Chunli Li

Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality. Although increasing evidence links vaginal microbiota to preterm birth, clinica

KRAS and TP53 co‐mutations are frequently associated with highly aggressive, therapy‐resistant cancers with limited treatment options. In this study, we have developed Autophagy‐Targeting Chimera–T‐cell Engager (AUTACE), a bifunctional nanoplatform composed of T‐cell receptor–engineered T (TCR‐T) cell–derived nanovesicles that display anti‐CD3 antibodies and encapsulate perfluoropentane (PFP) together with KPY, an autophagy‐targeting degrader active against mutant KRAS, for the treatment of KRAS/TP53 co‐mutant tumors. AUTACE targets tumors via TP53‐specific TCRs, elicits antitumor CD8 ⁺ T‐cell responses through surface anti‐CD3 antibodies, and employs low‐intensity focused ultrasound (LIFU) to trigger controlled release of KPY to degrade mutant KRAS. This achieved targeted tumor elimination. The therapeutic efficacy of AUTACE was validated in mice bearing PANC‐1 and MIA PaCa‐2 tumors. A comprehensive assessment of the post‐treatment tumor microenvironment revealed that KRAS degradation increased tumor‐derived CCL5 levels, thereby promoting CD8 ⁺ T‐cell recruitment and amplifying antitumor responses. Thus, AUTACE represents a promising strategy for the treatment of KRAS/TP53 co‐mutant tumors.

Respiratory infections, particularly those caused by influenza A virus (IAV), represent a major global health concern, contributing to substantial morbidity, mortality, and economic burden on healthcare systems worldwide. We conducted a retrospective cohort study of 21,191 patient records in Chongqing, spanning a five-year surveillance period. Logistic and Poisson regression analyses were performed to characterize IAV prevalence across age-stratified, gender-specific, and clinically defined subgroups. In addition, restricted cubic spline (RCS) models were applied to examine the nonlinear effects of meteorological factors on IAV transmission. The overall IAV positivity rate was 13.79%, with marked differences across demographic subgroups. Preschool children (ages 4–6) showed the strongest association with IAV infection (OR = 6.25, 95% CI: 4.98–7.85; RR = 5.14, 95% CI: 4.13–6.41; both P < 0.001), followed by school-aged children (ages 7–18; OR = 5.60, 95% CI: 4.45–7.06; RR = 4.70, 95% CI: 3.76–5.88; both P < 0.001). Following the relaxation of COVID-19 restrictions, IAV positivity rebounded to 21.66% in 2023, with epidemic peaks observed in March–April and November–March. Four distinct epidemic waves were identified during the 2020–2024 surveillance period. RCS models revealed significant nonlinear associations between IAV prevalence and mean temperature, temperature variation, and mean relative humidity (all P for overall and nonlinear < 0.05). The highest positivity rates occurred at mean temperatures of 7.16–16.80 °C, temperature differences > 10.92 °C, and relative humidity levels of 61.91–74.00% (all P < 0.05). Furthermore, IAV infection was significantly more common in female patients compared with male patients (14.79% vs. 12.57%), and among patients with upper respiratory tract infections compared with those with lower respiratory tract infections (15.84% vs. 11.42%). These findings highlight the importance of targeted public health interventions and sustained surveillance to reduce the burden of IAV-related respiratory infections and improve patient outcomes.

Objectives: Early-onset sepsis (EOS) is a common and serious neonatal infection that contributes significantly to morbidity and mortality. A comprehensive understanding of maternal risk factors and their association with EOS is essential for developing effective preventive strategies. Methods: In this study, Clinical and laboratory data of the patients were extracted from two hospitals in Chongqing, China (2017–2023). Collinearity analysis was performed to exclude variables with multicollinearity. Restricted cubic spline (RCS) analyses were applied to evaluate potential linear or nonlinear associations between continuous maternal variables and the risk of EOS. A multivariable Poisson regression model was developed to identify independent maternal predictors of EOS and construct a predictive model. Model performance was assessed using the area under the receiver operating characteristic curve (AUC). In addition, a nomogram based on the final Poisson regression model was established to enable individualized risk prediction and support clinical decision-making. Results: This multicenter retrospective cohort study included 79,570 mother-infant pairs, the incidence of EOS was 0.56%. Univariate and multivariable Poisson regression identified key risk factors, such as chorioamnionitis, puerperal infection, intrauterine fetal distress, preterm birth, twin pregnancy, and elevated maternal WBC, HGI, M%, and PWR. Conversely, higher maternal globulin and cesarean delivery were associated with reduced EOS risk. A predictive model with good discrimination (AUC = 0.762) was developed and visualized through a nomogram to facilitate individualized risk assessment. Conclusion: This study highlights the importance of maternal factors in early EOS prediction and supports their integration into perinatal risk assessment. Further research is needed to investigate the contribution of maternal psychosocial and nutritional status and validate the model across diverse populations.

