1.Research Progress of Endoplasmic Reticulum Stress PERK-eIF2α-AFT4-CHOP Signaling Pathway in Hematological Malignancies
Mengke HE ; Zizhen XU ; Junmin LI
Cancer Research on Prevention and Treatment 2024;51(2):140-146
The biosynthesis and maturation of proteins are primarily regulated by the endoplasmic reticulum in its physiological state. Thus, the disruption of physiological homeostasis initiates the buildup of unfolded and misfolded proteins in the endoplasmic reticulum, resulting in endoplasmic reticulum stress (ERS) and unfolded protein response (UPR). One of the important pathways by which UPR maintains intracellular homeostasis under ERS is activating protein kinase R-like endoplasmic reticulum kinase (PERK). The activation of the PERK pathway stimulates eukaryotic translation initiation factor 2 subunit-α (eIF2α) phosphorylation and the selective translation of active transcription factor 4 (ATF4), and PERK induces cell apoptosis by directly binding to the promoter of pro-apoptotic transcription factor C/EBP homologous protein (CHOP). This signaling pathway is also one of the important mechanisms by which UPR participates in the regulation of hematological malignancies and immune cells in a tumor microenvironment. This article provides an overview of advancements in research into the PERK-eIF2α-ATF4-CHOP signaling pathway in hematological malignancies and the potential therapeutic benefits of targeting this signaling pathway.
2.Effect of intraoperative regional cerebral oxygen saturation monitoring on perioperative neurocognitive disorders in elderly patients undergoing non-cardiac surgery: a meta-analysis
Xing ZHOU ; Suping ZHONG ; Junmin HE ; Lili HE ; Jie TIAN ; Fanfan PENG
Chinese Journal of Anesthesiology 2023;43(5):540-546
Objective:To systematically review and evaluate the effect of intraoperative regional cerebral oxygen saturation (rSO 2) monitoring on perioperative neurocognitive disorders (PNDs) in elderly patients undergoing non-cardiac surgery. Methods:China National Knowledge Infrastructure, Wanfang Database, China Biomedical Literature Database, China Science and Technology Journal Database, PubMed, Cochrane Library, Embase and Web of Science databases were searched from inception to October 2022 for randomized controlled trials involving the effects of intraoperative rSO 2 monitoring on PND in elderly patients underwent non-cardiac surgery. The primary outcome measure was the incidence of PND (1-7 days after surgery), and secondary outcome measures were intraoperative minimum rSO 2 (rSO 2min), intraoperative mean rSO 2 (rSO 2mean), maximum percentage of decrease (rSO 2% max) in rSO 2 from baseline (rSO 2baseline), and the Montreal Cognitive Assessment Scale was used to evaluate the quality of references that met the inclusion criteria, and data were extracted for meta-analysis using RevMan5.4 software. Results:Thirteen randomized controlled trials were enrolled, involving 1 134 patients with 557 patients in experimental group (anesthesia under rSO 2 monitoring) and 577 patients in control group. The results of meta-analysis showed that the incidence of PND was significantly lower in experimental group than in control group ( RR=0.32, 95% confidence interval [ CI] 0.25-0.41, P<0.001), the intraoperative rSO 2min was significantly higher in experimental group than in control group ( MD=7.46, 95% CI 5.05-9.86, P<0.001), and the intraoperative rSO 2mean was significantly higher in experimental group than in control group ( MD=5.49, 95% CI 3.97-7.02, P<0.001), the intraoperative rSO 2% max was significantly lower in experimental group than in control group ( MD=-6.55, 95% CI-9.03--4.07, P<0.001), and the postoperative Montreal Cognitive Assessment Scale score was significantly higher in experimental group than in control group ( MD=1.37, 95% CI 0.74-1.99, P<0.001). Conclusions:Intraoperative application of rSO 2 monitoring can reduce the occurrence of PND in elderly patients undergoing non-cardiac surgery.
