ObjectiveTo evaluate the therapeutic effects of modified Banxia Xiexintang（MBXT） on polycystic ovary syndrome with insulin resistance（PCOS-IR） rats and reveal its potential mechanisms based on the integrated analysis of transcriptomics and metabolomics. MethodsFemale SD rats were selected， and a PCOS-IR model was established by intragastric administration of letrozole combined with a high-fat diet for 21 days. The modeled rats were randomly divided into the model group， MBXT low-， medium-， and high-dose groups（6.62， 13.23， 26.46 g·kg^-1）， and metformin group（0.158 g·kg^-1）， with a normal group set up separately. After 14 days of administration， the estrous cycle was observed， ovarian morphology was examined by hematoxylin-eosin（HE） staining， and the levels of testosterone（T）， estradiol（E₂）， follicle-stimulating hormone（FSH）， and luteinizing hormone（LH） in serum were detected by enzyme-linked immunosorbent assay（ELISA）. Serum metabolites and ovarian tissue gene expression were detected using ultra-performance liquid chromatography-quadrupole-electrostatic orbitrap mass spectrometry（UPLC-Q-Orbitrap-MS） and RNA-Seq technology， respectively， followed by multi-omics integrated analysis. ResultsPharmacodynamic findings revealed that all MBXT dose groups could reversed abnormal estrous cycles in PCOS-IR rats， improve polycystic ovarian lesions， and normalize dysregulated serum hormone levels（T， LH， E₂， FS， P<0.05， P<0.01）. Metabolomic analysis revealed that compared with the model group， MBXT reversed 278 differential metabolites such as estrone and S-formylglutathione， mainly involving pathways such as steroid hormone biosynthesis， glutathione metabolism， and lipid peroxidation regulation. Transcriptomic analysis identified 434 differentially expressed genes， and enrichment analysis revealed that MBXT significantly regulated lipid peroxidation defense systems， including glutathione metabolism， peroxisome function， and fatty acid metabolism， thereby intervening in ferroptosis processes. It also engaged in inflammation-related pathways such as the chemokine signaling pathway. Integrated analysis revealed that both metabolomics and transcriptomics co-enriched metabolic pathways associated with ferroptosis and fatty acid metabolism. And key Hub genes［such as Ras-related C3 botulinum toxin substrate 2 gene（Rac2） and Fas ligand gene（Faslg）］ showed significant correlations with differential metabolites. ConclusionMBXT can effectively ameliorate reproductive dysfunction and metabolic disorders in PCOS-IR rats. Its mechanism may be related to remodeling the immune-metabolism network， particularly by regulating MHC-mediated immune responses， inhibiting local ovarian ferroptosis， and enhancing steroid hormone synthesis pathways.

