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.

In recent years,a growing body of research has demonstrated that acupuncture can be used to effectively treat a diverse range of diseases,including functional gastrointestinal disorders,cardiovascular diseases,as well as anxiety and depression,through the modulation of the paraventricular hypothalamic nucleus(PVN).Acupuncture may exert its therapeutic effect either by modulating specific neurons within the PVN,such as corticotropin releasing hormone(CRH)neurons,or by regulating the release of hormones,such as oxytocin(OXT)and vasopressin(VP),and the activity of neural circuits associated with the PVN.This review summarizes the mechanisms by which PVN is involved in acupuncture treatment,including its regulatory mechanisms in gastrointestinal diseases,cardiovascular diseases,and negative emotions and pain.Future research should be conducted to further explore the precise mechanisms by which acupuncture regulates PVN to treat diseases,focusing on clarifying the specific processes of signaling pathway transduction,and exploring the specific effects of acupunture of different acupoint combinations and stimulation frequencies and intensity on PVN.

Objective To analyze the prognosis and influencing factors in patients with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). Methods A retrospective analysis was conducted on 52 patients with RAIR-DTC who underwent ineffective ¹³¹I therapy at the Department of Nuclear Medicine, Cancer Hospital, Chinese Academy of Medical Sciences from October 2016 to January 2020. Patients were categorized into progression and stable groups based on disease progression within five years post-treatment. Differences between groups were analyzed using chi-square test and logistic regression. Independent prognostic risk factors were identified using a Cox proportional hazards model. The Kaplan-Meier method with log-rank test was used to evaluate the impact of treatment on the prognosis of the progression group. Results The 3-year and 5-year survival rates of the 52 patients with RAIR-DTC were 88.5% and 73.1%, respectively. In the progression group, the rates were 81.8% and 57.6%. In the stable group, the rates were 100% and 100%. There were significant differences between the two groups in terms of age, presence of extrathyroidal extension, and the initial ¹³¹I treatment dose (P < 0.05). Univariate analysis indicated that the age, pre-ablation stimulated thyroglobulin level before the first ¹³¹I treatment, the neutrophil-to-lymphocyte ratio before the first treatment, and the sites of recurrence and metastasis were significantly associated with overall survival (P < 0.05). Multivariate analysis showed that age > 55 years (HR=12.40, 95% CI= 2.09-73.57, P=0.001) and distant metastasis (HR=24.47, 95% CI=4.17-143.75, P < 0.001) were independent risk factors for poor prognosis. Kaplan-Meier curve analysis showed that local surgery and/or targeted therapy significantly prolonged progression-free survival in the progression group (P < 0.001). Conclusion The prognosis for RAIR-DTC is poor, with advanced age and distant metastasis significantly associated with unfavorable outcomes. In elderly patients and those with extrathyroidal invasion, the treatment dose during initial ¹³¹I therapy may be appropriately increased to delay disease progression. For patients with disease progression, prompt local surgical intervention and/or targeted therapy is recommended.

Objective To analyze the prognosis and influencing factors in patients with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). Methods A retrospective analysis was conducted on 52 patients with RAIR-DTC who underwent ineffective ¹³¹I therapy at the Department of Nuclear Medicine, Cancer Hospital, Chinese Academy of Medical Sciences from October 2016 to January 2020. Patients were categorized into progression and stable groups based on disease progression within five years post-treatment. Differences between groups were analyzed using chi-square test and logistic regression. Independent prognostic risk factors were identified using a Cox proportional hazards model. The Kaplan-Meier method with log-rank test was used to evaluate the impact of treatment on the prognosis of the progression group. Results The 3-year and 5-year survival rates of the 52 patients with RAIR-DTC were 88.5% and 73.1%, respectively. In the progression group, the rates were 81.8% and 57.6%. In the stable group, the rates were 100% and 100%. There were significant differences between the two groups in terms of age, presence of extrathyroidal extension, and the initial ¹³¹I treatment dose (P < 0.05). Univariate analysis indicated that the age, pre-ablation stimulated thyroglobulin level before the first ¹³¹I treatment, the neutrophil-to-lymphocyte ratio before the first treatment, and the sites of recurrence and metastasis were significantly associated with overall survival (P < 0.05). Multivariate analysis showed that age > 55 years (HR=12.40, 95% CI= 2.09-73.57, P=0.001) and distant metastasis (HR=24.47, 95% CI=4.17-143.75, P < 0.001) were independent risk factors for poor prognosis. Kaplan-Meier curve analysis showed that local surgery and/or targeted therapy significantly prolonged progression-free survival in the progression group (P < 0.001). Conclusion The prognosis for RAIR-DTC is poor, with advanced age and distant metastasis significantly associated with unfavorable outcomes. In elderly patients and those with extrathyroidal invasion, the treatment dose during initial ¹³¹I therapy may be appropriately increased to delay disease progression. For patients with disease progression, prompt local surgical intervention and/or targeted therapy is recommended.

