The Development of Chinese Herbal Formulae for Non-severe COVID-19 Based on Artificial Intelligence Technology and Investigation of Its Action Mechanisms / 中医杂志

ObjectiveTo develop traditional Chinese medicine （TCM） formulae for the treatment of nonsevere coronavirus disease 2019 （COVID-19） and to explore its anti-inflammatory mechanism. MethodsThe dysregulated signaling pathways were determined in macrophages from bronchoalveolar lavage fluid of COVID-19 patients and in lung epithelial cells infected with SARS-CoV-2 in vitro based on transcriptome analysis. A total of 102 TCM formulae for the clinical treatment of nonsevere COVID-19 were collected through literature. The pathway-reversing rates of these formulae in macrophages and lung epithelial cells were evaluated based on signature signaling pathways， and the basic formula was determined in conjunction with TCM theory. The commonly used Chinese materia medica for nonsevere COVID-19 were summarized from the 102 TCM formulae as abovementioned. And together with the screening results from the Pharmacopoeia of the People's Republic of China， a “Chinese materia medica pool” was esta-blished for the development of TCM formulae for COVID-19. The regulatory effects of each herb on signaling pathways were obtained based on targeted transcriptome analysis. Oriented at reversing dysregulated signaling pathways of COVID-19， the calculation was carried out， and the artificial intelligent methods for compositing formulae， that are exhaustive method and parallel computing， were used to obtain candidate compound formulas. Finally， with reference to professional experience， an innovative formula for the treatment of nonsevere COVID-19 was developed. The ethanol extract of the formula was evaluated for its anti-inflammatory effects by detecting the mRNA expression of interleukin 1b （Il1b）， C-X-C motif chemokine ligand 2 （Cxcl2）， C-X-C motif chemokine ligand 10 （Cxcl10）， C-C motif chemokine ligand 2 （Ccl2）， nitric oxide synthase 2 （Nos2）， and prostaglandin-endoperoxide synthase 2 （Ptgs2） using reverse transcription-quantitative polymerase chain reaction （RT-qPCR） in RAW264.7 cells treated with lipopolysaccharide （LPS）. ResultsIn macrophages and lung epithelial cells， 34 dysregulated signaling pathways associated with COVID-19 were identified respectively. The effects of the 102 formulae for clinical treatment of nonsevere COVID-19 were evaluated based on the dysregulated signaling pathways and targeted transcriptome， and the result showed that Yinqiao Powder and Pingwei Powder （银翘散合平胃散， YQPWP） ranked first， reversing 91.18% of the dysregulated signaling pathways in macrophages and 100% of the dysregulated signaling pathways in lung epithelial cells. Additionally， YQPWP had the function of scattering wind and clearing heat， resolving toxins and removing dampness in accordance with the pathogenesis of wind-heat with dampness in COVID-19. It was selected as the basic formula， and was further modified and optimized to develop an innovative fomula Qiaobang Zhupi Yin （翘蒡术皮饮， QBZPY） based on expert experience and artificial intelligence in composing formulae. QBZPY can reverse all the dysregulated signaling pathways associated with COVID-19 in macrophages and lung epithelial cells， with the reversing rates of 100%. The chief medicinal of QBZPY， including Lianqiao （Fructus Forsythiae）， Xixiancao （Herba Siegesbeckiae） and Niubangzi （Fructus Arctii）， can down-regulate multiple signaling pathways related with virus infection， immune response， and epithelial damage. RT-qPCR results indicated that compared with the model group， the QBZPY group down-regulated the mRNA expression of Il1b， tumor necrosis factor （Tnf）， Cxcl2， Cxcl10， Ccl2， Nos2 and Ptgs2 induced by LPS in RAW264.7 cells （P＜0.05 or P＜0.01）. ConclusionBased on targeted transcriptome analysis， expert experience in TCM and artificial intelligence， QBZPY has been developed for the treatment of nonsevere COVID-19. The ethanol extract of QBZPY has been found to inhibit mRNA expression of several pro-inflammatory genes in a cellular inflammation model.

Mechanism of Chir99021 regulating Wnt / β⁃catenin signaling pathway inhibiting osteogenic differentiation of rat dental pulp stem cells / 解剖学报

