Bear Bile Powder Ameliorates LPS-Induced Acute Lung Injury by Inhibiting CD14 Pathway and Improving Intestinal Flora: Exploration of "Fei (Lung)-Dachang (Large Intestine) Interaction".

OBJECTIVE: To explore the effect of bear bile powder (BBP) on acute lung injury (ALI) and the underlying mechanism. METHODS: The chemical constituents of BBP were analyzed by ultra-high-pressure liquid chromatography-mass spectrometry (UPLC-MS). After 7 days of adaptive feeding, 50 mice were randomly divided into 5 groups by a random number table (n=10): normal control (NC), lipopolysaccharide (LPS), dexamethasone (Dex), low-, and high-dose BBP groups. The dosing cycle was 9 days. On the 12th and 14th days, 20 µL of Staphylococcus aureus solution (bacterial concentration of 1 × 10-7 CFU/mL) was given by nasal drip after 1 h of intragastric administration, and the mice in the NC group was given the same dose of phosphated buffered saline (PBS) solution. On the 16th day, after 1 h intragastric administration, 100 µL of LPS solution (1 mg/mL) was given by tracheal intubation, and the same dose of PBS solution was given to the NC group. Lung tissue was obtained to measure the myeloperoxidase (MPO) activity, the lung wet/dry weight ratio and expressions of CD14 and other related proteins. The lower lobe of the right lung was obtained for pathological examination. The concentrations of inflammatory cytokines including interleukin (IL)-6, tumour necrosis factor α (TNF-α ) and IL-1ß in the bronchoalveolar lavage fluid (BALF) were detected by enzyme linked immunosorbent assay, and the number of neutrophils was counted. The colonic contents of the mice were analyzed by 16 sRNA technique and the contents of short-chain fatty acids (SCFAs) were measured by gas chromatograph-mass spectrometer (GC-MS). RESULTS: UPLC-MS revealed that the chemical components of BBP samples were mainly tauroursodeoxycholic acid and taurochenodeoxycholic acid sodium salt. BBP reduced the activity of MPO, concentrations of inflammatory cytokines, and inhibited the expression of CD14 protein, thus suppressing the activation of NF-κB pathway (P<0.05). The lung histopathological results indicated that BBP significantly reduced the degree of neutrophil infiltration, cell shedding, necrosis, and alveolar cavity depression. Moreover, BBP effectively regulated the composition of the intestinal microflora and increased the production of SCFAs, which contributed to its treatment effect (P<0.05). CONCLUSIONS: BBP alleviates lung injury in ALI mouse through inhibiting activation of NF-κB pathway and decreasing expression of CD14 protein. BBP may promote recovery of ALI by improving the structure of intestinal flora and enhancing metabolic function of intestinal flora.

Diagnostic value of 18F-FDG PET/CT and 68Ga-FAPI PET/CT in primary liver cancer: A systematic review and meta-analysis.

OBJECTIVE: To conduct a meta-analysis of the diagnostic efficacy of fluorine-18-fluorodeoxyglucose (18F-FDG) and gallium-68-labeled fibroblast-activation protein inhibitor (68Ga-FAPI) positron emission tomography/computed tomography (PET/CT) for primary liver cancer based on existing clinical evidence. MATERIALS AND METHODS: Meta-analysis was carried out according to PRISMA reporting specification. The clinical studies in PubMed/Medline, Embase and the Cochrane Library database were retrieved from the establishment to September 2022. Two researchers independently conducted literature screening and data extraction, evaluated the risk of bias according to QUADAS-2, conducted meta-analysis using Meta Disc 1.4 and Stata15.1 software, and calculated the summarized sensitivity (SEN), specificity (SPE), positive likelihood ratio (+LR), negative likelihood ratio (-LR), and diagnostic odds ratio (DOR). The diagnostic performance of 18F-FDG PET/CT and 68Ga-FAPI PET/CT for primary liver cancer was compared using summarized receiver operating characteristic (SROC) curve and area under curve (AUC). RESULTS: Four original studies on 18F-FDG PET/CT and 68Ga-FAPI PET/CT in the diagnosis of primary liver cancer were included, including 159 intrahepatic lesions in 106 patients. Taking lesions as a unit, in four original studies, the pooled results of 18F-FDG PET/CT diagnosis of primary liver cancer were Sen=0.5 (95% CI:95% CI: 0.41-0.59), Spe=0.87 (95% CI: 0.52-0.98), AUC=0.58 (95% CI:0.53-0.62); The pooled results of 68Ga-FAPI PET/CT in the diagnosis of primary liver cancer, Sen=0.5 (95% CI: 0.41-0.59), Spe=0.87 (95%CI:0.52-0.98), AUC=0.58 (95% CI:0.53-0.62). Besides, the Sen of 68Ga-FAPI PET/CT in the diagnosis of primary liver cancer was higher than that of 18F-FDG PET/CT (Z=2.323, P=0.02), the difference was statistically significant. CONCLUSION: Gallium-68-FAPI PET/CT is a promising tool. Compared with 18F-FDG, 68Ga-FAPI has higher sensitivity to detect more lesions in primary liver cancer and metastatic lesions, and has high performance in the diagnosis of primary liver cancer.

