This study aims to explore the effects of Buzhong Yiqi Decoction(BYD) on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING) signaling pathway in the mouse model of autoimmune thyroiditis(AIT) and the mechanism of BYD in alleviating the immune injury. Forty-eight NOD.H-2~(h4) mice were assigned into normal, model, low-, medium-, and high-dose BYD, and selenium yeast tablets groups(n=8). Mice of 8 weeks old were treated with 0.05% sodium iodide solution for 8 weeks for the modeling of AIT and then administrated with corresponding drugs by gavage for 8 weeks before sampling. High performance liquid chromatography was employed to measure the astragaloside Ⅳ content in BYD. Hematoxylin-eosin staining was employed to observe the pathological changes in the mouse thyroid tissue. Enzyme-linked immunosorbent assay was employed to measure the serum levels of thyroid peroxidase antibody(TPO-Ab), thyroglobulin antibody(TgAb), and interferon-γ(IFN-γ). Flow cytometry was employed to detect the distribution of T cell subsets in the spleen. The immunohistochemical method was used to detect the expression of cGAS, STING, TANK-binding kinase 1(TBK1), and interferon regulatory factor 3(IRF3). Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of markers related to the cGAS-STING signaling pathway in the thyroid tissue. The results showed that the content of astragaloside Ⅳ in BYD was(7.06±0.08) mg·mL~(-1). Compared with the normal group, the model group showed disrupted structures of thyroid follicular epithelial cells, massive infiltration of lymphocytes, and elevated levels of TgAb and TPO-Ab. Compared with the model group, the four treatment groups showed intact epithelial cells, reduced lymphocyte infiltration, and lowered levels of TgAb and TPO-Ab. Compared with the normal group, the model group showed increases in the proportions of Th1 and Th17 cells, a decrease in the proportion of Th2 cells, and an increase in the IFN-γ level. Compared with the model group, the four treatment groups presented decreased proportions of Th1 and Th17 cells and lowered levels of IFN-γ, and the medium-dose BYD group showed an increase in the proportion of Th2 cells. Compared with the normal group, the modeling up-regulated the mRNA levels of cGAS, STING, TBK1, and IRF3 and the protein levels of cGAS, p-STING, p-TBK1, and p-IRF3. Compared with the model group, the four treatment groups showed reduced levels of cGAS, STING, TBK1, and IRF3-positive products, down-regulated mRNA levels of cGAS, STING, and TBK1, and down-regulated protein levels of cGAS and p-STING. The high-dose BYD group showed down-regulations in the mRNA level of IRF3 and the protein levels of p-TBK1 and p-IRF3. The above results indicate that BYD can repair the imbalance of T cell subsets, alleviate immune injury, and reduce thyroid lymphocyte infiltration in AIT mice by inhibiting the cGAS-STING signaling pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Thyroiditis, Autoimmune/metabolism* ; Mice ; Membrane Proteins/metabolism* ; Mice, Inbred NOD ; Humans ; Female ; Nucleotidyltransferases/metabolism* ; Male ; Disease Models, Animal

As one of the chronic diseases with high incidence in contemporary society, cervical spondylosis has increasing patient groups who gradually present a low age, and it seriously affects social and public health. Although modern medicine has made great progress in the pathological research and clinical treatment of cervical spondylosis, patients still face gastrointestinal side effects of nonsteroidal anti-inflammatory drugs(NSAIDs), neck pain, limited mobility, upper limb numbness, and other symptoms after conservative or surgical treatment. In the theory of traditional Chinese medicine(TCM), cervical spondylosis belongs to the categories of "Bi syndrome" "stiff neck" "stiff Bi", etc. With the change of the times, the change of lifestyle, and the application of western medicine treatment, the etiology and pathogenesis of TCM in cervical spondylosis also show new characteristics. In terms of etiology and pathogenesis, it involves the invasion of wind, cold, and dampness, long-term strain, liver and kidney deficiency, Qi and blood stasis, which are associated with factors such as cervical degeneration, muscle tension and spasm, intervertebral disc herniation, and nerve root compression in modern medicine. In terms of the evolution of pathogenesis, in the early stage, wind, cold, and dampness, were more common in