Objective: To understand the epidemiological characteristics of a pertussis outbreak in Guangzhou, so as to provide references for outbreak response and prevention strategies. Methods: From April 5 to June 9, 2024, case screening was conducted among 246 preschool children, 35 staff members, and one full time school nurse in a kindergarten in Guangzhou based on case definition. Field epidemiological investigation methods were employed to collect relevant information, and screening samples were collected from individuals involved in the outbreak. The clinical manifestations, epidemiological characteristics, and risk factors for transmission of the outbreak were analyzed, with rate comparisons performed using the χ 2 test. Results: There were a total of 15 confirmed cases of pertussis in the kindergarten. The main clinical manifestations included intermittent cough in 14 cases ( 93.33 %), sputum production in 5 cases (33.33%), fever in 2 cases (13.33%), paroxysmal spasmodic cough in 1 case (6.67%), and vomiting in 1 case (6.67%). There was no statistically significant difference in the reporting rates of interrupted cough symptoms between pertussis cases (93.33%) and non pertussis cases (92.86%)( χ 2=3.74, P >0.05). The cases were aged 4-5 years, including 5 males and 10 females. The interval between symptom onset and diagnosis ranged from 2 to 25 days, with a median of 10 days. The outbreak involved two classes, with attack rates of 48.28% and 3.45%, respectively. Laboratory testing confirmed 14 close contacts positive for Bordetella pertussisnucleic acid. Among close contacts, only one received prophylactic medication as required. Conclusion The outbreak is a pertussis outbreak in a kindergarten caused by Bordetella pertussis infection, demonstrating distinct temporal and spatial clustering characteristics.

Objective To investigate the feasibility of the spatiotemporal filtering model in analysis of reported schistosomiasis cases, so as to provide insights into analysis of complicated data pertaining to schistosomiasis control. Methods Demographic and epidemiological data of reported schistosomiasis cases in Anhui Province from 1997 to 2010 were collected from Anhui Provincial Center for Disease Control and Prevention, and the annual prevalence of Schistosoma japonicum human infections was calculated. The meteorological data were captured from meteorological stations in counties (cities, districts) of Anhui Province where schistosomiasis cases were reported from 1997 to 2010 at the National Meteorological Information Center, including monthly average air temperature and precipitation. Meteorological data were interpolated using the inverse-distance weighting method, and the annual average air temperature and annual precipitation were calculated in each county (city, district). The centroid of the county (city, district) where schistosomiasis cases were reported was extracted using the software ArcGIS 10.0, and the Euclidean distance from each centroid to the Yangtze River was calculated as the distance between that county (city, district) and the Yangtze River. The global Moran’s I of the prevalence of S. japonicum human infections in Anhui Province for each year from 1997 to 2010 were calculated to analyze the spatial autocorrelation. A spatial weight matrix was constructed using Rook adjacency, and a first-order temporal weight matrix was built to quantify the relationship between disease changes over time. Subsequently, a spatiotemporal structure matrix was constructed. A negative binomial model was built based on the spatiotemporal structure matrix and data pertaining to reported schistosomiasis cases, and a linear model was created between the residual of the model and candidate set feature vectors to determine the optimal subset composition of the spatiotemporal filter through stepwise regression. Then, a spatio-temporal filtering model was constructed using the negative binomial model. Negative binomial models, Bayesian spatial models, and Bayesian spatiotemporal models were constructed and compared with the spatiotemporal filtering model to validate the performance of the spatiotemporal filtering model, and cross-validation was conducted for each model. The goodness of fit was evaluated using the deviance information criterion (DIC) and Watanabe-Akaike information criterion (WAIC), and the effectiveness of model validation was assessed using mean squared error (MSE), while the accuracy of assessment results was assessed using coefficients and their 95% confidence intervals (CI), and the computational efficiency was assessed based on the running time of the model. The four feature vectors with the largest Moran’s I values were selected to identify regions with autocorrelation through their schematic diagrams to investigate the differences in spatiotemporal patterns of specific regions. Results Of all models created, the spatiotemporal filtering model exhibited the highest goodness of fit (DIC = 3 240.70, WAIC = 3 257.80), the best model validation effectiveness (MSE = 42 617.52), and the runtime was 3.18 s, exhibiting the optimal performance. Across all modeling results, the distance from the Yangtze River showed a negative correlation with the number of reported schistosomiasis cases (coefficient values = −4.93 to −3.78, none of the 95% CIs included 0), and annual average air temperature or average precipitation posed no significant effects on numbers of reported schistosomiasis cases (both of the 95% CIs included 0). Schematic diagrams of feature vectors showed that the transmission of schistosomiasis might be associated with water systems in Anhui Province, and localized clustering patterns were primarily concentrated in the northern and western parts of schistosomiasis-endemic areas in the province. Conclusion The spatiotemporal filtering model is an effective spatiotemporal analysis characterized by simple modeling, user-friendly operation, accurate results and good flexibility, which may serve as an efficient alternative to conventional complex spatiotemporal models for data analysis in schistosomiasis researches.

