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Objective:To explore the clinical efficacy and safety of single-layer with full thickness of duct-to-mucosa pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy.Methods:The clinical data of 45 patients who underwent laparoscopic pancreaticoduodenectomy with the procedures of single-layer with full thickness in Second Hospital of Hebei Medical University from Jan 2020 to Jan 2022 were retrospectively collected and compared with 45 matched patients with traditional two-layer pancreaticojejunostomy.Results:The laparoscopic pancreaticoduodenectomy procedures were successfully performed in all the 90 cases. The mean operation time (285.6±92.4 minutes) and the media pancreaticojejunostomy time 20(15, 35) minutes) of the single-layer with full thickness pancreaticojejunostomy group were shorter than those of the two-layer pancreaticojejunostomy group [the mean operation time: 317.0±85.5 minutes, the media pancreaticojejunostomy time: 46(30, 58) minutes] with significantly statistical differences (all P value<0.05). There were no significantly statistical differences on intraoperative blood loss, the postoperative complications or hospital stay between the two groups. Conclusions:Compared with traditional pancreaticojejunostomy, the single-layer with full thickness of duct-to-mucosa pancreaticojejunostomy is simple and safe, which has the advantage of easy manipulation and less time-consuming and can be recommended for laparoscopic procedures.
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Objective:To evaluate the effect of surgery under propofol anesthesia during mid-pregnancy on the cognitive function and hippocampal histone deacetylase 2 (HDAC2)-cAMP response element-binding protein (CREB)-N-methyl-D-aspartate (NMDA) receptor 2B subunit (NR2B)-containing NMDA receptor (NR2B) signaling pathway in the offspring rats.Methods:Thirty healthy Sprague-Dawley rats at 14 days of gestation were divided into 3 groups ( n=10 each) using a random number table method: propofol anesthesia group (P group), surgery under propofol anesthesia group (S group) and control group (C group). In S group, propofol 20 mg/kg was injected via the caudal vein, and then propofol was continuously infused at a rate of 20 mg·kg -1·h -1 to maintain anesthesia for 4 h, and exploratory laparotomy was performed. Group P received no exploratory laparotomy and the other treatments were similar to those previously described in group S. The equal volume of normal saline was given instead in group C. The learning and memory of the offspring rats was assessed using Morris water maze test on postnatal day 30. The expression of HDAC2, phosphorylated CREB (p-CREB), NR2B, brain-derived neurotriphic factor (BDNF) and phosphorylated tyrosine kinase B (p-TrkB) in offspring′s hippocampi was evaluated by Western blot. Apoptosis in hippocampal neurons was detected by TUNEL staining. Results:Compared with group C, the escape latency was significantly prolonged, the frequency of crossing the original platform was decreased, the time spent in the second quadrant was shortened, the expression of HDAC2 was up-regulated, the expression of p-CREB, NR2B, BDNF and p-TrkB was down-regulated, and the apoptosis rate of the hippocampal neurons was increased in P and S groups ( P<0.05). Compared with P group, the escape latency was significantly prolonged, the frequency of crossing the original platform was decreased, the time spent in the second quadrant was shortened, the expression of HDAC2 was up-regulated, the expression of p-CREB, NR2B, BDNF and p-TrkB was down-regulated, and the apoptosis rate of the hippocampal neurons was increased in S group ( P<0.05). Conclusions:Surgery under propofol anesthesia during mid-pregnancy can decrease the cognitive function of offspring rats, and the mechanism is related to the regulation of HDAC2-CREB-NR2B signaling pathway and the promotion of apoptosis in hippocampal neurons.