Xuanfu, resulting in unfavorable muscles and bones, poor flow of Qi and blood, and cervical spondylosis and radiculopathy. Medium-term phlegm stasis and internal knots, sluggish muscles and veins, and long-term weathering and fire are more likely to occur in the vertebral artery and sympathetic radiculopathy. In the later stage, the positive Qi is depleted; the true Yin is damaged, and the viscera Qi and blood are deficient, which is most common in cervical myelopathy. The strategy of treating cervical spondylosis with TCM classic formulas applies Gegen Decoction, Wutou Decoction, Qianghuo Shengshi Decoction, Mahuang Jiazhu Decoction to patients with wind, cold, and dampness. Patients with phlegm dampness and blood stasis are treated with Huoxue Xiaoling Dan, Jinlingzi Powder, Siwu Decoction, Banxia Baizhu Tianma Decoction, Shuanghe Decoction, etc. For those patients with liver, spleen, and kidney deficiency, Huangqi Guizhi Wuwu Decoction, Tianma Gouteng Decoction, Guishao Dihuang Pills, Shenling Baizhu Powder, and Lizhong Decoction are used to invigorate the spleen, nourish Qi and blood, and tonify liver and kidney. In clinical practice, the authors advocate a safe and effective treatment plan of classic formulas based on deficiency and excess, the integration of formulas and syndromes, and the combination of modern research results, so as to relieve symptoms, reduce recurrence, and reduce medical burden.
Humans ; Spondylosis/drug therapy* ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/therapeutic use* ; Cervical Vertebrae/pathology*

[Objective] To conduct a retrospective statistical comparison of alanine aminotransferase (ALT) test values in blood donors prior to blood collection, aiming to analyze the objective characteristics of the population with elevated ALT levels (ALT>50 U/L) and provide reference data for adjusting the screening eligibility threshold for ALT. [Methods] The preliminary ALT screening data of 30 341 blood donor samples collected prior to blood donation from three smart blood donation sites at the Shenzhen Blood Center between 2022 and 2023 were extracted and compared with data from a health examination department of a tertiary hospital in Shenzhen (representing the general population, n=24 906). Both datasets were categorized and statistically described. A retrospective analysis was conducted to examine the associations between ALT test results and factors such as donors' gender, age, ethnicity, donation site, donation season, and frequency of blood donation. [Results] The ALT levels in both blood donors and the general population were non-normally distributed. The 95th percentile of ALT values was calculated as 61.4 U/L (male: 67.8 U/L, female: 39.3 U/L) for blood donors and 58.1 U/L (male: 63.7 U/L, female: 51.2 U/L) for the general population. The non-compliance rates (ALT>50 U/L) were 7.65% (2 321/30 341) in blood donors and 7.08% (1 763/24 906) in the general population. There were significant differences (P<0.05) in the ALT failure rate among blood donors based on gender, age, and donation site, but no significant differences (P>0.05) during the blood donation season. There was no statistically significant difference (P>0.05) in the positive rates of four serological markers (HBsAg, anti HCV, HIV Ag/Ab, anti TP) for blood screening pathogens between ALT unqualified and qualified individuals (2.05% vs 1.5%). If the ALT qualification threshold was raised from 50 U/L to 90 U/L, the non qualification rates of male and female blood donors would decrease from 9.82% (2 074/21 125) to 2.23% (471/21 125) and from 2.70% (249/9 216) to 0.75% (69/9 216), respectively. Among the 154 blood donors who donated blood more than 3 times, 88.31% of the 248 ALT test results were in the range of 50-90 U/L. Among them, 9 cases had ALT>130 U/L, and ALT was converted to qualified in subsequent blood donations. [Conclusion] There are differences in the ALT failure rate among blood donors of different genders and ages, and different blood donation sites and operators can also affect the ALT detection values of blood donors. The vast majority of blood donors with ALT failure are caused by transient and non pathological factors. With the widespread use of blood virus nucleic acid testing, appropriately increasing the ALT qualification threshold for blood donors can expand the qualified population and alleviate the shortage of blood sources, and the risk of blood safety will not increase.

