Study of clinical characteristics in patients with gp210 antibody-positive primary biliary cholangitis / 中华肝脏病杂志

Objective: To analyze the clinical characteristics and prognostic value of liver function in a large samples of patients with anti-glycoprotein 210 (gp210 antibody) positive primary biliary cholangitis (PBC). Methods: A retrospective study was performed on 931 PBC cases in Beijing You'an Hospital affiliated to Capital Medical University from 2010 to 2019. According to the detection of gp210 antibody, 318 cases were divided into gp210 antibody positive group (positive group) and 613 cases were divided into gp210 antibody negative group (negative group). The differences in demographic, medical history, clinical indicators, B-ultrasound and pathological indicators as well as the histopathological basis were compared between the two groups. SPSS 16.0 software was used for statistical analysis. Measurement data were analyzed by t-test or rank sum test, and enumeration data by χ2 test. Multivariate analysis was used for logistic test, and and survival analysis was used for prognosis. Results: The positive and the negative groups were compared. The ratio of male to female was significantly higher in positive than negative group (1:5.35 vs. 1:9.73, P＜0.05), and the difference was statistically significant. The proportion of hormone use in history of past diagnosed and treated was higher in positive than negative group (12.9% vs. 3.47%, P＜0.05), and the difference was statistically significant. The detection of biochemical indexes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), alkaline phosphatase (ALP), glutamyl transpeptidase (GGT) were higher in positive than the negative group (51.1 U/L vs. 41.1 U/L, 62.6 U/L vs. 49.6 U/L, 24.1 μmol/L vs. 17.9 μmol/L, 228.3 U/L vs. 169.6 U/L, 203.9 U/L vs. 147.6 U/L), (P＜0.05), and the differences were statistically significant. Antinuclear antibody (ANA)-positive rate, high titer ratio and immunoglobulin G (IgG) levels were higher in positive than negative group (95.2% vs. 81.6%, 69.7% vs. 48.8%, 17.2 g/L vs. 16.2 g/L), (P＜0.05), and the differences were statistically significant. The incidence of liver failure was higher in positive than negative group (P＜0.05). CK7 and inflammation score were higher in positive group than negative group in liver histopathological observations (0.83±0.53 vs. 0.28±0.47; 1.06±0.39 vs. 0.54±0.65), (P＜0.05), and the differences were statistically significant. Conclusion: The illness condition of patients with gp210 antibody positive PBC is more severe than patients with gp210 antibody negative PBC, and the incidence of liver failure is significantly increased. Cholangiocytes may be the histopathological basis of the clinical characteristics of gp210 antibody positive PBC patients.

Exploration on the experience of long-term external normothermic machine perfusion of discarded human kidney for the first time in China / 中华肾脏病杂志

Objective:To explore the long-term preservation value and repair effect of normothermic machine perfusion (NMP) on clinically discarded kidneys.Methods:A case of clinical discarded donor kidney was collected, and NMP was carried out in vitro for 9 hours with recovered blood. The dynamic changes of renal appearance, blood gas and biochemistry analysis of perfusate and renal pathology were recorded. Results:In the second to fifth hour of NMP, the appearance of renal was pink and ex vivo normothermic perfusion assessment score (EVNP) was grade Ⅰ. While, the sixth hour and beyond of NMP, the appearance of kidney turned to dark red and EVNP was grade Ⅲ. The renal perfusion blood flow maintained above 150 ml/min in the first 6 hours and decreased significantly after that, and at the end, was only 50 ml/min. During the whole process of perfusion, urine output was maintained at about 100 ml/h. PO 2 remained above 100 mmHg in the first 5 hours of perfusion and from the 6th hour, was lower than 80 mmHg and continued to decline, and was close to 0 at the end of perfusion. The results showed that although the K + concentration changes in blood and urine in the first 5 hours of NMP had a good consistency, the lactic acid level had been rising. In addition, there was no significant change in the histopathology at the fourth hour of perfusion compared with that before zero-point puncture, and the fibrinous thrombus in glomeruli was improved compared with that before perfusion. However, at the sixth hour after perfusion and before the end of perfusion, the pathological changes of renal tissue were significantly worse. There were a large of thrombosis in glomerular blood vessels, renal tubular atrophy and acute tubular necrosis. Conclusions:NMP can realize the evaluation of extended criteria donors before transplantation, and it proves the feasibility and repair potential of NMP in kidney to a certain extent. At the same time, NMP also provides a new way to expand the source of donor kidney and to pre-treat organ in vitro.