ObjectiveTo investigate the mechanism of modified Banxia Xiexintang（MBXT） in improving ovarian dysfunction in polycystic ovary syndrome with insulin resistance（PCOS-IR） rats by inhibiting ferroptosis through the adenosine monophosphate（AMP）-activated protein kinase（AMPK）/fatty acid synthase（FASN）/glutathione peroxidase 4（GPX4） signaling pathway. MethodsSeventy-six female SD rats were randomly divided into a normal group（n=13） and a modeling group（n=63）. The modeling group established a PCOS-IR model by intragastric administration of letrozole combined with a high-fat diet for 21 days. After successful modeling， these rats were randomly divided into the model group， MBXT low-， medium-， and high-dose groups（6.62， 13.23， 26.46 g·kg^-1）， metformin group（0.158 g·kg^-1）， and high-dose of MBXT combined with ferroptosis inducer Erastin group（15 mg·kg^-1）， with 10 rats in each group. After 14 days of intervention， ovarian pathological morphology was observed by hematoxylin-eosin（HE） staining， the mitochondrial ultrastructure of granulosa cells was observed by transmission electron microscopy（TEM）， ovarian reactive oxygen species（ROS） levels were detected by dihydroethidium（DHE） probe， biochemical methods were used to detect Fe²⁺， malondialdehyde（MDA）， glutathione（GSH） and other indicators in ovarian tissues， serum sex hormone and insulin levels were measured by enzyme-linked immunosorbent assay（ELISA）， and the protein expressions of AMPK， FASN， acyl-CoA synthetase long-chain family member 4（ACSL4）， GPX4， and solute carrier family 7 member 11（SLC7A11） in ovarian tissues were detected by Western blot. ResultsCompared with the normal group， the model group showed polycystic changes in the ovaries， with atrophy of mitochondria in granulosa cells and increased membrane density. Serum levels of testosterone（T）， luteinizing hormone（LH）， and insulin were significantly increased（P<0.01）. The levels of ROS， MDA， 4-hydroxynonenal（4-HNE）， and Fe²⁺ in ovarian tissues were significantly elevated（P<0.01）， while adenosine triphosphate（ATP）， GSH， and reduced nicotinamide adenine dinucleotide phosphate （NADPH） levels were significantly decreased（P<0.01）. The phosphorylation levels of AMPK and acetyl-CoA carboxylase （ACC）， as well as the protein expressions of SLC7A11， GPX4， and ferroptosis suppressor protein 1（FSP1） were significantly downregulated（P<0.01）， whereas the expressions of FASN， ACSL4， and nuclear receptor coactivator 4（NCOA4） were significantly upregulated（P<0.01）. Compared with the model group， MBXT intervention at various doses improved the above pathological changes and biochemical indicators in a dose-dependent manner， with the high-dose group showing the most significant effect（P<0.01）. Compared with the MBXT high-dose group， the high-dose of MBXT combined with ferroptosis inducer Erastin group restored ovarian ferroptosis characteristics in rats， with increased ROS and lipid peroxidation products， and altered expressions of key proteins（P<0.05， P<0.01）. ConclusionMBXT can effectively improve ovarian function and metabolic disorders in PCOS-IR rats. Its mechanism may be related to activating the AMPK/ACC signaling pathway， downregulating FASN and ACSL4 to reduce lipid peroxidation substrates， and restoring glucose-6-phosphate dehydrogenase/phosphoglycerate dehydrogenase（G6PD/PHGDH） metabolic flux to enhance the GPX4/FSP1 antioxidant defense system， thereby inhibiting ferroptosis in ovarian granulosa cells.

ObjectiveThis paper aims to explore the risk factors for chronic atrophic gastritis （CAG） with turbidity toxin accumulation syndrome and establish a prediction model. MethodsClinical data of 180 patients with CAG who participated in the "clinical study of Xianglian Huazhuo Particles blocking CAG cancer transformation" of Hebei Sheng Zhong Yi Yuan from July 2021 to March 2022 were collected. After confounding factors were controlled by propensity score matching， patients were divided into a training set （namely dev） and a validation set （namely vad） in a seven to three ratio. The risk factors for CAG with turbidity toxin accumulation syndrome in the training set were investigated by using univariate Logistic regression analysis and least absolute shrinkage and selection operator （namely Lasso） regression algorithms. Subsequently， a model， named model 1se， was developed by using the training set data to predict the risk factors for CAG with turbidity toxin accumulation syndrome. The accuracy of the prediction model was assessed by using various methods， including the receiver operating characteristic （ROC） curve， Hosmer-Lemeshow test （H-L）， calibration plot， and decision curve analysis （DCA）. ResultsAge， body mass index （BMI）， family history of cancer， job and life satisfaction， yellow and greasy fur with slippery pulse， and heavy body sensation were independent risk factors of the model. The prediction model showed excellent predictive value for both the training and validation sets. ConclusionThe established prediction model for CAG with turbidity toxin accumulation syndrome has high discrimination and excellent calibration， which could provide an excellent clinical basis for disease diagnosis and individualized treatment of patients.

ObjectiveThis paper aims to explore the risk factors for chronic atrophic gastritis （CAG） with turbidity toxin accumulation syndrome and establish a prediction model. MethodsClinical data of 180 patients with CAG who participated in the "clinical study of Xianglian Huazhuo Particles blocking CAG cancer transformation" of Hebei Sheng Zhong Yi Yuan from July 2021 to March 2022 were collected. After confounding factors were controlled by propensity score matching， patients were divided into a training set （namely dev） and a validation set （namely vad） in a seven to three ratio. The risk factors for CAG with turbidity toxin accumulation syndrome in the training set were investigated by using univariate Logistic regression analysis and least absolute shrinkage and selection operator （namely Lasso） regression algorithms. Subsequently， a model， named model 1se， was developed by using the training set data to predict the risk factors for CAG with turbidity toxin accumulation syndrome. The accuracy of the prediction model was assessed by using various methods， including the receiver operating characteristic （ROC） curve， Hosmer-Lemeshow test （H-L）， calibration plot， and decision curve analysis （DCA）. ResultsAge， body mass index （BMI）， family history of cancer， job and life satisfaction， yellow and greasy fur with slippery pulse， and heavy body sensation were independent risk factors of the model. The prediction model showed excellent predictive value for both the training and validation sets. ConclusionThe established prediction model for CAG with turbidity toxin accumulation syndrome has high discrimination and excellent calibration， which could provide an excellent clinical basis for disease diagnosis and individualized treatment of patients.

