MicroRNA-1246 Inhibits NFATc1 Phosphorylation and Regulates T Helper 17 Cell Activation in the Pathogenesis of Severe Alopecia Areata

Background@#We found microRNA (miR)-1246 to be significantly differentially expressed between severe active alopecia areata (AA) patients and healthy individuals. @*Objective@#To explore the role and mechanism of miR-1246 in severe AA. @*Methods@#Expression of miR-1246, dual-specific tyrosine phosphorylation-regulated kinase 1A (DYRK1A), and nuclear factor of activated T cells 1c (NFATc1) in peripheral CD4+ T cells and in scalp tissues of patients were detected using RT-qPCR, Western blot, and immunohistochemistry assays. Peripheral CD4+ T cells from the AA patients were transfected with lentiviral vectors overexpressing miR-1246. RT-qPCR and Western blot analysis were used to measure mRNA or protein expression of retinoic-acid-receptor-related orphan nuclear receptor gamma (ROR-γt), interleukin (IL)-17, DYRK1A, NFATc1, and phosphorylated NFATc1. Flow cytometry was used to assay the CD4+ IL-17+ cells proportion. ELISA was used to measure cytokine levels. @*Results@#miR-1246 levels decreased and DYRK1A and NFATc1 mRNA levels significantly increased in the peripheral CD4+ T cells and scalp tissues of severe active AA samples.NFATc1 protein expression was also significantly increased in the peripheral CD4+ T cells but not in the scalp tissues. NFATc1 positive cells were mainly distributed among infiltrating inflammatory cells around hair follicles. In peripheral CD4+ T cells of severe active AA, overexpression of miR-1246 resulted in significant downregulation of DYRK1A, NFATc1, ROR-γt, and IL-17 mRNA and phosphorylated NFATc1 protein, as well as a decrease in the CD4+ IL-17+ cells proportion and the IL-17F level. @*Conclusion@#miR-1246 can inhibit NFAT signaling and Th17 cell activation, which may be beneficial in the severe AA treatment.

The status and trend of child growth failure (CGF) burden in children aged < 5 years in China / 公共卫生与预防医学

Objective To analyze the status and trend for the mortality and DALY rates of child growth failure (CGF) in children aged < 5 years in China from 1990 to 2019, so as to provide a scientific basis for CGF prevention and control. Methods The mortality and DALY rates of CGF in children aged < 5 years from 1990 to 2019 were obtained from GBD 2019. The changes of these indicators with the years in China , the United States, Japan, Russia, India and the global were compared and analyzed. Results In 2019, the mortality of child wasting, child stunting and child underweight in children aged < 5 years in China were 9.62/100 000, 1.23/100 000, and 1.29/100 000 respectively, the mortality rates were 867.50/100 000 , 129.23/100 000 , and 112.87/100 000 rescpectively, higher than those of the United States, Japan, and Russia, and far lower than those of India and the global. The disease burden of three types of CGF were all higher in males than females, and higher in children aged < 1 years than children aged 1-4 years. From 1990 to 2019, the mortality and DALY rates of CGF in children aged < 5 years in China decreased from 300.41/100 000 and 26 445.38/100 000 to 10.49/100 000 and 943.57/100 000, respectively. China had the largest drop rate compared with all analyzed countries. As for children aged < 5 years in China, the DALY rate of lower respiratory infection ranked first in all the diseases caused by CGF. Conclusion From 1990 to 2019, the disease burden of CGF in children aged < 5 years has shown a significant decrease in China , but it is still far behind the developed countries. In the future, more attention should be paid to the problems of child growth in hope of reducing the mortality and DALY rates of CGF.

A case of dimethylformamide poisoning caused by skin contact / 中华劳动卫生职业病杂志

In this paper, the clinical data of a case of accidental poisoning of dimethylformamide in a traffic accident was analyzed. The patient was trapped in the driving room, his limbs were soaked in dimethylformamide for a long time, and dimethylformamide was inhaled at the same time. After 4 days of treatment in a local hospital, he was transferred to the Department of Poisoning & Occupational Diseases, Emergency Medicine of Qilu Hospital of Shandong University for treatment. The main clinical manifestation of the patient was liver damage and intractable abdominal pain, which was cured by active treatment.

Meta-analysis of Simotang Oral Liquid in treatment of functional dyspepsia in adults / 中国中药杂志

This study was conducted to evaluate the efficacy and safety of Simotang Oral Liquid in the treatment of functional dyspepsia in adults. "Simotang Oral Liquid" "Simotang" "Si Mo Tang" "Si Mo Tang Oral Liquid" were used for retrieval of the relevant papers from CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, Springer Link, and Web of Science from database inception to June 2021. Randomized controlled trial(RCT) of Simotang Oral Liquid in the treatment of functional dyspepsia in adults was screened out for Meta-analysis which was conducted in RevMan 5.3. A total of 16 RCTs were included. Meta-analysis showed that compared with the control group, Simotang Oral Liquid increased the total response rate and lowered the traditional Chinese medicine syndrome scores, serum cholecystokinin(CCK), serum nitric oxide(NO), and incidence of adverse reactions. However, the serum substance P(SP) had no statistical difference between the two groups. Simotang Oral Liquid is effective and safe in the treatment of functional dyspepsia in adults. However, this study has evidence and limitations, so the conclusions need to be further verified by large sample and multicenter clinical studies.