The causes of recurrent spontaneous abortion (RSA) are highly complex. A comprehensive analysis of the risk factors for RSA will be beneficial for its diagnosis and treatment. Peripheral blood from RSA patients were collected to test the levels of autoantibodies, thyroid antibodies, anticoagulant proteins, and lupus-anticoagulants. Then, 3 major electronic databases (PubMed, China National Knowledge Infrastructure, and Cochrane Library) were searched to include all detection indicators related to RSA. First, we found that 6 autoantibodies were significantly elevated in RSA patients. Among these, antinuclear antibody (RSA: 32.99 ± 3.85; control group: 13.51 ± 3.30, P < .001, R = 0.612) showed the highest correlation with RSA. Additionally, the expression levels of anti-double-stranded DNA antibody-IgG antibody (R = 0.306) and anti-RA33 IgG antibody (R = 0.265) were also highly correlated with RSA. The protein S activity in RSA patients was significantly lower than in the control group. The ratios of lupus-anticoagulants, thyroid peroxidase antibodies, and thyroglobulin antibodies were significantly higher in RSA patients. Then, the meta-analysis revealed that the levels of antinuclear antibody, thyroid peroxidase antibody, anticardiolipid antibody, lupus anticoagulant, DFI, and BMI were significantly elevated in RSA patients, while the activity of protein S and protein C were decreased. Finally, there were no statistically significant differences in the expression levels of these indicators between patients with 2 and 3 miscarriage histories. Given the complexity of the causes of RSA, early multi-indicator combined testing for patients with a history of ≥2 miscarriages can effectively improve the accuracy of diagnosing RSA. This approach can optimize treatment plans and improve the prognosis for patients with RSA.

Embryo implantation relies on complex mother-fetus interactions. Abnormal decidualization can cause various pregnancy complications such as placental abnormalities, preeclampsia, and fetal growth restriction. circRNAs play a key role in various cellular processes. This study focuses on the role of circ-Hdac4, a circRNA derived from the Hdac4 gene, in decidualization and placental function. Mouse models revealed a spatiotemporally regulated expression of circ-Hdac4 in the endometrium during early pregnancy, with enhanced expression surrounding implantation sites. In vitro and in vivo assays confirmed that circ-Hdac4 is crucial for stromal cell decidualization, as its knockdown resulted in reduced expression of decidualization markers and disrupted endometrial architecture. Furthermore, we found that circ-Hdac4 functions as a microRNA sponge for miR-30c, which negatively regulates RBPJ, a critical protein for decidual remodeling. Proteomic analysis revealed that RBPJ was downregulated upon circ-Hdac4 silencing, and we validated the direct interaction between miR-30c and RBPJ using luciferase reporter assays. A mouse preeclampsia model showed that downregulation of circ-Hdac4 during decidualization exacerbated preeclampsia-related phenotypes, including reduced fetal counts, weights, and placental weights. In addition, we observed decreased expression of circ-Hdac4 and RBPJ in the decidual surface of placental tissues from preeclampsia patients, further supporting our findings in the mouse model. Collectively, our study provides evidence that circ-Hdac4 regulates decidualization through the miR-30c-RBPJ axis and that its abnormal expression during decidualization contributes to placental dysfunction in preeclampsia. This research offers novel insights into the molecular mechanisms underlying pregnancy complications and potential therapeutic targets for their prevention and treatment. Graphical Abstract 1. circ-Hdac4 can regulate endometrial decidualization by targeting Mir-30c-RBPJ axis in early pregnancy mice 2. circ-Hdac4/miR-30c/RBPJ axis regulating decidualization through miRNA sponging, 3. Reduced circ-Hdac4 and RBPJ expression in human preeclampsia decidua correlates with placental dysfunction

Background and aims Human papillomavirus (HPV) infection is widespread. The regional differences in infection rates and dominant HPV types are a significant aspect of the virus’s epidemiological characteristics. In China, these differences are further influenced by the country’s diverse ethnic composition, as well as varying economic and cultural conditions across regions. Additionally, factors such as population migration contribute to the exacerbation of these regional disparities in HPV infection rates. Methods We conducted an analysis of the current prevalence of HPV among 108,863 patients in Chongqing from 2017 to 2022, along with an investigation into the interaction between HPV and vaginal microbiota. Additionally, we explored the relationship between HPV clearance time and disease outcomes. Results Our findings revealed an overall HPV positive rate of 30.14% (32,813/108,863) in Chongqing, China. The top five HPV positive rates were as follows: HPV52 (7.78%), HPV16 (5.85%), HPV58 (4.41%), HPV53 (3.17%), and HPV39 (2.47%). The age-related trend of HPV infection exhibited a bimodal curve. Importantly, the positive rate of high-risk HPV (BV: 24.74%, AV: 24.38%, VVC: 18.19%, TV: 22.81%) was significantly higher than those in the control group (all P<0.05). Follow-up for 4 years, we observed an overall clearance rate of HPV at 92.20%, with a median clearance time of 13 (1-61) months. Conclusion These findings hold significant implications for the Chinese government in evaluating the prevalence of HPV in the Chongqing region and formulating effective HPV prevention strategies. Moreover, these findings could contribute to the enhancement of public health initiatives related to HPV in the region.