Objective:To investigate the effects of diquat (DQ) on the expression of intestinal pyroptosis-related proteins and tight junction proteins in rats, and to analyze the role of pyroptosis in the intestinal injury of rats with acute DQ poisoning.Methods:A total of 36 Wistar male rats were randomly divided into control group, and 3 hours, 12 hours, 36 hours and 3 days exposure groups, with 6 rats in each group. Each exposure group was given 1/2 median lethal dose (LD50) of 115.5 mg/kg DQ by one-time gavage. The control group was given the same amount of normal saline by gavage. The control group was anesthetized at 3 hours after DQ gavage to take jejunal tissues; each exposure group was anesthetized at 3 hours, 12 hours, 36 hours, and 3 days after DQ gavage to take jejunal tissues, respectively. The general conditions of the rats were recorded. The pathological changes of jejunum tissue were observed by hematoxylin-eosin (HE) staining. The expression of intestinal pyroptosis-related proteins [NOD-like receptor protein 3 (NLRP3), cysteine aspartate-specific protease 1 (caspase-1), Gasdemin D (GSDMD)] in the intestinal tissues was observed by immunohistochemical staining. Western blotting was used to detect the expression of intestinal pyroptosis-related proteins and intestinal tight junction proteins (Occludin and Claudin-1).Results:Light microscopy showed that pathological changes occurred in jejunum tissue at the early stage of exposure (3 hours), and the injury was the most serious in the 12 hours exposure group, with a large number of inflammatory cells infiltrating in the tissue, and the damage was significantly reduced after 3 days exposure. Immunohistochemical results showed that NLRP3, caspase-1 and GSDMD were expressed in the jejunal mucosa of the control group and the exposure groups, and the positive cells in the control group were less expressed with light staining. The expression of the above proteins in the exposed group was increased significantly and the staining was deep. Western blotting results showed that compared with the control group, the expression of NLRP3 protein in jejunum tissues of all groups was increased, with the most significant increase in the 36 hours group (NLRP3/β-actin: 1.47±0.06 vs. 0.43±0.14, P < 0.01). Compared with the control group, the expression of GSDMD protein in the 3 hours, 12 hours and 36 hours exposure groups increased, and the expression of GSDMD protein in the 3 hours and 12 hours exposure groups increased significantly (GSDMD/β-actin: 1.04±0.40, 1.25±0.15 vs. 0.65±0.25, both P < 0.05). The expression of caspase-1 protein was increased in 36 hours exposure group compared with the control group (caspase-1/β-actin: 1.44±0.34 vs. 0.98±0.19, P > 0.05). Compared with the control group, the expression of Occludin and Claudin-1 proteins in each exposure group decreased, and the expression of Occludin proteins was significantly decreased in the 3 hours, 12 hours, and 36 hours exposure groups decreased significantly (Occludin/β-actin: 0.74±0.17, 0.91±0.20, 0.79±0.23 vs. 1.41±0.08, all P < 0.05). Although the protein expression of Claudin-1 decreased in each exposure group, the difference was not statistically significant. Conclusion:The intestinal injury caused by acute DQ poisoning may be related to the activation of pyroptosis pathway of small intestinal cells and the reduction of the density of intercellular junctions.