Association between body mass index with premature eruption of second permanent molars in children aged 9-12 in Bengbu City / 中国学校卫生

Objective@#To investigate the epidemiological characteristics of premature eruption of permanent molars and its aasociation with body mass index (BMI), to provide a reference for childhood oral health promotion.@*Methods@#A total of 861 children aged 9 to 12 years from two primary schools in Bengbu City were selected by cluster sampling method. Parental questionnaire was administered to collect socio demographic information. The eruption of second permanent molars were examined. Data was analyzed by multivariate Logistic regression model and margins command.@*Results@#The detection rate of premature eruption of second permanent molars was 26.5%(228), 27.5% in boys and 24.9% in girls( χ 2=0.73, P =0.39). Early detection rate of second permanent molars (39.0%) was significantly higher in obese group than normal weight group (21.5%)( χ 2=21.85, P <0.01). Logistic regression analysis showed that obesity was positively correlated with the risk of premature eruption of second permanent molars( OR= 3.55 , 95%CI=2.14-5.87, P <0.01). Overweight was not associated with higher risk of premature eruption of second permanent molars( OR=1.64, 95%CI=0.95-2.81, P =0.07). Being female was associated with higher risk of premature eruption of second permanent molars compared to age matched peers( OR=2.19, 95%CI=1.42-3.39, P <0.01).@*Conclusion@#Childhood obesity is associated with higher risk for premature eruption of second permanent molars. Girls are more likely to have second permanent molar erupted in advance compared to age matched boys.

Dose-enhanced immunochemotherapy followed by first-line autologous peripheral blood stem cell transplantation for young patients with high-risk aggressive B-cell lymphoma: an efficacy and prognostic factor analysis / 中华血液学杂志

Objective: This study aimed to determine the efficacy of dose-enhanced immunochemotherapy followed by autologous peripheral blood stem cell transplantation (ASCT) in young patients with newly diagnosed high-risk aggressive B-cell lymphoma. Methods: A retrospective study was conducted to examine the clinical and survival data of young patients with high-risk aggressive B-cell lymphoma who received dose-enhanced immunochemotherapy and ASCT as first-line treatment between January 2011 and December 2018 in Blood Diseases Hospital. Results: A total of 63 patients were included in the study. The median age range was 40 (14-63) years old. In terms of the induction therapy regimen, 52 cases received R-DA-EP (D) OCH, and the remaining 11 received R-HyperCVAD/R-MA. Sixteen (25.4% ) patients achieved partial response in the mid-term efficacy assessment, and ten of them were evaluated as complete response after transplantation. The median follow-up was 50 (8-112) months, and the 3-year progression-free survival (PFS) rate and overall survival (OS) rate were (83.9±4.7) % and (90.4±3.7) % , respectively. Univariate analysis demonstrated that age-adjusted international prognostic index ≥2 scores was a negative prognostic factor for OS (P=0.039) , and bone marrow involvement (BMI) was an adverse prognostic factor for OS (P<0.001) and PFS (P=0.001) . However, multivariate analysis confirmed that BMI was the only independent negative predictor of OS (P=0.016) and PFS (P=0.001) . Conclusions: The use of dose-enhanced immunochemotherapy in combination with ASCT as first-line therapy in the treatment of young, high-risk aggressive B-cell lymphoma results in good long-term outcomes, and BMI remains an adverse prognostic factor.

c-MYC-mediated TRIB3/P62+ aggresomes accumulation triggers paraptosis upon the combination of everolimus and ginsenoside Rh2

The mammalian target of rapamycin (mTOR) pathway is abnormally activated in lung cancer. However, the anti-lung cancer effect of mTOR inhibitors as monotherapy is modest. Here, we identified that ginsenoside Rh2, an active component of Panax ginseng C. A. Mey., enhanced the anti-cancer effect of the mTOR inhibitor everolimus both in vitro and in vivo. Moreover, ginsenoside Rh2 alleviated the hepatic fat accumulation caused by everolimus in xenograft nude mice models. The combination of everolimus and ginsenoside Rh2 (labeled Eve-Rh2) induced caspase-independent cell death and cytoplasmic vacuolation in lung cancer cells, indicating that Eve-Rh2 prevented tumor progression by triggering paraptosis. Eve-Rh2 up-regulated the expression of c-MYC in cancer cells as well as tumor tissues. The increased c-MYC mediated the accumulation of tribbles homolog 3 (TRIB3)/P62+ aggresomes and consequently triggered paraptosis, bypassing the classical c-MYC/MAX pathway. Our study offers a potential effective and safe strategy for the treatment of lung cancer. Moreover, we have identified a new mechanism of TRIB3/P62+ aggresomes-triggered paraptosis and revealed a unique function of c-MYC.

