Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.

OBJECTIVE To construct ensemble learning models for predicting high-use days of budesonide based on meteorological factors， thereby providing reference for hospital pharmacy management. METHODS Meteorological data for 2024 and outpatient budesonide usage data from the jurisdiction of Sanming Hospital of Integrated Traditional Chinese and Western Medicine were collected. High-use days were defined as the 75th percentile of outpatient budesonide usage， and a corresponding dataset was established. The prediction task was formulated as a classification problem， and three ensemble learning models were developed： Random Forest， Extreme Gradient Boosting （XGBoost）， and Histogram-based Gradient Boosting Classifier. Model performance was evaluated using accuracy， precision， recall， F1-score， and log-loss. Model interpretability was analyzed using Shapley Additive Explanations （SHAP）. RESULTS The Histogram-based Gradient Boosting Classifier achieved the best performance （accuracy＝0.75， F1-score＝0.48）， followed by XGBoost （accuracy＝0.74， F1-score＝0.43） and Random Forest （accuracy＝0.72， F1-score＝0.22）. SHAP results suggested that the prediction results of the last two models have the highest correction. CONCLUSIONS Ensemble learning models can effectively predict high-use days of budesonide， with the Histogram- based Gradient Boosting Classifier demonstrating the best predictive performance. Low temperature， high humidity， and low atmospheric pressure show significant positive impacts on the prediction of daily budesonide usage.

Objective:To investigate the protective effects and mechanism of Shenyan 1 Prescription on renal fibrosis of unilateral ureteral obstruction (UUO) rats through TGF- β 1/Smad homologous 3 (Smad3) pathway regulating ferroptosis.Methods:Totally 48 male SD rats were divided into four groups: sham-operation group, UUO model group, and Shenyan 1 Prescription low-(10 drug/kg) , and high-dosage (20 crude drug/kg) groups according to random number table method, with 12 rats in each group. The UUO model was induced by the method of unilateral ureteral obstruction except for those sham-operation group. After modeling, rats received corresponding drugs or normal saline by gavage for 4 weeks, once per day. After 4 weeks, the body mass and the left kidney weight were measured. The 24 h urine protein and the levels of serum albumin (ALB), alanine aminotransferase (ALT), serum creatinine (SCr) and blood urea nitrogen (BUN) were detected by biochemical analysis method; the ROS level in renal tissue was measured using a chemical fluorescence assay kit, and the SOD and MDA levels in left renal tissue of rats were measured using ELISA method; the morphology of renal tissue and the specific blue staining of hemosiderin were observed using HE and Prussian blue staining methods, respectively; the expressions of transforming growth factor-β1 (TGF-β1), Smad3, glutathione peroxidase 4 (GPX4), and solute carrier family 1 member 5 (SLC1A5) were detected by Western blot.Results:Compared with the model group, the 24 h urinary protein excretion in Shenyan 1 Prescription high-dosage group decreased ( P<0.05), the serum ALB level increased ( P<0.05), the ALT level decreased ( P<0.05), and the expression of SLC1A5 in renal tissue decreased ( P<0.05); the left kidney weight/body decreased in Shenyan 1 Prescription low- and high-dosage groups ( P<0.05); the levels of serum ROS and MDA decreased ( P<0.05), and the activity of SOD significantly increased ( P<0.05); the expressions of TGF-β1 and Smad3 in renal tissue decreased ( P<0.05), and the expression of GPX4 increased ( P<0.05), and the renal pathological injury and ion deposition were improved. Conclusion:Shenyan 1 Prescription has a protective effect on the structure and function of renal tissues in UUO rats through regulating ferroptosis via inhibition of the TGF-β1/ Smad3 pathway to inhibit renal fibrosis of UUO rats.