Objective To investigate the key elements for model establishment and determine the evaluation indicators of animal models for pelvic inflammatory disease(PID),providing a reference for improving modelling methods and optimizing the application of PID animal models.Methods The search query"Pelvic Inflammatory Disease"AND"Animal Model"OR"Rat"OR"Mouse"OR"Guinea Pig"OR"Rabbit"OR"Dog"OR"Pig"was used to retrieve relevant literature on PID animal models published from 2013 to 2023 in China Knowledge Network Infrastructure(CNKI),Wanfang,and PubMed databases.The studies were analyzed and categorized based on experimental animal types,modelling methods,modelling cycles,detection indicators,positive control drugs,and administration duration.A database was established for statistical analysis.Results A total of 214 research articles on PID animal models meeting the inclusion criteria were identified.The most commonly used model animals are Sprague Dawley(SD)rats,followed by Wistar rats.The most frequently employed modelling method is a combination of mechanical injury and bacterial infection,followed by the phenol mucilage method.The most common modelling cycles for acute pelvic inflammatory disease(APID)and chronic pelvic inflammatory disease(CPID)/sequelae of pelvic inflammatory disease(SPID)are 8 to 14 days,while for PID models without specific staging,the cycles are 7 days.High-frequency detection methods and indicators include histopathological observation using hematoxylin-eosin staining,enzyme-linked immunosorbent assay(ELISA)for serum-related indicators,morphological changes of tissues observed with the naked eye,and immunohistochemical detection of related protein expression in uterine tissues,and pathological scoring.The most frequently used positive control drugs are Fuke Qianjin Tablets,followed by Jingangteng Capsules.The most common administration duration for APID is 7 days,and for CPID/SPID models,it ranges from 15 to 21 days.Conclusion Currently,SD rats and Wistar rats are commonly used as experimental animals for PID models.The dual modelling method of mechanical injury combined with mixed bacterial infection aligns closely with clinical pathogenesis and can be used to establish a PID model that simulates postoperative uterine cavity infection.Depending on the research objectives,different positive drugs and detection indicators should be selected for comprehensive evaluation.Most existing PID animal model studies are based on western medical diagnosis,with fewer studies focusing on Traditional Chinese Medicine(TCM)syndromes.There is a need to integrate TCM theories of etiology and pathogenesis to construct PID animal models that are more in line with TCM clinical symptoms.

