Objective To construct machine learning models based on preoperative inflammatory and radiological features for the prediction of glioma grading and isocitrate dehydrogenase (IDH) mutation status, and to analyze application values of these models and identify the optimal predictive models. Methods A retrospective analysis was conducted on the data of pathologically confirmed glioma patients admitted to Tongji Hospital Affiliated to Tongji University from March 2019 to March 2023. LASSO regression was used to screen feature variables, and predictive models were constructed based on logistic regression (LR), random forest (RF), support vector machine (SVM), gradient boosting decision tree (XGBoost) and K-nearest neighbor (KNN) algorithms. The model performance was comprehensively evaluated using metrics including discrimination ability, area under the precision-recall curve (AUC), accuracy, F1 score and Brier score. The DeLong test was adopted to compare the AUC values among different models; Friedman rank-sum test was used to determine the overall performance differences of the models, with the Nemenyi test applied for multiple comparison correction. Results In the task of glioma grading prediction, the LR model achieved the highest comprehensive score (0.726), and no significant difference was observed between the LR model and the other four models; age was positively correlated with glioma grading (P=0.003). In the task of IDH mutation status prediction, the XGBoost model obtained the highest comprehensive score (0.832), which was superior to the LR (0.762, P=0.035) and KNN models (0.754, P=0.025), while no statistical differences were found between the XGBoost model and the RF or SVM models. Conclusions The LR model for glioma grading prediction and XGBoost model for IDH mutation prediction constructed based on a task-oriented strategy achieve a favorable interpretability while ensuring optimized performance, thereby providing reliable decision support for the individualized diagnosis and treatment of glioma.

Objective To analyze the prevalence of malignant tumors in cancer registration areas in Hubei Province in 2021. Methods Data on the incidence and mortality of malignant tumors from 31 cancer registries in Hubei Province in 2021 were collected. Incidence, mortality (crude rate, ASRC, and ASRW), and cumulative rates in the 0-74-year-old age group were calculated by gender, urban-rural area, and age group. Descriptive epidemiological methods were used to describe and analyze the incidence and mortality characteristics of malignant tumors in cancer registration areas in Hubei Province in 2021. Results In 2021, malignant tumors in cancer registration areas in Hubei Province had an incidence of 329.62/10⁵, an ASIRC of 189.33/10⁵, an ASIRW of 201.50/10⁵, and a cumulative rate of 20.81% in the 0-74-year-old age group. Malignant tumors had a mortality rate of 183.59/10⁵, an ASMRC of 90.36/10⁵, an ASMRW of 103.22/10⁵, and a cumulative rate of 10.26% in the 0-74-year-old age group. Incidence and mortality were higher in males than in females, with incidence rates in urban areas being significantly higher than those in rural areas, whereas urban and rural mortality rates showed no significant difference. The incidence of malignant tumors gradually increased with age, peaking in the 75-79-year-old age group. Mortality rose rapidly after 45 years and peaked in the 85+-year-old age group. Significant gender and urban–rural differences were found in the incidence and mortality of malignant tumors. The leading cause of incidence across the province was lung cancer, followed by female breast, thyroid, colorectal, and liver cancers. The top five causes of death were lung, liver, stomach, colorectal, and esophageal cancers. The incidence rates of female breast, thyroid, and colorectal cancers were higher in urban areas than in rural areas, whereas the burden of liver and cervical cancers was more prominent in rural areas than in urban areas. Significant differences were found in the incidence of malignant tumors among different cities and counties. Conclusion In 2021, the burden of malignant tumors in cancer registration areas in Hubei Province was primarily caused by lung, digestive tract, liver, and female breast cancers, with significant regional differences. This situation seriously endangers the health of residents. Comprehensive prevention and control measures should be continuously strengthened to reduce the burden of malignant tumors.