Suppression of HMGB1 inhibits neuronal autophagy and apoptosis to improve neurological deficits in rats following intracerebral hemorrhage / 南方医科大学学报

OBJECTIVE@#To investigate the effect of suppressing high-mobility group box 1 (HMGB1) on neuronal autophagy and apoptosis in rats after intracerebral hemorrhage (ICH) in rats.@*METHODS@#Rat models of ICH induced by intracerebral striatum injection of 0.2 U/mL collagenase Ⅳ were treated with 1 mg/kg anti-HMGB1 mAb or a control anti-IgG mAb injected via the tail immediately and at 6 h after the operation (n=5). The rats in the sham-operated group (with intracranial injection of 2 μL normal saline) and ICH model group (n=5) were treated with PBS in the same manner after the operation. The neurological deficits of the rats were evaluated using modified neurological severity score (mNSS). TUNEL staining was used to detect apoptosis of the striatal neurons, and the expressions of HMGB1, autophagy-related proteins (Beclin-1, LC3-Ⅱ and LC3-Ⅰ) and apoptosis-related proteins (Bcl-2, Bax and cleaved caspase-3) in the brain tissues surrounding the hematoma were detected using Western blotting. The expression of HMGB1 in the striatum was detected by immunohistochemistry, and serum level of HMGB1 was detected with ELISA.@*RESULTS@#The rat models of ICH showed significantly increased mNSS (P < 0.05), which was markedly lowered after treatment with anti- HMGB1 mAb (P < 0.05). ICH caused a significant increase of apoptosis of the striatal neurons (P < 0.05), enhanced the expressions of beclin-1, LC3-Ⅱ, Bax and cleaved caspase-3 (P < 0.05), lowered the expressions of LC3-Ⅰ and Bcl-2 (P < 0.05), and increased the content of HMGB1 (P < 0.05). Treatment with anti-HMGB1 mAb obviously lowered the apoptosis rate of the striatal neurons (P < 0.05), decreased the expressions of Beclin-1, LC3-Ⅱ, Bax and cleaved caspase-3 (P < 0.05), increased the expressions of LC3-Ⅰ and Bcl-2 (P < 0.05), and reduced the content of HMGB1 in ICH rats (P < 0.05).@*CONCLUSION@#Down- regulation of HMGB1 by anti-HMGB1 improves neurological functions of rats after ICH possibly by inhibiting autophagy and apoptosis of the neurons.

Berberine inhibits erastin-induced ferroptosis of mouse hippocampal neuronal cells possibly by activating the Nrf2-HO-1/GPX4 pathway / 南方医科大学学报

OBJECTIVE@#To explore the mechanism by which berberine inhibits ferroptosis of mouse hippocampal neuronal cells (HT22).@*METHODS@#Cultured HT22 cells were pretreated with 30 or 60 μmol/L berberine for 2 h before exposure to 0.5 μmol/L erastin for 8 h, and the cell proliferation, intracellular ferric iron level, changes in intracellular reactive oxygen species (ROS) and cell apoptosis were detected using CCK-8, Fe2+ fluorescent probe, fluorescent dye (DAPI) and fluorescent probe (H2DCFH-DA). RT-qPCR and Western blotting were used to detect the mRNA and protein expressions of Nrf2, HO-1 and GPX4 in the cells. We further tested the effects of treatments with 2 μmol/L ML385 (a Nrf2 inhibitor), 60 μmol/L berberine and erastin in the cells to explore the protective mechanism of berberine against erastin-induced ferroptosis in the neuronal cells.@*RESULTS@#Treatment with 0.5 μmol/L erastin significantly lowered the viability of HT22 cells (P < 0.05) and increased the production of ROS, cell apoptosis rate and ferric iron level (P < 0.05). Pretreatment with 30 and 60 μmol/L berberine both significantly increased the vitality of erastin-exposed cells (P < 0.05) and lowered the levels of intracellular ROS and ferric iron content (P < 0.05). RT-qPCR and Western blotting showed that berberine obviously promoted the expressions of Nrf2, HO-1 and GPX4 in the cells (P < 0.05), and treatment with ML385 significantly inhibited the Nrf2-HO-1/GPX4 pathway, increased intracellular ROS and ferric iron contents and mitigated the protective effect of berberine against erastin-induced ferroptosis (P < 0.05).@*CONCLUSION@#Berberine can inhibit erastin-induced ferroptosis in HT22 cells possibly by activating the Nrf2-HO-1/ GPX4 pathway.

Network Meta-analysis of Efficacy of Five Classical Prescriptions for Acute Attack of Asthma in Children / 中国实验方剂学杂志