Global Burden of Cardiovascular Disease Attributable to High Temperature in 204 Countries and Territories from 1990 to 2019 / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to estimate spatiotemporal variations of global heat-related cardiovascular disease (CVD) burden from 1990 to 2019.@*METHODS@#Data on the burden of heat-related CVD were derived from the Global Burden of Disease Study 2019. Deaths and disability-adjusted life years (DALYs) were used to quantify heat-induced CVD burden. We calculated the age-standardized mortality rate (ASMR) and DALY rate (ASDR) per 100,000 population to compare this burden across regions. Generalized linear models were applied to evaluate estimated annual percentage changes (EAPC) for temporal trends from 1990 to 2019. The correlation between the socio-demographic index (SDI) and age-standardized rate was measured using the Spearman rank test.@*RESULTS@#Heat-induced CVD caused approximately 90 thousand deaths worldwide in 2019. Global ASMR and ASDR of heat-related CVD in 2019 were 1.17 [95% confidence interval ( CI): 0.13-1.98] and 25.59 (95% CI: 2.07-44.17) per 100,000 population, respectively. The burden was significantly increased in middle and low-SDI regions and slightly decreased in high-SDI regions from 1990 to 2019. ASMR showed an upward trend, with the most considerable increase in low-latitude countries. We observed a negative correlation between SDI and EAPC in ASMR ( r s = -0.57, P < 0.01) and ASDR ( r s = -0.59, P < 0.01) among 204 countries.@*CONCLUSION@#Heat-attributable CVD burden substantially increased in most developing countries and tropical regions.

IL-6 promotes pluripotency of mouse embryonic stem cells and regulates cardiac differentiation in a development-dependent manner / 生理学报

Interleukin 6 (IL-6), an important component of cardiac microenvironment, favors cardiac repair by improving cardiomyocyte regeneration in different models. This study aimed to investigate the effects of IL-6 on stemness maintenances and cardiac differentiation of mouse embryonic stem cells (mESCs). The mESCs were treated with IL-6 for two days, and then subjected to CCK-8 essay for proliferation analysis and quantitative real-time PCR (qPCR) to evaluate the mRNA expression of genes related to stemness and germinal layers differentiation. Phosphorylation levels of stem cell-related signal pathways were detected by Western blot. siRNA was used to interfere the function of STAT3 phosphorylation. Cardiac differentiation was investigated by the percentage of beating embryoid bodies (EBs) and qPCR analysis of cardiac progenitor markers and cardiac ion channels. IL-6 neutralization antibody was applied to block the endogenous IL-6 effects since the onset of cardiac differentiation (embryonic day of 0, EB0). The EBs were collected on EB7, EB10 and EB15 to investigate the cardiac differentiation by qPCR. On EB15, Western blot was applied to investigate the phosphorylation of several signaling pathways, and immunochemistry staining was adopted to trace the cardiomyocytes. IL-6 antibody was administered for two days (short term) on EB4, EB7, EB10 or EB15, and percentages of beating EBs at late developmental stage were recorded. The results showed that exogenous IL-6 promoted mESCs proliferation and favored maintenances of pluripotency, evidenced by up-regulated mRNA expression of oncogenes (c-fos, c-jun) and stemness markers (oct4, nanog), down-regulated mRNA expression of germ layer genes (branchyury, FLK-1, pecam, ncam, sox17), and increased phosphorylation of ERK1/2 and STAT3. siRNA targeting JAK/STAT3 partially attenuated the effects of IL-6 on cell proliferation and mRNA expression of c-fos and c-jun. During differentiation, long term IL-6 neutralization antibody application decreased the percentage of beating EBs, down-regulated mRNA expression of ISL1, GATA4, α-MHC, cTnT, kir2.1, cav1.2, and declined the fluorescence intensity of cardiac α actinin in EBs and single cell. Long term IL-6 antibody treatment decreased the phosphorylation of STAT3. In addition, short term (2 d) IL-6 antibody treatment starting from EB4 significantly reduced the percentage of beating EBs in late development stage, while short term IL-6 antibody treatment starting from EB10 significantly increased the percentage of beating EBs on EB16. These results suggest that exogenous IL-6 promotes mESCs proliferation and favors stemness maintenance. Endogenous IL-6 regulates mESC cardiac differentiation in a development-dependent manner. These findings provide important basis for the study of microenvironment on cell replacement therapy, as well as a new perspective for understanding the pathophysiology of heart diseases.

