Objective To develop a predictive model for postoperative pulmonary complications (PPC) following video-assisted thoracic surgery (VATS) in lung cancer patients by integrating cardiopulmonary exercise testing (CPET) parameters and machine learning techniques. Methods A retrospective analysis was conducted on patients with early-stage non-small cell lung cancer who underwent CPET and VATS at Guangdong Provincial People’s Hospital between October 2021 and July 2023. Patients were divided into a PPC group and a non-PPC group. The least absolute shrinkage and selection operator (LASSO) regression was used to select important features associated with PPC. Six machine learning algorithms were utilized to construct prediction models, including logistic regression, support vector machine, k-nearest neighbors, random forest, gradient boosting machine, and extreme gradient boosting. The optimal model was interpreted using SHapley Additive exPlanations (SHAP). Results A total of 325 patients were included, with an average age of 60.36 years, and 55.1% were male. Significant differences were observed between the PPC and non-PPC groups in age, diabetes, coronary heart disease, surgical approach, forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FVC% predicted, peak oxygen uptake (peak VO2), anaerobic threshold (AT), and ventilatory equivalent for carbon dioxide slope (VE/VCO2 slope) (P<0.05). In the predictive model constructed by selecting 7 key features using LASSO regression, the random forest model demonstrated the best overall performance across various metrics, with an area under the receiver operating curve of 0.930, an F1 score of 0.836, and a Brier score of 0.133 in the training set. It also exhibited good predictive ability and calibration in the test set. SHAP analysis ranked feature importance as follows: peak VO2, VE/VCO2 slope, age, FEV1, smoking history, diabetes, and surgical approach. Conclusion Integrating CPET parameters, the random forest model can effectively identify high-risk patients for PPC and has the potential for clinical application.

Objective: To characterize longitudinal trajectories of testicular development in boys and breast development in girls, so as to provide reference data for understanding patterns of pubertal sexual maturation. Methods: Based on the Shanghai Pudong New Area Cohort Study on Growth, Development and Health in Children and Adolescents, a baseline survey was conducted in 2020 using a mult stage cluster random sampling method. A total of 2 184 children who completed all follow ups during the primary school period from 13 elementary schools in Pudong New Area,Shanghai,with annual follow ups during 2021-2025. Testicular volume and Tanner stage of breast development were assessed by professional physicians using standardized visual inspection and palpation. The age distribution of testicular volume and breast development was fitted by using cumulative link mixed models and Turnbull s nonparametric maximum likelihood estimation method. Results: Median ages for testicular volumes of 2, 3, 4 and 5 mL in boys were 7.07, 9.24, 10.29, and 11.57 years old, respectively. Median ages for Tanner breast stages Ⅱ, Ⅲ, Ⅳ, and Ⅴ in girls were 8.55 , 10.17, 11.18, and 13.78 years old, respectively. Based on overweight and obesity, stratified analysis showed that earlier pubertal onset among overweight/obesity children, and the key milestones for pubertal initiation were testicular volume reaching 4 mL in boys and breast Tanner II in girls for 10.29, 10.83; 8.18, 9.00 years. Conclusion Overweight and obesity are associated with earlier pubertal initiation,but there are certain gender and developmental stage specific patterns.

OBJECTIVES: To investigate the efficacy of Ag₂Se nanoparticles for eliminating intracellular Porphyromonas gingivalis (P. gingivalis) in esophageal cancer and examine the effect of P. gingivalis clearance on progression of esophageal cancer. METHODS: Ag₂Se nanoparticles were synthesized via a chemical synthesis method. The effects of Ag₂Se nanoparticles on P. gingivalis viability and colony-forming ability were assessed using fluorescence staining and colony formation assays. In a mouse model bearing subcutaneous murine esophageal cancer cell allograft with P. gingivalis infection, the effect of treatment with Ag₂Se nanoparticles on the abundance of P. gingivalis in the tumor tissues was quantified using RNAscope in situ hybridization and quantitative polymerase chain reaction (qPCR), and the changes in tumor volume were monitored. The biosafety of Ag₂Se nanoparticles was assessed by examining liver and kidney functions and pathological changes in the major organs of the mice. RESULTS: Transmission electron microscopy revealed that the synthesized Ag₂Se nanoparticles were uniformly dispersed spherical particles with a diameter around 50 nm. In vitro experiments demonstrated that exposure to Ag₂Se nanoparticles significantly reduced the viability and clonal proliferation capacity of P. gingivalis in a dose-dependent manner. In the tumor-bearing mice, treatment with Ag₂Se nanoparticles significantly reduced the abundance of P. gingivalis in tumor tissues and suppressed tumor cell proliferation. No significant damages to the liver and kidney functions or the major organs were observed in Ag₂Se nanoparticle-treated mice, demonstrating good biocompatibility of Ag₂Se nanoparticles. CONCLUSIONS Ag₂Se nanoparticles exhibit significant bactericidal and inhibitory effects against P. gingivalis, and can effectively eliminate intracellular P. gingivalis to suppress the growth of esophageal cancer allograft in mice, suggesting the potential of Ag₂Se nanoparticles in the treatment of esophageal cancer.
Animals ; Porphyromonas gingivalis/drug effects* ; Mice ; Esophageal Neoplasms/pathology* ; Nanoparticles ; Metal Nanoparticles ; Bacteroidaceae Infections ; Cell Line, Tumor

