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Establishment of rat models of liver transplantation provides an ideal animal model for resolving the problems of postoperative complications and perioperative treatment of liver transplantation. With in-depth study of the establishment of rat models of liver transplantation, classic "two-cuff" technique has been gradually employed. However, poor surgical field, vascular torsion, biliary tract injury and long anhepatic phase remain unresolved in the process of liver transplantation using traditional techniques. At present, the rat models of liver transplantation at home and abroad are modified mainly from the reconstruction of four vital anatomic structures including the suprahepatic inferior vena cava, portal vein, infrahepatic inferior vena cava and bile duct. Therefore, the latest progress in the reconstruction of the suprahepatic inferior vena cava, portal vein, infrahepatic inferior vena cava and bile duct was reviewed, aiming to provide reference for the establishment of rat models of liver transplantation and promote further development of liver transplantation techniques.
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Objective:To investigate the influencing factors for early tumor recurrence and the efficacy of adjuvant chemotherapy in gallbladder carcinoma (GBC) patients after curative-intent resection.Methods:The retrospective case-control study was conducted. The clinicopathological data of 506 patients with GBC in 11 medical centers, including The First Affiliated Hospital of Xi'an Jiaotong University et al, from January 2016 to December 2020 were collected. There were 168 males and 338 females, aged (62±11)years. All patients underwent curative-intent resection of GBC, and they were divided into patients with and without early recurrence based on time to postoperative recurrence. Observation indicators: (1) treatment; (2) follow-up and survival of patients; (3) analysis of influencing factors for early tumor recurrence after curative-intent resection of GBC; (4) efficacy of postoperative adjuvant chemotherapy. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the Mann-Whitney U test. Univariate analysis was conducted using the corresponding statistical methods based on data type. Multivariate analysis was conducted using the Logistic regression model with forward method. The Kaplan-Meier method was used to draw survival curve and calculate survival rate, and Log-Rank test was used for survival analysis. Results:(1) Treatment. Of 506 patients, there were 112 cases with postoperative adjuvant chemotherapy, and 394 cases without postopera-tive adjuvant chemotherapy. They underwent 5(range, 3-9)cycles of postoperative adjuvant chemo-therapy. (2) Follow-up and survival of patients. All 506 patients underwent postoperative follow-up, with the follow-up time of 55(range, 34-93)months. During the follow-up, there were 248 patients with tumor recurrence, including 158 cases of early recurrence and 90 cases of late recurrence, and there were 258 patients without tumor recurrence. Of 506 patients, 275 cases survived, and 231 cases died of multiple organ failure caused by tumor recurrence and metastasis. The postoperative recurr-ence-free survival time, overall survival time were 52(range,1-93)months, 62(range, 2-93)months. The 1-, 3-, 5-year disease-free survival rates and 1-, 3-, 5-year overall survival rates of the 506 pati-ents were 68.8%, 53.8%, 47.9% and 78.3%, 58.7%, 51.6%, respectively. Results of survival analysis showed that the median overall survival time of 158 patients with postoperative early recurrence and 348 patients without postoperative early recurrence (including 90 cases of late recurrence and 258 cases of no tumor recurrence) were 9(range, 2-73)months and unreached, showing a significant difference between them ( χ2=456.15, P<0.05). (3) Analysis of influencing factors for early tumor recurrence after curative-intent resection of GBC. Results of multivariate analysis showed that carcinoembryonic antigen (CEA) >5.0 μg/L, poorly differentiated tumor, liver invasion, and tumor N staging as stage N1-N2 were independent risk factors influencing early tumor recurrence after cura-tive-intent resection of GBC ( odds ratio=2.74, 6.20, 1.81, 2.93, 4.82, 95% confidence interval as 1.62-4.64, 1.82-21.12, 1.15-3.08, 1.68-5.09, 1.91-12.18, P<0.05), while postoperative adjuvant chemo-therapy was an independent protect factor ( odds ratio=0.39, 95% confidence interval as 0.21-0.71, P<0.05). (4) Efficacy of postoperative adjuvant chemotherapy. The median overall survival time of 394 patients without postoperative adjuvant chemotherapy and 112 patients with postoperative adjuvant chemotherapy were 57(range, 2-93)months and unreached, showing a significant differ-ence between them ( χ2=9.38, P<0.05). Of the 158 patients with postoperative early recurrence after curative-intent resection of GBC, 135 cases didn't receive adjuvant chemotherapy and 23 cases received adjuvant chemotherapy, with the overall survival time of 8(range, 2-73)months and 17(range, 8-61)months, respectively, showing a significant difference between them ( χ2=7.68, P<0.05). Conclusions:CEA >5.0 μg/L, poorly differentiated tumor, liver invasion, and tumor N staging as stage N1-N2 are independent risk factors influencing early tumor recurrence after curative-intent resection of GBC, while postoperative adjuvant chemotherapy is an independent protect factor. Postoperative adjuvant chemotherapy can prolong the overall survival time of patients with post-operative tumor early recurrence.
