1.Role of SIRT1/Nrf2 signaling pathway in berberine-induced reduction of renal ischemia-reperfusion injury in mice
Linlin SUN ; Mingyue HAO ; Mingwei SHENG ; Jingshu LYU ; Yuhua YANG ; Jiahao ZHI ; Yiqi WENG ; Wenli YU ; Hongyin DU
Chinese Journal of Anesthesiology 2021;41(5):598-602
Objective:To evaluate the role of silencing information regulator 1 (SIRT1)/nuclear factors E2-related factor2 (Nrf2) signaling pathway in berberine-induced reduction of renal ischemia-reperfusion (I/R) injury in mice.Methods:Thirty SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 18-22 g, were divided into 5 groups ( n=6 each) using a random number table method: sham operation group (S group), renal I/R group (RIR group), berberine+ I/R group (B group), berberine+ I/R+ SIRT1 inhibitor EX527 group (BE group) and berberine+ I/R+ Nrf2 inhibitor ATRA group (BA group). After the right kidney was removed, the left renal artery was clamped for 45 min followed by reperfusion to establish the model of renal I/R injury.In B, BE, and BA groups, berberine 100 mg·kg -1·d -1 was given for intragastric administration at 14 days before surgery.In group BE and group BA, EX527 5 mg·kg -1·d -1 and ATRA 10 mg·kg -1·d -1 were injected intraperitoneally at 3 days before surgery, respectively.The equal volume of normal saline was given for 14 consecutive days in group S and group RIR.Blood samples were collected from orbital vein at 24 h of reperfusion for measurement of serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations, for determination of the interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) contents (by enzyme-linked immunosorbent assay) and expression of SIRT1, Nrf2, apoptosis-associated speck-like protein containing CARD (ASC), caspase-1, nucleotide-binding oligomerization domain-like receptor containing pyrin domain (NLRP3) (by Western blot) and for examination of the pathological changes of renal tubules (with a light microscope). The damage to the renal tubules was scored. Results:Compared with group S, the concentrations of serum Cr and BUN, the contents of renal IL-1β and TNF-α and renal tubular injury score were significantly increased in RIR, B, BE and BA groups, the expression of SIRT1, Nrf2, ASC, caspase-1 and NLRP3 was up-regulated in RIR, BE and BA groups, and the expression of SIRT1, Nrf2, caspase-1 and NLRP3 was up-regulated in group B ( P<0.05). Compared with group RIR, the concentrations of serum Cr and BUN, the contents of renal IL-1β and TNF-α and renal tubular injury score were significantly decreased in B, BE and BA groups, the expression of SIRT1 and Nrf2 in group B, Nrf2 and ASC in BE group and SIRT1, ASC and caspase-1 in BA group was up-regulated, and the expression of ASC, caspase-1 and NLRP3 in group B, SIRT1 and NLRP3 in BE group and Nrf2 in BA group was down-regulated ( P<0.05). Compared with group B, the serum concentrations of Cr and BUN, the contents of IL-1β and TNF-α and renal tubular injury score were significantly increased in BE and BA groups, the expression of ASC, caspase-1 and NLRP3 in BE and BA groups was up-regulated, and the expression of SIRT1 in BE and Nrf2 in BA groups was down-regulated ( P<0.05). Conclusion:SIRT1/Nrf2 signaling pathway is involved in the process of berberine-induced reduction of renal I/R, which is related to inhibiting pyroptosis in mice.