Objective:To explore the spectrum of genetic variants and phenotypes of Phenylalanine hydroxylase deficiency (PAHD) in Lianyungang area and the correlation between genotype and phenotypes among the patients.Methods:Eighty children with Hyperphenylalaninemia (HPA) diagnosed at the Lianyungang Branch of Jiangsu Provincial Newborn Screening Center between January 2015 and December 2022 were enrolled. Peripheral blood samples were collected for genetic analysis using next generation sequencing (NGS), Sanger sequencing, and multiplex ligation-dependent probe amplification (MLPA) to identify the variants of PAH gene. Clinical and phenotypic data were concurrently analyzed to investigate the correlation between the types of PAH gene variant and phenotypes. This study was approved by the Medical Ethics Committee of Lianyungang Maternal and Child Health Care Hospital (Ethics No.: XM2022041). Results:① PAH variants were identified in 93.75% (75/80) of the children, classified as PAHD cases, while 6.25% (5/80) harbored PTS variants. ② Of the 150 PAH alleles from 75 PAHD children, a total of 152 variants (55 distinct types) were detected, with a detection rate of 100%. 80.26% (122/152) were located in exons, with the main types of variants were missense variants (67.11%, 102/152). 53.29% (81/152) of coding sequence variants occurred in the PAH gene catalytic center region of PAH protein, while 19.74% (30/152) of variants involved non-coding sequences. ③The phenotypes of the 75 PAHD children were evenly distributed. The rescreening Phe concentrations and Phe/Tyr ratios of classic-phenylketonuria (CPKU) and mild-phenylketonuria (MPKU) patients were markedly higher than initial screening values ( P<0.001, P<0.001; P=0.004, P=0.016). The genotypes of the PAHD patients mostly occurred as compound heterozygotes, and different mutation positions and variant types significantly affect the phenotype ( P=0.042, P=0.045). ④APV/GPV genotype-phenotype analysis of 61 patients showed high consistency between predicted and actual phenotypes ( κ=0.755, P<0.001). Conclusion:PAH variants were detected in the most of HPA children in Lianyungang area. The location and type of PAH variants were related to the severity of the phenotype, and the non-coding sequence variants and non-missense variants may aggravate the phenotype, and the APV/GPV model predicted the phenotype was highly consistent with the actual phenotype.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Aim To investigate the pharmacological mechanism of Ebselenin(Ebselen,EbSe)in the treat-ment of Escherichia coli(E.coli)infection,which had no significant inhibitory effect on Gram-negative bacte-ria,based on previous studies.Methods After EbSe intervention in E.coli infected Raw264.7 cells,the via-bility of Raw264.7 cells was determined by CCK-8 method,the morphology and structure of Raw264.7 cells were observed by electron microscope,and the in-tracellular bacterial load of Raw264.7 cells was calcu-lated by coated plate method.Polarization status of peritoneal macrophages,Raw264.7 intracellular NO and ROS content and intracellular HO-1 expression in Raw264.7 and E.coli acutely infected mice after E.co-li infection by flow cytometry.qPCR was used to detect the expression of related mRNAs in Raw264.7 cells.qPCR was used to detect the intracellular GSH content in Raw264.7 cells by spectrophotometric assay,and the state of cytoskeletal proteins was observed by immuno-fluorescence.Western blot assay was performed to de-tect the intracellular Txnrd1 expression level.Results Microtiter method,CCK-8,and electron microscopy observations showed that EbSe had no effect on the growth of E.coli and Raw264.7 cells in vitro.The re-sults of smear plate counting showed that EbSe reduced the intracellular bacterial load of Raw264.7 in the in-fected group.Flow cytometry results showed that EbSe upregulated the number of M2-type macrophages.The EbSe-treated infected group had reduced intracellular NO and ROS levels and increased GSH levels.The qPCR results showed that the expression of IL-6,IL-1β,and iNOS was decreased,and the expression of HO-1,Txnrd1,and Glut1 was increased in DHB4-in-fected Raw264.7 cells after EbSe treatment.Cytoskel-etal staining showed that the morphology of the EbSe-treated infected cells was similar to that of oxPAPC-in-duced cells.Western blot results showed the expres-sion of Txnrd1 protein in EbSe-treated infected cells in-creased.Conclusion EbSe exerts anti-E.coli acute infection effect by regulating macrophage polarization and inhibiting macrophage excessive inflammatory state.

Objective::To evaluate the early pregnancy loss (EPL) rates in women with and without low molecular weight heparin (LMWH) treatment during early pregnancy.Methods::A retrospective, non-randomized study was conducted at Guangzhou Women and Children’s Medical Center between June 2019 and March 2022, involving women diagnosed with polycystic ovary syndrome (PCOS). All participants conceived following standard preconception care and voluntarily chose either the control group or the LMWH intervention group during the first month of pregnancy. The intervention was administered throughout the entire first trimester. Early and final pregnancy outcomes were recorded, with a particular focus on EPL rates. In addition, venous blood samples and clinical data were collected to compare hormonal profiles, blood lipid levels, and anthropometric parameters between the two groups. Statistical analyses included the two-tailed unpaired Student’s t-test, Mann–Whitney U test, Chi-square test, and Kaplan–Meier survival analysis. A value of P < 0.050 was considered statistically significant. Results::Thirty-eight women in the LMWH group and 102 women in the control group were included. The EPL rates in the LMWH and control groups were 5.3% (2/38) and 26.5% (27/102), respectively ( χ2 = 7.582, P = 0.006, odds ratio ( OR) = 0.154, 95% confidence interval ( CI): 0.035-0.685). The age ( P = 0.005), PCOS subtype ( P = 0.012), and levels of total cholesterol ( P = 0.003), and high-density lipoprotein ( P = 0.018) were significantly different between these two groups. Continued follow-up was performed to observe the long-time effects of LMWH treatment in early pregnancy. Seventy-three patients were successfully delivered, 23 patients in the LMWH group and 50 patients in the control group. There was no significant difference between the LMWH and control groups in gestation length, bleeding during delivery, birth weight, gender of the newborn, or mode of delivery. In addition, Kaplan-Meier curve analysis revealed that LMWH treatment may decrease the risk of EPL in PCOS patients in the first trimester ( χ2 = 4.144, P = 0.040). Conclusion::LMWH treatment during early pregnancy may reduce the EPL rate in women with PCOS.