SASH1 (SAM and SH3 domain containing 1) has been increasingly reported as a tumor suppressor gene. However, there is limited research on the role of SASH1 in breast cancer. This manuscript aims to investigate the mechanism of SASH1 in the occurrence, development, and prognosis of breast cancer. Firstly, we obtained RNA-sequencing data of the tumors from the Genomic Data Commons data portal website, along with the corresponding clinical information of patients. Pan-cancer analysis was performed to analyze the expression of SASH1 across all tumors. Univariate Cox regression analysis was used to assess the correlation between SASH1 expression and the prognosis of breast cancer patients. Then, immunohistochemistry was utilized to evaluate the expression levels of SASH1, p-Akt, p-PI3K, and p-mTOR in breast cancer tissue. Finally, a cell assay was employed to analyze the impact of SASH1 on the proliferation and invasion of breast cancer cells (MDA-MB-231). The results revealed that SASH1 expression is decreased in BRCA, LUSC, LUAD, CESC, ESCA, and COAD. Meta-analysis also found that SASH1 is downregulated in most tumor tissues, and the expression level of SASH1 in breast cancer was significantly lower than that in the control group (OR = 0.14, 95% CI = 0.08–0.25; P < 0.001). Further experimental validation showed that SASH1 expression is significantly downregulated in breast cancer tissue (38.33%, 23/60), and the overexpression of SASH1 can inhibit the proliferation and invasion of breast cancer cells accompanied by the suppression of PI3K-Akt-mTOR signaling pathway. Additionally, SASH1 overexpression can improve OS and RFS of breast cancer patients.

Background: Previous study has indicated a potential link between gut microbiota and maternal pregnancy outcomes. However, the causal relationship between gut microbiota and premature rupture of membranes (PROM) remains a topic of ongoing debate.Methods: A two-sample Mendelian Randomization (MR) study was used to investigate the relationship between gut microbiota and PROM. Genetic data on gut microbiota was obtained from the MiBioGen consortium’s largest genome-wide association study (GWAS) (n=14,306). Genetic data on PROM (3011 cases and 104247 controls) were sourced from publicly available GWAS data from the Finnish National Biobank FinnGen consortium. Various methods including Inverse variance weighted (IVW), MR-Egger, simple mode, weighted median, and weighted mode were utilized to assess the causal relationship by calculating the odd ratio (OR) value and confidence interval (CI). Sensitivity analyses for quality control were performed using MR-Egger intercept tests, Cochran’s Q tests, and leave-one-out analyses.Results: The IVW method revealed that class Mollicutes (IVW, OR=0.773, 95%CI: 0.61-0.981, pval = 0.034), genus Marvinbryantia (IVW, OR=00.736, 95%CI: 0.555-0.977, pval = 0.034), genus Ruminooccaceae UCG003 (IVW, OR=0.734, 95%CI: 0.568-0.947, pval = 0.017) and phylum Tenericutes (IVW, OR=0.773, 95%CI: 0.566-1.067, pval = 0.034) were associated with a reduced risk of PROM, while genus Collinsella (IVW, OR=1.444, 95%CI: 1.028-2.026, pval = 0.034), genus Intestinibacter (IVW, OR=1.304, 95%CI: 1.047-1.623, pval = 0.018) and genus Turicibacter (IVW, OR=1.282, 95%CI: 1.02-1.611, pval = 0.033) increased the risk of PROM. Based on the other four supplementary methods, six gut microbiota may have a potential effect on PROM. Due to the presence of pleiotropy (pval=0.045), genus Lachnoclostridium should be ruled out. No evidence of horizontal pleiotropy or heterogeneity was found in other microbiota (pval >0.05).Conclusions: In this study, we have discovered a causal relationship between the presence of specific probiotics and pathogens in the host and the risk of PROM. The identification of specific gut microbiota associated with PROM through MR studies offers a novel approach to diagnosing and treating this condition, thereby providing a new strategy for clinically preventing PROM.