Objective To explore the effect and mechanism of Chir99021 on osteogenic differentiation of rat dental pulp stem cells. Methods Primary rat dental pulp stem cells were isolated from rat dental pulp and verified by fluorescence immunoassay. Different concentrations of Chir99021 were set, and the cell proliferation was detected by CCK⁃8 to select the optimal concentration. Osteogenic differentiation was detected by alizarin red staining. The expression of osteogenic differentiation related genes and proteins recombinant wingless type MMTV integration site famity member 1 (Wnt1), Wnt3a and Wnt3a β⁃expression of catenin, axis inhibition protein 2(Axin 2), dentin sialophosphoprotein(OCN) and dentin matrix acidic phosphoprotein 1(DMP1) was detected by Real⁃time PCR and Western blotting. Results The positive expression of dentin sialophosphoprotein (DSPP) and vimentin indicated that rat dental pulp stem cells were successfully isolated. After osteogenic induction of rat dental pulp stem cells, calcium deposits significantly increased with the addition of glycogen synthase kinase⁃3β(GSK⁃3β) inhibitor Chir99021, calcium deposits were significanted reduced. After osteogenic differentiation of rat dental pulp stem cells, the expression of Wnt1, Wnt3a, β⁃catenin, Axin2, OCN and DMP1 increased, while the expression of Wnt1, Axin2, OCN and DMP1 decreased with the addition of Chir99021. Conclusion Chir99021 can inhibit the osteogenic differentiation of rat dental pulp stem cells after 7 days of induction.

Follicular lymphoma with a predominantly diffuse growth pattern with 1p36 deletion: a clinicopathologic analysis of eight cases / 中华病理学杂志

Objective: To investigate the clinical and pathologic features and diagnosis of follicular lymphoma (FL) with a predominantly diffuse growth pattern (DFL) with 1p36 deletion. Methods: Eight cases of DFL with 1p36 deletion diagnosed at Department of Pathology, Beijing Friendship Hospital, Capital Medical University (n=5) and the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital (n=3) from January 2017 to January 2023 were included. Their clinicopathologic features and follow-up data were analyzed. Immunohistochemistry and fluorescence in situ hybridization (FISH) were performed. Results: There were five males and three females, with a median age of 67 years, and inguinal lymphadenopathy was found as the main symptom. Histologically, similar morphologic features were sheared among all cases, with effaced nodal structure and characterized by proliferation of centrocytes in a diffuse pattern, with or without follicular components. The germinal center-related markers such as CD10 and/or bcl-6 were expressed in the tumor cells, and 1p36 deletion but not bcl-2 translocation was appreciable in these cases. Conclusions: DFL with 1p36 deletion is a rare subtype of FL, with some overlaps with other types of FL or indolent B-cell lymphomas in their pathologic features. An accurate diagnosis requires comprehensive considerations based on their clinical, pathologic, immunohistochemical, and molecular features.

Clinicopathological features of fibrin-associated diffuse large B-cell lymphoma: a report of six cases / 中华病理学杂志

Objective: To investigate the clinical, pathological and immunophenotypic features, molecular biology and prognosis of fibrin-associated large B-cell lymphoma (LBCL-FA) in various sites. Methods: Six cases of LBCL-FA diagnosed from April 2016 to November 2021 at the Beijing Friendship Hospital, Capital Medical University, Beijing, China and the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China were collected. The cases were divided into atrial myxoma and cyst-related groups. Clinical characteristics, pathological morphology, immunophenotype, Epstein Barr virus infection status, B-cell gene rearrangement and fluorescence in situ hybridization of MYC, bcl-2, bcl-6 were summarized. Results: The patients' mean age was 60 years. All of them were male. Three cases occurred in atrial myxoma background, while the others were in cyst-related background, including adrenal gland, abdominal cavity and subdura. All cases showed tumor cells located in pink fibrin clot. However, three cyst-related cases showed the cyst wall with obviously fibrosis and inflammatory cells. All cases tested were non germinal center B cell origin, positive for PD-L1, EBER and EBNA2, and were negative for MYC, bcl-2 and bcl-6 rearrangements, except one case with MYC, bcl-2 and bcl-6 amplification. All of the 5 cases showed monoclonal rearrangement of the Ig gene using PCR based analysis. The patients had detailed follow-ups of 9-120 months, were treated surgically without radiotherapy or chemotherapy, and had long-term disease-free survivals. Conclusions: LBCL-FA is a group of rare diseases occurring in various sites, with predilection in the context of atrial myxoma and cyst-related lesions. Cyst-related lesions with obvious chronic inflammatory background show more scarcity of lymphoid cells and obvious degeneration, which are easy to be missed or misdiagnosed. LBCL-FA overall has a good prognosis with the potential for cure by surgery alone and postoperative chemotherapy may not be necessary.