INTRODUCTION: Visual impairment and obesity remain the major public health issues among school-age students in rural areas of China. Obesity is an underlying risk of vision problems. This study aimed to assess the association between visual impairment and body mass index (BMI) among school-age students in rural northwest China. METHODS: This study included 39,385 students from the 4 th to 9 th grade in rural northwest China. From 2018 to 2020, students underwent an assessment of visual acuity (VA) and completed a questionnaire on family demographics, and height and weight measurements. Multiple logistic regression analyses were used to analyse the data. RESULTS: The association between visual impairment and BMI groups was significant in the study population ( P = 0.002) and in different groups (at the different educational, provincial and national levels) ( P < 0.001, separately). Multiple logistic regression analyses revealed a positive relationship between visual impairment and obesity in the study population, including those attending primary school, Han students and the residents of Ningxia autonomous region. CONCLUSION The association between visual impairment and obesity was significant among school-age students in rural northwest China. There should be implementation of policies to address the problem about visual impairment and obesity among school-age students in rural areas.
Humans ; China/epidemiology* ; Body Mass Index ; Male ; Female ; Rural Population ; Vision Disorders/complications* ; Child ; Adolescent ; Students ; Surveys and Questionnaires ; Logistic Models ; Obesity/complications* ; Visual Acuity ; Cross-Sectional Studies