ObjectiveTo compare and evaluate the clinical efficacy of five classical prescriptions for acute attack of bronchial asthma （BA） and cough variant asthma （CVA） in children， and to further compare and assess the effect of them on cold-induced asthma or heat-induced asthma. MethodRandomized controlled trials （RCT） on the treatment of acute attack of asthma with five classical prescriptions （Sanzi Yangqintang， Maxing Shigantang， Shegan Mahuangtang， Xiao Qinglongtang， and Dingchuantang） were retrieved from China Science and Technology Journal Database （VIP）， China National Knowledge Infrastructure （CNKI）， and Wanfang Data （from establishment to August 15， 2021）. The eligible RCT were evaluated and the data were extracted for network Meta-analysis by Stata 16.0. ResultA total of eligible 47 RCT were screened out， involving 5 114 children with acute attack of asthma and 10 intervention measures. Among them， 16 RCT （1 912 children， 6 intervention measures） were about the cold-induced asthma and 10 RCT （1 054 cases， 4 intervention measures） focused on the heat-induced asthma. According to the Meta-analysis， among the 10 interventions， Maxing Shigantang + routine treatment of western medicine demonstrated the most significant effect， and the effect of the interventions was in the following order： Maxing Shigantang + routine treatment of western medicine > routine treatment of western medicine， Shegan Mahuangtang + routine treatment of western medicine> Xiao Qinglongtang + routine treatment of western medicine > Shegan Mahuangtang > Dingchuantang + routine treatment of western medicine. For the cold-induced asthma， the effect of Shegan Mahuangtang + routine treatment of western medicine was remarkable， and for the heat-induced asthma， the corresponding intervention was Dingchuantang + routine treatment of western medicine. Shegan Mahuangtang was outstanding in improving the percentage of forced expiratory volume in the first second in predicted value （FEV1%）. ConclusionThe combination of western medicine with the five prescriptions was more effective than the western medicine alone， particularly the combination with Maxing Shigantang. The combination of Shegan Mahuangtang and western medicine was outstanding in the treatment of cold-induced asthma， while the corresponding intervention for heat-induced asthma was the combination of Dingchuantang and western medicine. However， a large number of RCT with scientific design and higher quality are still needed to verify the conclusion.

Effect and Mechanism of Sangmei Zhike Granule on Airway Inflammation in Rats with Cough Variant Asthma / 中国实验方剂学杂志

ObjectiveTo explore the effect and mechanism of Sangmei Zhike granule （SMZK） on airway inflammation in rats with cough variant asthma（CVA）. MethodSix-week-old male SD rats were randomly divided into normal group， model group， and SMZK （2.48 g·kg-1） group. The rats in the model group and the SMZK group received intraperitoneal injection of a mixed solution containing 10% ovalbumin （OVA） and aluminium hydroxide on the 1st and 8th days and aerosol inhalation of 1% OVA solution from the 15th day for CVA model induction. The intervention lasted for two weeks from the 15th day. At the end of animal manipulation， the lung function was detected and inflammatory cells in the peripheral blood were counted. The serum interleukin-4 （IL-4）， interleukin-5 （IL-5）， and interleukin-10 （IL-10） levels were determined. Hematoxylin-eosin （HE） staining was performed on the lungs. Western blot was used to detect the protein expression of nuclear factor kappa-B （NF-κB） and its inhibitor α（IκBα） in lung tissues. ResultCompared with the normal group， the model group showed reduced forced expiratory volume in the first 0.1 second （FEV0.1），FEV0.1/forced vital capacity （FVC），and forced expiratory flow 50% （FEF50%） （P<0.05， P<0.01）， increased white blood cells and eosinophils （P<0.01）， and up-regulated serum IL-4， IL-5， and IL-10 （P<0.01）. As revealed by HE staining， the model group displayed shed epithelial cells of the bronchus， airway stenosis， hyperplasia and expansion of mucous glands， disarrangement of layer structures， disorderly arranged cells， and extensive infiltration of inflammatory cells. The protein expression of NF-κB p65 was higher （P<0.01） and that of IκBα was lower （P<0.01） in the lung tissues of the model group than that in the normal group. Compared with the model group， the SMZK group showed increased FEV0.1，FEV0.1/FVC，and FEF50% （P<0.05）， decreased white blood cells and eosinophils in the peripheral blood （P<0.01）， and declining serum IL-4， IL-5， IL-10 （P<0.01）. HE staining demonstrated mild bronchial mucosal injury and relieved inflammatory cell infiltration， gland hyperplasia， and epithelial degeneration and necrosis in the SMZK group. The protein expression of NF-κB p65 was decreased （P<0.05） and that of IκBα was increased （P<0.05） in lung tissues of the SMZK group than that in the model group. ConclusionSMZK can improve lung function and inhibit airway inflammation in rats with CVA. The underlying mechanism may be related to the regulation of IκBα/NF-κB protein expression in the lungs.