Objective To evaluate the relationship between diabetic nephropathy(DN)and diabetic retinopathy(DR)in patients with type 2 diabetes mellitus(T2DM)based on imaging and clinical testing data.Methods Totally 600 T2DM patients who visited the First People's Hospital of Ziyang from March 2021 to December 2022 were included.The fundus photography and fundus fluorescein angiography were performed on all these patients and their age,gender,T2DM duration,cardiovascular diseases,cerebrovascular disease,hypertension,smoking history,drinking history,body mass in-dex,systolic blood pressure,diastolic blood pressure and other clinical data were collected.The levels of fasting blood glu-cose(FPG),triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipo-protein cholesterol(LDL-C),glycosylated hemoglobin(HbA1c),24 h urinary albumin(UAlb),urinary albumin to creati-nine ratio(ACR),serum creatinine(Scr)and blood urea nitrogen(BUN)were measured.Logistic regression was used to analyze the risk factors associated with DR.DR staging was performed according to fundus images,and the convolutional neural network(CNN)algorithm was used as an image analysis method to explore the correlation between DR and DN based on emission computed tomography(ECT)and clinical testing data.Results The average lesion area rates of DR and DN detected by the CNN in the non-DR,mild-non-proliferative DR(NPDR),moderate-NPDR,severe-NPDR and pro-liferative DR(PDR)groups were higher than those obtained by the traditional algorithm(TCM).As DR worsened,the Scr,BUN,24 h UAlb and ACR gradually increased.Besides,the incidence of DN in the non-DR,mild-NPDR,moderate-NPDR,severe-NPDR and PDR groups was 1.67％,8.83％,16.16％,22.16％and 30.83％,respectively.Logistic regression analysis showed that the duration of T2DM,smoking history,HbA1c,TC,TG,HDL-C,LDL-C,24 h UAlb,Scr,BUN,ACR and glomerular filtration rate(GFR)were independent risk factors for DR.Renal dynamic ECT analysis demonstrated that with the aggravation of DR,renal blood flow perfusion gradually decreased,resulting in diminished renal filtration.Conclusion The application of CCN in the early stage DR and DN image analysis of T2DM patients will improve the diag-nosis accuracy of DR and DN lesion area.The DN is worsening as the aggravation of DR.

Erythropoietic protoporphyria （EPP） is a rare inherited metabolic disease that often involves skin， blood， and nervous systems， and EPP with the main manifestations of severe liver damage and acute abdominal pain is extremely rare. By reviewing the clinical data and genetic testing results of a patient with EPP， this article discusses the clinical features and pathogenic genes of this disease， in order to improve the understanding of the disease among hepatologists and achieve early diagnosis and treatment.

In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands of deaths and chronic physical disabilities every year.This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims.These recommendations are based on clinical experience and clinical research evidence.This guideline focuses on the following topics:snake venom,clinical manifestations,auxiliary examination,diagnosis,treatments,and prevention.

Objective:To analyze three reconstruction techniques and mid-term clinical outcomes of hip revision for acetabular bone defect after total hip arthroplasty (THA).Methods:This is a retrospective case series study. Included in the study were 109 patients (109 hips) with acetabular bone defect after THA reconstructions in hip revisions from January 2015 to December 2021 in the Senior Department of Orthopaedics, the Forth Medical Center of Chinese People′s Liberation Army General Hospital and the Department of Orthopaedics, the First Medical Center of Chinese People′s Liberation Army General Hospital. According to the preoperative simulated surgeries and different bone defect reconstruction techniques, patients were divided into a normal cup group, an augment group or a triflange group,respectively. There were 54 patients (54 hips) in the normal cup group, reconstructed with the uncemented porous metal cup (including Jumbo cup), with 23 males and 31 females, aged (59.6±9.9) years (range:32 to 76 years); 44 patients (44 hips) in the augment group, reconstructed with the individualized three-dimensional (3D) printed porous metal augment and uncemented porous metal cup, with 18 males and 26 females, aged (52.8±13.6) years(range:17 to 76 years); 11 patients (11 hips) in the triflange group, reconstructed by the individualized 3D printed porous metal triflange cup, with 5 males and 6 females, aged (59.4±11.2) years (range: 43 to 78 years). Radiographic results, including rotation center height, rotation center offset, and leg length discrepancy (LLD) and clinical results, including Harris hip score (HHS) and visual analogue scale(VAS) were evaluated outpatient at 3, 6, 12 months after the operation and annually thereafter. The last follow-up was completed in March 2024, and all parameters at the last follow-up and before the operation were compared. Paired sample t test and repeated measurement ANOVA were used for the radiographic and clinical parameters before and after the operation. Results:All hip revisions for patients with acetabular bone defect after THA were completed and followed for more than two years. The follow-up time of the normal cup group was (6.5±1.7) years (range: 2.8 to 9.3 years), and that of the augment group was (6.0±1.3) years (range: 3.5 to 9.0 years). The follow-up time of the triflange group was (2.8±0.6) years (range: 2.0 to 3.8 years). At the last follow-up, the rotation center height, rotation center offset and LLD of 54 hips in the normal cup group were (24.2±5.6) mm, (29.1±5.5) mm and (4.6±3.3) mm, respectively, and the rotation center height and LLD were significantly lower than those of the preoperative hips ( t=9.671, P<0.01; t=6.073, P<0.01). In the augment group, the rotational center height, the rotation center offset and the LLD of 44 hips were (22.4±9.0) mm, (25.4±5.5) mm and (6.0±4.0) mm, respectively, which were significantly lower than those of the preoperative hips ( t=9.071, P<0.01; t=11.345, P<0.01; t=4.927, P<0.01). In the triflange group, the rotational center height, the rotation center offset and LLD of 11 hips were (22.7±6.0) mm,(30.9±8.0) mm and (5.3±2.2) mm, respectively, and the rotation center height and LLD were significantly lower than those of the preoperative hips ( t=2.716, P=0.022; t=6.226, P<0.01). At the last follow-up, fractures occurred in 3 patients and dislocation occurred in 1 patient in the normal cup group, and fracture reduction and closed reduction were administered under anesthesia, respectively. In the augment group, dislocation occurred in 1 patient and open reduction under anesthesia was performed. The HHS and VAS of the three groups improved significantly after surgery and the differences were statistically significant (all P<0.01). There was no complication in the triflange group. The X-ray at the last follow-up showed that all prostheses and augments were in stable positions and no loosening or migration was observed. Conclusions:For patients with acetabular bone defect after THA undergoing hip revisions, preoperative surgical simulation and rehearsal could help surgeons choose convenient and efficient reconstruction techniques. The targeted selection of Jumbo cup, individualized 3D printed metal augment, and customized triflange cup could achieve satisfactory clinical outcomes.

