This study employed the "disease-medicine-dose" pattern to mine the medication rules of traditional Chinese medicine(TCM) prescriptions containing Astragali Radix in ancient Chinese medical books, aiming to provide a scientific basis for the clinical application of Astragali Radix and the development of new medicines. The TCM prescriptions containing Astragali Radix were retrieved from databases such as Chinese Medical Dictionary and imported into Excel 2020 to construct the prescription library. Statical analysis were performed for the prescriptions regarding the indications, syndromes, medicine use frequency, herb effects, nature and taste, meridian tropism, dosage forms, and dose. SPSS statistics 26.0 and IBM SPSS Modeler 18.0 were used for association rules analysis and cluster analysis. A total of 2 297 prescriptions containing Astragali Radix were collected, involving 233 indications, among which sore and ulcer, consumptive disease, sweating disorder, and apoplexy had high frequency(>25), and their syndromes were mainly Qi and blood deficiency, Qi and blood deficiency, Yin and Yang deficiency, and Qi deficiency and collateral obstruction, respectively. In the prescriptions, 98 medicines were used with the frequency >25 and they mainly included Qi-tonifying medicines and blood-tonifying medicines. Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Ginseng Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma, and Citri Reticulatae Pericarpium were frequently used. The medicines with high frequency mainly have warm or cold nature, and sweet, pungent, or bitter taste, with tropism to spleen, lung, heart, liver, and kidney meridians. In the treatment of sore and ulcer, Astragali Radix was mainly used with the dose of 3.73 g and combined with Glycyrrhizae Radix et Rhizoma to promote granulation and heal up sores. In the treatment of consumptive disease, Astragali Radix was mainly used with the dose of 37.30 g and combined with Ginseng Radix et Rhizoma to tonify deficiency and replenish Qi. In the treatment of sweating disorder, Astragali Radix was mainly used with the dose of 3.73 g and combined with Glycyrrhizae Radix et Rhizoma to consolidate exterior and stop sweating. In the treatment of apoplexy, Astragali Radix was mainly used with the dose of 7.46 g and combined with Glycyrrhizae Radix et Rhizoma to dispell wind and stop convulsions. Astragali Radix can be used in the treatment of multiple system diseases, with the effects of tonifying Qi and ascending Yang, consolidating exterior and stopping sweating, and expressing toxin and promoting granulation. According to the manifestations of different diseases, when combined with other medicines, Astragali Radix was endowed with the effects of promoting granulation and healing up sores, tonifying deficiency and Qi, consolidating exterior and stopping sweating, and dispelling wind and replenishing Qi. The findings provide a theoretical reference and a scientific basis for the clinical application of Astragali Radix and the development of new medicines.
Drugs, Chinese Herbal/history* ; Humans ; Medicine, Chinese Traditional/history* ; History, Ancient ; Astragalus Plant/chemistry* ; China ; Astragalus propinquus

Glucocorticoid-induced osteoporosis(GIOP) is a serious metabolic bone disease caused by long-term application of glucocorticoids(GCs). Traditional Chinese medicine(TCM) has unique advantages in improving bone microstructure and antagonizing hormone toxicity. This paper systematically reviews the theoretical research, clinical application, and basic research progress of TCM intervention in GIOP. In terms of theoretical research, the theory of "kidney governing bone and generating marrow" indicates that the kidney is closely related to bone development, revealing that core pathogenesis of GIOP is Yin-Yang disharmony, which can be discussed using the theories of "Yin fire", "ministerial fire", and "Yang pathogen damaging Yin". Thus, regulating Yin and Yang is the basic principle to treat GIOP. In terms of clinical application, effective empirical prescriptions(such as Bushen Zhuanggu Decoction, Bushen Jiangu Decoction, and Zibu Ganshen Formula) and Chinese patent medicines(Gushukang Capsules, Hugu Capsules, Xianling Gubao Capsules, etc.) can effectively increase bone mineral density(BMD) and improve calcium and phosphorus metabolism. The combination of traditional Chinese and western medicine can reduce the risk of fracture and play an anti-GIOP role. In terms of basic research, it has been clarified that active ingredients of TCM(such as fraxetin, ginsenoside Rg_1, and salidroside) reduce bone loss and promote bone formation by inhibiting oxidative stress, ferroptosis, and other pathways, effectively improving bone homeostasis. Additionally, classical prescriptions(Modified Yiguan Decoction, Modified Qing'e Pills, Zuogui Pills, etc.) and Chinese patent medicines(Gushukang Granules, Lurong Jiangu Dropping Pills, Gubao Capsules, etc.) can improve bone marrow microcirculation, promote osteoblast differentiation, and inhibit bone cell apoptosis through multiple pathways, multiple targets, and multiple mechanisms. Through the above three aspects, the TCM research status on GIOP is elucidated in the expectation of providing reference for its diagnosis and treatment using traditional Chinese and western medicine treatment programs.