Therapeutic Effect and Antioxidant Mechanism of Xiaochuanning Granule on Psychological Stress Related Asthma in Rats / 中国实验方剂学杂志

ObjectiveTo observe the therapeutic effect and antioxidant mechanism of Xiaochuanning granule on psychological stress-related asthma in rats. MethodThe 6-week-old male SD rats were randomly divided into the normal group， asthma group， stress group， stress-related asthma group， western medicine group （atomization of budesonide suspension） and traditional Chinese medicine （TCM） group （Xiaochuanning granule 2.48 g·kg-1）. The asthma model was established during 28 days by intraperitoneal injection of 10% ovalbumin（OVA）on the 1st and 8th days and inhaling of vapourized 1% OVA started at the 15th day. Stress group， stress-related asthma group， western medicine group and TCM group were given restraint stimulation during the 28 days to establish the psychological stress-related asthma model. Rats in each group were administered with corresponding drug for 14 days from the 15th day. The sucrose preference test and open field test were performed at the 15th and 28th days. At the end of experiment， the body weight， serum interleukin-4 （IL-4）， interleukin-5 （IL-5） and interleukin-13 （IL-13） levels， as well as the levels of malondialdehyde （MDA）， superoxide dismutase （SOD） and glutathione （GSH） in lung tissues were detected by assay kits. Hematoxylin-eosin（HE） staining was conducted to observe the pathological changes in lung tissues. Meanwhile， Western blot was used to detect the protein expression of nuclear factor erythroid 2-related factor 2 （Nrf2） and hemeoxygenase-1 （HO-1） in lung tissues. ResultCompared with the stress-related asthma group， the body weight， sugar water consumption rate and open field distance in the TCM group were significantly increased （P<0.05）， and the serum IL-4， IL-5， IL-13 levels were significantly decreased （P<0.05）， the levels of SOD and GSH in lung tissues increased significantly （P<0.05）， while the level of MDA decreased significantly （P<0.05）. HE staining showed that the bronchial mucosal injury， inflammatory cell infiltration， gland hyperplasia， epithelial degeneration and necrosis were significantly ameliorated in the TCM group than in the stress-related asthma group. The expression of Nrf2 and HO-1 protein in lung tissues also increased significantly （P<0.05）. ConclusionXiaochuanning Granule can regulate the psychological stress state of stress-related asthmatic rats， alleviate airway inflammatory reaction， and suppress oxidation， which is related to its up-regulation of the Nrf2/HO-1 protein expression.

Effect of Baofeikang Granule on Pulmonary Fibrosis in Rats by Regulating Wnt/β-catenin Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the intervention effect of Baofeikang granule （BFK） on the rat model of pulmonary fibrosis through the Wnt/β-catenin signaling pathway. MethodAfter adaptive feeding for one week， 50 healthy rats were randomly divided into a blank group （n=8） and an experimental group （n=42）. After anesthesia， the rats in the experimental group were injected with bleomycin sulfate solution （5 mg·kg-1） into the trachea for the induction of the pulmonary fibrosis model. Those in the blank group were injected with the same amount of normal saline under the same manipulation. On the 7th day after modeling， one of the remaining 33 rats alive was randomly removed， and the other 32 model rats were assigned into a model group （n=8）， a prednisone acetate （1.17 mg·kg-1） group （n=8）， a low-dose BFK （13.59 g·kg-1） group （n=8）， and a high-dose BFK （27.18 g·kg-1） group （n=8）. The rats in the groups with drug intervention were treated correspondingly by gavage once per day for 21 days， and those in the blank group and the model group received the same amount of normal saline. The pulmonary compliance and ventilatory function， the scores of pathological changes and fibrosis， the levels of type Ⅰ collagen （Col Ⅰ） in lung tissues and hydroxyproline （HYP） in the serum， and the relative expression of Wnt3a and β-catenin protein in lung tissues were compared. ResultCompared with the blank group， the model group showed reduced pulmonary function indexes， such as forced vital capacity （FVC）， peak expiratory flow （PEF）， the resistance of lung （RL）， and dynamic compliance （Cdyn） （P<0.05， P<0.01）， severely damaged lung tissue morphology， massive formed continuous fibrous foci， increased fibrosis score （P<0.01）， elevated levels of Col Ⅰ in lung tissues and HYP in the serum （P<0.01）， and up-regulated expression of Wnt3a and β-catenin （P<0.01）. FVC， PEF， and Cdyn levels in the prednisone acetate group and the BFK groups were higher than those in the model group （P<0.05， P<0.01）. Pathological changes were improved in the groups with drug intervention， and fibrosis scores were decreased as compared with the model group （P<0.05， P<0.01）. The scores in the BFK groups were lower than that in the prednisone acetate group （P<0.01）. The levels of Col Ⅰ and HYP in the groups with drug intervention were lower than those in the model group （P<0.05， P<0.01）. The level of Col Ⅰ in the prednisone acetate group was higher than that in the high-dose BFK group （P<0.01）. The levels of serum HYP in the BFK groups was lower than that in the prednisone acetate group （P<0.01）. The protein expression of Wnt3a in lung tissues of the high-dose BFK group was lower than that of the model group （P<0.05）. The protein expression of β-catenin in the prednisone acetate group and the BFK groups was lower than that in the model group （P<0.05， P<0.01）， and the expression level in the high-dose BFK group was lower than that in the prednisone acetate group （P<0.01）. ConclusionBFK can relieve bleomycin sulfate-induced pulmonary fibrosis， reduce collagen deposition， improve pulmonary compliance， and enhance pulmonary ventilatory function in rats. One of its mechanisms is presumedly the inhibition of the Wnt/β-catenin signaling pathway.

