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Objective: To investigate surgical strategies and the corresponding benefits for patients with perihilar cholangiocarcinoma(pCCA). Methods: A total of 81 patients with pCCA who underwent radical excision in the Department of Biliary and Pancreatic Surgery of Sun Yat-Sen Memorial Hospital between January 2014 and December 2021 were retrospectively collected.The cohort consisted of 50 male and 31 female patients,with an age of (62.5±11.5)years(range:26 to 83 years).Seventy-five cases were diagnosed with jaundice,60 of whom received preoperative biliary drainage,while 20 patients received portal vein embolization.Their serum bilirubin level within one week before the operation(M(IQR)) was 44.3 (41.9) μmol/L(range:8.0 to 344.2 μmol/L).Preoperative imaging examinations were performed to evaluate the Bismuth-Corlette type of pCCA,showing 3,6,21,27,and 24 cases of Bismuth-Corlette type Ⅰ,Ⅱ,Ⅲa,Ⅲb,and Ⅳ,respectively.The primary outcome was overall survival (OS),and the secondary outcomes were relapse-free survival (RFS),90-day postoperative morbidity and 90-day postoperative mortality.OS and RFS were estimated using the Kaplan-Meier method and compared by the Log-rank test.Significant prognostic factors were determined using univariate and multivariable Cox proportional hazard regression analyses. Results: In the cohort of 81 pCCA patients,67 cases(82.7%) underwent major hepatectomy while 3 cases received major hepatectomy combined with pancreaticoduodenectomy.Thirty-four patients underwent hepatectomy combined with vascular resection and reconstruction(18 cases of portal vein resection and reconstruction alone;9 cases of hepatic artery resection and reconstruction alone;7 cases of combination of portal vein and hepatic artery resection and reconstruction).Margin negative(R0 excision) were achieved in 53.1%(43/81) of these patients.The operation duration was (627±136)minutes(range:565 to 940 minutes),and the intraoperative blood loss was 400(455)ml(range:200 to 2 800 ml).The 90-day postoperative mortality was 3.7%(3/81).Grade 3-4 postoperative morbidity was 23.4% (19/81) according to the Clavien-Dindo classification of surgical complications.Up to the last follow-up at September 2022,the follow-up time was 34.0(24.2)months (range:0.4 to 103.6 months).Three patients who died within 90 days after surgery were excluded from the survival analysis.The median OS was 36.10 months (95%CI:18.23 to 42.97 months) and the 1-,3-and 5-year OS rates were 85.3%,46.8% and 27.3%,respectively.The median OS of 41 patients with negative margins was 47.83 months(95%CI:36.90 to 58.80 months) and that of 37 patients with positive margins was 20.47 months(95%CI:10.52 to 30.58 months).The median RFS of 70 patients with R0 and R1 resection was 24.50 months(95%CI:12.15 to 31.85 months)and the 1-,3-and 5-year RFS rates were 65.2%,45.7% and 29.9%,respectively.The median RFS of 41 patients with R0 resection was 38.57 months(95%CI:21.50 to 55.63 months) and that of 29 patients with R1 resection was 10.83 months(95%CI:2.82 to 19.86 months). Conclusions: The primary therapy for pCCA is radical surgical resection.A precise preoperative evaluation and sufficient preparation can reduce postoperative morbidity.Surgical treatment can achieve a better survival outcome by increasing the radical resection rate.
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@#Abstract: Objective To detect and analyze the antiserum of Yersinia pestis phage in Marmota himalayana blood from the natural plague foci of Qinghai-Tibet Plateau by micro-bolus technique, to provide a theoretical basis for interaction between phages and mammalian immunology, phage therapy and interaction between bacteriophage and ecology in future. Methods Using diagnostic Yersinia pestis phage and 3 wild plague phages from Qinghai-Tibet Plateau Natural Plague Foci as antigens, 847 serums of Marmota Himalayana blood, from Tongde, Guinan, Gonghe, Xinghai, Tianjun foci counties in Qinghai Plateau, were collected from July to September in 2020, 2021 and determined on antiserum of Yersinia pestis phage by microplate method and double agar plate method. Results The neutralization reaction experiment lasted for 24 hours between 4 phage and 847 serums by microplate method independently. These mixtures were tested by double agar plate method. All results were negative on antiserum of Yersinia pestis bacteriophage. Conclusions The positive antiserum of Yersinia pestis phage in Marmota himalayana were not found the natural plague foci of Qinghai-Tibet Plateau, which agreed with plague epidemiology in 5 foci counties in Qinghai plateau from 2020-2021, that was a characteristic of the resting period. In other words, it was in the absence of plague pathogen. It also showed indirectly that the absence or weak presence of Yersinia pestis bacteriophage in the plague foci. It showed a lower frequency on host animals coming into contact with phages naturally. The antiserum of Yersinia pestis phage may be related to the form of plague infection and the intensity of the disease.
