Effect of type of carrier material on the in vitro properties of solid dispersions of progesterone / 药学学报

This study investigated the effect of different carrier materials on the in vitro properties of progesterone solid dispersions. The solid dispersions of the insoluble drug progesterone were prepared by hot melt extrusion technique using rheological properties as the index of investigation, and the in vitro properties of the solid dispersions were characterized. Scanning electron microscope revealed solid dispersions with rough surfaces and agglomerated microstructures into irregular lumpy particles. Differential scanning calorimetry and powder X-ray diffraction showed the change of progesterone crystalline form in solid dispersions from crystalline to amorphous state. In vitro dissolution studies showed that solid dispersions prepared with different carrier materials can effectively improve the dissolution rate of drugs. The results of the study showed that the type of carrier material had a significant effect on the in vitro properties of solid dispersions, providing a reference for the study of solid dispersions in the controlled release of insoluble drugs.

Blaps rynchopetera combined with cyclophosphamide affects proliferation and apoptosis of lung cancer cells via Wnt/β-catenin signaling pathway / 中国中药杂志

This study aims to investigate the effects of Blaps rynchopetera Fairmaire and/or cyclophosphamide on the proliferation and apoptosis of lung cancer cells and decipher the underlying mechanism. B. rynchopetera and cyclophosphamide-containing serum and blank serum were prepared from SD rats. Cell counting kit-8(CCK-8) assay was employed to examine the proliferation of lung cancer cell lines A549 and Lewis treated with corresponding agents. The Jin's formula method was used to evaluate the combined effect of the two drugs. According to the evaluation results, appropriate drug concentrations and lung cancer cell line were selected for subsequent experiments, which included control, B. rynchopetera, cyclophosphamide, B. rynchopetera + cyclophosphamide, and B. rynchopetera + Wnt/β-catenin pathway agonist lithium chloride(LiCl) groups. Immunocytochemistry was employed to measure the expression of proliferation-related proteins in Lewis cells after drug interventions. Flow cytometry was employed to determine the cell cycle and apoptosis. The expression levels of proliferating cell nuclear antigen(PCNA), cyclinD1, B-cell lymphoma 2(Bcl-2), Bcl-2-assiocated X protein(Bax), Wnt1, and β-catenin were determined by Western blot. The results showed that B. rynchopetera and/or cyclophosphamide significantly inhibited the proliferation of A549 and Lewis cells. Compared with B. rynchopetera alone, the combination increased the inhibition rate on cell proliferation. The combination of B. rynchopetera and cyclophosphamide demonstrated a synergistic effect according to Jin's formula-based evaluation. Compared with the control group, the B. rynchopetera, cyclophosphamide, and B. rynchopetera + cyclophosphamide groups showed increased proportion of Lewis cells in G_0/G_1 phase, increased apoptosis rate, up-regulated expression of Bax, and down-regulated expression of PCNA, cyclinD1, Bcl-2, Wnt1, and β-catenin. Compared with the cyclophosphamide group, the combination group showed increased proportion of cells in G_0/G_1 phase, increased apoptosis rate, up-regulated expression of Bax, and down-regulated expression of PCNA, cyclinD1, Bcl-2, Wnt1, and β-catenin. Compared with the B. rynchopetera group, the B. rynchopetera + LiCl group had deceased proportion of cells in G_0/G_1 phase, decreased apoptosis rate, down-regulated expression of Bax, and up-regulated expression of PCNA, cyclinD1, Bcl-2, Wnt1, and β-catenin. The results indicated that B. rynchopetera could inhibit the proliferation, arrest the cell cycle, and induce the apoptosis of lung cancer cells by inhibiting the Wnt/β-catenin signaling pathway. Moreover, B. rynchopetera had a synergistic effect with cyclophosphamide.

Yinlai Decoction Protects Microstructure of Colon and Regulates Serum Level of D-Lactic Acid in Pneumonia Mice Fed with High-Calorie and High-Protein Diet / 中国结合医学杂志

OBJECTIVE@#To investigate the effect of Yinlai Decoction (YD) on the microstructure of colon, and activity of D-lactic acid (DLA) and diamine oxidase (DAO) in serum of pneumonia mice model fed with high-calorie and high-protein diet (HCD).@*METHODS@#Sixty male Kunming mice were randomly divided into 6 groups by the random number table method: normal control, pneumonia, HCD, HCD with pneumonia (HCD-P), YD (229.2 mg/mL), and dexamethasone (15.63 mg/mL) groups, with 10 in each group. HCD mice were fed with 52% milk solution by gavage. Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water, twice daily, for 3 days. After hematoxylin-eosin staining, the changes in the colon structure were observed under light microscopy and transmission electron microscope, respectively. Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice.@*RESULTS@#The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact. The colonic mucosal goblet cells in the pneumonia group tended to increase, and the size of the microvilli varied. In the HCD-P group, the mucosal goblet cells showed a marked increase in size with increased secretory activity. Loose mucosal epithelial connections were also observed, as shown by widened intercellular gaps with short sparse microvilli. These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment, while there was no significant improvement after dexamethasone treatment. The serum DLA level was significantly higher in the pneumonia, HCD, and HCD-P groups as compared with the normal control group (P<0.05). Serum DLA was significantly lower in the YD group than HCD-P group (P<0.05). Moreover, serum DLA level significantly increased in the dexamethasone group as compared with the YD group (P<0.01). There was no statistical significance in the serum level of DAO among groups (P>0.05).@*CONCLUSIONS@#YD can protect function of intestinal mucosa by improving the tissue morphology of intestinal mucosa and maintaining integrity of cell connections and microvilli structure, thereby reducing permeability of intestinal mucosa to regulate the serum levels of DLA in mice.