The expression and function of PD-L1 in CD133(+) human liver cancer stem-like cells / 中华肿瘤杂志

Objective: To investigate the expression of programmed death protein-ligand 1 (PD-L1) in liver cancer stem-like cells (LCSLC) and its effect on the characteristics of tumor stem cells and tumor biological function, to explore the upstream signaling pathway regulating PD-L1 expression in LCSLC and the downstream molecular mechanism of PD-L1 regulating stem cell characteristics, also tumor biological functions. Methods: HepG2 was cultured by sphere-formating method to obtain LCSLC. The expressions of CD133 and other stemness markers were detected by flow cytometry, western blot and real-time quantitative polymerase chain reaction (RT-qPCR) were used to detect the expressions of stemness markers and PD-L1. The biological functions of the LCSLC were tested by cell function assays, to confirm that the LCSLC has the characteristics of tumor stem cells. LCSLC was treated with cell signaling pathway inhibitors to identify relevant upstream signaling pathways mediating PD-L1 expression changes. The expression of PD-L1 in LCSLC was down regulated by small interfering RNA (siRNA), the expression of stem cell markers, tumor biological functions of LCSLC, and the changes of cell signaling pathways were detected. Results: Compared with HepG2 cells, the expression rate of CD133 in LCSLC was upregulated [(92.78±6.91)% and (1.40±1.77)%, P<0.001], the expressions of CD133, Nanog, Oct4A and Snail in LCSLC were also higher than those in HepG2 cells (P<0.05), the number of sphere-formating cells increased on day 7 [(395.30±54.05) and (124.70±19.30), P=0.001], cell migration rate increased [(35.41±6.78)% and (10.89±4.34)%, P=0.006], the number of transmembrane cells increased [(75.77±10.85) and (20.00±7.94), P=0.002], the number of cloned cells increased [(120.00±29.51) and (62.67±16.77), P=0.043]. Cell cycle experiments showed that LCSLC had significantly more cells in the G(0)/G(1) phase than those in HepG2 [(54.89±3.27) and (32.36±1.50), P<0.001]. The tumor formation experiment of mice showed that the weight of transplanted tumor in LCSLC group was (1.32±0.17)g, the volume is (1 779.0±200.2) mm(3), were higher than those of HepG2 cell [(0.31±0.06)g and (645.6±154.9)mm(3), P<0.001]. The expression level of PD-L1 protein in LCSLC was 1.88±0.52 and mRNA expression level was 2.53±0.62, both of which were higher than those of HepG2 cells (P<0.05). The expression levels of phosphorylation signal transduction and transcription activation factor 3 (p-STAT3) and p-Akt in LCSLC were higher than those in HepG2 cells (P<0.05). After the expression of p-STAT3 and p-Akt was down-regulated by inhibitor treatment, the expression of PD-L1 was also down-regulated (P<0.05). In contrast, the expression level of phosphorylated extracellular signal-regulated protein kinase 1/2 (p-ERK1/2) in LCSLC was lower than that in HepG2 cells (P<0.01), there was no significant change in PD-L1 expression after down-regulated by inhibitor treatment (P>0.05). After the expression of PD-L1 was knockdown by siRNA, the expressions of CD133, Nanog, Oct4A and Snail in LCSLC were decreased compared with those of siRNA-negative control (NC) group (P<0.05). The number of sphere-formating cells decreased [(45.33±12.01) and (282.00±29.21), P<0.001], the cell migration rate was lower than that in siRNA-NC group [(20.86±2.74)% and (46.73±15.43)%, P=0.046], the number of transmembrane cells decreased [(39.67±1.53) and (102.70±11.59), P=0.001], the number of cloned cells decreased [(57.67±14.57) and (120.70±15.04), P=0.007], the number of cells in G(0)/G(1) phase decreased [(37.68±2.51) and (57.27±0.92), P<0.001], the number of cells in S phase was more than that in siRNA-NC group [(30.78±0.52) and (15.52±0.83), P<0.001]. Tumor formation in mice showed that the tumor weight of shRNA-PD-L1 group was (0.47±0.12)g, the volume is (761.3±221.4)mm(3), were lower than those of shRNA-NC group [(1.57±0.45)g and (1 829.0±218.3)mm(3), P<0.001]. Meanwhile, the expression levels of p-STAT3 and p-Akt in siRNA-PD-L1 group were decreased (P<0.05), while the expression levels of p-ERK1/2 and β-catenin did not change significantly (P>0.05). Conclusion: Elevated PD-L1 expression in CD133(+) LCSLC is crucial to maintain stemness and promotes the tumor biological function of LCSLC.