OBJECTIVE: To investigate the association between long-term glycemic control and cerebral infarction risk in patients with diabetes through a large-scale cohort study. METHODS: This prospective, community-based cohort study included 12,054 patients with diabetes. From 2006 to 2012, 38,272 fasting blood glucose (FBG) measurements were obtained from these participants. FBG trajectory patterns were generated using latent mixture modelling. Cox proportional hazards models were applied to assess the subsequent risk of cerebral infarction associated with different FBG trajectory patterns. RESULTS: At baseline, the mean age of the participants was 55.2 years. Four distinct FBG trajectories were identified based on FBG concentrations and their changes over the 6-year follow-up period. After a median follow-up of 6.9 years, 786 cerebral infarction events were recorded. Different trajectory patterns were associated with significantly varied outcome risks (Log-Rank P < 0.001). Compared with the low-stability group, Hazard Ratio ( HR) adjusted for potential confounders were 1.37 for the moderate-increasing group, 1.23 for the elevated-decreasing group, and 2.08 for the elevated-stable group. CONCLUSION Sustained high FBG levels were found to play a critical role in the development of ischemic stroke among patients with diabetes. Controlling FBG levels may reduce the risk of cerebral infarction.
Humans ; Cerebral Infarction/blood* ; Middle Aged ; Male ; Female ; Blood Glucose/analysis* ; Fasting/blood* ; Aged ; Prospective Studies ; Risk Factors ; Diabetes Mellitus/blood* ; Adult ; Proportional Hazards Models

Objective:To explore the short-term clinical effects of deep cervical lymph node-venous anastomosis in the treatment of Alzheimer’s disease (AD).Methods:A prospective exploratory study was conducted on the treatment of AD patients using the cervical deep lymph node-venous anastomosis technique in Scar and Wound Treatment Department, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, from September to October 2024. The patients underwent high-frequency ultrasound to locate deep cervical lymph nodes and the external jugular vein. Under general anesthesia, bilateral deep cervical lymph node-venous anastomoses were performed. Indocyanine green (ICG) lymphography was conducted via subcutaneous injection behind the ear to visualize lymph nodes in levels Ⅱ and Ⅲ. After making a skin incision along the posterior margin of the sternocleidomastoid muscle, the external jugular vein, internal jugular veins, and associated lymph nodes were exposed. Adjacent veins were selected for anastomosis of lymph node. Using microsurgical techniques, end-to-side or end-to-end anastomosis was completed for lymph nodes in levels Ⅱ and Ⅲ. Preoperative assessments included the mini-mental state examination (MMSE, a higher score indicates better cognitive function), Alzheimer’s disease assessment scale-cognitive subscale (ADAS-Cog, a higher score indicates greater impairment of cognitive function), Alzheimer’s disease cooperative study scale for activities of daily living (ADCS-ADL, a higher score indicates better ability to perform daily activity), and neuropsychiatric inventory (NPI, a higher score indicates more severe behavioral and emotional symptom). Postoperative follow-up included the same scales to observe changes in cognitive function, activities of daily living, and emotional communication.Results:Four patients (1 male, 3 females, aged 58-79 years) with AD were included. All were diagnosed based on cerebrospinal fluid biomarkers. All patients successfully underwent bilateral deep cervical lymph node-venous anastomoses. On average, 4.3 (2-7 per person) anastomoses were performed per patient. Surgical procedures lasted an average of 6.5 h (5.5-8.5 h) with minimal blood loss (less than 50 ml). Patients resumed normal activity within 6 hours postoperatively and were discharged after an average of 4.1 d (3.5-5.0 d). Postoperative complications included one case each of aspiration pneumonia, lower limb venous thrombosis, and transient delirium, all of whom resolved without long-term effects. Clinical symptoms, including memory decline, mood swings, and anxiety, showed varying degrees of improvement. Patients reported enhanced quality of life, emotional stability, and social engagement, confirming the procedure’s safety and potential cognitive benefits. At one month postoperatively, the MMSE scores of the four patients increased by an average of 0.8 points compared to preoperative levels. Additionally, the two patients who completed the ADAS-Cog assessments showed a decrease in their scores (reduced by 1.0 points and 11.3 points, respectively, compared to preoperative scores), indicating a certain degree of improvement in cognitive function during this period. The ADCS-ADL and NPI scores of four patients varied significantly, without showing any clear pattern.Conclusion:Lymphovenous anastomosis of the deep cervical lymph node-venous anastomosis may provide a new surgical intervention approach for AD, but further large-scale studies and long-term follow-up are needed to validate its safety and effectiveness.