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Objective:To analyze the predictive value of neutrophil gelatinase-associated lipocalin(NGAL)in high-risk elderly patients with acute kidney injury(AKI).Methods:A retrospective study was conducted to collect 183 patients over 65 years old in the Department of Geriatrics, the First Affiliated Hospital of Nanjing Medical University from January 2018 to October 2019.The patients were combined with at least one risk factor.The diagnostic effect of NGAL for AKI prediction in high-risk patients was evaluated.According to the initial serum creatinine(SCr)and basic glomerular filtration rate(eGFR), the patients were divided into chronic kidney disease(CKD)group and non-CKD group.The optimal diagnostic threshold for A-on-C is determined by determining the area under the subject curve(AuROC). Univariate and independent predictors multivariate regression analysis was used to assess the risk of AKI.Results:The serum NGAL(NGAL)level in AKI group was higher than that in non-AKI group[702.5 μg/L(499.2, 813.2) vs.233.9 μg/L(147.2, 315.7), Z=8.002, P<0.001]. In CKD patients, serum NGAL in AKI group was higher than that in non-AKI group[1033 μg/L(845.5, 1447) vs.288.2 μg/L(221.4, 423.3), Z=4.867, P<0.001]. In all patients, model 3 with four variables showed better AKI prediction ability than model 0, 1 and 2( R2=0.743, P<0.001). In the CKD group, the AuROC of serum NGAL for AKI prediction was larger than that of CYS-C group, whereas in the non-CKD group, the AuROC of serum NGAL for AKI prediction was smaller than that of CYS-C group. Conclusions:Serum NGAL may serve as a useful biomarker for AKI prediction in AKI high-risk elderly patients.Especially in patients with CKD, Serum NGAL has a better predictive value for AKI than traditional indicators.
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Objective:To study the clinical characteristics and management strategies of late bleeding after laparoscopic pancreaticoduodenectomy (LPD).Methods:The clinical data of 58 patients with post-pancreaticoduodenectomy hemorrhage (PPH) admitted to the Department of Hepatobiliary Surgery of the Second Hospital of Hebei Medical University from March 2018 to March 2022 were retrospectively analyzed, including 42 males and 16 females, aged (61.88±11.02) years old. According to the occurrence of intra-abdominal erosion factors (e.g., pancreatic fistula, biliary fistula, gastrointestinal anastomotic fistula, intra-abdominal abscess), patients were divided into the erosion group ( n=42) and non-erosion group ( n=16). All patients underwent standard lymphadenectomy. Clinical data including the PPH time-point, occurrence of rebleeding, and treatment outcomes were accessed. The management strategies of PPH in the two groups of patients were analyzed. Results:The PPH time-point in the erosion group and non-erosion patients was 8.00 (5.00, 19.25) d and 21.50 (12.75, 26.75) d, respectively ( P=0.001). PPH can occurred within one month after surgery in both erosion and non-erosion groups. In the erosion group, 31 cases (73.81%, 31/42) were treated by re-operation, two (4.76%, 2/42) by interventional radiology and nine (21.43%, 9/42) with conservative protocol, respectively. In the non-erosion group, five cases (31.25%, 5/16) were treated by re-operation, seven (43.75%, 7/16) by interventional radiology and four (25.00%, 4/16) with conservative protocol, respectively. The incidence of re-bleeding is higher in the erosion group [47.6% (20/42) vs 12.5% (2/16), P<0.05]. Clinical manifestations, sites and severity of bleeding, and treatment outcomes were also different in the erosion and non-erosion groups (all P<0.05). Conclusions:The occurrence of intra-abdominal erosion factors can affect the clinical characteristics and treatment strategy of late bleeding after laparoscopic pancreaticoduodenectomy. Surgery remains the treatment of choice for post-pancreaticoduodenectomy hemorrhage either as an urgent or last resort.
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E2F1, a nucleoprotein gene belongs to transcription factor, is closely associated with the development of malignant tumours. Long non-coding RNAs (lncRNAs) are aberrantly expressed in a variety of tumors. In studies of molecular mechanisms associated with lncRNAs and tumours, E2F1 has been identified as a key factor that can play a critical role as an upstream regulator or downstream target of lncRNAs, and even inter-regulate to form a positive feedback loop. This paper reviews the significance of the interaction between E2F1 and lncRNA in malignant tumors in recent years, and aims to provide ideas for the study of tumor mechanisms.