Progressively transformed germinal center-like follicular T-cell lymphoma:a clinicopathological analysis of 14 cases / 中华病理学杂志

Objective: To investigate the clinicopathologic features of progressively transformed germinal center-like follicular T-cell lymphoma (PTGC-like FTCL). Methods: The clinicopathologic data of 14 PTGC-like FTCL cases that were diagnosed at the Beijing Friendship Hospital Affiliated to the Capital Medical University from January 2017 to January 2022 were retrospectively collected. Clinicopathological features, immunophenotype, and Epstein-Barr virus (EBV) infection status were analyzed in these cases. Polymerase chain reaction (PCR) was performed to detect the clonal gene rearrangements of T cell receptor (TCR) and the immunoglobulin (Ig) in 10 and 8 cases, respectively. Results: The male to female ratio was 5∶2. The median age was 61 years (range 32-70 years). All patients had lymphadenopathy at the time of diagnosis. By using the Ann Arbor system staging, seven cases were classified as stage Ⅰ-Ⅱ, and seven cases as stage Ⅲ-Ⅳ. Seven cases had B symptoms, four cases had splenomegaly, and two cases had skin rash and pruritus. Previously, three cases were diagnosed as classic Hodgkin's lymphoma, three cases as small B-cell lymphoma, two cases as atypical lymphoid hyperplasia unable to exclude angioimmunoblastic T-cell lymphoma (AITL), one case as EBV-associated lymphoproliferative disorder, and one case as peripheral T-cell lymphoma (PTCL) associated with the proliferation of B cells. All the 14 cases showed that the large nodules were composed of mature CD20+, IgD+B lymphocytes admixed with small aggregates of neoplastic cells with pale to clear cytoplasm. Moreover, hyperplastic germinal centers (GCs) and Hodgkin/Reed-Sternberg-like (HRS-like) cells were seen within these nodules in two and five cases, respectively. The neoplastic cells expressed CD3 (14/14), CD4 (14/14), PD1 (14/14), ICOS (14/14), CD10 (9/14), bcl-6 (12/14), CXCL13 (10/14), and CD30 (10/14). The HRS-like cells in five cases expressed CD20 (2/5), PAX5 (5/5), CD30 (5/5), CD15 (2/5), LCA (0/5), OCT2 (5/5) and BOB1 (2/5). Moreover, neoplastic T cells formed rosettes around HRS-like cells. EBV-encoded RNA (EBER) in situ hybridization showed scattered, small, positive bystander B lymphocytes in 8/14 cases, including 3/5 cases containing HRS-like cells. All tested cases (including five with HRS-like cells) showed monoclonal TCR gene rearrangement and polyclonal Ig gene rearrangement. Conclusions: PTGC-like FTCL is a rare tumor originated from T-follicular helper cells. It could be distinguished from angioimmunoblastic T-cell lymphoma by the formation of follicular structure, and lack of follicular dendritic cell proliferation outside the follicles and the polymorphous inflammatory background. In addition, it should be differentiated from lymphocyte-rich classical Hodgkin's lymphoma and low-grade B cell lymphoma.

Clinicopathological features and prognosis of cytotoxic T-cell lymphoma: analysis of 134 cases / 中华病理学杂志

Objective: To investigate the clinicopathological features and prognosis of cytotoxic T-cell lymphoma (CTL). Methods: The clinicopathological data of 134 CTL patients in Beijing Friendship Hospital Affiliated to Capital Medical University, the 989 Hospital of PLA Joint Logistics Support force (formerly the 152 Hospital) and the Fourth Hospital of Hebei Medical University from 2008 to 2020 were retrospectively collected. Immunophenotype, Epstein-Barr virus infection status and T cell receptor (TCR) clonality of tumor cells were assessed, and clinicopathological features and prognosis of patients were analyzed. Results: Among the 134 CTL patients, the male to female ratio was 1.7∶1.0, the median age was 49.5 years (range 3-83 years), and 100 cases (74.6%) were under 60 years old. Forty-six point nine percent of the patients (53/113) had B symptoms. Most of the patients presented with systemic superficial lymphadenopathy. According to the Ann Arbor staging system, 36.8% (39/106) of the patients were in stage Ⅰ-Ⅱ, and 63.2% (67/106) in stage Ⅲ-Ⅳ. The rate of extranodal involvement was 51.6% (66/128). Spleen was involved in 24.2% (31/128) of the cases. Morphology showed diffuse growth of abnormal lymphocytes, infiltrating and destroying normal tissue structure. Immunohistochemical staining showed that tumor cells expressed T cell antigens (CD2, CD3, CD5, and CD7), and 72.0% (77/107) of them had decreased or lost expression of one or more antigens. According to the numbers of CD4 and CD8 expression in tumor cells, 70 cases (52.2%) were grouped into CD8+>CD4+group. The expression rates of TIA-1 and granzyme B were 99.2% (119/120) and 79.8% (95/119), respectively. CD20 abnormal expression rate was 27.6% (37/134) and CD56 was negative in all cases. The median Ki-67 proliferative index was 45.0% (range 5%-80%). In situ hybridization of small RNA encoded by Epstein-Barr virus was negative. Clonal TCR gene rearrangement analysis was performed on 49 cases and was positive in all cases. Ninety-one patients were followed up for a median of 36 months (range, 1 to 240 months), and 40 of the 91 patients (44.0%) died. The twenty-three patients were in complete remission (including 13 cases with localized single extranodal mass). The 3-year and 5-year overall survival rates were 53.5% and 49.4%, respectively. Univariate analysis showed that B symptom, spleen involvement, extranodal involvement, clinical stage, CD8+>CD4+phenotype, abnormal expression of CD20 and Ki-67 proliferation index (>60%) were associated with overall survival (P<0.05). The multivariate Cox regression analyses showed that spleen involvement and CD8+>CD4+ phenotype were independent prognostic factors for overall survival in CTL patients. Conclusions: CTL are more commonly found in adult males under 60 years old, often accompanied by B symptom, with a high proportion of extranodal involvement and more CD8 positive phenotypes. Spleen involvement and CD8+>CD4+phenotype are independent predictors of CTL overall survival. Some patients with localized extranodal CTL may have a good prognosis.