2.Risk factors for early acute lung injury after pediatric living-related liver transplantation and the predictive value
Yingli CAO ; Mingwei SHENG ; Chen ZHANG ; Jiahao ZHI ; Yimei CAO ; Hongyin DU ; Wenli YU
Chinese Journal of Anesthesiology 2023;43(3):274-277
Objective:To identify the risk factors for early acute lung injury (ALI) after living-related liver transplantation in pediatric patients and evaluate the value of the risk factors in prediction of ALI.Methods:Perioperative data of patients were obtained through the electronic medical records system. Patients were divided into non-ALI group and ALI group according to whether ALI occurred within the first week after surgery. The risk factors of which P values were less than 0.05 would enter the multiple logistic regression analysis to stratify ALI-related risk factors. Area under the ROC curve was used to analyze the value of the risk factors in prediction of postoperative ALI. Results:A total of 67 patients were enrolled, including 45 cases in non-ALI group and 22 cases in ALI group. Increased intraoperative blood transfusion volume and up-regulated expression of miR-122 and miR-21 were independent risk factors for the occurrence of postoperative ALI ( P<0.05), and the area under the ROC curve (95% confidence interval) of serum miR-122 and miR-21 expression was 0.946 (0.875 to 1.00), with sensitivity and specificity of 95% and 90%, respectively. Conclusions:Increased intraoperative blood transfusion volume and up-regulated expression of serum miR-122 and miR-21 are independent risk factors for early postoperative ALI, and serum miR-122 and miR-21 levels have a high value in prediction of the development of postoperative ALI in pediatric patients undergoing living-related liver transplantation.
3.An exploratory study of quantitative analysis of gait characteristics in patients with early Parkinson′s disease
Jiahao ZHAO ; Ying WAN ; Lu SONG ; Juanjuan DU ; Na WU ; Yu ZHANG ; Jie ZHUANG ; Jing GAN ; Zhenguo LIU
Chinese Journal of Neurology 2020;53(7):485-492
Objective:To identify and quantify spatiotemporal and kinematic gait parameters in a group of early-stage Parkinson′s disease (PD) patients compared with healthy subjects.Methods:Eight patients with PD (PD group, Hoehn-Yahr stage≤2.5) and seven age-matched healthy subjects (control group) were enrolled from the Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine between May 2017 and August 2018 for the study. The spatiotemporal and kinematic gait parameters were obtained by Vicon 3D optical motion analysis system under three conditions: single-task walking, dual-task walking and turning. The linear mixed model was used to compare the gait parameters between the two groups and analyze the interactive effects.Results:Arm swing amplitude in the PD group was lower than that in the control group ((0.63±0.15) m vs (0.89±0.27) m in single-task walking, (0.64±0.16) m vs (0.99±0.22) m in dual-task walking, β=-0.353, 95% CI -0.558--0.148, P=0.002). The PD group showed significantly higher arm swing asymmetry than the control group (12.48%±5.48% vs 6.96%±4.39% in single-task walking, 17.13%±4.05% vs 7.67%±5.23% in dual-task walking, β=8.992, 95% CI 4.148-13.836, P=0.001). A notable interactive effect of groups and task factors in arm swing asymmetry was found. The arm swing asymmetry of the PD group increased more than the control group in dual-task walking than in single-task walking (β=3.916, 95% CI 1.367-6.466, P=0.003). As for the gait characteristics of the lower limbs, stride length and step length of the PD group were lower than those of the control group ((1.10±0.17) m vs (1.31±0.10) m in stride length, β=-0.169, 95% CI -0.300--0.038, P=0.015; (0.55±0.09) m vs (0.65±0.04) m in step length, β=-0.081, 95% CI -0.150--0.013, P=0.023). For both groups, statistically significant differences were not observed in step width, stride length and step length between single-task and dual-task walking ( P>0.05). The PD group completed the turning process faster than the control group ((1.66±0.30) s vs (1.37±0.23) s, β=0.302, 95% CI 0.049-0.555, P=0.023). As for the rotation-onset pattern, no statistically significant differences were found between the PD and the control group for the onset of the head, trunk and pelvic rotation ( P>0.05). Participants started to rotate their heads before the pelvis in all groups (β=-0.060, 95% CI-0.107--0.014, P=0.011). Conclusions:The quantified gait parameters can more accurately reflect the gait characteristics of early PD. Patients with PD exhibited smaller arm swing magnitude, greater arm swing asymmetry, shorter stride length, and slower turning speed compared to the controls. Arm swing asymmetry further differs between subjects with early PD and controls under dual-task walking.
