ObjectiveTo unveil the mechanism of Jianpi Huogu prescription （JPHGP） in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head （SONFH） by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal， model， low-， medium-， and high-dose （2.5， 5， 10 g·kg^-1， respectively） JPHGP， and Jiangushengwan （1.53 g·kg^-1） groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg^-1 on days 1 and 2， and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg^-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection， and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head， and the number of adipocytes， the rate of empty bone lacunae， and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）， apolipoprotein A1 （ApoA1）， and apolipoprotein B （ApoB）. At the same time， the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed， and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking， immunohistochemistry， and Western blot. ResultsCompared with the normal group， the model group showcased thinning of the femoral head， trabecular fracture， karyopyknosis， subchondral cystic degeneration， increases in the number of adipocytes and the rate of empty bone lacunae （P<0.01）， a reduction in the trabecular area （P<0.01）， decreases in BMD， Tb.Th， Tb.N， and BV/TV， and increases in Tb.Sp and BS/BV （P<0.01）. Compared with the model group， the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae， an increase in the trabecular area （P<0.05， P<0.01）， rises in BMD， Tb.Th， Tb.N， and BV/TV， and decreases in Tb.Sp and BS/BV （P<0.05， P<0.01）. Compared with the normal group， the model group showcased raised serum levels of TG， TC， LDL， and ApoB and lowered serum levels of HDL and ApoA1 （P<0.01）. Compared with the model group， the JPHGP groups had lowered serum levels of TG， TC， LDL， and ApoB （P<0.05， P<0.01） and a risen serum level of ApoA1 （P<0.05， P<0.01）. Moreover， the serum level of HDL in the high-dose JPHGP group increased （P<0.01）. A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head， and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation， lipids， apoptosis， and osteoclast differentiation. Molecular docking， immunohistochemistry， and Western blot results showed that compared with the normal group， the model group displayed increased content of 5-lipoxygenase （5-LO） and peroxisome proliferator-activated receptor γ （PPARγ） in the femoral head （P<0.01）. Compared with the model group， medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ （P<0.05， P<0.01）. ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.

ObjectiveTo unveil the mechanism of Jianpi Huogu prescription （JPHGP） in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head （SONFH） by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal， model， low-， medium-， and high-dose （2.5， 5， 10 g·kg^-1， respectively） JPHGP， and Jiangushengwan （1.53 g·kg^-1） groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg^-1 on days 1 and 2， and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg^-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection， and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head， and the number of adipocytes， the rate of empty bone lacunae， and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）， apolipoprotein A1 （ApoA1）， and apolipoprotein B （ApoB）. At the same time， the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed， and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking， immunohistochemistry， and Western blot. ResultsCompared with the normal group， the model group showcased thinning of the femoral head， trabecular fracture， karyopyknosis， subchondral cystic degeneration， increases in the number of adipocytes and the rate of empty bone lacunae （P<0.01）， a reduction in the trabecular area （P<0.01）， decreases in BMD， Tb.Th， Tb.N， and BV/TV， and increases in Tb.Sp and BS/BV （P<0.01）. Compared with the model group， the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae， an increase in the trabecular area （P<0.05， P<0.01）， rises in BMD， Tb.Th， Tb.N， and BV/TV， and decreases in Tb.Sp and BS/BV （P<0.05， P<0.01）. Compared with the normal group， the model group showcased raised serum levels of TG， TC， LDL， and ApoB and lowered serum levels of HDL and ApoA1 （P<0.01）. Compared with the model group， the JPHGP groups had lowered serum levels of TG， TC， LDL， and ApoB （P<0.05， P<0.01） and a risen serum level of ApoA1 （P<0.05， P<0.01）. Moreover， the serum level of HDL in the high-dose JPHGP group increased （P<0.01）. A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head， and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation， lipids， apoptosis， and osteoclast differentiation. Molecular docking， immunohistochemistry， and Western blot results showed that compared with the normal group， the model group displayed increased content of 5-lipoxygenase （5-LO） and peroxisome proliferator-activated receptor γ （PPARγ） in the femoral head （P<0.01）. Compared with the model group， medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ （P<0.05， P<0.01）. ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.