Objective:To analyze three reconstruction techniques and mid-term clinical outcomes of hip revision for acetabular bone defect after total hip arthroplasty (THA).Methods:This is a retrospective case series study. Included in the study were 109 patients (109 hips) with acetabular bone defect after THA reconstructions in hip revisions from January 2015 to December 2021 in the Senior Department of Orthopaedics, the Forth Medical Center of Chinese People′s Liberation Army General Hospital and the Department of Orthopaedics, the First Medical Center of Chinese People′s Liberation Army General Hospital. According to the preoperative simulated surgeries and different bone defect reconstruction techniques, patients were divided into a normal cup group, an augment group or a triflange group,respectively. There were 54 patients (54 hips) in the normal cup group, reconstructed with the uncemented porous metal cup (including Jumbo cup), with 23 males and 31 females, aged (59.6±9.9) years (range:32 to 76 years); 44 patients (44 hips) in the augment group, reconstructed with the individualized three-dimensional (3D) printed porous metal augment and uncemented porous metal cup, with 18 males and 26 females, aged (52.8±13.6) years(range:17 to 76 years); 11 patients (11 hips) in the triflange group, reconstructed by the individualized 3D printed porous metal triflange cup, with 5 males and 6 females, aged (59.4±11.2) years (range: 43 to 78 years). Radiographic results, including rotation center height, rotation center offset, and leg length discrepancy (LLD) and clinical results, including Harris hip score (HHS) and visual analogue scale(VAS) were evaluated outpatient at 3, 6, 12 months after the operation and annually thereafter. The last follow-up was completed in March 2024, and all parameters at the last follow-up and before the operation were compared. Paired sample t test and repeated measurement ANOVA were used for the radiographic and clinical parameters before and after the operation. Results:All hip revisions for patients with acetabular bone defect after THA were completed and followed for more than two years. The follow-up time of the normal cup group was (6.5±1.7) years (range: 2.8 to 9.3 years), and that of the augment group was (6.0±1.3) years (range: 3.5 to 9.0 years). The follow-up time of the triflange group was (2.8±0.6) years (range: 2.0 to 3.8 years). At the last follow-up, the rotation center height, rotation center offset and LLD of 54 hips in the normal cup group were (24.2±5.6) mm, (29.1±5.5) mm and (4.6±3.3) mm, respectively, and the rotation center height and LLD were significantly lower than those of the preoperative hips ( t=9.671, P<0.01; t=6.073, P<0.01). In the augment group, the rotational center height, the rotation center offset and the LLD of 44 hips were (22.4±9.0) mm, (25.4±5.5) mm and (6.0±4.0) mm, respectively, which were significantly lower than those of the preoperative hips ( t=9.071, P<0.01; t=11.345, P<0.01; t=4.927, P<0.01). In the triflange group, the rotational center height, the rotation center offset and LLD of 11 hips were (22.7±6.0) mm,(30.9±8.0) mm and (5.3±2.2) mm, respectively, and the rotation center height and LLD were significantly lower than those of the preoperative hips ( t=2.716, P=0.022; t=6.226, P<0.01). At the last follow-up, fractures occurred in 3 patients and dislocation occurred in 1 patient in the normal cup group, and fracture reduction and closed reduction were administered under anesthesia, respectively. In the augment group, dislocation occurred in 1 patient and open reduction under anesthesia was performed. The HHS and VAS of the three groups improved significantly after surgery and the differences were statistically significant (all P<0.01). There was no complication in the triflange group. The X-ray at the last follow-up showed that all prostheses and augments were in stable positions and no loosening or migration was observed. Conclusions:For patients with acetabular bone defect after THA undergoing hip revisions, preoperative surgical simulation and rehearsal could help surgeons choose convenient and efficient reconstruction techniques. The targeted selection of Jumbo cup, individualized 3D printed metal augment, and customized triflange cup could achieve satisfactory clinical outcomes.