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ObjectiveTo investigate the effects of Linggui Zhugantang on mitochondrial fission and fusion and silencing information regulator 3(Sirt3)/adenosine monophosphate dependent protein kinase (AMPK) signaling pathway in chronic heart failure (CHF) rats after myocardial infarction (MI). MethodSD rats randomly divide into sham operation group (normal saline ,thread only without ligature), model group (normal saline, ligation of the left anterior descending coronary artery proximal to the heart), Linggui Zhugantang group (4.8 g·kg-1) and Captopril group (0.002 57 g·kg-1), with 10 rats in each group. Administere drug continuously for 28 days. Echocardiography detected cardiac function parameters. Hematoxylin eosin (HE) staining observed the pathological changes of the heart. Immunofluorescence detected the levels of reactive oxygen species (ROS). JC-1 detect mitochondrial membrane potential. Colorimetry measure adenosine triphosphate (ATP), superoxide dismutase (SOD), malondialdehyde (MDA), mitochondrial respiratory chain complex activity (Ⅰ-Ⅳ). TdT-mediated dUTP nick end labeling (TUNEL) staining detected the apoptosis rate of myocardial tissue. Western blot detected protein expression levels of Sirt3, phosphorylated AMPK (p-AMPK), phosphorylated dynamic-related protein 1(p-Drp1), mitochondrial fission protein 1(Fis1), mitochondrial fission factor (MFF), optic atrophy protein 1(OPA1). ResultCompared to the sham group, the left ventricular end diastolic diameter (LVIDd) and left ventricular end systolic diameter (LVIDs) were significantly increased in model group (P<0.01), while the left ventricular short axis shortening rate (LVFS) and left ventricular ejection fraction (LVEF) were significantly decreased (P<0.01). There were inflammatory cell infiltration and obvious pathological injury in myocardial tissue. ROS, MDA levels and myocardial cell apoptosis rate were significantly increased (P<0.01), SOD level, ATP content, and membrane potential were significantly decreased (P<0.01). The activity of mitochondrial respiratory chain complexes (Ⅰ-Ⅳ) was significantly decreased (P<0.01). Levels of p-Drp1, Fis1, MFF proteins were significantly up-regulated (P<0.01), while Sirt3, p-AMPK, OPA1 proteins level were significantly down-regulated (P<0.01). Compared with model group, LVIDd and LVIDs were significantly decreased (P<0.01), LVEF and LVFS were significantly increased (P<0.01). Inflammatory cell infiltration and pathological damage of myocardial tissue were significantly relieved. ROS, MDA levels and myocardial cell apoptosis rate were significantly decreased in Linggui Zhugantang group and Captopril group (P<0.01), SOD level, ATP content, and membrane potential significantly increased (P<0.01). The activity of mitochondrial respiratory chain complexes (Ⅰ-Ⅳ) increased significantly (P<0.01),and p-Drp1, Fis1, MFF protein levels were significantly down-regulated (P<0.01), Sirt3, p-AMPK, OPA1 protein were significantly up-regulated (P<0.01). ConclusionLinggui Zhugantang can alleviate oxidative stress and apoptosis damage of myocardial cells, maintain mitochondrial function stability, and its effect may be related to mitochondrial mitosis fusion and Sirt3/AMPK signaling pathway.
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AIM: To investigate and analyze the current situation and needs of clinical research nurses in China, in order to provide scientific basis for constructing a training system for research nurses, promoting standardized training, and achieving standardized management for them. METHODS:A self-made questionnaire was used to investigate 102 research nurses from nearly 70 well-known clinical trial institutions in China. The contents of the questionnaire mainly included the general information, professional experience and work content of the research nurses, the sense of accomplishment and training needs of clinical trial work. RESULTS: Among the 102 research nurses surveyed, 92.15% have a bachelor's degree or above; 53.92% of those have intermediate or higher professional titles; 74.51% of them are part-time research nurse. Among professional experiences, 19.61% have more than 10 years of clinical trial experience; 47.06%, 40.20%, and 21.17% of surveyed research nurses were authorized to participate in clinical trial drug management, sample management, and quality control; 70.59% of research nurses have a high sense of achievement in their daily work. In terms of education and training needs, clinical trial related laws and regulations, standardized training for clinical trial protocol implementation, and good clinical practice (GCP) are the three most important aspects. CONCLUSION: Clinical research nurses in China have a relatively high level of education and nursing experience, but there is still a large gap in the amount of professional full-time clinical research nurses in China. Due to the rapid development of innovative drugs and devices, as well as the urgent need to improve the clinical research system, it is necessary to establish a training, assessment, and evaluation system for research nurses that is in line with China's national conditions in order to improve the professional level of research nurses, and improve the quantity and quality of clinical trial research on innovative drugs and devices in China.