[Objective] : To improve the accuracy and professionalism of question-answering (QA) model in traditional Chinese medicine (TCM) lung cancer by integrating large language models with structured knowledge graphs using the knowledge graph (KG) to text-enhanced retrieval-augmented generation (KG2TRAG) method. [Methods] : The TCM lung cancer model (TCMLCM) was constructed by fine-tuning ChatGLM2-6B on the specialized datasets Tianchi TCM, HuangDi, and ShenNong-TCM-Dataset, as well as a TCM lung cancer KG. The KG2TRAG method was applied to enhance the knowledge retrieval, which can convert KG triples into natural language text via ChatGPT-aided linearization, leveraging large language models (LLMs) for context-aware reasoning. For a comprehensive comparison, MedicalGPT, HuatuoGPT, and BenTsao were selected as the baseline models. Performance was evaluated using bilingual evaluation understudy (BLEU), recall-oriented understudy for gisting evaluation (ROUGE), accuracy, and the domain-specific TCM-LCEval metrics, with validation from TCM oncology experts assessing answer accuracy, professionalism, and usability. [Results] : The TCMLCM model achieved the optimal performance across all metrics, including a BLEU score of 32.15%, ROUGE-L of 59.08%, and an accuracy rate of 79.68%. Notably, in the TCM-LCEval assessment specific to the field of TCM, its performance was 3% − 12% higher than that of the baseline model. Expert evaluations highlighted superior performance in accuracy and professionalism. [Conclusion] TCMLCM can provide an innovative solution for TCM lung cancer QA, demonstrating the feasibility of integrating structured KGs with LLMs. This work advances intelligent TCM healthcare tools and lays a foundation for future AI-driven applications in traditional medicine.

ObjectiveTo investigate the risk factors of fertility behaviors with preterm birth and low birth weight， and to develop a nomogram model to predict the occurrence of low birth weight. MethodsBirth registration information in Shanghai from 2010 to 2020 was collected， and ANOVA and Chi-square tests were used to compare the differences in reproductive behavior factors and newborn health status across time. The odds ratio （OR） value and 95%CI were calculated by a multi-classification logistic regression model to determine the association between reproductive behavior factors and preterm birth or low birth weight infants. A nomogram model was established based on logistic model and the area under the ROC curve was used to assess the effect of the model. ResultsThis analysis included 2 089 384 live newborns. The incidence of full-term low birth weight， preterm normal weight and preterm low birth weight in Shanghai was 0.94%， 2.48% and 2.01%， respectively. From 2010 to 2020， 40.00% women had a history of abortion， the proportion of women who gave birth at age ≥40 years old increased from 1.05% to 2.24%， the proportion of fathers aged ≥40 years increased from 4.79% to 7.48%， and the proportion of women with postgraduate or above increased from 4.81% to 11.74%. The incidence of preterm low birth weight in Shanghai showed an increasing trend over time. Logistic regression analysis showed that the risk of preterm low birth weight was lower in female than in male infants （OR=0.97， 95%CI： 0.95‒0.98）， and the risk of full-term low birth weight was higher than in male infants （OR=1.85， 95%CI： 1.80‒1.90）. The risk of preterm birth and low birth weight was lower for couples of childbearing age with higher education. The risk of preterm low birth weight in newborns tended to increase with maternal age at childbirth >30 years， paternal age ≥40 years， and the number of abortions >2 times. Mother <25 or >35 years， father aged 30‒34 years， and the number of abortions >3 times were the risk factors of full-term low birth weight infants. ConclusionCouples of childbearing age who choose to have children at too high or too low age may increase the risk of preterm birth or low birth weight， so it is necessary to strengthen population awareness and promote age-appropriate childbirth. Multiple abortions are also associated with preterm birth and low birth weight， and it is advisable to popularize the scientific knowledge of contraception and birth control to reduce unnecessary abortions. The nomogram in the study can visualize the risk of full-term and low birth weight infant at different levels of factors， which can assist couples preparing for pregnancy in making decisions about the timing of childbirth and understanding the level of risk.