Biological clock is a pattern of rhythms in which organisms exhibit cycles approaching 24 h in order to adapt to periodic changes in the external environment.Gut microbiota is the sum of extremely large number of microorganisms parasitized in humans and animals.Disorders of the biological clock increase the risk of metabolic diseases,and the occurrence of these disorders is closely related to the interaction with the dysbiosis of the gut microbiota.With the deepening of the understanding of the brain-gut axis,targeting gut microbiota to ameliorate biological clock disorders and associated diseases has achieved major theoretical breakthroughs and was partially applied in clinical practice,including dietary interventions such as time restricted feeding,development of microbial-related products(probiotics and postbiotics),and fecal microbiota transplantation.This article reviews the research progress of intestinal flora and rhythmicity,as well as targeting intestinal flora for the treatment of biological clock disorders,so as to provide new ideas for the prevention and treatment of rhythm disorders and concurrent diseases.

Objective To construct a prognostic model of centrosome amplification-related genes(CARGs)by machine learning and evaluate its prediction performance for the prognosis of esophageal squamous cell carcinoma(ESCC).Methods CARGs were obtained from Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)datasets.The RNA-sequencing(RNA-seq)transcriptome datasets of ESCC were retrieved from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO),and assigned into training and validation sets,respectively.Subsequently,single-sample gene set enrichment analysis(ssGSEA)and weighted gene co-expression network analysis(WGCNA)were employed to screen CARGs.A prognostic model of CARGs was constructed by incorporating 12 machine learning algorithms,and univariate and multivariate Cox regression analyses were applied to evaluate whether the 12 models as an independent prognostic factor or not.Eventually,15 paired ESCC and adjacent non-tumor tissue samples were collected from the Department of Gastroenterology of the Second Affiliated Hospital of Army Medical University,and real-time quantitative PCR(RT-qPCR)and immunohistochemistry staining were performed to detect the expression of these genes ESCC samples.Results Our 9-CARGs prediction model for ESCC prognosis was constructed.RT-qPCR confirmed that the mRNA expression levels of DENR,TRIP13,BRCA2,TTF2,TCFL5 and NUP188 were significantly higher in ESCC tissues than normal tissues(P<0.05),and the protein levels of DENR,TRIP13,TTF2 and TCFL5 were also elevated when compared to normal tissues.Conclusion DENR,TRIP13,TTF2 and TCFL5 are highly expressed and closely associated with poor prognosis of ESCC,suggesting their potential roles in the pathogenesis and progression of this malignancy.