Amygdalin Ameliorates Liver Fibrosis through Inhibiting Activation of TGF-β/Smad Signaling / 中国结合医学杂志

OBJECTIVE@#To observe the effect of amygdalin on liver fibrosis in a liver fibrosis mouse model, and the underlying mechanisms were partly dissected in vivo and in vitro.@*METHODS@#Thirty-two male mice were randomly divided into 4 groups, including control, model, low- and high-dose amygdalin-treated groups, 8 mice in each group. Except the control group, mice in the other groups were injected intraperitoneally with 10% carbon tetrachloride (CCl4)-olive oil solution 3 times a week for 6 weeks to induce liver fibrosis. At the first 3 weeks, amygdalin (1.35 and 2.7 mg/kg body weight) were administered by gavage once a day. Mice in the control group received equal quantities of subcutaneous olive oil and intragastric water from the fourth week. At the end of 6 weeks, liver tissue samples were harvested to detect the content of hydroxyproline (Hyp). Hematoxylin and eosin and Sirius red staining were used to observe the inflammation and fibrosis of liver tissue. The expressions of collagen I (Col-I), alpha-smooth muscle actin (α-SMA), CD31 and transforming growth factor β (TGF-β)/Smad signaling pathway were observed by immunohistochemistry, quantitative real-time polymerase chain reaction and Western blot, respectively. The activation models of hepatic stellate cells, JS-1 and LX-2 cells induced by TGF-β1 were used in vitro with or without different concentrations of amygdalin (0.1, 1, 10 µmol/L). LSECs. The effect of different concentrations of amygdalin on the expressions of liver sinusoidal endothelial cells (LSECs) dedifferentiation markers CD31 and CD44 were observed.@*RESULTS@#High-dose of amygdalin significantly reduced the Hyp content and percentage of collagen positive area, and decreased the mRNA and protein expressions of Col-I, α-SMA, CD31 and p-Smad2/3 in liver tissues of mice compared to the model group (P<0.01). Amygdalin down-regulated the expressions of Col-I and α-SMA in JS-1 and LX-2 cells, and TGFβ R1, TGFβ R2 and p-Smad2/3 in LX-2 cells compared to the model group (P<0.05 or P<0.01). Moreover, 1 and 10 µmol/L amygdalin inhibited the mRNA and protein expressions of CD31 in LSECs and increased CD44 expression compared to the model group (P<0.05 or P<0.01).@*CONCLUSIONS@#Amygdalin can dramatically alleviate liver fibrosis induced by CCl4 in mice and inhibit TGF-β/Smad signaling pathway, consequently suppressing HSCs activation and LSECs dedifferentiation to improve angiogenesis.

Anti-glioma mechanism of pterostilbene by regulating apoptosis and GSDME-mediated pyroptosis pathways: a study based on network pharmacology and experimental research / 中国中药杂志

This study aimed to explore the anti-glioma effect of natural compound pterostilbene(PTE) through regulating pyroptosis and apoptosis pathways, and to analyze the possible anti-glioma pathways and targets of PTE by network pharmacology and molecular docking. In this study, the action targets of PTE and the glioma targets were obtained by network pharmacology to construct a target network and a protein-protein interaction(PPI) network to predict the possible action targets of PTE against glioma. Molecular docking was performed on the core targets by AutoDock and the action pathways of PTE against glioma were predicted by enrichment analysis. In addition, the effect of PTE on the viability of U87MG and GL261 glioma cells was detected by CCK-8 assay. Clone formation assay and cell scratching assay were used to explore the effect of different concentrations of PTE on the proliferation and migration, respectively of glioma cells. Hoechst staining was used to observe PTE-induced apoptosis in glioma cells. The changes in mitochondrial membrane potential were detected by JC-1 staining. The pyroptosis-inducing effect of PTE on glioma cells was observed by inverted microscopy and lactate dehydrogenase(LDH) assay. Hoechst 33342/PI dual staining assay was performed to detect the integrity of glioma cell membranes. The expressions of pyroptosis and apoptosis-related proteins in glioma cells after PTE induction were determined by Western blot. In this study, 37 anti-glioma targets of PTE were obtained, and enrichment analysis suggested that PTE exerted anti-glioma effects through various signaling pathways including cancer pathway, proteoglycan in cancer, PI3K/AKT pathway, and apoptosis regulatory pathway. Molecular docking revealed that PTE had good binding activity with the main targets. Compared with the control group, PTE significantly reduced the viability as well as the proliferation, migration and adhesion abilities of U87MG and GL261 cells; it induced the apoptosis of the two glioma cells and the decrease of mitochondrial membrane potential in U87MG cells, and the effects increased with the increase of drug concentration. Compared with the conditions in the control group, glioma cells in the PTE group had increased pyroptosis-specific appearance and gradually increased LDH release; the number of PI positive cells was significantly elevated with the increase of PTE concentration as revealed by Hoechst 33342/PI staining; the expression levels of apoptosis-related factors cleaved PARP1 and B-cell lymphoma-2(Bcl-2) associated X(BAX) in the PTE group were markedly up-regulated, while the expression level of Bcl-2 was markedly down-regulated; the activation levels of pyroptosis-related proteins cleaved caspase-3 and gasdermin E-N(GSDME-N) had a remarkable rise in the PTE group, while no significant changes were found in the activation levels of gasdermin D-N(GSDMD-N) and cleaved caspase-1. In summary, PTE plays an anti-glioma role by inhibiting cell viability, proliferation, and migration and activating the caspase-3/GSDME-mediated pyroptosis pathway and mitochondrial apoptosis pathway.