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AIM To investigate the protective effects and the mechanism of the Liuwei Dihuang Pills on mouse brain microvascular endothelial(bEnd.3)cells damaged by β-Amyloid protein1-40(Aβ1-40).METHODS CCK8 method was used to detect the effects of Aβ1-40 and medicated serum of Liuwei Dihuang Pills(MSLDP)on cell activity,and to screen the appropriate concentration.bEnd.3 cells of the control group,the Aβ1-40 group,the MSLDP+Aβ1-40 group and the MSLDP group had their low density lipoprotein-associated protein 1(LRP1),receptor for advanced glycation end products(RAGE),matrix metalloproteinase-2(MMP-2),MMP-9,scaffold protein zonule protein-1(ZO-1)detected by Western blot.bEnd.3 cells assigned into the control group,the Aβ1-40 group,the FPS-ZM1(RAGE inhibitor)+Aβ1-40 group and the FPS-ZM1+Aβ1-40+MSLDP group had their expressions of RAGE,MMP-9,MMP-2 and ZO-1 detected by Western blot as well.RESULTS The cell activity of bEnd.3,was dose-dependently decreased by Aβ1-40(P<0.01),but was protected by MSLDP(P<0.05,P<0.01).And 10 μmol/L Aβ1-40 and 10%MSLDP were selected for subsequent experiments.Compared with the control group,the Aβ1-40 group displayed increased protein expressions of RAGE,MMP-2 and MMP-9(P<0.01),decreased protein expressions of LRP1,ZO-1 and BDNF(P<0.05,P<0.01),and decreased fluorescence intensities of LRP1 and ZO-1(P<0.01).Compared with the Aβ1-40 group,the MSLDP group shared decreased expressions of RAGE,MMP-2,MMP-9 proteins and RAGE fluorescence intensity(P<0.05,P<0.01),and increased expressions of LRP1,ZO-1 and BDNF proteins,and the fluorescence intensity of LRP1 and ZO-1(P<0.05,P<0.01);the Aβ1-40+FPS-ZM1 group displayed decreased protein expressions of MMP-2,MMP9 and RAGE(P<0.05,P<0.01),and increased ZO-1 protein expression(P<0.05);and the Aβ1-40+FPS-ZM1+ MSLDP group displayed an even more decreased protein expressions of MMP-2,MMP9 and RAGE(P<0.01),increased ZO-1 protein expression(P<0.01)due to the the combination use of FPS-ZM1 and MSLDP.CONCLUSION Liuwei Dihuang Pills can protect the tight junction of bEnd.3 injured by Aβ1-40 and neurovascular units from Alzheimer's disease by alleviating the dysfunction of the blood-brain barrier via RAGE-mediated MMP-2/MMP-9 pathway inhibition.
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With an ageing population, healthy longevity is becoming an important scientific concern. The longevity phenomenon is closely related to the intestinal microflora and is highly complicated; it is challenging to identify and define the core gut microbiota associated with longevity. Therefore, in this study, 16S rRNA sequencing data were obtained from a total of 135 faecal samples collected as part of the latest sampling and pre-collection initiative in the Guangxi longevity area, and weighted gene co-expression network analysis (WGCNA) was used to find a mediumpurple3 network module significantly associated with the Guangxi longevity phenomenon. Five core genera, namely, Alistipes, Bacteroides, Blautia, Lachnospiraceae NK4A136 group, and Lactobacillus, were identified via network analysis and random forest (RF) in this module. Two potential probiotic strains, Lactobacillus fermentum and Bacteroides fragilis, were further isolated and screened from the above five core genera, and then combined and used as an intervention in naturally ageing mice. The results show a change in the key longevity gut microbiota in mice toward a healthy longevity state after the intervention. In addition, the results show that the probiotic combination effectively ameliorated anxiety and necrosis of hippocampal neuronal cells in senescent mice, improving their antioxidant capacity and reducing their inflammation levels. In conclusion, this longer-term study provides a new approach to the search for longevity hub microbiota. These results may also provide an important theoretical reference for the healthification of the intestinal microflora in the general population, and even the remodelling of the structure of the longevity-state intestinal microflora.
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Gastrointestinal Microbiome , Probiotics , Humans , Mice , Animals , Gastrointestinal Microbiome/physiology , RNA, Ribosomal, 16S/genetics , China , Aging/physiologyABSTRACT
Moyamoya disease(MMD)is a bilateral stenosis occlusional disease that selectively affects the superior segment of clinoid of the internal carotid artery with secondary abnormal vascular network formation at the base of the skull.Intracranial and extracranial vascular reconstruction is the main treatment of moyamoya disease.However,moyamoya disease revasectomy still faces many challenges,with high requirements of surgical techniques and high risk of complications.In this paper,the perioperative management of cerebrovascular reconstruction in moyamoya disease was discussed in terms of surgical indications,surgical timing,patient management,surgical methods of cerebrovascular reconstruction and postoperative complications,so as to provide reference for improving the prognosis of patients.