Objective:To observe the efficacy and safety of combined lienal polypeptide injection therapy in the treatment of Mycoplasma pneumoniae pneumonia（MPP）in children aged 3 to 14 years old in multiple clinical centers.Methods:A randomized，controlled，multi-center clinical study design was adopted.A total of 240 hospitalized children aged 3 to 14 years old with MPP from 7 hospitals from September 1，2023 to January 31，2024 were included.According to the severity of pneumonia，they were divided into the mild MPP group with 80 cases and the severe MPP/refractory MPP（SMPP/RMPP）group with 160 cases，and then randomly divided into the control group and the experimental group at a ratio of 1 ∶1，using the random number table method.After screening，subjects entered a treatment period of 5 to 7 days.The control group was treated with azithromycin，while the experimental group was treated with azithromycin plus lienal polypeptide injection .The recovery of lung CT，length of hospital stay，duration of fever，cough score，whether mild cases developed into severe or refractory cases，duration of hormone use，use of intravenous immunoglobulin（IVIG），bronchoscopy treatment，and immune function were observed between the two groups to evaluate the efficacy of lienal polypeptide injection.Adverse events after medication，vital signs，blood routine，urine routine，liver function，myocardial enzymes，renal function，and electrocardiogram were observed to evaluate the safety. Results:A total of 231 subjects have completed the trial in the 7 hospitals，including 118 cases in the experimental group and 113 cases in the control group.Main observation index：the rate of lung CT aggravation in the experimental group was lower than that in the control group（2.6% vs 15.3%， P<0.01），and the difference was statistically significant.Secondary indexes：there were no statistically significant differences in the length of hospital stay，duration of fever，cough score，duration of hormone use，whether IVIG treatment was used，the number of bronchoscopy treatment cases，and immunoglobulin between the two groups（all P>0.05）.However，the rate of cases of plastic bronchitis（PB）found under bronchoscopy in the experimental group was lower than that in the control group（0 vs 18.8%， P=0.03），and the difference was statistically significant.Among the mild MPP（72 cases），there were no statistically significant differences in the length of hospital stay，duration of fever，cough score，duration of hormone use，whether IVIG treatment was used，the number of bronchoscopy treatment cases，and the improvement rate of lung CT between the two groups（all P>0.05）.However，compared with the control group，the rate of cases developing into SMPP/RMPP in the experimental group was less（24.3% vs 48.6%， P=0.03），and the difference in IgG before and after treatment was small［0.53（-0.04，1.18）g/L vs 1.33（0.48，2.25）g/L， P=0.01］.Among the SMPP/RMPP cases（159 cases），the rate of cases of PB found under bronchoscopy in the experimental group was less than that in the control group（0 vs 20%， P=0.04），and the rate of cases with aggravated lung CT in the experimental group was less than that in the control group（1.3% vs 19.5%， P<0.01），and the improvement rate of lung CT in the experimental group was higher than that in the control group（88.8% vs 75.3%， P=0.03），with statistically significant differences.There were no statistically significant differences in the length of hospital stay，duration of fever，cough score，duration of hormone use，whether IVIG treatment was used，the number of bronchoscopy treatment cases，and immunoglobulin between the two groups（all P>0.05）.Two cases in the experimental group developed rashes，which improved after the drug was discontinued.There were no serious adverse reactions such as abnormal vital signs like dyspnea and cyanosis due to the use of lienal polypeptide injection.There were no obvious changes in blood routine，liver function，myocardial enzymes，renal function，electrocardiogram，and urine routine values before and after medication compared with the baseline. Conclusion:The combined use of lienal polypeptide injection in the treatment of MPP in children can reduce the probability of the transformation from mild cases to SMPP/RMPP，reduce the rate of aggravation of the image findings，promote the absorption of lung inflammation，reduce the rate of PB found under bronchoscopy，and has good safety.

Objective To investigae microbial community structure of lower respiratory tract in severe hospital-acquired pneumonia(SHAP)patients in intensive care unit(ICU)using metagenomic next-generation sequencing(mNGS).Methods mNGS was performed on bronchoalveolar lavage fluid(BALF)of 84 patients with SHAP.Patients were grouped based on age,smoking status,underlying diseases and duration of artificial airway.The differences in α diversity,β diversity,microbial composition and community structure of airway microbiota were compared between different groups.The differential airway microbiota associated with artificial airway were screened,and microbial co-occurrence networks was constructed to observe the interaction in microorganisms.Results Results of α diversity analysis revealed that diversity and evenness of the microbial community were higher in young adults compared to those of middle-aged patients,while microbial diversity and evenness were significantly reduced in patients with comorbid stroke.In the group of artificial airway treatment,the diversity and uniformity of microorganisms decreased as the duration of artificial airway treatment increased.The diversity was the lowest when the artificial airway treatment lasted for more than 3 days.β diversity analysis confirmed that there were significant differences in the distinct microbial community structures between the>3 days support group and the non-intubated and≤3 days support cohorts.Acinetobacter baumannii was dominant in all groups.The bacterial diversity was significantly higher in the middle-aged group,the non-smoking group,the group without artificial airway therapy,the group without diabetes mellitus,the group with artificial airway therapy≥3 days and the group with chronic lung disease than those of other groups.In particular,pseudomonas aeruginosa,corynebacterium striatum and veillonella parvula were enriched in these groups.Difference analysis showed that there were significant differences in pseudomonas aeruginosa and corynebacterium striatum between the group with artificial airway treatment>3 days,the group without artificial airway therapy and the group with artificial airway treatment≤3 days.Network co-occurrence showed that there may be synergistic or antagonistic relationships between some microorganisms.Conclusion The microbial diversity of the lower respiratory tract in patients with SHAP significantly decreases in the elderly,those with concurrent stroke and those receiving artificial airway treatment.For these groups,rational use of antibiotics should be adopted to guide precise anti-infection treatment.