4.Effects of berberine on necroptosis of non-alcoholic fatty liver disease in mice: Relationship with AMPK/STAT6 pathway
Mingyue HAO ; Linlin SUN ; Mingwei SHENG ; Jingshu LYU ; Yuanbang LIN ; Yuhua YANG ; Jiahao ZHI ; Wenli YU ; Hongyin DU
Chinese Journal of Endocrinology and Metabolism 2022;38(3):225-230
Objective:To evaluate the effects of berberine on necroptosis of non-alcoholic fatty liver disease in mice and its relationship with adenosine monophosphate-activated protein kinase(AMPK)/ signal transducer and activator of transcription 6(STAT6) pathway.Methods:Twenty-five 8-week-old male C57BL/6N mice were divided into control group, steatotic liver group, berberine treatment group(200 mg·kg -1·d -1), AMPK inhibitor Compound C treatment group(0.2 mg·kg -1·d -1), and STAT6 inhibitor AS1517499 treatment group(10 mg·kg -1·d -1). After 12 weeks of intervention, the mice and liver tissue were weighed, and serum aspartate aminotransferase(AST), alanine aminotransferase(ALT), triglyceride, tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) as well as liver malondialdehyde and superoxide dismutase were measured; liver tissue HE, Masson, and oil red O staining were performed. Western blotting was used to detect the expressions of necroptosis related proteins[receptor interaction protein kinase 3(RIPK3), phosphorylated(p-) mixed lineage kinase domain-like(MLKL)], AMPK, p-AMPK, and p-STAT6. Results:Compared with control group, the steatotic liver group had higher quality of liver and liver index, and higher levels of serum AST, ALT, triglyceride, TNF-α, IL-1β, and oxidative stress( P<0.05); Liver tissue was full of cavity changes and inflammatory cell infiltration, widely distributed red lipid droplets and obvious blue fiber dyeing; The expressions of RIPK3 and p-MLKL were up-regulated ( P<0.05), but the levels of p-AMPK and p-STAT6 were relatively reduced ( P<0.05). Compared with the steatotic liver group, berberine intervention decreased liver quality and liver index, improved liver function, reduced blood lipid levels, pro-inflammatory factor expression and oxidative stress level, and significantly alleviated the degree of liver steatosis and fibrosis, the levels of RIPK3 and p-MLKL ( P<0.05), while the expressions of p-AMPK and p-STAT6 were increased significantly ( P<0.05). As compared with the berberine treatment, AMPK and STAT6 inhibitor treatment could offset the protective effect of berberine on steatotic liver, moreover, the expressions of RIPK3 and p-MLKL were increased ( P<0.05). There was no statistical difference in AMPK total protein content among the five groups ( P>0.05). Conclusion:Berberine can activate AMPK/STAT6 pathway to inhibit the necroptosis of hepatocyte, thus plays a protective role on non-alcoholic fatty liver disease in mice.
5.Comparison of myocardial protection in pediatric patients undergoing living-donor liver transplantation performed under propofol- versus desflurane-based anesthesia
Jiahao ZHI ; Yimei CAO ; Yingli CAO ; Hengchang REN ; Lili JIA ; Yiqi WENG ; Hongyin DU ; Wenli YU
Chinese Journal of Anesthesiology 2023;43(3):265-268
Objective:To compare the myocardial protection in pediatric patients undergoing living-donor liver transplantation (LDLT) performed under propofol- versus desflurane-based anesthesia. Methods:Sixty American Society of Anesthesiologists Physical Status classification Ⅲ or Ⅳ pediatric patients of both sexes, aged 5-24 months, weighing 5-15 kg, scheduled for elective LDLT under general anesthesia, were divided into 2 groups ( n=30 each) using a random number table method: propofol group (group P) and desflurane anesthesia group (group D). During anesthesia maintenance, propofol 5-10 mg·kg -1·min -1 was intravenously infused in group P, desflurane 0.65 MAC-1.30 MAC was inhaled in group D. At 5 min after induction of anesthesia, at 1 h of reperfusion, at the end of surgery, at 1, 2, 3, 7 and 14 days after surgery, and on the day of discharge, the concentrations of serum high-sensitivity cardiac troponin I, creatine kinase isoenzyme, N-terminal pro-B-type natriuretic peptide were determined by enzyme-linked immunosorbent assay, the occurrence of nausea and vomiting, agitation, and shivering, postoperative tracheal extubation time, intensive care unit stay time, and postoperative length of hospital stay were recorded within 24 h after surgery. Results:Compared with group P, the concentrations of serum high-sensitivity cardiac troponin I and creatine kinase isoenzyme were significantly decreased after surgery, the extubation time and intensive care unit stay time were shortened ( P<0.05), and no significant change was found in serum N-terminal pro-B-type natriuretic peptide concentrations, postoperative length of hospital stay and incidence of postoperative adverse effects at each time point in group D ( P>0.05). Conclusions:Desflurane has better myocardial protection than propofol in pediatric patients undergoing LDLT, which is helpful for early prognosis.