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Objective:To investigate the technical key points and clinical effects of laparoscopic surgery using the subgastric approach for infected pancreatic necrosis (IPN).Methods:From October 2020 to October 2021, The clinical data of 6 patients with IPN after severe acute pancreatitis (SAP) undergoing laparoscopic surgery using the subgastric approach at First Hospital and Second Hospital of Hebei Medical University was retrospectively analyzed. Parameters in this report included the operation time, estimated blood loss, and the patient's vital signs, inflammatory marker CRP, and WBC before operation and postoperative 24 h, 3 d, and 1 w, and postoperative complications including pancreatic leakage, organ failure, bleeding, and abdominal infection and incision infection. Follow-up after surgery was completed in outpatient checkups and long-term complications were recorded.Results:There were 4 male and 2 female patients. The median age of the 6 patients was 50 (43.5, 56.5) years. Laparoscopic debridement surgery using the subgastric approach was successfully completed in all the patients and no reoperation was needed. The median operation time was 65 (52.5, 85) min; the median estimated blood loss was 20 (25, 37.5) ml. Median APACHEⅡ score one day before surgery was 11.5 (10.25, 12.75) and the median MCTSI score at initial admission was 8 (7, 8). The inflammatory parameters including CRP, WBC, and neutrophil count on postoperative day 3 and 1w were significantly lower than those before surgery, and all the differences were statistically significant (all P value <0.05). One patient had a postoperative pancreatic fistula and was alleviated after ERCP with pancreatic stent implantation. Another patient had a incision infection after surgery and recovered after complete surgical drainage of the abdominal wall incision. No patients had complications such as heart, lung, and kidney failure, abdominal hemorrhage and infection. During the follow-up, 5 of 6 patients had no newly-occurred diabetes, except one patient who had diabetes before the operation. None of the 6 patients had recurrent IPN. Conclusions:Laparoscopic surgery using the subgastric approach for infected IPN in lesser omental sac is safe and feasible.
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Objective:To evaluate the influence of sex on age-related changes in the glomerular filtration rate(GFR)in healthy individuals.Methods:A retrospective survey was performed.A total of 36 911 healthy subjects, of whom 43.61%(16 096 cases)were men, were enrolled and divided into six age groups: 18-29, 30-39, 40-49, 50-59, 60-69, and ≥70 years old.The estimated glomerular filtration rate(eGFR)was evaluated by the full age spectrum(FAS)equation.General linear regression analysis was used to calculate the annual decline rate of eGFR, and differences between the sexes in the same age group were evaluated using analysis of covariance.The chi-square test was used to compare the proportions of subjects with different eGFR levels between the sexes.Results:Regardless of sex, body mass index(BMI), systolic blood pressure(SBP)and fasting blood glucose(FBG)all increased gradually with age, while diastolic blood pressure(DBP)increased initially and then turned downward.The means of above results in men were generally higher than those in women of the same age.Before the age of 40, the levels of eGFR in men and women were relatively stable, with the mean eGFR in women higher than that in men[(121.98±16.77)ml·min -1·1.73 m -2vs.(111.01±13.36)ml·min -1·1.73 m -2, t=-53.793, P=0.000]; After the age of 40, eGFR decreased with age in both sexes, and the decline rate of eGFR in women was faster than that in men before the age of 70.Men had generally higher mean serum creatinine(Scr), blood urea nitrogen(BUN)and serum uric acid(UA)than women.With the increase of age, BUN levels increased gradually in men and women, but Scr levels started to increase after the age of 40 only in women and did not show a clear increase in men. Conclusions:There are sex-related differences with aging, as measured with many parameters.Young and middle-aged women have significantly higher eGFR than men of the same age, but eGFR declines faster with aging in women.
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Objective:To study the single purse-string parachute suturing technique for pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy, and to determine its feasibility and safety.Methods:The clinical data of 71 patients who underwent laparoscopic pancreaticoduodenectomy using the single purse-string parachute suturing technique for pancreaticojejunostomy from October 2018 to October 2021 at the Second Hospital of Hebei Medical University were retrospectively analyzed. There were 41 males and 30 females, with age (59.1±9.7) years old. The operative time, intraoperative blood loss, complication rate and other data were analyzed.Results:All 71 patients successfully underwent total laparoscopic pancreaticoduodenectomy, with 5 patients who underwent 2D laparoscopic surgery and 66 patients 3D laparoscopic surgery. There were additional vascular resection and reconstruction in 2 patients. The operative time was (388.9±92.9) min, the intraoperative blood loss was (411.3±176.9) ml, and the postoperative hospital stay was (14.1±5.8) d. The operation time of 71 patients who underwent the single purse-string parachute technique of pancreaticojejunostomy was (26.9±6.8) min. Postoperative complications occurred in 18 patients (25.4%). Grade B pancreatic fistula occurred in 2 patients (2.8%), and the longest time for removal of abdominal drain was 17 days after operation. Among the 71 patients, complications including biliary fistula occurred in 6 patients (8.5%), delayed gastric emptying in 5 patients (7.0%), pulmonary infection in 4 patients (5.6%), non-pancreatic fistula-related abdominal infection in 4 patients (5.6%), non-pancreatic fistula-related abdominal bleeding in 1 patient (1.4%), biliary tract bleeding in 1 patient (1.4%), and chylous leakage in 2 patients (2.8%).Conclusion:The single purse-string parachute technique of pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy had the advantages of being safe and reliable. The procedure is worthy of furthers promotion.
