ObjectiveTo study on the different therapeutic effects and potential mechanisms of Rhei Radix et Rhizoma（RH） before and after steaming with wine on constipation model mice. MethodsFifty-four male ICR mice were randomly divided into control group， model group， lactulose group（1.5 mg·kg^-1）， high， medium and low dose groups of RH and RH steaming with wine（PRH）（8， 4， 1 g·kg^-1）. Except for the control group， the constipation model was replicated by gavage of loperamide hydrochloride（6 mg·kg^-1） in the other groups. After 2 weeks of modeling， each administration group was gavaged with the corresponding dose of drug solution， and the control and model groups were given an equal volume of normal saline， 1 time/d for 2 consecutive weeks. After administration， the feces were collected for 16S rRNA sequencing， the levels of gastrin（GAS）， motilin（MTL）， interleukin-6（IL-6）， γ-interferon（IFN-γ） in the colonic tissue were detected by enzyme-linked immunosorbent assay（ELISA）， the histopathological changes of colon were observed by hematoxylin-eosin（HE） staining， flow cytometry was used to detect the proportion changes of CD4⁺， CD8⁺ and regulatory T cell（Treg） in peripheral blood. ResultsCompared with the control group， the model group showed significantly decrease in fecal number in 24 h， fecal quality and fecal water rate（P<0.01）， the colon was seen to have necrotic shedding of mucosal epithelium， localized intestinal glands in the lamina propria were degenerated， necrotic and atrophied， a few lymphocytes were seen to infiltrate in the necrotic area in a scattered manner， the contents of GAS and MTL， the proportions of CD4⁺， CD8⁺ and Treg were significantly reduced（P<0.01）， the contents of IL-6 and IFN-γ were significantly elevated（P<0.05， P<0.01）. Compared with the model group， the fecal number in 24 h， fecal quality and fecal water rate of high-dose groups of RH and PRH were significantly increased（P<0.05， P<0.01）， the pathological damage of the colon was alleviated to varying degrees， the contents of GAS， MTL， IL-6 and IFN-γ were significantly regressed（P<0.05， P<0.01）， and the proportions of CD4⁺ and CD8⁺ were significantly increased（P<0.01）， although the proportion of Treg showed an upward trend， there was no significant difference. In addition， the results of intestinal flora showed that the number of amplicon sequence variant（ASV） and Alpha diversity were decreased in the model group compared with the control group， and there was a significant difference in Beta diversity， with a decrease in the relative abundance of Lactobacillus and an increase in the relative abundances of Bacillus and Helicobacter. Compared with the model group， the ASV number and Alpha diversity were increased in the high-dose groups of RH and PRH， and there was a trend of regression of Beta diversity to the control group， the relative abundance of Lactobacillus increased， and the relative abundances of Bacillus and Helicobacter decreased. ConclusionRH and PRH can improve dysbacteriosis， promote immune system activation， inhibit the release of inflammatory factors for enhancing the gastrointestinal function， which may be one of the potential mechanisms of their therapeutic effect on constipation.

ObjectiveTo construct a large language model （LLM）-based intelligent pre-consultation system for traditional Chinese medicine （TCM） to improve efficacy of clinical practice. MethodsA TCM large language model was fine-tuned using DeepSpeed ZeRO-3 distributed training strategy based on YAYI 2-30B. A weighted undirected graph network was designed and an agent-based syndrome differentiation model was established based on relationship data extracted from TCM literature and clinical records. An agent collaboration framework was developed to integrate the TCM LLM with the syndrome differentiation model. Model performance was comprehensively evaluated by Loss function， BLEU-4， and ROUGE-L metrics， through which training convergence， text generation quality， and language understanding capability were assessed. Professional knowledge test sets were developed to evaluate system proficiency in TCM physician licensure content， TCM pharmacist licensure content， TCM symptom terminology recognition， and meridian identification. Clinical tests were conducted to compare the system with attending physicians in terms of diagnostic accuracy， consultation rounds， and consultation duration. ResultsAfter 100 000 iterations， the training loss value was gradually stabilized at about 0.7±0.08， indicating that the TCM-LLM has been trained and has good generalization ability. The TCM-LLM scored 0.38 in BLEU-4 and 0.62 in ROUGE-L， suggesting that its natural language processing ability meets the standard. We obtained 2715 symptom terms， 505 relationships between diseases and syndromes， 1011 relationships between diseases and main symptoms， and 1 303 600 relationships among different symptoms， and constructed the Agent of syndrome differentiation model. The accuracy rates in the simulated tests for TCM practitioners， licensed pharmacists of Chinese materia medica， recognition of TCM symptom terminology， and meridian recognition were 94.09%， 78.00%， 87.50%， and 68.80%， respectively. In clinical tests， the syndrome differentiation accuracy of the system reached 88.33%， with fewer consultation rounds and shorter consultation time compared to the attending physicians （P＜0.01）， suggesting that the system has a certain pre- consultation ability. ConclusionThe LLM-based intelligent TCM pre-diagnosis system could simulate diagnostic thinking of TCM physicians to a certain extent. After understanding the patients' natural language， it collects all the patient's symptom through guided questioning， thereby enhancing the diagnostic and treatment efficiency of physicians as well as the consultation experience of the patients.