Influencing Factors and Prediction Model of Performance of Needle Visualization in Fine Needle Aspiration of Thyroid Nodules / 中国医学科学院学报

Objective To investigate the influencing factors and establish a model predicting the performance of needle visualization in fine-needle aspiration (FNA) of thyroid nodules. Methods This study prospectively included 175 patients who underwent FNA of thyroid nodules in the Department of Ultrasound in China-Japan Friendship Hospital and compared the display of the needle tips in the examination of 199 thyroid nodules before and after the application of needle visualization.We recorded the location,the positional relationship with thyroid capsule,ultrasonic characteristics,and the distribution of the soft tissue strip structure at the puncture site of the nodules with unclear needle tips display before using needle visualization.Furthermore,according to the thyroid imaging reporting and data system proposed by the American College of Radiology,we graded the risk of the nodules.Lasso-Logistic regression was employed to screen out the factors influencing the performance of needle visualization and establish a nomogram for prediction. Results The needle tips were not clearly displayed in the examination of 135 (67.8%) and 53 (26.6%) nodules before and after the application of needle visualization,respectively,which showed a significant difference (P<0.001).Based on the positional relationship between the nodule and capsule,anteroposterior/transverse diameter (A/T) ratio,blood supply,and the distribution of subcutaneous strip structure at the puncture site,a nomogram was established to predict the probability of unclear display of the needle tips after application of needle visualization.The C-index of the prediction model was 0.75 (95%CI=0.67-0.84) and the area under the receiver operating characteristic curve was 0.72.The calibration curve confirmed the appreciable reliability of the prediction model,with the C-index of 0.70 in internal validation. Conclusions Needle visualization can improve the display of the needle tip in ultrasound-guided FNA of thyroid nodules.The nomogram established based on ultrasound features such as the positional relationship between the nodule and capsule,A/T ratio,blood supply,and the distribution of subcutaneous strip structure at the puncture site can predict whether needle visualization is suitable for the examination of nodules.

Nomogram-Based Prediction of Risk of Cervical Lymph Node Metastasis in Differentiated Thyroid Carcinoma / 中国医学科学院学报

Objective To establish a nomogram for predicting the risk of cervical lymph node metastasis in differentiated thyroid carcinoma (DTC). Methods The patients with complete clinical data of DTC and cervical lymph node ultrasound and diagnosed based on pathological evidence from January 2019 to December 2021 were assigned into a training group (n=444) and a validation group (n=125).Lasso regression was performed to screen the data with differences between groups,and multivariate Logistic regression to establish a prediction model with the factors screened out by Lasso regression.C-index and calibration chart were employed to evaluate the prediction performance of the established model. Results The predictive factors for establishing the model were lymph node short diameter≥0.5 cm,long-to-short-axis ratio<2,disappearance of lymph node hilum,cystic transformation,hyperechogenicity,calcification,and abnormal blood flow (all P<0.001).The established model demonstrated a good discriminative ability,with the C index of 0.938 (95%CI=0.926-0.961) in the training group. Conclusion The nomogram established based on the ultrasound image features of cervical lymph nodes in DTC can accurately predict the risk of cervical lymph node metastasis in DTC.