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@#Abstract: Objective To analyze the pathogenic characteristics and epidemiological significance of human plague related strains in Qinghai Province in recent 30 years, so as to provide scientific basis for on-the-spot disposal and prevention and control measures of plague outbreak in Qinghai Province. Methods A total of 35 strains of Yersinia pestis isolated from 29 typical human plague outbreaks in Qinghai Province from 1980 to 2011 were selected and studied by biochemical fermentation experiments. Virulence factors detection of Fraction 1 antigen (Fra1), virulence antigen (VW), pigmentation (Pgm) and Yersinia pestis Ⅰ (PstⅠ), determinants and genotyping of differential regions (DFRs) were used to study the pathogenic characteristics. At the same time, according to the epidemic situation of human and animal plague in Qinghai Province in recent years, the current situation of plague prevention and control and epidemic characteristics were analyzed. Results The biotypes of 35 strains of Yersinia pestis were classical, and the biotypes of 29 strains (82.86%) were of Qinghai-Tibet Plateau type, mainly distributed in southern Qinghai and around lake areas, 2 strains (5.71%) belonged to Qilian Mountains type, mainly distributed in Qilian mountains, and 6 genotypes were identified by DFR. Among them, 16 were type 5, 12 were type 8, 2 were type 10, 1 was type 36, 3 were type 30 and 1 was type 1b, the strains of type 5 and 1b were mainly distributed around the lake and the southern foot of Qilian Mountains, while the strains of type 8, 10, 36 and 30 were mainly distributed in the southern part of Qinghai. Conclusions The pathogen of Yersinia pestis in Qinghai Plateau has complex biochemical types, the epidemic situation among animals is continuous year after year, the situation of prevention and control is serious, the occurrence and prevalence of plague seriously endanger people's health and social development, so it is necessary to do a solid job in the prevention and control of plague to ensure the safety of people's lives.
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ObjectiveTo investigate the effect of Jingangwan on the expression of osteoclast， c-Jun N-terminal kinase（JNK）， p38 mitogen-activated protein kinase（p38 MAPK）， and interleukin-1（IL-1） in the osteoporosis model rats， explore the mechanism of Jingangwan in the treatment of osteoporosis， and determine the optimal dosing concentration of Jingangwan. MethodFifty-six rats of SPF grade were randomized into a blank group，a sham operation group，a model group， model group，high-， medium-， and low-dose Jingangwan groups （0.72， 0.36， 0.18 g·kg-1·d-1， ig），and an estradiol valerate group （0.009 g·kg-1·d-1， ig）， with eight rats in each group. The rats in the model group， the blank group， and the sham operation group received 3 mL of normal saline， respectively. Samples were collected 12 weeks after drug administration. The number of osteoclasts was observed by tartrate-resistant acid phosphatase （TRAP） staining. Serum levels of JNK， p38 MAPK， and IL-1 were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression levels of p38 MAPK and JNK were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultThe TRAP staining results showed that compared with the model group， the estradiol valerate group and the Jingangwan groups could inhibit the formation of osteoclasts to different degrees. As revealed by ELISA results， compared with the model group and the sham operation group， the model group showed increased serum levels of p38 MAPK， JNK， and IL-1 （P<0.01）， while compared with the model group， all the groups with drug intervention showed decreased levels of p38 MAPK， JNK， and IL-1 （P<0.01）. The serum levels of JNK and IL-1 in the high-dose Jingangwan group were lower than those in the estradiol valerate group （P<0.05）. Real-time PCR results showed that compared with the blank group， the model group showed increased relative mRNA expression of p38 MAPK and JNK in the thighbone （P<0.01）， while compared with the model group， all the groups with drug intervention showed decreased relative mRNA expression of p38 MAPK and JNK in the thighbone （P<0.01）. ConclusionJingangwan can inhibit the formation of osteoblasts，reduce the diameter of the bone marrow cavity，improve bone quality，suppress the production of inflammatory factors，affect the metabolism of the MAPK signaling pathway，and blunt p38 MAPK and JNK activities to inhibit the differentiation and proliferation of osteoblasts and regulate bone metabolism， thereby preventing osteoporosis. Therefore，Jingangwan may be of application value in maintaining bone health and treating osteoporosis.
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Abstract Objective Tongue squamous cell carcinoma (TSCC) is an oral cancer, with high malignancy and frequent early migration and invasion. Only a few drugs can treat tongue cancer. Ginsenoside Rd is a ginseng extract with anti-cancer effects. Many noncoding RNAs are abnormally expressed in tongue cancer, thus influencing its occurrence and development. H19 and miR-675-5p can promote cancer cell growth. This study aimed to analyze the regulation effect of ginsenoside Rd on H19 and miR-675-5p in tongue cancer. Methodology We used CCK8 and flow cytometry to study the growth and apoptosis. Transwell assay was used to assess invasion; wound-healing assay to assess migration; and colony formation assays to test the ability of cells to form colonies. H19, miR-675-5p, and CDH1 expressions were analyzed by qPCR. E-cadherin expression was detected using western blot. CRISPR/cas9 system was used for CDH1 knockout. Results Ginsenoside Rd inhibited the growth and increased the apoptosis of SCC9 cells. Ginsenoside Rd also inhibited the migration and invasion of SCC9 cells. H19 and miR-675-5p were highly expressed, while CDH1 and E-cadherin expressions were low. H19 and miR-675-5p promoted SCC9 metastasis. In contrast, CDH1 and E-cadherin inhibited the metastasis of SCC9 cells. Bioinformatics analysis showed that miR-675-5p was associated with CDH1. H19 and miR-675-5p expressions decreased after ginsenoside Rd treatment, while CDH1 and E-cadherin expressions increased. Conclusions Ginsenoside Rd inhibits tongue cancer cell migration and invasion via the H19/miR-675-5p/CDH1 axis.