6.Predictive value of Pv-aCO 2/Ca-vO 2 combined blood lactate concentration for primary peritonitis-related septic shock in children
Le MA ; Jiahao TIAN ; Yipei LI ; Ying WANG ; Yanqiang DU ; Yi WANG
Chinese Critical Care Medicine 2023;35(1):77-81
Objective:To investigate the prognostic value of the ratio of veno-arterial carbon dioxide partial pressure difference to arterio-venous oxygen content difference (Pv-aCO 2/Ca-vO 2) in children with primary peritonitis-related septic shock. Methods:A retrospective study was conducted. Sixty-three children with primary peritonitis-related septic shock admitted to department of intensive care unit of the Children's Hospital Affiliated to Xi'an Jiaotong University from December 2016 to December 2021 were enrolled. The 28-day all-cause mortality was the primary endpoint event. The children were divided into survival group and death group according to the prognosis. The baseline data, blood gas analysis, blood routine, coagulation, inflammatory status, critical score and other related clinical data of the two groups were statistics. The factors affecting the prognosis were analyzed by binary Logistic regression, and the predictability of risk factors were tested by the receiver operator characteristic curve (ROC curve). The risk factors were stratified according to the cut-off, Kaplan-Meier survival curve analysis compared the prognostic differences between the groups.Results:A total of 63 children were enrolled, including 30 males and 33 females, the average age (5.6±4.0) years old, 16 cases died in 28 days, with mortality was 25.4%. There were no significant differences in gender, age, body weight and pathogen distribution between the two groups. The proportion of mechanical ventilation, surgical intervention, vasoactive drug application, and procalcitonin, C-reactive protein, activated partial thromboplastin time, serum lactate (Lac), Pv-aCO 2/Ca-vO 2, pediatric sequential organ failure assessment, pediatric risk of mortality Ⅲ in the death group were higher than those in the survival group. Platelet count, fibrinogen, mean arterial pressure were lower than those in the survival group, and the differences were statistically significant. Binary Logistic regression analysis showed that Lac and Pv-aCO 2/Ca-vO 2 were independent risk factors affecting the prognosis of children [odds ratio ( OR) and 95% confidence interval (95% CI) were 2.01 (1.15-3.21), 2.37 (1.41-3.22), respectively, both P < 0.01]. ROC curve analysis showed that the area under curve (AUC) of Lac, Pv-aCO 2/Ca-vO 2 and their combination were 0.745, 0.876 and 0.923, the sensitivity were 75%, 85% and 88%, and the specificity were 71%, 87% and 91%, respectively. Risk factors were stratified according to cut-off, and Kaplan-Meier survival curve analysis showed that the 28-day cumulative probability of survival of Lac ≥ 4 mmol/L group was lower than that in Lac < 4 mmol/L group [64.29% (18/28) vs. 82.86% (29/35), P < 0.05]. Pv-aCO 2/Ca-vO 2 ≥ 1.6 group 28-day cumulative probability of survival was less than Pv-aCO 2/Ca-vO 2 < 1.6 group [62.07% (18/29) vs. 85.29% (29/34), P < 0.01]. After a hierarchical combination of the two sets of indicator variables, the 28-day cumulative probability of survival of Pv-aCO 2/Ca-vO 2 ≥ 1.6 and Lac ≥ 4 mmol/L group significantly lower than that of the other three groups (Log-rank test, χ2 = 7.910, P = 0.017). Conclusion:Pv-aCO 2/Ca-vO 2 combined with Lac has a good predictive value for the prognosis of children with peritonitis-related septic shock.