OBJECTIVE: To explore the corrective strategies and effectiveness of osteotomy surgery for severe lower limb deformities in hypophosphatemic rickets. METHODS: A retrospective analysis was conducted on 29 patients with severe lower limb deformities of hypophosphatemic rickets who underwent surgical treatment between February 2012 and August 2024. There were 9 males and 20 females. The age ranged from 13 to 53 years, with an average of 24.6 years. All patients were deformities of both lower limbs, presenting as 24 cases of O-shaped legs, 2 cases of wind-blown deformities, and 3 cases of X-shaped legs. Based on the full-length films of both lower limbs in the standing position before operation, the osteotomy planes of the femur, tibia, and fibula were designed. Among them, if both the same-sided thigh and leg were deformed, staged surgeries of both lower limbs were selected. If only the thigh or leg were deformed, simultaneous surgeries of both lower limbs were selected. The femur deformity was corrected immediately after osteotomy at the deformed plane; the osteotomy fragment was temporarily controlled with an external fixator, which was removed after perform internal fixation with a steel plate. After fibular osteotomy, the Ilizarov frame or Taylor frame was installed on the tibia and fibula. The threaded rods were removed and then tibial osteotomy was performed on the deformed plane. Patients using the Taylor frame did not undergo deformity correction during operation. The external fixators were adjusted starting 7 days after operation to correct the varus, valgus, and rotational deformities of the lower limb. Patients using the Ilizarov frame corrected the rotational deformity of the tibia during operation. The external fixator was adjusted starting 7 days after operation to correct the varus and valgus deformities of the lower limb. During the treatment period, the patient could walk with partial weight-bearing on the operated limb with crutches. The external fixator was removed after the bone healed. Before operation and at last follow-up, the medial proximal tibial angle (MPTA), lateral distal tibial angle (LDTA), posterior proximal tibial angle (PPTA), anterior distal tibial angle (ADTA), anatomic lateral distal femoral angle (aLDFA), posterior distal femoral angle (PDFA), and mechanical axis deviation (MAD), lower limb rotation, limb length discrepancy (LLD) were measured. The self-made scoring criteria were adopted to evaluate the degree of lower limb deformity of the patients. RESULTS: All operations were successfully completed, and no complications such as nerve or vascular injury occurred. The adjustment time of the external fixator of the lower limb after operation was 28-46 days, with an average of 37.4 days. The wearing time of the external fixator ranged from 134 to 398 days, with an average of 181.5 days. Mild pin tract infections occurred in 2 limbs. The osteofascial compartment syndrome occurred in 1 limb after operation. No complications related to orthopedic adjustment of the external fixator occurred in other patients. All patients were followed up 6-56 months, with an average of 28.2 months. At last follow-up, full-length films of both lower limbs in the standing position showed that the coronal mechanical axes of the lower limbs of all patients returned to the normal. At last follow-up, MPTA, LDTA, PPTA, aLDFA, PDFA, MAD, lower limb rotation, LLD, and the score of lower limb deformity significantly improved when compared with those before operation ( P<0.05). There was no significant difference in ADTA between pre- and post-operation ( P>0.05). The degree of lower limb deformity were rated as moderate in 2 cases and poor in 27 cases before operation and as excellent in 7 cases, good in 18 cases, and moderate in 4 cases at last follow-up, with an excellent and good rate of 86.2%. CONCLUSION For severe lower limb deformities in hypophosphatemic rickets, immediate correction of deformities with femoral osteotomy and internal plate fixation, as well as gradually correction of deformities with tibiofibular osteotomy and circular external fixation (Ilizarov frame or Taylor frame), have satisfactory therapeutic effects.
Humans ; Male ; Osteotomy/instrumentation* ; Female ; Adult ; Retrospective Studies ; Tibia/abnormalities* ; Adolescent ; Femur/abnormalities* ; Middle Aged ; Fibula/surgery* ; Rickets, Hypophosphatemic/complications* ; Young Adult ; Treatment Outcome ; External Fixators ; Bone Plates ; Lower Extremity Deformities, Congenital/etiology*

Addressing the enduring challenge of evaluating traditional Chinese medicines (TCMs), the integrated evidence chain-based effectiveness evaluation of TCMs (Eff-iEC) has emerged. This paper explored its capacity through a demonstration study that evaluated the effectiveness evidence of six commonly used anti-hepatic fibrosis Chinese patent medicines (CPMs), including Biejiajian Pill (BP), Dahuang Zhechong Pill (DZP), Biejia Ruangan Compound (BRC), Fuzheng Huayu Capsule (FHC), Anluo Huaxian Pill (AHP), and Heluo Shugan Capsule (HSC), using both Eff-iEC and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The recognition of these CPMs within the TCM academic community was also assessed through their inclusion in relevant medical documents. Results showed that the evidence of BRC and FHC received higher assessments in both Eff-iEC and GRADE system, while the assessments for others varied. Analysis of community recognition revealed that Eff-iEC more accurately reflects the clinical value of these CPMs, exhibiting superior evaluative capabilities. By breaking through the conventional pattern of TCMs effectiveness evaluation, Eff-iEC offers a novel epistemology that better aligns with the clinical realities and reasoning of TCMs, providing a coherent methodology for clinical decision-making, new drug evaluations, and health policy formulation.