The endoplasmic reticulum is an important organelle responsible for the synthesis,folding and processing of proteins.When the endoplasmic reticulum protein folding ability is affect-ed,internal unfolded proteins or misfolded proteins accumulate in the endoplasmic reticulum accumulation,leading to endoplasmic reticulum structural dysfunction resulting in endoplasmic reticu-lum stress.Autophagy is the process by which cells selectively remove stress endoplasmic reticulum and error proteins.Under stress,the endoplasmic reticulum can maintain normal physiolog-ical functions through unfolded protein responses and autophagy.Postmenopausal osteoporosis is mainly due to an imbalance be-tween bone resorption by osteoclasts and bone formation by oste-oblasts.Endoplasmic reticulum stress and autophagy both modu-late bone cells status with consequences for bone homeostasis.This article provides a review of the progress of research on en-doplasmic reticulum stress and autophagy interaction in the path-ogenesis of postmenopausal osteoporosis.

OBJECTIVE: To explore the spectrum of genetic variants and phenotypes of Phenylalanine hydroxylase deficiency (PAHD) in Lianyungang area and the correlation between genotype and phenotypes among the patients. METHODS: Eighty children with Hyperphenylalaninemia (HPA) diagnosed at the Lianyungang Branch of Jiangsu Provincial Newborn Screening Center between January 2015 and December 2022 were enrolled. Peripheral blood samples were collected for genetic analysis using next generation sequencing (NGS), Sanger sequencing, and multiplex ligation-dependent probe amplification (MLPA) to identify the variants of PAH gene. Clinical and phenotypic data were concurrently analyzed to investigate the correlation between the types of PAH gene variant and phenotypes. This study was approved by the Medical Ethics Committee of Lianyungang Maternal and Child Health Care Hospital (Ethics No.: XM2022041). RESULTS: PAH gene variants were identified in 93.75% (75/80) of the children, classified as PAHD cases, while 6.25% (5/80) harbored PTS gene variants. Of the 150 PAH alleles from 75 PAHD children, a total of 152 variants (55 distinct types) were detected, with a detection rate of 100%. 80.26% (122/152) of the variants were located in exons, with the main types being missense variants (67.11%, 102/152). 53.29% (81/152) of coding sequence variants have occurred in the PAH gene's catalytic center region, while 19.74% (30/152) of the variants involved non-coding sequences. The phenotypes of the 75 PAHD children were evenly distributed. The re-screened Phe concentrations and Phe/Tyr ratios of classic-phenylketonuria (CPKU) and mild-phenylketonuria (MPKU) patients were markedly higher than initial screening values (P < 0.001, P < 0.001; P = 0.004, P = 0.016). The genotypes of the PAHD patients mostly occurred as compound heterozygotes, and different mutation positions and variant types have significantly affected the phenotypes (P = 0.042, P = 0.045). APV/GPV genotype-phenotype analysis of 61 patients showed high consistency between predicted and actual phenotypes (κ = 0.755, P < 0.001). CONCLUSION PAH gene variants were detected in most HPA children from Lianyungang area. The location and type of PAH gene variants has correlated with the severity of the phenotype, and the non-coding sequence variants and non-missense variants may aggravate the phenotype, and the APV/GPV model has predicted the phenotype with high consistency with the actual phenotype.
Humans ; Phenylalanine Hydroxylase/genetics* ; Female ; Phenylketonurias/enzymology* ; Male ; Phenotype ; Genotype ; Child ; Infant ; Infant, Newborn ; Child, Preschool ; China ; Mutation ; Alleles

