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Objective@#To analyze the spatial temporal distribution characteristics of tuberculosis among high school students at county levels in Gansu Province from 2018 to 2022,so as to provide a scientific basis for tuberculosis prevention and control in schools.@*Methods@#Tuberculosis data from high school students in counties (districts) reported in Gansu Province from 2018 to 2022 was collected from the Tuberculosis Information Management System and Infectious Disease Information Reporting System of the Chinese Disease Prevention and Control Information Management System. Demographic data of high school students in counties (districts) came from the General Management System of the Chinese Disease Prevention and Control Information Management System, and the spatial clustering of the reported incidence rate of pulmonary tuberculosis among high school students in Gansu Province in the past five years was analyzed using the methods of global spatial autocorrelation (Moran s I) and local indicators of spatial audocorrelation(LISA).@*Results@#A total of 41 885 pulmonary tuberculosis cases were reported in various counties of Gansu Province From 2018 to 2022, with an average reported incidence rate of 32.81/100 000. During the same period, 1 170 high school students cases were reported, with an average reported incidence rate of 13.72/100 000. With the exception of 2020, the reported incidence rate of pulmonary tuberculosis among high school students was non random distribution in other 4 years, showed a moderate intensity of spatial clustering. From 2018 to 2022, most counties in Gansu Province reported that the incidence rate of pulmonary tuberculosis among high school students was 10.00/100 000 or below, the counties with reported incidence rate >40.00/100 000 were mainly distributed in Luqu County, Maqu County, Diebu County, Hezuo City, Xiahe County of Gannan Prefecture, Gangu County and Wushan County of Tianshui Prefecture, Wenxian County and Kangxian County of Longnan Prefecture, Huachi County of Pingliang Prefecture, Huanxian County of Qingyang Prefecture. The number of counties where the reported incidence rate of tuberculosis among high school students more than 30.00/100 000 gradually decreased from 2018 to 2022. In the past five years, the reported incidence rate of tuberculosis among high school students in all counties of Gannan Prefecture remained above 40.00/ 100 000 . The LISA analysis results showed that the high incidence areas were mainly concentrated in Gannan Prefecture.@*Conclusions@#The epidemic situation of pulmonary tuberculosis among high school students in Gansu province from 2018 to 2022 is still a serious condition, showing the characteristics of unbalanced regional distribution. The reported incidence rate shows a strong spatial clustering, and the hot spots are concentrated in the counties (districts) of Gannan prefecture in Gansu Province.
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Objective: To develop and validate a deep learning model based on fundus photos for the identification of coronary heart disease (CHD) and associated risk factors. Methods: Subjects aged>18 years with complete clinical examination data from 149 hospitals and medical examination centers in China were included in this retrospective study. Two radiologists, who were not aware of the study design, independently evaluated the coronary angiography images of each subject to make CHD diagnosis. A deep learning model using convolutional neural networks (CNN) was used to label the fundus images according to the presence or absence of CHD, and the model was proportionally divided into training and test sets for model training. The prediction performance of the model was evaluated in the test set using monocular and binocular fundus images respectively. Prediction efficacy of the algorithm for cardiovascular risk factors (e.g., age, systolic blood pressure, gender) and coronary events were evaluated by regression analysis using the area under the receiver operating characteristic curve (AUC) and R2 correlation coefficient. Results: The study retrospectively collected 51 765 fundus images from 25 222 subjects, including 10 255 patients with CHD, and there were 14 419 male subjects in this cohort. Of these, 46 603 fundus images from 22 701 subjects were included in the training set and 5 162 fundus images from 2 521 subjects were included in the test set. In the test set, the deep learning model could accurately predict patients' age with an R2 value of 0.931 (95%CI 0.929-0.933) for monocular photos and 0.938 (95%CI 0.936-0.940) for binocular photos. The AUC values for sex identification from single eye and binocular retinal fundus images were 0.983 (95%CI 0.982-0.984) and 0.988 (95%CI 0.987-0.989), respectively. The AUC value of the model was 0.876 (95%CI 0.874-0.877) with either monocular fundus photographs and AUC value was 0.885 (95%CI 0.884-0.888) with binocular fundus photographs to predict CHD, the sensitivity of the model was 0.894 and specificity was 0.755 with accuracy of 0.714 using binocular fundus photographs for the prediction of CHD. Conclusion: The deep learning model based on fundus photographs performs well in identifying coronary heart disease and assessing related risk factors such as age and sex.