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BACKGROUND@#Recent cardiovascular outcome trials (CVOTs) changed the therapeutic strategy of guidelines for type 2 diabetes. We compared the characteristics of patients from real-world hospital settings with those of participants in recent pragmatic randomized trials.@*METHODS@#This electronic medical record (EMR)-based retrospective observational study investigated the data of patients with diabetes from inpatient and outpatient settings in West China Hospital of Sichuan University from January 1, 2011, to June 30, 2019. We identified patients meeting the inclusion criteria of a pragmatic randomized trial (EMPA-REG OUTCOME) based on EMRs and compared their baseline characteristics with those of the trial participants. The cutoff for the clinical significance of each characteristic was set as its minimal clinically important difference based on expert consultation.@*RESULTS@#We included 48,257 inpatients and 36,857 outpatients with diabetes and found that 8389 (17.4%) inpatients and 2646 (7.2%) outpatients met the inclusion criteria for the EMPA-REG OUTCOME trial. Compared with the trial population, the real-world inpatients meeting the eligibility criteria of the EMPA-REG OUTCOME had similar age, blood pressure, and lipid profiles but comprised of fewer males, metformin users, anti-hypertensive drug users, and aspirin users, and had a lower body mass index. The group of outpatients meeting the eligibility criteria had fewer males, similar age, fewer metformin users, fewer insulin users, fewer anti-hypertensive drug users, and fewer aspirin users compared with the trial population.@*CONCLUSIONS@#The trial population in EMPA-REG OUTCOME represents only a small portion of patients with diabetes from the inpatient and outpatient departments of a Chinese tertiary medical center. Evidence localization in different clinical settings and validation are essential to enabling extrapolation of the results from CVOTs in patients with diabetes to Chinese clinical practice.
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Humans , Male , Benzhydryl Compounds , Canagliflozin , Cardiovascular Diseases , China , Diabetes Mellitus, Type 2/drug therapy , Glucosides , Sodium-Glucose Transporter 2 Inhibitors , Tertiary Care CentersABSTRACT
Objective:To evaluate the role of nuclear receptor subfamily 1, group D, member 1/brain and muscle Arnt-like 1(Rev-erbα/Bmal1) signaling pathway in myocardial ischemia-reperfusion (I/R) injury in diabetic rats and its relationship with autophagy.Methods:SPF-grade adult male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-220 g, were used in this study.Type I diabetes mellitus was induced by intraperitoneal streptozotocin 60 mg/kg.The rats were continuously fed for 8 weeks after successful establishment of the model.Thirty rats with type 1 diabetes mellitus were divided into 3 groups by a random number table method: diabetic sham operation group (DS group, n=6), diabetic myocardial I/R group (DI/R group, n=12) and diabetic myocardial I/R plus Rev-erbα antagonist SR-8278 group (DI/R+ SR group, n=12). Eighteen non-diabetic rats were divided into 2 groups by a random number table method: non-diabetic sham operation group (NS group, n=6) and non-diabetic myocardial I/R group (NI/R group, n=12). The myocardial I/R model was established by ligation of the left anterior descending coronary artery for 30 min followed by 120-min reperfusion in anesthetized rats.SR-8278 2 mg/kg was intravenously injected via the femoral vein at 1 h before ischemia in group DI/R+ SR.Blood samples were collected from the carotid artery immediately after the end of reperfusion for determination of serum troponin I (cTnI), creatine kinase-MB (CK-MB) and lactic dehydrogenase (LDH) levels (by enzyme-linked immunosorbent assay). Then the rats were sacrificed, and myocardial tissues were obtained for determination of myocardial infarct size (by TTC method), expression of Rev-erbα and Bmal1 mRNA (by real-time polymerase chain reaction) and expression of Rev-erbα, Bmal1, microtubule-associated protein 1 light chain (LC3) Ⅱ and LC3Ⅰ (by Western blot) and for calculation of the ratio of LC3 Ⅱ/LC3Ⅰand the number of autophagosomes (with a transmission electron microscope). Results:Compared with group NS, the percentage of myocardial infarct size, serum levels of cTnI, CK-MB and LDH and the number of autophagosomes were significantly increased, the expression of Rev-erbα and its mRNA in myocardial tissues was up-regulated, the expression of Bmall and its mRNA was down-regulated, and the ratio of LC3 Ⅱ/LC3Ⅰwas increased in group NI/R, and serum levels of cTnI, CK-MB and LDH were increased, the number of autophagosomes was decreased, the expression of Rev-erbα and its mRNA in myocardial tissues was up-regulated, the expression of Bmall and its mRNA was down-regulated and the ratio of LC3 Ⅱ/LC3Ⅰwas decreased in group DS ( P<0.05). Compared with group NI/R, the percentage of myocardial infarct size and serum levels of cTnI, CK-MB and LDH were significantly increased, the number of autophagosomes was decreased, the expression of Rev-erbα and its mRNA in myocardial tissues was up-regulated, the expression of Bmall and its mRNA was down-regulated, and the ratio of LC3 Ⅱ/LC3Ⅰwas decreased in group DI/R ( P<0.05). Compared with group DS, the percentage of myocardial infarct size, serum levels of cTnI, CK-MB and LDH and the number of autophagosomes were were significantly increased, the expression of Rev-erbα and its mRNA in myocardial tissues was up-regulated, the expression of Bmall and its mRNA was down-regulated, and the ratio of LC3 Ⅱ/LC3Ⅰwas increased in group DI/R ( P<0.05). Compared with group DI/R, the percentage of myocardial infarct size, serum levels of cTnI, CK-MB and LDH and the number of autophagosomes were significantly decreased, the expression of Rev-erbα and its mRNA in myocardial tissues was down-regulated, the expression of Bmall and its mRNA was up-regulated, and the ratio of LC3 Ⅱ/LC3Ⅰwas increased in group DI/R+ SR ( P<0.05). Conclusion:Rev-erbα/BMAL1 signaling pathway is involved in the process of myocardial I/R injury by regulating cell autophagy in diabetic rats.