Purpose: Molecular residual disease (MRD) is a promising biomarker in colorectal cancer (CRC) for prognosis and guiding treatment, while the whole-exome sequencing (WES) based tumor-informed assay is standard for evaluating MRD based on circulating tumor DNA (ctDNA). In this study, we assessed the feasibility of a fixed-panel for evaluating MRD in CRC. Materials and Methods: Seventy-five patients with resectable stage I-III CRC were enrolled. Tumor tissues obtained by surgery, and preoperative and postoperative day 7 blood samples were collected. The ctDNA was evaluated using the tumor-agnostic and tumor-informed fixed assays, as well as the WES-based and panel-based personalized assays in randomly selected patients. Results: The tumor-informed fixed assay had a higher preoperative positive rate than the tumor-agnostic assay (73.3% vs. 57.3%). The preoperative ctDNA status failed to predict disease-free survival (DFS) in either of the fixed assays, while the tumor-informed fixed assay-determined postoperative ctDNA positivity was significantly associated with worse DFS (hazard ratio [HR], 20.74; 95% confidence interval [CI], 7.19 to 59.83; p < 0.001), which was an independent predictor by multivariable analysis (HR, 28.57; 95% CI, 7.10 to 114.9; p < 0.001). Sub-cohort analysis indicated the WES-based personalized assay had the highest preoperative positive rate (95.1%). The two personalized assays and the tumor-informed fixed assay demonstrated same results in postoperative landmark (HR, 26.34; 95% CI, 6.01 to 115.57; p < 0.001), outperforming the tumor-agnostic fixed panel (HR, 3.04; 95% CI, 0.94 to 9.89; p=0.052). Conclusion Our study confirmed the prognostic value of the ctDNA positivity at postoperative day 7 by the tumor-informed fixed panel. The tumor-informed fixed panel may be a cost-effective method to evaluate MRD, which warrants further studies in future.

BACKGROUND: Significant brain volume deviation is an essential phenotype in children with neurodevelopmental delay (NDD), but its genetic basis has not been fully characterized. This study attempted to analyze the genetic factors associated with significant whole-brain deviation volume (WBDV). METHODS: We established a reference curve based on 4222 subjects ranging in age from the first postnatal day to 18 years. We recruited only NDD patients without acquired etiologies or positive genetic results. Cranial magnetic resonance imaging (MRI) and clinical exome sequencing (2742 genes) data were acquired. A genetic burden test was performed, and the results were compared between patients with and without significant WBDV. Literature review analyses and BrainSpan analysis based on the human brain developmental transcriptome were performed to detect the potential role of genetic risk factors in human brain development. RESULTS: We recruited a total of 253 NDD patients. Among them, 26 had significantly decreased WBDV (<-2 standard deviations [SDs]), and 14 had significantly increased WBDV (>+2 SDs). NDD patients with significant WBDV had higher rates of motor development delay (49.8% [106/213] vs . 75.0% [30/40], P  = 0.003) than patients without significant WBDV. Genetic burden analyses found 30 genes with an increased allele frequency of rare variants in patients with significant WBDV. Analyses of the literature further demonstrated that these genes were not randomly identified: burden genes were more related to the brain development than background genes ( P  = 1.656e -9 ). In seven human brain regions related to motor development, we observed burden genes had higher expression before 37-week gestational age than postnatal stages. Functional analyses found that burden genes were enriched in embryonic brain development, with positive regulation of synaptic growth at the neuromuscular junction, positive regulation of deoxyribonucleic acid templated transcription, and response to hormone, and these genes were shown to be expressed in neural progenitors. Based on single cell sequencing analyses, we found TUBB2B gene had elevated expression levels in neural progenitor cells, interneuron, and excitatory neuron and SOX15 had high expression in interneuron and excitatory neuron. CONCLUSION Idiopathic NDD patients with significant brain volume changes detected by MRI had an increased prevalence of motor development delay, which could be explained by the genetic differences characterized herein.
Child ; Humans ; Neurodevelopmental Disorders/epidemiology* ; Genetic Testing ; Phenotype ; Brain/pathology* ; Genetic Background ; SOX Transcription Factors/genetics*