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Objective:To investigate the clinical characteristics of choledocholithiasis com-bined with periampullary diverticulum and influencing factor for difficult cannulation of endoscopic retrograde cholangiopancreatography (ERCP).Methods:The retrospective case-control study was conducted. The clinical data of 1 920 patients who underwent ERCP for choledocholithiasis in 15 medical centers, including the First Hospital of Lanzhou University, et al, from July 2015 to December 2017 were collected. There were 915 males and 1 005 females, aged (63±16)years. Of 1 920 patients, there were 228 cases with periampullary diverticulum and 1 692 cases without periampullary diverticulum. Observation indicators: (1) clinical characteristics of patients with choledocholithiasis; (2) intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis; (3) influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Measurement 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(range) or M( Q1, Q3), and com-parison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Logistic regression model was used for univariate and multivariate analyses. Results:(1) Clinical characteristics of patients with choledocholithiasis. Age, body mass index, cases with complications as chronic obstructive pulmonary disease, diameter of common bile duct, cases with diameter of common bile duct as <8 mm, 8?12 mm, >12 mm, diameter of stone, cases with number of stones as single and multiple were (69±12)years, (23.3±3.0)kg/m 2, 16, (14±4)mm, 11, 95, 122, (12±4)mm, 89, 139 in patients with choledocholithiasis combined with periampullary diverticulum, versus (62±16)years, (23.8±2.8)kg/m 2, 67, (12±4)mm, 159, 892, 641, (10±4)mm, 817, 875 in patients with choledocholithiasis not combined with periampullary diver-ticulum, showing significant differences in the above indicators between the two groups ( t=?7.55, 2.45, χ2=4.54, t=?4.92, Z=4.66, t=?7.31, χ2=6.90, P<0.05). (2) Intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis. The balloon expansion diameter, cases with intraoperative bleeding, cases with hemorrhage management of submucosal injection, hemostatic clip, spray hemostasis, electrocoagulation hemostasis and other treatment, cases with endoscopic plastic stent placement, cases with endoscopic nasal bile duct drainage, cases with mechanical lithotripsy, cases with stone complete clearing, cases with difficult cannulation, cases with delayed intubation, cases undergoing >5 times of cannulation attempts, cannulation time, X-ray exposure time, operation time were 10.0(range, 8.5?12.0)mm, 56, 6, 5, 43, 1, 1, 52, 177, 67, 201, 74, 38, 74, (7.4±3.1)minutes, (6±3)minutes, (46±19)minutes in patients with choledocholithiasis combined with periampullary diverticulum, versus 9.0(range, 8.0?11.0)mm, 243, 35, 14, 109, 73, 12, 230, 1 457, 167, 1 565, 395, 171, 395, (6.6±2.9)minutes, (6±5)minutes, (41±17)minutes in patients with choledocholithiasis not combined with periampullary diverticulum, showing significant differences in the above indicators between the two groups ( Z=6.31, χ2=15.90, 26.02, 13.61, 11.40, 71.51, 5.12, 9.04, 8.92, 9.04, t=?3.89, 2.67, ?3.61, P<0.05). (3) Influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Results of multivariate analysis showed total bilirubin >30 umol/L, number of stones >1, combined with periampullary diverticulum were indepen-dent risk factors for difficult cannulation in patients with periampullary diverticulum who underwent ERCP for choledocholithiasis ( odds ratio=1.31, 1.48, 1.44, 95% confidence interval as 1.06?1.61, 1.20?1.84, 1.06?1.95, P<0.05). Results of further analysis showed that, of 1 920 patients undergoing ERCP for choledocholithiasis, the incidence of postoperative pancreatitis was 17.271%(81/469) and 8.132%(118/1 451) in the 469 cases with difficult cannulation and 1 451 cases without difficult cannula-tion, respectively, showing a significant difference between them ( χ2=31.86, P<0.05). In the 1 692 patients with choledocholithiasis not combined with periampullary diverticulum, the incidence of postopera-tive pancreatitis was 17.722%(70/395) and 8.250%(107/1 297) in 395 cases with difficult cannula-tion and 1 297 cases without difficult cannulation, respectively, showing a significant difference between them ( χ2=29.00, P<0.05). In the 228 patients with choledocholithiasis combined with peri-ampullary diverticulum, the incidence of postoperative pancreatitis was 14.865%(11/74) and 7.143%(11/154) in 74 cases with difficult cannulation and 154 cases without difficult cannulation, respectively, showing no significant difference between them ( χ2=3.42, P>0.05). Conclusions:Compared with patients with choledocholithiasis not combined with periampullary divertioulum, periampullary divertioulum often occurs in choledocholithiasis patients of elderly and low body mass index. The proportion of chronic obstructive pulmonary disease is high in choledocholithiasis patients with periampullary diverticulum, and the diameter of stone is large, the number of stone is more in these patients. Combined with periampullary diverticulum will increase the difficult of cannulation and the ratio of patient with mechanical lithotripsy, and reduce the ratio of patient with stone complete clearing without increasing postoperative complications of choledocholithiasis patients undergoing ERCP. Total bilirubin >30 μmol/L, number of stones >1, combined with periampullary diverticulum are independent risk factors for difficult cannulation in patients of periampullary diverticulum who underwent ERCP for choledocholithiasis.
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Objective:To evaluate the autogenous arteriovenous fistula(AVF) insufficiency by ultrasound monitoring of brachial artery resistance index(RI).Methods:The brachial artery RI and blood flow volume(FV) data of 828 patients who underwent color-Doppler ultrasound detection after AVF in the General Hospital of Western Theater Command from January 2019 to June 2021 were retrospectively analyzed. The patients were grouped according to the adequacy of clinical dialysis, including 668 patients in the group with normal AVF function and 160 patients in the group with insufficient AVF function. The general information and ultrasonic measurement parameters were compared between the two groups. The correlation between brachial artery FV and RI was analyzed. The evaluation of brachial artery flow RI for AVF insufficiency was analyzed by ROC curve.Results:There were statistically significant differences between the two groups in brachial artery RI and FV(both P<0.001). The results of Pearson correlation analysis showed that brachial artery FV was negatively correlated to RI ( r=-0.657, P<0.001). The area under ROC curve for assessing AVF function by brachial artery RI was 0.970, with 95% CI was 0.955-0.986, the optimal cut-off value was 0.665, and the sensitivity and specificity were 0.888 and 0.955, respectively. Conclusions:Brachial artery RI in patients with AVF insufficiency is significantly higher than that in patients with normal AVF function. The optimal cutoff value of brachial artery RI can be used as an evaluation parameter for rapid screening of AVF function.