Clinical application and research progress of 225Ac for tumor targeted therapy / 中华核医学与分子影像杂志

In recent years, the application of alpha particle-based nuclide targeted therapy in tumors has shown great potential. 225Ac is a nuclide that can be used for alpha radionuclide targeted therapy which has been studied at home and abroad. A number of preclinical and clinical trials have been carried out, and some achievements have been obtained. This article summarizes the current research status of several malignant tumors, and analyzes the challenges and progress faced by 225Ac in radionuclide targeted therapy.

Association between cardiometabolic diseases and quality of life and the mediation effect of perceived stress / 中华心血管病杂志

Objective: To explore the association between cardiometabolic diseases (CMD) and quality of life, the association between CMD and perceived stress, and the mediation effect of perceived stress on the association between CMD and quality of life, and to provide evidence for the prevention and treatment of CMD and the improvement of quality of life in these patients. Methods: This is a cross-sectional study. Data were collected by the employees' physical examination of a company in Xi'an in 2021. Multiple linear regression models were used to analyze the association between the status of CMD (divided into three categories: no CMD, presence of one kind of CMD, and with≥2 kinds of CMD (≥2 kinds of CMD were defined as cardiometabolic multimorbidity (CMM)), quality of life, and perceived stress. Mediation analysis with a multi-categorical independent variable was conducted to determine the mediation effect of perceived stress on the association between CMD and quality of life. Results: Among all 4 272 participants, 1 457 (34.1%) participants had one kind of CMD and 677 (15.8%) participants had CMM. The average scores for quality of life and perceived stress were (57.5±15.7) and (16.9±7.9), respectively. Compared with participants without CMD, after adjusting for demographic and lifestyle factors, no statistically significant associations were observed between one kind of CMD and perceived stress or quality of life (both P>0.05). Perceived stress did not mediate the association between one kind of CMD and quality of life. However, participants with CMM had lower quality of life and higher perceived stress than participants without CMD. The relative total effect coefficient c (95%CI) and the relative direct effect coefficient c' (95%CI) between CMM and quality of life were -3.71 (-5.04--2.37) and -2.52 (-3.81--1.24) (both P<0.05), respectively. The relative indirect effect coefficient a2b (95%CI) of perceived stress on the association between CMM and quality of life was -1.18 (-1.62--0.77) (P<0.05). The mediation effect size was 31.8%. Conclusions: CMM is negatively associated with quality of life and positively associated with perceived stress. Perceived stress partially mediates the association between CMM and quality of life. Our results suggest that, in addition to preventing and treating CMM actively, efforts should be taken to relieve the perceived stress of people with CMM to improve their quality of life.

Kunxian Capsule Extract Inhibits Angiogenesis in Zebrafish Embryos via PI3K/AKT-MAPK-VEGF Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the anti-angiogenic activity of Kunxian Capsule (KX) extract and explore the underlying molecular mechanism using zebrafish.@*METHODS@#The KX extract was prepared with 5.0 g in 100 mL of 40% methanol followed by ultrasonication and freeze drying. Freeze dried KX extract of 10.00 mg was used as test stock solution. Triptolide and icariin, the key bioactive compounds of KX were analyzed using ultra-high performance liquid chromatography. The transgenic zebrafish Tg(flk1:GFP) embryos were dechorionated at 20-h post fertilization (hpf) and treated with PTK 787, and 3.5, 7, 14 and 21 µg/mL of KX extract, respectively. After 24-h post exposure (hpe), mortality and malformation (%), intersegmental vessels (ISV) formation, and mRNA expression level of angiogenic pathway genes including phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), extracellular signal-regulated kinases (ERKs), mitogen-activated protein kinase (MAPK), vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF-2) were determined. Further, the embryos at 72 hpf were treated with KX extract to observe the development of sub-intestinal vein (SIV) after 24 hpe.@*RESULTS@#The chromatographic analysis of test stock solution of KX extract showed that triptolide and icariin was found as 0.089 mg/g and 48.74 mg/g, respectively, which met the requirements of the national drug standards. In zebrafish larvae experiment, KX extract significantly inhibited the ISV (P<0.01) and SIV formation (P<0.05). Besides, the mRNA expression analysis showed that KX extract could significantly suppress the expressions of PI3K and AKT, thereby inhibiting the mRNA levels of ERKs and MAPK. Moreover, the downstream signaling cascade affected the expression of VEGF and its receptors (VEGFR and VEGFR-2). FGF-2, a strong angiogenic factor, was also down-regulated by KX treatment in zebrafish larvae.@*CONCLUSION@#KX extract exhibited anti-angiogenic effects in zebrafish embryos by regulating PI3K/AKT-MAPK-VEGF pathway and showed promising potential for RA treatment.