Subject(s)
Humans , Male , Retrospective Studies , Deep Learning , Fundus Oculi , ROC Curve , Algorithms , Risk Factors , Coronary Disease/diagnostic imagingABSTRACT
Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.
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The combination of Shuanghuanglian injection (SHLI) and ciprofloxacin injection (CIPI) is frequently prescribed in clinical practice, but the basis for the combination is weak. In this study, isothermal titration calorimetry and ultraviolet-visible absorption spectrometry were applied to identify the molecular interactions of SHLI and its main components, chlorogenic acid and neochlorogenic acid with CIPI. Scanning electron microscopy, Fourier-transform infrared spectroscopy, and cold-spray ionization mass spectrometry were performed to confirm that this molecular interaction was related to the formation of self-assembled supramolecular systems induced by chlorogenic acid and neochlorogenic acid with CIPI through weak intermolecular bonds. The antibacterial activity toward Pseudomonas aeruginosa (P. aeruginosa) was evaluated via molecular interactions, and the inhibitory ability of SHLI, chlorogenic acid and neochlorogenic acid against P. aeruginosa was significantly reduced after interaction with CIPI. A molecular docking study demonstrated that the reduced antibacterial ability was closely related to the competitive binding of drug molecules to the same binding site of the DNA gyrase B (GyrB) subunit of P. aeruginosa. The present study uncovered the intermolecular interactions of SHLI and its main components chlorogenic acid and neochlorogenic acid with CIPI from the perspective of molecular self-assembly and contribute to the reduction of its antibacterial ability, providing a basis for the clinical combination of SHLI and CIPI.
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The joint application of traditional Chinese medicine injection containing chlorogenic acid (CA) and cefotaxime sodium (CS) is sometimes appeared in clinical practice, but the scientific basis of drug molecular compatibility is still weak. This study proposes a sequential analysis strategy based on isothermal titration calorimetry (ITC), cold-spray ionization mass spectrometry (CSI-MS) and antibacterial activity test to evaluate the molecular interactions between CA and CS. The results of ITC experiments showed that the Gibbs free energy ΔG < 0 and it was driven by enthalpy change when CA titrated CS, suggesting CA could spontaneously chemically react with CS. Subsequently, the parent ions (m/z 808.143 5) of binding molecular of CA and CS was detected by CSI-MS, indicating CA could chemically bond with CS. Furtherly, the antibacterial experiments found the antibacterial ability of CS against Klebsiella pneumonia was significantly reduced (P < 0.01) by CA in mixed solution. Finally, molecular docking technology showed CA and CS have a common target of penicillin binding protein 3 (PBP3), suggesting that the phenomenon of CA reduced the antibacterial ability of CS may be related to the competitive binding of two components with PBP3. Our studies have shown that CA could spontaneously chemically bond to CS and reduced its antibacterial ability, providing scientific data for molecular interaction evaluation of CA and CS.
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The characteristics of meridian sinew theory at the early era have been collected. It is believed that the running courses and indications of twelve meridian sinew regions in Lingshu (Miraculous Pivot) are closely associated with Zubi Shiyimai Jiujing (Moxibustion Therapy on the Eleven Meridians of Legs and Arms) and Yinyang Shiyimai Jiujing (Moxibustion Therapy on the Eleven Meridians of Yin and Yang). Due to the attachment of twelve regular meridians, the development of its own theory is blocked. Meridian sinew theory guides the diagnosis and treatment of many dominant disorders (e.g. pain disorder and bi syndrome) with acupuncture and moxibustion. The defensive qi is circulated among meridian sinews, which is the core of meridian sinew theory. The acupoint selection relies on the meridian sinew theory at the early era, such as "consolidating muscles when they involved in disorders, using painful sites as acupoints to treat diseases" "interaction of the associated muscles" and "conducting meridian qi along with the running courses of meridians". The crack needling (one of the nine needling techniques exerted between two muscles to treat muscular pain) is adopted generally to mobilize the defensive qi so as to resist pathogens, relieve the compression in foci and promote qi and blood circulation in meridians. The rational understanding of meridian sinew theory may improve the accuracy of diagnosis and treatment of meridian sinew disorders, "reduce the pressure" on meridian theory and contribute to the enrichment of the theoretical framework of acupuncture and moxibustion.
