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.

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.

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.

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 pathological spectrum and variation of adult renal biopsies in People's Hospital of Xinjiang Uygur Autonomous Region from 1986 to 2020.Methods:The pathological data of 5 652 adult renal biopsies from August 1986 to December 2020 were retrospectively collected, and characteristics of pathological spectrum were analyzed. Regarding every 5 years as a research stage, the whole period was divided into 7 stages to analyze the pathological features and variation of renal biopsies. The first stage (P1) started from August 1986 to December 1990. The second stage (P2) started from January 1991 to December 1995. The third stage (P3) started from January 1996 to December 2000. The fourth stage (P4) started from January 2001 to December 2005. The fifth stage (P5) started from January 2006 to December 2010. The sixth stage (P6) started from January 2011 to December 2015. The seventh stage (P7) started from January 2016 to December 2020.Results:The age was (36.47±14.86) years old (18-83 years old) in 5 652 renal biopsies. There were 2 961 males (52.39%). There were 5 636 cases of autologous kidney biopsy and 16 cases of transplanted kidney biopsy. The descending order of incidence classified by disease types were primary glomerular disease (PGD, 4 470 cases, 79.31%), secondary glomerular disease (SGD, 994 cases, 17.64%), tubular-interstitial disease (160 cases, 2.84%), and hereditary nephropathy (12 cases, 0.21%). IgA nephropathy (IgAN, 1 573 cases, 35.19%) was the most frequent pathologic type of PGD, followed by membranous nephropathy (MN, 1 028 cases, 23.00%), mesangial proliferative glomerulonephritis (MsPGN, 878 cases, 19.64%), minimal change disease (MCD, 427 cases, 9.55%), and focal segmental glomerulosclerosis (345 cases, 7.72%). Lupus nephritis (LN, 251 cases, 25.25%) was the most common type of SGD, followed by hypertension nephropathy (193 cases, 19.42%), diabetic kidney disease (168 cases, 16.90%), purpura nephritis (138 cases, 13.88%), and ischemic nephropathy (90 cases, 9.05%). IgAN was the most common type of primary glomerulonephritis and mainly occurred in the age group of 18-59 years old. PGD was the most common glomerular disease in Han nationality (78.33%), Uygur nationality (81.72%) and other ethnic (77.15%) groups. Using Bonferroni correction method, the incidence of PGD in Uygur nationality was higher than that in Han nationality ( P<0.017). From P1 to P7, the detection rates of MN and MCD were increased in common renal pathological types, meanwhile, the ratio of MsPGN was decreased (all P<0.05). From P5 to P7, the detection rates of MN in Han nationality and Uygur nationality increased in the common pathological types of PGD, meanwhile, the ratio of MsPGN decreased (all P<0.05). LN was the most common SGD. The incidence of LN in females was higher than that in males ( P<0.001). Using Bonferroni correction method, the incidence of SGD in Uygur nationality was lower than that in Han nationality ( P<0.017). There was no significant variation in the common pathological type of SGD in Han and Uygur nationalities. Chronic rejection was the main pathological type of transplanted kidney biopsies. Conclusions:PGD is the main type of kidney disease spectrum in People's Hospital of Xinjiang Uygur Autonomous Region. IgAN is the most common PGD and mainly occurrs in the age group of 18-59 years old. As time goes by, the proportion of MN and MCD is increased, meanwhile the proportion of MsPGN is decreased significantly. LN is the most common SGD.

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*

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.

Objective: To investigate the variability of the time and frequency of Moderate to Vigorous Physical Activity (MVPA) during the school days and weekends of junior high school students, and to explore the correlation between MVPA and physical fitness. Methods: A cluster sampling method was used to investigate 79 students of grade 1 and grade 2 in Beijing Huilongguan Middle School. Adapted one day physical activity recording tool was implemented to investigate students’ physical activity from 8:00 to 23:00 a week, activity records were classified into daily MVPA parts and non MVPA parts based on MET values. Physical activity time series for 5 consecutive days and 2 weekends, as well as MVPA total time and the lempel ziv complexity of the sequence was calculated. Investigated the correlation between the MVPA situation and the results of national students’ physical fitness standard test. Results: There was no statistical difference in MVPA time between males and females during school days( t =-0.90, P >0.05). Females had greater variability in MVPA than males(58.9%, 53.5%). There was also no statistical difference in MVPA complexity between genders( t =-0.55, P >0.05). During weekends, there was no significant difference in the total MVPA time between men and women( t =-0.13, P >0.05). The CV of male MVPA time was lower than that of female(141.5%, 152.8%). There was also no significant difference( t =-0.63, P >0.05), and male MVPA complex CV was slightly higher than that of female ( 55.1% , 48.1%). The MVPA time CV of adolescents during weekdays was slightly lower for males (weekdays vs weekends: 53.5%, 141.5%) than females(58.9%, 152.8%). The MVPA complexity in weekdays among males was moderately correlated with BMI( r =0.41), and the MVPA time and weight of females ( r =-0.30) and BMI ( r =-0.31) were low. The complexity was related to body weight ( r =-0.31) and BMI ( r =-0.33) to a low degree( P <0.05). Conclusion Junior middle school students are more active on school days than weekend, but the MVPA time series are limited. Schools can effectively improve physical fitness by spreading out the activity period of MVPA in one day. MVPA complexity, as a more comprehensive indicator, may be more sensitive to BMI of junior middle school students.