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Objective To design a mobile container-based negative pressure chamber compatible with kinds of carriers to isolate and treat patients with respiratory infectious diseases.Methods A negative pressure chamber with standard container sizes was developed whose enclosure structure involved in 2 mm-thick galvanized steel plate,10 mm-thick high-performance thermal isolation polyurethane foam board,2 mm-thick galvanized steel plate and 10 mm-thick integral inner panel.There were three functional areas included in the chamber for clean office area,semi-polluted passage and polluted ward with toilet.Negative pressure differences between the functional areas were generated by full DC air supply and exhaust system to form directional air flow in the chamber.The patient's exhaled air was purified before emission with the high-efficiency particulate air filtration system.The negative pressure chamber was equipped with a portable life monitoring and support device,a remote consultation and guidance system,a water and electricity support system and etc.Results Air quality tests showed that the negative pressure chamber met the national standards in air cleanliness,static pressure difference,number of dust particles,settled bacteria,microorganisms on the surface of the object and etc.Conclusion The negative pressure chamber compatible with kinds of carriers can be used for the isolation and emergency treatment of patients with respiratory infectious diseases and the long-distance transport of critically ill patients.[Chinese Medical Equipment Journal,2023,44(9):24-28]
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Objective To compare the surgical results of cholesteatoma of external auditory canal under the otoscope and the microscope.Methods Clinical data of 44 patients with cholesteatoma from January 2015 to December 2019 were analyzed retrospectively.According to the operation mode,the patients were divided into observation group and control group.The cholesteatoma in the observation group was cleaned under the otoscope,and the cholesteatoma in the control group was cleaned under the microscope.The clinical effects of the two groups were compared.Results The patients in both groups were cured and their hearing was improved in different degrees.Compared with the control group,the difference of speech frequency hearing threshold between the observation group and the control group was statistically significant(t = 19.71,t = 13.41,P<0.05).The operation time of the observation group was short than that of the control group,and the local discomfort of the observation group was lighter than that of the control group after operation,which was statistically significant(t =-3.68,t =-2.44,P<0.05).All the patients were followed up for 6 months with dry ears and no recurrence.Conclusion Endoscopic treatment of cholesteatoma of external auditory canal is simple and effective,which is worthy of clinical application.
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OBJECTIVE@#To investigate the distribution and antimicrobial susceptibility of causative microorganisms recovered from patients with intra-abdominal infections (IAIs).@*METHODS@#A total of 2,926 bacterial and fungal strains were identified in samples collected from 1,679 patients with IAIs at the Peking Union Medical College Hospital between 2011 and 2021. Pathogenic bacteria and fungi were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Antimicrobial susceptibility testing (AST) was performed using the VITEK 2 compact system and the Kirby-Bauer method. AST results were interpreted based on the M100-Ed31 clinical breakpoints of the Clinical and Laboratory Standards Institute.@*RESULTS@#Of the 2,926 strains identified, 49.2%, 40.8%, and 9.5% were gram-negative bacteria, gram-positive bacteria, and fungi, respectively. Escherichia coli was the most prevalent pathogen in intensive care unit (ICU) and non-ICU patients; however, a significant decrease was observed in the isolation of E. coli between 2011 and 2021. Specifically, significant decreases were observed between 2011 and 2021 in the levels of extended-spectrum β-lactamase (ESBL)-producing E. coli (from 76.9% to 14.3%) and Klebsiella pneumoniae (from 45.8% to 4.8%). Polymicrobial infections, particularly those involving co-infection with gram-positive and gram-negative bacteria, were commonly observed in IAI patients. Moreover, Candida albicans was more commonly isolated from hospital-associated IAI samples, while Staphylococcus epidermidis had a higher ratio in community-associated IAIs. Additionally, AST results revealed that most antimicrobial agents performed better in non-ESBL-producers than in ESBL-producers, while the overall resistance rates (56.9%-76.8%) of Acinetobacter baumanmii were higher against all antimicrobial agents than those of other common gram-negative bacteria. Indeed, Enterococcus faecium, Enterococcus faecalis, S. epidermidis, and S. aureus were consistently found to be susceptible to vancomycin, teicoplanin, and linezolid. Similarly, C. albicans exhibited high susceptibility to all the tested antifungal drugs.@*CONCLUSION@#The distribution and antimicrobial susceptibility of the causative microorganisms from patients with IAIs were altered between 2011 and 2021. This finding is valuable for the implementation of evidence-based antimicrobial therapy and provides guidance for the control of hospital infections.
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Humans , Anti-Bacterial Agents , Escherichia coli , Gram-Negative Bacteria , Gram-Positive Bacteria , Retrospective Studies , Staphylococcus aureus , Intraabdominal Infections/epidemiology , Candida albicans , CoinfectionABSTRACT
As one of the most frequent complications of diabetes, diabetic neuropathy often involves peripheral and central nervous systems. Neuroinflammation is the key pathogenic factor of secondary nerve injury in diabetes. NOD-like receptor pyrin domain-containing 3(NLRP3) inflammasome is a group of subcellular multiprotein complexes, including NLRP3, apoptosis associated speck-like protein(ASC), and pro-cysteinyl aspartate specific proteinase 1(pro-caspase-1). NLRP3 inflammasome is an inducer of innate immune responses. Its activation stimulates the inflammatory cascade reaction, promotes the release of inflammatory mediators, triggers cell death and uncontrolled autophagy, activates glial cells, facilitates peripheral immune cell infiltration, and initiates amyoid β(Aβ)-tau cascade reactions. As a result, it contributes to the central nerve, somatic nerve, autonomic nerve, and retinal nerve cell damage secondary to diabetes. Therefore, due to its key role in the neuroinflammation responses of the body, NLRP3 inflammasome may provide new targets for the treatment of diabetic neuropathy. With multi-target and low-toxicity advantages, traditional Chinese medicine plays a vital role in the treatment of diabetic neuropathy. Accumulating evidence has shown that traditional Chinese medicine exerts curative effects on diabetic neuropathy possibly through regulating NLRP3 inflammasome. Although the role of NLRP3 inflammasome in diabetes and related complications has been investigated in the literature, systematical studies on drugs and mechanism analysis for secondary neuropathy are still lacking. In this article, the role of NLRP3 inflammasome in diabetic neuropathy was explored, and the research progress on traditional Chinese medicine in the treatment of diabetic neuropathy through NLRP3 inflammasome was reviewed.