Colorectal cancer is a common clinical malignant tumor. As the main therapeutic method of colorectal cancer, radiotherapy has a good inhibitory effect on tumor progression. In recent years, because of its good physical and biological advantages, carbon ion has shown better clinical efficacy than traditional radiotherapy in the treatment of local recurrence or distant metastasis of colorectal cancer. In this article, basic and clinical studies related to the efficacy of carbon ion therapy for the recurrence of colorectal cancer in recent years were reviewed, aiming to provide theoretical basis for preventing and reducing adverse reactions after radiotherapy and prolonging the survival of colorectal cancer patients.

  Objective  To establish a model that can predict the occurrence of acute kidney disease (AKD) in liver cirrhotic patients and evaluate its performance.  Methods  Liver cirrhotic patients who hospitalized in the department of gastroenterology of the First Hospital of Lanzhou University from January 2017 to January 2022 were retrospectively included. They were divided into AKD and non-AKD groups according to whether they were combined with AKD during hospitalization, and were randomized into training and validation sets in a 7∶3 ratio. The clinical data of patients in the two groups were collected, and LASSO regression and multifactorial Logistic regression were used to screen the influencing factors for the occurrence of AKD in patients with liver cirrhosis and to establish a prediction model. The model was then evaluated by using the receiver operating characteristic curve, the calibration curve and the clinical decision curve.  Results  A total of 796 cases of liver cirrhotic patients who met the inclusion and exclusion criteria were enrolled. Among them, 103 cases were in the AKD group and 693 cases were in the non-AKD group; 561 cases were in the training set and 235 cases were in the validation set. The results of LASSO regression and multifactorial Logistic regression showed that a history of diabetes (OR=2.922, 95% CI: 1.290-6.564, P=0.009), hepatic encephalopathy (OR=6.210, 95% CI: 2.278-17.479, P < 0.001), gastrointestinal bleeding (OR=2.501, 95% CI: 1.236-5.073, P=0.011), ascites (OR=3.219, 95% CI: 1.664-6.539, P < 0.001), male (OR=0.477, 95% CI: 0.254-0.879, P=0.019), hemoglobin (OR=0.987, 95% CI: 0.975-0.999, P=0.044), albumin (OR=0.952, 95% CI: 0.911-0.991, P=0.023), and prothrombin time (OR=0.865, 95% CI: 0.779-0.920, P < 0.001) were the independent influences on the occurrence of AKD in liver cirrhotic patients, and were used to construct a prediction model. The area under the curve of the model in the training set and validation set for predicting the occurrence of AKD in liver cirrhotic patients was 0.895 (95% CI: 0.865-0.925) and 0.869 (95% CI: 0.807-0.930), respectively. The calibration curves showed that the model had good fit and consistency and the clinical decision curves showed that the use of the model for predicting the risk of AKD could benefit liver cirrhotic patients overall.  Conclusions  A prediction model for the occurrence of AKD in liver cirrhotic patients was established based on eight influencing factors, including gender, history of diabetes, and hepatic encephalopathy. It was validated to have good discrimination, calibration, and clinical utility, and is expected to assist in the clinical early screening and identification of liver cirrhosis-associated AKD.