Associação entre Nível de Big Endotelina-1 Plasmática e a Gravidade da Doença Arterial Coronariana em Pacientes com Infarto do Miocárdio sem Supradesnivelamento do Segmento ST / Association between Plasma Big Endothelin-1 Level and The Severity of Coronary Artery Disease in Patients with Non-ST Segment-Elevated Myocardial Infarction

Resumo Fundamento A estratificação de risco precoce com biomarcadores simples é essencial em pacientes com infarto do miocárdio sem supradesnivelamento do segmento ST (IAMSSST). Objetivo Este estudo tem o objetivo de avaliar a associação entre nível de big endotelina-1 plasmática (ET-1) e o escore SYNTAX (SS) em pacientes com IAMSSST. Métodos Foram recrutados 766 pacientes com IAMSSST que passaram por angiografia coronária. Os pacientes foram divididos em três grupos: SS baixo (≤22), SS intermediário (23-32), e SS alto (>32). A correlação de Spearman, o ajuste de curva suave, a regressão logística, e a análise de curva característica de operação do receptor (ROC) foram realizados para avaliar a associação entre o nível de big ET-1 plasmática e o SS. Um p-valor <0.05 foi considerado estatisticamente significativo. Resultados Foi identificada uma correlação significativa entre a big ET-1 e o SS (r=0,378, p<0,001). A curva suavizada indicou uma correlação positiva entre o nível de big ET-1 plasmática e o SS. A análise de curva ROC demonstrou que a área sob a curva foi de 0,695 (0,661-0,727) e o ponto de corte ideal do nível de big ET-1 plasmática foi de 0,35 pmol/l. A regressão logística demonstrou que a big ET-1 elevada era um preditor independente de SS intermediário a alto em pacientes com IAMSSST, seja como variável contínua [RC (IC 95%: 1,110 (1,053-1,170), p<0,001] ou como variável categórica [RC (IC 95%: 2,962 (2,073-4,233), p<0,001]. Conclusão Em pacientes com IAMSSST, o nível de big ET-1 plasmática estava significativamente correlacionado ao SS. O nível de big ET-1 plasmática elevado foi um preditor independente para SS intermediário a alto.

Abstract Background Early risk stratification with simple biomarkers is essential in patients with non-ST segment-elevation myocardial infarction (NSTEMI). Objective This study aimed to evaluate the association between plasma big endothelin-1 (ET-1) level and the SYNTAX score (SS) in patients with NSTEMI. Methods A total of 766 patients with NSTEMI undergoing coronary angiography were recruited. Patients were divided into three groups: low SS (≤22), intermediate SS (23-32), and high SS (>32). Spearman correlation, smooth curve fitting, logistic regression, and receiver operating characteristic (ROC) curve analysis were performed to evaluate the association between plasma big ET-1 level and the SS. A p-value <0.05 was considered statistically significant. Results There was a significant correlation between the big ET-1 and the SS (r=0.378, p<0.001). The smoothing curve indicated a positive correlation between the plasma big ET-1 level and the SS. The ROC curve analysis showed that the area under the curve was 0.695 (0.661-0.727) and the optimal cutoff of plasma big ET-1 level was 0.35pmol/l. Logistic regression showed that elevated big ET-1 was an independent predictor of intermediate-high SS in patients with NSTEMI, whether entered as a continuous variable [OR (95% CI): 1.110 (1.053-1.170), p<0.001] or as a categorical variable [OR (95% CI): 2.962 (2.073-4.233), p<0.001]. Conclusion In patients with NSTEMI, the plasma big ET-1 level was significantly correlated with the SS. Elevated plasma big ET-1 level was an independent predictor for intermediate-high SS.

A new flavonoid glycoside from Epimedium sagittatum / 药学学报

Fourteen flavonoids were isolated and purified from Epimedium sagittatum by various chromatography techniques such as macroporous adsorbent resin, silica gel, ODS, Sephadex LH-20, HW-40C and semi-preparative HPLC. Their structures were identified by analysis of physicochemical properties and spectral data, and determined as 3′-hydroxy-baohuoside-Ⅱ (1), huazhongilexone-7-O-β-D-glucopyranoside (2), kaempferol-3-O-α-L-rhamnoside (3), baohuoside-Ⅱ (4), icariside-Ⅱ (5), kaempferol 3,7-di-O-α-L-rhamnopyranoside (6), (+)-aromadendrin (7), kaempferol 3-O-(2-O-β-D-apiofuranosyl)-α-L-rhamnopyranoside (8), sagittatoside A (9), 2″-O-rhamnosyl icariside-II (10), apigenin-7-O-β-D-glucoside (11), quercetin 3-O-β-D-apiofuranoyl-(1→2)-α-L-rhamnopyranoside (12), kaempferol (13), icariin (14). Among them, compound 1 is a new compound, while compounds 2, 6-8, 11, and 12 were isolated from E.sagittatum for the first time.