Dendrocalamus latiflorus and its component rutin exhibit glucose-lowering activities by inhibiting hepatic glucose production via AKT activation

The potential medicinal value of Ma bamboo (Dendrocalamus latiflorus), one of the most popular and economically important bamboo species in China, has been underestimated. In the present study, we found that D. latiflorus leaf extract (DLE) reduced fasting blood glucose levels, body weight, and low-density lipoprotein cholesterol with low liver toxicity in db/db mice. In addition, gene expression profiling was performed and pathway enrichment analysis showed that DLE affected metabolic pathways. Importantly, DLE activated the AKT signaling pathway and reduced glucose production by downregulating glucose-6-phosphatase (G6PC) and phosphoenolpyruvate carboxykinase 1 (PCK1) expression. Moreover, network pharmacology analysis identified rutin as an active component in DLE through targeting insulin growth factor 1 receptor (IGF1R), an upstream signaling transducer of AKT. Due to its hypoglycemic effects and low toxicity, DLE may be considered an adjuvant treatment option for type 2 diabetes patients.

Effect of the Seasonal Adaptability on Carbohydrate-electrolyte Beverage Efforts on Post-exercise Rehydration in Healthy Young Men / 中国医学科学院学报

Objective To compare the effects of carbohydrate-electrolyte beverage on post-exercise rehydration of healthy young men in different seasons,and to explore the influence of seasonal adaptability on fluid and electrolyte balance.Methods Fifteen healthy men,aged(24.4±0.5)years,completed 2 trails in a random crossover design both in summer and winter.During recovery,they consumed a drink volume equivalent to 100% of their sweat loss with plain boiled water(the water group)or carbohydrate-electrolyte beverage(the beverage group).Recovery was monitored for further 180 minutes by the collection of blood and urine samples.Results The dehydration time in summer was significantly shorter by about 20 minutes than that in winter(

Establishment of high-fat diet-induced obesity and insulin resistance model in rats / 北京大学学报(医学版)

OBJECTIVE@#To investigate the appropriate conditions and duration for establishing a high-fat diet-induced obesity and insulin resistance model in rats.@*METHODS@#Forty-five 6-week-old male Sprague-Dawley (SD) rats were randomly assigned into 2 groups: (1) control group (CON), (2) high-fat diet group (HFD). HFD was fed with a high-fat diet (45% kcal from fat) while CON with chow diet. After four-weeks of high-fat diet feeding, the rats of obesity resistance (OR) were eliminated according to body weight sorting, whereas obese (OB) rats were continued feeding a high-fat diet until 12 weeks. Body weight and food intake were recorded weekly. Glucose tolerance was evaluated by oral glucose tolerance test (OGTT) in 4 weeks, 8 weeks and 12 weeks. At the end of 12 weeks, insulin releasing test and visceral fat mass were measured and HE staining of the liver, adipose tissue and pancreatic tissue were conducted.@*RESULTS@#After 4 weeks of a high-fat diet, the body weight of HFD was 17.8% higher than that of CON (P=0.001), and the rate of obesity was 67.6%-78.4%. Glucose tolerance of OB rats was impaired with a higher blood glucose concentration at 120 min (P<0.001) and a higher area under the curve (AUC, P=0.037) in OGTT compared with CON. The rate of obesity and insulin-resistance rats was 79.3%. After 8 weeks of feeding, the body weight in OB was 30.4% higher than CON (P<0.001). In OGTT, blood glucose levels at 60 min and 120 min were 35.6% and 36.4% higher than those in CON (both P<0.001), and AUC was 21.7% (P<0.001) higher than that of CON. The rate of obesity and insulin-resistance rats was 100.0%. After 12 weeks of feeding, the body weight in OB was 36.9% higher than that in CON (P<0.001). In OGTT, the blood glucose levels at 60 min and 120 min were 24.8% (P=0.001) and 34.6% (P<0.001) higher than those in CON, and AUC was 16.1% (P=0.019) higher than that of CON. The rate of obesity and insulin-resistance rats was 93.3%. The insulin releasing test showed that serum insulin concentration at each time point (0, 30, 60, 120 min) was higher than that in CON, with a 6.3-times higher than that in CON at 120 min (P=0.008). Pathological changes were observed in islets and liver in the OB rats.@*CONCLUSION@#After 4 weeks of a high-fat diet (45% kcal from fat) feeding in six-weeks SD rats, the rats of OR were eliminated. Impaired glucose tolerance was found in OB rats after 4 weeks of feeding, and the rate was higher after 8-12 weeks of high-fat diet feeding.