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Acupuncture , Acupuncture Points , Acupuncture Therapy , Meridians , MoxibustionABSTRACT
Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Subject(s)
Female , Humans , Male , Chemotherapy, Adjuvant , Gastrectomy , Neoadjuvant Therapy , Neoplasm Staging , Prognosis , Retrospective Studies , Stomach Neoplasms/surgeryABSTRACT
Drug resistance resulting from bacterial biofilms can invalidate antibacterial agents. Therefore,eradicating bacterial biofilms to reverse drug resistance is a hotspot in the pharmaceutical research. In recent years,numerous studies have revealed the complicated mechanism of bacterial biofilm formation and strong drug resistance with multiple influential factors involved. This paper gives a comprehensive review on the process of biofilm formation and intervention by natural drugs,which can provide some reference and evidence for the following studies.
Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteria/genetics , Biofilms , Drug Resistance , Pharmaceutical PreparationsABSTRACT
OBJECTIVE：To study the effects of costunolide （COS）on the cell cycle distribution and apoptosis of human breast cancer SK-BR- 3 cells and its mechanism. METHODS ：Human breast cancer SK-BR- 3 cells were divided into blank control group，and COS groups of 10，20，30，40，50 μmol/L. MTT assay was used to detect the effects of COS on cell proliferation. SK-BR-3 cells were divided into blank control group ，COS low ，medium and high concentration groups （10，20，30 μmol/L）. After cultured for 24 h，flow cytometry was used to detect the distribution of cell cycle. Hoechst 33258 fluorescence staining was used to detect cell apoptosis. Western blot assay was used to detect the expression of p 53，caspase-3，Bcl-2，Bax，p21，CDK2 and cyclinE. RESULTS ：Compared with blank control group ，COS could significantly inhibit the proliferation of SK-BR- 3 cells（P＜ 0.05 or P＜0.01），and in a dose and time-dependent manner. Low ，medium and high concentrations of COS could induce cell apoptosis and arrest cell at G 1/S phase （P＜0.05 or P＜0.01），could significantly up-regulate the protein expression of p 53， caspase-3，Bax and p 21（P＜0.05 or P＜0.01），and could significantly down-regulate the protein expression of Bcl- 2，CDK2 and cyclinE（P＜0.01）. CONCLUSIONS ：COS can inhibit the proliferation of human breast cancer SK-BR- 3 cells and induce cell apoptosis and cell cycle arrest. The mechanism may be related to the regulation of p 53/Bax/Bcl-2/caspase-3 apoptosis signal pathway.
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Objective:To explore the effect of hydrotherapy combined with breathing training on lung function and mobility of patients with thoracolumbar spinal cord injury.Methods:A total of 80 patients with thoracolumbar spinal cord injury admitted to Beijing Rehabilitation Hospital Affiliated to Capital Medical University from April 2018 to March 2020 were selected as observation objects.A prospective cohort study was conducted and randomly divided into observation group and control group with 40 cases in each group.The control group was given routine rehabilitation therapy combined with respiratory training.On the basis of the control group, the observation group was treated with water therapy.The indexes of lung function, motor function, lower limb muscle tension, function evaluation and activities of daily living were compared between the two groups.Results:After intervention, the observation group′s forced vital capacity (FVC) was (3.86±0.82) L, the forced expiratory volume in the first second (FEV1) was (3.76±0.68) L, the maximum ventilation (MVV) was (102.34±10.38) L/min, the maximum suction pressure (MIP) is (50.36±4.62) cmH 2O; the control group FVC was (3.41±0.76) L, and FEV1 was ( 3.35±0.63) L, MVV was (90.67±11.68) L/min, MIP was (44.38±4.85) cmH 2O, the difference between the two groups is statistically significant ( t=2.546, 2.797, 4.723, 5.646, respectively, all P<0.05). After the intervention, the motor function score of the american spinal injury association (ASIA) of the observation group was (58.62±7.56) points, and the modified ashworth scale (MAS) score was (2.74±0.89) points; The ASIA motor function score of the control group was (42.24±6.40) points, and the MAS score was (3.36±0.94) points.The difference between the two groups was statistically significant ( t=10.459 and -3.029, respectively, all P<0.05). After intervention, the observation group′s spinal cord independence measure (SCIM III) score was (75.33±10.72) points, and the modified barthel index (MBI) was (66.64±6.34) points; the SCIM III score of the control group was (68.34±9.55) points, and the MBI score was (57.52±6.77) points, the difference between the two groups was statistically significant ( t=3.079 and 6.219, respectively, all P<0.05). Conclusion:Hydrotherapy combined with breathing training can significantly improve lung function and respiratory muscle strength in patients with thoracolumbar spinal cord injury, and improve motor function and ability of daily living.