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Humans , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Diabetic Neuropathies/drug therapy , Medicine, Chinese Traditional , Neuroinflammatory Diseases , Inflammation , Diabetes MellitusABSTRACT
OBJECTIVE To establish the estimation model for the exposure of mycophenolic acid (MPA) in early renal transplant recipients [calculated by the area under the plasma concentration-time curve with 12 h (AUC0-12 h)]. METHODS Twenty kidney transplant recipients, who received triple immunosuppressive therapy of mycophenolate mofetil (MMF)+tacrolimus+ methylprednisolone, were selected and given MMF dispersible tablets (750 mg, q12 h) on the 15th day after the operation; the blood samples were collected from the patients before and 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0 hours after the administration, respectively. The blood concentration of MPA was determined, and the pharmacokinetic parameters of MPA were calculated. The multivariate linear stepwise regression analysis method was used to fit an estimation formula for the finite sampling method suitable for MPA-AUC0-12 h of the recipients. Bland-Altman analysis was used to evaluate the agreement between the estimation formula and the classical pharmacokinetic method. RESULTS The main pharmacokinetic parameters of MPA in 20 renal transplant recipients: c0 was (1.53±0.84) μg/mL, cmax was (12.07±5.97) μg/mL, t1/2 was (5.41±3.67) h, tmax was (1.58±0.75) h, and the average AUC0-12 h calculated by the classical pharmacokinetic method was (33.95±13.40) μg·h/mL. MPA-AUC0-12 h was estimated with sampling points of “4.0, 8.0, 12.0 h”; the simplified calculation formula was AUC0-12 h=12.058+2.819c4.0+7.045c8.0+ 3.879c12.0 (R 2=0.934). The predicted value had a good correlation and consistency with the measured value, and 95.0% of predicted values did not exceed the x±1.96SD (standard deviation) range. CONCLUSIONS The estimation model is established successfully for the exposure of MPA in early renal transplant recipients; the model has better prediction accuracy and fewer sampling points.
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Objective:To investigate the influencing factors of textbook outcomes in liver surgery (TOLS) after radical resection of gallbladder carcinoma.Methods:The retrospective case-control study was conducted. The clinicopathological data of 530 patients who underwent radical resection of gallbladder carcinoma in 15 medical centers, including the First Affiliated Hospital of Army Medical University et al, from January 2014 to January 2020 were collected. There were 209 males and 321 females, aged (61±10)years. Patients underwent radical resection of gallbladder carcinoma, including cholecystectomy, hepatectomy, invasive bile duct resection, and lymph node dissection. Observation indicators: (1) situations of TOLS; (2) influencing factors of TOLS. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the Mann-Whitney U test. The univariate analysis was conducted using the corresponding statistical methods based on data type, and variables with P<0.10 were included in multivariate analysis. Multivariate analysis was conducted using the Logistic stepwise regression model. Results:(1) Situations of TOLS. All 530 patients underwent radical resection of gallbladder carcinoma, and there were 498 cases achieving R 0 resection, 508 cases without ≥grade 2 intra-operative adverse events, 456 cases without postoperative grade B and grade C biliary leakage, 513 cases without postoperative grade B and grade C liver failure, 395 cases without severe com-plications within postoperative 90 days, 501 cases did not being re-admission caused by severe com-plications within postoperative 90 days. Of the 530 patients, 54.53%(289/530) of patients achieved postoperative TOLS, while 45.47%(241/530) of patients did not achieve postoperative TOLS. (2) Influencing factors of TOLS. Results of multivariate analysis showed that American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy were independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma ( odds ratio=2.65, 1.87, 5.67, 5.65, 2.55, 3.34, 95% confidence interval as 1.22?5.72, 1.18?2.95, 2.51?12.82, 2.83?11.27, 1.41?4.63, 1.88?5.92, P<0.05). Conclusion:American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy are independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma.