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Objective To evaluate the clinical efficacy of endoscopic retrograde cholangiopancreatography (ERCP)-based comprehensive minimally invasive treatment for biliary anastomotic stenosis (BAS) after liver transplantation. Methods Clinical data of 60 BAS recipients after liver transplantation were retrospectively analyzed, 54 male and 6 female, aged (48±10) years. ERCP was initially carried out. If it succeeded, plastic or metallic stents were placed into the biliary tract. If it failed, percutaneous transhepatic cholangial drainage (PTCD) or single-operator cholangioscopy (SpyGlass) was adopted to pass through the stenosis. If all these procedures failed, magnetic anastomosis or other special methods were delivered. The incidence and treatment of BAS after liver transplantation were summarized. The efficacy, stent removal and recurrence were observed. Results The median time of incidence of BAS after liver transplantation was 8 (4, 13) months. Within postoperative 1 year, 1-2 years and over 2 years, 39, 16 and 5 recipients were diagnosed with BAS, respectively. All 60 BAS recipients after liver transplantation were successfully treated, including 56 cases initially receiving ERCP, and 41 completing BAS treatment, with a success rate of 73%. The failure of guide wire was the main cause of ERCP failure. The success rates of PTCD, SpyGlass and magnetic anastomosis were 5/9, 5/7 and 7/8, respectively. Two recipients were successfully treated by percutaneous choledochoscope-assisted blunt guide wire technique and stent placement in the biliary and duodenal fistula. After 3 (3, 4) cycles of ERCP and 13 (8, 18) months of stent indwelling, 38 recipients reached the stent removal criteria, including 25 plastic stents and 13 metallic stents. The indwelling time of plastic stents was longer than that of metallic stents (P < 0.05). Six cases suffered from stenosis recurrence at 12 (8, 33) months after stent removal, and the recurrence rate was 16%. Six patients were treated with ERCP, and 5 of them did not recur after the stents were successfully removed. Multivariate analysis showed that delayed diagnosis of stenosis and frequent ERCP before stent removal were the independent risk factors for BAS recurrence (both P < 0.05). Conclusions ERCP-based comprehensive minimally invasive treatment may improve the success rate of BAS treatment after liver transplantation and yield satisfactory long-term efficacy. Delayed diagnosis of BAS and high frequent ERCP required for stent removal are the independent risk factors for BAS recurrence.
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Objective:To investigate the efficacy and influencing factors of anlotinib in treatment of elderly patients with small cell lung cancer after second-line treatment failure.Methods:A total of 56 elderly patients with small cell lung cancer who were diagnosed and treated in the Tumor Hospital Affiliated to Xinjiang Medical University from September 2018 to February 2020 were collected. All patients were treated with anlotinib capsule after failure of second-line chemotherapy, objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) were calculated, and ORR, DCR and PFS of patients with different clinical characteristics were compared. Cox proportional hazards model was used to analyze the factors influencing PFS in elderly patients with small cell lung cancer, and adverse drug reactions were observed.Results:After 2 cycles of treatment, the ORR and DCR of 56 elderly patients with small cell lung cancer were 10.7% (6/56) and 53.6% (30/56) respectively. Among them, the ORR and DCR of patients without brain metastasis were 20.8% (5/24) and 75.0% (18/24), which were higher than 3.1% (1/32) and 37.5% (12/32) in patients with brain metastasis, with statistically significant differences ( χ2=4.496, P=0.034; χ2=7.754, P=0.005). The ORR and DCR of patients with Eastern Cooperative Oncology Group (ECOG) score of 0-1 were 21.7% (5/23) and 69.6% (16/23), which were higher than those of patients with ECOG score of 2-3 [3.0% (1/33), 42.4% (14/33)], with statistically significant differences ( χ2=4.959, P=0.026; χ2=4.014, P=0.045). ORR and DCR were not related to gender, age, clinical stage or smoking status (all P>0.05). The median PFS of 56 patients was 3.8 months. The median PFS of patients aged ≤70 years was 5.0 months, and that of patients aged >70 years was 3.4 months, with a statistically significant difference ( χ2=5.452, P=0.020). The median PFS of patients without brain metastasis was 5.1 months, and that of patients with brain metastasis was 3.2 months, with a statistically significant difference ( χ2=8.895, P=0.003). The median PFS of patients with ECOG score of 0-1 was 5.0 months, and that of patients with ECOG score of 2-3 was 2.9 months, with a statistically significant difference ( χ2=5.923, P=0.015). The median PFS of patients with limited stage was 5.0 months, and that of patients with extensive stage was 3.1 months, with a statistically significant difference ( χ2=5.141, P=0.023). Cox multivariate analysis showed that ECOG score ( HR=2.522, 95% CI: 1.378-4.615, P=0.003) and brain metastasis or not ( HR=0.323, 95% CI: 0.168-0.622, P=0.001) were independent prognostic factors of PFS. During the treatment of anlotinib, the main adverse reactions were grade Ⅰ-Ⅱ, grade Ⅲ-Ⅳ adverse reactions were mainly hypertension and hand-foot syndrome, which improved after drug reduction and symptomatic treatment, and could be tolerated later. The incidence of drug reduction was 3.6% (2/56), and there were no patients with drug interruption or termination of treatment. Conclusion:Anlotinib has good short-term efficacy and survival benefits in the treatment of elderly patients with small cell lung cancer after second-line treatment failure. It has good therapeutic effect for patients with low ECOG score and without brain metastasis, and has tolerable adverse reactions and high safety.