Objective To investigate the differences in health empowerment,perceived control and experiential avoidance between patients with coronary heart disease(CHD)with type D personality and non-type D personality. Methods From January to October,2022,using the convenient sampling method,a questionnaire survey was conducted on 195 patients with CHD from Affiliated Hospital of Shandong Second Medical University.Assessment tools in-cluded Type D Personality Scale,Chinese Version of Patient Perception Empowerment Scale(CV-PPES),Con-trol Attitudes Scale-Revised(CAS-R)and Acceptance Action Questionnaire-Ⅱ(AAQ-Ⅱ). Results A total of 185 effective questionnaires were returned,and 68 patients with type D personality.Compared with the patients with non-type D personality,the scores of negative affectivity and social inhibition were higher(|t|＞9.783,P＜0.001),the total score of CV-PPES and the scores of four dimensions(information,decision,individu-al and self-management)were lower(t＞5.843,P＜0.001),the score of CAS-R was lower(t=2.858,P=0.005),and the score of AAQ-Ⅱ was higher(t=-9.414,P＜0.001)in CHD patients with type D personality. Conclusion Compared with non-D-type patients,CHD patients with D-type personality exhibit lower levels of health empowerment and perceived control,and higher level of experiential avoidance,which may negatively impact on health behaviors.

Objective To construct and validate a risk prediction model for enteral nutrition feeding intolerance (FI) in patients with severe cerebral hemorrhage based on machine learning algorithms. Methods The clinical data of 485 patients with cerebral hemorrhage admitted to the neurological intensive care unit of Northern Jiangsu People's Hospital Affiliated to Yangzhou University from January 2020 to December 2022 were retrospectively analyzed. The patients were randomly divided into training set (n=339) and validation set (n=146) in a 7 to 3 ratio. Five machine learning algorithms were used to construct FI risk prediction models. The receiver operating characteristic (ROC) curve was plotted, and the model with the best predictive performance was selected based on the area under the curve (AUC). A nomogram model was constructed based on the optimal model. The calibration curve and decision curve analysis (DCA) were used to evaluate the calibration and clinical net benefit of the nomogram model. Results The incidence of enteral nutrition FI in patients with severe cerebral hemorrhage was 38.4%(186/485). Among the five machine learning algorithm models, the Logistic regression model had the best predictive performance(AUC=0.88). The analysis results of the Logistic regression model showed that the use of diuretics, mechanical ventilation, Glasgow Coma Scale score ≤5, vasoactive drugs, and albumin level<35 g/L were risk factors for enteral nutrition FI in patients with severe cerebral hemorrhage. A nomogram model was further constructed based on these five risk factors. The calibration curve analysis showed that the calibration curve fitted well with the ideal curve, indicating a high calibration degree of the nomogram model. The DCA results showed that when the threshold probability was 5% to 73%, the application of the nomogram model for screening could clinically benefit patients. Conclusion The construction of a nomogram model for predicting the risk of enteral nutrition FI in patients with severe cerebral hemorrhage based on machine learning methods can help to early screen high-risk patients for enteral nutrition FI and timely formulate preventive measures, thereby reducing the incidence of enteral nutrition FI in patients with severe cerebral hemorrhage.

Objective:The nasal swell body（NSB） consists of the nasal septal cartilage, nasal bone, and swollen soft tissue, all of which are visible during endoscopic and imaging examinations. Although the function of the NSB remains uncertain, there is evidence to suggest that it plays a vital role in regulating nasal airflow and filtering inhaled air. Based on anatomical and histological evidence, it is hypothesized that the NSB is indispensable in these processes. This study aims to investigate the impact of NSB on nasal aerodynamics and the deposition of allergen particles under physiological conditions. Methods:The three-dimensional （3D） nasal models were reconstructed from computed tomography （CT） scans of the paranasal sinus and nasal cavity in 30 healthy adult volunteers from Northwest China, providing basis for the construction of models without NSB following virtual NSB-removal surgery. To analyze the distribution of airflow in the nasal cavity, nasal resistance, heating and humidification efficiency, and pollen particle deposition rate at various anatomical sites, we employed the computed fluid dynamics（CFD） method for numerical simulation and quantitative analysis. In addition, we created fully transparent segmented nasal cavity models through 3D printing, which were used to conduct bionic experiments to measure nasal resistance and allergen particle deposition. Results:①The average width and length of the NSB in healthy adults in Northwest China were （12.85±1.74） mm and （28.30±1.92） mm, respectively. ②After NSB removal, there was no significant change in total nasal resistance, and cross-sectional airflow velocity remained essentially unaltered except for a decrease in topical airflow velocity in the NSB plane. ③There was no discernible difference in the nasal heating and humidification function following the removal of the NSB; ④After NSB removal, the deposition fraction（DF） of Artemisia pollen in the nasal septum decreased, and the DFs post-and pre-NSB removal were（22.79±6.61）% vs （30.70±12.27）%, respectively; the DF in the lower airway increased, and the DFs post-and pre-NSB removal were（24.12±6.59）% vs （17.00±5.57）%, respectively. Conclusion:This study is the first to explore the effects of NSB on nasal airflow, heating and humidification, and allergen particle deposition in a healthy population. After NSB removal from the healthy nasal cavities: ①nasal airflow distribution was mildly altered while nasal resistance showed no significantly changed; ②nasal heating and humidification were not significantly changed; ③the nasal septum's ability to filter out Artemisia pollen was diminished, which could lead to increased deposition of Artemisia pollen in the lower airway.
Adult ; Humans ; Cross-Sectional Studies ; Nasal Cavity/surgery* ; Allergens ; Pollen ; Artemisia ; Hydrodynamics