Evading host immunity killing is a critical step for virus survival. Inhibiting viral immune escape is crucial for the treatment of viral diseases. Serine/threonine kinase 39 (STK39) was reported to play an essential role in ion homeostasis. However, its potential role and mechanism in viral infection remain unknown. In this study, we found that viral infection promoted STK39 expression. Consequently, overexpressed STK39 inhibited the phosphorylation of interferon regulatory factor 3 (IRF3) and the production of type I interferon, which led to viral replication and immune escape. Genetic ablation or pharmacological inhibition of STK39 significantly protected mice from viral infection. Mechanistically, mass spectrometry and immunoprecipitation assays identified that STK39 interacted with PPP2R1A (a scaffold subunit of protein phosphatase 2A (PP2A)) in a kinase activity-dependent manner. This interaction inhibited DDB1 and CUL4 associated factor 1 (DCAF1)-mediated PPP2R1A degradation, maintained the stabilization and phosphatase activity of PP2A, which, in turn, suppressed the phosphorylation of IRF3, decreased the production of type I interferon, and then strengthened viral replication. Thus, our study provides a novel theoretical basis for viral immune escape, and STK39 may be a potential therapeutic target for viral infectious diseases.

Gastrointestinal (GI) cancers are a leading cause of cancer morbidity and mortality worldwide. Despite advances in treatment, cancer relapse remains a significant challenge, necessitating novel therapeutic strategies. In this study, we engineered nanobody-based chimeric antigen receptor (CAR) natural killer (NK) cells targeting cadherin 17 (CDH17) for the treatment of GI tumors. In addition, to enhance the efficacy of CAR-NK cells, we also incorporated CV1, a CD47-SIRPα axis inhibitor, to evaluate the anti-tumor effect of this combination. We found that CDH17-CAR-NK cells effectively eliminated GI cancers cells in a CDH17-dependent manner. CDH17-CAR-NK cells also exhibit potent in vivo anti-tumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the anti-tumor activity of CDH17-CAR-NK cells is synergistically enhanced by CD47-signal regulatory protein α (SIRPα) axis inhibitor CV1, likely through augmented macrophages activation and an increase in M1-phenotype macrophages in the tumor microenvironment. Collectively, our findings suggest that CDH17-targeting CAR-NK cells are a promising strategy for GI cancers. The combination of CDH17-CAR-NK cells with CV1 emerges as a potential combinatorial approach to overcome the limitations of CAR-NK therapy. Further investigations are warranted to speed up the clinical translation of these findings.

Photodynamic immunotherapy is a promising strategy for cancer treatment. However, the dysfunctional tumor vasculature results in tumor hypoxia and the low efficiency of drug delivery, which in turn restricts the anticancer effect of photodynamic immunotherapy. In this study, we designed photosensitive lipid nanoparticles. The synthesized PFBT@Rox Lip nanoparticles could produce type I/II reactive oxygen species (ROS) by electron or energy transfer through PFBT under light irradiation. Moreover, this nanosystem could alleviate tumor hypoxia and promote vascular normalization through Roxadustat. Upon irradiation with white light, the ROS produced by PFBT@Rox Lip nanoparticles in situ dysregulated calcium homeostasis and triggered endoplasmic reticulum stress, which further promoted the release of damage-associated molecular patterns, enhanced antigen presentation, and stimulated an effective adaptive immune response, ultimately priming the tumor microenvironment (TME) together with the hypoxia alleviation and vessel normalization by Roxadustat. Indeed, in vivo results indicated that PFBT@Rox Lip nanoparticles promoted M1 polarization of tumor-associated macrophages, recruited more natural killer cells, and augmented infiltration of T cells, thereby leading to efficient photodynamic immunotherapy and potentiating the anti-primary and metastatic tumor efficacy of PD-1 antibody. Collectively, photodynamic immunotherapy with PFBT@Rox Lip nanoparticles efficiently program TME through the induction of immunogenicity and oxygenation, and effectively suppress tumor growth through immunogenic cell death and enhanced anti-tumor immunity.