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The coronavirus disease 2019(COVID-19) is developing rapidly and posing great threat to public health. There is no effective intervention for the severe patients, and their prognosis is poor. It is worth noting that in the fight against COVID-19, China has always put equal emphasis on both Chinese and Western medicine. Traditional Chinese medicine has played an important role in the whole process. It is of great significance to discuss the rules and characteristics of the prescription of traditional Chinese medicine in the treatment of COVID-19. In this study, information was collected from 444 severe COVID-19 patients who were admitted to a hospital designated to treat patients with severe COVID-19 in Wuhan before March 20, 2020. We collected traditional Chinese medicine prescriptions for patients with severe COVID-19, referred to Chinese Pharmacopoeia to standardize the names of traditional Chinese medicine, and extract the property, flavor and channel tropism of traditional Chinese medicines to analyze the rules of the prescriptions. IBM SPSS Modeler 18.0 software was used to conduct correlation analysis of traditional Chinese medicine. Effective traditional Chinese medicines against COVID-19 was identified by the TCMATCOV platform. In the end, 1 532 effective prescriptions were included. Among them, the high-frequency drugs are Poria, Astragali Radix, Pogostemonis Herba, Armeniacae Semen Amarum, Atractylodis Macrocephalae Rhizoma, Pinelliae Rhizoma, Glycyrrhizae Radix et Rhizoma, Magnoliae Officinalis Cortex, Ephedrae Herba, Cinna-momi Ramulus. Most of the drugs have the following functions: resolving dampness, replenishing deficiency, resolving phlegm, cough, and asthma. The core combinations are Pogostemonis Herba-Poria, Astragali Radix-Pogostemonis Herba-Poria, Amomi Fructus-Poria, Amomi Fructus-Pogostemonis Herba, Amomi Fructus-Astragali Radix. The majority of the medicines are with cold and warm properties, and the proportions are 41.03% and 38.46%, respectively. The medicinal flavors are mainly concentrated in sweet and bitter, and the proportions are 34.71% and 30.58%, respectively. The meridian of the drug is more into the lung, stomach and spleen, with lung accounting for 22.87%. From the analysis of high-frequency drugs to the core combinations, one can see that the main treatment principle for severe COVID-19 is to remove internal and external dampness, protect the spleen and stomach, remove evil energy, and support righteousness. TCMATCOV platform was used to calculate the network disturbances of the high-frequency drugs. It was found that the traditional Chinese medicine with a high disturbance score accounted for a high proportion of the classic anti-COVID-19 prescriptions used by clinicians. Among them, the drugs with top scores are Ephedrae Herba, Citri Reticulatae Pericarpium, Eupatorii Herba, Platycodonis Radix, Cinnamomi Ramulus, Astragali Radix, Magnoliae Officinalis Cortex, Atractylodis Macrocephalae Rhizoma, Pogostemonis Herba, Scutellariae Radix. After a further exploration of the action targets, it was showed that disease-specific factor TNF was the target of the above ten drugs, and traditional Chinese medicine can exert anti-inflammatory and immune-modulating effects.
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Humans , Betacoronavirus , China , Coronavirus Infections , Drug Therapy , Drugs, Chinese Herbal , Medicine, Chinese Traditional , Pandemics , Pneumonia, Viral , Drug TherapyABSTRACT
This paper introduces the application and financing of programs of efficacy material base of traditional Chinese medicine funded by the National Natural Science Foundation of China(NSFC), the Youth Science Fund and the Regional Science Fund from 2016 to 2019, and conducts analysis and summary in terms of research objects and analysis methods, with the aim to provide reference for applicants for programs of efficacy material base of traditional Chinese medicine.