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Multiple myeloma (MM), ranking the second most common malignancy in the blood system, is a heterogeneous disease characterized by clonal proliferation of plasma cells producing immunoglobulin. Due to the wide use of new drugs, including proteinase inhibitor (PI), immune modulators (IMiD) and monoclonal antibodies, great progress has been made in the treatment of MM, but almost all patients eventually develop drug resistance. Pomalidomide is the third generation of IMiD and a very well tolerated regimen for relapsed/refractory MM. This paper summarizes the combined therapy based on pomalidomide to provide the theoretical basis for a better clinical application of pomalidomide.
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Objective:To evaluate the effect of TBK1 overexpression on hypoxia-reoxygenation (H/R) injury in isolated mouse cardiomyocytes subjected to high glucose and the relationship with mitochondrial autophagy.Methods:Normally cultured log-phase HL-1 mouse cardiomyocytes were inoculated in a 6-well plate at a density of 1×10 6 cells/ml and were divided into 4 groups ( n=10 each) using a random number table method: control group (group C), high glucose group (group HG), high glucose and H/R group (group HG+ H/R), and TBK1 overexpression group (group TBK1). The cells were incubated in culture medium with 1% fetal bovine serum and 1% double antibody for 24 h when the cell density reached 50%.When the cell density reached 80%, pcDNA3.1 (+ ) was used as a vector to achieve TBK1 overexpression.The cells were cultured with high glucose medium (33 mmol/L) for 24 h, exposed to 94% N 2+ 5% CO 2+ 1% O 2 for 24 h in an incubator at 37℃ followed by 12 h reoxygenation in an incubator containing 5% CO 2 at 37°C to establish the model of H/R injury to cardiomyocytes subjected to high glucose.After reoxygenation, CCK-8 assay was used to detect cell viability, the activity of lactic dehydrogenase (LDH) in supernatant was detected using LDH kit, mitochondrial contents were determined using Mito-Tracter green fluorescent probe, and the expression of TBK1 and mitophagy-related proteins PINK1, Parkin, LC3B and P62 was detected by Western blot. Results:Compared with group C, the cell viability was significantly decreased, the activity of LDH in supernatant was increased, mitochondrial contents were decreased, the expression of TBK1, PINK1, Parkin and LC3B was down-regulated, and the expression of P62 was up-regulated in HG group and HG+ H/R group ( P<0.05). Compared with group HG, the cell viability was significantly decreased, the activity of LDH in supernatant was increased, mitochondrial contents were decreased, the expression of TBK1, PINK1, Parkin and LC3B was down-regulated, and the expression of P62 was up-regulated in group HG+ H/R ( P<0.05). Compared with group HG+ H/R, the the cell viability was significantly increased, the activity of LDH in supernatant was decreased, mitochondrial contents were increased, the expression of TBK1, PINK1, Parkin and LC3B was up-regulated, and the expression of P62 was down-regulated in group TBK1 ( P<0.05). Conclusion:The mechanism by which TBK1 overexpression reduces the H/R injury is related to restoring mitophagy in isolated mouse cardiomyocytes subjected to high glucose.
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Objective:To evaluate the role of hypoxia-inducible factor-1α (HIF-1α) in the renal injury induced by myocardial ischemia-reperfusion (I/R) in diabetic rats and its relationship with solute carrier family7 member11 (SLC7A11).Methods:SPF-grade healthy male Sprague-Dawley rats, aged 4 weeks, weighing 100-130 g, were fed with high-fat and high-sucrose diet freely.The weight of the rats was measured once a week.After the weight of the animals reached 240 g, 1% streptozotocin (STZ)-citrate buffer 35 mg/kg was injected intraperitoneally to induce type 2 diabetes mellitus.After injection of STZ, the animals were fed with high-fat and high-sucrose diet continuously.Blood samples were collected from the tail vein for determination of blood glucose concentrations 1 week later.When random blood glucose was ≥16.7 mmol/L for 3 times, the model of type 2 diabetes mellitus was considered to be established successfully.After the model was established successfully, the animals were fed with high-fat and high-sucrose diet continuously for 6 weeks.Eighteen rats with type 2 diabetes mellitus were selected and divided into 3 groups ( n=6 each) using a random number table method: diabetic sham operation group (group DS), diabetic myocardial I/R group (group DIR) and diabetic myocardial I/R+ HIF-1α agonist DMOG group (DIR+ DMOG group). Twelve non-diabetic rats were divided into 2 groups ( n=6 each) using a random number table method: non-diabetic sham operation group (NS group) and non-diabetic myocardial I/R group (NIR group). The rat myocardial I/R injury model was established by ligating the anterior descending branch of the left coronary artery for 30 min followed by 120 min reperfusion in anesthetized rats.Blood samples were collected from the right internal carotid artery at 120 min of reperfusion for determination of the serum creatinine (Cr), urea nitrogen (BUN) and neutrophil gelatinase-associated lipocalin (NGAL) concentrations (by enzyme-linked immunosorbent assay). Renal tissues were obtained for examination of the pathological changes (by HE staining method) and for determination of the expression of HIF-1α and SLC7A11 (by Western blot). The damage to the renal tubules was scored. Results:Compared with group NS, the concentrations of serum Cr, BUN and NGAL and renal tubular damage score were significantly increased in group DS and group NIR, the expression of HIF-1α and SLC7A11 was down-regulated in group DS, and the expression of HIF-1α and SLC7A11 was up-regulated in group NIR ( P<0.05). Compared with group DS, the concentrations of serum Cr, BUN and NGAL and renal tubular damage score were significantly increased, and the expression of HIF-1α and SLC7A11 was up-regulated in group DIR ( P<0.05). Compared with group NIR, the concentrations of serum Cr, BUN and NGAL and renal tubular damage score were significantly increased, and the expression of HIF-1α and SLC7A11 was down-regulated in group DIR ( P<0.05). Compared with group DIR, the concentrations of serum Cr, BUN and NGAL and renal tubular damage score were significantly decreased, and the expression of HIF-1α and SLC7A11 was up-regulated in group DIR+ DMOG ( P<0.05). Conclusion:HIF-1α is involved in the renal injury induced by myocardial I/R, which is related to regulation of the expression of SLC7A11 in rats.