OBJECTIVE: To establish a machine learning model based on extreme gradient boosting (XGBoost) algorithm for early prediction of severe acute pancreatitis (SAP), and explore its predictive efficiency. METHODS: A retrospective cohort study was conducted. The patients with acute pancreatitis (AP) who admitted to the First Affiliated Hospital of Soochow University, the Second Affiliated Hospital of Soochow University and Changshu Hospital Affiliated to Soochow University from January 1, 2020 to December 31, 2021 were enrolled. Demography information, etiology, past history, and clinical indicators and imaging data within 48 hours of admission were collected according to the medical record system and image system, and the modified CT severity index (MCTSI), Ranson score, bedside index for severity in acute pancreatitis (BISAP) and acute pancreatitis risk score (SABP) were calculated. The data sets of the First Affiliated Hospital of Soochow University and Changshu Hospital Affiliated to Soochow University were randomly divided into training set and validation set according to 8 : 2. Based on XGBoost algorithm, the SAP prediction model was constructed on the basis of hyperparameter adjustment by 5-fold cross validation and loss function. The data set of the Second Affiliated Hospital of Soochow University was served as independent test set. The predictive efficacy of the XGBoost model was evaluated by drawing the receiver operator characteristic curve (ROC curve), and compared it with the traditional AP related severity score; variable importance ranking diagram and Shapley additive explanation (SHAP) diagram were drawn to visually explain the model. RESULTS: A total of 1 183 AP patients were enrolled finally, of which 129 (10.9%) developed SAP. Among the patients from the First Affiliated Hospital of Soochow University and Changshu Hospital Affiliated to Soochow University, there were 786 patients in the training set and 197 in the validation set; 200 patients from the Second Affiliated Hospital of Soochow University were used as the test set. Analysis of all three datasets showed that patients who advanced to SAP exhibited pathological manifestation such as abnormal respiratory function, coagulation function, liver and kidney function, and lipid metabolism. Based on the XGBoost algorithm, an SAP prediction model was constructed, and ROC curve analysis showed that the accuracy for prediction of SAP reached 0.830, the area under the ROC curve (AUC) was 0.927, which was significantly improved compared with the traditional scoring systems including MCTSI, Ranson, BISAP and SABP, the accuracy was 0.610, 0.690, 0.763, 0.625, and the AUC was 0.689, 0.631, 0.875, and 0.770, respectively. The feature importance analysis based on the XGBoost model showed that the top ten items ranked by the importance of model features were admission pleural effusion (0.119), albumin (Alb, 0.049), triglycerides (TG, 0.036), Ca²⁺ (0.034), prothrombin time (PT, 0.031), systemic inflammatory response syndrome (SIRS, 0.031), C-reactive protein (CRP, 0.031), platelet count (PLT, 0.030), lactate dehydrogenase (LDH, 0.029), and alkaline phosphatase (ALP, 0.028). The above indicators were of great significance for the XGBoost model to predict SAP. The SHAP contribution analysis based on the XGBoost model showed that the risk of SAP increased significantly when patients had pleural effusion and decreased Alb. CONCLUSIONS A SAP prediction scoring system was established based on the machine automatic learning XGBoost algorithm, which can predict the SAP risk of patients within 48 hours of admission with good accuracy.
Humans ; Pancreatitis ; Acute Disease ; Retrospective Studies ; Hospitalization ; Algorithms

Acute pancreatitis （AP） is a gastrointestinal disease that requires early intervention， and when it progresses to moderate-severe AP （MSAP） or severe AP （SAP）， there will be a significant increase in the mortality rate of patients. Machine learning （ML） has achieved great success in the early prediction of AP using clinical data with the help of its powerful computational and learning capabilities. This article reviews the research advances in ML in predicting the severity， complications， and death of AP， so as to provide a theoretical basis and new insights for clinical diagnosis and treatment of AP through artificial intelligence.