Subject(s)
China , Financial Management , Foundations , Medicine, Chinese Traditional , Natural Science DisciplinesABSTRACT
Objective:To evaluate the relationship between silence information regulator 1 (SIRT1) and NOD-like receptor protein 3 (NLRP3) inflammasomes during myocardial ischemia-reperfusion (I/R) in diabetic rats.Methods:SPF-grade healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-220 g, were used in this study.Type 1 diabetes mellitus was induced by intraperitoneal 1% streptozotocin diluted in citrate buffer solution 60 mg/kg.The rats were continuously fed for 8 weeks after successful establishment of the model.Forty-two rats with type 1 diabetes mellitus were divided into 4 groups by a random number table method: diabetic sham operation group (DS group, n=6), diabetic myocardial I/R group (DIR group, n=12), diabetic myocardial I/R plus SIRT1 agonist SRT1720 group (DIR+ SR group, n=12) and diabetic myocardial I/R plus SIRT1 inhibitor EX-527 group (DIR+ EX group, n=12). Eighteen non-diabetic rats were divided into 2 groups by a random number table method: non-diabetic sham operation group (NS group, n=6) and non-diabetic myocardial I/R group (NIR group, n=12). The myocardial I/R model was established by ligation of the left anterior descending coronary artery for 30 min followed by 120-min reperfusion in anesthetized rats.Blood samples were collected from the carotid artery immediately after the end of reperfusion for determination of serum troponin I (cTnI), creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) levels (by enzyme-linked immunosorbent assay). Then the rats were sacrificed, and myocardial tissues were obtained for determination of myocardial infarct size (by TTC method) and expression of SIRT1, NLRP3 and IL-1β (by Western blot) and for microscopic examination of pathological changes of myocardial tissues (by HE staining). The percentage of myocardial infarct size was calculated. Results:Compared with group NS, the serum levels of cTnI, CK-MB and LDH were significantly increased, the expression of SIRT1 in myocardial tissues was down-regulated, and the expression of NLRP3 and IL-1β was up-regulated in group NIR ( P<0.05). Compared with group DS, the serum levels of cTnI, CK-MB and LDH were significantly increased, the expression of SIRT1 in myocardial tissues was down-regulated, and the expression of NLRP3 and IL-1β was up-regulated in group DIR ( P<0.05). Compared with group NIR, the percentage of myocardial infarct size and serum levels of cTnI, CK-MB and LDH were significantly increased, the expression of SIRT1 in myocardial tissues was down-regulated, the expression of NLRP3 and IL-1β was up-regulated ( P<0.05), and the pathological changes were accentuated in group DIR.Compared with group DIR, the percentage of myocardial infarct size and serum levels of cTnI, CK-MB and LDH were significantly decreased, the expression of SIRT1 in myocardial tissues was up-regulated, the expression of NLRP3 and IL-1β was down-regulated ( P<0.05), and the pathological changes were significantly attenuated in group DIR+ SR, and the percentage of myocardial infarct size and serum levels of cTnI, CK-MB and LDH were significantly increased, the expression of SIRT1 in myocardial tissues was down-regulated, the expression of NLRP3 and IL-1β was up-regulated ( P<0.05), and the pathological changes were accentuated in group DIR+ EX. Conclusion:The up-regulated expression of SIRT1 can inhibit the activation of NLRP3 inflammasomes and produces endogenous protection during myocardial I/R in diabetic rats.
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To study the antidepressant effect of Shugan Hewei Tang on chronic stress depression model rats, and select the effective substance fractions. Several male SD rats were randomly divided into 17 groups: blank control group, model group, positive control group(fluoxetine), Shugan Hewei Tang high and low dose groups, 6 high and low dose groups of different substance fractions. After modeling for 3 weeks and administration for 1 week, the effective substance fractions were selected according to the body mass and behavioral performance of SD rats in each group; several neurotransmitters in hippocampus of rats were determined by LC-MS/MS method, including norepinephrine(NE), serotonin(5-HT), 5-indoleacetic acid(5-HIAA), r-aminobutyric acid(GABA), and glutamic acid(Glu). Behavioral results after modeling showed that as compared with the blank group, the body mass growth of the model group was significantly reduced(P<0.01); the sugar water consumption was reduced(P<0.01); the distance between the open field and the number of crossing the central area were also significantly reduced(P<0.01, P<0.01); the resting time was increased significantly(P<0.01); and the forced swimming time was significantly prolonged(P<0.01), indicating that the depression model was effective. After intragastric administration, as compared with the model group, the above detection indicators of volatile oils, total polysaccharides and terpenoid in Fluoxetine, Shugan Hewei Tang groups were all changed(P<0.05 or P<0.01). The levels of NE, 5-HT and GABA in the hippocampus of the model group were significantly lower than those in the blank group(P<0.01), and the levels of 5-HIAA and Glu were significantly increased(P<0.01). As compared with the model group, neurotransmitters of the treatment groups were changed obviously or significantly(P<0.05 or P<0.01). Shugan Hewei Tang showed obvious anti-depressant effects, and the volatile oils, total polysaccharides and terpenoids acted as the main active substances. The mechanism of anti-depression may be related to its regulation of various neurotransmitter levels in the hippocampus.
Subject(s)
Animals , Male , Rats , Chromatography, Liquid , Depression , Drug Therapy , Disease Models, Animal , Drugs, Chinese Herbal , Pharmacology , Hippocampus , Metabolism , Neurotransmitter Agents , Metabolism , Oils, Volatile , Pharmacology , Random Allocation , Rats, Sprague-Dawley , Stress, Psychological , Tandem Mass SpectrometryABSTRACT
Objective@#To evaluate the role of histone deacetylase 3 (HDAC3) in renal injury induced by myocardial ischemia-reperfusion (I/R) in diabetic rats.@*Methods@#SPF healthy adult male Sprague-Dawley rats, weighing 210-220 g, were used in this study.Diabetes mellitus was induced by intraperitoneal injection of 1% streptozotocin 60 mg/kg.Eighteen diabetic rats were divided into 3 groups (n=6 each) using a random number table method: sham operation group (group S), group I/R and HDAC3 inhibitor RGFP966 group (RG). The myocardial I/R model was established by ligation of the left anterior descending coronary artery for 30 min followed by 120-min reperfusion.RGFP966 10 mg/kg was intraperitoneally injected at 1 h before myocardial ischemia in group RG.The right internal carotid artery was isolated at 120 min of reperfusion for measurement of serum lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), creatinine (Cr) and urea nitrogen concentrations.Renal tissues were obtained for examination of the pathological changes and for determination of the expression of HDAC3, silent information regulator 1 (SIRT1) and interleukin-1β (IL-1β). The damage to the renal tubules was scored.@*Results@#Compared with S group, the serum LDH, CK-MB, Cr and urea nitrogen concentrations and renal tubular damage score were significantly increased, the expression of HDAC3 and IL-1β was up-regulated, and the expression of SIRT1 was down-regulated in group I/R (P<0.05). Compared with group I/R, the serum LDH, CK-MB, Cr and urea nitrogen concentrations and renal tubular damage score were significantly decreased, the expression of HDAC3 and IL-1β was down-regulated, and the expression of SIRT1 was up-regulated in group RG (P<0.05).@*Conclusion@#Up-regulated expression of HDAC3 is involved in renal injury induced by myocardial I/R in diabetic rats.