Establishment of Feedforward Control Model for Dry Granulation of Polysaccharide Components Based on Quality by Design / 中国实验方剂学杂志

ObjectiveA feedforward control model for dry granulation of polysaccharide components was established to guide the adjustment and optimization of critical process parameters （CPPs） in the design space， so as to reduce the impact of fluctuations in raw materials properties on the quality of medicines. MethodTaking Astragali Radix extract powder as the model drug， the design space of dry granulation CPPs was determined by Box-Behnken design. Astragali Radix mixed powder with different powder properties were prepared by mixture design， the variance inflation factor （VIF） was used to diagnose the multicollinearity of the powder properties， and principal component analysis （PCA） was used to extract the characteristic data of the model. Radial basis function neural network （RBFNN） was used to establish a feedforward control model for reflecting the relationship between the powder properties of polysaccharide components， dry granulation CPPs and one-time molding rate. ResultThe design space for dry granulation CPPs of polysaccharide components was 16-35 Hz for feeding speed， 10-23 Hz for roller speed， and 10-46 kg·cm-2 for roller pressure. The established RBFNN feedforward control model had a good predictive effect on the one-time molding rate of dry granulation of polysaccharide components， which could be used to guide the adjustment and optimization of CPPs in the design space， the relative error was 0.38%-6.73%， and the average relative error was 3.42%. ConclusionThe established feedforward control model can well reflect the relationship between the powder properties of the polysaccharide components， the dry granulation CPPs and the one-time molding rate of the granules， which can be used to guide the adjustment and optimization of CPPs in the design space， reduce the impact of material property fluctuation on product quality， and provide ideas for promoting the quality of traditional Chinese medicine from passive control to active control.

Mechanism of Xiaochuanning Granules in Treatment of Bronchial Asthma via PI3K/Akt Signaling Pathway Based on Network Pharmacology and Experimental Verification / 中国实验方剂学杂志

ObjectiveTo explore the underlying molecular mechanism of Xiaochuanning granules in the treatment of bronchial asthma based on the network pharmacology and experimental verification through the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway on ovalbumin （OVA） sensitization-induced bronchial asthma model in rats. MethodThe main active ingredients and targets of Xiaochuanning Granules were screened out from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）. The targets related to bronchial asthma were obtained from five disease databases such as GeneCards and Online Mendelian Inheritance in Man （OMIM）. The common targets were screened out through the Venn diagram. STRING was used to construct the protein-protein interaction （PPI） network of "compound-disease"， and Cytoscape 3.8.0 was used to establish a network of key active ingredients of Xiaochuanning granules and core target genes （"ingredient-gene" network）. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were performed through DAVID. The bronchial asthma model was induced by OVA stimulation in rats. Bronchial and lung tissue inflammation was observed by hematoxylin-eosin （HE） staining， and the enrichment analysis results of the network pharmacology were verified by Western blot. ResultIn this experiment， 232 active ingredients and 4 687 related targets of Xiaochuanning granules were screened out， and 233 common targets of Xiaochuanning granules and bronchial asthma were collected， including eosinophil-derived neurotoxin 1 （EDN1）， cyclic AMP response element-binding protein 1 （CREB1）， cyclin-dependent kinase inhibitor 1A （CDKN1A）， epidermal growth factor receptor （EGFR）， mitogen-activated protein kinase 14 （MAPK14）， and Akt1. KEGG pathway analysis revealed 186 related signaling pathways， indicating that the PI3K/Akt signaling pathway presumedly played a key role in the treatment of bronchial asthma by Xiaochuanning granules. The animal experiment showed that Xiaochuanning granules relieved the airway inflammation and smooth muscle hyperplasia in rats and down-regulated the gene expression of PI3K and Akt as compared with the conditions in the model group （P<0.05）. ConclusionXiaochuanning granules have the characteristics of multi-component， multi-target， and multi-pathway synergistic effect in the treatment of asthma. Xiaochuanning granules may exert anti-inflammatory effects by regulating the expression of genes related to the PI3K/Akt signaling pathway. The present study is expected to provide a theoretical basis for follow-up in-depth research on the complex mechanism of Xiaochuanning granules in the treatment of bronchial asthma.

Expert consensus on early childhood caries management / 国际口腔科学杂志·英文版

Early childhood caries (ECC) is a significant chronic disease of childhood and a rising public health burden worldwide. ECC may cause a higher risk of new caries lesions in both primary and permanent dentition, affecting lifelong oral health. The occurrence of ECC has been closely related to the core microbiome change in the oral cavity, which may be influenced by diet habits, oral health management, fluoride use, and dental manipulations. So, it is essential to improve parental oral health and awareness of health care, to establish a dental home at the early stage of childhood, and make an individualized caries management plan. Dental interventions according to the minimally invasive concept should be carried out to treat dental caries. This expert consensus mainly discusses the etiology of ECC, caries-risk assessment of children, prevention and treatment plan of ECC, aiming to achieve lifelong oral health.

