Objective To develop and evaluate a fine-tuned large language model(LLM)for traditional Chinese medicine(TCM)prescription recommendation named TCMLLM-PR.Methods First,we constructed an instruction-tuning dataset containing 68 654 samples(ap-proximately 10 million tokens)by integrating data from eight sources,including four TCM textbooks,Pharmacopoeia of the People's Republic of China 2020(CHP),Chinese Medicine Clinical Cases(CMCC),and hospital clinical records covering lung disease,liver disease,stroke,diabetes,and splenic-stomach disease.Then,we trained TCMLLM-PR using Chat-GLM-6B with P-Tuning v2 technology.The evaluation consisted of three aspects:(i)compari-son with traditional prescription recommendation models(PTM,TCMPR,and PresRecST);(ii)comparison with TCM-specific LLMs(ShenNong,Huatuo,and HuatuoGPT)and general-domain ChatGPT;(iii)assessment of model migration capability across different disease datasets.We employed precision,recall,and F1 score as evaluation metrics.Results The experiments showed that TCMLLM-PR significantly outperformed baseline models on TCM textbooks and CHP datasets,with F1@10 improvements of 31.80%and 59.48%,respectively.In cross-dataset validation,the model performed best when migrating from TCM textbooks to liver disease dataset,achieving an F1@10 of 0.155 1.Analysis of real-world cases demonstrated that TCMLLM-PR's prescription recommendations most closely matched actual doctors'prescriptions.Conclusion This study integrated LLMs into TCM prescription recommendations,leverag-ing a tailored instruction-tuning dataset and developing TCMLLM-PR.This study will pub-licly release the best model parameters of TCMLLM-PR to promote the development of the decision-making process in TCM practices(https://github.com/2020MEAI/TCMLLM).

Objective To develop and evaluate a fine-tuned large language model(LLM)for traditional Chinese medicine(TCM)prescription recommendation named TCMLLM-PR.Methods First,we constructed an instruction-tuning dataset containing 68 654 samples(ap-proximately 10 million tokens)by integrating data from eight sources,including four TCM textbooks,Pharmacopoeia of the People's Republic of China 2020(CHP),Chinese Medicine Clinical Cases(CMCC),and hospital clinical records covering lung disease,liver disease,stroke,diabetes,and splenic-stomach disease.Then,we trained TCMLLM-PR using Chat-GLM-6B with P-Tuning v2 technology.The evaluation consisted of three aspects:(i)compari-son with traditional prescription recommendation models(PTM,TCMPR,and PresRecST);(ii)comparison with TCM-specific LLMs(ShenNong,Huatuo,and HuatuoGPT)and general-domain ChatGPT;(iii)assessment of model migration capability across different disease datasets.We employed precision,recall,and F1 score as evaluation metrics.Results The experiments showed that TCMLLM-PR significantly outperformed baseline models on TCM textbooks and CHP datasets,with F1@10 improvements of 31.80%and 59.48%,respectively.In cross-dataset validation,the model performed best when migrating from TCM textbooks to liver disease dataset,achieving an F1@10 of 0.155 1.Analysis of real-world cases demonstrated that TCMLLM-PR's prescription recommendations most closely matched actual doctors'prescriptions.Conclusion This study integrated LLMs into TCM prescription recommendations,leverag-ing a tailored instruction-tuning dataset and developing TCMLLM-PR.This study will pub-licly release the best model parameters of TCMLLM-PR to promote the development of the decision-making process in TCM practices(https://github.com/2020MEAI/TCMLLM).

BACKGROUND: Thyroid dysfunction is associated with cardiovascular diseases. However, the role of thyroid function in lipid metabolism remains partly unknown. The present study aimed to investigate the causal association between thyroid function and serum lipid metabolism via a genetic analysis termed Mendelian randomization (MR). METHODS: The MR approach uses a genetic variant as the instrumental variable in epidemiological studies to mimic a randomized controlled trial. A two-sample MR was performed to assess the causal association, using summary statistics from the Atrial Fibrillation Genetics Consortium (n = 537,409) and the Global Lipids Genetics Consortium (n = 188,577). The clinical measures of thyroid function include thyrotropin (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) levels, FT3:FT4 ratio and concentration of thyroid peroxidase antibodies (TPOAb). The serum lipid metabolism traits include total cholesterol (TC) and triglycerides, high-density lipoprotein, and low-density lipoprotein (LDL) levels. The MR estimate and MR inverse variance-weighted method were used to assess the association between thyroid function and serum lipid metabolism. RESULTS: The results demonstrated that increased TSH levels were significantly associated with higher TC (β = 0.052, P = 0.002) and LDL (β = 0.041, P = 0.018) levels. In addition, the FT3:FT4 ratio was significantly associated with TC (β = 0.240, P = 0.033) and LDL (β = 0.025, P = 0.027) levels. However, no significant differences were observed between genetically predicted FT4 and TPOAb and serum lipids. CONCLUSION Taken together, the results of the present study suggest an association between thyroid function and serum lipid metabolism, highlighting the importance of the pituitary-thyroid-cardiac axis in dyslipidemia susceptibility.
Lipid Metabolism/genetics* ; Mendelian Randomization Analysis ; Thyroid Function Tests ; Thyroid Gland ; Thyrotropin ; Thyroxine ; Triiodothyronine