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Human epidermal growth factor receptor 2 (HER2)-targeted therapy has greatly improved the prognosis of HER2-positive breast cancer. HER2-targeted therapy combined with chemotherapy dominated by trastuzumab+ pertuzumab is important in the neoadjuvant therapy, postoperative adjuvant therapy and late-stage standard treatment for HER2-positive breast cancer. Antibody-drug conjugates (ADCs) and tyrosine kinase inhibitors (TKIs) have further improved the efficacy of therapy. However, advanced breast cancer will eventually get a recurrence or drug resistance. HER2-positive breast cancer is characterized by moderate immunogenicity with the presence of large tumor-infiltrating lymphocytes (TILs), which provides a theoretical basis for immunotherapy. The application of HER2-targeted cancer vaccines and immune checkpoint inhibitors is promising and would offer more treatment options for the patients.
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Objective:To observe the variation rend of serum creatinine(SCr)and estimated glomerular filtration rate(eGFR)with aging, and to explore the warning range of SCr for screening low eGFR of the elderly.Methods:A retrospective cross-sectional study was performed in 10 3513 participants, including 14 221 in 18-29 years old, 29 763 in 30-39 years old, 23 151 in 40-49 years old, 18 838 in 50-59 years old, 10 019 in 60-69 years old, 5 009 in 70-79 years old, 2 512 aged ≥80 years old.We adopted CKD-EPI formula based on Chronic Kidney Disease Epidemiology Collaboration(CKD-EPISCR)formula recommended by the Global Organization for Improving Outcomes in Kidney Disease 2012 to calculate eGFR.The SCr and eGFR levels were calculated according to age to show the trend of these with aging.Further, we used percentage to investigate the distribution of eGFR in population with normal SCr, and the percentile method to establish the warning range of SCr in the older adults.Results:With aging, SCr level showed an elevating trend in women( F=340.80, P<0.001), and gradually increased in men older than 50 years( F=111.05, P<0.001)and eGFR declined with increasing age( F=8 301.60, 9 114.53, P<0.001). In population with normal SCr, the proportions of eGFR<60 and 60-75 ml·min -1·1.73m -2 were 3.83%(661/17 280)and 12.50%(2 160/17 280)in older adults aged 60-74 years respectively, but were 10.39%(488/4 699)and 22.75%(1 069/4 699)in old-older adults aged 75 years and over respectively, and were 0.07%(56/84 145)and 0.91%(762/84 145)in younger adults below 60 years old respectively.In the same distribution of eGFR, SCr levels of older adults aged 60-74 years and old-older adults aged 75 years and over were lower than that of younger population( P<0.001). In old-older adults aged 75 years and over, the warning range of SCr was 98.76-126.03 μmol/L for men and 95.12-130.00 μmol/L for women in individuals with 45 ≤ eGFR<60 ml·min -1·1.73m -2. Conclusions:The SCr level of older adults is lower than younger individuals in same distribution of eGFR.SCr level is still in the reference range in some of older individuals with eGFR-confirmed renal function impairment.The warning range of SCr is needed, especially in older adults, so as to provide reference for the rational use of medicine and disease management.