Clinical features of primary sclerosing cholangitis and inflammatory bowel disease / 中华内科杂志

Objective: To explore disease characteristics of primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) and compare the differences between PSC with and without IBD. Methods: Study design was cross sectional. Forty-two patients with PSC who were admitted from January 2000 to January 2021 were included. We analyzed their demographic characteristics, clinical manifestations, concomitant diseases, auxiliary examination, and treatment. Results: The 42 patients were 11-74(43±18) years of age at diagnosis. The concordance rate of PSC with IBD was 33.3%, and the age at PSC with IBD diagnosis was 12-63(42±17) years. PSC patients with IBD had higher incidences of diarrhea and lower incidences of jaundice and fatigue than in those without IBD (all P<0.05). Alanine aminotransferase, total bilirubin, direct bilirubin, total bile acid and carbohydrate antigen 19-9 levels were higher in PSC patients without IBD than in those with IBD (all P<0.05). The positive rates for antinuclear antibodies and fecal occult blood were higher in PSC patients with IBD than in those without IBD (all P<0.05). Patients with PSC complicated with ulcerative colitis mainly experienced extensive colonic involvement. The proportion of 5-aminosalicylic acid and glucocorticoid application in PSC patients with IBD was significantly increased compared with that of PSC patients without IBD (P=0.025). Conclusions: The concordance rate of PSC with IBD is lower at Peking Union Medical College Hospital than in Western countries. Colonoscopy screening may benefit PSC patients with diarrhea or fecal occult blood-positive for early detection and diagnosis of IBD.

Blaps rynchopetera affects proliferation, migration, and invasion of non-small cell lung cancer: a study based on network pharmacology and in vivo and in vitro experiments / 中国中药杂志

Network pharmacology, molecular docking, and in vivo and in vitro experiments were employed to study the molecular mechanism of Blaps rynchopetera Fairmaire in the treatment of non-small cell lung cancer(NSCLC). The components of B. rynchopetera were collected by literature review, and the active components were screened out through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). PharmMapper was used to obtain the targets of the active components. The targets of NSCLC were obtained from DrugBank, GeneCards, OMIM, TTD, and PharmGKB. The Venn diagram was drawn to identify the common targets shared by the active components of B. rynchopetera and NSCLC. The "drug component-target" network and protein-protein interaction(PPI) network were constructed by Cytoscape, and the key targets were screened by Centiscape. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the above key targets were performed by DAVID. AutoDock and PyMOL were used for the molecular docking between the key targets and corresponding active components. A total of 31 active components, 72 potential targets, and 11 key targets of B. rynchopetera against NSCLC were obtained. The active components of B. rynchopetera had good binding activity with key targets. Further, the serum containing B. rynchopetera was prepared and used to culture human lung adenocarcinoma A549 cells. The CCK-8 assay was employed to determine the inhibition rates on the growth of A549 cells in blank control group and those exposed to different concentrations of B. rynchopetera-containing serum, cisplatin, and drug combination(B. rynchopetera-containing serum+cisplatin) for different time periods. The cell migration and invasion of A549 cells were detected by cell scratch assay and Transwell assay, respectively. Western blot was employed to determine the expression levels of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X(Bax), caspase-3, cell division cycle 42(CDC42), proto-oncogene tyrosine-protein kinase SRC, and vascular endothelial growth factor(VEGF) in A549 cells. C57BL/6 mice were inoculated with Lewis cells and randomly assigned into a model control group, a B. rynchopetera group, a cisplatin group, and a drug combination(B. rynchopetera+cisplatin) group, with 12 mice per group. The body weight and the long diameter(a) and short diameter(b) of the tumor were monitored every other day during treatment, and the tumor volume(mm~3) was calculated as 0.52ab~2. After 14 days of continuous medication, the mice were sacrificed for the collection of tumor, spleen, and thymus, and the tumor inhibition rate and immune organ indexes were calculated. The tissue morphology of tumors was observed by hematoxylin-eosin(HE) staining, and the positive expression of Bax, Bcl-2, caspase-3, CDC42, SRC, and VEGF in the tumor tissue was detected by immunohistochemistry. The results indicated that B. rynchopetera and the drug combination regulated the expression levels of Bax, Bcl-2, caspase-3, CDC42, SRC, and VEGF to inhibit the proliferation, migration, and invasion of A549 cells and Lewis cells, thus playing a role in the treatment of NSCLC via multiple ways.