Profiles and differences of submucosal microbial in peri-implantitis and health implants: A cross-sectional study / 北京大学学报(医学版)

OBJECTIVE@#To describe the submucosal microbial profiles of peri-implantitis and healthy implants, and to explore bacteria that might be correlated with clinical parameters.@*METHODS@#In the present cross-sectional study, 49 patients were recruited. Each patient contributed with one implant, submucosal biofilms were collected from 20 healthy implants and 29 implants with peri-implantitis. DNA was extracted and bacterial 16S ribosomal RNA (16S rRNA) genes were amplified. Submucosal biofilms were analyzed using 16S rRNA sequencing at Illumina MiSeq platform. Differences between the groups were determined by analyzing α diversity, microbial component and microbial structure. The potential correlation between the bacteria with pocket probing depth (PPD) of peri-implant calculated by Spearman correlation analysis.@*RESULTS@#The α diversity of submucosal microbial of health group was significantly lower than that in peri-implantitis group (Chao1 index: 236.85±66.13 vs. 150.54±57.43, P < 0.001; Shannon index: 3.42±0.48 vs. 3.02±0.65, P=0.032). Principal coordinated analysis showed that the submucosal microbial structure had significant difference between healthy and peri-implantitis groups [R2=0.243, P=0.001, analysis of similarities (ANOSIM)]. Compared with healthy implants, relative abundance of periodontal pathogens were higher in peri-implantitis, including members of the red complex (Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola) and some members of orange complex (Precotella intermedia, Eubacterium nodatum, Parvimonas micra), as well as some new periodontal pathogens, such as Fillifactor alocis, Fretibacterium fastidiosum, Desulfobulbus sp._HMT_041, and Porphyromonas endodontalis. Spearman correlation analysis revealed that the relative abundance of Treponema denticola (r=0.686, P < 0.001), Tannerella forsythia (r=0.675, P < 0.001), Fretibacterium sp. (r=0.671, P < 0.001), Desulfobulbus sp._HMT_041 (r=0.664, P < 0.001), Filifactor alocis (r=0.642, P < 0.001), Fretibacterium fastidiosum (r=0.604, P < 0.001), Porphyromonas gingivalis (r=0.597, P < 0.001), Porphyromonas endodontalis (r=0.573, P < 0.001) were positive correlated with PPD. While the relative abundance of Rothia aeria (r=-0.615, P < 0.001) showed negatively correlation with PPD.@*CONCLUSION@#Marked differences were observed in the microbial profiles of healthy implants and peri-implantitis. The members of red and orange complex as well as some new periodontal pathogens seem to play an important role in peri-implant disease. Compared with healthy implants, the submucosal microbial of peri-implantitis were characterized by high species richness and diversity.

Clinical study of using basement membrane biological products in pelvic floor reconstruction during pelvic exenteration / 中华胃肠外科杂志