BACKGROUND: Recently, adjustable-loop devices (ALDs) have been widely used, and their reliability has always been the focus of attention. This study compared loop length changes under pull stress caused by flexion and extension of the cadaver knee between ALDs and fixed-loop devices (FLDs) in terms of femoral fixation after anterior cruciate ligament (ACL) reconstruction. METHODS: ACL reconstruction in cadaveric knee joints was performed under arthroscopy with femoral suspension devices and tibial fixation by tying sutures on staples. The knee joint was repeatedly flexed and extended 30 times after fixation. According to the femoral fixation device used (Endobutton or Ultrabutton), the knee joints were divided into two groups: the ALD group (12 specimens) and the FLD group (ten specimens). The length of the loop before and after fixation was measured, and the loop length of the ALD group was re-measured 1 day after reconstruction. RESULTS: There was no significant difference in the length of the loop between the two groups (t = 0.579, P = 0.569). One day later, the loop length of the ALDs retracted by 0.29 ± 0.33 (0-1.1) mm, and there was no retraction in three specimens. CONCLUSION There was no significant difference in the loop length under flexion and extension stress after ACL reconstruction between ALDs and FLDs.

OBJECTIVE: To estimate the prevalence rate of bone and joint injury in China and to describe the three-dimension distribution of the disease (area, time and people). METHODS: Based on a cross-sectional design, a retrospective study was conducted by using Chinese basic medical insurance database from January 1, 2013 to December 31, 2017 to analyze the epidemiological characteristics of bone and joint injury. The prevalence rate of bone and joint injury in each city was calculated, and then using meta-analyses to estimate the pooled prevalence of each area and the whole country. The pooled prevalence rates were compared among the different groups of populations, in terms of geographical area, time and population characteristics (age and gender). RESULTS: A total of 28 419 264 subjects were included in this study, including 705 793 patients with bone and joint injury. From 2013 to 2017, in Chinese basic medical insurance database, the overall prevalence rate of bone and joint injury was 141.5(95%CI: 90.4－203.7) per 10 000 population, and the prevalence rates of non-specific or polyarticular disease, knee disease, and shoulder disease were 101.6 (95%CI: 63.5－148.4)per 10 000 population, 22.5(95%CI:15.1－31.4)per 10 000 population and 10.9 (95%CI: 6.4－16.4)per 10 000 population. The prevalence rates varied across the areas, the highest rate was observed in North China, with the prevalence of 310.6 (95%CI: 12.6－989.7) per 10 000 population, and the lowest rate was observed in Southwest China, with the prevalence of 59.0 (95%CI: 37.5－85.2) per 10 000 population. The prevalence rate of bone and joint injury increased over the study period, from 111.1 (95%CI: 56.0－182.5)per 10 000 population in 2013 to 175.5 (95%CI: 116.8－245.5)per 10 000 population in 2017. The prevalence of bone and joint injury in the female population was 149.1 (95%CI: 94.2－215.9) per 10 000 population, which was higher than that of men [133.6(95%CI: 86.2－190.9) per 10 000 population]. The higher prevalence of knee disease, unspecified or polyarticular disease, and bone and joint injury were observed in people aged 60 years and older, while the prevalence of shoulder disease peaked in 40－59 years old people [20.6 (95%CI: 12.5－30.5) per 10 000 population]. CONCLUSION This study reported a relative low prevalence of bone and joint injury in China from 2013 to 2017. The prevalence increased over the study period, and the highest prevalence rate was observed in North China. The prevalence rate showed differences among different groups of populations, and higher rates were observed in females and people aged 60 years and older.
Adult ; China ; Databases, Factual ; Female ; Humans ; Insurance, Health ; Male ; Middle Aged ; Prevalence ; Retrospective Studies ; Urban Population

