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.

Objective To analyze the changes in the ratio of helper T cell 17 to regulatory T cells (Th17/Treg), serum ferritin (SF), microRNA-145 (miR-145), and microRNA-132 (miR-132) levels in breast cancer patients and their relationships with pathological parameters. Methods A total of 92 breast cancer patients from January 2022 to December 2023 were enrolled as study group, and 105 patients with benign breast diseases during the same period were selected as control group. Changes in SF, miR-132, Th17/Treg, and miR-145 were compared between the two groups, and the diagnostic value of these indicators for breast cancer was analyzed. Results Compared with the control group, the study group had higher peripheral blood Th17/Treg and serum SF levels, and lower serum miR-145 and miR-132 expression levels (P < 0.05). Patients with tumor diameters >2 cm, clinical stages of Ⅲ to Ⅳ, moderately or poorly differentiated tumors, and lymph node metastasis had lower serum miR-145 and miR-132 expression levels than those with tumor diameters ≤2 cm, clinical stages of Ⅰ to Ⅱ, highly differentiated tumor, and no lymph node metastasis (P < 0.05). Compared with patients with clinical stages of Ⅰ to Ⅱ, highly differentiated tumors, and no lymph node metastasis, those with clinical stages of Ⅲ to Ⅳ, moderately or poorly differentiated tumors, and lymph node metastasis had higher serum SF levels (P < 0.05). Patients with lymph node metastasis had higher Th17/Treg levels than those without (P < 0.05). The area under the curve (AUC) for combined detection of Th17/Treg, SF, miR-145, and miR-132 levels in breast cancer patients was higher than that for individual detection (P < 0.05), with higher sensitivity and specificity. Conclusion Th17/Treg, SF, miR-145, and miR-132 are abnormally expressed in the blood of breast cancer patients and are correlated with their pathological parameters. Combined detection of these four indicators has higher value in the clinical diagnosis of breast cancer.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by abnormal lipid deposition in the liver and its mechanism is closely related to insulin resistance, lipid metabolism disorders, oxidative stress, and abnormalities of the gut-liver axis. Currently, there is no effective treatment for this disease. Silent information regulator 2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase which performs various pathophysiological functions by interacting with different substrates. For example, it is involved in improving metabolic homeostasis, alleviating liver inflammation, promoting liver regeneration, and delaying the progression of MASLD. In this paper, we present a review of the mechanism of action of SIRT2 in MASLD to analyze the potential value of SIRT2 as a therapeutic target in MASLD.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), a transmembrane protein of the immunoglobulin superfamily, is involved in mediating cell adhesion, tissue metastasis, control of immune response, and metabolic homeostasis. Studies have shown that CEACAM1 protects the liver by promoting insulin clearance and preventing fat deposition. The down-regulation of the CEACAM1 expression level leads to a vicious cycle of insulin resistance and aggravates metabolic disorders. As CEACAM1 is critical in controlling metabolic dysfunction-associated steatotic liver disease (MASLD), stimulating its pathway or regulating its expression level might be a potential new therapeutic approach for MASLD. In this paper, therefore, we summarize the research progress of CEACAM1 in MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by abnormal lipid deposition in the liver and its mechanism is closely related to insulin resistance, lipid metabolism disorders, oxidative stress, and abnormalities of the gut-liver axis. Currently, there is no effective treatment for this disease. Silent information regulator 2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase which performs various pathophysiological functions by interacting with different substrates. For example, it is involved in improving metabolic homeostasis, alleviating liver inflammation, promoting liver regeneration, and delaying the progression of MASLD. In this paper, we present a review of the mechanism of action of SIRT2 in MASLD to analyze the potential value of SIRT2 as a therapeutic target in MASLD.

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.

Objective To investigate the influencing factors of opioid analgesics need within 48 hours after arthroscopic rotator cuff repair.Methods Clinical data of 90 consecutive arthroscopic rotator cuff repairs by the same operator from March 2017 to July 2022 were retrospectively analyzed.The patients were divided into opioid group(62 patients)and control group(28 patients)according to whether they used opioid analgesics within 48 hours after surgery.The control group consisted of patients who did not use analgesics or who had good analgesic effects with conventional analgesic regimens(non-steroidal anti-inflammatory drugs or non-opioid central analgesics)after surgery,and the opioid group consisted of patients who required opioid analgesics as assessed by the surgeon or who need opioid analgesics because of inefficacy of conventional analgesic regimens.The following factors were selected as independent variables:gender,age(whether≥65 years old),duration of disease(whether≥4 weeks),body mass index(BMI)(whether≥25),occupation(whether employed),with or without a history of smoking and alcohol consumption,hypertension,diabetes,heart disease,and trauma,duration of surgery(whether≤180 min),number of torn tendons(whether≥2),number of screws(whether≥2),large nodular osteophyte,and whether there was moderate-to-severe impingement.Single factor analysis was used to screen the factors influencing the need for opioid analgesics within 48 hours after arthroscopic rotator cuff repair.Results The results of univariate analysis showed that among the above independent variables,only the number of torn tendons≥2 was the factor affecting the need for opioid analgesics within 48 hours after arthroscopic rotator cuff repair(OR = 5.263,P = 0.007).Conclusions Patients with rotator cuff tears with≥2 tendons had more severe pain within 48 hours after rotator cuff repair,requiring opioid analgesics.Focus should be placed on postoperative pain in such patients,and a diverse analgesic regimen should be used early.

