Differentiated thyroid cancer demonstrates a wide range of clinical presentations, from very indolent cases to those with an aggressive prognosis. Therefore, diagnosing and treating each cancer appropriately based on its risk status is important. The Korean Thyroid Association (KTA) has provided and amended the clinical guidelines for thyroid cancer management since 2007. The main changes in this revised 2024 guideline include 1) individualization of surgical extent according to pathological tests and clinical findings, 2) application of active surveillance in low-risk papillary thyroid microcarcinoma, 3) indications for minimally invasive surgery, 4) adoption of World Health Organization pathological diagnostic criteria and definition of terminology in Korean, 5) update on literature evidence of recurrence risk for initial risk stratification, 6) addition of the role of molecular testing, 7) addition of definition of initial risk stratification and targeting thyroid stimulating hormone (TSH) concentrations according to ongoing risk stratification (ORS), 8) addition of treatment of perioperative hypoparathyroidism, 9) update on systemic chemotherapy, and 10) addition of treatment for pediatric patients with thyroid cancer.

Aim To verify the role of Shengjiang Powder in sepsis and explore its molecular mechanism. Methods The targets of drug active ingredients and disease-related targets were searched by TCMSP, Disgenet and other databases, and the intersection of the two was selected. DAVID database was used to carry out enrichment analysis of GO and KEGG pathways for intersection targets, and molecular docking was performed between drug active ingredients and core genes of key pathways. Mouse model of sepsis was constructed by cecal ligation puncture (CLP). Spleen tissue and serum of mice were collected. The percentage of T cell subsets in spleen was detected by flow cytometry, and IL-6 and IL-10 levels in serum were detected by ELISA. Results A total of 25 active ingredients, 238 targets of active ingredients, 2797 disease-related targets, 90 genes of intersection between active ingredients and disease-related targets, potential targets were AKT, JUN, EGFR, MMP9, etc. GO enrichment analysis showed 1021 items, including 942 biological processes, 23 cell compositions and 55 molecular functions. KEGG pathway analysis found that the intersection genes were mainly enriched in THE PD-1/PD-L1 signaling pathway, HIF-1 signaling pathway, TNF signaling pathway and inflammatory mediators signaling pathway, indicating that the therapeutic effect may be related to these pathways. The molecular docking results showed that quercetin, kamanol, emodin and other core compounds could be well combined with key genes. Flow cytometry results showed that after seven days of CLP, the proportion of CD4 T cells in spleen decreased, the proportion of CD4 PD-1 T cells increased, the release of IL-6 decreased, the content of IL-10 increased, and the mice were immunosuppressed. The percentage of CD4 T cells in spleen increased, the number of CD4 PD-1 T cells decreased, the release of IL-6 was enhanced, the content of IL-10 decreased, and the immunosuppression was improved. Conclusions It is proved that Shengjiang Powder can increase the release of pro-inflammatory cytokine IL-6, increase the ratio of CD4 T/CD8 T cells, and decrease the expression of anti-inflammatory cytokine IL-10 in the late stage of sepsis, so as to improve immune suppression in the late stage of sepsis and improve the survival rate of mice.