Aim To investigate the effect of total gly-cosides of peony on Th17/Treg balance in autoimmune thyroiditis(AIT)by regulating miR-155 expression.Methods Sixty female SD rats were randomly divided into a blank control group,a model group,high-dose,medium,and low-dose groups of total glycosides of peony,and a Western medicine control group(seleni-um yeast group).After eight weeks of modeling,the pathological changes in thyroid tissue were observed by HE staining,the expression of miR-155 in the thyroid of rats was detected by RT-PCR,the targeting effect of miR-155 on SOCS1 was verified by dual luciferase method,and the levels of TGAb,TPOAb,IL-10,and IL-17 in peripheral serum were detected by ELISA,the expression of thyroid SOCS1 was detected by WB,and the proportion of Th17 and Treg in CD4+cells of the spleen was detected by flow cytometry.Results Com-pared with the blank group,the expression of miR-155 in the thyroid gland of the model group rats significant-ly increased,and the serum levels of TGAb,TPOAb,and IL-17 significantly increased,with an increase in the proportion of Th17;the IL-10 level significantly decreased,the proportion of Treg decreased,and the expression of SOCS1 protein decreased,with statistical significance(P＜0.01);compared with the model group,the high,medium,and low dose groups of total glycosides of peony and selenium yeast groups showed a decrease in miR-155 expression,a decrease in TGAb,TPOAb,IL-17 levels,a decrease in Th17 pro-portion,an increase in IL-10 level,an increase in Treg proportion,and an increase in SOCS1 expression,all with statistical significance(P＜0.01).Moreover,the improvement in the medium dose group of total glyco-sides of peony was more significant.Conclusion To-tal glycosides of peony downregulate miR-155 expres-sion,regulate Th17/Treg balance,alleviate inflamma-tory response,and exert immune regulatory effects.

Objective:To establish and validate a multimodal model based on radiomics and deep learning for predicting acute pancreatitis (AP) complicated with acute respiratory distress syndrome (ARDS).Methods:Patients diagnosed with AP from The First Affiliated Hospital of Soochow University, Donghai County People's Hospital and Jintan Affiliated Hospital of Jiangsu University between January 2017 and December 2023 were enrolled. Based on the diagnosis of ARDS within 1 week after admission, the patients were classified into the ARDS group and the non-ARDS group. Patients in the First Affiliated Hospital of Soochow University ( n=406) was used as the training set (non-ARDS group n=212 vs ARDS group n=194), while Donghai and Jintan hospitals served as the test set ( n=175; non-ARDS group n=104 vs ARDS group n=71). Clinical data, laboratory tests and the occurrence of systemic inflammatory response syndrome (SIRS) within 24 hours after admission were collected. Scoring systems such as bedside index for severity in acute pancreatitis (BISAP), Ranson score and modified CT severity index (MCTSI) were calculated. Radiomics features were extracted from three-dimensional CT images to develop a radiomics model based on XGBoost algorithm. At the same time, a deep learning model was constructed using deep convolutional networks to extract deep features. Finally, clinical features and the predictions from the aforementioned models were integrated to establish a multimodal model based on XGBoost algorithm. To enhance model visualization, variable importance ranking and local interpretable visualization were used. The receiver operating characteristic (ROC) curves of the three models and the three scores including BISAP, Ranson and MCTSI were plotted and the area under the curves (AUCs) were calculated to evaluate the prediction performance for ARDS in AP patients, as well as sensitivity and specificity. Results:In the multimodal model for predicting ARDS in AP patients, predictions of the deep learning model and the radiomics model were the most important variables, followed by SIRS, C-reactive protein, procalcitonin, albumin, glucose, creatinine, neutrophil, and Ca 2+. In the training set, the multimodal model achieved an AUC of 0.933 for predicting ARDS in AP patients, higher than the radiomics model (0.727), the deep learning model (0.877), MCTSI (0.870), Ranson (0.620) and BISAP (0.898). In the test set, the model's AUC was 0.916 for predicting ARDS in AP patients, higher than the radiomics model (0.660), the deep learning model (0.864), MCTSI (0.851), Ranson (0.609), and BISAP (0.860). Conclusions:Based on clinical structured data, radiomics and deep learning features, the multimodal model could predict the risk of ARDS in AP patients at an early stage, whose performance is better than the single-modal models and the traditional scoring systems.