Osteoporosis/physiopathology* ; Humans ; Glucocorticoids/adverse effects* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Medicine, Chinese Traditional ; Bone Density/drug effects*

Objective To develop a predictive model for postoperative mortality risk in patients with acute aortic dissection(AAD)using the Extreme Gradient Boosting(XGBoost)algorithm combined with Shapley Additive Explanation(SHAP),and to establish a prediction website to serve as a diagnostic and therapeutic support platform for clinicians and patients.Methods A retrospective cohort study design was adopted.Data from 782 AAD patients who underwent surgical treatment at the Fourth Hospital of Hebei Medical University from January 2013 to December 2023 were collected,including basic information and initial serum biomarker test results.Patients were randomly divided into training and test sets at a 7:3 ratio.An external validation set consisting of 313 AAD patients admitted to the Second Hospital of Hebei Medical University from January 2020 to December 2023 was also established for further model validation.Variables were screened using LASSO regression,and an XGBoost machine learning model was constructed and interpreted using SHAP.The predictive performance of the model was evaluated using receiver operating characteristic(ROC)curve analysis.Using the Shiny package,the XGBoost model was deployed to shinyapps.io to create a prediction website for postoperative mortality risk in AAD patients.One patient was selected by simple random sampling from the test set and the external validation set respectively for the prediction example on the Shiny webpage.Results The XGBoost model demonstrated high predictive performance for postoperative mortality in AAD patients,with area under the ROC curve(AUC)values of 0.928(95%CI 0.901-0.956)in the training set,0.919(95%CI 0.891-0.949)in the test set,and 0.941(95%CI 0.915-0.967)in the external validation set.SHAP values indicated the following order of variable importance in the model(from highest to lowest):"lactate dehydrogenase""blood chlorine""multiple organ injury""carbon dioxide combining power""prothrombin time""α-hydroxybutyric acid""creatine kinase isoenzyme""Stanford classification""combined use of bedside blood purification""gender""acute kidney injury""gastrointestinal bleeding""brain injury"and"shock".A risk prediction website for adverse postoperative outcomes in AAD patients was developed using XGBoost-SHAP method(https://dun-dunxiaolu.shinyapps.io/document/)and validated with examples.One randomly selected patient from each of the test and external validation sets was applied:the predicted mortality risk value for patient 1(who died postoperatively)was 0.9539,and that for patient 2(who survived postoperatively)was 0.0206.Conclusions The XGBoost-SHAP model demonstrates high accuracy in predicting postoperative mortality risk for AAD patients.The online prediction tool established based on this model enhances the identification efficiency of high-risk postoperative mortality patients.