Objective:To explore application effect of early respiratory training schemes based on 4E mode (Engage, Educate, Execute, Evaluate) in children with bronchiolitis obliterans (BO) and provide evidence for the clinical implementation of early respiratory rehabilitation in children with BO.Methods:This was a quasi-experimental study. The children with BO who were admitted to 2 wards of the Department of Respiratory Medicine of Hunan Children's Hospital from January 1 to December 31, 2021 were selected as the research objects. They were randomly divided into the control group and the experimental group, with 23 cases in each group. The control group received routine treatment, nursing and rehabilitation guidance. The experimental group established a multidisciplinary team based on the control group, and used the early respiratory training program based on the 4E model to implement intervention. The clinical symptom severity scale was used to evaluate the improvement of the clinical symptoms of the children within 24 hours of being diagnosed as BO, the day of discharge, and 1 and 3 months after discharge for re-examination, and the hospitalization time of the children and the incidence of adverse events related to respiratory training were counted by using medical records and questionnaires.Results:The clinical symptom severity scores of the experimental group within 24 hours of admission diagnosis and the day of discharge were (20.00 ± 2.51) and (11.30 ± 2.46)points respectively, while those of the control group were (20.57 ± 2.21) and (11.70 ± 2.42) points respectively, with no statistically significant difference ( t=0.81, 0.54, both P>0.05). The clinical symptom severity scores of the experimental group were(10.52 ± 2.31) and (8.55 ± 1.06) points, lower than (12.32 ± 1.39) and (12.45 ± 2.19) points of the control group when they returned to the hospital for re-examination 1 and 3 months after discharge, with a statistically significant difference ( t=3.14, 7.25, both P<0.05). The experimental group was hospitalized for (11.78 ± 1.17) days, which was showter than (13.74 ± 1.63) days in the control group, with a statistically significant difference ( t=4.68, P<0.05). No respiratory training-related adverse events occurred in both groups of children during hospitalization. During home respiratory training after discharge, 1 and 2 respiratory training-related adverse events occurred in the experimental group 1 and 3 months after discharge, respectively, compared with 6 and 9 in the control group. The difference was statistically significant ( χ2=4.64, 5.94, both P<0.05). Conclusions:Early respiratory training solutions based on the 4E mode can improve the clinical symptoms of BO children, shorten the hospitalization time, reduce the number of adverse events related to respiratory training, and promote the recovery of children.

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve

ObjectiveTo observe the pharmacodynamic effects of Cinnamomi Cortex on the incretin effect in the rat model of diabetes mellites （DM） induced by streptozotocin （STZ） and explore the underlying mechanism from glucagon-like peptide-1 （GLP-1） and dipeptidyl peptidase-4 （DPP-4）. MethodForty SD rats were randomly assigned into blank， model， sitagliptin （0.1 g·kg^-1）， and low- and high-dose Cinnamomi Cortex （0.45 and 0.9 g·kg^-1， respectively） groups. The DM rat model was established by a high-fat diet combined with intraperitoneal injection of 40 mg·kg^-1 STZ in other groups except the blank group. The intervention lasted for 8 weeks. The status， body weight， water intake， food intake， and fasting blood glucose （FBG） of the rats were observed and determined. Hematoxylin-eosin staining was employed to reveal the pathological changes of the pancreas， and immunohistochemistry to detect the expression of glucagon in the pancreas. Biochemical assay was employed to measure the serum levels of lipid metabolism indexes such as total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein （LDL）， and high-density lipoprotein （HDL）. Enzyme-linked immunosorbent assay was employed to determine the levels of glycosylated hemoglobin， insulin， glucagon， GLP-1， and glucose-dependent insulinotropic polypeptide （GIP） in rat serum， and Western blot to determine the protein levels of GLP-1 and DPP-4 in the pancreas. ResultAfter 8 weeks of intervention， the model group showed higher body weight， FBG， TC， TG， LDL， glycosylated hemoglobin， glucagon， insulin， and insulin resistance index and lower HDL， GLP-1， and GIP than the blank group （P<0.05， P<0.01）. The Cinnamomi Cortex groups showed lower body weight， FBG， TC， TG， LDL， glycosylated hemoglobin， glucagon， insulin， and insulin resistance index and higher HDL， GLP-1， and GIP than the model group （P<0.05， P<0.01）. The Cinnamomi Cortex groups showed recovered morphology of islet cells and no nucleus aggregation. Compared with the model group， the Cinnamomi Cortex groups showed declined levels of glucagon in the center of islet cells. Compared with the blank group， the model group showed up-regulated protein level of DPP-4 and down-regulated protein level of GLP-1 （P<0.01）. Compared with the model group， the high-dose Cinnamomi Cortex groups showed down-regulated protein level of DPP-4 and up-regulated protein level of GLP-1 （P<0.05）. ConclusionCinnamomi Cortex may reduce blood glucose and improve incretin effect to lower the blood glucose level by regulating DPP-4 and GLP-1 in DM rats.