Aim To investigate the effect of total gly-cosides of peony on Th17/Treg balance in autoimmune thyroiditis(AIT)by regulating miR-155 expression.Methods Sixty female SD rats were randomly divided into a blank control group,a model group,high-dose,medium,and low-dose groups of total glycosides of peony,and a Western medicine control group(seleni-um yeast group).After eight weeks of modeling,the pathological changes in thyroid tissue were observed by HE staining,the expression of miR-155 in the thyroid of rats was detected by RT-PCR,the targeting effect of miR-155 on SOCS1 was verified by dual luciferase method,and the levels of TGAb,TPOAb,IL-10,and IL-17 in peripheral serum were detected by ELISA,the expression of thyroid SOCS1 was detected by WB,and the proportion of Th17 and Treg in CD4+cells of the spleen was detected by flow cytometry.Results Com-pared with the blank group,the expression of miR-155 in the thyroid gland of the model group rats significant-ly increased,and the serum levels of TGAb,TPOAb,and IL-17 significantly increased,with an increase in the proportion of Th17;the IL-10 level significantly decreased,the proportion of Treg decreased,and the expression of SOCS1 protein decreased,with statistical significance(P＜0.01);compared with the model group,the high,medium,and low dose groups of total glycosides of peony and selenium yeast groups showed a decrease in miR-155 expression,a decrease in TGAb,TPOAb,IL-17 levels,a decrease in Th17 pro-portion,an increase in IL-10 level,an increase in Treg proportion,and an increase in SOCS1 expression,all with statistical significance(P＜0.01).Moreover,the improvement in the medium dose group of total glyco-sides of peony was more significant.Conclusion To-tal glycosides of peony downregulate miR-155 expres-sion,regulate Th17/Treg balance,alleviate inflamma-tory response,and exert immune regulatory effects.

Objective:To establish and validate a multimodal model based on radiomics and deep learning for predicting acute pancreatitis (AP) complicated with acute respiratory distress syndrome (ARDS).Methods:Patients diagnosed with AP from The First Affiliated Hospital of Soochow University, Donghai County People's Hospital and Jintan Affiliated Hospital of Jiangsu University between January 2017 and December 2023 were enrolled. Based on the diagnosis of ARDS within 1 week after admission, the patients were classified into the ARDS group and the non-ARDS group. Patients in the First Affiliated Hospital of Soochow University ( n=406) was used as the training set (non-ARDS group n=212 vs ARDS group n=194), while Donghai and Jintan hospitals served as the test set ( n=175; non-ARDS group n=104 vs ARDS group n=71). Clinical data, laboratory tests and the occurrence of systemic inflammatory response syndrome (SIRS) within 24 hours after admission were collected. Scoring systems such as bedside index for severity in acute pancreatitis (BISAP), Ranson score and modified CT severity index (MCTSI) were calculated. Radiomics features were extracted from three-dimensional CT images to develop a radiomics model based on XGBoost algorithm. At the same time, a deep learning model was constructed using deep convolutional networks to extract deep features. Finally, clinical features and the predictions from the aforementioned models were integrated to establish a multimodal model based on XGBoost algorithm. To enhance model visualization, variable importance ranking and local interpretable visualization were used. The receiver operating characteristic (ROC) curves of the three models and the three scores including BISAP, Ranson and MCTSI were plotted and the area under the curves (AUCs) were calculated to evaluate the prediction performance for ARDS in AP patients, as well as sensitivity and specificity. Results:In the multimodal model for predicting ARDS in AP patients, predictions of the deep learning model and the radiomics model were the most important variables, followed by SIRS, C-reactive protein, procalcitonin, albumin, glucose, creatinine, neutrophil, and Ca 2+. In the training set, the multimodal model achieved an AUC of 0.933 for predicting ARDS in AP patients, higher than the radiomics model (0.727), the deep learning model (0.877), MCTSI (0.870), Ranson (0.620) and BISAP (0.898). In the test set, the model's AUC was 0.916 for predicting ARDS in AP patients, higher than the radiomics model (0.660), the deep learning model (0.864), MCTSI (0.851), Ranson (0.609), and BISAP (0.860). Conclusions:Based on clinical structured data, radiomics and deep learning features, the multimodal model could predict the risk of ARDS in AP patients at an early stage, whose performance is better than the single-modal models and the traditional scoring systems.