Microglial Depletion does not Affect the Laterality of Mechanical Allodynia in Mice / 神经科学通报·英文版

Mechanical allodynia (MA), including punctate and dynamic forms, is a common and debilitating symptom suffered by millions of chronic pain patients. Some peripheral injuries result in the development of bilateral MA, while most injuries usually led to unilateral MA. To date, the control of such laterality remains poorly understood. Here, to study the role of microglia in the control of MA laterality, we used genetic strategies to deplete microglia and tested both dynamic and punctate forms of MA in mice. Surprisingly, the depletion of central microglia did not prevent the induction of bilateral dynamic and punctate MA. Moreover, in dorsal root ganglion-dorsal root-sagittal spinal cord slice preparations we recorded the low-threshold Aβ-fiber stimulation-evoked inputs and outputs of superficial dorsal horn neurons. Consistent with behavioral results, microglial depletion did not prevent the opening of bilateral gates for Aβ pathways in the superficial dorsal horn. This study challenges the role of microglia in the control of MA laterality in mice. Future studies are needed to further understand whether the role of microglia in the control of MA laterality is etiology-or species-specific.

Association between dietary quality and bone mass among middle-aged and elderly people in Gansu Province / 西安交通大学学报(医学版)

【Objective】 To evaluate the dietary quality with the dietary balance index (DBI_16) and the association between dietary quality and bone mass among middle-aged and elderly people in Gansu Province so as to provide evidence for improving dietary quality and bone health status of Gansu population. 【Methods】 Based on the information of the type and quantity of food intake and the bone mass of middle-aged and elderly people aged 35 years and above collected by the Gansu Project in the Regional Ethnic Cohort Study in Northwest China, DBI_16 was used to evaluate the intake level of cereals, vegetables, fruits, milk, beans, fish and shrimp, eggs and other foods, and the degree of inadequate, excessive and unbalanced dietary intake of the participants. Multiple linear regression was used to evaluate the associations of three component indexes of DBI_16, high bound score (DBI_HBS), low bound score (DBI_LBS), diet quality distance (DBI_DQD), and seven single indexes of DBI_16 with bone mass. 【Results】 Analyses of the dietary and bone mass data of 11,840 participants showed that 44.8% of participants consumed excessive amounts of cereals compared to the dietary recommendation. 96.3%, 90.6%, 90.1%, 71.9%, 95.1% and 60.3% of participants’ intake of vegetables, fruits, milk, soybeans, fish and shrimp, and eggs, respectively, were inadequate. 47.7% participants consumed less than 10 types of food. 2.3% participants’ DBI_LBS levels were appropriate. 54.7% participants’ DBI_HBS levels were appropriate. Only 1.2% participants’ DBI_DQD reached a balanced level. The bone mass level in the study population was (2.5±0.6) kg [(2.8±0.5) kg for men and (2.3±0.5) kg for women]. After adjusting for sociodemographic characteristics, lifestyle, total dietary energy intake and body mass index, DBI_LBS and DBI_DQD were negatively associated with bone mass [β and 95% CI was -0.002 01 (-0.003 62--0.000 40) and -0.001 76 (-0.003 09--0.000 43), respectively]. 【Conclusion】 Dietary intake imbalance is common among middle-aged and elderly people in Gansu Province, and the more severe the dietary intake imbalance, the lower the bone mass level.

Prevalence, associated factors and patterns of multimorbidity of non-communicable diseases among adults in Shaanxi Province / 西安交通大学学报(医学版)

