Objective:To investigate the sero-conversion rate of HIV antibody and influencing factors in cross-border couples in Dehong Dai and Jingpo Autonomous Prefecture(Dehong).Methods:A cohort design was used to recruit HIV-negative people in cross-border couples in Dehong in 2017. Follow-up was conducted in 2023, and questionnaire survey and HIV test were carried out to calculate the sero-conversion rate of HIV antibody. Univariate and multivariate logistic regression models were used to analyze the influence factors for HIV infections.Results:A total of 36 278 HIV-negative persons in cross-border couples were included in the 2017 baseline survey, of whom 22 438 (61.9%) were tested in follow-up in 2023. The sero-conversion rate between 2017 and 2023 was 0.51% (115/22 438). Multivariate logistic regression analysis showed that length of marriage <6 years, Jingpo ethnic group, education level of primary school or below, drug use, illegal marriage and HIV infected spouse were the risk factors of HIV infection in male spouses, and length of marriage <6 years, Jingpo ethnic group, illegal marriage and HIV infected spouse were the risk factors in female spouses.Conclusions:The sero-conversion rate of HIV antibody in cross-border couples in Dehong was relatively high. HIV infection was mainly caused by secondary transmission in the couples, and men might also be infected through drug use. It is necessary to strengthen the registration and management of cross-border couples, especially the couples with discordant HIV infection status, and the intervention in drug users to reduce the risk for secondary transmission of HIV in the cross-border couples.

Objective:To investigate the sero-conversion rate of HIV antibody and influencing factors in cross-border couples in Dehong Dai and Jingpo Autonomous Prefecture(Dehong).Methods:A cohort design was used to recruit HIV-negative people in cross-border couples in Dehong in 2017. Follow-up was conducted in 2023, and questionnaire survey and HIV test were carried out to calculate the sero-conversion rate of HIV antibody. Univariate and multivariate logistic regression models were used to analyze the influence factors for HIV infections.Results:A total of 36 278 HIV-negative persons in cross-border couples were included in the 2017 baseline survey, of whom 22 438 (61.9%) were tested in follow-up in 2023. The sero-conversion rate between 2017 and 2023 was 0.51% (115/22 438). Multivariate logistic regression analysis showed that length of marriage <6 years, Jingpo ethnic group, education level of primary school or below, drug use, illegal marriage and HIV infected spouse were the risk factors of HIV infection in male spouses, and length of marriage <6 years, Jingpo ethnic group, illegal marriage and HIV infected spouse were the risk factors in female spouses.Conclusions:The sero-conversion rate of HIV antibody in cross-border couples in Dehong was relatively high. HIV infection was mainly caused by secondary transmission in the couples, and men might also be infected through drug use. It is necessary to strengthen the registration and management of cross-border couples, especially the couples with discordant HIV infection status, and the intervention in drug users to reduce the risk for secondary transmission of HIV in the cross-border couples.

Sick sinus syndrome(SSS)refers to damage to the sinoatrial node and its surrounding tissues,which leads to excitation and conduction dysfunction of the sinoatrial node,Resultsing in arrhythmia diseases.A better understanding of the pathogenesis of SSS is required to provide a basis for its treatment,including establishing an animal model that can simulate human sinus node dysfunction.In this paper,we review the animal selection,the principles and method of modeling,and the evaluation method and detection indicators of the models,to provide a basis for further studies of the pathogenesis of SSS.

Purpose To investigate the expression of fork-head box protein A1(FOXA1)in esophageal squamous cell car-cinoma(ESCC)and its association with clinicopathologic char-acteristics and prognosis.Methods Immunohistochemistry was used to detect FOXA1 protein expression in 532 cases of esopha-geal squamous cell carcinoma.The correlation between FOXA1 protein expression and clinicopathologic features and prognosis of patients was analyzed.Results In 532 cases of esophageal squamous cell carcinoma,183 cases overexpressed FOXA1 pro-tein(34.4％).FOXA1 overexpression was associated with ES-CC vascular infiltration(P=0.032),poorly differentiation(P=0.032),and tumor size(P＜0.001).The overall survival(OS)and disease free survival(DFS)of patients with stage Ⅰ+Ⅱ esophageal squamous cell carcinoma with high FOXA1 ex-pression tended to be poor(OS:P=0.094;DFS:P=0.107).In ESCC patients with survival longer than 24 months,the high FOXA1 expression group had significantly shorter OS and DFS(OS:P=0.048;DFS:P=0.047).Multivariate survival anal-ysis showed that the depth of tumor invasion was an independent prognostic factor affecting the prognosis of esophageal squamous cell carcinoma.Conclusion FOXA1 is overexpressed in e-sophageal squamous cell carcinoma,and its high expression is related to tumor size,vascular infiltration and poorly differentia-tion.Patients with high FOXA1 expression tended to have poor prognosis in OS and DFS.When OS and DFS≥24 months,high FOXA1 expression may be used as a reference indicator for poor prognosis in ESCC patients.