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Objective:To evaluate the role of Notch1/hairy and enhancer of split homolog1(Hes1) signaling pathway in high glucose and hypoxia-reoxygenation (H/R) injury to cardiomyocytes.Methods:H9c2 cardiomyocytes were cultured in low-glucose DMEM culture medium supplemented with 10% fetal bovine serum.The cells were divided into 6 groups ( n=12 each) using a random number table method: control group (group C), H/R group, H/R+ Jagged-1 group (group H/R+ J), high glucose group (group HG), high glucose+ H/R group (group HG+ H/R) and high glucose+ H/R+ Jagged-1 group (group HG+ H/R+ J). The cells were incubated in low-glucose culture medium for 72 h in group C. After incubated in low-glucose culture medium for 72 h, the cells were exposed to 24-h hypoxia in an incubator filled with 95% N 2-5% CO 2 at 37℃, immediately followed by 6-h reoxygenation in an incubator filled with 95% O 2-5% CO 2 at 37℃ in group H/R.In group H/R+ J, Jagged-1 (Notch1/Hes1 signaling pathway specific activator) 5μg/ml was added to low-glucose culture medium and the cells were incubated for 72h before H/R.In group HG, H9c2 cardiomyocytes were incubated in high-glucose culture medium containing 33 mmol/L glucose for 72 h. In group HG+ H/R, the cells were incubated in high-glucose medium for 72 h before H/R.In group HG+ H/R+ J, Jagged-1 5μg/ml was added to high-glucose culture medium, and the cells were incubated for 72 h before H/R.At 6 h of reoxygenation, the supernatant of the culture medium was collected for detection of the activities of superoxide dismutase (SOD) and lactic dehydrogenase (LDH), the cell viability (by CCK-8 assay) and the cell apoptosis rate (by flow cytometry) and for determination of expression of Notch1, Hes1 and c-caspase-3 (by Western blot). Results:Compared with group C, the cell survival rate and SOD activity were significantly decreased, and apoptosis rate and LDH activity were increased in H/R, H/R+ J and HG groups, expression of Notch1, Hes1 and c-caspase-3 was up-regulated in H/R and H/R+ J groups, and the expression of Notch1 and Hes1 was down-regulated and c-caspase-3 expression was up-regulated in group HG ( P<0.05). Compared with group H/R, the cell survival rate and SOD activity was significantly increased, apoptosis rate and LDH activity were decreased, expression of Notch1 and Hes1 was up-regulated, and c-caspase-3 expression was down-regulated in group H/R+ J, and the cell survival rate and SOD activity were significantly decreased, apoptosis rate and LDH activity were increased, expression of Notch1 and Hes1 was down-regulated, and c-caspase-3 expression was up-regulated in group HG+ H/R ( P<0.05). Compared with group HG, the cell survival rate and SOD activity were significantly decreased, and apoptosis rate and LDH activity were increased in HG+ H/R and HG+ H/R+ J groups ( P<0.05), and expression of Notch1 and Hes1 was down-regulated, and c-caspase-3 expression was up-regulated in group HG+ H/R ( P<0.05). Compared with group HG+ H/R, the cell survival rate and SOD activity were significantly increased, apoptosis rate and LDH activity were decreased, expression of Notch1 and Hes1 was up-regulated, and c-caspase-3 expression was down-regulated in group HG+ H/R+ J ( P<0.05). Compared with group H/R+ J, the cell survival rate and SOD activity were significantly decreased, apoptosis rate and LDH activity were increased, expression of Notch1 and Hes1 was down-regulated, and c-caspase-3 expression was up-regulated in group HG+ H/R+ J ( P<0.05). Conclusion:Activation of Notch1/Hes1 signaling pathway is the endogenous protective mechanism of high glucose and H/R injury to cardiomyocytes.
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Objective:To evaluate the role of nuclear factor E2-related factor 2 (NRF2) in myocardial ischemia-reperfusion (I/R) injury and the relationship with ferroptosis in diabetic rats.Methods:Forty-eight SPF healthy adult male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-220 g, were divided into 5 groups by a random number table method: sham operation group (group S, n=6), myocardial I/R group (group NIR, n=12), diabetes mellitus+ sham operation group (group DS, n=6), diabetes mellitus+ myocardial I/R group (group DIR, n=12) and diabetes mellitus+ myocardial I/R+ NRF2 agonist sulforaphane group (group DIR+ SFN, n=12). Type 1 diabetes mellitus was induced by intraperitoneal injection of 1% streptozotocin-citrate buffer 60 mg/kg.Sulforaphane 500 μg·kg -1·d -1 was injected intraperitoneally before ischemia for 3 consecutive days in group DIR+ SFN.At the 8th week after establishing the model, myocardial I/R was produced by occlusion of the anterior descending branch of the left coronary artery for 30 min followed by reperfusion.At 2 h of reperfusion, the left ventricular systolic pressure (LVSP), HR, and the maximum rate of increase and decrease of left ventricular systolic pressure (±dp/dt max) were recorded.Blood samples were taken from the carotid artery and the animals were then sacrificed for determination of concentration of cardiac troponin I (cTnI) in serum (using enzyme-linked immunosorbent assay), myocardial Fe 2+ and malondialdehyde (MDA) contents, superoxide dismutase (SOD) activity (by colorimetry) and myocardial infarct size (using TTC) and for determination of expression of NRF2, ferroportin1 (FPN1) and acyl-CoA synthetase long-chain family member 4 (ACSL4) (by Western blot), and the pathological changes of lung tissues were observed by hematoxylin-eosin staining. Results:Compared with group S, LVSP, HR, and ±dp/dt max were significantly decreased, serum cTnI concentration and myocardial Fe 2+ and MDA contents were increased, SOD activity was decreased, expression of ACSL4 was up-regulated and expression of NRF2 and FPN1 was down-regulated in group NIR ( P<0.05). Compared with group DS, LVSP, HR, and ±dp/dt max were significantly decreased, serum cTnI concentration and myocardial Fe 2+ and MDA contents were increased, SOD activity