【Objective】 To estimate the prevalence, associated factors and patterns of multimorbidity of non-communicable diseases among adults in Shaanxi Province so as to provide evidence for the prevention and control of non-communicable diseases. 【Methods】 We used the data of adults aged 18 years and older collected in the baseline survey of Shaanxi Project in the Regional Ethnic Cohort Study in Northwest China. Multinomial logistic regression was used to explore the associated factors for multimorbidity. Exploratory factor analysis was used to extract patterns of multimorbidity. 【Results】 The prevalence of multimorbidity was 10.7% among the 44 442 participants. Age increase, being males, urban residence, and being overweight or obesity were positively associated with multimorbidity. Compared with women, men had a higher risk of multimorbidity. The OR and 95% CI was 1.25 (1.12-1.39). The risk of multimorbidity increased with age among adults. Compared with participants aged 18.0-34.9 years, the ORs and 95% CIs of those aged 35.0-44.9, 45.0-54.9, 55.0-64.9, and ≥65.0 years were 4.73 (3.47-6.46), 15.61 (11.60-21.00), 41.39 (30.76-55.70) and 90.04 (66.58-121.77), respectively. The primary multimorbidity patterns among adults in Shaanxi were cardiovascular-metabolic multimorbidity (5.4%), viscero-articular multimorbidity (1.0%), and respiratory multimorbidity (0.3%). 【Conclusion】 More than one in ten adults in Shaanxi Province had multimorbidity, and the predominant pattern of multimorbidity was cardiovascular-metabolic multimorbidity. The prevention and control of non-communicable diseases should be reinforced in middle-aged and older people, males, people living in the urban, and overweight or obese people. More attention should be paid to the prevention and control of cardiovascular-metabolic diseases.

Extracellular vesicles derived from host and gut microbiota as promising nanocarriers for targeted therapy in osteoporosis and osteoarthritis.

Osteoporosis (OP), a systemic bone disease that causes structural bone loss and bone mass loss, is often associated with fragility fractures. Extracellular vesicles (EVs) generated by mammalian and gut bacteria have recently been identified as important mediators in the intercellular signaling pathway that may play a crucial role in microbiota-host communication. EVs are tiny membrane-bound vesicles, which range in size from 20 to 400 nm. They carry a variety of biologically active substances across intra- and intercellular space. These EVs have developed as a promising research area for the treatment of OP because of their nanosized architecture, enhanced biocompatibility, reduced toxicity, drug loading capacity, ease of customization, and industrialization. This review describes the latest development of EVs derived from mammals and bacteria, including their internalization, isolation, biogenesis, classifications, topologies, and compositions. Additionally, breakthroughs in chemical sciences and the distinctive biological features of bacterial extracellular vesicles (BEVs) allow for the customization of modified BEVs for the therapy of OP. In conclusion, we give a thorough and in-depth summary of the main difficulties and potential future of EVs in the treatment of OP, as well as highlight innovative uses and choices for the treatment of osteoarthritis (OA).

Clinical and laboratory features compared between JAK2 exon12 and JAK2 V617F mutated polycythemia vera / 中华血液学杂志

Objective: To compare clinical and laboratory features between JAK2 exon12 and JAK2 V617F mutated polycythemia vera (PV) . Method: We collected data from 570 consecutive newly-diagnosed subjects with PV and JAK2 mutation, and compared clinical and laboratory features between patients with JAK2 exon12 and JAK2 V617F mutation. Results: 543 (95.3%) subjects harboured JAK2 V617F mutation (JAK2 V617F cohort) , 24 (4.2%) harboured JAK2 exon12 mutations (JAK2 exon12 cohort) , and 3 (0.5%) harboured JAK2 exon12 and JAK2 V617F mutations. The mutations in JAK2 exon12 including deletion (n=10, 37.0%) , deletion accompanied insertion (n=10, 37.0%) , and missense mutations (n=7, 25.9%) . Comparing with JAK2 V617F cohort, subjects in JAK2 exon12 cohort were younger [median age 50 (20-73) years versus 59 (25-91) years, P=0.040], had higher RBC counts [8.19 (5.88-10.94) ×10(12)/L versus 7.14 (4.11-10.64) ×10(12)/L, P<0.001] and hematocrit [64.1% (53.7-79.0%) versus 59.6% (47.2%-77.1%) , P=0.001], but lower WBC counts [8.29 (3.2-18.99) ×10(9)/L versus 12.91 (3.24-38.3) ×10(9)/L, P<0.001], platelet counts [313 (83-1433) ×10(9)/L versus 470 (61-2169) ×10(9)/L, P<0.001] and epoetin [0.70 (0.06-3.27) versus 1.14 (0.01-10.16) IU/L, P=0.002] levels. We reviewed bone marrow histology at diagnosis in 20 subjects with each type of mutation matched for age and sex. Subjects with JAK2 exon12 mutations had fewer loose megakaryocyte cluster (40% versus 80%, P=0.022) compared with subjects with JAK2 V617F. The median follow-ups were 30 months (range 4-83) and 37 months (range 1-84) for cohorts with JAK2 V617F and JAK2 exon12, respectively. There was no difference in overall survival (P=0.422) and thrombosis-free survival (P=0.900) . Conclusions: Compared with patients with JAK2 V617F mutation, patients with JAK2 exon12 mutation were younger, and had more obvious erythrocytosis and less loose cluster of megakaryocytes.