OBJECTIVE: To observe the toxicokinetic parameters, absorption characteristics and pathomorphological damage in different parts of the gastrointestinal tract of rats poisoned with different doses of diquat (DQ). METHODS: Ninety-six healthy male Wistar rats were randomly divided into a control group (six rats) and low (115.5 mg/kg), medium (231.0 mg/kg) and high (346.5 mg/kg) dose DQ poisoning groups (thirty rats in each dose group), and then the poisoning groups were randomly divided into 5 subgroups according to the time after exposure (15 minutes and 1, 3, 12, 36 hours; six rats in each subgroup). All rats in the exposure groups were given a single dose of DQ by gavage. Rats in the control group was given the same amount of saline by gavage. The general condition of the rats was recorded. Blood was collected from the inner canthus of the eye at 3 time points in each subgroup, and rats were sacrificed after the third blood collection to obtain gastrointestinal specimens. DQ concentrations in plasma and tissues were determined by ultra-high performance liquid chromatography and mass spectrometry (UPHLC-MS), and the toxic concentration-time curves were plotted to calculate the toxicokinetic parameters; the morphological structure of the intestine was observed under light microscopy, and the villi height and crypt depth were determined and the ratio (V/C) was calculated. RESULTS: DQ was detected in the plasma of the rats in the low, medium and high dose groups 5 minutes after exposure. The time to maximum plasma concentration (Tmax) was (0.85±0.22), (0.75±0.25) and (0.25±0.00) hours, respectively. The trend of plasma DQ concentration over time was similar in the three dose groups, but the plasma DQ concentration increased again at 36 hours in the high dose group. In terms of DQ concentration in gastrointestinal tissues, the highest concentrations of DQ were found in the stomach and small intestine from 15 minutes to 1 hour and in the colon at 3 hours. By 36 hours after poisoning, the concentrations of DQ in all parts of the stomach and intestine in the low and medium dose groups had decreased to lower levels. Gastrointestinal tissue (except jejunum) DQ concentrations in the high dose group tended to increase from 12 hours. Higher doses of DQ were still detectable [gastric, duodenal, ileal and colonic DQ concentrations of 6 400.0 (1 232.5), 4 889.0 (6 070.5), 10 300.0 (3 565.0) and 1 835.0 (202.5) mg/kg respectively]. Light microscopic observation of morphological and histopathological changes in the intestine shows that acute damage to the stomach, duodenum and jejunum of rats was observed 15 minutes after each dose of DQ, pathological lesions were observed in the ileum and colon 1 hour after exposure, the most severe gastrointestinal injury occurred at 12 hours, significant reduction in villi height, significant increase in crypt depth and lowest V/C ratio in all segments of the small intestine, damage begins to diminish by 36-hour post-intoxication. At the same time, morphological and histopathological damage to the intestine of rats at all time points increased significantly with increasing doses of the toxin. CONCLUSIONS The absorption of DQ in the digestive tract is rapid, and all segments of the gastrointestinal tract may absorb DQ. The toxicokinetics of DQ-tainted rats at different times and doses have different characteristics. In terms of timing, gastrointestinal damage was seen at 15 minutes after DQ, and began to diminish at 36 hours. In terms of dose, Tmax was advanced with the increase of dose and the peak time was shorter. The damage to the digestive system of DQ is closely related to the dose and retention time of the poison exposure.
Animals ; Male ; Rats ; Diquat/toxicity* ; Gastrointestinal Diseases ; Intestines ; Poisons ; Rats, Wistar ; Toxicokinetics

ObjectiveTo analysis the modeling characteristics of diminished ovarian reserve (DOR) animal models, and provide the reference for the standardization of DOR animal models.MethodsThe research articles on DOR animal models were retrieved. Microsoft Excel 2010 software was used to summarize the experimental animal species, modeling methods, modeling cycles, high-frequency detection indexes and types of positive drugs documented in the literature, and the data results were evaluated and analyzed by NoteExpress software.ResultsA total of 93 research articles on DOR that met the criteria were enrolled. And it was found that, SD rat was the most frequently used animal type (68 times, 73.12%), followed by C57BL/6 mouse (13 times, 13.98%), while the tripterygium wilfordii treatment was the most frequently used modeling method (38 times, 40.86%), followed by the cyclophosphamide treatment (28 times, 30.11%) for DOR animal models. The high frequency detection indicators were vaginal exfoliation cytology detection (93 times, 23.97%) and HE staining to observe histopathological changes (72 times, 18.56%). Among these 64 research articles containing positive control drugs, the most frequently used western drug was estrogen (50 times,62.50%) and Chinese Traditional medicine was Kuntai capsules (2 times, 2.50%).ConclusionsSD rats are mostly used to induce modeling in animal experiments on DOR through tripterygium wilfordii and cyclophosphamide, which can effectively improve the experimental efficiency. It is recommended to integrate the results of ovarian histopathology and serum biochemical indexes for model assessment.