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With the increasing incidence of hepatobiliary diseases, it is particularly important to understand the role of molecular, cellular and physiological factors in the clinical diagnosis and treatment with traditional Chinese medicine(TCM) in the development of liver disease. Appropriate animal models can help us identify the possible mechanisms of relevant diseases. Danio rerio(zebrafish) model was traditionally used to study embryonic development, and has been gradually used in screening and evaluation of liver diseases and relevant drug in recent years. Zebrafish embryos develop rapidly and the digestive organs of 5-day-old juvenile fish are all mature. At this stage, they may develop hepatobiliary diseases induced by developmental defects or compounds. Zebrafish liver is similar to human liver in cell composition, function, signal transduction, response to injury and cell process mediating liver disease. Furthermore, due to the high conservation of genes and proteins between humans and zebrafish, zebrafish becomes an alternative system for studying basic mechanisms of liver disease. Therefore, genetic screening could be performed to identify new genes involving specific disease processes, and chemical screening could be made for drugs in specific processes. This paper briefly introduced the experimental properties of zebrafish as model system, emphasized the study progress of zebrafish models for pathological mechanism of liver diseases, especially fatty liver, and drug screening and evaluation, so as to provide ideas and techniques for the future liver toxicity assessment of TCM.
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Animals , Humans , Drug Evaluation, Preclinical , Liver , Liver Diseases/genetics , Medicine, Chinese Traditional , Zebrafish/geneticsABSTRACT
Heart failure is a complex clinical syndrome，which is the final result of compensatory failure of heart injury caused by various reasons. Long-term persistent cardiac stress leads to mitochondrial dysfunction，which in turn further damages cardiomyocytes and leads to disease progression. Timely removal of damaged mitochondria in cardiomyocytes and maintaining a good living environment of viable mitochondria is not only an effective means to protect cardiomyocytes，but also a new way to prevent and treat heart failure and ventricular remodeling. Mitochondrial quality control is a series of cellular activities for mitochondria to maintain their structural and functional stability，including oxidative stress response，regulation of mitochondrial dynamics，mitochondrial autophagy，intracellular calcium regulation and so on. Traditional Chinese medicine（TCM） mostly uses drugs of replenishing Qi and activating blood circulation in the treatment of chronic heart failure，and Qi and mitochondria are similar in function. According to TCM，the performance of the body as "static，descending and inhibitory" in the case of Qi deficiency can also be compared with the energy defect of mitochondria. The classical method of tonifying qi and activating blood circulation in TCM can be applied here. In recent years，TCM takes mitochondria as the target and carries out many related experimental studies from the point of view of myocardial energy supply. It is found that Chinese herbs for replenishing Qi and activating blood circulation can participate in regulating the quality control mechanism of intracellular mitochondria with multiple targets and links. It is proved by experiments that Chinese herbs for replenishing Qi and activating blood circulation can exert myocardial protective effect through this mechanism.