Dexmedetomidine protects acute myocardial ischemic injury in rats by inhibiting TXNIP / 中国药理学通报

Aim To investigate the protective effect of dexmedetomidine(DEX)on acute myocardial ischemia in rats and its mechanism.Methods Sixty SD rats were randomly divided into five groups: control group(C), model group(M), and dexmedetomidine 10, 25, 50 μg·kg

Comparison of different obesity indices in predicting risk of hypertension among adults in Gansu Province / 西安交通大学学报(医学版)

【Objective】 To compare the ability of body mass index （BMI）， body fat percentage （BFP）， waist circumference （WC）， waist-to-height ratio （WHtR）， visceral fat index （VFI） and the combinations of two kinds of obesity indices to predict the risk of hypertension. 【Methods】 Data collected in the baseline survey of “Gansu Province’s Urban and Rural Natural Population Cohort Establishment and Tumor Follow-up Study” were analyzed. Area under the curve （AUC） of ROC curve with covariates was used to analyze and compare the effects of individual obesity evaluation index and the combination of two kinds of obesity indices in predicting the risk of hypertension. 【Results】 Analyses of data of 20，079 adults showed that the AUC of BMI， WC， WHtR， BFP and VFI was 0.636， 0.604， 0.615， 0.614 and 0.619， respectively. AUC of the combination of BMI and WC （0.643） was higher than that of BMI （0.636）； however， the change rate of AUC was only 1.09%. AUC of the combinations of WC， WHtR and VFI， the three central obesity evaluation indices， and BFP， a general obesity evaluation index， were lower than that of BMI. The optimal cutoff value for BMI was 24.2 kg/m2. 【Conclusion】 The effect of BMI in predicting the risk of hypertension is better than that of BFP， WC， WHtR and VFI. The effects of the combinations of the two kinds of obesity evaluation indices are not better than that of BMI. To prevent and control hypertension， adults should keep their BMI under overweight.

Effect of electrical stimulation combined with pulmonary rehabilitation on patients with mechanical ventilation / 西安交通大学学报(医学版)

【Objective】 To explore whether the effect of functional electrical stimulation combined with respiratory training on patients with mechanical ventilation is superior to that of single lung rehabilitation scheme. 【Methods】 We selected 90 patients with mechanical ventilation hospitalized in the central ICU of our hospital from March 2018 to October 2019 and randomly assigned them into the functional electrical stimulation group (30 cases), respiratory function training group (30 cases), and the combined rehabilitation group (functional electrical stimulation combined with respiratory training) (30 cases). The treatment time in the three groups was 40 minutes each time. The treatment was given once a day, 6 times a week, and lasted for 2 weeks. B-ultrasound was used to measure the changes of the diaphragm and calculate the score of diaphragm thickening. The success rate of weaning, incidence of ventilator-associated pneumonia (VAP), duration of mechanical ventilation, and length of stay in ICU can be quantified according to the clinical nursing records. 【Results】 There were significant differences in the success rate of weaning, incidence of VAP, time of mechanical ventilation, and length of ICU stay in the three groups. However, the success rate of weaning, incidence of VAP, time of mechanical ventilation, and the length of ICU stay in the combined rehabilitation group were better than those in the other two groups (P<0.05). 【Conclusion】 The effect of functional electrical stimulation combined with respiratory training on patients with mechanical ventilation is significantly better than that of single lung rehabilitation scheme. The former one is superior to the single rehabilitation scheme in improving the success rate of weaning, increasing the activity of diaphragm, shortening the time of mechanical ventilation, and the length of stay in ICU.