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Objective:To investigate the association of monocyte to lymphocyte ratio (MLR) with all-cause mortality and cardiovascular disease (CVD) mortality in patients with continuous ambulatory peritoneal dialysis (CAPD).Methods:It was a retrospective cohort study. The clinical data of 495 incident CAPD patients in the First Affiliated Hospital of Zhengzhou University from January 1, 2013 to December 31, 2019 were retrospectively analyzed. The optimal cut-off value of baseline MLR was determined by the receiver operating characteristic (ROC) curve for predicting all-cause death in the first year of CAPD, and then the patients were divided into high MLR group and low MLR group. The differences of clinical data and laboratory tests were compared between the two groups. The endpoint events were death (all-cause death and CVD death), conversion to hemodialysis, conversion to kidney transplantation, or follow-up until March 31, 2020. The survival curve was drawn by the Kaplan-Meier method, and the Log-rank test was used to compare the survival difference between the two groups. A Cox regression model was established to analyze the relevant factors of all-cause mortality and CVD mortality in CAPD patients.Results:The study included 495 patients, with age of (43.79±12.16) years and 308 (62.22%) males. The median age of dialysis was 17(10, 30) months. By the end of follow-up, 61(12.32%) of 495 patients had died, 51(10.51%) had been converted to hemodialysis, and 28(5.66%) had been converted to kidney transplantation. Of the 61 patients who died, 36(59.02%) died of cardiovascular events. ROC curve analysis results showed that the optimal cut-off value was 38.24%, so there were 246 cases in the high MLR group (MLR>38.24%) and 249 cases in the low MLR group (MLR≤38.24%). The all-cause mortality rates were 6.83% in the low MLR group and 17.89% in the high MLR group, and the CVD mortality rates were 3.21% in the low MLR group and 11.38% in the high MLR group, respectively. The Kaplan-Meier survival curve showed that the survival rate of the low MLR group was significantly higher than that of the high MLR group (all-cause mortality, Log-rank χ2=18.369, P<0.001; CVD mortality, Log-rank χ2=16.142, P<0.001). Using all-cause death as the end event, the 1-year, 3-year and 5-year cumulative survival rates were 99.5%, 89.4% and 79.9%, respectively, with a median survival time of 64 months in the low MLR group. The 1-year, 3-year and 5-year cumulative survival rates were 95.0%, 68.3% and 49.6%, respectively, with a median survival time of 54 months in the high MLR group. Using CVD death as the end event, the 1-year, 3-year and 5-year cumulative survival rates were 99.5%, 95.2% and 91.2%, respectively, with a median survival time of 69 months in the low MLR group. The 1-year, 3-year, and 5-year cumulative survival rates were 97.8%, 78.6%, and 60.8%, respectively, with a median survival time of 60 months in the high MLR group. Multivariate Cox regression analysis showed that MLR was independently associated with all-cause mortality ( HR=2.744, 95% CI 1.484-5.075, P=0.001) and CVD death ( HR=3.249, 95% CI 1.418- 7.443, P=0.005) in CAPD patients. According to the competing risk model analysis, MLR was still independently associated with all-cause mortality and CVD mortality in CAPD patients. Conclusion:MLR is associated with all-cause mortality and CVD mortality in CAPD patients, and can be used as a valuable indicator for judging the prognosis of CAPD patients.
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Myocardial infarction is one of the leading causes of death worldwide, appearing at the last point of atherosclerotic plaque progression and unstable rupture. Impaired cellular signals after myocardial infarction leads to maladaptive changes, leading to ventricular remodeling and heart failure. MicroRNAs (miRNAs/miRs) are a kind of non-coding small RNAs that negatively regulate gene expression and regulate protein synthesis rate by changing the stability of targeted mRNA. This article reviews the latest research progress on the involvement of miRNAs in the progression of atherosclerotic plaques, the molecular mechanism of cardiac injury and subsequent remodeling during infarction, as well as the results of clinical studies, and puts forward the problems and limitations of targeted miRNAs in the treatment of cardiovascular diseases such as myocardial infarction and ventricular remodeling.
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ObjectiveTo evaluate the efficacy and safety of Linggui Zhugantang in the treatment of heart failure. MethodCNKI,Wanfang Data,VIP,CBM,PubMed,ClinicalKey,Cochrane Library ,Web of Science ,Medline and Embase were systematically searched to screen randomized controlled trials(RCT)of Linggui Zhugantang in the treatment of heart failure. Meta-analysis was performed on the included studies using RevMan 5.3 ResultTwenty-seven studies were included with a total sample size of 3 569 cases,including 1 816 in experimental group and 1 753 in control group. Meta-analysis showed that compared with conventional drugs alone,combination of Linggui Zhugantang and conventional drugs improved the marked effective rate [relative risk(RR)=1.41,95% confidence interval(CI)[1.29,1.54],P<0.000 01] and the total effective rate(RR=1.21,95%CI[1.17,1.25],P<0.000 01),decreased the levels of serum B-type brain natriuretic peptide (BNP)[mean difference(MD)=-390.08,95%CI[-538.84,-241.52],P<0.000 01] and serum N-terminal pro-brain natriuretic peptide(NT-proBNP)(MD=-713.83,95%CI[-828.41, -599.25],P<0.000 01), left ventricular end-diastolic diameter(LVDD)(MD=-5.23,95%CI[-7.18, -3.29],P<0.000 01), left ventricular end-systolic diameter(LVSD)(MD=-4.54,95%CI[-6.75,-2.33],P<0.000 01), tumor necrosis factor-α(TNF-α)(MD=-37.53,95%CI [-50.72,-24.34],P<0.000 01)and interleukin-6(IL-6)(MD=-23.64,95%CI [-47.40,0.11],P=0.05), increased left ventricular ejection fraction(LVEF)(MD=5.73,95%CI [3.33,8.14],P<0.000 01),and cardiac output [stroke volume (SV) ](MD=5.90,95%CI[4.56,7.25],P<0.000 01). In addition, the combination prolonged the 6 minute walking test distance(MD=51.08,95%CI [33.01,69.16],P<0.000 01),reduced the traditional Chinese medicine (TCM) syndrome score(MD=-3.50,95%CI [-4.92,-2.07],P<0.000 01),and improved quality of life(MD=-7.26,95%CI [-10.43,-4.09],P<0.000 01),with higher safety(RR=0.36,95%CI [0.17,0.79],P=0.01). ConclusionLinggui Zhugantang combined with conventional drug therapy could improve cardiac function,reduce cardiac fibrosis,and improve prognosis, with high safety.