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Objective:To explore the effect of comorbidities on the risk of chronic kidney disease with aging.Methods:A total of 103 682 subjects were recruited at the health management center of the First Affiliated Hospital of Nanjing Medical University from January 2018 to January 2020 for a retrospective cross-sectional study.Participants were divided into four groups according to age 18-44(55 055 case), 45-59(31 023 case), 60-74(12 793 case), ≥75(4 811 case)age group.We calculated and compared the prevalences of estimated glomerular filtration rate(eGFR)<60 ml/min/1.73m 2, which was used as a parameter for kidney dysfunction, indifferent age groups and participants with different comorbidities.The association between comorbidities and the prevalence of kidney dysfunction was analyzed by Logistic regression. Results:Levels of blood pressure, body mass index, serum creatinine, eGFR and blood lipids varied with aging, as did the prevalences of hypertension, diabetes, obesity and comorbidities.In all participants and groups based on the types of chronic diseases, the prevalence of kidney dysfunction increased with aging, substantially so in ≥75 age group.After adjustment for age and sex, there was a marked increase in the risk of kidney dysfunction in 45-59 age group adults with hypertension or diabetes( OR=9.163, 95% CI: 3.264-25.727; OR=4.640, 95% CI: 1.028-20.936), and the risk of renal dysfunction increased in people with hypertension+ diabetes or with the coexistence of three diseases, compared with people with a single disease( OR=16.441, 95% CI: 5.325-50.783; OR=15.985, 95% CI: 4.237-60.312); In the 60-74 age group, hypertension alone also significantly increased the risk of renal dysfunction( OR=3.950, 95% CI: 1.911-8.165). With comorbidities, the most significant influence was the coexistence of three diseases( OR=6.245, 95% CI: 2.521-15.468), followed by hypertension+ obesity( OR=5.640, 95% CI: 2.550-12.476)and hypertension+ diabetes( OR=4.330, 95% CI: 1.990-9.421); In ≥75 age group, chronic diseases and comorbidities were associated with a high risk of renal dysfunction, with obesity alone and hypertension obesity posing the highest risk( OR=6.746, 95% CI: 2.193-20.757; OR=6.570, 95% CI: 3.178-13.582), followed by the coexistence of three diseases( OR=4.749, 95% CI: 2.110-10.687). Conclusions:The prevalence of hypertension, diabetes, and obesity varies with aging.The effect of chronic diseases on the risk of chronic kidney disease with reduced renal function in the elderly population is different from that in the non-elderly population.
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Objective:To study the safety and feasibility of laparosocpic left-liver-first anterior radical modular orthotopic right hemihepatectomy (Lap-Larmorh) in treatment of Bismuth-Corlette type Ⅲa hilar cholangiocarcinoma.Methods:From June 2020 to April 2022, 13 patients with Bismuth-Corlette type Ⅲa hilar cholangiocarcinoma underwent Lap-Larmorh at the Department of Hepatobiliary Surgery of the Second Hospital of Hebei Medical University. There were 8 males and 5 females, aged (60.9±8.4) years. The operation time, intraoperative blood loss, complications and postoperative survival were analyzed.Results:Five patients were treated with percutaneous transhepatic cholangial drainage to reduce jaundice before surgery. All 13 patients successfully underwent the Lap-Larmorh and there was no conversion to laparotomy. The operative time was [ M( Q1, Q3)] 390.0 (355.0, 435.0) minutes, and the intraoperative blood loss was [ M( Q1, Q3)] 800.0 (300.0, 1 100.0) ml. Postoperative complications occurred in 4 patients with pleural effusion, and 1 patient had portal vein thrombosis associated with pleural effusion, who was managed successfully using low molecular weight heparin sodium anticoagulation therapy and pleural effusion tapping. The postoperative hospital stay was (12.5±5.5) days, and there was no perioperative death. Intraoperative frozen pathology showed 12 patients with left hepatic duct with negative margins, and 1 patient with moderate dysplasia. Postoperative paraffin pathology showed 12 patients with bile duct adenocarcinoma, 1 patient with bile duct mucinous adenocarcinoma, 2 patients with tumors of high differentiation, 10 patients with moderate differentiation, and 1 patient with poor differentiative. The R 0 resection rate was 100.0% (13/13) and the tumor diameter was (2.9±0.9) cm. Follow-up by telephone or outpatient clinics after operation showed 1 patients to be lost to follow-up. The 1-year survival rate after operation was 66.7% (8/12). Conclusion:For Bismuth-Corlette type Ⅲa hilar cholangiocarcinoma, the new laparoscopic approach of Lap-Larmorh was safe and feasible.