Objective To study the mechanism of the amelioration of renal injury in immunoglobulin A nephropathy(IgAN)rats by multi-glycosides of Tripterygium wilfordii(GTW)based on the sphingosine kinase 1(Sphk1)/sphingosine 1-phosphate receptor 2(S1PR2)signalling pathway.Methods An IgAN rat model was established by means of bovine serum albumin gavage+castor oil and carbon tetrachloride subcutaneous injection+lipopolysaccharide tail vein injection.The rats were randomly divided into the model,control and experimental groups,with 9 rats in each group,and 10 normal rats were taken as the blank group.In the control group,6.25 mg·kg-1·d-1 prednisone was given by gavage;in the experimental group,9.375 mg·kg-1·d-1GTW was given by gavage;and in the blank and model groups,0.5 mL·100 g-1·d-1 0.9％NaCl was given by gavage,and the drugs were administered to the rats once a day in each group.At the end of the 15th week,urine samples were collected and blood albumin(ALB),blood urea nitrogen(BUN),24 hour-urine protein quantification(24 h-UTP),and urine erythrocyte counts were determined in each group,and the expression levels of Sphk1/S1PR2 proteins in each group were detected by Western blotting.Results The renal pathological changes in the control and experimental groups were significantly reduced compared with those in the model group by hematoxylin-eosin staining and immunofluorescence.The levels of ALB in the blank,model,control and experimental groups were(32.49±2.23),(22.98±0.51),(26.01±1.33)and(26.53±1.92)g·L-1;the levels of BUN were(6.11±1.71),(13.75±2.96),(6.71±1.35)and(4.77±0.99)mmol·L-1;the levels of 24 h-UTP were(5.72±1.96),(9.12±2.15),(5.78±2.05)and(4.75±1.50)mg·24 h-1;the urine erythrocyte counts were(9.73±2.40),(14.62±2.60),(9.90±1.59)and(9.46±2.94)cell·μL-1;the relative expression levels of Sphk1 protein were 0.85±0.02,1.47±0.02,1.06±0.02 and 1.09±0.02;the relative expression levels of S1PR2 protein were 0.27±0.02,0.88±0.01,0.43±0.02,and 0.42±0.02,respectively.The above indexes in the model group were statistically significant when compared with those of the control group and the experimental group(all P＜0.01).Conclusion GTW may reduce the proliferation of mesangial cells by inhibiting the Sphk1/S1PR2 signalling pathway,thus attenuating kidney injury in IgAN rats.

Objective This study aimed to analyze the current epidemic situation of cancer in Yunnan province in 2020,and to provide theoretical basis for the prevention and treatment of cancer in Yunnan province.Methods The data on the incidence and mortality of cancer were collected from 129 cancer registration areas in Yunnan province in 2020.A total of 89 counties(cities,dis-tricts)that met the quality control standards were included in this analysis.Among them,there were 16 in urban areas,covering a pop-ulation of 7,593,622(24.16%),and 73 in rural areas,covering a population of 23,838,542(75.84%).The number of malignant tumor cases,deaths,the crude incidence and China age-standardized incidence(China Standardized Incidence),the crude mortality and China age-standardized mortality(China Standardized Mortality),the cumulative incidence and mortality from 0 to 74 years old,as well as the order of cancer incidence and death were statistical analyzed.Results In 2020,66,719 new cases of cancer were re-ported from 89 tumor registration areas in Yunnan province,with a crude rate of 212.26/100,000 and the China age-standardized in-cidence of 150.33/100,000;The reported number of deaths from cancer was 39,251,with a crude mortality of 124.88/100,000 and the China age-standardized mortality of 82.45/100,000.The incidence and mortality of cancer were higher in men than those in fe-male,and higher in rural than those in urban areas.According to the crude incidence rate and crude mortality,the top 5 cancers with the highest crude incidence were lung cancer,female breast cancer,colo-rectum cancer,liver cancer and thyroid cancer,and the top 5 cancers with the highest crude mortality were lung cancer,liver cancer,colo-rectum cancer,stomach cancer and female breast cancer.Conclusion Lung cancer,liver cancer,colo-rectum cancer and female breast cancer are still the key cancers for prevention and con-trol in Yunnan province.The incidence of thyroid cancer is relatively high,and there are significant differences in the incidence and mortality of cancer between urban and rural areas and between sexes.The corresponding cancer prevention should be carried out ac-cording to the current epidemic situation of cancer in Yunnan province.