Objective: To investigate the value of reconstruction of pelvic floor with biological products to prevent and treat empty pelvic syndrome after pelvic exenteration (PE) for locally advanced or recurrent rectal cancer. Methods: This was a descriptive study of data of 56 patients with locally advanced or locally recurrent rectal cancer without or with limited extra-pelvic metastases who had undergone PE and pelvic floor reconstruction using basement membrane biologic products to separate the abdominal and pelvic cavities in the Department of Anorectal Surgery of the Second Affiliated Hospital of Naval Military Medical University from November 2021 to May 2022. The extent of surgery was divided into two categories: mainly inside the pelvis (41 patients) and including pelvic wall resection (15 patients). In all procedures, basement membrane biologic products were used to reconstruct the pelvic floor and separate the abdominal and pelvic cavities. The procedures included a transperitoneal approach, in which biologic products were used to cover the retroperitoneal defect and the pelvic entrance from the Treitz ligament to the sacral promontory and sutured to the lateral peritoneum, the peritoneal margin of the retained organs in the anterior pelvis, or the pubic arch and pubic symphysis; and a sacrococcygeal approach in which biologic products were used to reconstruct the defect in the pelvic muscle-sacral plane. Variables assessed included patients' baseline information (including sex, age, history of preoperative radiotherapy, recurrence or primary, and extra-pelvic metastases), surgery-related variables (including extent of organ resection, operative time, intraoperative bleeding, and tissue restoration), post-operative recovery (time to recovery of bowel function and time to recovery from empty pelvic syndrome), complications, and findings on follow-up. Postoperative complications were graded using the Clavien-Dindo classification. Results: The median age of the 41 patients whose surgery was mainly inside the pelvis was 57 (31-82) years. The patients comprised 25 men and 16 women. Of these 41 patients, 23 had locally advanced disease and 18 had locally recurrent disease; 32 had a history of chemotherapy/immunotherapy/targeted therapy and 24 of radiation therapy. Among these patients, the median operative time, median intraoperative bleeding, median time to recovery of bowel function, and median time to resolution of empty pelvic syndrome were 440 (240-1020) minutes, 650 (200-4000) ml, 3 (1-9) days, and 14 (5-105) days, respectively. As for postoperative complications, 37 patients had Clavien-Dindo < grade III and four had ≥ grade III complications. One patient died of multiple organ failure 7 days after surgery, two underwent second surgeries because of massive bleeding from their pelvic floor wounds, and one was successfully resuscitated from respiratory failure. In contrast, the median age of the 15 patients whose procedure included combined pelvic and pelvic wall resection was 61 (43-76) years, they comprised eight men and seven women, four had locally advanced disease and 11 had locally recurrent disease. All had a history of chemotherapy/ immunotherapy and 13 had a history of radiation therapy. The median operative time, median intraoperative bleeding, median time to recovery of bowel function, and median time to relief of empty pelvic syndrome were 600 (360-960) minutes, 1600 (400-4000) ml, 3 (2-7) days, and 68 (7-120) days, respectively, in this subgroup of patients. Twelve of these patients had Clavien-Dindo < grade III and three had ≥ grade III postoperative complications. Follow-up was until 31 October 2022 or death; the median follow-up time was 9 (5-12) months. One patient in this group died 3 months after surgery because of rapid tumor progression. The remaining 54 patients have survived to date and no local recurrences have been detected at the surgical site. Conclusion: The use of basement membrane biologic products for pelvic floor reconstruction and separation of the abdominal and pelvic cavities during PE for locally advanced or recurrent rectal cancer is safe, effective, and feasible. It improves the perioperative safety of PE and warrants more implementation.

Efficacy and safety of using DAAs to treatment the special populations with chronic hepatitis C / 中国热带医学

@#Abstract:Chronic hepatitis C (CHC) is a global health problem, which is prevalent all over the world. China is a low epidemic area. Hepatitis C virus (HCV) is mainly transmitted through blood, and nowadays, intravenous drug addicts are the key population for the prevention and treatment of hepatitis C. HCV has multiple genotypes and gene subtypes, and the distribution of these genotypes and gene subtypes varies significantly among the regions of the world. Nowadays, the treatment of hepatitis C has entered the era of direct-acting antiviral agents, which have high efficacy and safety in the general population. However, when special populations use direct-acting antiviral agents to treatment hepatitis C, we don't know how its efficacy and safety will be. The special populations include children, adolescents, drug users, HCV/HBV co-infected patients, HCV/HIV co-infected patients, and patients who have comorbidity of HCV and chronic kidney disease. This review will discuss the efficacy and safety of using direct-acting antiviral agents to treat hepatitis C in these special populations.

An excerpt of Society for Maternal-Fetal Medicine Consult Series #56: Hepatitis C in pregnancy—updated guidelines: Replaces Consult Number 43, November 2017 / 中国热带医学

@#Abstract: In the United States, it is estimated that 1% to 4% of pregnant women are infected with hepatitis C virus （HCV）, which carries approximately a 5% risk of transmission from mother to infant. Hepatitis C virus can be transmitted to the infant in utero or during the peripartum period, and infection during pregnancy is associated with an increased risk of adverse fetal outcomes, including fetal growth restriction and low birthweight. The purpose of an excerpt of Society for Maternal-Fetal Medicine Consult Series #56: Hepatitis C in pregnancy—updated guidelines: Replaces Consult Number 43, November 2017 is to discuss the current evidence, provide updated recommendations regarding screening, review treatment, and address management of hepatitis C virus during pregnancy.

Andrographolide Inhibits Proliferation and Promotes Apoptosis in Bladder Cancer Cells by Interfering with NF- κ B and PI3K/AKT Signaling In Vitro and In Vivo / 中国结合医学杂志

OBJECTIVE@#To explore the influences of andrographolide (Andro) on bladder cancer cell lines and a tumor xenograft mouse model bearing 5637 cells.@*METHODS@#For in vitro experiments, T24 cells were stimulated with Andro (0-40 µmol/L) and 5637 cells were stimulated with Andro (0 to 80 µmol/L). Cell growth, migration, and infiltration were assessed using cell counting kit-8, colony formation, wound healing, and transwell assays. Apoptosis rate was examined using flow cytometry. In in vivo study, the antitumor effect of Andro (10 mg/kg) was evaluated by 5637 tumor-bearing mice, and levels of nuclear factor κ B (NF- κ B) and phosphoinositide 3-kinase/AKT related-proteins were determined by immunoblotting.@*RESULTS@#Andro suppressed growth, migration, and infiltraion of bladder cancer cells (P⩽0.05 or P⩽0.01). Additionally, Andro induced intrinsic mitochondria-dependent apoptosis in bladder cancer cell lines. Furthermore, Andro inhibited bladder cancer growth in mice (P⩽0.01). The expression of p65, p-AKT were suppressed by Andro treatment in vitro and in vivo (P⩽0.05 or P⩽0.01).@*CONCLUSIONS@#Andrographolide inhibits proliferation and promotes apoptosis in bladder cancer cells by interfering with NF- κ B and PI3K/AKT signaling in vitro and in vivo.