Objective To study the genotoxicities of raceanisodamine hydrochloride injection. Methods Bacterial reverse mutation test, in vitro Chromosomal aberration test and in vivo Micronucleus test were performed to investigate the genotoxicities of raceanisodamine hydrochloride injection. Results The Ames test showed that raceanisodamine hydrochloride injection did not increase mutagenicity for TA1535, TA102, TA100, TA98 and TA97 strains at the dosage of 0.5, 5, 50, 500, 5000 μg per plate under two parallel system conditions (±S9). Results of CA test indicated that there was no statistical difference between raceanisodamine hydrochloride injection groups (doses of 58.75,117.5 and 235.0 μg/ml) and the solvent control group under two parallel system conditions (±S9). In MNT test, with doses of 7.5, 15.0 and 30.0 mg/kg respectively, the micronucleus induction rate of bone marrow of ICR mice was not statistically significant (P>0.05) when compared with that of vehicle control group in all dose groups. Conclusion Under the conditions of these study, the results indicated that raceanisodamine hydrochloride injection had no mutagenicity to Salmonella typhimurium, had no aberration effect on the chromosome of mammalian cultured cells, and had no effect on inducing micronucleus of bone marrow polychromatic erythrocytes in ICR mouse. All test results showed that raceanisodamine hydrochloride injection had no potential carcinogenicities and genetic toxicities under the test conditions.

As the largest ecosystem of human body, intestinal microorganisms participate in the synthesis and metabolism of uric acid. Developing and utilizing intestinal bacteria to degrade uric acid might provide new ideas for the treatment of hyperuricemia. The fecal samples of people with low uric acid were inoculated into uric acid selective medium with the concentration of 1.5 mmol/L for preliminary screening, and the initially screened strains that may have degradation ability were domesticated by concentration gradient method, and the strains with high uric acid degradation rate were identified by 16S rRNA sequencing method. A strain of high-efficiency uric acid degrading bacteria was screened and domesticated from the feces of people with low uric acid. The degradation rate of uric acid could reach 50.2%. It was identified as Escherichia coli. The isolation and domestication of high efficient uric acid degrading strains can not only provide scientific basis for the study of the mechanism of intestinal microbial degradation of uric acid, but also reserve biological strains for the treatment of hyperuricemia and gout in the future.
Bacteria/metabolism* ; Domestication ; Ecosystem ; Escherichia coli/genetics* ; Humans ; Hyperuricemia ; RNA, Ribosomal, 16S/metabolism* ; Uric Acid/metabolism*

Objective To evaluate the developmental toxicity and genotoxicity of leonurine. Methods Leonurine was given orally to SD pregnant rats on the 6th to 15th day of pregnancy at the dose of 500, 1 000 and 2 000 mg/kg body weight. The control group received 0.5% CMC-Na solution orally. Pregnant rats were sacrificed on the 20th day of pregnancy to analyze the reproductive toxicity. Ames test, in vitro chromosomal aberration test of CHO cell and in vivo micronucleus assay were performed to investigate the genotoxicity of leonurine. Results There was no difference statistically in weight gain of pregnant mice between two groups at the dose of 500, 1 000 and 2 000 mg/kg of motherwort alkaloids. In vitro CHO cell chromosomal aberration test indicated that there was no statistical difference between leonurine groups (doses of 250, 500 and 1 000 μg/ml) and the solvent control group with and without metabolic activation system S9. The number of micronuclei in ICR mice did not increase (P>0.05) in the mouse bone marrow micronucleus test at the doses of 100, 500 and 2 000 mg/kg. Conclusion No significant maternal toxicity, embryo toxicity, fetal toxicity and teratogenic effects were observed with leonurine at 500, 1 000 and 2 000 mg/kg doses. Leonurine was not genotoxic in Salmonella typhimurium reverse mutation test, in vitro CHO cells chromosome aberration test or mouse bone marrow micronucleus test. It showed that leonurine had no developmental toxicity and genotoxicity under the conditions of the experiment.