was decreased, expression of ACSL4 was up-regulated and expression of NRF2 and FPN1 was down-regulated in group DIR ( P<0.05). Compared with group NIR, LVSP, HR, and ±dp/dt max were significantly decreased, serum cTnI concentration and myocardial Fe 2+ and MDA contents were increased, SOD activity was decreased, myocardial infarct size was increased, expression of ACSL4 was up-regulated and expression of NRF2 and FPN1 was down-regulated in group DIR ( P<0.05). Compared with group DIR, LVSP, HR, and ±dp/dt max were significantly increased, serum cTnI concentration and myocardial Fe 2+ and MDA contents were decreased, SOD activity was increased, myocardial infarct size was decreased, expression of ACSL4 was down-regulated and expression of NRF2 and FPN1 was up-regulated in group DIR+ SFN ( P<0.05). Conclusion:NRF2 is involved in the process of myocardial I/R injury, which is related to promoting ferroptosis in diabetic rats
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Objective:To evaluate the role of phosphoglycerate mutase 5 (phosphoglycerate mutase family member 5, PGAM5) in myocardial ischemia-reperfusion (I/R) injury in diabetic rats and the relationship with mitochondrial quality.Methods:SPF 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 1% streptozotocin diluted in citrate buffer solution 60 mg/kg.The rats were continuously fed for 8 weeks after successful establishment of the model.Seventy-two rats with type 1 diabetes mellitus were divided into 4 groups ( n=18 each) by a random number table method: diabetic sham operation group (DS group), diabetic myocardial I/R group (DIR group), diabetic myocardial I/R plus AAV9-PGAM5 shRNA group (DIR+ PGAM5 shRNA group), and diabetic myocardial I/R plus AAV9-GFP group (DIR+ GFP group). The myocardial I/R model was established by ligation of the left anterior descending coronary artery for 30 min followed by reperfusion for 2 h starting from 8 weeks after establishment of type 1 diabetes mellitus model.AAV9-PGAM5 shRNA and AAV9-GFP 2×10 12 μg/kg were slowly injected via tail vein 3 weeks before ischemia.In group AAV9-PGAM5 shRNA, left ventricular systolic pressure (LVSP) and the maximum rate of increase or decrease in left ventricular systolic pressure (±dp/dt max) were monitored and recorded at the end of reperfusion, and then blood samples from the the right carotid artery were collected for determination of serum troponin Ⅰ(cTnI), creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) levels (by enzyme-linked immunosorbent assay). The animals were sacrificed and hearts were obtained for determination of myocardial infarct size (by Evans Blue plus TTC double staining method) and expression of PGAM5, autophagy-related proteins (LC3B, p62), dynamin-related protein 1 (Drp1), and mitochondrial autophagy receptor protein (FUNDC1) (by Western blot) and for microscopic examination of pathological changes of myocardial tissues (by HE staining). Results:Compared with group DS, the LVSP and ±dp/dt max were significantly decreased, the serum levels of cTnI, CK-MB and LDH were increased, myocardial infarct size was increased, the expression of PGAM5, LC3B, Drp1 and FUNDC1 was up-regulated, and the expression of p62 was down-regulated in group DIR and group DIR+ GFP ( P<0.05). Compared with group DIR, LVSP and ±dp/dt max were significantly increased, the serum levels of cTnI, CK-MB and LDH were decreased, myocardial infarct size was decreased, the expression of PGAM5, LC3B, Drp1 and FUNDC1 was down-regulated, and the expression of p62 was up-regulated in group DIR+ PGAM5 shRNA ( P<0.05), and no significant change was found in the parameters mentioned above in group DIR+ GFP ( P>0.05). Conclusion:PGAM5 is involved in the myocardial I/R injury in diabetic rats, which is related to the reduction of mitochondrial quality.
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Objective:To discuss the type, treatment and results of different therapies of biliary fistula after orthotopic liver tansplantation(OLT).Methods:Data of 24 patients who developed biliary fistula after OLT in the First Affiliated Hospital of Xi′an Jiaotong University from January 2000 to March 2019 were retrospectively analyzed. Patients with biliary fistula were classified into 4 types according to presence or absence of stricture. All patients were treated by endoscopic retrograde cholangiopancreatography (ERCP) or interventional therapy, including endoscopic nasobiliary drainage (ENBD), endoscopic retrograde biliary drainage (ERBD) or percuteneous transhepatic cholangial drainage (PTCD). Main outcome measurements were the onset time of biliary fistula, the site of biliary fistula, the complications of ERCP or PTCD, the time of removing abdominal or biliary drainage tube, and the onset of new biliary stricture.Results:Biliary fistula was found in (46.5±36.6) days (6-122 days) after OLT. The numbers of patients in four types of biliary fistula were 6, 14, 2 and 2, respectively. Biliary fistula was cured in 22 patients, with clinical cure rate of 91.7%. All patients underwent ERCP first, and the technical success rate and clinical cure rate were 87.5% (21/24) and 85.7% (18/21), respectively. The clinical cure rates of ERCP forⅠ-Ⅳ biliary fistula were 6/6, 84.6%(11/13), 1/2, and 0, respectively. The clinical cure rates of ENBD and ERBD were 8/10 and 6/8, respectively. Five cases in whom ERCP failed, underwent PTCD, with technical success and clinical cure rates of 4/5 and 3/4 respectively. Eight patients(33.3%)developed cholangitis after treatment, and the incidence rate seemed higher in type Ⅱ biliary fistula than that in type Ⅰ [35.7% (5/14) VS 16.7% (1/6)]. Incidence of cholangitis was higher in patients with non-anastomotic stricture than those with anastomotic stricture [83.3%(5/6) VS 16.7%(3/18)].Conclusion:The first line treatment for biliary fistula after OLT is ERCP, followed by PTCD. The best procedures of biliary fistula typeⅠ-Ⅳ were ENBD, ENBD combined with ERBD, ENBD and PTCD, respectively.