Objective:To compare the clinical effects of two enteral nutritional emulsions, TP-HE and TPF, in elderly patients with severe pneumonia.Methods:This was a randomized study with contemporaneous controls.A total of 56 elderly patients over 65 years old who met the diagnostic criteria for severe pneumonia and were receiving insulin were enrolled.They were randomly divided into the observation group(n=28, enteral TPF-HE at a uniform rate through a nasogastric tube)and the control group(n=28 cases, enteral TPF at a uniform rate through a nasogastric tube). The total daily energy supply was calculates based on the ideal weights of patients.Prealbumin(PA), serum albumin(ALB), body mass index(BMI)and hemoglobin(Hb)were continuously measured at 1, 2, 3, 4, 5, 6 and 7 days after treatment.The effects of the enteral nutritional emulsions in elderly patients with severe pneumonia were analyzed by using repeated measures analysis of variance in a general linear model.Results:There was no significant difference in PA(244.5±55.1)mg/L vs.(237.8±40.4)mg/L, ALB(37.6±5.6)mg/L vs.(38.3±5.5)mg/L, BMI(21.9±0.2)kg/m 2vs.(22.4±0.2)kg/m 2)or Hb(104.4±26.8)mg/L vs.(103.6±25.6)mg/L between the TP-HE group and the TPF group before admission( P>0.05). The energy received from the enteral nutritional emulsions was not significantly different between the TP-HE group and the TPF group(79.8±4.8)kcal/d vs.(79.3±6.6)kcal/d( P>0.05). PA and serum ALB levels had significant differences between the TP-HE group and the TPF group at 1, 2, 3, 4, 5, 6 and 7 days after treatment( P<0.01 or 0.05). Increases in PA and serum ALB levels varied at certain time points between the TP-HE group and the TPF group.Hb levels had no significant difference at 1 and 2 days( P>0.05), but were significantly different at other time points between the two groups( P<0.01). There was no significant difference in BMI between the two groups( F=1.709, P>0.05). Conclusions:Both of the enteral nutrition emulsions can improve PA, ALB and Hb levels, with TP-HE offering more significant effects on PA, ALB and Hb levels.There is no difference in BMI at any time point whether patients receive TP-HE or TPF.

A splicing mutation in VPS4B can cause dentin dysplasia type I (DD-I), a hereditary autosomal-dominant disorder characterized by rootless teeth, the etiology of which is genetically heterogeneous. In our study, dental follicle cells (DFCs) were isolated and cultured from a patient with DD-I and compared with those from an age-matched, healthy control. In a previous study, this DD-I patient was confirmed to have a loss-of-function splicing mutation in VPS4B (IVS7 + 46C > G). The results from this study showed that the isolated DFCs were vimentin-positive and CK14-negative, indicating that the isolated cells were derived from the mesenchyme. DFCs harboring the VPS4B mutation had a significantly higher proliferation rate from day 3 to day 8 than control DFCs, indicating that VPS4B is involved in cell proliferation. The cells were then replenished with osteogenic medium to investigate how the VPS4B mutation affected osteogenic differentiation. Induction of osteogenesis, detected by alizarin red and alkaline phosphatase staining in vitro, was decreased in the DFCs from the DD-I patient compared to the control DFCs. Furthermore, we also found that the VPS4B mutation in the DD-I patient downregulated the expression of osteoblast-related genes, such as ALP, BSP, OCN, RUNX2, and their encoded proteins. These outcomes confirmed that the DD-I-associated VPS4B mutation could decrease the capacity of DFCs to differentiate during the mineralization process and may also impair physiological root formation and bone remodeling. This might provide valuable insights and implications for exploring the pathological mechanisms underlying DD-I root development.
ATPases Associated with Diverse Cellular Activities ; genetics ; Case-Control Studies ; Cell Differentiation ; genetics ; Cells, Cultured ; Dental Sac ; cytology ; Dentin Dysplasia ; genetics ; pathology ; physiopathology ; Endosomal Sorting Complexes Required for Transport ; genetics ; Humans ; Mutation ; genetics ; Osteogenesis ; genetics ; RNA Splicing ; genetics