Objective This study aimed to analyze the incidence and mortality of cervical cancer in tumor registration areas of Yunnan province in 2020,as well as the trend of incidence and mortality from 2012 to 2020,in order to provide a basis for the pre-vention and treatment of cervical cancer in Yunnan province.Methods The data of cervical cancer incidence and mortality were col-lected and sorted out in tumor registration areas of Yunnan province from 2012 to 2020.The crude incidence,crude mortality,age-standardized incidence rate by World standard population(ASIRW)(referred to the World standard incidence),age-standardized mortality rate by World standard population(ASMRW)(referred to the World standard mortality)and other indicators of cervical canc-er in 2020 were statistically analyzed according to the urban and rural areas.The annual percent change(APC)was used to evaluate the changing trend of cervical cancer incidence and mortality from 2012 to 2020,and the GM(1,1)model was used to predict the crude incidence and ASIRW from 2021 to 2025.Results In 2020,there were 2426 new cases of cervical cancer in tumor registration area of Yunnan province,ranking fifth in the incidence of female malignant tumors.The crude incidence and ASIRW were 15.83/100,000 and 11.16/100,000,respectively.There were 831 deaths from cervical cancer,ranking sixth deaths of female malignant tumors.The crude mortality and ASMRW were 5.42/100,000 and 3.52/100,000,respectively.ASIRW was higher in rural areas(11.86/100,000)than that in urban areas(9.11/100,000).ASMRW was slightly higher in urban areas(3.63/100,000)than that in rural areas(3.48/100,000).The age-specific incidence of cervical cancer increased rapidly after the age of 20,and reached a peak in the 55-59 age group;The age-specific mortality of cervical cancer increased rapidly after the age of 35,reaching a peak in the 75-79 age group.ASIRW of cervical cancer in Yunnan province from 2012 to 2020 showed a downward trend with annual changes(APC=-7.54%,95%CI:-13.19%--1.53%),and the trend change was statistically significant(P<0.05).The prediction of the GM(1,1)model showed that the crude incidence and ASIRW of cervical cancer in Yunnan province would continue to decline from 2021 to 2025.Conclusion The incidence and mortality of cervical cancer are relatively low in Yunnan province,but it is still a common malignant tumor in women.The incidence of cervical cancer in Yunnan province is showing a trend of becoming younger,and rural women are the key population for prevention and treatment.

Objective This study aimed to analyze the current epidemic situation of cancer in Yunnan province in 2020,and to provide theoretical basis for the prevention and treatment of cancer in Yunnan province.Methods The data on the incidence and mortality of cancer were collected from 129 cancer registration areas in Yunnan province in 2020.A total of 89 counties(cities,dis-tricts)that met the quality control standards were included in this analysis.Among them,there were 16 in urban areas,covering a pop-ulation of 7,593,622(24.16%),and 73 in rural areas,covering a population of 23,838,542(75.84%).The number of malignant tumor cases,deaths,the crude incidence and China age-standardized incidence(China Standardized Incidence),the crude mortality and China age-standardized mortality(China Standardized Mortality),the cumulative incidence and mortality from 0 to 74 years old,as well as the order of cancer incidence and death were statistical analyzed.Results In 2020,66,719 new cases of cancer were re-ported from 89 tumor registration areas in Yunnan province,with a crude rate of 212.26/100,000 and the China age-standardized in-cidence of 150.33/100,000;The reported number of deaths from cancer was 39,251,with a crude mortality of 124.88/100,000 and the China age-standardized mortality of 82.45/100,000.The incidence and mortality of cancer were higher in men than those in fe-male,and higher in rural than those in urban areas.According to the crude incidence rate and crude mortality,the top 5 cancers with the highest crude incidence were lung cancer,female breast cancer,colo-rectum cancer,liver cancer and thyroid cancer,and the top 5 cancers with the highest crude mortality were lung cancer,liver cancer,colo-rectum cancer,stomach cancer and female breast cancer.Conclusion Lung cancer,liver cancer,colo-rectum cancer and female breast cancer are still the key cancers for prevention and con-trol in Yunnan province.The incidence of thyroid cancer is relatively high,and there are significant differences in the incidence and mortality of cancer between urban and rural areas and between sexes.The corresponding cancer prevention should be carried out ac-cording to the current epidemic situation of cancer in Yunnan province.