Objective:To explore the effect of oseltamivir phosphate combined with Astragalus and Angelica on treatment of diabetics with influenza virus infection and immunologic function, and observe the influence on the serum inflammatory factors.Methods:A total of 84 diabetics with influenza virus infection who were treated in the Third Affiliated Hospital Qiqihar Medical College March 2016 to December 2019 were recruited as the study objects and randomly divided into the combination group and the control group, with 42 cases in each group. The control group was treated with oseltamivir phosphate capsules on basis of the conventional therapy, while the combination group was given combined Astragalus and Angelica on basis of the treatment of the control group. The effective rate of treatment was compared between the two groups of patients, the time of disappearance of clinical symptoms and adverse reactions during treatment were recorded. The immunologic function and levels of serum inflammatory factors C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were compared between the two groups of patients before and after the treatment.Results:The time of clinical symptoms of influenza was significantly shorter than those of the control group ( P<0.05); the immune function of the patients in the combination group was significantly enhanced compared with that in the control group ( P<0.05); The total effective rate of treatment of the combination group was, significantly higher than of the control group ( P<0.05); The levels of serum inflammatory factors CRP, IL-6 and TNF-α of the two groups of patients declined after the treatment, and the above measurements were improved better in the combination group than in the control group ( P<0.05); the patients of the combination group did not have any adverse reactions that were related to the combined use of the medicines. Conclusions:Oseltamivir phosphate combined with Astragalus and Angelica effectively relieved the clinical symptoms of the patients with influenza virus infection, alleviated the inflammatory reactions and accelerated the recovery of the patients.

OBJECTIVE: To explore the mechanisms of angiogenesis in chronic myeloid leukemia (CML) through detecting the levels of angiogenesis-related factors secreted from K562 cells after overexpression and interference of HIF-1α gene in K562 cells. METHODS: The K562 cells were transfected by lentiviruses carried and interfered HIF-1α gene, then the transtected K562 cells with carried and interfered with HIF-1α gene were enrolled in overexpression and interference groups respectively, at the same time the K562 cells transfected by the empty virus were enrolled in control group. The cells were harvested after culture for 72 hours under normoxid condition. The transfection efficient in 3 groups was detected by fluorescence microscopy; the mRNA expression of HIF-1α gene and angiogenesis-related factors was detected by RT-PCR; the concentration of angiogenesis-related factors in the caltured supernatant was detected by ELISA. RESULTS: The optimal MOI of K562 cells transfected with lentivirus was 10 and the transfection efficiency was about 50%. The positive rate of transfection after screening by puromycin was more than 90%. The mRNA expression of ANG-I, ANG-II, TGF-α and VEGF in the interference group was lower than that in the over-expression group, and the TGF-β1 mRNA expression in the interference group was higher than in the over-expression group. The mRNA expression of ANG-I and VEGF in the interference group was lower than that in the control group. TGF-αdid not could be detected, and the culture supernatant concentration of ANG-I and TNF-α in the interference group was lower than in the over-expression group, while the VEGF concentration in the interference group was higher than that in the over-expression group. All of the above-mentioned differences were statistically significant (P＜0.05). CONCLUSION The positive K562 cells transfected with leutivirus have been harvested by screening with puromycin. The HIF-1α mRNA positively regulates the mRNA expression of ANG-1, ANG-2, TGF-α, VEGF in K562 cells, promotes the antocrine ability of ANG-1 and TNF-α, moreover not stimulates the autocrine of TGF-α, the up-regulation of HIF-1α expression can inhibit the expression TGF-β1 in K562 cells and the autocrine of TGF-β1.
Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; K562 Cells ; RNA, Messenger ; Vascular Endothelial Growth Factor A

BACKGROUNDHigh rate of in-stent restenosis (ISR) remained an unsolved clinical problem in clinical practice, especially among patients with diabetes mellitus (DM). Diabetic patients often had hypertriglyceridemia with elevated levels of very low-density lipoprotein cholesterol (VLDL-C). Increasing evidence suggested that VLDL-C was known as a significant risk factor for atherosclerosis and had been recommended as a treatment target by current dyslipidemia guidelines. However, the role of VLDL-C in the occurrence and development of ISR in coronary artery disease (CAD) patients with DM had not been studied. The aim of this study was to evaluate the association between the elevated levels of VLDL-C and the risk of ISR in CAD patients with DM.