Myricetin inhibits interferon-γ-induced programmed death ligand-1 and indoleamine 2, 3-dioxygenase 1 expression in lung cancer cells / 中国药理学与毒理学杂志

OBJECTIVE Programmed death ligand-1 (PD-L1) and indoleamine 2, 3-dioxygenase 1 (IDO1) are immune checkpoints which can be induced by interferon-γ(IFN-γ) in the tumor microenvironment, leading to immune escape of tumors. Myricetin (MY) is a flavonoid distributed in many edible and medicinal plants. The aim of this study is to clarify the effect and the mechanism of MY on inhibiting IFN-γ-induced PD-L1 and IDO1 in lung cancer cells. METHODS Expressions of PD-L1 and major histocompatibility complex-I (MHC-I) were evaluated by flow cytometry and Western blotting, and the expression of IDO1 was measured by Western blotting. qRT-PCR was used to detect their mRNA levels. The function of T cells was evaluated using a co-culture system consist of lung cancer cells and the Jurkat-PD-1 T cell line that overexpressing PD-1. Molecular docking analysis, Western blotting and immunofluorescence were used for mechanism study. RESULTS MY potently inhibited IFN-γ-induced PD-L1 and IDO1 expression in human lung cancer cells, while didn't show obvious effect on the expression of MHC-I. In addition, MY restored the survival, proliferation, CD69 expression and interleukin-2 (IL-2) secretion of Jurkat-PD-1 T cells suppressed by IFN-γ-treated lung cancer cells in the co-culture system. Mechanistically, IFN-γ up-regulated PD-L1 and IDO1 at the transcriptional level through the JAK-STAT-IRF1 axis, which was targeted and inhibited by MY. CONCLUSION Our research revealed a new insight into the anti-tumor effects of MY which inhibited IFN-γ-induced PD-L1 and IDO1 expression, supporting the potential of MY in anti-tumor immunotherapy.

Neurological Diseases Responding Specifically to Traditional Chinese Medicine / 中国实验方剂学杂志

In recent years， the incidence of neurological diseases has been increasing year by year. To give full play to the advantages of traditional Chinese medicine （TCM） in the treatment of neurological disorders， identify the breakthrough point of integrating TCM with western medicine， and further standardize the clinical diagnosis and treatment of TCM， the China Association of Chinese Medicine organized neurologists in TCM and western medicine to carry out in-depth discussion on the neurological diseases responding specifically to TCM and integrated TCM and western medicine， such as stroke， headache， vertigo， multiple sclerosis， and epilepsy， aiming to formulate a well-recognized and integrated treatment protocol for TCM and western medicine and improve the efficacy of neurological disorders. Furthermore， the treatment suggestions of the corresponding diseases in TCM and western medicine were proposed to provide references for clinical practice and scientific research.

China experts' consensus on preventive and interceptive orthodontic treatments of malocclusions of children / 华西口腔医学杂志

Malocclusion is one of the three most common oral diseases reported by World Health Organization(WHO). In China, its incidence rate is rising. Malocclusion seriously affects the dental and maxillofacial function, facial appearance and growth development of nearly 260 million children in China, and what is more, it affects their physical and mental health development. Malocclusion occurrence is related to genetic and environmental factors. Early treatment of malocclusion can create a good dental and maxillofacial development environment, correct abnormal growth and control the adverse effects of abnormal genetic factors. It can effectively reduce the prevalence of children's malocclusion and enhance their physical and mental health. This is an urgent need from the economic perspective of our society, so it has great practical and social significance. Experts from the project group "standard diagnose and treatment protocols for early orthodontic intervention of malocclusions of children" which initiated by China National Health Institute of Hospital Administration wrote the "China Experts' Consensus on Preventive and Interceptive Orthodontic Treatments of Malocclusions of Children", which aims to guide and popularize the clinical practice, improve the clinical theory and practice level, and accelerate the disciplinary development of early treatment of children's malocclusion in China. The consensus elaborates the harmfulness of malocclusion and the necessity of early treatment, and brings up the principles and fundamental contents. Based on the law of dental and maxillofacial development, this paper puts forward the guiding suggestions of preventive and interceptive treatments in different stages of dental development ranging from fetus to early permanent dentition. It is a systematic project to promote and standardize the early treatment of malocclusion. Through scientific and comprehensive stratified clinical practice and professional training, the clinical system of early treatment of malocclusion in China will eventually be perfected, so as to comprehensively care for children's dental and maxillofacial health, and improve their oral and physical health in China.