Objective This study aimed to analyze the incidence and mortality of cervical cancer in tumor registration areas of Yunnan province in 2020,as well as the trend of incidence and mortality from 2012 to 2020,in order to provide a basis for the pre-vention and treatment of cervical cancer in Yunnan province.Methods The data of cervical cancer incidence and mortality were col-lected and sorted out in tumor registration areas of Yunnan province from 2012 to 2020.The crude incidence,crude mortality,age-standardized incidence rate by World standard population(ASIRW)(referred to the World standard incidence),age-standardized mortality rate by World standard population(ASMRW)(referred to the World standard mortality)and other indicators of cervical canc-er in 2020 were statistically analyzed according to the urban and rural areas.The annual percent change(APC)was used to evaluate the changing trend of cervical cancer incidence and mortality from 2012 to 2020,and the GM(1,1)model was used to predict the crude incidence and ASIRW from 2021 to 2025.Results In 2020,there were 2426 new cases of cervical cancer in tumor registration area of Yunnan province,ranking fifth in the incidence of female malignant tumors.The crude incidence and ASIRW were 15.83/100,000 and 11.16/100,000,respectively.There were 831 deaths from cervical cancer,ranking sixth deaths of female malignant tumors.The crude mortality and ASMRW were 5.42/100,000 and 3.52/100,000,respectively.ASIRW was higher in rural areas(11.86/100,000)than that in urban areas(9.11/100,000).ASMRW was slightly higher in urban areas(3.63/100,000)than that in rural areas(3.48/100,000).The age-specific incidence of cervical cancer increased rapidly after the age of 20,and reached a peak in the 55-59 age group;The age-specific mortality of cervical cancer increased rapidly after the age of 35,reaching a peak in the 75-79 age group.ASIRW of cervical cancer in Yunnan province from 2012 to 2020 showed a downward trend with annual changes(APC=-7.54%,95%CI:-13.19%--1.53%),and the trend change was statistically significant(P<0.05).The prediction of the GM(1,1)model showed that the crude incidence and ASIRW of cervical cancer in Yunnan province would continue to decline from 2021 to 2025.Conclusion The incidence and mortality of cervical cancer are relatively low in Yunnan province,but it is still a common malignant tumor in women.The incidence of cervical cancer in Yunnan province is showing a trend of becoming younger,and rural women are the key population for prevention and treatment.

Objective: Single-cell RNA sequencing (scRNA-seq) was used to analyze the developing mouse molars, in order to construct a spatiotemporal development atlas of pulp cells, and further to reveal the developmental process and regulatory mechanism of tooth development. Methods: Ten mandibular first molars from C57BL/6 mice in postnatal day (PN) 0 and 3 were respectively dissected and digested to obtain single-cell suspensions. scRNA-seq was performed on 10× Genomics platform. PN 7 mouse molar scRNA-seq data were obtained from our previous study. PN 0, 3, and 7 scRNA-seq data were integrated for following analysis. The initial quality control, mapping and single cell expression matrix construction were performed by Cell Ranger. Quality control, standardization, dimensional reduction and cluster analysis were performed by using Seurat. Monocle was used to generate the pseudotime trajectory. Scillus was used to perform gene ontology analysis. In order to detect the spatiotemporal change of different population of pulp cells, the marker genes of each cluster were demonstrated by RNAscope in situ hybridization. Results: There were twenty-six cell clusters within mouse molars, which were identified as eight different cell types, including dental pulp cells, dental follicle cells, epithelial cells, immune cells, endothelial cells, perivascular cells, glial cells and erythrocytes. We further re-clustered and analyzed dental pulp cells. Cluster 0 were mature pulp cells, which located at the upper portion of crown. The main functions of cluster 0 were osteogenesis and extracellular structure organization. Cluster 1 were apical papilla cells, which located at the apical part of roots, whose main functions were extracellular structure organization and organ development. Cluster 2 were cycling cells, which were actively proliferated, resided in the lower portion of the crown. Cluster 3 and 4 were preodontoblasts and odontoblasts, respectively. Their functions were closely related to biomineralization. The proportion of mature pulp cells increased with the development process, while the proportion of cycling cells and odontoblast lineage decreased. According to the expression pattern of marker genes of each cluster, we constructed a cell atlas of dental pulp. Pseudotime trajectory analysis found there were two development trajectories within dental pulp. They both started from SPARC related modular calcium binding 2 (Smoc2)+ dental papilla cells, then went through DNA topoisomerase Ⅱ alpha (Top2a)+ cycling cells, and finally divided into coxsackie virus and adenovirus receptor (Cxadr)+ mature pulp cells or dentin sialophosphoprotein (Dspp)+ odontoblasts two lineages. Conclusions: scRNA-seq could fully discover the intercellular heterogeneity of cells on transcriptome level, which provides a powerful tool to study the process and regulatory mechanism of organ development.