Tripterygium wilfordii multiglycoside-induced hepatotoxicity via inflammation and apoptosis in zebrafish / 中国天然药物

Tripterygium wilfordii multiglycoside (GTW) is a commonly used compound for the treatment of rheumatoid arthritis (RA) and immune diseases in clinical practice. However, it can induce liver injury and the mechanism of hepatotoxicity is still not clear. This study was designed to investigate GTW-induced hepatotoxicity in zebrafish larvae and explore the mechanism involved. The 72 hpf (hours post fertilization) zebrafish larvae were administered with different concentrations of GTW for three days and their mortality, malformation rate, morphological changes in the liver, transaminase levels, and histopathological changes in the liver of zebrafish larvae were detected. The reverse transcription-polymerase chain reaction (RT-PCR) was used to examine the levels of microRNA-122 (miR-122) and genes related to inflammation, apoptosis, cell proliferation and liver function. The results showed that GTW increased the mortality of zebrafish larvae, while significant malformations and liver damage occurred. The main manifestations were elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), significant liver atrophy, vacuoles in liver tissue, sparse cytoplasm, and unclear hepatocyte contours. RT-PCR results showed that the expression of miR-122 significantly decreased by GTW; the mRNA levels of inflammation-related genes il1β, il6, tnfα, il10, cox2 and ptges significantly increased; the mRNA level of tgfβ significantly decreased; the mRNA levels of apoptosis-related genes, caspase-8 and caspase-9, significantly increased; the mRNA level of bcl2 significantly decreased; the mRNA levels of cell proliferation-related genes, top2α and uhrf1, significantly reduced; the mRNA levels of liver function-related genes, alr and cyp3c1, significantly increased; and the mRNA level of cyp3a65 significantly decreased. In zebrafish, GTW can cause increased inflammation, enhanced apoptosis, decreased cell proliferation, and abnormal expression of liver function-related genes, leading to abnormal liver structure and function and resulting in hepatotoxicity.

Inhibition of YAP-c-Myc signaling pathway involved effect of ORI on anti-glioma / 中国药理学通报

Aim To investigate the effects of oridonin on proliferation, migration and apoptosis of U87 glioma cells and to explore the involvement of the mechanism in the inhibition of Yes-associated protein (YAP)-c - Myc signaling pathway. Methods The effect of oridonin on U87 viability was measured by MTT assay; the migration and invasiveness of cells were measured by transwell assays; the apoptotic rates of cells were assessed by flow cytometry; the caspase-3, B c l - 2, Bax, YAP, c - MycmRNA expression in U87 glioma cells was detected by real-time quantitative P C R; the caspase-3, Bcl-2, Bax, YAP, p-YAP (Seri 27), c-Myc protein expressions were detected by Western blot. Results The proliferation of U87 cells was significantly inhibited by oridonin in a dose-dependent manner (P < 0. 05), and the ability of cell migration and invasion was weakened (P <0. 01), cell apoptosis rate in flow cytometry analysis increased significantly (P <0. 01), the protein and mRNA expression of caspase-3 increased (P < 0. 05), the mRNA and protein expression of Bcl-2/Bax decreased (P < 0. 05), the mRNA and protein expression of Y A P and c-Myc decreased (P < 0. 05), and the protein expression of p - Y A P increased (P < 0. 05). Conclusions Oridonin can significantly inhibit the proliferation and migration of U87 glioma cells and promote the transformation apoptosis of glioma cells; the mechanism may be related to the inhibition of YAP-c-Myc signaling pathway.

Values of the Quantitative Parameters of Contrast-enhanced Ultrasound in the Diagnosis of Thyroid Benign and Malignant Nodules / 中国医学科学院学报

To investigate the value of contrast-enhanced ultrasound(CEUS)quantitative parameters in the diagnosis of thyroid benign and malignant nodules. The CEUS features of 85 histopathologically confirmed thyroid nodules were quantitatively analyzed using five parameters including rising time(RT),time to peak(TTP),area under the curve(AUC),maximum intensity(Imax),and mean transit time(mTT).The dynamic vascular pattern(DVP)curves were also drawn. The Imax(=-7.08,=0.01)and AUC(=-2.03,=0.04)of thyroid malignant nodules were significantly smaller than those of thyroid tissue,and the Imax(=-1.35,=0.02)and AUC(=-0.21,=0.02)of thyroid benign nodules were significantly larger than those of thyroid tissue.There were significant differences between thyroid benign and malignant nodules in Imax(=-4.16,=0.00),AUC(=-3.01,=0.01),and DVP curve types(=0.00).RT(=-0.28,=0.62),TTP(=-0.10,=0.89),and mTT(=-0.79,=0.05)were not significantly different between thyroid benign and malignant nodules. The quantitative parameters of CEUS,especially Imax and AUC parameters,are valuable in the diagnosis of benign and malignant thyroid nodules.