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Objective:To study the retrocolonic approach for laparoscopic pancreaticoduodenec-tomy (LPD).Methods:The clinical data of 53 patients who underwent LPD using the retrocolonic approach at the Second Hospital of Hebei Medical University from January 2019 to December 2021 were analyzed retrospectively. There were 36 males and 17 females, aged (61.9±8.8) years old. The operation time, intraoperative bleeding and postoperative complications were analysed.Results:LPD was successfully performed in 53 patients via the retrocolonic approach. The operation time was (285.7±49.8) min, and the resection time for specimens was (120.0±10.5) min. The median intraoperative blood loss was 200 ml and blood loss ranged from 50 to 800 ml. Among the 53 patients, 3 patients underwent combined portal vein resection and reconstruction (end-to-end anastomosis). The operation time was 300, 325 and 385 min, respectively, and the intraoperative blood loss was 400-800 ml. During the operation, 5 patients (9.43%) had transection of the middle colonic artery and underwent resection of part of the transverse mesocolon due to invasion of the transverse mesocolon by tumours. Postoperative complications occurred in 5 patients (9.43%), including 4 patients with pancreatic fistula and 1 patient with hemorrhage and with delayed gastric emptying. The postoperative passage of first flatus was (5.40±1.14) days in 5 patients with transection and (2.92±1.03) days in 48 patients without transection of the middle colonic artery. All patients were discharged home successfully. The postoperative pathological results showed all patients to achieve R 0 resection. Conclusion:Laparoscopic pancreaticoduodenectomy via the retrocolonic approach was safe and feasible for patients with a large duodenal tumor, pancreatic head uncinate process tumor with or without invasion of the portal vein and mesenteric vessels.
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Objective:To evaluate the safety and effectiveness of clinical application of " variable diameter measurable pancreatic duct" in laparoscopic pancreaticoduodenectomy (LPD).Methods:A retrospective study was conducted at the Second Hospital, Hebei Medical University Liver Surgical Team from July 2019 to July 2020 using the " HongShi single stitch" method of pancreatic duct to jejunum anastomosis on 147 patients who underwent LPD. According to the type of pancreatic duct, the patients were divided into having normal pancreatic ducts (the normal group, n=61) and those having " variable diameter measuring pancreatic duct" (the variable diameter group, n=86). The perioperative data and postoperative complications were compared and analyzed. Results:There were 89 males and 58 females, aged (56.7±1.5) years. There were no significant differences in age, gender and body mass index between groups ( P>0.05). For the variable diameter group, the diameter of the divided pancreatic stump was (3.2±0.1) mm, and the depth of internal pancreatic duct stenting was (4.7±0.2) cm. However, it could not be measured accurately in the normal group. The incidence of postoperative pancreatic fistula rate was significantly lower in the variable diameter group than the normal group [2.32% (2/61) vs. 11.47% (7/86), P=0.023]. Conclusion:The variable diameter measurement of pancreatic duct was safe and effective in choosing patients to undergo LPD.
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Objective:To explore the mechanism of circular permuted tumor necrosis factor-related apoptosis-inducing ligand (CPT) reversing the resistance to imatinib in chronic myeloid leukemia (CML) cells.Methods:Five patients with CML in the Affiliated Hospital of Inner Mongolia Medical University from 2016 to 2020 were selected, and heparinized bone marrow blood samples were collected at the first diagnosis and imatinib resistance phase, and mononuclear cells were isolated. The mononuclear cells collected at the first diagnosis were named A1-E1, and the mononuclear cells collected after imatinib resistance were named A2-E2. Human CML wild-type K562 cell line (K562-W) was given gradually increasing small doses of low-concentration imatinib to obtain imatinib-resistant K562 cells (K562-R). K562-R cells were cultured with 20 μg/L CPT and these cells were set as CPT-K562-R group. The CCK-8 method was used to detect the half inhibitory concentration ( IC50) of cells for imatinib. K562-W and K562-R cells were used to establish CML xenografts nude mice models, then the nude mice were divided into K562-W, K562-R and CPT-K562-R xenograft groups. Imatinib was perfused orally in all three groups, and CPT was injected subcutaneously in the CPT-K562-R group at the same time. The tumor volume of the three groups of nude mice before and 4 weeks after treatment with imatinib, and the survival time of the three groups of nude mice were compared. Western blot was used to detect the changes of tyrosine protein kinase receptor B4 (EphB4) and myeloid cell leukemia protein 1 (Mcl-1) protein levels in bone marrow mononuclear cells, K562 cell line and transplanted tumor tissues of CML patients. Results:The expressions of EphB4 protein in A2-E2 cells