Preliminary study on the existing problems in health economic evaluation study of acupuncture in China / 中国针灸

The literature of health economic evaluation study in the field of acupuncture in China was systematically summarized and analyzed, and the existing problems in the current research were discussed from the aspects of research perspective, cost calculation scope, data analysis method selection. Moreover, the key points of the health economic evaluation research were summarized, and the research objectives, the relationship between the expected research results and data analysis methods and the process of thinking were sorted out, and several suggestions for research report writing were proposed, aiming to provide a reference for the quality improvement of the acupuncture health economic evaluation research in China.

WU Lian-zhong's experience in treating spasmodic torticollis by Kaiqiao Shunjin method / 中国针灸

Professor WU Lian-zhong's experience in treating spasmodic torticollis by Kaiqiao Shunjin method (resuscitation and regulating muscle) is summarized in this paper. The pathogenesis of spasmodic torticollis is the occluded brain orifices and delirium, qi disorder of meridian tendons, specifically divided into five categories: damp-heat, liver-yang hyperactivity, liver-kidney yin deficiency, deficiency of the governor vessel, excess of the governor vessel. The treatment should be based on the symptoms and the root causes, the symptoms should be the main treatment, and the root cause should be treated based on syndrome differentiation. The main treatment is Kaiqiao Shunjin method (resuscitation and regulating muscle), and to take the chief (five heart acupoints-Shuigou [GV 26], Laogong [PC 8], Yongquan [KI 1]), deputy (Yintang [GV 24+], Shangxing [GV 23] through Baihui [GV 20], Ximen [PC 4]), assistant (Fenglong [ST 40], Lianquan [CV 23], combined with tongue needle prick), envoy (Hanyan [GB 4]) as the basic main acupoints, at the same time cooperate with local acupoints to remove knots and accumulation. Finally, syndrome differentiation is adopted to dredge meridians and disperse knots, regulate the governor vessel, and nourish yin and dispel wind.

Efficacy of combined application of glycine powder air-polishing in non-surgical treatment of peri-implant diseases / 北京大学学报(医学版)

OBJECTIVE@#To compare the clinical efficacy of combined application of glycine powder air-polishing and mechanical submucosal debridement in non-surgical treatment of peri-implant diseases.@*METHODS@#A randomized controlled clinical study was carried out on patients diagnosed with peri-implant diseases in the Department of Periodontology, Peking University School and Hospital of Stomatology, between May of 2020 and June of 2021.Twenty-eight patients with totally sixty-two implants were enrolled.The patients were randomly divided into the test group and control group. The patients in the test group (13 subjects/32 implants) received mechanical submucosal debridement using titanium curettes combined with application of glycine powder air-polishing, while the control group (15 subjects/30 implants) received mechanical submucosal debridement using titanium only. Clinical parameters, such as plaque index (PLI), pocket probing depth (PPD), bleeding index (BI) and the percentage of suppuration on probing on implants' level (SoP%) were measured at baseline and 8 weeks after non-surgical intervention. Changes and group differences of clinical parameters of the implants before and 8 weeks after non-surgical intervention were compared.@*RESULTS@#Mean PLI, PPD, BI of both the test group and control group significantly reduced 8 weeks after non-surgical intervention (P < 0.05). Compared with the control group, the test group achieved lower BI (2.7±0.8 vs. 2.2±0.7, P < 0.05), more reduction of BI (0.6±0.7 vs. 1.1±0.6, P < 0.01) and more reduction of SoP% (21.9% vs. 10%, P < 0.05) after non-surgical intervention. Both the control and test groups exhibited comparable PLI and PPD reductions (P>0.05). For the implants diagnosed with peri-implant mucositis, the test group revealed more signi-ficant reduction in BI and SoP% than the control group (1.0±0.7 vs. 0.4±0.7, P=0.02; 6.3% vs. 0, P=0.012). There was no significant difference existing in PLI and PD improvement between the control group and test group (P>0.05). For the implants diagnosed with peri-implantitis, there was no significant difference existing in PLI, PPD, BI and SoP% improvement values between the test and control groups (P>0.05). No complications or discomforts were reported during the study.@*CONCLUSION@#Both treatment procedures could relieve the inflammation of peri-implant soft tissue. Non-surgical mechanical submucosal debridement combined application of glycine powder air-polishing is associated with significant reduction of soft tissue bleeding and suppuration on probing especially in the implants diagnosed with peri-implant mucositis.