Objective To explore the potential targets and pathways of Yanghe Decoction for the treatment of granulomatous lobular mastitis(GLM)using network pharmacology and molecular docking;To experimentally validate its mechanism.Methods Active components and targets of Yanghe Decoction were screened through TCMSP and TCM-ID.GLM targets were retrieved from GeneCards and OMIM databases,the intersection of drug targets and disease targets was taken,and a protein interaction network was constructed.GO and KEGG pathway enrichment analysis was performed.Molecular docking of main components and key targets was conducted.Totally 60 SD rats were randomly divided into blank group,model group,prednisolone group(0.005 g/kg),and Yanghe Decoction low-,medium-and high-dosage groups(2.5,5.0,10.0 g/kg).Except for the blank group,GLM models were constructed for all other groups,and corresponding drug interventions were given to each treatment group for 14 consecutive days.The body mass and breast mass size of rats were recorded,breast ultrasound images were collected,and the inflammatory index score was scored.The pathological morphology of rat breast tissue was observed through HE staining.ELISA was used to detect the contents of IL-1β,IL-6 and TNF-α in serum.Western blot was used to detect the protein expressions of IL-1β,IL-6,TNF-α,IκBα,TLR4 and p65 in breast tissue.Results Yanghe Decoction was screened for 140 active components,363 targets,and 32 intersecting targets with GLM,mainly involving NF-κB,PI3K-Akt signaling pathway,etc.Molecular docking showed that the main components had good binding activities with key targets.Compared with the blank group,rats in the model group showed obvious redness and swelling of the breasts with a large range of lumps and a significant increase in mammary inflammation index score(P<0.01),and ultrasound could detect a large range of patchy hypoechoic areas,and pathological changes showed a variety of inflammatory cell infiltration in the mammary lobules and the formation of tiny abscesses,and the serum contents of IL-1β,IL-6 and TNF-α in the model group significantly increased(P<0.01),the protein expressions of IL-1β,IL-6,TNF-α,TLR4 and p65 in breast tissue significantly increased(P<0.01),and the protein expression of IκBα significantly decreased(P<0.05).Compared with the model group,the erythema of the breasts of the rats in each treatment group was improved,and the extent of the lumps was reduced,and the reduction in the size of the lumps in the prednisolone group and the Yanghe Decoction high-dosage group was obvious(P<0.05).The inflammatory index score of prednisolone group and Yanghe Decoction groups decreased to different degrees(P<0.01),ultrasound showed a smaller range of hypoechoic area,pathology showed a reduction in the infiltration of inflammatory cells,and a reduction in the formation of granulomas and abscesses,and the prednisolone group and Yanghe Decoction groups significantly down-regulated the contents of IL-1β and TNF-α in serum(P<0.01),and the prednisolone group and Yanghe Decoction middle-and high-dosage groups significantly down-regulated the content of IL-6 in serum(P<0.05,P<0.01),the expression of TLR4 protein in breast tissue was significantly decreased in Yanghe Decoction high-dosage group(P<0.05),the expressions of IL-1β,IL-6,TNF-α and p65 proteins in prednisolone group and Yanghe Decoction groups were significantly decreased(P<0.05,P<0.01),and the expression of the protein of IκBα significantly increased(P<0.01).Conclusion Yanghe Decoction can reduce the inflammatory response in GLM rats,and its mechanism may be related to the inhibition of TLR4/NF-κB signalling pathway.

This study aims to screen epitope antigens targeting the receptor binding domain(RBD)of porcine epidemic diarrhea virus(PEDV)based on its amino acid sequence(GenBank accession number:AKN45969.1),prepare PEDV RBD polyclonal antibody,and perform their identification.Bioinformatics analysis software was used to predict the potential antigenic epitopes of PEDV RBD and sequence comparison with porcine coronavirus strains was performed,the selected dominant antigen epitopes were then conjugated with keyhole limpet hemocyanin(KLH),to synthesize pep-tides directly and immunize mice to generate specific antibody,Western blot technique and indirect immunofluorescence assay were utilized to identify the specificity of the antibodies,and indirect ELISA method was further applied to determine the antibody potency.Results showed the selected PEDV RBD dominant epitope sequence shared 100％similarity with 18 other PEDV strains,while exhibiting low sequence similarity with 11 TGEV strains(27.8％—29.3％)and 16 PDCoV strains(10.5％—13.4％),indicating good epitope conservation.Western blot showed that the specificity of the prepared peptide antibody specifically recognized the PEDV RED protein overexpressed in Ex-pi293F cells and overexpressed in baculovirus system,and at the same time,the antibody was still able to detect the PEDV S protein expressed in PEDV-infected Vero cells at a 1∶2 000 dilution,while it did not react with TGEV-and PDCoV-infected ST cells,indicating that the good specificity of the peptide antibody.ELISA revealed that the potency of specific antibodies in mouse serum could reach up to 1∶25 600.The above results indicate that bioinformatics techniques were suc-cessfully utilized to predict antigenic epitopes of PEDV RBD protein,and specific PEDV RBD pep-tide antibodies were prepared.