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Objective To evaluate the role of histone deacetylase 3 (HDAC3) in renal injury induced by myocardial ischemia-reperfusion (I/R) in diabetic rats.Methods SPF healthy adult male Sprague-Dawley rats,weighing 210-220 g,were used in this study.Diabetes mellitus was induced by intraperitoneal injection of 1％ streptozotocin 60 mg/kg.Eighteen diabetic rats were divided into 3 groups (n =6each) using a random number table method:sham operation group (group S),group I/R and HDAC3 inhibitor RGFP966 group (RG).The myocardial I/R model was established by ligation of the left anterior descending coronary artery for 30 min followed by 120-min reperfusion.RGFP966 10 mg/kg was intraperitoneally injected at 1 h before myocardial ischemia in group RG.The right internal carotid artery was isolated at 120 min of reperfusion for measurement of serum lactate dehydrogenase (LDH),creatine kinase-MB (CKMB),creatinine (Cr) and urea nitrogen concentrations.Renal tissues were obtained for examination of the pathological changes and for determination of the expression of HDAC3,silent information regulator 1 (SIRT1) and interleukin-1β (IL-1β).The damage to the renal tubules was scored.Results Compared with S group,the serum LDH,CK-MB,Cr and urea nitrogen concentrations and renal tubular damage score were significantly increased,the expression of HDAC3 and IL-1β was up-regulated,and the expression of SIRT1 was down-regulated in group I/R (P＜0.05).Compared with group I/R,the serum LDH,CK-MB,Cr and urea nitrogen concentrations and renal tubular damage score were significantly decreased,the expression of HDAC3 and IL-1β was down-regulated,and the expression of SIRT1 was up-regulated in group RG (P＜0.05).Conclusion Up-regulated expression of HDAC3 is involved in renal injury induced by myocardial I/R in diabetic rats.
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Objective To investigate the therapeutic effect of all-trans retinoic acid (ATRA) for lupus nephritis(LN) in mice.Methods Eighteen MRL/lpr mice were randomly divided into control group,cyclophosphamide treatment group and ATRA treatment group,with 6 rats in each group.The mice in control group were administered saline (10 mg· kg-1 · d-1) by intragastric administration for 8 weeks;the mice in ATRA treatment group were administered ATRA (10 mg · kg-1 · d-1) by intragastric administration for 8 weeks;the mice in cyclophosphamide treatment group were given cyclophosphamide (100 mg · kg-1 · d-1) by intraperitoneal injection for 2 days.Blood samples and kidney specimens were collected at the end of the experiment.The levels of blood urea nitrogen (BUN),serum creatinine (Scr) and urine creatinine (Ucr) were detected by full automatic biochemical analyzer;the changes of renal tissue structure was observed by periodic acid schiff;the expression of transforming growth factor-β1 (TGF-β1) and monocyte chemotactic protein-1 (MCP-1) was detected by immunohistochemistry.Results The levels of Scr and BUN of mice in ATRA treatment group and cyclophosphamide treatment group were significantly lower than those in the control group,and the Ucr level was significantly higher than that in the control group (P ＜ 0.01);the BUN level of mice in ATRA treatment group was significantly higher than that in the cyclophosphamide treatment group,but the Ucr level was significantly lower than that in the cyclophosphamide treatment group (P ＜ 0.01);there was no statistic difference in the Scr level of mice between the ATRA treatment group and cyclophosphamide treatment group (P ＞ 0.05).In control group,the glomerular basement nembrane and renal tubular basement membrane of mice was thicken,the mesangial of mice was proliferated;the thicken glomerular basement membrane,renal tubular basement membrane and proliferated mesangial were also seen in ATRA treatment group and cyclophosphamide treatment group which was lighten than control group,and cyclophosphamide treatment group was lighten than ATRA treatment group.The expression of MCP-1,TGF-β1 of mice in cyclophosphamide treatment group and ATRA treatment group were significantly lower than those in the control group (P ＜ 0.05);the expression of MCP-1,TGF-β1 of mice in ATRA treatment group were significantly higher than those in cyclophosphamide treatment group(P ＜ 0.05).Conclusion Both cyclophosphamide and ATRA can reduce the levels of Scr and BUN,lighten the pathological changes of renal and decrease the expression of TGF-β1 and MCP-1 in LN mice;but the effect of cyclophosphamide is better than ATRA.