Effects of chlorogenic acid on glucose tolerance and its curve characteristics in high-fat diet-induced obesity rats / 北京大学学报(医学版)

OBJECTIVE@#To observe the effect of chlorogenic acid (chlorogenic acid, CGA) on the glucose tolerance and its curve characteristics in high fat diet-induced obesity (diet-induced-obesity, DIO) rats, so as to provide scientific grounds for the development and utilization of CGA in early prevention and reversal of prediabetes.@*METHODS@#Eight of forty-six male Sprague-Dawley rats were randomly selected as the normal diet group (CON group), and the rest were fed with high-fat diet. After 4 weeks, 24 high-fat-induced obese rats were screened according to the criteria and then randomly divided into high fat diet group (HFD group), 50% CGA group and 98% CGA group. The CGA groups received intragastric administrations of 50% CGA and 98% CGA orally via a gavage needle once a day for 8 weeks, respectively, while the CON and HFD groups received a carrier solution (phosphate buffer saline, PBS). Their body weights were measured weekly and oral glucose tolerance test (OGTT) was performed every 4 weeks. Fasting insulin and insulin release were measured at the end of the study. Meanwhile, HOMA-IR and visceral fat percentage were calculated. Histopathological examination by hematoxylin and eosin staining method were evaluated in the pancreatic tissues.@*RESULTS@#Before the intervention of chlorogenic acid, blood glucose levels 120 min after glucose loading (P<0.05) and AUC-G (P<0.05) were increased in the HFD group when compared with the CON group, and the time to glucose peak was delayed after 4 weeks of chlorogenic acid intervention (P<0.05). After 8 weeks of intervention, the HOMA-IR index, the insulin levels at 0 min, 30 min, 60 min, and 120 min after glucose loading and AUC-I increased (P<0.05), and the histopathological examination showed obvious hyperplasia of pancreatic islets (P<0.05). Compared with the HFD group, there was no significant change in glucose tolerance and glucose peak time in 50%CGA and 98%CGA groups at the end of 4 weeks of intervention. However, after 8 weeks of intervention, OGTT-60min,OGTT-120min blood glucose (P<0.05) were lower, HOMA-IR index and OGTT-0min, OGTT-120min serum insulin level decreased (P<0.05), the time to glucose peak shifted to an earlier timepoint (P<0.05), abnormal islet hyperplasia attenuated (P<0.05) in 50% CGA and 98% CGA groups. Also, the OGTT-30min serum insulin level was decreased (P<0.05) in 50% CGA group.@*CONCLUSION@#Delay in time to glucose peak during the OGTT was one of the manifestations of impaired glucose tolerance in DIO rats, and 50% and 98% CGA could improve the glucose tolerance and delay in glucose peak time.

Effect of Modified Wuzi Yanzong Pill () on Tip60-Mediated Apoptosis in Testis of Male Rats after Microwave Radiation / 中国结合医学杂志

OBJECTIVE@#To investigate the effect of a modified Wuzi Yanzong Pill (, WZYZP) on the male rats' testis after microwave radiation, as well as its potential mechanism.@*METHODS@#Forty-five male rats were randomly assigned to three groups: the control group, the radiation group, and the WZYZP group. The rats in the radiation group and WZYZP group were exposed to microwave radiation for 15 min once, while the rats in the control group were not exposed to any radiation. The rats in the WZYZP group were given a modified of WZYZP by gavage daily for 7 days. Apoptosis in the testis was evaluated using terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay. Histopathological alterations of the testis were observed by haematoxylin-eosin (HE) staining. Tat-interactive protein, 60kD (Tip60) and p53 expressions were determined by Western blotting.@*RESULTS@#The apoptosis index (AI) in the radiation group was higher than that of the WZYZP group and control group on day 1 (D1), day 7 (D7) day 14 (D14) after radiation (P<0.05). The seminiferous tubules were of normal morphology in the control group. In the radiation group, the partial seminiferous tubules were collapsed, basement membranes of the seminiferous epithelia became detached. WZYZP could restore the morphological changes. There was no expression of Tip60 among the three groups on D7 and D14. The expression of p53 was higher in the radiation group than in the control group (P<0.05). WZYZP could down-regulate the rising p53 induced by radiation on D7 and D14 (P<0.05).@*CONCLUSION@#A modified WZYZP may affect germ cells, and its protective effects may partly result from its ability to intervene in Tip60 mediated apoptosis.