Objective To analyze the positive rate of serum mycoplasma pneumoniae antibody IgM in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Liangjiang New Area of Chongqing and the related risk factors, so as to provide a theoretical basis for clinical diagnosis and treatment of AECOPD. Methods Retrospective analysis of 728 cases of AECOPD patients from January 2020 to December 2021 in Chongqing Liangjiang New Area Third Class Hospital. ELISA was used to determine Mycoplasma pneumoniae IgM antibodies. According to the detection of Mycoplasma pneumoniae IgM antibodies, the patients were divided into infection group and non-MP infection group. Clinical data such as gender, age, length of stay, place of residence, smoking status, home oxygen therapy, GOLD grade of COPD, number of acute exacerbations in the previous year, mechanical ventilation, and application of anti-infective drugs were collected. Univariate analysis and logistic regression were used to analyze the risk factors of MP infection in AECOPD patients. Results The positive rate of MP-IgM in 728 AECOPD patients was 15.38% (112/728), including 67 males and 45 females. There was no significant difference in the positive rate of MP-IgM in AECOPD patients between different seasons (χ²=2.840, P>0.05). Age ≥60 (OR=3.243), smoking (OR=2.559) and GOLD grade 3-4 (OR=3.760) were independent risk factors for MP infection in AECOPD patients. Conclusion The incidence of MP infection in AECOPD patients in Liangjiang New Area of Chongqing is relatively high, especially in AECOPD patients with age ≥ 60, smoking, GOLD grade 3-4, which should be warned of the possibility of mycoplasma pneumoniae infection , and targeted treatment measures can improve the cure rate.

ObjectiveTo observe the intervention effect of Ruyi Zhenbao pills （RYZBP） on central pain after thalamic stroke in mice and explore the underlying mechanism. MethodThe central post-stroke pain syndrome （CPSP） model was induced by stereotactic injection of type Ⅳ collagenase into the hypothalamus in mice. The mice were divided into a sham group， a model group， low-， medium-， and high-dose RYZBP groups （0.65， 1.3， 2.6 g·kg^-1）， and a pregabalin group （0.075 g·kg^-1）. Seven days after modeling， the mice in the groups with drug intervention were administered with corresponding drugs by gavage according to the body mass， once per day for 25 days， while those in the sham group and the model group received an equal volume of normal saline. During this period， mechanical pain and cold pain were detected at different time points， and the apoptotic state of brain tissue cells was detected by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL）. The 36 classical broad-spectrum inflammatory factors were quantitatively analyzed by liquid-phase chip technology， and differential molecules were screened out and verified by Western blot and enzyme-linked immunosorbent assay （ELISA）. ResultCompared with sham operation group, mechanical pain threshold and cold sensitive pain threshold in model group were significantly changed （P<0.01）. TUNEL results showed that apoptosis of brain cells was obvious. Western blot and ELISA results showed that the expressions of interleukin-1α (IL-1α) and chemokine ligand 5 (CCL5) increased in hypothalamus tissue and serum， while the expressions of Ang-2, granulocyte-colony-stimulating factor (G-CSF) and IL-4 decreased significantly （P<0.01）. Compared with model group， RYZBW dose groups significantly increased mechanical pain threshold， decreased cold sensitivity pain threshold， decreased hypothalamus cell apoptosis ratio （P<0.01）， decreased the expression of IL-1α and CCL5 in hypothalamus tissue and serum， while the expression of ANG-2， G-CSF and IL-4 were significantly increased （P<0.05）. ConclusionRYZBP can relieve hyperalgesia in CPSP mice， and its mechanism is related to the regulation of the expression of pro-/anti-inflammatory factors IL-1α， CCL5， IL-4， G-CSF， and Ang-2.