Effect of acupuncture on default mode network in patients with migraine based on functional Magnetic Resonance Imaging: a preliminary study / 中国针灸

OBJECTIVE@#To investigate the effect of acupuncture on default mode network (DMN) in migraine patients without aura based on functional Magnetic Resonance Imaging (fMRI).@*METHODS@#Fifteen patients with migraine were included and treated with acupuncture based on "root-knot" theory (Zuqiaoyin [GB 44] for @*RESULTS@#Compared before acupuncture, the functional connections of left parahippocampal cortex (PHC) and anterior medial prefrontal cortex (aMPFC), dorsal medial prefrontal cortex (dMPFC) and lateral temporal cortex (LTC) in DMN after acupuncture were weakened (@*CONCLUSION@#Acupuncture shows good clinical efficacy for migraine without aura, and could adjust the functional connection of DMN.

Anti-tumor Mechanism of Xihuangwan and Research Progress on Its Combined Use in Anti-tumor Treatment / 中国实验方剂学杂志

Xihuangwan is composed of four Chinese medicines： Bovis Calculus， Olibanum， Myrrha， and Moschus. Modern pharmacology studies have shown that Xihuangwan has anti-inflammatory， antibacterial， anti-tumor， anti-mammary gland hyperplasia effect， and can enhance the body's immune function. Cancer seriously endangers public health and safety-of-life， and is a major cause of mortality of Chinese citizens. It is a disease with intricate etiopathogenesis caused by the joint action of circumstances and hereditary factors. At present， anti-tumor chemotherapy drugs in clinical application not only have toxic and side effect， but also affect clinical efficacy and prognosis of patients. Long-term use will also lead to drug resistance of tumors. As a traditional classic anti-cancer prescription， Xihuangwan has been used more and more in tumor research with the rise of Chinese medicine culture. It is provided with remarkable inhibitory effect on liver cancer， gastric cancer， carcinoma of the lungs， mammary gland， colorectal carcinoma and other malignant tumors. In clinical practice， Xihuangwan ， mostly used as adjuvant drugs in combined use with chemotherapy drugs for anti-tumor effect， can reduce the side effect of chemotherapy drugs and the untoward reaction of sufferers， improve the survivability of patients to chemotherapy， reduce or delay postoperative tumor recurrence， enhance the body's immune function， and reverse the tolerance of tumor cells. Based on the anti-tumor research of Xihuangwan， we summarized its mechanisms in inducing cell apoptosis， regulating amino acid metabolism， reversing drug resistance， interfering with cell cycle， resisting tumor metastasis and invasion， regulating immune function， improving tumor microenvironment， and regulating signal pathways， as well as its clinical combination with chemotherapeutic anti-tumor drugs， analyzed the current anti-tumor research status of Xihuangwan's research， and put forward the shortcomings and unresolved problems in order to provide theoretical basis for further research and clinical application of Xihuangwan.

Experimental study of urokinase concentration after in vivo thrombolysis with urokinase targeting microbubbles combined with ultrasound / 中华超声影像学杂志

Objective:To prepare urokinase targeted thrombus microbubbles combined with low frequency ultrasound to dissolve thrombus in rabbit femoral artery, and to explore the mechanism of thrombolysis through the change of urokinase concentration.Methods:Twenty-four rabbits with thrombosed femoral artery were randomly divided into four treatment groups: urokinase alone (UK) group, ultrasound with non-targeted microbubble and urokinase (US+ M+ UK) group, platelet-targeted microbubble with urokinase (R+ UK) group, ultrasound with platelet-targeted microbubble and urokinase (US+ R+ UK) group. Thrombus-targeted microbubbles were injected through the ear vein and irradiated by ultrasound for 30 minutes, and the pulsed Doppler blood flow meter was used to continuously monitor the blood flow at 0 min, 10 min, 20 min, 30 min, 60 min, 90 min and 120 min after injection. At the same time, the changes in urokinase concentration were monitored, and the characteristics of blood flow and urokinase concentration changes were analyzed.Results:UK and US+ M+ UK groups failed to show recanalization at 120 minutes after treatment.In contrast, the US+ R+ UK and R+ UK groups both achieved persistent recanalization( P<0.001). Compared with the basal state. Both the R+ UK group and R+ UK+ US group showed a decrease at 60 minutes, and the difference was statistically significant( P<0.05). Conclusions:In the thrombolysis process of low-frequency ultrasound combined with a targeted contrast agent carrying urokinase, the targeting can make the local urokinase concentration of thrombus reach the highest level. At the same time, ultrasound and targeted microbubbles promote urokinase to enter the thrombus, and finally achieve the strongest thrombolytic effect.