Effects of Dendrobium officinale Polysaccharides on Gene Expression Profile of HUVEC / 中国药房

OBJECTIVE： To investigate the effects of Dendrobium officinale polysaccharides on gene expression profile of HUVEC. METHODS： HUVEC was selected as objects. MTS method was used to detect the effects of different doses of D. officinale polysaccharides （50， 100， 200， 400， 800 μg/mL） on the proliferation activity of HUVEC. The growth inhibitory concentration of 30％ cells （IC30） was calculated to screen the dose of follow-up tests. cDNA microarray assay was used to detect the changes of gene expression profile for HUVEC after treated with D. officinale polysaccharides for 24 h， so as to screen differentially expressed genes. GO enrichment analysis and KEGG pathway enrichment analysis were performed for top 5 differentially expressed genes by using DAVID bioinformatics resource database. Real-time fluorescence quantitative polymerase chain reaction （qRT-PCR） was used to validate the results of microarray detection with immunity-related differentially expressed genes as objects. RESULTS： After treated with 100， 200， 400， 800 μg/mL D. officinale polysaccharides， survival rate of HUVEC  were decreased significantly （P＜0.05 or P＜0.01）. IC30 value was 408 μg/mL. After treated with 400 μg/mL （by IC30） D. officinale polysaccharides， there were 91 differentially expressed genes in HUVEC cells， of which 84 were up-regulated and 7 were down-regulated. Top 5 genes of up-regulated and down- regulated expression were SELE， CCL2， CXCL6， IL8， ICAM1 as well as VWCE， CPT1A， CLU， CCL14， CINS4， which may be mainly associated with immune conditions and inflammatory responses. The differentially expressed genes mainly distributed in extracellular domain， and were enriched in biological processes such as production and response of cytokines and stimulus response， and played molecular functions such as chemokine and its receptor activity. The up-regulated genes as SELE， ICAM1 and CXCL2 were mainly enriched in TNF signaling pathway， influenza A （H1N1）， herpes simplex virus infection and other pathways. The down-regulated gene CCL14 was mainly enriched in chemokine signaling pathway. Results of qRT-PCR validation tests showed that relative expression of ICAM1 was increased significantly， while that of CCL14 was decreased significantly （P＜0.05）， which was in agreement with microarray detection results. CONCLUSIONS： After treated with D. officinale polysaccharides， the expression of 91 genes in HUVEC cells are different significantly， mainly being up-regulated. The differentially expressed genes may participate in immune regulation through TNF signaling pathway， influenza A （H1N1） and herpes simplex virus infection.

Role of kallistatin in protecting hepatic stellate cells against oxidation through inhibition of oxidative stress and activation of Akt-eNOS signaling / 药学学报

The present study was aimed to investigate the role and mechanisms of kallistatin in protection against oxidative stress-induced hepatic stellate cell damage. The effects of kallistatin on the viability, the intracellular superoxide level and Akt, eNOS molecules were investigated in human hepatic stellate cell line LX-2 and the incompletely activated primary rat hepatic stellate cells. Two different oxidative-stress related models, the hydrogen peroxide model and the iron-overload model were used in the experiments. The results show that kallistatin protected the hepatic stellate cells from oxidative damage and repaired the cell damage by oxidative stress. The main mechanism is antioxidant activity of kallistatin, which can remove the oxidized substances inside the cells. On the other way, kallistatin activates Akt and eNOS molecules to generate the antioxidant effect. Our results help to explore new anti-fibrotic targets.

Clinical research on Placenta Polypeptides Injection combined with chemotherapy in treating advanced ovarian cancer / 重庆医学

Objective To observe the clinical effect of the Placenta Polypeptides injection combined with paclitaxel plus paraplatin(TC)chemotherapy in the treatment of advanced ovarian cancer.Methods Eighty patients with advanced ovarian cancer receiving tumor cytoreductive surgery were divided into the treatment group and control group,40 cases in each group.The control group accepted single TC chemotherapy,while on this basis the treatment group was added with the Placenta Polypeptides injection.The short-term effect,KPS scores and occurrence of chemotherapeutic toxic reactions were observed in both groups.Results The short-term effective rates in the treatment group and control group were 90.00％ and 87.50 ％ respectively,the difference was not statistically significant (P＞0.05);the living quality KPS score in the treatment group was significantly better than that in the control group,the difference indicated statistical significance(P＜0.05).The occurrence rates of adverse reactions,including leukopenia,nausea and vomiting,liver function damage,heart toxicity,muscle and joint pain were significantly lower than those in the control group (P＜0.05).Conclusion The Placenta Polypeptides injection combined with TC chemotherapeutic regimen in the treatment of advanced ovarian cancer could improve the quality of life of the patients,reduce the toxic and adverse reactions of chemotherapeutic drugs.