Objective To explore the expression and clinical significance of Yes-associated protein 1(YAP1)in esophageal squamous cell carcinoma.Methods Immunohistochemical method was used to detect YAP1 expression in 439 cases of esophageal squamous cell carcinoma.The differences of YAP1 expression and clinical parameters were analyzed between YAP1 positive group and YAP1 negative group.Kaplan-Meier curve was used to analyze the influence of YAP1 expression on survival of patients.Results The positive rate of YAP1 in esophageal squamous cell carcinoma was 30.52% .The tumor invasion was deeper in YAP1 positive group(P＜0.001).Kaplan-Meier survival analysis showed that YAP1 positive patients had longer disease-free survival(DFS)and overall survival(OS)among patients surviving longer than 30 months(P＜0.05).The multivariate Cox regression analysis showed that the invasion depth of tumor was an independent factor affecting DFS(HR=1.371,95% CI 0.993-1.894,P=0.035)and OS(HR=1.489,95% CI 1.066-2.080,P=0.020).Conclusions YAP1 has a certain percentage of positive rate in esophageal squamous cell carcinoma;for patients with survival longer than 30 months,YAP1 positive indicates a better prognosis.

Objective:To explore the clinical characteristics and pathogenic variant in a child with Cantú syndrome (CS).Methods:A male who was admitted to the Children′s Hospital Affiliated to Zhengzhou University on February 23, 2022 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and subjected to whole-exome sequencing (WES). Candidate variant was verified by Sanger sequencing. This study was approved by Medical Ethics Committee of the Children′s Hospital Affiliated to Zhengzhou University (Ethics No. 2023-K-087).Results:The child, a 3-year-and-2-month-old male, was born with hirsutism, with heavy hair all over the body and peculiar facial features. Routine echocardiography 1 month before had discovered atrial septal defect. Sequencing revealed that the child has harbored a heterozygous c. 2438G>C (p.S813T) variant of the ABCC9 gene, which was de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 2438G>C variant was classified as likely pathogenic (PS2+ PM2_Supporting+ PP3). Conclusion:The heterozygous c. 2438G>C variant of the ABCC9 gene probably underlay the pathogenesis of CS in this child.

Objective:To explore the effects of tensile force on vascular lumen formation in three-dimensional printed tissue.Methods:The experimental research method was used. Human umbilical vein endothelial cells (HUVECs) were extracted from discarded umbilical cord tissue of 3 healthy women (aged 22 to 35 years) who gave birth in the Department of Gynaecology and Obstetrics of Suzhou Ruihua Orthopaedic Hospital from September 2020 to May 2021. Human skin fibroblasts (HSFs) were extracted from discarded normal skin tissue of 10 male patients (aged 20 to 45 years) who underwent wound repair in the Department of Hand Surgery of Suzhou Ruihua Orthopaedic Hospital from September 2020 to September 2022. After identification of the two kinds of cells, the 4 th to 6 th passage of cells were taken for the follow-up experiments. HUVECs and HSFs were used as seed cells, and polycaprolactone, gelatin, hyaluronic acid, and fibrin were used as scaffold materials, and the three-dimensional printed vascularized tissue was created by three-dimensional bioprinting technology. The printed tissue with polycaprolactone scaffold of 6 and 10 mm spacing, and without polycaprolactone scaffold were set as 6 mm spacing polycaprolactone group, 10 mm spacing polycaprolactone group, and non-polycaprolactone group, respectively. After 4 days of culture, the printed tissue in 10 mm spacing polycaprolactone group was selected to detect the cell survival by cell viability detection kit, and the cell survival rate was calculated. After 14 days of culture, the printed tissue in three groups were taken, and the shape change of tissue was observed by naked eyes; immunofluorescence staining was performed to observe the arrangement of filamentous actin, and lumen diameter, total length, and number of branches of vessel in the tissue. The tissue with micro-spring structure in the above-mentioned three groups was designed, printed, and cultured for 9 days, and the tensile force applied in the printed tissue was measured according to the force-displacement curve. The number of samples was all 3 in the above experiments. Data were statistically analyzed with one-way analysis of variance and Tukey test. Results:After 4 days of culture, the cell survival rate in printed tissue in 10 mm spacing polycaprolactone group was (91.3±2.2)%. After 14 days of culture, the shape change of printed tissue in non-polycaprolactone group was not obvious, while the shape changes of printed tissue in 6 mm spacing polycaprolactone group and 10 mm spacing polycaprolactone group were obvious. After 14 days of culture, the arrangement of filamentous actin in the printed tissue in non-polycaprolactone group had no specific direction, while the arrangement of filamentous actin in the printed tissue in 6 mm spacing polycaprolactone group and 10 mm spacing polycaprolactone group had a specific direction. After 14 days of culture, The vascular lumen diameters of the printed tissue in 6 mm spacing polycaprolactone group and 10 mm spacing polycaprolactone group were (6.0±1.3) and (10.8±1.3) μm, respectively, which were significantly larger than 0 μm in non-polycaprolactone group ( P<0.05), and the vascular lumen diameter of printed tissue in 10 mm spacing polycaprolactone group was significantly larger than that in 6 mm spacing polycaprolactone group ( P<0.05); the total length and number of branches of blood vessel in the printed tissue in 6 mm spacing polycaprolactone group and 10 mm spacing polycaprolactone group were significantly shorter or less than those in non-polycaprolactone group ( P<0.05), and the total length and number of branches of blood vessel in the printed tissue in 10 mm spacing polycaprolactone group were significantly shorter or less than those in 6 mm spacing polycaprolactone group. After 9 days of culture, the tensile forces applied in the printed tissue in 6 mm spacing polycaprolactone group and 10 mm spacing polycaprolactone group were (2 340±59) and (4 284±538) μN, respectively, which were significantly higher than 0 μN in non-polycaprolactone group ( P<0.05), and the tensile force applied in the printed tissue in 10 mm spacing polycaprolactone group was significantly higher than that in 6 mm spacing polycaprolactone group ( P<0.05). Conclusions:The three-dimensional printed scaffold structure can exert different tensile force in the printed tissue, and the vascular lumen diameter of the printed tissue can be regulated by adjusting the tensile force.