Path analysis of the relationships among health knowledge of chronic diseases, lifestyle and utilization of workplace health services of teachers in a district of Beijing / 中华疾病控制杂志

Objective To understand the influence path of occupational health knowledge, behavior and lifestyle, and utilization of workplace health service on chronic diseases of teachers in a district of Beijing. Method A self-designed questionnaire was used among teachers in a district of Beijing through path analysis. Results The prevalence rate of chronic diseases in occupational population was 51.5%. The top three diseases were lumbar or spinal diseases (19.0%), hypertension (12.5%) and gastroenteritis (11.1%). The rate of overweight and obesity increased with age, and male teachers were higher than that of female teachers which was statistically significant ( 2=119.313，P<0.001).Overweight-obesity, health related knowledge and utilization of workplace services made direct effects on chronic diseases. Healthy behaviors and lifestyles made indirect effects on chronic diseases by overweight-obesity. Conclusions The teachers’ health in this district was not bad. It is recommended that we should pay attention to the population of teachers, especially the male so that to prevent and control the incidence of overweight and obesity, improve their health knowledge level and develop healthy habits, and increase the input of health resources in the workplace.

Effects of Decitabine Combined with Bortezomib on the Proliferation of Mantle Cell Lymphoma Cell Lines and Its Underling Mechanisms / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of decitabine combined with bortezomib on the proliferation of mantle cell lymphoma cell lines (Jeko-1 and Grante519) in vitro and explore the underlying mechanisms.@*METHODS@#Jeko-1 and Grante519 cells were treated with different concentrations of decitabine and/or bortezomib alone and their combination.The cell proliferation was determined by CCK-8 assay. the cell apoptosis were detected by flow cytometry, the mRNA and protein expression levels of genes related with the cell cycle and apoptosis were analyzed by RT-PCR and Western blot respactively.@*RESULTS@#Low dose DAC could significantly inhibit the proliferation and induce apoptosis of Jeko-1 and Grante519 cells which shows a dose-and time-dependent manner. After DAC treatment, caspase 3, BAX and PCDH8 expression levels increased, while BCL-2 and CCND1 expression levels decreased in Jeko-1 and Grante519 cells, but there was no significant difference in NF-κB expression. High dose BTZ could significantly inhibit the proliferation and induce apoptosis of Jeko-1 and Grante519 cells which shows a dose-and time-dependent manner; single drug BTZ could increase the expression level of Caspase 3 and BAX, and decrease the expression level of NF-κB, BCL-2 and CCDN1 in Jeko-1 and Grante519 cells, but there was significant difference in PCDH8 expression level. Compared with single-drug treatment group, DAC combined with BTZ significantly increased the inhibitory rate and apoptotic rate of Jeko-1 and Grante519 cells; PCDH8, Caspase 3 and BAX expression levels significantly increased, and the expression levels of NF-κB, BCL-2 and CCND1 significantly decreased in Jeko-1 and Grante519 cells.@*CONCLUSION@#The combination of DAC and BTZ has obviously synergistic effects on the growth inhibition of Jeko-1 and Grante519 cells which maybe relates with enhancing inbibitory effect on NF-κB signal pathway, down-regulating BAX expression, up-regulating BAX expression as well as increasing cospase 3 expression. This study provides a novel therapeutic approach for mantle cell lymphoma.

Analysis of epidemic characteristics and spatial clustering of pulmonary tuberculosis in Wuhan , 2011-2018 / 公共卫生与预防医学

Objective To explore the epidemic characteristics and spatial clustering of pulmonary tuberculosis in Wuhan from 2011 to 2019, and to provide a scientific basis for formulating intervention strategies and measures. Methods Descriptive statistical analysis was conducted on the epidemic characteristics of tuberculosis data in Wuhan registered in the national tuberculosis information management system in the last 9 years, and spatial autocorrelation analysis was performed on the incidence of tuberculosis in 155 communities or in the city using Arcgis10.5 software. Results From 2011 to 2019, there were 56,432 cases of tuberculosis reported in Wuhan, and the annual average reported incidence rate of tuberculosis was 59.24/100 000. The overall incidence rate showed a fluctuating downward trend, with an average annual decline rate of 1.99%. The ratio of the number of cases between men and women was 2.35:1, and the incidence rate in males was higher than that in females (χ2=285.36，P0,P<0.001), and the high-high aggregation areas of tuberculosis were mainly distributed in Erqi community, Baibuting community, Liujiaoting community, Yijiadun community, Heping Street, Changqian Street, Tonghu farm, Yuxian Town, Zhifang Town, Wulijie Town, Fenghuang Street, Liji Street, and Daoguanhe Street. Conclusion The overall epidemic situation of pulmonary tuberculosis in Wuhan showed a slow downward trend. The main population and the clustering time of cases were relatively fixed, and the overall epidemic showed a certain spatial clustering. Active screening should be carried out for high-risk populations and high-aggregation areas, and effective prevention and control strategies should be developed based on time and location classification.