Objective: Total neoadjuvant therapy has been used to improve tumor responses and prevent distant metastases in patients with locally advanced rectal cancer (LARC). Patients with complete clinical responses (cCR) then have the option of choosing a watch and wait (W&W) strategy and organ preservation. It has recently been shown that hypofractionated radiotherapy has better synergistic effects with PD-1/PD-L1 inhibitors than does conventionally fractionated radiotherapy, increasing the sensitivity of microsatellite stable (MSS) colorectal cancer to immunotherapy. Thus, in this trial we aimed to determine whether total neoadjuvant therapy comprising short-course radiotherapy (SCRT) combined with a PD-1 inhibitor improves the degree of tumor regression in patients with LARC. Methods: TORCH is a prospective, multicenter, randomized, phase II trial (TORCH Registration No. NCT04518280). Patients with LARC (T3-4/N+M0, distance from anus ≤10 cm) are eligible and are randomly assigned to consolidation or induction arms. Those in the consolidation arm receive SCRT (25Gy/5 Fx), followed by six cycles of toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Those in the induction arm receive two cycles of ToriCAPOX, then undergo SCRT, followed by four cycles of ToriCAPOX. Patients in both groups undergo total mesorectal excision (TME) or can choose a W&W strategy if cCR has been achieved. The primary endpoint is the complete response rate (CR, pathological complete response [pCR] plus continuous cCR for more than 1 year). The secondary endpoints include rates of Grade 3-4 acute adverse effects (AEs) etc. Results: Up to 30 September 2022, 62 patients attending our center were enrolled (Consolidation arm: 34, Induction arm:28). Their median age was 53 (27-69) years. Fifty-nine of them had MSS/pMMR type cancer (95.2%), and only three MSI-H/dMMR. Additionally, 55 patients (88.7%) had Stage III disease. The following important characteristics were distributed as follows: lower location (≤5 cm from anus, 48/62, 77.4%), deeper invasion by primary lesion (cT4 7/62, 11.3%; mesorectal fascia involved 17/62, 27.4%), and high risk of distant metastasis (cN2 26/62, 41.9%; EMVI+ 11/62, 17.7%). All 62 patients completed the SCRT and at least five cycles of ToriCAPOX, 52/62 (83.9%) completing six cycles of ToriCAPOX. Finally, 29 patients achieved cCR (46.8%, 29/62), 18 of whom decided to adopt a W&W strategy. TME was performed on 32 patients. Pathological examination showed 18 had achieved pCR, four TRG 1, and 10 TRG 2-3. The three patients with MSI-H disease all achieved cCR. One of these patients was found to have pCR after surgery whereas the other two adopted a W&W strategy. Thus, the pCR and CR rates were 56.2% (18/32) and 58.1% (36/62), respectively. The TRG 0-1 rate was 68.8% (22/32). The most common non-hematologic AEs were poor appetite (49/60, 81.7%), numbness (49/60, 81.7%), nausea (47/60, 78.3%) and asthenia (43/60, 71.7%); two patients did not complete this survey. The most common hematologic AEs were thrombocytopenia (48/62, 77.4%), anemia (47/62, 75.8%), leukopenia/neutropenia (44/62, 71.0%) and high transaminase (39/62, 62.9%). The main Grade III-IV AE was thrombocytopenia (22/62, 35.5%), with three patients (3/62, 4.8%) having Grade IV thrombocytopenia. No Grade V AEs were noted. Conclusions: SCRT-based total neoadjuvant therapy combined with toripalimab can achieve a surprisingly good CR rate in patients with LARC and thus has the potential to offer new treatment options for organ preservation in patients with MSS and lower-location rectal cancer. Meanwhile, the preliminary findings of a single center show good tolerability, the main Grade III-IV AE being thrombocytopenia. The significant efficacy and long-term prognostic benefit need to be determined by further follow-up.
Humans ; Middle Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Chemoradiotherapy ; Immune Checkpoint Inhibitors/therapeutic use* ; Neoadjuvant Therapy ; Prospective Studies ; Rectal Neoplasms/pathology* ; Thrombocytopenia/drug therapy* ; Treatment Outcome ; Adult ; Aged