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Objective:To investigate the clinical application of placental growth factor (PLGF) combined with uterine artery pulsation index in predicting early-onset preeclampsia.Methods:From March 2018 to March 2019, 69 cases of early-onset preeclampsia in the Maternal and Child Health Hospital of Jiaxing were selected as observation group, including 37 cases in mild group and 32 cases in severe group.And 58 cases of normal pregnant women in our hospital from March 2018 to March 2019 were selected as control group.The changes of plasma PLGF and uterine artery index, the changes of plasma PLGF and uterine artery index in different degrees of illness, and the diagnostic sensitivity and specificity of PLGF combined with uterine artery index were compared between the two groups.Results:The level of plasma PLGF in the observation group was (1.29±0.25)μg/L, which was lower than that in the control group[(1.70±0.34)μg/L]( t=7.816, P<0.05). The PI (1.48±0.31), RI (0.83±0.12) and S/D(2.97±0.65) of the observation group were higher than those of the control group[(0.91±0.18), (0.58±0.09) and (1.71±0.53)]( t=12.357, 13.071, 11.823, all P<0.05). The level of PLGF in the severe group was (1.13±0.27)μg/L, which was lower than that in the mild group[(1.45±0.23)μg/L]( t=5.317, P<0.05). The PI(1.71±0.36), RI(0.97±0.14) and S/D(3.45±0.71) in the severe group were higher than those in the mild group[(1.16±0.24), (0.72±0.10) and (2.43±0.57)]( t=7.556, 8.618, 6.616, all P<0.05). The diagnostic sensitivity and specificity of PLGF combined with uterine pulsation index were higher than those of PLGF and uterine pulsation index alone. Conclusion:PLGF combined with uterine pulsation index can predict the condition of early-onset preeclampsia, and the combination can improve the sensitivity and specificity.
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Objective:To summarize the experience of diagnosis and treatment of primary thyroid lymphoma (PTL) and improve the level of diagnosis and treatment.Methods:The clinical and pathological data of 19 patients with PTL admitted to the Department of Breast and Thyroid Surgery, Daping Hospital, Army Medical University From Mar. 2000 to Jul. 2019 were retrospectively reviewed.Results:among the 19 PTL patients, 4 were male and 15 were female, with an average age of 69 years (51-88 years) . 15 cases showed rapid enlargement of neck mass, 9 cases with swallowing obstruction, 7 cases with hoarseness and 5 cases with dyspnea. 13 cases were diagnosed by intervention, the other 6 cases were diagnosed by biopsy. There were 1 case of Hodgkin’s lymphoma and 18 cases of non Hodgkin’s lymphoma, including 13 cases of diffuse large B cell lymphoma and 4 cases of mucosa associated lymphoid tissue lymphoma. 12 cases received chemotherapy and 1 case received radiotherapy. The median follow-up period was 28 months (0-88 months) , 5 cases were lost, 6 cases died, 3 cases died of recurrence and spread of lymphoma, 3 cases died of others.Conclusions:PTL is more likely to occur in the elderly women, which is characterized by sudden enlargement of cervical mass and its related compression symptoms. The diagnosis can be confirmed by coarse needle biopsy or surgical intervention. PTL needs comprehensive treatment including surgery, chemotherapy and targeted treatment.
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Gallstone is one of the most common diseases in hepatobiliary, cholesterol gallstone is the most common type of gallstone. One of the important causes of gallstone formation is the precipitation of cholesterol crystals caused by cholesterin supersaturation. Scavenger receptor type BI (SR-BI) is a kind of multifunctional membrane receptor protein, which can mediate the selective uptake of cholesterol in liver and then affect the content of cholesterol in bile. Its role in the formation of gallstone has been initially revealed. In this paper, the relationship between the occurrence of cholesterol gallstones and scavenger receptor type B type I was summarized in order to provide new ideas for the further study of the pathogenesis of gallstone.