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Objective:To systematically evaluate the effect of SRSF2 gene mutation on the prognosis of patients with myelodysplastic syndromes (MDS).Methods:Databases including PubMed, Embase and Cochrane Library were searched for relevant studies that conducted the effect of SRSF2 gene mutation on the prognosis of MDS. The retrieval time limit was from the time of establishing database to December 2018. All cohort studies related to the effect of SRSF2 gene mutation on the prognosis of MDS were screened according to the inclusion and exclusion criteria. Data extraction and bias risk assessment were conducted for the eligible literature. The observation indicators were statistically analyzed by using RevMan 5.3 software.Results:A total of 11 studies were included in the final Meta-analysis. Compared with MDS patients without SRSF2 mutation, MDS patients with SRSF2 mutation had shorter overall survival time (HR = 1.67, 95% CI 1.40-2.00, P < 0.01) and progression-free survival time (HR = 6.20, 95% CI 2.64-14.58, P < 0.01). MDS patients with SRSF2 mutation was easier to transform into acute myeloid leukemia (AML) with shorter time (HR = 2.02, 95% CI 1.49-2.74, P < 0.01) compared to patients without SRSF2 mutation.Conclusion:SRSF2 gene mutation is an independent poor prognosis factor in patients with MDS.
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Objective To investigate the clinical effects and prognostic factors of radical surgery for primary gallbladder cancer (GBC).Methods The retrospective case-control study was conducted.The clinicopathological data of 305 patients with primary GBC who underwent radical Ro resection in the First Affiliated Hospital of Xi'an Jiaotong University from 2013 to 2017 were collected,including 108 males and 197 females,aged from 30 to 88 years,with a median age of 62 years.According to the different tumor staging,patients underwent corresponding operation and adjuvant treatment based on the postoperative indication of chemotherapy.Observation indicators:(1) results of imaging and laboratory examinations;(2) treatment situations:① surgical situations,② postoperative adjuvant treatment;(3) results of postoperative pathological examination;(4) followup;(5) prognostic factors analysis.Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival up to December 5,2018,and death was used as the end point.Measurement data with normal distribution were represented as Mean±SD.Measurement data with skewed distribution were described as M (range).Count data were represented as percentage.The survival curve and survival rate were respectively drawn and calculated using the Kaplan-Meier method.The univariate analysis and multivariate analysis were respectively done using the Log-rank test and COX regression model.Results (1) Results of imaging and laboratory examinations:results of imaging examination showed that diagnostic rates of ultrasound,CT and MRI examination were respectively 84.06％ (174/207),85.71％ (168/196) and 63.11％ (65/103).Results of laboratory examination showed that the positive rates of CA19-9,CA125 and carcinoembryonic antigen (CEA) were respectively 55.34％ (145/262),48.06％ (124/258) and 46.15％ (126/273).(2) Treatment situations:① surgical situations:305 patients underwent radical R0 resection for primary GBC,including 145 undergoing liver wedge resection + D2 lymph node dissection,61 undergoing liver wedge resection + D1 lymph node dissection,55 undergoing liver Ⅳ B and Ⅴ segmentectomy + D2 lymph node dissection,11 undergoing liver Ⅳ B and Ⅴ segrnentectomy + D1 lymph node dissection,9 undergoing right hepatectomy + D2 lymph node dissection,5 undergoing liver wedge resection + D2 lymph node dissection + partial colectomy,4 undergoing pancreaticoduodenectomy,3 undergoing simple cholecystectomy in Tis stage,3 undergoing right hepatectomy + D1 lymph node dissection,2 undergoing liver ⅣB and Ⅴ segmentectomy + D2 lymph node dissection + partial colectomy,1 undergoing liver Ⅳ B and Ⅴ segmentectomy + resection and reconstruction of portal vein + D2 lymph node dissection,1 undergoing liver ⅣB and Ⅴ segmentectomy + D2 lymph node dissection + partial resection of the stomach or duodenum,1 undergoing pancreaticoduodenectomy + resection and reconstruction of portal vein,1 undergoing right hepatectomy + pancreaticoduodenectomy,1 undergoing right hepatic lobectomy + partial gastrectomy + D2 lymph node dissection,1 undergoing right hepatic lobectomy + D1 lymph node dissection and 1 undergoing right hepatic trilobectomy + D2 lymph node dissection.Of 94 patients with unsuspected GBC,78 who were diagnosed in the other hospitals received salvage surgery in the authors' center.Twenty-one patients had postoperative surgery-related complications,including 11 with bile leakage,8 with pulmonary infection and 2 with abdominal bleeding.Two patients died in the perioperative period.② Postoperative adjuvant treatment:26 patients underwent postoperative adjuvant chemotherapy.Chemotherapy regimen:gemcitabine + oxaliplatin were used in 12 patients,gemcitabine + tegafur in 7 patients,gemcitabine + cisplatin in 6 patients,oxaliplatin + tegafur in 1 patient.(3) Results of postoperative pathological examination.The postoperative pathological type of 305 patients:257,23,6,5,4,3,3,2,1 and 1 patients were respectively confirmed as pure adenocarcinoma,adenocarcinoma combined with squamous cell carcinoma,adenocarcinoma combined with neuroendocrine carcinoma,mucinous adenocarcinoma,neuroendocrine carcinoma,adenocarcinoma combined with mucinous carcinoma,squamous cell carcinoma,sarcomatoid carcinoma,adenocarcinoma combined with sarcomatoid carcinoma,adenocarcinoma combined with signet-ring cell carcinoma.Degree of tumor differentiation:highdifferentiated,moderate-differentiated and low-differentiated tumors were detected in 37,130 and 121 patients,respectively,17 with unknown differentiated degree.Of 305 patients,16 and 32 patients had respectively vascular invasion and nerve invasion.The number of lymph node dissected of 305 patients was 8±5,with positive lymph node of 0 (range,0-9),including 121 with lymphatic metastasis (26 with jumping lymphatic metastasis).TNM staging of 305 patients:stage 0,Ⅰ,Ⅱ,ⅢA,ⅢB,ⅣA and ⅣB were detected in 7,18,13,137,57,11 and 62 patients,respectively.(4) Follow-up:245 of 305 patients were followed up for 18.0 months (range,6.0-70.0 months).The survival time,1-and 3-year survival rates were respectively 29.5 months (range,0.5-69.9 months),71.6％ and 45.8％.One hundred and twenty-two patients died during the follow-up.(5) Prognostic factors analysis:the results of univariate analysis showed that preoperative level of bilirubin,pathological type,degree of tumor differentiation,liver invasion,vascular invasion,nerve invasion,T staging,N staging and postoperative chemotherapy were factors affecting prognosis of patients with primary GBC (x2 =10.26,3.96,45.89,34.64,12.75,27.05,35.09,39.44,4.40,P＜0.05).The results of multivariate analysis showed that low-differentiated tumor,liver invasion and N2 staging were independent risk factors affecting prognosis of patients with primary GBC [odds ratio (OR)=1.90,1.71,1.46,95％ confidence interval (CI):1.34-2.70,1.15-2.52,1.17-1.82,P＜0.05],and postoperative chemotherapy was a protective factor affecting prognosis of patients with primary GBC (OR=0.35,95％ CI:0.15-0.82,P＜0.05).Conclusions For patients with primary GBC undergoing radical resection,D2 lymph node dissection should be performed routinely.The low-differentiated tumor,liver invasion and N2 staging are independent risk factors affecting prognosis of patients,and postoperative chemotherapy is a protective factor.