Transcranial direct current stimulation promotes hippocampal neurogenesis in mice with cerebral ischemia involving up-regulation of nmda receptors / 中国药理学通报

Aim To investigate the improving effect of transcranial direct current stimulation (tDCS) on endogenous hippocampal neurogenesis in mice with cerebral ischemiaand the possible mechanism. Methods The model of acute cerebral ischemia in mice was established by bilateral common carotid artery occlision (BCCAO). The pathological changes of mice were detected by hippocampal HE staining. The learning and memory function of mice was assessed by Morris water maze. The number of BrdU, DCX and BrdU/NeuN-positive cells was observed through immunofluorescence staining for detecting hippocampal neurogenesis. The mRNA and protein expressions of NMDAR subunits NR2a and NR2b in hippocampus were detected by qRT-PCR and Western blot. Results The neuronal damage in the hippocampal CA1 region was marked (P <0. 01), and the learning and memory function significantly decreased (P<0. 01) in cerebral ischemia mice, suggesting the successful establishment of cerebral ischemia model. At the same time, the number of BrdU, DCX and BrdU/NeuN positive cells was up-reg-ulated significantly (P < 0. 01 ) , indicating the occurrence of neurogenesis in hippocampus after cefebral ischemia. Treatment with tDCS significantly ameliorated the pathological damage in CA1 region of mice, improved learning and memory, and promoted hippocam-pal neurogenesis. Meanwhile, the mRNA and protein expression levels of NR2a and NR2b in hippocampus were also up-regulated (P < 0. 05 or P < 0.01). Conclusions tDCS can promote hippocampal neurogenesis and improve learning and memory function in cerebral ischemia mice, which may be related to theup-regula-tion ofNR2a and NR2b expression.

Late infantile neuronal ceroid lipofuscinosis caused by a CLN6 homozygous mutation:One case report and the literature review / 中国实用儿科杂志

OBJECTIVE: To collect the clinical features and gene mutation types of children with neuronal ceroid lipofuscinosis(NCLs)in China,and to help to make genetic diagnosis of NCLs patients. METHODS: The clinical manifestations and examinations of one case with complaints of language disorder for 1.5 years,dyskinesia for 0.5 years and repeated convulsions for one week were collected,and literatures of NCLs from China were reviewed. RESULTS: The electroencephalogram(EEG)showed multiple spikes and slow-wave discharges bilaterally. The brain MRI scan showed high hyperintensities adjacent to the bilateral posterior horns of the lateral ventricles on T2-weighted images and broadened cerebellar fissures. The "leukoencephalopathies and symptomatic epilepsy" was diagnosed. The genetic analysis showed that the proband had a homozygous missense point mutation c.892 G>A(p.Glu298 Lys)(reference sequence:NM＿017882.2)in exon 7 of CLN6 and that both his parents were heterozygous for the mutation. The diagnosis of late infantile neuronal ceroid lipofuscinosis(LINCLs)was confirmed according to the clinical features and genetic analysis results. In CNKI,WANFANG and WIPP Databases,we reviewed the relevant domestic reports about NCLs(28 articles). A total of 3 cases of CLN6 gene mutation were reported,including 2 cases of LINCLs caused by heterozygous mutation and 1 case of JNCLs caused by homozygous mutation. Here we reported the first case of LINCLs caused by a CLN6 homozygous mutation in China. CONCLUSION: This is the first case of LINCLs caused by CLN6 homozygous mutation reported in China. Our report expands the genotype data for NCLs.The mutant genes reported in NCLs patients are CLN1,CLN2,CLN3,CLN5,CLN6 and CLN7,and the clinical manifestations are intractable epilepsy,decreased vision,decreased intelligence,mental and motor dysfunction,personality and behavior changes,and memory decline. A gene sequencing panel for investigating unexplained seizures,leukoencephalopathies and inherited metabolic disorder can help to make the diagnosis.