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ObjectiveTo explore the effect of Xiao Xianxiongtang (XXXT) on the transforming growth factor (TGF)-β1-induced invasion, metastasis, and epithelial-mesenchymal transition (EMT) of gastric cancer MGC-803 cells and the underlying mechanism. MethodThe molecular docking between XXXT and nuclear factor of activated T cells (NFAT) was performed by CB-DOCK (http://clab.labshare.cn/cb-dock/). The invasion and metastasis model of MGC-803 cells was established with 10 μg·L-1 TGF-β1. MGC-803 cells were classified into blank group, model group, 0.1 g·L-1 XXXT group, 0.2 g·L-1 XXXT group, and 0.4 g·L-1 XXXT group. For further clarifying the key role of Wnt5a/Ca2+/NFAT signaling pathway in the inhibition of XXXT on gastric cancer, MGC-803 cells were transfected with Wnt5a overexpression plasmid, and then the cells were classified into blank plasmid group, Wnt5a-OE group, blank plasmid + XXXT (0.4 g·L-1) group, and Wnt5a-OE + XXXT (0.4 g·L-1) group. Cell viability was determined by cell counting kit-8 (CCK-8) assay, cell invasion and migration ability by Transwell invasion assay and wound healing assay, expression of EMT-related proteins (E-cadherin, N-cadherin, Vimentin, Snail) and Wnt5a/Ca2+/NFAT signaling pathway-related key proteins [Wnt5a, calcineurin (CaN), NFAT1, and p-NFAT1] by Western blot, and changes in intracellular Ca2+ concentration by immunofluorescence assay. ResultMolecular docking suggested that XXXT acted on Wnt5a/Ca2+/NFAT signaling pathway. XXXT (0.1, 0.2, 0.4 g·L-1) significantly promoted the loss of MGC-803 cell viability (P<0.05,P<0.01). It inhibited cells from invading the transwell lower chamber and slowed down the healing of cell wounds in a dose-dependent manner (P<0.05, P<0.01). Moreover, it promoted the expression of E-cadherin while suppressed the expression of N-cadherin, Vimentin, and Snail (P<0.05, P<0.01). Further experiments showed that XXXT could inhibit the expression of Wnt5a, CaN, NFAT1, and p-NFAT1, and reduce the nuclear expression of NFAT1 and the transcription activity mediated by NFAT1, so as to reduce the cellular Ca2+ concentration (P<0.05, P<0.01). XXXT can reverse the effect of Wnt5a (P<0.05, P<0.01). ConclusionXXXT can attenuate the invasion, metastasis, and EMT of MGC-803 cells via the Wnt5a/Ca2+/NFAT pathway, thereby weakening the tumor-promoting effect of TGF-β1. In summary, XXXT may exert therapeutic effect on gastric cancer by regulating the invasion, metastasis, and EMT of gastric cancer cells.
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ObjectiveTo investigate the effect of Liuwei Dihuangwan on memory function of senescence-accelerated mouse prone 8 (SAMP8) mice by regulating autophagy through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/forkhead box O3a (FoxO3a) pathway. MethodSix male senescence-accelerated mouse resistant 1 (SAMR1) mice of SPF grade aging 6 months were assigned to a normal group, and 24 male SAMP8 mice of SPF grade aging 6 months were randomly divided into a model group, a donepezil group (0.747 mg·kg-1), and high- and low-dose Liuwei Dihuangwan groups (2.700 and 1.350 g·kg-1), with 6 mice in each group. The mice were treated with drugs by gavage for 2 months. Morris water maze was used to detect the learning and memory abilities of mice in each group. Nissl staining was used to observe the neurons in the cortex and hippocampus. The positive expression of microtubule-associated protein 1 light chain 3B (LC3B) in the cortex and hippocampus was detected by immunohistochemistry (IHC). Western blot was used to detect the protein expression of the mammalian ortholog of yeast ATG6 (Beclin-1), B cell lymphoma-2 (Bcl-2), autophagy-related gene 5 (ATG5), cysteinyl aspartate-specific protease 3 (Caspase-3), Caspase-9, Akt, p-Akt, FoxO3a, and p-FoxO3a. ResultCompared with the normal group, the model group showed prolonged escape latency (P<0.05,P<0.01), reduced number of platform crossings and the residence time in the target quadrant (P<0.01), decreased neurons with reduced volume and dispersed distribution in the cortex and hippocampus, increased positive expression of LC3B (P<0.01), elevated expression of Beclin-1 and ATG5 in the cortex (P<0.01), declined Bcl-2 expression (P<0.01), up-regulated Caspase-3 and Caspase-9 expression (P<0.01), and decreased expression levels of p-Akt/Akt and p-FoxO3a/FoxO3a (P<0.01). Compared with the model group, the donepezil group and the Liuwei Dihuangwan groups showed shortened 3 d escape latency (P<0.05,P<0.01), increased number of platform crossings (P<0.01), and prolonged residence time in the target quadrant (P<0.01). In the donepezil group, the number of neurons in the cortex and hippocampus was increased. In the Liuwei Dihuangwan groups, the number of neurons and Nissl bodies increased with denser distribution and lower degree of cell damage. The positive expression of LC3B in the cortex and hippocampus was decreased in the donepezil group and Liuwei Dihuangwan groups (P<0.01). The expression of Beclin-1 was decreased in the Liuwei Dihuangwan groups (P<0.01). The expression of ATG5 was decreased in the donepezil group and the low-dose Liuwei Dihuangwan group (P<0.01). The donepezil group and the Liuwei Dihuangwan groups showed the increased expression level of Bcl-2 in the cortex (P<0.01), decreased expression level of Caspase-3 (P<0.01), reduced expression level of Caspase-9 (P<0.05,P<0.01), and elevated expression levels of p-Akt/Akt and p-FoxO3a/FoxO3a (P<0.01). ConclusionLiuwei Dihuangwan can effectively improve the learning and memory abilities of the SAMP8 mice and protect neurons. Its mechanism may be related to the regulation of the PI3K/Akt/FoxO3a signaling pathway, down-regulation of the expression of ATG5, Beclin-1, and LC3B, and the inhibition of apoptosis.