OBJECTIVE: To investigate whether auraptene (AUR) exerts a protective effect on acute diquat (DQ)-induced liver injury in mice and explore its underlying mechanisms. METHODS: Forty SPF-grade healthy male C57BL/6 mice were randomly divided into normal control group (Control group), DQ poisoning model group (DQ group), AUR treatment group (DQ+AUR group), and AUR control group (AUR group), with 10 mice in each group. The DQ poisoning model was established via a single intraperitoneal injection of 40 mg/kg DQ aqueous solution (0.5 mL); Control group and AUR group received an equal volume of pure water intraperitoneally. Four hours post-modeling, DQ+AUR group and AUR group were administered 0.5 mg/kg AUR aqueous solution (0.2 mL) by gavage once daily for 7 consecutive days, while Control group and DQ group received pure water. Blood and liver tissues were collected after anesthesia on day 7. Liver ultrastructure was observed by transmission electron microscopy. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured via enzyme-linked immunosorbent assay (ELISA). Hepatic glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were detected using WST-1, thiobarbituric acid (TBA), and enzymatic reaction methods, respectively. Protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and activated caspase-9 in liver tissues was analyzed by Western blotting. RESULTS: Transmission electron microscopy revealed that mitochondria in the Control group exhibited mild swelling, uneven distribution of matrix, and a small number of cristae fractures. In the AUR group, mitochondria showed mild swelling, with no obvious disruption of cristae structure. In the DQ group, mitochondria demonstrated marked swelling and increased volume, matrix dissolution, loss and fragmentation of cristae, and extensive vacuolization. In contrast, the DQ+AUR group showed significantly reduced mitochondrial swelling, volume increase, matrix dissolution, cristae loss and fragmentation, and vacuolization compared to the DQ group. Compared with the DQ group, the DQ+AUR group exhibited significantly lower serum AST levels (U/L: 173.45±23.60 vs. 255.33±41.51), ALT levels (U/L: 51.77±21.63 vs. 100.70±32.35), and hepatic MDA levels (μmol/g: 12.40±2.76 vs. 19.74±4.10), along with higher hepatic GSH levels (mmol/g: 37.65±14.95 vs. 20.58±8.52) and SOD levels (kU/g: 124.10±33.77 vs. 82.81±22.00), the differences were statistically significant (all P < 0.05). Western blotting showed upregulated Nrf2 expression (Nrf2/β-actin: 0.87±0.37 vs. 0.53±0.22) and HO-1 expression (HO-1/β-actin: 1.06±0.22 vs. 0.49±0.08), and downregulated Keap1 expression (Keap1/β-actin: 0.82±0.12 vs. 1.52±0.76) and activated caspase-9 expression (activated caspase-9/β-actin: 1.16±0.28 vs. 1.71±0.30) in the DQ+AUR group compared to the DQ group (all P < 0.05). CONCLUSION AUR attenuates DQ-induced acute liver injury in mice by activating the Keap1/Nrf2 signaling pathway.
Animals ; Male ; Mice ; Mice, Inbred C57BL ; Liver/pathology* ; Chemical and Drug Induced Liver Injury/drug therapy* ; Diquat/poisoning* ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress ; Apoptosis ; Coumarins

Microfibrino-associated protein (MFAP) 2 is an extracellular matrix glycoprotein and a member of the MFAP family. It participates in the assembly of extracellular elastic microfibers.Upregulation of MFAP2 can promote the occurrence and development of various tumors and regulate multiple cancer-related signaling pathways and is related to their prognosis, making it a potential target for tumor treatment. This article summarizes the research progress on the pathogenesis, targeted therapy and prognosis of MFAP2 in malignant tumors.