Objective To analyze the clinical features and prognosis of adult optic neuritis patients with positive serum myelin oligodendrocyte glycoprotein antibody (MOG-ON) or aquaporin 4 antibody (AQP4-ON).Methods A retrospective study. From December 2015 to February 2018, in the Beijing Chaoyang Hospital of Capital Medical University and Chinese PLA General Hospital, 162 eyes of 132 patients with positive serum MOG antibody and AQP4 were included in the study. There were 42 MOG-ON patients (49 eyes, 31.8％), 90 AQP4-ON patients (113 eyes, 68.2％). The clinical features of optic neuritis (annual recurrence frequency, incidence of optic disc edema), brain and optic nerve enhanced MRI, serum autoimmune antibodies and cerebrospinal fluid test results were compared between MOG-ON and AQP4-ON patients. All patients were treated with intravenous methylprednisolone sodium succinate in the acute phase and then switched to oral prednisone acetate tablets. The average follow-up time was 15 months. The glucocorticoid dependence, visual prognosis, spinal cord symptoms, and myelitis at the last follow-up were comparatively analyzed between MOG-ON and AQP4-ON patients. The comparison of the count data was performed by χ2 test, and the measurement data were compared byt test.Results Compared with AQP4-ON patients, MOG-ON patients had higher annual recurrence frequency (t=3.760,P=0.005), higher incidence of optic disc edema (χ2=14.777,P<0.001), higher incidence of hormone dependence (χ2=25.496,P<0.001), and better visual prognosis (χ2=28.759, P<0.001). MOG-ON patients were more likely to involve the optic nerve, AQP4-ON patients were more likely to involve the optic chiasm and the optic tract. There was a significant difference in the location of lesions between MOG-ON and AQP4-ON patients (χ2= 5.447,P= 0.015). The proportion of AQP4-ON patients with autoimmune antibodies was significantly higher than that of MOG-ON patients (χ2 = 20.453,P<0.001). The results of cerebrospinal fluid test showed that the white blood cell count of patients with MOG-ON and AQP4-ON were within the normal range, but the IgG level of AQP4-ON patients was significantly higher than that of MOG-ON patients (t=8.669,P<0.001). At the last follow-up, there were 7 and 29 patients of myelitis in MOG-ON and AQP4-ON patients respectively (χ2=3.494,P=0.046).Conclusions The clinical characteristics of MOG-ON were different from AQP4-ON. The incidence of optic disc edema and recurrence rate were higher, but the proportion of autoimmune antibodies was lower. MOG-ON was more likely to show hormone dependence, but the visual prognosis was better. AQP4-ON was easily involved in optic chiasm and optic tract, and the incidence of myelitis was higher.

Objective To observe the effects of penetrance,different time of onset and mutation sites on retinal nerve fiber layer (RNFL) and macular thickness in patients with Leber's hereditary optic neuropathy (LHON).Methods This was a cross-sectional observational study.A total of 88 patients with LHON and 1492 relatives of the maternal relatives (gene carriers) who received treatment in People's Liberation Army General Hospital from 2015 to 2017 were included in the study.Among the 1492 family members,there were 694 males and 798 females.Peripheral venous blood was extracted from all subjects for mitochondrial DNA testing,and penetrance was calculated.A total of 117 patients underwent BCVA and SD-OCT examinations,including 82 patients and 35 gene carriers.The BCVA examination was performed using the Snellen visual acuity chart,which was converted into logMAR visual acuity.The thickness of RNFL,ganglion cell complex (GCC) and inner limiting membrane (ILM)-RPE were measured with OCT instrument.The mean follow-up was 50.02± 86.27 months.The disease course was divided into 6 stages including ≤3 months,4-6 months,7-12 months and ＞ 12 months.The thickness of RNFL,GCC and ILM-RPE in patients with different time of onset and mutation sites were comparatively analyzed by covariance analysis.Categorical variables were expressed as a percentage,and the x2 test was used for comparison among multiple groups.Results Among the 1492 family members,285 were diagnosed with LHON and highly suspected clinical manifestations (19.10％),including 190 males (21.98％) and 95 females (11.90％).The total penetrance rates of 11778,14484 and rare mutation sites were 19.84％ (228/1149),20.50％ (33/161),and 13.19％ (24/182) respectively;male penetrance rates were 28.87％ (153/530),27.28％ (20/72),and 18.48％ (17/92) and female penetrance rates were 12.12％ (75/619),14.61％ (13/89) and 7.78％ (7/90).There was no significant difference in total (x2=4.732),male (x2=4.263) and female (x2=4.263) penetrance between different mutation sites (P=0.094,0.110,0.349).Compared with non-pathogenic carriers,the thickness of the RNFL,GCC and ILM-RPE were all different in the four stages (≤3months,4-6 months,7-12 months and ＞12 months).The thickness ofRNFL,GCC and ILM-RPE decreased with the time of onset (P=0.000).There were significant differences in the thickness of each of the GCC and ILM-RPE layers in the macular area of LHON patients with different mutation sites (P＜ 0.05).Among them,the site 11778 and 3460 had the most severe damage in all quadrants of macular GCC and ILM-RPE layer,followed by 14484 site,and the rare site had the least damage in all quadrants.Conclusions The penetrance of LHON patients is 19.10％.With the extension of the onset time (within 1 year),the RNFL layer of the optic disc and all quadrants of the macular GCC and ILM-RPE layer gradually thinned.Compared with 11778 and rare site,14484 site,and the rare site had the lighter damage on the thickness of RNFL,GCC and ILM-RPE.