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Chronic heart failure(CHF), a serious and end stage of various heart diseases, is a common chronic cardiovascular disease in the 21 st century. Literature data show that the 5-year mortality rate of hospitalized patients with heart failure is as high as 50%. Nowadays, the development of drugs treating heart failure has become a hot spot, meanwhile, traditional Chinese medicine(TCM) has shown the advantages in the treatment of chronic heart failure. In this article, four stages to develop traditional Chinese medicine for chronic heart failure were proposed. Firstly, discuss and screen ideas and methods with regard to the development of TCM and its prescriptions based on clinical needs. Secondly, study the preparation process and quality control method by referring to the existing clinical background of TCM prescriptions and analyzing the chemical compositions and pharmacological action characteristics of each herb in the prescription. Then, design non-clinical evaluation programs and carry out researches on pharmacodynamics and toxicology by combining the experience of clinical use of TCM prescriptions and future clinical positioning, and gradually adjust and improve the programs during implementation. Finally, conduct clinical trial application(IND) by submitting registration application data which are base on the clinical drug experience, preclinical research pharmacy, main pharmacodynamics, safety test results of the prescription, clinical positioning, and reasonable clinical trial plan designed by the theory of TCM. After passing the IND technical review, the clinical trial study shall be officially launched to achieve the desired results and obtain effective Chinese patent medicines for heart failure treatment.
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Humans , Chronic Disease , Drugs, Chinese Herbal , Heart Failure , Medicine, Chinese Traditional , Quality ControlABSTRACT
Thioredoxin reductase (TrxR) is one class of the most important antioxidant selenoproteins and is involved in regulating tumor genesis and progression. It has been reported that naphthoquinones can target and inhibit TrxR1 activity therefore produce reactive oxygen species (ROS) mediated by TrxR1, resulting into cellular redox imbalance and making the naphthoquinone compounds to become potential antitumor chemotherapy drugs. The purpose of this work is to explore the interaction between TrxR1 and menadione using biochemical and mass-spectrometric (MS) analyses, to further reveal the detailed mechanisms of TrxR1-mediated naphthoquinone reduction and inhibition of TrxR1 by naphthoquinone compounds. Using the site-directed mutagenesis and recombinantly expressed TrxR1 variants, we measured the steady-state kinetic parameters of menadione reduction mediated by TrxR1 and its variants, performed the inhibition analysis of menadione on TrxR1 activity, and eventually identified the interaction between menadione and TrxR1 through MS analysis. We found that Sec-to-Cys mutation at residue of 498 significantly enhanced the efficiency of TrxR1-mediated menadione reduction, though the Sec⁴⁹⁸ is capable to catalyze the menadione reduction, indicating that TrxR1-mediated menadione reduction is dominantly in a Se-independent manner. Mutation experiments showed that Cys⁴⁹⁸ is mainly responsible for menadione catalysis in comparison to Cys⁴⁹⁷, while the N-terminal Cys⁶⁴ is slightly stronger than Cys⁵⁹ regarding the menadione reduction. LC-MS results detected that TrxR1 was arylated with one molecule of menadione, suggesting that menadione irreversibly modified the hyper-reactive Sec residue at the C-terminus of selenoprotein TrxR1. This study revealed that TrxR1 catalyzes the reduction of menadione in a Se-independent manner meanwhile its activity is irreversibly inhibited by menadione. Hereby it will be useful for the research and development of naphthoquinone anticancer drugs targeting TrxR1.
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Catalysis , Drug Development , Oxidation-Reduction , Thioredoxin Reductase 1/metabolism , Vitamin K 3/metabolismABSTRACT
Cerebral infarction is a clinical disease with corresponding neurological symptoms caused by cerebral ischemia and hypoxia caused by cerebral blood supply disorder. It is one of the most common cerebrovascular diseases and a serious threat to human health. The prevention and treatment of cerebral infarction has an important social significance. Angiogenesis is the key starting point for medical treatment of cerebral infarction, and signal transduction and transcriptional activators (STAT)/hypoxia inducing factor-1(HIF-1)/vascular endothelial growth factor (VEGF) pathway are important pathways to mediate angiogenesis after cerebral infarction. This paper took the angiogenesis as the starting point and the upstream molecules of STAT/HIF-1/VEGF signal pathway STAT3 and miRNA as the main study objects, and comprehensively discussed the results of chip sequencing, experimental research, traditional Chinese medicine (TCM) pathogenesis and TCM treatment. Based on the regulatory mode of "TF-miRNA" and the idea of "micro-whole", it is suggested that under the guidance of the basic theory of TCM, cubic compound prescriptions of TCM and its active components might activate the STAT/HIF-1/VEGF signal pathway through STAT3/miRNA feedback loop to promote angiogenesis after cerebral infarction, which puts forward a deep molecular mechanism and new direction for the treatment of cerebral infarction with TCM.