3.Analysis of risk factors of fetal residue after delivery combined with uterine arteriovenous fistula
Xiaojie YANG ; Yun CHEN ; Hua HE ; Mengxue LI ; Lihua YANG ; Junmin HUANG ; Xuesong ZHANG ; Ying WANG
Clinical Medicine of China 2021;37(4):339-343
Objective:To investigate the risk factors of postpartum embryo residues associated with uterine arteriovenous fistula.Methods:From January 2000 to December 2020, 26 cases of postpartum embryo residue complicated with uterine arteriovenous fistula in Tangshan Maternal and Child Health Hospital were selected as the case group, and 32 cases of postpartum embryo residue without uterine arteriovenous fistula were selected as control group.Both the case group and the control group had embryo residue in cesarean scar.Univariate and multivariate logistic analysis were used to screen the risk factors of postpartum embryo residue combined with uterine arteriovenous fistula.Results:There were 26 patients in the case group, including 3 patients after medical abortion, 17 patients after artificial abortion, 2 patients after cesarean section, and 4 patients after mid-term induced labor.There were 32 patients in the control group, including 7 patients after medical abortion, 11 patients after induced abortion, 8 patients after cesarean section, and 6 patients after mid-term induced labor.There were 11 patients in the case group and 3 patients in the control group.Univariate analysis showed that: the occurrence of postpartum embryo residue combined with uterine arteriovenous fistula was related to the time of vaginal bleeding, HCG value before and after treatment, hemoglobin value before treatment, platelet count and residual embryo area(all P<0.05). Multivariate regression analysis showed that the increase of hCG before treatment ( OR 20.319, 95% CI 1.348-306.187) and the decrease of hemoglobin before treatment ( OR 0.870, 95% CI 0.788-0.960) were the independent risk factors of postpartum embryo residue combined with uterine arteriovenous fistula (all P<0.05). Conclusion:The risk factors of uterine arteriovenous fistula in postpartum embryo residue patients with elevated hCG value and decreased hemoglobin value before treatment should be highly vigilant to reduce the rate of clinical missed diagnosis.
4.Perioperative safety of pancreaticoduodenectomy in elderly patients
Zhe LI ; Jingyong XU ; Xiuwen HE ; Jiangchun QIAO ; Jinghai SONG ; Jian CHEN ; Junmin WEI
Chinese Journal of Geriatrics 2021;40(6):752-755
Objective:To evaluate the perioperative safety of pancreaticoduodenectomy(PD)in elderly patients.Methods:Clinical data of 152 patients undergoing PD in Beijing Hospital between 2016 and 2019 were retrospectively analyzed.According to the age, patients were divided into the elderly group(age≥65 years)and the non-elderly group(age<65 years). The perioperative and postoperative parameters were compared between the two groups.Results:There was no significant difference in the operative time, intraoperative blood loss and intraoperative urine output between the elderly group and the non-elderly group(352.7±69.5)min vs.(359.0±94.4)min, (708.7±672.7) vs.(662.6±896.7)ml and(875.8±497.3)ml vs.(1010.6±568.2)ml, all P>0.05). The perioperative mortality, postoperative complications(Clavien-Dindo classification ≥ grade Ⅲ)and reoperation rate had no significant difference between elderly group and the non-elderly group(6.1% vs.1.2%, 21.2% vs.19.8%, 10.6% vs.8.1%, respectively, χ2=1.487, 0.048 and 0.272, all P>0.05). The incidences of operation-related complications, cardiovascular or cerebrovascular adverse events in elderly group were comparable to non-elderly group( P>0.05). The postoperative hospital stay had no significant difference between the elderly group and the non-elderly group[(28±19)d vs.(27±18)d, P>0.05]. Conclusions:PD is safe in elderly patients.Age is not a contraindication to pancreaticoduodenectomy.The comprehensive systemic evaluation, intraoperative delicate operation and enhanced perioperative management are necessary in the elderly patients undergoing PD.
5.Expression and significance of miR-138 and programmed cell death protein 1 in the patients with HBV-related hepatocellular carcinoma
Wei LIU ; Quanli HE ; Junmin LI ; Heshui HUO ; Zhizhong LU ; Wei LI ; Fuguo JIANG
Chinese Journal of Clinical Laboratory Science 2019;37(4):269-273
Objective:
Abstract: Objective: To investigate the expression and significance of miR-138 and programmed cell death protein 1 (PD-1) in the patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).
Methods:
A total of 30 patients with HBV-related HCC, 20 with HBV-related cirrhosis (LC) and 30 with chronic hepatitis B (CHB) were recruited from Jiaozuo People′s Hospital. The blood samples from all patients and the peritoneal effusion samples from HCC and LC patients were collected. The levels of miR-138 and soluble PD-1 (sPD-1) in blood and peritoneal effusion samples were detected by real-time PCR and ELISA, respectively. The expressions of PD-1 in T lymphocytes were measured with flow cytometry and western blot. The targeting effect of miR-138 on the 3′-non-coding region (3′-UTR) of PD-1 gene was verified by the dual-luciferase reporter gene system.
Results:
The relative expression levels of miR-138 in the peritoneal effusion and plasma of HBV-related HCC patients were significantly lower than those in LC and CHB patients (P<0.05). The serum sPD-1 levels and the expression levels of PD-1 in CD3 + T lymphocytes of HBV-related HCC patients were significantly higher than those in LC and CHB patients (P<0.05). The relative expression levels of miR-138 were negatively correlated with serum sPD-1 levels and the expression levels of PD-1 in CD3 + T lymphocytes (P<0.05). The dual-luciferase reporter gene system and western blot results demonstrated that there was a targeting relationship between miR-138 and the 3′-UTR of PD-1 gene. After miR-138 was transfected, the expression level of PD-1 was significantly down-regulated.