Effect of acupuncture on analgesia and sedation in elderly patients with severe pneumonia during invasive mechanical ventilation / 中国针灸

OBJECTIVE@#To observe the analgesic and sedative effects of acupuncture in elderly patients with severe pneumonia during invasive mechanical ventilation.@*METHODS@#A total of 188 elderly patients with severe pneumonia were randomly divided into an observation group and a control group, 94 cases in each group. Both groups were treated with routine nursing and treatment of severe pneumonia such as invasive mechanical ventilation, analgesia and sedation. Based on these, the observation group was treated with acupuncture at Neiguan (PC 6), Hegu (LI 4), Yintang (GV 29) and Baihui (GV 20), twice a day until the mechanical ventilation was offline. The critical care pain observation tool (CPOT) score and Richmond agitation-sedation score (RASS) were observed before treatment and 0.5 h after analgesia and sedation; the average time of reaching the standard, the reaching standard rate of shallow sedation and analgesia within 0.5 h and 72 h as well as the dosage of analgesic and sedative drugs and compilations were compared between the two groups. The mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR) and blood oxygen saturation (SpO@*RESULTS@#At the time point of 0.5 h after treatment, the CPOT and RASS scores in the two groups were lower than those before treatment (@*CONCLUSION@#Acupuncture has analgesic and sedative effect in elderly patients with severe pneumonia during invasive mechanical ventilation, which could reduce the dosage of sedative and analgesic drugs and the occurrence of complications, improve blood oxygen, and has good safety.

Value of lymphocyte subsets in the differential diagnosis of BK virus nephropathy and acute rejection in renal transplantation recipients / 中华器官移植杂志

Objective:To explore the clinical value of peripheral blood lymphocyte subsets in the differential diagnosis of BK virus nephropathy (BKVN) in renal transplantation recipients.Methods:From 2014 to 2018, a total of 172 renal transplant recipients were recruited. Their peripheral blood lymphocyte subsets were detected. According to the pathological puncture results of transplanted kidney, they were divided into acute rejection group (AR, n=68), BKVN group ( n=73) and stable graft function group (STA, n=31). The proportion and absolute number of peripheral blood lymphocyte subsets in each group were measured by flow cytometry and the proportion and absolute count of peripheral blood lymphocyte subsets in each group compared. Results:The proportion and absolute number of CD19 + B cells were markedly lower in BKVN group than those in AR group ( P=0.005, 0.003; 8.5% vs 13.2%, 0.094×10 9/L vs 0.202×10 9/L) and STA group ( P=0.005, 0.003; 8.5% vs 14.8%, 0.094×10 9/L vs 0.198×10 9/L); the proportion of CD3 + CD8 + T cells was significantly higher in BKVN group than that in AR group ( P=0.013; 36.9% vs 31.2%). In addition, no obvious difference existed in the proportion and absolute number of lymphocytes, CD3 + T, CD3 + CD4 + T and CD16 + CD56 + natural killer (NK) among three groups ( P>0.05). No obvious difference existed in the proportion of CD3 + CD4 + / CD3 + CD8 + T cells among three groups ( P>0.05). Conclusions:No difference exists in T cell-related lymphocyte subsets between BKVN and acute rejection recipients. However, the number and proportion of CD19 + B cells decrease markedly in BKVN.

The correlation between different smoking status and serum uric acid in a middle-aged male population / 中华老年医学杂志

Objective:To explore the correlation between different smoking status and serum uric acid(SUA)in a middle-aged male in health check-up population.Methods:In this cross-sectional study, a total of 26701 middle-aged men who underwent health check-up in Taihu Sanatorium of Jiangsu Province from January 2014 to June 2015 were studied.The correlation between smoking status and SUA was analyzed by questionnaires, physical examination and serum biochemical assay.Smoking state was divided into no smoking, a occasional smoking and smoking groups.Results:With the increase of age, there was a downward trend of SUA( F=7.38, P=0.000). Among the three smoking groups, the group with occasional smoking had the highest level of SUA.The smoking group had lower level of SUA than the non-smoking group and occasional smoking group( P=0.000 and 0.005). In the non-smoking group, the fourth quartile of SUA(41.5%)had a higher percentage than that in first quartile of SUA(38.4%)( χ2=12.266, P=0.000). In the smoking group, the fourth quartile of SUA(54.9%)had lower percentage than that in the first quartile of SUA(58.4%)( χ2=7.049, P=0.008). Compared with the non-smoking group, the prevalence of hyperuricemia(HUA)in smoking group was lower( OR=0.872, 95% CI: 0.821~0.927, P=0.000), the prevalence of HUA in occasional smoking group was higher( OR=1.194, 95% CI: 1.013~1.408, P=0.035). Conclusions:As compared with the non-smoking group, the prevalence of HUA is lower in smoking group and is higher in occasional smoking group.