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Objective@#To investigate the efficacy of periprocedural use of bivalirudin for patients with chronic total occlusion(CTO) lesion undergoing percutaneous coronary intervention(PCI) therapy. @*Methods@#In this randomized controlled study, 74 patients with CTO lesions confirmed by coronary angiography or CT angiography, hospitalized in the general hospital of Shenyang military region from September 2015 to December 2016, were randomly divided into unfractionated heparin(UFH) group (n=38) and bivalirudin group (n=36) by the random number table.Patients in the UFH group were treated with injection of UFH 5 000 U through the artery sheath catheter before coronary angiography,and the UFH was intravenously administered at 100 U/kg before PCI. Patients in the bivalirudin group received intravenous injection of bivalirudin (0.75 mg/kg) before coronary angiography, followed by intravenous infusion of 1.75 mg·kg-1·h-1 until at least 2 hours after the PCI. The values of the activated coagulation time (ACT) were measured,and the value was remained at 250 to 350 seconds during the PCI. The incidence rate of adverse events including hemorrhage events, no-reflow/slow flow, and contact thrombus in perioperative period were observed in all patients. In addition, the incidence rate of the major adverse cardiovascular events (MACE) including recurrent angina, heart failure, target vessel revascularization, cardiac death, non-fatal myocardial infarction,and stroke within 1 year follow-up period were also observed in the 2 groups. @*Results@#Baseline clinical and PCI data were similar between the 2 groups (all P>0.05). During the perioperative period, the incidence of the bleeding was significantly lower in the bivalirudin group than in the UFH group(5.6% (2/36) vs. 23.7% (9/38) , P=0.028).The incidence of no-reflow/slow flow was also significantly lower in the bivalirudin group than in the UFH group(0 vs. 15.8% (6/38) , P=0.025). There was no significant difference in the incidence of contact thrombosis between bivalirudin group and UFH group(8.3% (3/36) vs. 0, P=0.110). There was no cardiac death or non-fatal myocardial infarction in the 2 groups within 1 year after PCI, and there was no significant difference in the incidence of MACE in 1 year follow-up after operation between bivalirudin group and UFH group (11.1% (4/36) vs. 21.1% (8/38) , P=0.246). @*Conclusion@#The application of the anticoagulant bivalirudin during PCI in patients with CTO lesion can reduce the incidence of perioperative bleeding and no-reflow/slow flow, and does not increase the risk of MACE within 1 year after PCI.
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In the present study, three compounds were isolated from Argyreia acuta, among them, compounds 1 and 2 were new and Compounds 1 and 3 were isomers. They were separated by several types of columns, such as normal phase, RP, size exclusion and preparative HPLC, and their structures were elucidated by several spectroscopic methods, such as 1D- and 2D-NMR and HR-TOF-MS.
Subject(s)
Convolvulaceae , Chemistry , Drugs, Chinese Herbal , Chemistry , Glycosides , Chemistry , Isomerism , Mass Spectrometry , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Plant Components, Aerial , Chemistry , Resins, Plant , Chemistry , SpectrophotometryABSTRACT
In the present study, three compounds were isolated from Argyreia acuta, among them, compounds 1 and 2 were new and Compounds 1 and 3 were isomers. They were separated by several types of columns, such as normal phase, RP, size exclusion and preparative HPLC, and their structures were elucidated by several spectroscopic methods, such as 1D- and 2D-NMR and HR-TOF-MS.