Accuracy of Xpert® MTB/RIF for the detection of tuberculosis and rifampicin-resistance tuberculosis in China: A systematic review and meta-analysis / 北京大学学报(医学版)

OBJECTIVE@#To systematically review the diagnostic accuracy of Xpert® Mycobacterium tuberculosis/rifampicin (Xpert® MTB/RIF) for the detection of active tuberculosis (TB) and rifampicin-resistance TB in Chinese patients.@*METHODS@#Four Chinese databases (SinoMed, CNKI, WanFang database, and VIP) and three English databases (PubMed, Embase, and The Cochrane Library) were searched from January 1, 2000 to September 15, 2017, to identify diagnostic tests about the accuracy of Xpert® MTB/RIF in Chinese patients. Two investigators screened the articles and extracted the information independently, and then the quality of each included study was evaluated by Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2. Bivariate random-effects meta-analysis was conducted to pool the sensitivity and specificity. In addition, subgroup analyses were performed based on patient type (TB patient and TB suspected patient), sample type (sputum, bronchoalveolar lavage fluid and others). All statistical analyses were conducted with Stata version 13.0.@*RESULTS@#A total of 47 articles were included in this systematic review. Most of them (38 articles) were in Chinese and only 9 articles were in English. All the articles were published during 2014 to 2017, and the sample size ranged from 31 to 3 151. Forty articles including 42 comparisons about TB were finally included with the pooled sensitivity of 0.94 (95%CI: 0.92, 0.95) and the pooled specificity of 0.87 (95%CI: 0.84, 0.91). Subgroup analysis showed that different patient and specimen types had no significant differences on sensitivity, but the specificity of sputum group was higher than that of bronchoalveolar lavage fluid. As for the detection of rifampicin-resistant TB, 33 articles (38 comparisons) were analyzed, the pooled sensitivity and specificity were 0.92 (95%CI: 0.89, 0.94) and 0.98 (95%CI: 0.97, 0.99) respectively. There were no significant differences between the patient and specimen in the subgroup analyses. The Deeks funnel plot showed a possible publication bias for detecting active tuberculosis (P=0.08) and no publication bias for rifampicin-resistant TB (P=0.24). The likelihood ratio scatter gram showed that in clinical applications, Xpert® MTB/RIF had a good diagnostic ability for detecting active tuberculosis, and it had good clinical diagnostic value in detecting rifampicin-resistant TB.@*CONCLUSION@#Xpert® MTB/RIF has good sensitivity and specificity in detecting TB and rifampicin-resistant TB in Chinese people. In particular, it has good clinical value in diagnosing rifampicin-resistance TB.

Calculation of the prevalence of progressive muscular atrophy among adults in China based on urban medical insurance data from 15 provinces / 北京大学学报(医学版)

OBJECTIVE@#To analyze the characteristics of patients with progressive muscular atrophy (PMA) and calculate the prevalence of PMA in China in 2016.@*METHODS@#A retrospective analysis based on China's urban employee basic medical insurance data and the urban residence basic medical insu-rance data from January 1, 2016 to December 31, 2016 was carried out. Children under 18 years old were excluded. Patients with progressive muscular atrophy were identified by disease names and codes. Subgroup analyses by gender, region and age were carried out to calculate the gender-specific, region-specific and age-specific prevalences. Age-adjusted national prevalence was estimated based on 2010 Chinese census data. Sensitivity analyses were done by only considering the observed cases and by excluding the top 10% provinces regarding the missing rate of diagnostic information, respectively.@*RESULTS@#A total of 996.09 million person-years were included in this study, with 518.41 million person-years in males and 477.67 million person-years in females. The age and gender distribution of the study population was similar to that of the 2010 Chinese census data, therefore the study population was nationally representative. The prevalence of PMA in China in 2016 was 0.28 per 100 000 person-years (95%CI: 0.24-0.33), with 0.21 per 100 000 person-years (95%CI: 0.16-0.26) and 0.35 per 100 000 person-years (95%CI: 0.28-0.42) for females and males, respectively. Regional disparity existed in the Chinese PMA prevalence, with the lowest prevalence in Southwest region (0.11 per 100 000 person-years, 95%CI: 0.07-0.15) and the highest prevalence in Northwest region (3.47 per 100 000 person-years, 95%CI: 0.80-7.99). Age trend in the PMA prevalence was not obvious, but the prevalence among those aged 70 years and older was relatively higher. The age-adjusted prevalence based on 2010 Chinese census data was 0.29 per 100 000 person-years (95%CI: 0.27-0.31). The national prevalences calculated by only considering the observed cases and by excluding the top 10% provinces regar-ding the missing rate of diagnostic information were 0.17 per 100 000 person-years (95%CI: 0.14-0.20) and 0.24 per 100 000 person-years (95%CI: 0.20-0.28), respectively.@*CONCLUSION@#This study is to calculate the prevalence of PMA among adults in urban China, which can provide basic statistics for the enactment of PMA related medical policies, and clues for the studies on the mechanisms of PMA.