Analysis of vaginal microenvironment in 435 cases with nonneoplastic epithelial disorders of vulva / 解放军医学杂志

Objective To explore the relationship of vaginal micro-ecological condition with the nonneoplastic epithelial disorders of vulva (NNEDV) in order to provide clues on diagnosis and treatment of NNEDV. Methods The outpatient data of 435 cases of NNEDV as diagnosed by biopsy, collected from Jan. 2012 to Jun. 2015 at the Second Affiliated Hospital of Chongqing Medical University, were retrospectively analyzed to evaluate their vaginal microflora. Results Fifty-four of the 435 patients (12.4%) were proved to harbor normal vaginal microflora, and in 381 patients imbalanced vaginal microflora was found (87.6%), and among them the pathogens were clearly diagnosed in 161 cases, accounting for 37.0% (161/435); the incidence of bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) was 13.1% and 10.4%, respectively, and it was significantly higher than the incidence of other vaginitis (P<0.05). Conclusion Most of NNEDV patients are suffering from unbalanced vaginal micro-ecological imbalance, and vaginitis such as BV and VVC may be associated with the NNEDV.

Propofol attenuates hydrogenperoxide-induced apoptosis in human umbilical vein endothelial cells via multiple signaling pathways / 대한마취과학회지

BACKGROUND: Propofol has been reported to protect vascular endothelial cells against oxidative stress. In this study we investigated its effect on hydrogen peroxide (H2O2)-induced apoptosis of human umbilical vein endothelial cells (HUVECs) and examined the possible signaling pathways. METHODS: HUVECs were pretreated with propofol (1, 5, 25, and 50 microM) for 30 min and then co-incubated with 0.4 mM H2O2 for 4 h. Cell viability was assessed using a Cell Counting Kit-8. Cell apoptosis was analyzed using flow cytometry with annexin V/propidium iodide staining, and evaluated by quantifying caspase-3, Bax, and Bcl-2 expression levels. The expression levels of p38 mitogen activated protein kinase (MAPK), phosphorylated (p)-p38 MAPK, cJun-N-terminal kinases (JNK), phosphorylated (p)-JNK, Akt and phosphorylated Akt [(p)-Akt] (Ser473) were measured by western blotting. RESULTS: H2O2 treatment induced the activation of caspase-3, downregulated Bcl-2 expression, and up-regulated Bax expression, all of which were dose-dependently attenuated by propofol pretreatment. Furthermore, propofol significantly ameliorated H2O2-induced phosphorylation of p38 MAPK, JNK, and Akt in HUVECs. CONCLUSIONS: Propofol can protect HUVECs against H2O2-induced apoptosis via a mechanism that may involve p38 MAPK, JNK, and Akt signaling pathways.

Discovery of new core scaffold of Mer tyrosine kinase selective inhibitors by virtual screening / 国际药学研究杂志

Objective To discover the core structures for a series of new selective Mer tyrosine kinase inhibitors(TKI ) and design their compounds accordingly. Method The pharmacophore of the core domain was respectively generated by cocrystal of Mer tyrosine kinase (Mer TK) and bound inhibitors 1 (UNC569), 2 and 3 (PDB code: 3TCP, 4MHA and 4M3Q) and used to proceed virtual screening with online platform ZINCPharmer. Core structures were obtained after analyzing and classifying the virtual screening results and used for new inhibitors design. Results Totally 16 253 compounds were screened out, and classified to 12 core structures. Based on structure 12, 16a-16d were designed and docked with Mer TK. Among them, 16c exhibited the lowest binding energy, which could be used for future drug design. Concludsion A series of core structures keeping critical interaction with Mer TK are discovered and can be used for the new selective Mer TKI design and development. The procedure can also be applied to other targets drug discovery.