Conclusion
miR-138 participates in the development and progression of HBV-related HCC probably by targeting PD-1.
6. The effect of standardized lymphectomy and sampling of resected lymph nodes on TNM staging of resectable pancreatic head cancer
Jingyong XU ; Zhe LI ; Hongyuan CUI ; Jun DU ; Jian CHEN ; Jiangchun QIAO ; Xiuwen HE ; Jinghai SONG ; Junmin WEI ; Yinmo YANG
Chinese Journal of Surgery 2019;57(8):572-577
Objective:
To examine the effect of standardized lymphectomy and sampling of resected lymph nodes (LN) on TNM staging of resectable pancreatic head cancer.
Methods:
Consecutive patients with resectable pancreatic head cancer who received standard pancreatoduodenctomy at Department of General Surgery in Beijing Hospital from December 2017 to November 2018 were recruited as study group. After operation, the surgeon sampled lymph nodes from the fresh specimen following the Japanese Gastric Cancer Guidelines.Thirty-three cases were recruited in the study group and the mean age was (59.8±15.2) years.Pathologic reports from December 2015 to November 2016 were taken as control group, containing 29 cases with age of (57.0±13.0) years. Number of lymph nodes, standard-reaching ratio and positive nodes ratio were compared between two groups. According to the seventh edition and eighth edition of TNM staging, the changes of N staging and TNM staging were analysed. The quantitative data conforming to normal distribution were tested by independent sample
7.Laparoscopic excision of retroperitoneal cysts
Qiuxia YAN ; Xiuwen HE ; Junmin WEI ; Yannan LIU
Chinese Journal of General Surgery 2019;34(7):583-585
Objective To investigate the diagnosis and treatment of retroperitoneal cysts.Methods Data of 7 patients with retroperitoneal cysts undergoing laparoscopy surgery in Beijing Hospital were analyzed.Result All the seven patients received laparoscopy surgery without the residual of cyst wall,and recovered successfully.The blood loss was from 50 ml to 400 ml.The average operation time was (151 ± 113) min.The average post-op hospital stay was(5.9 ± 5.4) d.There was no major post-op complication,nor recurrence.Conclusion Laparoscopy for retroperitoneal cyst is safe and effective Comparing to laparotomy.
8.Influencing factors analysis of microvascular invasion in patients with hepatocellular carcinoma
Peiyuan DU ; Jinghai SONG ; Jiangchun QIAO ; Xiuwen HE ; Jinsong ZHANG ; Jian CHEN ; Hua LYU ; Mingwei ZHU ; Junmin WEI
Chinese Journal of Hepatobiliary Surgery 2019;25(1):26-29
Objective To evaluate the correlation between microvascular invasion(MVI) and prognosis in patients with hepatocellular carcinoma (HCC),and to analyse the influencing factors of MVI in patients with HCC.Methods Total of 81 patients with hepatocellular carcinoma treated in Beijing Hospital from January 2014 to December 2016 were retrospectively studied.There were 65 males and 16 females.The mean age was 59.6± 12.7 years,and the age ranged from 21 to 87 years old.Pathological examination showed presence of MVI in 35 patients.Results Total of seventy-six patients with hepatocellular carcinoma were followed-up.The 1-,2-,3-and 4-year overall survival rates in the 35 patients with microvascular invasion of hepatocellular carcinoma were 78.6%,55.4%,38.3%,and 32.2%,respectively.The 1-,2-,3-,and 4-year overall survival rates of the 41 patients without microvascular invasion were 93.4%,76.5%,68.2% and 68.2%,respectively.The difference was significant (P<0.05).Cox multivariate regression analysis showed that microvascular invasion was an independent risk factor of overall survival after surgery (HR=3.071,95% CI:1.239~7.610,P<0.05).Sub-group analysis was done on patients with microvascular invasion based on pathological results which included the number of MVI lesions,the call number in the MVI lesion,the distance of the MVI to the primary liver cancer,and the gradings of MVI.There were no significant differences in the overall survival outcomes (P>0.05).Multivariate logistic regression analysis showed the maximum diameter of tumor > 5 cm (OR =6.340,95% CI:2.000 ~ 20.096),preoperative total bilirubin (TBil) > 17 μmol/L (OR =5.067,95%CI:1.386 ~ 18.525),and preoperative alpha-fetoprotein (AFP) >400 μg/L (OR =6.042,95% CI:1.435 ~ 25.444) were independent risk factors of microvascular invasion (P< 0.05).Conclusion Hepatocellular carcinoma patients with microvascular invasion had poor prognosis.Preoperative AFP,preoperative TBil,and diameter of tumor were independent risk factors of microvascular invasion in patients with hepatocellular carcinoma.