An Optimized Protocol of Azoxymethane-Dextran Sodium Sulfate Induced Colorectal Tumor Model in Mice / 中国医学科学杂志(英文版)

Since azoxymethane (AOM)-dextran sodium sulfate (DSS) induced tumorigenesis was used to explore inflammation-associated carcinogenesis of sporadic colorectal cancer (CRC), different administration modes of AOM or DSS have been reported. In this article we optimized the protocol of the AOM-DSS modeling using C57BL/6 mice for study on sporadic CRC by intraperitoneal injecting AOM solution at a proper concentration with a 100 μl sterile syringe once, feeding with DSS solution for 7 days in a roll and change DSS solution every day. More than 100 C57BL/6 mice had been treated with the optimized protocol, and all mice were demonstrated suffering from colorectal tumors when sacrificed in 8 to 20 weeks after AOM injection. These tumors mainly occurred in distal segment of colorectum with an increase in tumor density, which was similar to CRC in human beings. Tumor per mouse was high, and variation of tumor number per mouse was low. The histology of tumor developed through the defined stage ranged from precursor lesions, adenomatous lesions, adenomas to adenocarcinomas. The modified protocol of AOM-DSS model is easy, cheap, with high tumor formation rate of colorectal tumors.

Pharmacological mechanism of Shenghua Decoction in treatment of abdominal pain based on network pharmacology / 中国中药杂志

The Shenghua Decoction recorded in Fu Qing Zhu's Gynaecology,is a commonly used postpartum prescription,widely used in treating postpartum and gynecological diseases. However,its mechanism of action in treating lower abdominal pain remains unclear. In this paper,network pharmacology was used to explore the mechanism of Shenghua Decoction in the treatment of lower abdomen pain,so as to provide data support for better clinical application of Shenghua Decoction. The drug targets of lower abdominal pain and Shenghua Decoction were retrieved in SymMap. String and Cytoscape were adopted for enrichment analysis to construct the disease-drug-target biological network. Relevant gene search results showed that there were 400 targets in Shenghua Decoction,11 of which coincided with the disease genes of lower abdomen pain. In String analysis,18 gene interactions were obtained. Gene modularizationbased analysis results indicated that one module containing six genes was obtained after modularization processing. Furthermore,there were 170 enrichment results of biological process,2 enrichment results of molecular function and 30 enrichment results of KEGG pathways in String enrichment analysis. Shenghua Decoction may play a role in treating lower abdomen pain through neuro-endocrine-immune,metabolism and other means. Its mechanism may be achieved by accelerating the repair and growth of endometrial tissue cells,improving microcirculation,promoting endometrial cell renewal and inflammation subsidence,and accelerating uterine involution; at the same time,it can regulate the autoimmunity,regulate and control the function of some natural immune cells in the process of antiinfection by using signaling pathway,supplement the vital energy,and induce elimination of pathogens from the body,thereby achieving the effect of treating lower abdomen pain.

Effects of probiotics and prebiotics on intestinal microbiota in mice with acute colitis based on 16S rRNA gene sequencing / 中华医学杂志(英文版)

BACKGROUND@#Imbalance of intestinal microbiota was closely related to colitis. Under these circumstances, regulation of enteric flora may be beneficial to the repair of inflammation. We aimed to investigate the effects of probiotics (Bifidobacterium and Lactobacillus), prebiotics and their combination on inflammation, and microflora in mice of acute colitis.@*METHODS@#C57BL/6J mice were divided into six groups randomly (blank control group, model control group, probiotics group, synbiotics group, lactitol group and probiotics + lactitol group). Each group was given 2.5% dextran sulfate sodium drinking water for 5 days other than the blank control group. Except for the model control group, the other four groups were intervened with probiotics, synbiotics (probiotics and inulin), lactitol, and probiotics + lactitol. Mice were sacrificed after 1 week of gavage, and pathologic scores were calculated. The feces of different periods and intestinal mucosa samples were collected to analyze the differences of intestinal microbiota by 16S rRNA sequencing. Differences of two groups or multiple groups were statistically examined through unpaired Student t test and analysis of variance (ANOVA), respectively. ANOVA, Tukey, Anosim, and metastats analysis were used to compare differences of microbiota among different groups.@*RESULTS@#After gavage for 1 week, the pathologic scores of groups with the intervention were significantly lower than those in the model control group, and the difference was statistically significant (P < 0.05). The model control group was higher in the genus of Bacteroides (relative abundance: 0.3679 vs. 0.0099, P = 0.0016) and lower in Lactobacillus (relative abundance: 0.0020 vs. 0.0122, P = 0.0188), Roseburia (relative abundance: 0.0004 vs. 0.0109, P = 0.0157), compared with the blank control group. However, the same phenomenon was not found in groups gavaged with probiotics and lactitol. Compared with model control group, mice with intervention were increased with Bifidobacterium (relative abundance: 0.0172 vs. 0.0039, P = 0.0139), Lachnospiraceae_NK4A136_group (relative abundance: 0.1139 vs. 0.0320, P = 0.0344), Lachnospiraceae_UCG-006 (relative abundance: 0.0432 vs. 0.0054, P = 0.0454), and decreased with Alistipes (relative abundance: 0.0036 vs. 0.0105, P = 0.0207) in varying degrees. The mucosal flora was more abundant than the fecal flora, and genus of Mucispirillum (relative abundance: 0.0207 vs. 0.0001, P = 0.0034) was more common in the mucosa. Lactitol group showed higher level of Akkermansia than model control group (relative abundance: 0.0138 vs. 0.0055, P = 0.0415), probiotics group (relative abundance: 0.0138 vs. 0.0022, P = 0.0041), and synbiotics group (relative abundance: 0.0138 vs. 0.0011, P = 0.0034), while probiotics + lactitol group had more abundant Akkermansia than synbiotics group (relative abundance: 0.0215 vs. 0.0013, P = 0.0315).@*CONCLUSIONS@#Probiotics and prebiotics reduce the degree of inflammation in acute colitis mice obviously. Mice with acute colitis show reduced beneficial genera and increased harmful genera. Supplementation of probiotics and prebiotics display the advantage of increasing the proportion of helpful bacteria and regulating the balance of intestinal microbiota. Lactitol might promote the proliferation of Akkermansia.