Subject(s)
Convolvulaceae , Chemistry , Drugs, Chinese Herbal , Chemistry , Glycosides , Chemistry , Isomerism , Mass Spectrometry , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Plant Components, Aerial , Chemistry , Resins, Plant , Chemistry , SpectrophotometryABSTRACT
Objective To explore the application value of plastic biliary stent and fully covered self-expandable metallic stent (FCSEMS) in endoscopic retrograde cholangio pancreatography (ERCP) for treatment of benign biliary stricture after liver transplantation.Methods The retrospective cross-sectional study was conducted.The clinical data of 54 patients with benign biliary stricture after liver transplantation undergoing ERCP treatment who were admitted to the First Affiliated Hospital of Xi'an Jiaotong University between January 2010 and August 2016 were collected.Among 54 patients,44 had simple anastomotic stricture and 10 had non-anastomotic stricture.All the patients underwent stent implantation by ERCP.Patients with stricture within 1 month postoperatively initially selected single plastic stent or endoscopic nasobiliary drainage (ENBD),and then changed into multiple plastic stents at the second stent replacement.Patients with stricture after 1 month postoperatively selected multiple plastic stents,multiple plastic stents after balloon dilation or FCSEMS.Observation indicators:ERCP situations,stent implantation,time of stent indwelling,postoperative complications,stent dislocation,treatment outcome and follow-up situations.Patients were followed up by outpatient examination and telephone interview up to November 2016.Clinical symptoms of patients were observed within 1 month postoperatively and liver function and abdominal ultrasound were retested.Liver function and remission degree of biliary stricture were monitored regularly once every 3 months.Measurement data were described as average (range).Results All the patients underwent successful ERCP,of which 53 completed the process of ERCP and 1 rejected treatment due to economic problems.All the 54 patients received 140 times ERCPs with an average of 2.59 times per person,21 times ENBDs,11 times FCSEMSs and 108 times plastic stent implantations (including 35 times single stent implantations,46 times double stents implantations,23 times 3-stents implantations and 4 times 4-stents implantations).All the 54 patients were followed up for 3-143 months,with an average time of 73 months.Of 44 with anastomotic stricture,34 received plastic stent implantation and 98 times ERCPs,with an average number of stent implantation of 2 (range,1-4) and an average time of stent indwelling of 10.7 months (range,9.0-13.0months);the postoperative acute pancreatitis,biliary infection,hyperamylasemia and adverse stent implantation or dislocation were detected in 4 persons every time,7 persons every time,10 persons every time and 3 persons every time,respectively;26 patients were cured and 5 were improved,with an effective rate of 91.2％ (31/34);3 patients with noneffective treatment continued to undergo ERCP and 3 patients had recurrence of anastomotic stricture.Among 10 patients with initial FCSEMS implantation,12 times ERCPs were performed,with an average time of stent indwelling of 7.6 months (range,6.0-12.0 months);postoperative biliary infection,hyperamylasemia and stent dislocation were detected in 1 person every time,1 person every time and 1 person every time,respectively;8 patients were cured,with an effective rate of 8/10;of 2 patients with persistent stricture,1 patient received contrast examination after stent removal,showing a comparative stricture in level 1 branch of intrahepatic duct and considering combined ischaemia,and then underwent the second implantation using multiple plastic stents;the other patient had elevated level of jaundice at 3 months after stents removal and received ERCP,showing anastomotic inflammatory polyp,and then underwent FCSEMS implantation again.Ten patients with non-anastomotic stricture received plastic stent implantation and 30 times ERCPs,with an average number of stent implantation of 3 (range,2-4) and an average time of stent indwelling of 11.3 months (range,10.0-14.0 months);the postoperative acute pancreatitis,biliary infection,hyperamylasemia and adverse stent implantation or dislocation were detected in 2 persons every time,5 persons every time,2 persons every time and 1 person every time,respectively;3 patients were cured and 3 were improved,with an effective rate of 6/10;of 4 patients with noneffective treatment,2 died of gradually deteriorating liver function and 2 underwent the second liver transplantation.Conclusions Stent implantation in ERCP is safe and effective for treatment of benign biliary stricture after liver transplantation,single plastic stent should be used in the early period (within 1 month) and multiple plastic stents should be used in the later period.Although FCSEMS has a higher displacement rate,it should be recommended due to a better clinical effect,lower incidence of complications and simple operation.For patients with non-anastomotic stricture,plastic stent should be used for extrahepatic biliary stricture,with a good clinical effect,and there is worse effect in stent implantation through ERCP for multiple intrahepatic biliary strictures.
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In this study, a multiplex RT-PCR method was developed for detection of seven diarrhea-associated porcine viruses, including porcine teschovirus (PTV), porcine sapovirus (PSV), porcine deltacornavirus (PDCoV), porcine kobuvirus (PKV), porcine sapovirus (PSaV), porcine astrovirus (PAstV) and porcine torovirus (PToV). A total of 419 samples were screened by this method and results showed that PKV had the highest positive rate of 26.98%?45.79% and its mixed infection rate reached 9.52%-18.54%. On account of high positive rate of PKV and its important role in diarrhea disease, complete genomic sequences of three PKV positive samples were further sequenced. Three PKV labeled as PD-PKV, JS-PKV and CM-PKV were classified into porcine kobuvirus genus and had far genetic distance with other kobuviruses. The complete genome homologies among them were 88.1%-89.1%. CM-PKV had the highest identity with the Chinese strain JS-02a-CHN/2013 reported in 2013 while JS-PKV and PD-PKV were most closed to the K-30-HUN/2008/HUN strain reported in Hungary in 2008. This illustrates the significant genetic differences of the different PKV isolates in Shanghai while its relationship with the viral pathogenicity still needs to be explored. This research provides references for further understanding the prevalence of PKV and its role in swine diarrhea.
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Objective To investigate the causes, diagnosis and surgical treatment of ERCP related duodenal per﹣foration. Methods Clinical data of 6 cases of surgical treatment of ERCP related duodenal perforation were retro﹣spective analyzed. All the 6 perforation patients underwent emergency surgical procedure, including 3 cases trans﹣fered from other hospital after duodenal perforation. 4 cases with a history of abdominal surgery. Preoperative con﹣firmed bravery manager stone 4 cases, 1 case of obstructive jaundice after gallbladder surgery, bile duct expansion in 1 case. Results Perforation causes include duodenum mirror improper operation related in 2 cases, duodenal papilla sphincterotomy related 3 cases (1 case of pre-dissection operation with needle knife), small endoscopic sphincteroto﹣my combined with endoscopic papillary balloon dilation lead to perforation in 1 case.4 cases of intraoperative found right kidney week pneumatosis, 2 cases of postoperative CT found after peritoneal pneumatosis, effusion. All patients with surgery including common bile duct exploration, T tube drainage, duodenal perforation repair, jejunum colostomy, among them 2 cases at the same time line of gastrointestinal anastomosis. 5 cases recovered, 1 case died. Conclusions Inappropriate duodenal papilla sphincter incision indications and Many previous abdominal surgery have higher perforated ration;Found in time, reasonable treatment is the most important;For serious typeⅠand typeⅡperforation, active surgical treatment in time, can effectively reduce serious consequences caused by the ERCP related perforation.
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In the present study, two new compounds from Ipomoea cairica were identified and demonstrated to have α-glucosidase inhibitory activity. They were isolated by column chromatography on silica gel and sephadex LH-20 and finally purified by prep-HPLC, with their structures being elucidated by spectroscopic methods, such as 1D- and 2D-NMR and HR-TOF-MS, and chemical methods. Compounds 1 and 2, named cairicoside A and cairicoside B, were evaluated for α-glucosidase inhibitory activity by the MTT method, with the IC50 values being 25.3 ± 1.6 and 28.5 ± 3.3 μmol·L(-1), respectively.