9.Advances in molecular biological studies of the mangrove Kandelia obovata Sheue, Liu & Yong.
Zhaokui DU ; He CHEN ; Junmin LI
Chinese Journal of Biotechnology 2017;33(2):196-204
Kandelia obovata Sheue, Liu & Yong, a mangrove species which distributed in tropical, subtropical coastal and estuarine intertidal, has important ecological functions in coastal ecosystems. Here, we reviewed several aspects of the recent research progress in molecular biological studies of K. obovata. We focused the phylogeography and genetic diversity of this species by several types of molecular markers, proteome analyses based on two-dimensional electrophoresis platform accomplished for this species, and functional genes isolated under non-biotic stress environment. Finally, based on the current research progress, we proposed some orientations for future molecular biological research on K. obovata.
10.Influence of dexmedetomidine combined with sufentanil on postoperative analgesia effect and immune function for patients undergoing lower limb fracture surgery
Xing ZHOU ; Suping ZHONG ; Hengfa LEI ; Chuntao YANG ; Chunlian CAO ; Jie TIAN ; Yuanyuan LIU ; Ji'an YANG ; Jun LI ; Na MI ; Junmin HE
Chinese Journal of Postgraduates of Medicine 2017;40(6):531-535
Objective To explore the influence of dexmedetomidine combined with sufentanil on postoperative analgesia effect and immune function for patients undergoing lower limb fracture surgery. Methods One hundred cases patients of lower limb fracture undergoing open reduction and internal fixation of elective surgery in our hospital from January 2016 to November 2016 were selected ( ASAⅠ-Ⅱgrade, male 51 cases and female 49 cases, 30-65 years old, 50-75 kg). All cases were randomly divided into sufentanil group (Group S) and dexmedetomidine combined with sufentanil group (Group DS) according to the random number table, who used patient-controlled intravenous analgesia (PCIA). The PCIA drug formulations of two groups were as followings: sufentanil group (Group S) used 3 μg/h sufentanil+ondansetron 16 mg, dissolved in 0.9%sodium chloride injection 100 ml;dexmedetomidine combined with sufentanil group (Group DS) used dexmedetomidine 0.1μg/(kg · h)+sufentanil 2μg/h+ondansetron 16 mg, dissolved in 0.9%sodium chloride injection 100 ml;background infusion rate was 2 ml/h, and loading dose was 2 ml. Dose for patient-controlled analgesia (PCA) was 0.5 ml, and locking time was 15 min. The changes of pain, MAP, HR , sedation scores were recorded at 4 h (T1), 8 h (T2), 24 h (T3) and 48 h (T4) after operation; nausea and vomiting, hypotension, bradycardia, respiratory depression and other adverse reactions were aslo recorded at the same time. At 10 min before induction of anesthesia (T0) and T1-T4 after operation, the CD3+, CD4+, CD8+and NK cell activity of peripheral blood T lymphocyte subsets were determined using flow cytometry, and CD4 +/CD8 + ratio was calculated. Results The levels of MAP and HR in DS group at each time point after operation were lower than those in group S (P<0.05), the level of visual analogue score (VAS) in DS group at different time points were significantly lower than those of s group: (1.8 ± 0.3) scores vs. (2.5 ± 0.5) scores, (1.1 ± 0.5) scores vs. (1.9 ± 0.3) scores, (1.0 ± 0.5) scores vs. (1.8 ± 0.5) scores, (0.8 ± 0.3) scores vs. (1.5 ± 0.6) scores (P < 0.05), Ramsay Sedation score was significantly higher than that of s group: (3.5 ± 0.3) scores vs. (2.4 ± 0.6) scores, (3.3 ± 0.5) scores vs. (2.5 ± 0.3) scores, (3.5 ± 0.6) scores vs. (2.3 ± 0.5) scores, (3.2 ± 0.4) scores vs. (2.2 ± 0.5)scores (P<0.05);nausea and vomiting occurred in two patients after the operation of group DS , which was significantly lower than that of S group (P<0.05);compared with those at T0, CD3+, CD4+, CD4+/CD8+and NK cells in the two groups of patients decreased significantly at the time of T1-T4 (P<0.05);The levels of CD3+, CD4+, CD4+/CD8+and NK cells were significantly higher in group DS at T1- T4 than those in group S(P < 0.05). Conclusions Dexmedetomidine combined with sufentanil for analgesia in patients with lower limb fracture surgery has better effect. It decreases the incidence of nausea and vomiting, and improves the cellular immune function of patients.

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