7.Clinical characteristics of patients >65 years old with acute exacerbation of chronic obstructive pulmonary disease and COVID-19 infection
Yuanzhen JIAN ; Caijun WU ; Li LI ; Jiahao DU ; Aiguo ZHANG ; Zhiyuan NIE ; Qiaojie SUN
Journal of Chinese Physician 2024;26(2):166-171
Objective:To investigate the clinical characteristics of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and corona virus disease 2019 (COVID-19) infection.Methods:Clinical data of AECOPD patients over 65 years old who were diagnosed in the Respiratory and Emergency Departments of the Dongzhimen Hospital, Beijing University of Chinese Medicine from September 2022 to September 2023 were collected. AECOPD patients were divided into a COVID-19 group ( n=29) and a non COVID-19 group ( n=31). The platelet count, white blood cell count, lymphocyte count, neutrophil count, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), C-reactive protein (CRP), procalcitonin (PCT), partial pressure of oxygen (PO 2), partial pressure of carbon dioxide (PCO 2), D-dimer (D-D), and interleukin-6 (IL-6) were compared between two groups of patients upon admission Confusion, Uremia, Respiratory, BP, Age 65 Years (CURB-65) was used to compare length of hospital stay, AECOPD grading, and mortality endpoint days. Results:There was no statistically significant difference in platelet count, white blood cell count, lymphocyte count, neutrophil count, NLR, and PLR between the COVID-19 group and the non COVID-19 group (all P>0.05). The proportion of males, CRP, PCO 2, D-D, IL-6, and CURB-65 scores in the COVID-19 group were higher than those in the non COVID-19 group, while PCT and PO 2 were lower than those in the non COVID-19 group, with statistically significant difference (all P<0.05). The proportion of AECOPD grade Ⅲ in the COVID-19 group was significantly higher than that in the non COVID-19 group, and the progression rate of the disease was higher in the COVID-19 group (37.9% vs 22.6%, P<0.05). COVID-19 was an independent influencing factor for the progression of AECOPD. Conclusions:Patients over 65 years old with AECOPD infected with COVID-19 have a more pronounced inflammatory response, and CRP, IL-6, and CURB-65 scores can be used as indicators to evaluate the degree of inflammation. AECOPD infected with COVID-19 are more prone to coagulation disorders, hypoxemia, more severe illness, and easier progression, suggesting that COVID-19 infection is an independent influencing factor for the progression of AECOPD.
8.Effect of visceral obesity on the short-term outcomes following robotic-assisted radic-al resection of rectal cancer
Xuetao ZHANG ; Liang LI ; Renyi YANG ; Yongkang MENG ; Jiahao SUN ; Shuxiang DU ; Yingzhi ZHAO ; Dongli XU ; Wei ZHANG ; Gang WU
Chinese Journal of Clinical Oncology 2023;50(22):1153-1158
Objective:To investigate the effect of visceral obesity on the short-term curative effect of Da Vinci robotic-assisted radical resec-tion for rectal cancers.Methods:Clinical and pathological data of patients with rectal cancer undergoing Da Vinci robotic-assisted surgery,admitted to People's Hospital of Zhengzhou University and Cancer Hospital of Zhengzhou University from November 2019 to June 2022 were retrospectively analyzed.Visceral fat area(VFA)≥100 cm2 was used as the standard to define visceral obesity.Patients were categorized in-to visceral and non-visceral obesity groups.The short-term efficacy of the two groups was evaluated,and the influencing factors of post-operative complications were analyzed using univariate and multivariate Logistic regression.Results:Among a total of 169 patients,93 were included in the visceral obesity group and 76 in the non-visceral obesity group.There was no significant difference in the baseline data between the two groups(P>0.05).There was no conversion to laparotomy in the non-visceral obesity group,and the conversion rate was 1.1%(1/93)in the visceral obesity group.The second operation rate was 2.2%(2/93)in the visceral obesity group and 1.3%(1/76)in the non-visceral obesity group with no statistical difference between the two groups.There were no significant differences in the operation dur-ation,intraoperative blood loss,number of lymph node dissections,and total postoperative complication rate between the two groups(P>0.05).Multivariate Logistic regression analysis revealed that an NRS≥3 independently contributed as a risk factor for postoperative com-plications(OR=3.190,95%CI:1.240-8.210,P=0.016).Conclusions:An NRS≥3 is an independent risk factor for complications post-robotic rad-ical rectal cancer surgery.The robotic surgical platform can overcome obesity-related limitations and is equally safe and effective for pa-tients with visceral obesity presenting with rectal cancer.