Similarities and differences in clinical and pathologic features of inflammatory bowel disease-associated colorectal cancer in China and Canada / 中华医学杂志(英文版)

Background@#Colorectal cancer (CRC) has become one of the major life-threatening complications in patients with inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD). This study aimed to explore the clinicalpathologic similarities and differences in the IBD-associated CRC (IBD-CRC) between patients in China and Canada.@*Methods@#Data of 78 patients with IBD-CRC retrospectively retrieved from two representative medical institutions in Beijing (China) and Calgary (Canada) over the same past 13 years, including 25 (22 UC-associated and three CD-associated) from Beijing group and 53 (32 UC-associated and 21 CD-associated) from Calgary group, were compared with regards to their clinical and pathologic characteristics.@*Results@#Several known features of IBD-CRC were seen in both groups, including long duration and large extent of colitis, active inflammation background, multifocal lesions, and advanced tumor-node-metastasis stage. Beijing group showed a significantly higher percentage of UC (88.0% vs. 60.4%, P = 0.018), younger age at diagnosis of CRC (48.6 ± 12.8 years vs. 61.6 ± 14.7 years, P < 0.001), lower ratio of mucinous adenocarcinoma (7.1% vs. 42.4%, P = 0.001) compared with Calgary group. None of the Beijing group had concurrent primary sclerosing cholangitis, while 5.7% of Calgary group did. Surveillance colonoscopy favored the detection rate of precancerous lesions (41.4% vs.17.0%, P = 0.002).@*Conclusions@#As compared with patients from the Calgary group, the IBD-CRC patients in Beijing group were younger, less CD-associated and had less mucinous features, otherwise they were similar in many common features.

Effects of probiotics and prebiotics on intestinal microbiota in mice with acute colitis based on 16S rRNA gene sequencing / 中华医学杂志(英文版)