Objective:To investigate the correlation of intratumoral fibrosis with the prognosis of clear cell renal cell carcinoma (ccRCC).Methods:The correlation of the transcriptional expression of the primary collagen with the prognosis in ccRCC was evaluated using the Cancer Genome Atlas (TCGA) database, including 530 ccRCC patients with complete information. Of them, 344 cases were male, 186 cases were female. The age of 264 cases was ≤ 60 years, and the age of 266 cases was > 60 years. The pathology grade of 241 patients was G 1-2 grade, and the pathology of 281 cases were G 3-4 grade, 8 cases were undetermined grade. There were 322 cases with AJCC stage Ⅰ-Ⅱ and 205 cases with AJCC stage Ⅲ-Ⅳ, and 3 cases with undetermined stage. There were 420 cases in M 0 and 78 cases in M 1, and 32 cases without distant metastases information. Furthermore, the paraffin sections of 158 non-cystic ccRCC patients confirmed by pathology from November 2005 to November 2017 were further used to evaluate the level of collagen of ccRCC and the status of the pseudocapsule by the Masson staining, Sirius red staining and multicolor immunofluorescence staining of collagen Ⅰ and collagen Ⅲ. Of them, 112 cases were male, 46 cases were female. There were 100 cases with age ≤ 60 years, and 58 cases with age > 60 years. The pathology grade of 111 cases were G 1-2, and the pathology grade of 47 cases were G 3-4. There were 144 cases with AJCC stage Ⅰ-Ⅱ, 14 cases with AJCC stage Ⅲ-Ⅳ. Kaplan-Meier survival curve were used to analyze the relationship between tumor collagen parameters and the overall survival prognosis of patients with ccRCC. Results:The transcriptome results of the TCGA database indicated that the expression level of COL1A1 in ccRCC tissues was significantly higher than that in adjacent normal tissues ( P<0.001). The high expression of collagen suggested a worse overall survival prognosis ( HR=1.165, P=0.002). In addition, the high ratio of COL1A1/COL3A1 indicated a worse overall survival prognosis ( HR=1.901, P<0.001) compared with the low ratio. We further confirmed that the abundance of collagen in tumor was significantly increased compared with the normal adjacent tissues by the Masson staining [41.0 (14.0-75.0) vs.15.0 (3.0-57.0), P<0.001] and the Sirius red staining [42.5 (10.0-90.0) vs.10.0 (2.5-60.0), P<0.001] on 30 ccRCC tissues and adjacent normal tissues. Based on the Masson staining, we found that high collagen abundance in tumor tissue was associated with more G 3-4 grade of tumor compared with low collagen abundance (38.5% vs.21.3%, OR=2.316, 95% CI 1.146-4.681, P=0.023). Kaplan-Meier survival curve showed that higher collagen abundance was associated with a worse overall survival prognosis in ccRCC ( HR=2.630, P=0.007). However, incomplete fibrous pseudocapsule was associated with a worse overall survival prognosis ( HR=11.140, P<0.001). Conclusions:In ccRCC, intratumoral collagen fiber level was overexpressed. High intratumoral collagen level and incomplete fibrous pseudocapsule may indicate a poor overall survival prognosis.

BACKGROUND: Health literacy is a public health goal which can be used as an independent factor of health outcomes. This study aimed to assess the association between health literacy and health status, as well as the two mediating factors of behavior and self-efficacy among residents aged 15-69 years in Qingdao. METHODS: A cross-sectional survey was implemented among residents aged 15-69 years (N = 3793) in Qingdao, China. A combination of stratified cluster random and proportional probability sampling methods was used to select subjects for this study. Data were collected using "The Chinese Citizen Health Literacy Questionnaire (2019)". We proposed a hypothetical model for the relationship between sociodemographic characteristics, health literacy, self-efficacy, health behavior, and health status, and used path analysis to validate the hypothesis. RESULTS: The path analysis showed that higher education (β = 0.293) and income (β = 0.135) are positively and directly associated with greater health literacy, which was positively associated with health status (β = 0.057). Health literacy is a direct influencing factor of health behavior (β = 0.070) and self-efficacy (β = 0.099). Health behavior (β = 0.041) and self-efficacy (β = 0.173) exerted a positive direct effect on health status. The model explained 14.1% of variance for health literacy, 3.8% for self-efficacy, 5.7% for health behavior, and 15.0% for health status. CONCLUSIONS Health literacy was identified to be a critical factor in health status. The results emphasized that the dissemination of health knowledge, development of healthy behavior, and cultivation of self-efficacy should be jointly promoted to reinforce the level of health status among residents in future work.
Adolescent ; Adult ; Aged ; China ; Cross-Sectional Studies ; Female ; Health Behavior ; Health Knowledge, Attitudes, Practice ; Health Literacy/statistics & numerical data* ; Health Status ; Humans ; Male ; Middle Aged ; Young Adult