METHODSA total of 1390 diabetic patients, who underwent coronary drug-eluting stent (DES) implantation at Beijing Anzhen Hospital and followed up by angiography within 6-24 months, were consecutively enrolled. Patients' demographic and clinical characteristics, including age, gender, CAD risk factors, family history, life style, medical history, and coronary angiographic information, were collected carefully at baseline percutaneous coronary intervention and follow-up angiography. Multivariate Cox's proportional hazards regression modeling using the step-wise method (entry, 0.05; removal, 0.05) was used to determine the independent risk associated with ISR in diabetic patients.

RESULTSFinally, 1206 of patients were included in this study. ISR occurred in 132/1206 diabetic patients (10.9%) by follow-up angiography. Patients with ISR had elevated median serum VLDL-C levels compared with those without ISR (0.65 mmol/L vs. 0.52 mmol/L, P = 0.030). The multivariate regression analysis showed that VLDL-C was significantly associated with the risk of ISR in diabetic CAD patients (hazard ratio [HR] = 1.15, 95% confidence interval [CI]: 1.03-1.29, P = 0.017). The HR for the risk of ISR associated with VLDL-C level ≥0.52 mmol/L was 3.01 (95% CI: 1.24-7.34, P = 0.015).

CONCLUSIONThe elevated level of serum VLDL-C was a significant and independent risk factor for ISR in diabetic CAD patients after coronary DES implantation.

Objective To evaluate the clinical efficacy of endoscopic transnasal palatal nerve block for persistent allergic rhinitis.Methods 123 patients with heavy persistent allergic rhinitis who aged over 17 years old in Longhua central hospital affiliated to Guangdong medical university from October 2013 to February 2015 were divided into observation group and control group.The patients in the observation group(72 cases) were blocked with endoscopic sphenopalatine,the control group (51 cases) treated with medicine.The rhinoconjunctivitis quality of life questionnaire (RQLQ) and VAS were assessed before and after treatment for 6 months,1 year and 2 year survival.Results 106 patients were followed up for 2 years.In observation group,the average score of RQLQ and VAS before treatment were (2.39 ± 0.43),(7.45 ±1.24) respectively;6 months after treatment,the average scores of RQLQ and VAS were (0.82 ± 0.38),(2.47 ± 1.42) respectively;1 years (0.93 ± 0.41) and (2.53 ± 1.54);2 years (1.05 ± 0.47) and (2.67 ± 1.69);the differences were statistically significant (P ＜ 0.05).The control group showed no obvious difference in RQLQ and VAS before and after treatment.Conclusion Endoscopic sphenopalatine nerve block can effectively improve the quality of life of patients with persistent rhinitis allergic,which is safe and effective in the treatment of severe persistent allergic rhinitis.

Background: High rate of in?stent restenosis (ISR) remained an unsolved clinical problem in clinical practice, especially among patients with diabetes mellitus (DM). Diabetic patients often had hypertriglyceridemia with elevated levels of very low?density lipoprotein cholesterol (VLDL?C). Increasing evidence suggested that VLDL?C was known as a significant risk factor for atherosclerosis and had been recommended as a treatment target by current dyslipidemia guidelines. However, the role of VLDL?C in the occurrence and development of ISR in coronary artery disease (CAD) patients with DM had not been studied. The aim of this study was to evaluate the association between the elevated levels of VLDL?C and the risk of ISR in CAD patients with DM. Methods: A total of 1390 diabetic patients, who underwent coronary drug?eluting stent (DES) implantation at Beijing Anzhen Hospital and followed up by angiography within 6–24 months, were consecutively enrolled. Patients' demographic and clinical characteristics, including age, gender, CAD risk factors, family history, life style, medical history, and coronary angiographic information, were collected carefully at baseline percutaneous coronary intervention and follow?up angiography. Multivariate Cox's proportional hazards regression modeling using the step?wise method (entry, 0.05; removal, 0.05) was used to determine the independent risk associated with ISR in diabetic patients. Results: Finally, 1206 of patients were included in this study. ISR occurred in 132/1206 diabetic patients (10.9%) by follow?up angiography. Patients with ISR had elevated median serum VLDL?C levels compared with those without ISR (0.65 mmol/L vs. 0.52 mmol/L, P = 0.030). The multivariate regression analysis showed that VLDL?C was significantly associated with the risk of ISR in diabetic CAD patients (hazard ratio [HR] = 1.15, 95% confidence interval [CI]: 1.03–1.29, P = 0.017). The HR for the risk of ISR associated with VLDL?C level ≥0.52 mmol/L was 3.01 (95% CI: 1.24–7.34, P = 0.015). Conclusion: The elevated level of serum VLDL?C was a significant and independent risk factor for ISR in diabetic CAD patients after coronary DES implantation.