The rise of nanotechnology has opened new horizons for cancer immunotherapy. However, most nanovaccines fabricated with nanomaterials suffer from carrier-related concerns, including low drug loading capacity, unpredictable metabolism, and potential systemic toxicity, which bring obstacles for their clinical translation. Herein, we developed an antigen self-assembled nanovaccine, which was resulted from a simple acryloyl modification of the antigen to induce self-assembly. Furthermore, a dendritic cell targeting head mannose monomer and a mevalonate pathway inhibitor zoledronic acid (Zol) were integrated or absorbed onto the nanoparticles (denoted as MEAO-Z) to intensify the immune response. The synthesized nanovaccine with a diameter of around 70 nm showed successful lymph node transportation, high dendritic cell internalization, promoted costimulatory molecule expression, and preferable antigen cross-presentation. In virtue of the above superiorities, MEAO-Z induced remarkably higher titers of serum antibody, stronger cytotoxic T lymphocyte immune responses and IFN-γ secretion than free antigen and adjuvants. In vivo, MEAO-Z significantly suppressed EG7-OVA tumor growth and prolonged the survival time of tumor-bearing mice. These results indicated the translation promise of our self-assembled nanovaccine for immune potentiation and cancer immunotherapy.

Designing and manufacturing safe and effective vaccines is a crucial challenge for human health worldwide. Research on adjuvant-based subunit vaccines is increasingly being explored to meet clinical needs. Nevertheless, the adaptive immune responses of subunit vaccines are still unfavorable, which may partially be attributed to the immune cascade obstacles and unsatisfactory vaccine design. An extended understanding of the crosstalk between vaccine delivery strategies and immunological mechanisms could provide scientific insight to optimize antigen delivery and improve vaccination efficacy. In this review, we summarized the advanced subunit vaccine delivery technologies from the perspective of vaccine cascade obstacles after administration. The engineered subunit vaccines with lymph node and specific cell targeting ability, antigen cross-presentation, T cell activation properties, and tailorable antigen release patterns may achieve effective immune protection with high precision, efficiency, and stability. We hope this review can provide rational design principles and inspire the exploitation of future subunit vaccines.

Osteoporosis (OP) is a systemic skeletal disease that primarily affects the elderly population, which greatly increases the risk of fractures. Here we report that Kindlin-2 expression in adipose tissue increases during aging and high-fat diet fed and is accompanied by decreased bone mass. Kindlin-2 specific deletion (K2KO) controlled by Adipoq-Cre mice or adipose tissue-targeting AAV (AAV-Rec2-CasRx-sgK2) significantly increases bone mass. Mechanistically, Kindlin-2 promotes peroxisome proliferator-activated receptor gamma (PPARγ) activation and downstream fatty acid binding protein 4 (FABP4) expression through stabilizing fatty acid synthase (FAS), and increased FABP4 inhibits insulin expression and decreases bone mass. Kindlin-2 inhibition results in accelerated FAS degradation, decreased PPARγ activation and FABP4 expression, and therefore increased insulin expression and bone mass. Interestingly, we find that FABP4 is increased while insulin is decreased in serum of OP patients. Increased FABP4 expression through PPARγ activation by rosiglitazone reverses the high bone mass phenotype of K2KO mice. Inhibition of FAS by C75 phenocopies the high bone mass phenotype of K2KO mice. Collectively, our study establishes a novel Kindlin-2/FAS/PPARγ/FABP4/insulin axis in adipose tissue modulating bone mass and strongly indicates that FAS and Kindlin-2 are new potential targets and C75 or AAV-Rec2-CasRx-sgK2 treatment are potential strategies for OP treatment.