of 5 patients with CML were higher than those in A1-E1 cells (all P < 0.01). The IC50 of K562-W, K562-R and CPT-K562-R cells for imatinib were (0.160±0.015) mg/L, (5.450±0.460) mg/L, (0.300±0.035) mg/L, and the difference was statistically significant ( F = 390.65, P < 0.01). In cells of K562-W group, EphB4 and Mcl-1 proteins were expressed at low levels (0.54±0.02 and 0.70±0.08); in cells of K562-R group, the expressions of EphB4 and Mcl-1 proteins were enhanced (3.04±0.11 and 2.88±0.04); in cells of CPT-K562-R group, the expressions of EphB4 and Mcl-1 proteins decreased (0.57±0.03 and 0.38±0.04). Before imatinib treatment, there was no statistically significant difference in the tumor volumes of nude mice among the K562-W, K562-R and CPT-K562-R xenograft groups ( F = 0.39, P = 0.68), suggesting the transplanted tumors formed in nude mice were balanced; after imatinib treatment, the difference in the tumor volumes among the three groups were statistically significant ( F = 26.16, P < 0.01). The survival time of nude mice in the K562-W, K562-R and CPT-K562-R xenograft groups was (18.5±3.3) d, (10.0±2.4) d and (17.5±1.6) d, and the difference was statistically significant ( F = 20.45, P < 0.01). In K562-W xenograft group, both EphB4 and Mcl-1 proteins were expressed at low levels (0.55±0.06 and 0.67±0.06); in K562-R xenograft group, the expressions of EphB4 and Mcl-1 proteins were enhanced (1.95±0.08 and 6.21±0.53); the expressions of EphB4 and Mcl-1 in CPT-K562-R xenograft group decreased (0.59±0.04 and 0.37±0.04) and were close to their expressions in K562-W xenograft group. Conclusion:CPT may enhance the sensitivity of CML to imatinib by inhibiting the expressions of EphB4 and Mcl-1, and this may be a targeted pathway for imatinib therapy.
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The development of comorbidity-based disease progression and mortality prediction models incorporating demographic and sociological characteristics and the type and severity of comorbidities has been a hot topic in recent clinical studies.The elderly population now constitutes the majority of patients on maintenance dialysis(MHD)and is still rising.It is difficult to predict outcomes for elderly MHD patients, who are often associated with comorbidities, late start on hemodialysis and high mortality.However, very few researchers have closely followed the development of comorbidity-based predictive models for these patients.Therefore, this article reviews relevant studies and offers insights on this topic, in order to attract the attention of colleagues in this county and, as we work together, to improve the survival of elderly patients on dialysis.
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Objective:To compare aging models for renal tubular epithelial cells induced by different drugs.Methods:Different concentrations of D-galactose(D-gal), hydrogen peroxide(H 2O 2)and cisplatin(CDDP)were administered to the human proximal tubular epithelial cell line(HK2). Cell activity and the half maximal inhibitory concentration(IC50)were measured by the CCK-8 assay; cell senescence was assessed by senescence-related β-galactosidase staining(SA-β-gal); senescence-related gene expression was detected by Western blotting; cell cycle distribution and apoptosis were determined by flow cytometry.Pathological changes in renal tubules and interstitial tissues were examined in D-gal-induced and naturally aging mice using HE staining, and p16 expression was detected using immunohistochemistry. Results:CCK-8 assay results showed that HK2 cell activity was inhibited treatment with each of the three compounds.The 48-hour IC50 values were(365.8±9.7)mmol/L for D-gal, (385.4±20.8)μmol/L for H 2O 2 and(8.4±1.6)μmol/L for CDDP.Light microscopic observation revealed slowed growth of HK2 cells in the three groups.The rate of SA-β-gal-positive cells increased, compared with the control group( P<0.05). Treatment resulted in an increase in G0/G1 phase cells by(22.9±1.0)% in the 400 mmol/L D-gal group and by(13.0±4.4)% in the 400 μmol/L H 2O 2 group, while G2/M phase cells increased by(14.4±1.9)%( t=48.07, 6.40, 16.53, P<0.05)in the 8 μmol/L CDDP group, compared with the control group.Also, compared with the control group, HK2 cell apoptosis increased by(50.3±1.0)% in the 400 μmol/L H 2O 2 group and by(41.9±2.0)% in the 8 μmol/L CDDP group, which was significantly higher than(7.7±0.4)% in the 400 mmol/L D-gal group( t=77.47, 33.73, 28.35, all P<0.05). Western blotting results indicated that the expression of CCND1 was down-regulated after any of the three drugs reached a certain concentration.The expression of p16 in the D-gal group was up-regulated( F=92.88, P<0.05), but there was no statistical difference in the expression of p16 after H 2O 2 or CDDP treatment.Mice of the D-gal model showed a decline in renal tubular cells, thickened basement membrane, widened interstitial spaces and increased expression of p16 in renal tubules similar to those observed in naturally aging mice. Conclusions:For HK2 cell senescence models induced by three different drugs, the renal tubular epithelial cell senescence model induced by D-gal is relatively close to the natural senescence model.