Objective:To analyze the clinicopathological characteristics of IgG4-related sialadenitis (IgG4-RS).Methods:A total of 40 cases diagnosed with IgG4-RS were collected from the Department of Oral Pathology, Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine from January 2019 to December 2022. Among them, there were 26 males and 14 females. The age range was 29-77 years old [(59.4±11.8) years old], with 23 patients being older than 60 years. The lesion site, imaging manifestations, histopathological features, serological test and treatment information of patients were collected. The expression of IgG4 and IgG proteins was detected by immunohistochemistry.Results:Submandibular region swelling was the most common initial symptom of IgG4-RS (38/40, 95.0%). All the patients having serum IgG4 levels> 1.35 g/L. Serum IgG4 levels were significantly increased in patients aged>60 years ( Z=-2.45, P=0.014) and those involving multiple glands ( Z=-2.04, P=0.042). Thirty six cases received major salivary gland biopsy, and all the cases showed dense lymphocyte and plasma cell infiltration. Lymphoid follicle, storiform fibrosis and obliterative phlebitis were seen in 88.9% (32/36), 63.9% (23/36), 30.6% (11/36) of the cases, respectively. Twenty one cases received labial salivary gland biopsy, 66.7% (14/21) showed lymphocyte and plasma cell infiltration, 19.0% (4/21) had lymphoid follicle structures, and 33.3% (7/21) showed no obvious histological abnormalities. No signs of fibrosis or obliterative phlebitis were observed in all labial salivary gland biopsies. And 95.0% (38/40) of cases had IgG4 positive plasma cell>10/HPF, 82.5% (33/40) of cases had IgG4/IgG positive plasma cell ratio>40%. All the patients had a decrease in serum IgG4 levels after glucocorticoid treatment, but only 21.4% (6/28) of cases had reduced to normal levels (≤1.35 g/L), and there were still significant fluctuations in serum IgG4 levels thereafter. Conclusions:IgG4-RS has a predilection for middle-aged and elderly male patients, and serum IgG4 levels are significantly related to the patient′s age and whether multiple glands are involved. Labial salivary gland biopsy cannot replace submandibular gland for histopathological evaluation. It is a common phenomenon that serum IgG4 levels cannot restored to normal levels after glucocorticoid treatment. This study provides certain assistance for clinical and pathological diagnosis of IgG4-RS. This study is beneficial for further understanding IgG4-RS and improving the clinical and pathological diagnosis of the disease.

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.

Precious Tibetan medicine formula is a characteristic type of medicine commonly used in the clinical treatment of central nervous system diseases. Through the summary of modern research on the precious Tibetan medicine formulas such as Ratnasampil, Ershiwuwei Zhenzhu Pills, Ershiwewei Shanhu Pills, and Ruyi Zhenbao Pills, it is found that they have obvious advantages in the treatment of stroke, Alzheimer's disease, epilepsy, angioneurotic headache, and vascular dementia. Modern pharmacological studies have shown that the mechanisms of precious Tibetan medicine formulas in improving central nervous system diseases are that they promote microcirculation of brain tissue, regulate the permeability of the blood-brain barrier, alleviate inflammation, relieve oxidative stress damage, and inhibit nerve cell apoptosis. This review summarizes the clinical and pharmacological studies on precious Tibetan medicine formulas in prevention and treatment of central nervous system diseases, aiming to provide a reference for future in-depth research and innovative discovery of Tibetan medicine against central nervous diseases.
Blood-Brain Barrier ; Brain ; Central Nervous System Diseases ; Humans ; Medicine, Tibetan Traditional ; Stroke/drug therapy*