The incidence rate of suspected adverse events following immunization (AEFI) after single administration of pentavalent recombinant rotavirus attenuated live vaccine (RV5) in Chaoyang District, Beijing City from 2019 to 2021 was 362.3 per 100 000 doses. The incidence rate of AEFI after simultaneous administration with oral polio vaccine (OPV), inactivated polio vaccine (IPV), hepatitis B vaccine (HBV), Haemophilus influenzae type b (Hib), and pneumococcal conjugate vaccine 13-valent (PCV13) was 239.3 per 100 000, 643.4 per 100 000, 346.8 per 100 000, 438.1 per 100 000, and 434.0 per 100 000, respectively. The specific incidence rates for common AEFI symptoms such as fever, local allergic rash, irritability, and vomiting under different vaccination regimens were as follows: RV5 alone (fever: 88.3 per 100 000, rash: 9.1 per 100 000, irritability: 100.5 per 100 000, vomiting: 83.3 per 100 000), RV5 and IPV simultaneous administration (fever: 239.4 per 100 000, rash: 104.7 per 100 000, irritability: 134.7 per 100 000, vomiting: 89.8 per 100 000), RV5 and OPV simultaneous administration (fever: 119.6 per 100 000, rash: 32.6 per 100 000, irritability: 32.6 per 100 000, vomiting: 32.6 per 100 000), RV5 and HBV simultaneous administration (fever: 111.0 per 100 000, rash: 69.4 per 100 000, irritability: 83.2 per 100 000, vomiting: 41.6 per 100 000), RV5 and Hib simultaneous administration (fever: 159.3 per 100 000, rash: 238.9 per 100 000, irritability: 0 per 100 000, vomiting: 39.8 per 100 000), and RV5 and PCV13 simultaneous administration (fever: 142.8 per 100 000, rash: 98.0 per 100 000, irritability: 126.0 per 100 000, vomiting: 25.2 per 100 000).

Objective:To investigate the relationship between expression of secreted protein acidic and rich in cysteine (SPARC) in hormone receptor (HR) -positive breast cancer tissues and clinicopathological characteristics and axillary lymph node metastasis.Methods:The clinical data of 202 patients with breast cancer in Shaanxi Provincial Cancer Hospital were retrospectively analyzed from Mar. 2021 to Mar. 2023. The expression of SPARC protein in the lesion tissues of all subjects at admission was detected by immunohistochemistry. On the basis of molecular typing, the patients were classified into HR-positive subgroup and non-HR-positive subgroup, and the difference in SPARC protein expression in the lesion tissues at admission was compared. According to the axillary lymph node metastasis status at 1 year of follow-up, patients with HR-positive breast cancer were assigned into metastasis group and non-metastasis group, and the expression of SPARC protein in the lesion tissues at admission was compared. HR-positive breast cancer patients were divided into positive group and negative group by means of the expression of SPARC protein at admission. The clinicopathological characteristics [age, tumor size, breast cancer TNM staging, vascular tumor thrombus, histological grading, estrogen receptor (ER), progesterone receptor (PR) ] were compared.Results:The positive expression of SPARC protein was significantly higher in HR-positive subgroup than in non-HR-positive subgroup ( χ2=7.28, P<0.05), and was significantly higher in metastasis group than in non-metastasis group ( χ2=7.29, P<0.05). The expression of SPARC protein in HR-positive breast cancer tissues was significantly different between ER and PR groups ( χ2=10.89, 11.08, P<0.05), and there was no statistical significance between the other groups ( χ2=0.25, 0.36, 1.24, 1.10, 2.41, P>0.05) . Conclusion:The expression of SPARC in HR-positive breast cancer tissues is higher, and it is related to clinicopathological characteristics ER and PR and axillary lymph node metastasis.