OBJECTIVE: To investigate the therapeutic effects of Banxia Xiexin Decoction (BXD), a herbal medicine formula, on inflammation and the imbalance of the gut microbiota in a rat model of colorectal cancer (CRC) induced by azoxymethane (AOM) /dextran sulfate sodium (DSS). METHODS: A total of 75 male C57BL/6 mice were randomly divided into five groups: normal control group (NC), model group (MODEL), low-dose BXD treatment group (L-BXD), high-dose BXD treatment (H-BXD) group and MS treatment group (MS). BXD and MS were used in CRC mice at the doses of 3.915 g/kg, 15.66 g/kg, 0.6 g/kg for 3 weeks consecutively. Histopathological changes in the colon were observed using hematoxylin-eosin (HE) staining. The content of inflammatory factors in serum was detected by an enzyme-linked immunosorbent assay (ELISA), and the expression of mRNA and protein of genes related to immunity, apoptosis, inflammation, and inflammatory factors was evaluated. Changes in the intestinal flora of mouse fecal were determined based on high-throughput sequencing of the 16S rRNA microbial gene. RESULTS: Compared to the model group, the low-dose BXD and high-dose BXD groups decreased the number of colon tumors, reversed weight loss, and shortened colon length of mice. The pathological examination showed that BXD alleviated the malignancy of intestinal tumors. It also suppressed signal transducer and activator of transcription 3 (STAT3), matrix metalloproteinase-9 (MMP-9), and transforming growth factor beta 1 (TGF-β1) expression, while increasing the expression of the tight junction protein ZO-1 in colon tissues. Additionally, the levels of key pathway proteins involved in inflammation (phosphorylated-STAT3, Bcl-2, COX-2) and cell cycle regulatory molecules (c-Myc and PCNA) were reduced. According to 16S rRNA sequence analysis, BXD enhanced the relative abundance of potentially beneficial bacteria, while that of cancer-related bacteria decreased. CONCLUSION BXD plays a preventive role in developing colorectal cancer; its mechanisms are related to the inhibition of inflammation and tumor proliferation, as well as maintenance of intestinal homeostasis.

Glioma is the most common primary malignant tumor of the central nervous system in adults. Despite the standard treatment of surgery combined with radiotherapy and chemotherapy, the prognosis for high-grade glioma patients remains poor, highlighting the urgent need to further explore its pathogenesis and develop new therapeutic strategies. This article reviews the research progress in the field of glioma in China in 2024, covering tumorigenesis mechanisms, tumor immune microenvironment composition, advances in imaging techniques and novel imaging agents, improvements in surgical approaches, mechanisms of radio- and chemoresistance, and explorations of new therapeutic modalities. These studies provide a solid theoretical foundation for advancing clinical diagnosis and treatment of gliomas and may offer new opportunities to improve patient outcomes.

Malignant tumors are one of the major diseases that endanger human life and health. Chinese medicine has unique advantages in clinical anti-tumor treatment. However， how to translate the anti-tumor effects of Chinese medicine into clinical practice is the core issue that must be addressed in the process of treating malignant tumors with traditional Chinese medicine （TCM）. Unlike modern chemical drugs， the compatibility application of Chinese medicine is the key factor that determines whether Chinese medicine can achieve optimal anti-tumor efficacy and realize the goal of "enhancing efficacy and reducing toxicity". The formulation structure based on this compatibility is the basic form for the safe， efficient， and rational clinical use of anti-tumor Chinese medicine， and it mainly includes three categories： herb pairs， tri-herbal combinations， and compound compatibility. Although herb pairs have the characteristics of a simple structure and strong targeting （enhancing efficacy and reducing toxicity）， they often have a single effect and cannot fully address the complex pathogenesis of tumors. As a result， herb pairs are rarely used alone in practice. Compared to herb pairs， tri-herbal combinations broaden the application scope of herbs in clinical treatment， but their therapeutic range remains limited. The traditional "sovereign， minister， assistant， and guide" compound prescription， which includes herb pairs and tri-herbal combinations， improves the efficacy of herbs in treating serious diseases， hypochondriasis， chronic diseases， and miscellaneous disorders. However， due to the limitations of its historical background， it has not been integrated with modern clinical practice and modern pharmacological research， which restricts the development of compound compatibility theory. With the emergence of modern medical technology， it has been combined with traditional compatibility theory of Chinese medicine to create an innovative modern compatibility theory. This includes the "aid medicine" theory derived from modern Chinese medicine pharmacology， which compensates for the inability of the "sovereign， minister， assistant， and guide" theory to accurately apply medicine. Additionally， the "state-targeted treatment based on syndrome differentiation" theory， developed from pharmacology and modern medicine， addresses the deficiency in disease cognition in the "sovereign， minister， assistant， and guide" theory. Under the guidance of these compatibility forms and theories， clinical anti-tumor Chinese medicine can exert its maximum anti-tumor efficacy， which is of great significance for the application of Chinese medicine in clinical tumor treatment.