Activation of γ-aminobutyric Acid (A) Receptor Protects Hippocampus from Intense Exercise-induced Synapses Damage and Apoptosis in Rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Our previous study has confirmed that one bout of exhaustion (Ex) can cause hippocampus neurocyte damage, excessive apoptosis, and dysfunction. Its initial reason is intracellular calcium overload in hippocampus triggered by N-methyl-D-aspartic acid receptor (NMDAR) over-activation. NMDAR activation can be suppressed by γ-aminobutyric acid (A) receptor (GABAAR). Whether GABAAR can prevent intense exercise-induced hippocampus apoptosis, damage, or dysfunction will be studied in this study.</p><p><b>METHODS</b>According to dose test, rats were randomly divided into control (Con), Ex, muscimol (MUS, 0.1 mg/kg) and bicuculline (BIC, 0.5 mg/kg) groups, then all rats underwent once swimming Ex except ones in Con group only underwent training. Intracellular free calcium concentration ([Ca2+]i) was measured by Fura-2-acetoxymethyl ester; glial librillary acidic protein (GFAP) and synaptophysin (SYP) immunofluorescence were also performed; apoptosis were displayed by dUTP nick end labeling (TUNEL) stain; endoplasmic reticulum stress-induced apoptosis pathway was detected by Western blotting analysis; Morris water maze was used to detect learning ability and spatial memory.</p><p><b>RESULTS</b>The appropriate dose was 0.1 mg/kg for MUS and 0.5 mg/kg for BIC. Ex group showed significantly increased [Ca2+]i and astrogliosis; TUNEL positive cells and levels of GFAP, B cell lymphoma-2 (Bcl-2) associated X protein (Bax), caspase-3, caspase-12 cleavage, CCAAT/enhancer binding protein homologous protein (CHOP), and p-Jun amino-terminal kinase (p-JNK) in Ex group also raised significantly compared to Con group, while SYP, synapse plasticity, and Bcl-2 levels in Ex group were significantly lower than those in Con group. These indexes were back to normal in MUS group. BIC group had the highest levels of [Ca2+]i, astrogliosis, TUNEL positive cell, GFAP, Bax, caspase-3, caspase-12 cleavage, CHOP, and p-JNK, it also gained the lowest SYP, synapse plasticity, and Bcl-2 levels among all groups. Water maze test showed that Ex group had longer escape latency (EL) and less quadrant dwell time than Con group; all indexes between MUS and Con groups had no significant differences; BIC had the longest EL and least quadrant dwell time among all groups.</p><p><b>CONCLUSIONS</b>Activation of GABAA R could prevent intense exercise-induced synapses damage, excessive apoptosis, and dysfunction of hippocampus.</p>

Genome-wide association study based risk prediction model in predicting lung cancer risk in Chinese / 中华流行病学杂志

<p><b>OBJECTIVE</b>To evaluate the predictive power of risk model by combining traditional epidemiological factors and genetic factors.</p><p><b>METHODS</b>Our previous GWAS data of lung cancer in Chinese were used in training set (Nanjing and Shanghai: 1473 cases vs. 1962 control) and testing set (Beijing and Wuhan: 858 cases vs. 1 115 control). All the single nucleotide polymorphisms (SNPs) associated with lung cancer risk were systematically selected and stepwise logistic regression analysis was used to select independent factors in the training set. The wGRS (weighted genetic score) was further used to calculate genetic risk score. To evaluate the contribution of the genetic factors, 3 risk models were established by using the training set, i.e. smoking model (based on smoking status) , genetic risk model (based on genetic risk score) and combined model (based on smoke and genetic risk score). The predictability of the models were evaluated by the areas under the receiver operating characteristic (ROC) curves, area under curve (AUC), net reclassification improvement (NRI) and integrated discrimination index (IDI). Besides, the results were further verified in the testing set.</p><p><b>RESULTS</b>In the training set, it was found that the AUC of the smoking, genetic risk and combined models were 0.65 (0.63-0.66), 0.60 (0.59-0.62) and 0.69 (0.67-0.71), respectively. Compared with combined model, the predictive power of other two models significantly declined, the difference was statistically significant (P<0.001). Furthermore, compared with the smoking model, the NRI of the combined model increased by 4.57% (2.23%-6.91%) and IDI increased by 3.11% (2.52%-3.69%) in the training set, the difference was statistically significant (P<0.001). Similarly, in the testing set NRI increased by 2.77%, the difference was not statistically significant (P=0.069) , and IDI increased by 3.16%, the difference was statistically significant (P<0.001).</p><p><b>CONCLUSION</b>This study showed that combining 14 genetic variants with traditional epidemiological factors could improve the predictive power of risk model for lung cancer. The model could be used in the screening of high-risk population of lung cancer in Chinese and provide evidence for the early diagnosis and treatment of lung cancer.</p>

Genetic risk score: principle, methods and application / 中华流行病学杂志

Genetic risk score (GRS) is used for evaluating the effects of genetic susceptible factors in risk prediction models.Five methods are commonly used for GRS:i.e.simple count genetic risk score (SC-GRS),odds ratio weighted genetic risk score (OR-GRS),direct logistic regression genetic risk score (DL-GRS),polygenic genetic risk score (PG-GRS) and explained variance weighted genetic risk score (EV-GRS).This paper summarizes the models,application conditions,advantages and limitations of the five methods.The complexity of prediction models increased along with the inclusion of more susceptible SNPs,some method have been developed to solve the problems,but the effects of new methods needs further evaluation.