Background@#Imbalance of intestinal microbiota was closely related to colitis. Under these circumstances, regulation of enteric flora may be beneficial to the repair of inflammation. We aimed to investigate the effects of probiotics (Bifidobacterium and Lactobacillus), prebiotics and their combination on inflammation, and microflora in mice of acute colitis.@*Methods@#C57BL/6J mice were divided into six groups randomly (blank control group, model control group, probiotics group, synbiotics group, lactitol group and probiotics + lactitol group). Each group was given 2.5% dextran sulfate sodium drinking water for 5 days other than the blank control group. Except for the model control group, the other four groups were intervened with probiotics, synbiotics (probiotics and inulin), lactitol, and probiotics + lactitol. Mice were sacrificed after 1 week of gavage, and pathologic scores were calculated. The feces of different periods and intestinal mucosa samples were collected to analyze the differences of intestinal microbiota by 16S rRNA sequencing. Differences of two groups or multiple groups were statistically examined through unpaired Student t test and analysis of variance (ANOVA), respectively. ANOVA, Tukey, Anosim, and metastats analysis were used to compare differences of microbiota among different groups.@*Results@#After gavage for 1 week, the pathologic scores of groups with the intervention were significantly lower than those in the model control group, and the difference was statistically significant (P < 0.05). The model control group was higher in the genus of Bacteroides (relative abundance: 0.3679 vs. 0.0099, P = 0.0016) and lower in Lactobacillus (relative abundance: 0.0020 vs. 0.0122, P = 0.0188), Roseburia (relative abundance: 0.0004 vs. 0.0109, P = 0.0157), compared with the blank control group. However, the same phenomenon was not found in groups gavaged with probiotics and lactitol. Compared with model control group, mice with intervention were increased with Bifidobacterium (relative abundance: 0.0172 vs. 0.0039, P = 0.0139), Lachnospiraceae_NK4A136_group (relative abundance: 0.1139 vs. 0.0320, P = 0.0344), Lachnospiraceae_UCG-006 (relative abundance: 0.0432 vs. 0.0054, P = 0.0454), and decreased with Alistipes (relative abundance: 0.0036 vs. 0.0105, P = 0.0207) in varying degrees. The mucosal flora was more abundant than the fecal flora, and genus of Mucispirillum (relative abundance: 0.0207 vs. 0.0001, P = 0.0034) was more common in the mucosa. Lactitol group showed higher level of Akkermansia than model control group (relative abundance: 0.0138 vs. 0.0055, P = 0.0415), probiotics group (relative abundance: 0.0138 vs. 0.0022, P = 0.0041), and synbiotics group (relative abundance: 0.0138 vs. 0.0011, P = 0.0034), while probiotics + lactitol group had more abundant Akkermansia than synbiotics group (relative abundance: 0.0215 vs. 0.0013, P = 0.0315).@*Conclusions@#Probiotics and prebiotics reduce the degree of inflammation in acute colitis mice obviously. Mice with acute colitis show reduced beneficial genera and increased harmful genera. Supplementation of probiotics and prebiotics display the advantage of increasing the proportion of helpful bacteria and regulating the balance of intestinal microbiota. Lactitol might promote the proliferation of Akkermansia.

Delay on care-seeking and related influencing factors among tuberculosis patients in Wuhan, 2008-2017 / 中华流行病学杂志

Objective@#To analyze the epidemiological characteristics, trend and related factors of tuberculosis patients that delayed for care, in Wuhan from 2008 to 2017.@*Methods@#Data regarding tuberculosis (TB) patients was collected from the tuberculosis management information system (TMIS), a part of the China information system for disease control and prevention from 2008 to 2017. A total of 64 208 tuberculosis patients, aged 0 to 95 years were included for the analysis. Unconditional logistic regression method was used to estimate those factors that associated with this study.@*Results@#Days of delay among TB patients appeared as M=10 (P25-P75: 3-28) day, in Wuhan, 2008-2017. The prevalence of the delay was 52.5% (33 703/64 208), presenting a downward trend from 2008 to 2017 (trend χ2=10.64, P<0.001), but the proportions of women and ≥65 year-olds were gradually increasing. Results from the multivariate logistic regression analysis showed that factors as: patients living far away from the city vs. near the city (OR=1.29, 95%CI: 1.25-1.35), and age above 45 years vs. younger than 25 years (the age 45-64 years group vs. aged less than 25 years group, OR=1.22, 95%CI: 1.15-1.29; the age 65 or above group vs. aged less than 25 years group, the OR=1.30, 95%CI: 1.22-1.39) were under higher risk on the delay of seeking care. Occupation, way of case-finding and classification of tuberculosis patients also appeared as influencing factors on this issue.@*Conclusions@#Prevalence on the delay of care was 52.5% among tuberculosis patients in Wuhan, 2008-2017, but with an annual decrease. Attention should be paid to female, wrinkly or elderly tuberculosis patients regarding the delay of care on TB, in Wuhan.

Protein kinase D1 regulates the growth and metabolism of oral squamous carcinoma cells in tumor microenvironment / 华西口腔医学杂志

OBJECTIVE@#To observe the effect of protein kinase D1 (PKD1) on the growth and metabolism of oral squamous cell carcinoma HSC-4 cells and related molecular mechanisms in the tumor microenvironment.@*METHODS@#HSC-4 cell lines were transfected with shRNA plasmids. Three groups (Wild, control-shRNA, and PKD1-shRNA) were cultured under acidic or hypoxic environment for a certain time. Western blot was used to detect the expression of autophagy-related and glycolytic-related proteins. The proliferation changes were detected by CCK-8 kits.@*RESULTS@#The PKD1-knockdown HSC-4 cell line was established. PKD1 silencing increased autophagy activity. Under hypoxic and acidic conditions, the PKD1-knockdown HSC-4 cells showed lower proliferation than the parental cells. PKD1-knockdown also decreased the expression of hypoxia induciblefactor 1α (HIF-1α) and pyruvate kinase M2 (PKM2).@*CONCLUSIONS@#Under hypoxic and acidic conditions, PKD1 gene silencing can increase apoptotic autophagy activity. Downregulated PKD1 gene expression can reduce the glycolysis of oral squamous cell carcinoma cells and inhibit tumor cell proliferation. This study revealed the important role of PKD1 in the metabolism and growth of oral squamous cell carcinoma, making it a possible target for the treatment of oral squamous cell carcinoma.