Objective:To explore differences in the radiation-induced intestinal injury in mice exposed to ultra-high dose rate (FLASH) and conventional-dose-rate (CONV) pulsed X-ray irradiation in order to provide evidence for the application of ultra-high dose rate pulsed X-rays in gastrointestinal radiotherapy.Methods:Using the random number table method, 32 C57BL/6J mice were randomly divided into four groups: a sham irradiation group (SHAM), two conventional dose rate groups (CONV0.067 and CONV0.1), and an ultra-high dose rate group (F215), with each group containing eight mice. All groups, except SHAM, received a single 12 Gy abdominal X-ray irradiation at dose rates of 0.067, 0.1, and 215 Gy/s, respectively. At 3 d post-irradiation, histopathological (hematoxylin-eosin staining, HE staining), immunohistochemical, and Western blot analysis were performed to assess the histopathological markers and oxidative stress indicators of intestinal tissues, as well as relevant proteins involved in signaling pathways.Results:At 3 d post-irradiation, mice in all irradiation groups suffered from varying degrees of intestinal tissue degeneration and necrosis, epithelial cell shedding, villus shortening, and crypt loss ( t = 5.75, 8.79, 5.71, P < 0.05). Regarding oxidative stress, at 3 d post-irradiation, mice in the CONV0.067 and CONV0.1 groups showed significantly lower levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), glutathione (GSH), and total antioxidant capacity (T-AOC) compared to those in the F215 group ( t = 7.06-10.64, P < 0.01). In contrast, their malondialdehyde (MDA) levels were significantly elevated ( t = 11.06, 8.31, P < 0.01), with no statistical significance observed between them and mice in the F215 group ( P > 0.05). Immunohistochemical and Western blot analyses indicated that at 3 d post-irradiation, mice in the three irradiation groups exhibited an upward trend in the Nrf2 and HO-1 protein levels and a downward trend in the Keap1 protein level compared to those in the SHAM group. Notably, statistical significance was observed between the F215 group and the two conventional dose rate groups ( t = 4.89-20.95, P < 0.05). These result were consistent with the prior changes in antioxidant markers. Conclusions:Ultra-high-dose-rate X-ray irradiation reduces acute RIII by alleviating oxidative stress and modulating the expression of the Keap1-Nrf2-HO-1 signaling pathway.

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a child with neurodevelopmental disorder caused by homozygous frameshift variant of the TRAPPC6B gene, and to provide reference for the diagnosis of the disease. METHODS: A child with neurodevelopmental disorder caused by homozygous variant of TRAPPC6B gene who was admitted to the Children's Hospital Affiliated to Zhengzhou University in March 2023 due to "inability to stand and walk independently at 1 year and 3 months old" was selected as the study object. The clinical data were collected by retrospective analysis method. Target region high-throughput sequencing was carried out on the child and parental peripheral blood samples, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. The pathogenicity of variant was rated according to the Standards and Guidelines for the Interpretation of Sequence Variants released by American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as ACMG guidelines). The study has been approved by the Medical Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University (Ethic No.2022-K-L025). RESULTS: The child was a 1-year-and-3-months-old boy whose parents were sib mating. The child presented with global developmental delay, microcephaly and short stature. MRI showed poor white matter myelination, abnormal signals of bilateral periventricular white matter and bilateral external sac, thin corpus callosum, and widening of the third ventricle. Genetic testing revealed that the TRAPPC6B gene of the child had a homozygous variant of c.240_241delAA (p.Q80Hfs*34), which was inherited from his parents. According to the ACMG guidelines, this variant was judged to be potentially pathogenic (PVS1_Strong+PM2_Supporting+PM3_Supporting), resulting in premature occurrence of terminator codons and a change in the three-dimensional structure of protein. The variant was located in the functional domain, which may directly affect the functional domain of the protein, resulting in functional domain defects. CONCLUSION The frameshift variation of TRAPPC6B gene c.240_241delAA (p.Q80Hfs*34) has not been reported, which may be the genetic cause of neurodevelopmental disorders in child in this study. These findings expand the variation spectrum of TRAPPC6B gene and provide basis for genetic counseling and prenatal diagnosis of this family.
Humans ; Infant ; Male ; Frameshift Mutation ; Homozygote ; Neurodevelopmental Disorders/genetics* ; Phenotype