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<p><b>OBJECTIVE</b>To evaluate the effects of the combination of basic fibroblast growth factor (bFGF), transforming growth factor-Β1 (TGF-Β1), bone marrow mesenchymal stem cells (BMSCs), and temperature-responsive chitosan hydrogel (TCH) gel on the repair of degenerative intervertebral disc in rat models.</p><p><b>METHODS</b>Rat models of intervertebral disc degeneration were established by acupuncture. The degenerative effects were observed under magnetic resonance imaging (MRI). The BMSCs was cultured in vitro and then transfected by adenovirus with enhanced green fluorescent protein to make it carry the gene of enhanced green fluorescent protein,which functioned as fluorescence labeling. The SD rat models of intervertebral disc degeneration were divided into four groups: group A, treated with the combination of bFGF, TGF-Β1,BMSCs,and TCH gel; group B, treated with the combination of BMSCs and TCH gel;group C, treated with the combination of bFGF,TGF-Β1, and TCH gel;and group D, treated with PBS buffer solution. After the corresponding reagents were injected into the degenerative intervertebral discs of each group, the rats were cultivated for another four weeks and then the repair effects of the intervertebral discs were observed under MRI. Furthermore,the intervertebral discs of each group were taken out and observed by HE and Masson staining. The nucleus pulposus was aspirated and the expressions of aggrecan,collagen 2,Sox-9,and collagen I of nucleus pulposus of each group were tested by reverse transcription polymerase chain reaction and Western blot.</p><p><b>RESULTS</b>The transplanted BMSCs survived in the intervertebral disc and differentiated into nucleus pulposus-like cells. MRI showed that:the signal intensity of the nucleus pulposus of group A was much higher than that of the rest groups, the signal intensity of group B was higher than that of group C, and the signal intensity of group D was the lowest,in which the dura mater spinalis was in compression and the spinal cord changed in beaded shape. The differences of the Pfirrmann grading among the four groups had statistical significance (P<0.05). The results of the HE and Masson stains showed:the intervertebral disc of group A was well-structured,the quantity of nucleus pulposus cells was larger than that of the other three groups,and the boundary between the nucleus pulposus and the annulus fibrosus was clearly defined;the quantity of the nucleus pulposus cells of group B was larger than that of group C, and the broken annulus fibrosus was not observed in group B, while the broken annulus fibrosus could be observed in group C; and, the nucleus pulposus cells of group D were replaced by fibrous tissue. The results of the reverse transcription polymerase chain reaction and Western blot tests showed that,in terms of the expressions of aggrecan,collagen 2 and Sox-9,group A was the highest, followed by group B,group C,and group D (P<0.05); in terms of the expression of collagen 1,there was no obvious difference among these four groups (P>0.05).</p><p><b>CONCLUSIONS</b>The transplanted BMSCs can survive in the degenerative intervertebral disc and differentiate into nucleus pulposus-like cells. The combination of bFGF, TGF-Β1, BMSCs,and TCH gel has obvious repair effect on the degenerative intervertebral discs. The effect of the combination of BMSCs and TCH gel on transplantation therapy of the degenerative intervertebral discs is better than that of the combination of bFGF, TGF-Β1 and TCH gel but worse than that of the combination of bFGF, TGF-Β1, BMSCs, and TCH gel.</p>
Subject(s)
Animals , Rats , Bone Marrow Cells , Bone Marrow Transplantation , Cell Differentiation , Collagen , Disease Models, Animal , Fibroblast Growth Factor 2 , Hematopoietic Stem Cells , Intervertebral Disc , Intervertebral Disc Degeneration , Rats, Sprague-Dawley , Transforming Growth Factor beta1 , Wound HealingABSTRACT
The incompatibility of traditional Chinese medicines is related to the clinical medication safety, so has attracted wide attentions from the public. With the deepening of studies on the incompatibility of traditional Chinese medicines represented by 18 incompatible herbs, the incompatibility of theory traditional Chinese medicines has raised to new heights. From the origin of incompatibility theory of traditional Chinese medicines, relationship of herbs, harms of incompatible herbs and principle of prevention to toxic effects of specific incompatible medicines, the innovation and development of the traditional Chinese medicine incompatibility theory was explored. Structurally, the incompatibility of traditional Chinese medicines refers to the opposition of two herbs based on seven emotions and clinical experience. The combination of incompatible herbs may lead to human harms, especially latent harm and inefficacy of intervention medicines. The avoidance of the combination of incompatible herbs and the consideration of both symptoms and drug efficacy are the basic method to prevent adverse reactions. The recent studies have revealed five characteristics of incompatible herbs. Toxicity potentiation, toxication, efficacy reduction and inefficacy are the four manifestations of the incompatible relations. The material changes can reflect the effects of toxicity potentiation and toxication of opposite herbs. The accumulation of toxicity and metabolic changes are the basis for latent harms. The antagonistic effect of main efficacies and the coexistence of positive and negative effects are the distinctive part of the incompatibility. The connotation of incompatible herbs plays an important role in the innovation of the traditional Chinese medicine incompatibility theory.