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OBJECTIVE：To study the effects of costunolide on the proliferation ，migration and apoptosis of breast cancer SK-BR-3 cells and its mechanism. METHODS ：SK-BR-3 cells in logarithmic growth period were collected and cultured with different concentrations （10，20，30，40，50 μmol/L）of costunolide for 24，48，72 h. Inhibitory rate of costunolide on cell proliferation was detected with CCK- 8. The cells were divided into blank control group and costunolide group （10，20，30 μmol/L）. Hoechst 33258 fluorescence was used to observe the morphology and apoptosis of cells ，and apoptotic rate of cells were calculated. Cell scratch test was used to detect the migration ability of cells and calculate the migration rate. Western blotting was used to detect the relative expression level of Bcl- 2，Bax，Caspase-3 and Cleaved Caspase- 3 in cells. RESULTS ：The proliferation of SK-BR-3 cells were significantly inhibited by costunolide （P＜0.05 or P＜0.01），and it shows a trend of concentration and time dependence. In the blank control group ，cells possessed clear contour ，regular shape and good adherence . Compared with blank control group，the number of cells were decreased significantly in 10，20，30 μmol/L costunolide groups，the cell structure was loose，the volume was reduced ，and the gap became larger ，and most of the cell contour disappeared and became round ，the cell adherence was poor ；cell migration rate and Bcl- 2 protein relative expression level were decreased significantly ，while apoptosis rate and the relative expression level of Bax ，Caspase-3 and Cleaved Caspase- 3 protein were significantly increased （P＜0.05 or P＜0.01）. CONCLUSIONS ： Costunolide can inhibit the proliferation and migration ，and induce apoptosis of human breast cancer SK-BR- 3 cells，mechanism of which may be through up-regulating the expression of Bax ，Caspase-3 and Cleaved Caspase- 3 while down-regulating the expression ofBcl-2.
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Objective@#To investigate the expressional levels and diagnostic values of miR-18a and miR-21 in esophageal carcinoma.@*Methods@#The expressions of miR-18a and miR-21 in esophageal cancer tissues and adjacent tissues from 45 esophageal cancer patients, peripheral blood from 45 esophageal cancer patients and 50 healthy donors respectively were detected by RT-PCR. The expressions of miR-18a and miR-21 in normal esophageal epithelial cell HET-1A, esophageal cancer cell lines including ECA109, KYSE150 and TE1 were also detected. Chemiluminescence immunoassay was used to quantitatively detect the concentrations of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), CYRFA21-1 and TPA (tissue polypeptide antigen) in peripheral blood serum from esophageal cancer patients and healthy controls. Meanwhile, the diagnostic effects of miR-18a and miR-21 on esophageal cancer were compared with those of tumor markers in serum.@*Results@#The expression levels of miR-18a and miR-21 in esophageal cancer cells ECA109, KYSE150 and TE1 were 1.64±0.17, 1.62±0.19, 1.46±0.12 and 20.52±1.48, 6.73±0.73, 1.43±0.19, respectively, higher than those in normal esophageal epithelial cells (both P<0.01). The expressions of miR-18a and miR-21 in esophageal cancer tissues were 32.48±28.62 and 8.67±11.98, respectively, significantly higher than those in adjacent tissues (all P<0.001). The expression levels of miR-18a and miR-21 in peripheral blood of patients with esophageal cancer were 12.66±11.92 and 9.15±8.14, respectively, significantly higher than those in the normal control group (both P<0.001). The receiver operating characteristic (ROC) curve analysis showed that the area under the curve of miR-18a and miR-21 for diagnosis of esophageal cancer were 0.948 and 0.913 5, respectively. Compared with traditional esophageal tumor markers, the expressions of miR-18a and miR-21 were more sensitive in the diagnosis of esophageal cancer. The sensitivity and accuracy of the expressions of miR-18a and miR-21 combined with traditional esophageal tumor markers in diagnosis of esophageal cancer can be further improved to 97.8% and 68.4%, respectively.@*Conclusion@#Our study reveals that the expressions of miR-18a and miR-21 play important roles in the diagnosis of esophageal cancer and may be potentially novel biomarkers.