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Objective:To evaluate changes in the estimate glomerular filtration rate(eGFR)with aging and the risk factors.Methods:A retrospective cross-sectional study was performed based on people receiving physical examinations at the First Affiliated Hospital of Nanjing Medical University from January 2017 to January 2018.Subjects were divided into seven subgroups according to age: 18-29, 30-39, 40-49, 50-59, 60-69, 70-79, and ≥80 years old.eGFR was estimated by the Chronic Kidney Disease Epidemiology Collaboration(CKD-EPIScr)equation.Multivariate linear regression was used to analyze the correlation between eGFR and the influencing variables.The chi-square test was used to compare the incidences of eGFR<60 ml·min -1·1.73m -2in different age groups. Results:A total of 33 824 participants were included in this study.There was a negative linear eGFR-age correlation in the subjects.The mean annual rate of decline in eGFR was 0.83 ml·min -1·1.73m -2.Furthermore, the decline was steady and accelerated from the third and seventh decade onward( F=9.51, 5.37, both P=0.000). Multiple linear regression analysis showed that aging was the most prominent factor( β=-0.604, -0.534, both P=0.000), followed by serum uric acid(BUA)( β=-0.270, -0.280, both P=0.000), fasting blood-glucose(FBG)( β=-0.064, -0.046, both P=0.000), systolic blood pressure(SBP)( β=-0.015, -0.028, both P<0.05), and diastolic blood pressure(DBP)( β=-0.010, -0.026, both P<0.05). In non-elderly subjects, eGFR was found to have negative associations with body mass index(BMI)and albumin(ALB)( β=-0.028, -0.047, all P=0.000). However, in the elderly, eGFR was positively associated with ALB( β=0.022, P=0.031). eGFR showed no statistically significant correlation with BMI, TC and LDL-C.The prevalence of eGFR<60 ml·min -1·1.73m -2increased with age, at 1.55%(523/33 824)for all subjects, of whom 73.80%(386/523)were aged over 60.The incidence obviously increased from 0.22%(14/6 453)for aged 18-29 to 22.57%(214/948)for aged 80 and above( χ2=2433.71, P=0.000). Conclusions:eGFR decreases significantly with age.The incidence of eGFR<60 ml·min -1·1.73m -2in the elderly is high; eGFR is significantly correlated with BUA, FBG, SBP, DBP, and ALB in the elderly.
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There is a high incidence of thromboembolic events in patients with nephrotic syndrome(NS), and the risk of thrombosis and bleeding increases in the elderly.On the basis of the guidelines of Kidney Disease: Improving Global Outcomes(KDIGO)glomerulonephritis 2020, the risk assessment of thromboembolism and bleeding, the timing of anticoagulant therapy and prevention and the selection of drugs for elderly NS individuals are discussed in this review.
RESUMO
Membranous nephropathy(MN)is the most common cause of nephrotic syndrome in the elderly.In recent years, the prevalence of MN has been increasing every year.The diagnosis and treatment of MN has entered the new era of molecular medicine with the identification of autoantibodies against the phospholipase A2 receptor(PLA2R). This review focuses on recent advances in the treatment and diagnosis of MN based on the 2020 Kidney Disease: Improving Global Outcomes(KDIGO)guidelines.