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ObjectiveTo investigate the protective effect of Liuwei Dihuangwan on neurovascular injury in SAMP8 mice. MethodThe Alzheimer's disease (AD) model with insufficiency of kidney essence was induced in 75 SAMP8 mice aging 6 months. The model mice were divided into model group, positive control group (donepezil hydrochloride, 0.747 mg·kg-1·d-1), and high-, medium-, and low-dose Liuwei Dihuangwan groups (2.700, 1.350, 0.675 g·kg-1·d-1), with 15 mice in each group. Fifteen SAMR1 mice were assigned to a normal control group. All mice were administered continuously for 2 months. The spatial memory of mice was tested by the Morris water maze. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in the hippocampus and cortex of brain tissues. The immunohistochemical method (IHC) was used to detect the deposition of amyloid β-protein (Aβ) and the expression of von Willebrand factor (vWF) and CD34 in the hippocampus and cortex of brain tissues. Electron microscopy was used to observe the ultrastructural changes in cerebral microvessels. Western blot was used to detect the protein expression levels of the receptor of advanced glycation endproduct (RAGE), low-density lipoprotein receptor-related protein 1 (LRP1), vascular endothelial growth factor A (VEGF-A), and P-selection in the hippocampus and cortex of brain tissues. ResultCompared with the normal control group, the model group showed prolonged escape latency and swimming distance (P<0.01), increased number of glial cells, decreased number of nerve cells, blurred tight junctions or enlarged gap of the brain microvascular endothelial cells, severely injured membrane structure, swollen mitochondria of endothelial cells, ruptured membrane, massive dissolution in cristae, increased protein expression of Aβ and vWF in the hippocampus and cortex (P<0.01), reduced protein expression of CD34 (P<0.05), elevated protein expression of RAGE and P-selection in the cortex (P<0.01), and decreased protein expression level of LRP1 and VEGF-A (P<0.01). Compared with the model group, the Liuwei Dihuangwan groups showed shortened escape latency and swimming distance (P<0.05), reduced number of glial cells in the cortex and hippocampus, increased number of microvessels in the cortex, clear double-layer membrane structure in tight junctions between the microvascular endothelial cells, increased number of mitochondria with intact membrane and recovered mitochondrial cristae, decreased protein expression of Aβ, vWF, RAGE, and P-selection in the hippocampus and cortex (P<0.05), and increased protein expression of CD34, LRP1, and VEGF-A (P<0.05). ConclusionLiuwei Dihuangwan can regulate Aβ metabolism through the RAGE/LRP1 receptor system and promote cerebral microvascular angiogenesis by inhibiting vWF expression and increasing VEGF-A and CD34, thereby improving cerebral microvascular injury in SAMP8 mice.
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Objective:To evaluate the correlation between endemic arsenic poisoning and abnormal electrocardiogram (ECG).Methods:PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), Wanfang data, VIP and other databases were used for literature retrieval, and epidemiological literatures related to abnormal ECG of endemic arsenic poisoning published in domestic and abroad were included in the study. The time limit was from the establishment of the database to December 1, 2020. RevMan 5.3 was used for Meta-analysis of binary variables. Random effect model was selected according to the results of heterogeneity, and odds ratio ( OR) was used as the effect index. Characteristic changes were found by subgroup analysis. Bias was published by funnel plot. Results:Nine articles were included in this Meta-analysis, with 6 articles in Chinese and 3 articles in English, respectively. The abnormal ECG changes included QTc prolongation, ST-T segment change, left axis deviation and arrhythmia. Finally, 1 975 cases were included in the exposure group, including 575 cases of abnormal ECG; 750 cases of control group, including 145 cases of abnormal ECG. Meta-analysis showed that the combined OR value [95% confidence interval ( CI)] of abnormal ECG changes was 4.41 (2.83 - 6.87), with statistical significance between the two groups ( Z = 6.56, P < 0.05); the results of subgroup analysis showed that the combined OR values (95% CI) of QTc prolongation, ST-T segment change, left axis deviation and arrhythmia were 12.30 (5.91 - 25.59), 2.74 (1.39 - 5.41), 2.93 (0.89 - 9.62) and 4.13 (2.38 - 7.17), respectively. Conclusions:Endemic arsenic poisoning may cause abnormal ECG. Prolongation of QTc caused by arsenic exposure may be the characteristic change of abnormal ECG.