The present study investigated the mechanism of the Tibetan medicine Ershiwuwei Songshi Pills(ESP) against the liver injury induced by acetaminophen(APAP) in mice based on the kelch-like ECH-associated protein 1(Keap1)/nuclear transcription factor E2 related factor 2(Nrf2) and Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) p65 signaling pathways. Kunming mice were randomly divided into a blank control group, a model group, an N-acetyl-L-cysteine(NAC) group, and high-(400 mg·kg~(-1)), medium-(200 mg·kg~(-1)), and low-dose(100 mg·kg~(-1)) ESP groups. After 14 days of continuous administration, except for those in the control group, the mice were intraperitoneally injected with 200 mg·kg~(-1) APAP. After 12 h, the serum and liver tissues of mice were collected. Hematoxylin-eosin(HE) staining was performed on pathological sections of the liver, and the levels of aspartate aminotransferase(AST) and alanine aminotransferase(ALT) in the serum and the levels of glutathione(GSH), malondialdehyde(MDA), superoxide dismutase(SOD), catalase(CAT), myeloperoxidase(MPO), and total antioxidant capacity(T-AOC) in liver tissue homogenate were detected to observe and analyze the protective effect of ESP on APAP-induced liver injury in mice. The serum levels of tumor necrosis factor-alpha(TNF-α), interleukin-1 beta(IL-1β), and interleukin-6(IL-6) were determined by enzyme-linked immunosorbent assay(ELISA). The protein expression of Nrf2, Keap1, TLR4, and NF-κB p65 in the liver was determined by Western blot. Quantitative real-time was used to determine the mRNA expression of glutamate-cysteine ligase catalytic subunit(GCLC), glutamate-cysteine ligase regulatory subunit(GCLM), heme oxygenase-1(HO-1), and NAD(P)H dehydrogenase quinone 1(NQO-1) in the liver to explore the mechanism of ESP in improving APAP-induced liver damage in mice. As revealed by results, compared with the model group, the ESP groups showed improved liver pathological damage, decreased ALT and AST levels in the serum and MDA and MPO content in the liver, increased GSH, SOD, CAT, and T-AOC in the liver, reduced TNF-α and IL-6 levels in the serum, down-regulated expression of Keap1 in the liver cytoplasm and NF-κB p65 in the liver nucleus, up-regulated expression of Nrf2 in the liver nucleus, insignificant change in TLR4 expression, and elevated relative mRNA expression levels of antioxidant genes GCLC, GCLM, HO-1, and NQO-1. ESP can reduce the oxidative damage and inflammation caused by APAP, and the mechanism may be related to the Keap1/Nrf2 signaling pathway and the signal transduction factors on the TLR4/NF-κB p65 pathway.
Acetaminophen/toxicity* ; Animals ; Antioxidants/pharmacology* ; Glutamate-Cysteine Ligase/pharmacology* ; Glutathione ; Interleukin-6/metabolism* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Liver ; Medicine, Tibetan Traditional ; Mice ; NF-E2-Related Factor 2/metabolism* ; NF-kappa B/metabolism* ; RNA, Messenger/metabolism* ; Signal Transduction ; Superoxide Dismutase/metabolism* ; Toll-Like Receptor 4/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*

The present study investigated the mechanism of the Tibetan patent medicine Ershiwuwei Shanhu Pills(ESP) in alleviating Alzheimer's disease in mice via Akt/mTOR/GSK-3β signaling pathway. BALB/c mice were randomly assigned into a blank control group, a model group, low(200 mg·kg~(-1)), medium(400 mg·kg~(-1)) and high(800 mg·kg~(-1)) dose groups of ESP, and donepezil hydrochloride group. Except the blank control group, the other groups were given 20 mg·kg~(-1) aluminum chloride by gavage and 120 mg·kg~(-1) D-galactose by intraperitoneal injection for 56 days to establish Alzheimer's disease model. Morris water maze was used to detect the learning and memory ability of mice. The level of p-tau protein in mouse hippocampus and the levels of superoxide dismutase(SOD), malondialdehyde(MDA), catalase(CAT), and total antioxidant capacity(T-AOC) in hippocampus and serum were detected. Hematoxylin-eosin staining and Nissl staining were performed for the pathological observation of whole brain in mice. TdT-mediated dUTP nick-end labeling(TUNEL) staining was employed for the observation of apoptosis in mouse cortex. Western blot was adopted to detect the protein levels of p-mTOR, p-Akt, and GSK-3β in the hippocampus. Compared with the model group, the ESP groups showcased alleviated pathological damage of the whole brain, decreased TUNEL positive cells, reduced level of p-tau protein in hippocampus, and risen SOD, CAT, and T-AOC levels and declined MDA level in hippocampus and serum. Furthermore, the ESP groups had up-regulated protein levels of p-mTOR and p-Akt while down-regulated protein level of GSK-3β in hippocampus. Therefore, ESP can alleviate the learning and memory decline and oxidative damage in mice with Alzheimer's disease induced by D-galactose combined with aluminum chloride, which may be related to Akt/mTOR/GSK-3β signaling pathway.
Aluminum Chloride/adverse effects* ; Alzheimer Disease/drug therapy* ; Animals ; Galactose/metabolism* ; Glycogen Synthase Kinase 3 beta/metabolism* ; Hippocampus/metabolism* ; Mice ; Mice, Inbred BALB C ; Plant Extracts ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; Superoxide Dismutase/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; tau Proteins