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with Osteopathia striata with cranial sclerosis (OSCS) due to variant of AMER1 gene. METHODS: A child presented at the Affiliated Children's Hospital of Zhengzhou University in July 2024 due to growth and development retardation was selected as the study subject. A retrospective study was conducted to collect the child's clinical data. Peripheral blood samples (2 mL each) were collected from the child and her parents, and genomic DNA was extracted for whole exome sequencing (WES). Sanger sequencing was used for the verification of candidate variants. The pathogenicity of variant was rated according to the guidelines from American College of Medical Genetics and Genomics (ACMG). The study has been approved by the Medical Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University (Ethics No.: 2024-108-001). RESULTS: The patient, a 4-year-and-10-month-old girl, presented with global developmental delay, short stature, cleft palate, distinct facial features, and hearing impairment. WES revealed that she has harbored a heterozygous c.790_794dup (p.Cys265Trpfs*19) variant of the AMER1 gene, which was not detected in either parent. Based on the guidelines from ACMG, the gene variant was classified as pathogenic (PVS1 + PS2 + PM2_supporting). As the result of a non-triplet base insertion in the coding region of the AMER1 gene, it has converted a codon originally encoding an amino acid into a stop codon, and led to a truncated protein, causing severe alteration and dysfunction of the protein. CONCLUSION The child was diagnosed with OSCS for clinical features such as global developmental delay, short stature, cleft palate, distinctive facial features, and hearing impairment, for which the de novo heterozygous frameshift variant AMER1: c.790_794dup (p.Cys265Trpfs*19) may be accountable. Above finding has expanded the mutational spectrum of OSCS and provided a basis for genetic counseling and prenatal diagnosis for the family.
Humans ; Female ; Child, Preschool ; Osteosclerosis/genetics* ; Adaptor Proteins, Signal Transducing/genetics* ; Mutation ; Exome Sequencing ; Retrospective Studies ; Tumor Suppressor Proteins

Objective:To explore the clinical phenotype and genetic characteristics of a child with neurodevelopmental disorder caused by homozygous frameshift variant of the TRAPPC6B gene, and to provide reference for the diagnosis of the disease. Methods:A child with neurodevelopmental disorder caused by homozygous variant of TRAPPC6B gene who was admitted to the Children′s Hospital Affiliated to Zhengzhou University in March 2023 due to " inability to stand and walk independently at 1 year and 3 months old" was selected as the study object. The clinical data were collected by retrospective analysis method. Target region high-throughput sequencing was carried out on the child and parental peripheral blood samples, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. The pathogenicity of variant was rated according to the Standards and Guidelines for the Interpretation of Sequence Variants released by American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as ACMG guidelines). The study has been approved by the Medical Ethics Committee of the Children′s Hospital Affiliated to Zhengzhou University (Ethics No.2022-K-L025). Results:The child was a 1-year-and-3-months-old boy whose parents were sib mating. The child presented with global developmental delay, microcephaly and short stature. MRI showed poor white matter myelination, abnormal signals of bilateral periventricular white matter and bilateral external sac, thin corpus callosum, and widening of the third ventricle. Genetic testing revealed that the TRAPPC6B gene of the child had a homozygous variant of c. 240_241delAA (p.Q80Hfs*34), which was inherited from his parents. According to the ACMG guidelines, this variant was judged to be potentially pathogenic (PVS1_Strong+ PM2_Supporting+ PM3_Supporting), resulting in premature occurrence of terminator codons and a change in the three-dimensional structure of protein. The variant was located in the functional domain, which may directly affect the functional domain of the protein, resulting in functional domain defects. Conclusion:The frameshift variation of TRAPPC6B gene c. 240_241delAA (p.Q80Hfs*34) has not been reported, which may be the genetic cause of neurodevelopmental disorders in child in this study. These findings expand the variation spectrum of TRAPPC6B gene and provid basis for genetic counseling and prenatal diagnosis of this family.