BACKGROUND: Little was known about the association among time in range (TIR), time above range (TAR), time below range (TBR), and cancer mortality among patients with type 2 diabetes. We aimed to investigate the association among TIR, TAR, TBR, and the risk of cancer mortality among patients with type 2 diabetes. METHODS: A total of 6225 patients with type 2 diabetes were prospectively recruited in Shanghai, China. TIR was measured with continuous glucose monitoring at baseline and was defined as the average percentage of time in the target glucose range during a 24 h period. Cox proportion hazard regression analysis was used to determine the association between TIR and the risk of cancer mortality. RESULTS: During a mean follow-up of 7.10 years, we confirmed 237 death events related to cancer. The multivariable-adjusted hazard ratio (HR) for cancer mortality was 1.32 (95% confidence interval [CI]: 1.01-1.75) in patients with TIR ≤70% compared with those with TIR >70%. When TIR was considered as a continuous variable, the multivariable-adjusted HR for cancer mortality associated with each 10% decrease in TIR was 1.07 (95% CI: 1.02-1.14). In the site-specific analysis, a significant association between TIR as a continuous variable and the risk of hepatocellular cancer was found (HR: 1.24; 95% CI: 1.09-1.41). However, no relationship between hemoglobin A1c and cancer mortality was observed (HR: 1.04; 95% CI: 0.97-1.10). CONCLUSIONS The present study found an inverse association of TIR with the risk of cancer mortality among patients with type 2 diabetes. New evidence of TIR was added into the clinical practice that TIR may be an optimal target of glycemic control among patients with type 2 diabetes.
Blood Glucose ; Blood Glucose Self-Monitoring ; China ; Diabetes Mellitus, Type 2/complications* ; Humans ; Neoplasms ; Prospective Studies

Objective:To investigate the risk factors of lymph node metastasis and the clinical significance of deep submucosal invasion in patients with T1 stage colorectal cancer.Methods:From January 30, 2010 to December 31, 2019, at Shandong Provincial Hospital Affiliated to Shandong First Medical University, among patients with T1 stage colorectal cancer, 41 patients underwent radical surgery for colorectal cancer (surgery group) and 23 patients received endoscopic submucosal dissection (ESD) (ESD group) were enrolled. The tumor gross type, maximum diameter, histologically poorly differentiated components, degree of invasion (the type of mucosal muscle destruction, the width and depth of invasion), the budding grade of tumor, and whether with vascular tumor thrombus were recorded. The additional treatment and prognosis of patients were collected by telephone follow-up. The risk factors of lymph node metastasis in stage T1 colorectal cancer, the correlation between the complete muscularis mucosa destruction and the width and depth of invasion in the ESD group, and the effects of additional treatment after operation on the prognosis of patients were analyzed. Independent sample t test and chi-square test were used for statistical analysis. Results:The rate of lymph node metastasis in patients with poorly differentiated components or vascular tumor thrombus was higher than that in patients without poorly differentiated components or vascular tumor thrombus (3/6 vs. 12.1%, 7/58; 3/4 vs. 11.7%, 7/60), and the differences were statistically significant ( χ2=5.934 and 11.409, both P<0.05). All patients in the surgery group had complete muscularis mucosa destruction. In ESD group, the width of tumor invasion was ≥ 2 mm in 16 cases, including complete destruction of muscularis mucosa in 15 cases and partial destruction in one case; the width of tumor invasion was <2 mm in seven cases, including complete destruction of muscularis mucoa in two cases and partial destruction in five cases; the depth of infiltration was ≥ 2 000 μm in 14 cases, including complete destruction of muscularis mucosa in 13 cases and partial destruction in one case; the depth of infiltration was <2 000 μm in nine cases, including complete destruction of muscularis mucosa in four cases and partial destruction in five cases. The complete muscularis mucosa destruction was related with tumor of invasion width ≥ 2 mm and invasion depth ≥ 2 000 μm (15/16 vs.2/7, 13/14 vs. 4/7), and the differences were statistically significant ( χ2=10.729, 6.659, both P<0.05). Among the 64 patients with T1 stage colorectal cancer in this study, six cases (9.4%) had poor prognosis; five cases (7.8%) died, and three of them (4.7%) were tumor-related deaths. Adjuvant therapy was added in 10 cases in surgery group and 10 cases in ESD group, and there were no poor prognosis in those patients. There were no significant difference in the incidences of poor prognosis of patients without additional treatment and patients with additional treatment of the two groups (9.7% (3/31) vs. 0 (0/10) and 23.1% (3/13) vs. 0 (0/10)) (both P>0.05). Conclusion:When T1 stage colorectal cancer with tumor submucosal invasion, clinicians should comprehensively evaluate the prognostic risk based on various pathological characteristics such as the degree of tumor differentiation, vascular tumor thrombus and mucosal muscle destruction.