Subject(s)
Humans , Drug Incompatibility , Drug Therapy , History , Drugs, Chinese Herbal , Chemistry , History , Pharmacology , History, Ancient , Medicine in Literature , Medicine, Chinese TraditionalABSTRACT
<p><b>BACKGROUND</b>At present, China has listed the compound tablet containing a fixed dose of rosiglitazone and metformin, Avandamet, which may improve patient compliance. The aim of this study was to evaluate the efficacy and safety of Avandamet or uptitrated metformin treatment in patients with type 2 diabetes inadequately controlled with metformin alone.</p><p><b>METHODS</b>This study was a 48-week, multicenter, randomized, open-labeled, active-controlled trial. Patients with inadequate glycaemic control (glycated hemoglobin [HbA1c] 7.5-9.5%) receiving a stable dose of metformin (≥1500 mg) were recruited from 21 centers in China (from 19 November, 2009 to 15 March, 2011). The primary objective was to compare the proportion of patients who reached the target of HbA1c ≤7% between Avandamet and metformin treatment.</p><p><b>RESULTS</b>At week 48, 83.33% of patients reached the target of HbA1c ≤7% in Avandamet treatment and 70.00% in uptitrated metformin treatment, with significantly difference between groups. The target of HbA1c ≤6.5% was reached in 66.03% of patients in Avandamet treatment and 46.88% in uptitrated metformin treatment. The target of fasting plasma glucose (FPG) ≤6.1 mmol/L was reached in 26.97% of patients in Avandamet treatment and 19.33% in uptitrated metformin treatment. The target of FPG ≤7.0 mmol/L was reached in 63.16% of patients in Avandamet treatment and 43.33% in uptitrated metformin treatment. Fasting insulin decreased 3.24 ± 0.98 μU/ml from baseline in Avandamet treatment and 0.72 ± 1.10 μU/ml in uptitrated metformin treatment. Overall adverse event (AE) rates and serious AE rates were similar between groups. Hypoglycaemia occurred rarely in both groups.</p><p><b>CONCLUSIONS</b>Compared with uptitrated metformin, Avandamet treatment provided significant improvements in key parameters of glycemic control and was generally well tolerated.</p><p><b>REGISTRATION NUMBER</b>ChiCTR-TRC-13003776.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Blood Glucose , C-Reactive Protein , Metabolism , Diabetes Mellitus, Type 2 , Blood , Drug Therapy , Drug Combinations , Drug Therapy, Combination , Hypoglycemic Agents , Therapeutic Uses , Metformin , Therapeutic Uses , Thiazoles , Therapeutic UsesABSTRACT
<p><b>OBJECTIVE</b>To study the effectiveness of waist circumference cut-off values in predicting the prevalence of metabolic syndrome (MetS) and risk factors in adults in China.</p><p><b>METHODS</b>A cross-sectional survey was condcuted in 14 provinces (autonomous region, municipality) in China. A total of 47,325 adults aged⋝20 years were selected by multistage stratified sampling, and questionnaire survey and physical and clinical examination were conducted among them. MetS was defined according to the International Diabetes Federation (IDF) criteria and modified IDF criteria.</p><p><b>RESULTS</b>The age-standardized prevalence of MetS was 24.2% (22.1% in men and 25.8% in women) and 19.5% (22.1% in men and 18.0% in women) according to the IDF criteria and modified IDF criteria respectively. The age-standardized prevalence of pre-MetS was 8.1% (8.6% in men and 7.8% in women) according to the modified IDF criteria. The prevalence of MetS was higher in urban residents than rural residents and in northern China residents than in southern China residents. The prevalence of central obesity was about 30% in both men and women according to the ethnicity-specific cut-off values of waist circumference for central obesity (90 cm for men and 85 cm for women). Multivariate regression analysis revealed no significant difference in risk factors between the two MetS definitions.</p><p><b>CONCLUSION</b>Using both the modified IDF criteria and ethnicity-specific cut-off values of waist circumference can provide more useful information about the prevalence of MetS in China. Conclusion Using both the modified IDF criteria and ethnicity-specific cut-off values of waist circumference can provide more useful information about the prevalence of MetS in China.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , China , Epidemiology , Cross-Sectional Studies , Metabolic Syndrome , Diagnosis , Epidemiology , Obesity , Epidemiology , Prevalence , Risk Assessment , Risk Factors , Waist CircumferenceABSTRACT
Anterior lumbar interbody fusion (ALIF) followed by posterior pedicle screw fixation (PSF) in a second procedure is mostly used to implement lumbar spine fusion. ALIF followed by anterior lumbar screw-plate has a lot of advantages, but its biomechanical stability requires confirmation. This study evaluated the biomechanical stability of a novel anterior lumbar locked screw-plate (ALLSP) by comparison with posterior lumbar PSF. Twelve fresh human cadaveric lumbar specimens (L4-L5) were assigned to four groups: ALIF+PSF group, ALIF+ALLSP (both fixed) group, ALIF group and an untreated control (both non-fixed) group. The first three groups received implantation of a rectangular titanium cage. Tests under axial compression, flexion, extension, lateral bending, or rotation showed that the fixed groups had significantly stronger stability than the non-fixed groups (P=0.000 for all). The ALIF+ALLSP group had significantly greater axial stiffness under applied axial compression and significantly less angular displacement under rotational forces than the ALIF+PSF group. The angular displacement of the ALIF+ALLSP group was less under flexion than that of the ALIF+PSF, and the angular displacement under lateral bending and extension was greater, but these differences were not statistically significant. In summary, the ALLSP conforms to the anterior lumbar spine and has good biomechanical stability. It is a reliable choice for enhancing the stability of ALIF.
Subject(s)
Adult , Female , Humans , Male , Bone Plates , Bone Screws , Lumbar Vertebrae , Pathology , Materials TestingABSTRACT
Objective To establish an ultrasonic viscoelastic detection system to measure the viscoelasticity of in vitro tissues. Methods Based on the method of shear wave dispersion ultrasound vibration (SDUV), this system applied acoustic radiation force to excite harmonic vibration in soft tissues. The propagation of shear waves induced by the vibration was detected and the tissue viscoelasticity properties were calculated. The standard phantom and rat liver experiment were conducted using this system, and preliminary assessment of the system was completed. Results The measured result of standard phantom was close to the calibration value. The viscous and elastic coefficient of rat liver were (1.12±0.41) Pa•s and (0.81±0.40) kPa, respectively. Conclusions The results about the standard phantom and rat liver experiment approved feasibility of the system for viscoelasticity measurement on in vitro animal experiment, which is a preliminary exploration for the realization of liver fibrosis detection of human body.