adjusting for potential confounding factors, compared with women in the IPI of 24-59 months group, the risk of premature delivery, premature rupture of membranes, and oligohydramnios were increased by 42% ( OR=1.42, 95% CI: 1.07-1.88, P=0.015), 46% ( OR=1.46, 95% CI: 1.13-1.88, P=0.004), and 64% ( OR=1.64, 95% CI: 1.13-2.38, P=0.009) respectively for women in the IPI≥60 months group. No effects of IPI on other pregnancy outcomes were found in this study ( P>0.05). (3) After stratified by age and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of oligohydramnios for women with advanced age ( OR=2.87, 95% CI: 1.41-5.83, P=0.004); and <18 months could increase the risk of premature rupture of membranes for women under the age of 35 ( OR=1.59, 95% CI: 1.04-2.43, P=0.032). Both the risk of premature rupture of membranes ( OR=1.58, 95% CI: 1.18-2.13, P=0.002) and premature delivery ( OR=1.52, 95% CI: 1.07-2.17, P=0.020) were significantly increased in the IPI≥60 months group. After stratified by history of GDM and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would lead to an increased risk of postpartum hemorrhage for women with a history of GDM ( OR=5.34, 95% CI: 1.45-19.70, P=0.012) and an increased risk of premature rupture of membranes for women without a history of GDM ( OR=1.44, 95% CI: 1.10-1.90, P=0.009). After stratified by history of macrosomia and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months could increase the proportion of cesarean section for women with a history of macrosomia ( OR=4.11, 95% CI: 1.18-14.27, P=0.026) and the risk of premature rupture of membranes for women without a history of macrosomia ( OR=1.46, 95% CI: 1.12-1.89, P=0.005). After stratified by history of premature delivery and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of premature rupture of membranes for women without a history of premature delivery ( OR=1.47, 95% CI: 1.13-1.92, P=0.004). Conclusions:Both IPI≥60 months and <18 months would increase the risk of adverse pregnancy outcomes in the subsequent pregnancy. Healthcare education and consultation should be conducted for women of reproductive age to maintain an appropriate IPI when they plan to pregnant again, to reduce the risk of adverse pregnancy outcomes in the subsequent pregnancy.

Zika virus (ZIKV) is an emerging pathogen associated with neurological complications, such as Guillain-Barré syndrome in adults and microcephaly in fetuses and newborns. This mosquito-borne flavivirus causes important social and sanitary problems owing to its rapid dissemination. However, the development of antivirals against ZIKV is lagging. Although various strategies have been used to study anti-ZIKV agents, approved drugs or vaccines for the treatment (or prevention) of ZIKV infections are currently unavailable. Repurposing clinically approved drugs could be an effective approach to quickly respond to an emergency outbreak of ZIKV infections. The well-established safety profiles and optimal dosage of these clinically approved drugs could provide an economical, safe, and efficacious approach to address ZIKV infections. This review focuses on the recent research and development of agents against ZIKV infection by repurposing clinical drugs. Their characteristics, targets, and potential use in anti-ZIKV therapy are presented. This review provides an update and some successful strategies in the search for anti-ZIKV agents are given.
Adult ; Animals ; Drug Repositioning ; Humans ; Infant, Newborn ; Microcephaly ; Pharmaceutical Preparations ; Zika Virus ; Zika Virus Infection/prevention & control*