1.Opportunities and challenges of marginal donor liver
Xinyi LU ; Fei TENG ; Hong FU ; Yuanyu ZHAO ; Liye ZHU ; Jiayong DONG ; Jiaxi MAO ; Wenyuan GUO
Organ Transplantation 2024;15(3):463-468
With persistent breakthrough and maturity of surgical procedures and postoperative immunosuppressive therapy, the survival rate of liver transplant recipients and grafts has been significantly increased. The shortage of donor liver has become the main obstacle for clinical development of liver transplantation. How to expand the source of donor liver has become an urgent issue. Groundbreaking progresses have been made in the use of common marginal donor livers in clinical liver transplantation, such as elderly donor liver, steatosis donor liver, viral hepatitis donor liver and liver from donation after cardiac death. Nevertheless, multiple restrictions still exist regarding the use of marginal donor liver. Consequently, the definition of marginal donor liver and research progress in the application of common marginal donor livers were reviewed, and the opportunities and challenges of mariginal donoor liver were illustrated, aiming to provide reference for expanding the donor pool for clinical liver transplantation and bringing benefits to more patients with end-stage liver disease.
2.Immunological mechanisms in steatotic liver diseases: An overview and clinical perspectives
Mengyao YAN ; Shuli MAN ; Long MA ; Lanping GUO ; Luqi HUANG ; Wenyuan GAO
Clinical and Molecular Hepatology 2024;30(4):620-648
Steatotic liver diseases (SLD) are the principal worldwide cause of cirrhosis and end-stage liver cancer, affecting nearly a quarter of the global population. SLD includes metabolic dysfunction-associated alcoholic liver disease (MetALD) and metabolic dysfunction-associated steatotic liver disease (MASLD), resulting in asymptomatic liver steatosis, fibrosis, cirrhosis and associated complications. The immune processes include gut dysbiosis, adiposeliver organ crosstalk, hepatocyte death and immune cell-mediated inflammatory processes. Notably, various immune cells such as B cells, plasma cells, dendritic cells, conventional CD4+ and CD8+ T cells, innate-like T cells, platelets, neutrophils and macrophages play vital roles in the development of MetALD and MASLD. Immunological modulations targeting hepatocyte death, inflammatory reactions and gut microbiome include N-acetylcysteine, selonsertib, F-652, prednisone, pentoxifylline, anakinra, JKB-121, HA35, obeticholic acid, probiotics, prebiotics, antibiotics and fecal microbiota transplantation. Understanding the immunological mechanisms underlying SLD is crucial for advancing clinical therapeutic strategies.
3.Comparison of Diagnostic Performance Between PI-RADS v2.1 and PI-RADS v2 for Prostate Cancer: A Meta-analysis
Guojie BAI ; Kexin LI ; Wenyuan LIU ; Guang LAN ; Hong GUO ; Yaping SUN ; Yu WANG ; Weiling TONG ; Keyu ZHANG
Cancer Research on Prevention and Treatment 2023;50(10):981-987
Objective To compare the diagnostic performance of PI-RADS v2.1 and PI-RADS v2 in the detection of clinically significant prostate cancer(csPCa) by Meta-analysis. Methods The major biomedical databases were searched (CNKI, CBM, Medline, and Embase) with the keywords "PIRADS v2.1" or "PI-RADS v2.1". The Quality Assessment of Diagnostic Accuracy Studies Tool v2 (QUADAS-2) was used to evaluate literature quality. Meta-analysis was performed using STATA17.0 and ReMan5.4 software. Forest plots were used to represent the sensitivity and specificity of PI-RADS v2.1 and PI-RADS v2 for each study. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were combined, and diagnostic performance was evaluated using asummary receiver operating characteristic curve (SROC). Subgroup analysis was performed on three covariables: tumor location, threshold, and the nationality of authors. Results A total of 12 studies were included, involving 3 158 patients and 3 243 lesions. Forall zones and the whole gland, PI-RADS v2.1 had a larger area under the SROC curve (AUC) for csPCa performance, compared with PI-RADS v2. Subgroup analysis: PI-RADS v2.1 also had a larger area under the SROC (AUC) to detect transitional zone csPCa. Different diagnostic thresholds: when a score of 4 was used for the threshold, PI-RADS v2.1 had the maximum area under SROC (AUC) for csPCa performance detection. Author nationality: Researches of PI-RADS v2.1 in Chinese authors had the largest area under the SROC (AUC) in detecting csPCa performance. Conclusion Compared with PI-RADS v2, the diagnostic performance of PI-RADS v2.1 in detecting csPCa is not obviously improved and overall specificity is still low.
4.Research advances in total pancreatectomy with autologous islet cell transplantation
Jingjing LI ; Yuanyu ZHAO ; Hong FU ; Fei TENG ; Jiaxi MAO ; Wenyuan GUO
Journal of Clinical Hepatology 2023;39(10):2506-2512
Since the 1970s, patients with chronic pancreatitis (CP) have benefited from total pancreatectomy with autologous islet cell transplantation (TPAIT). With the continuous development of surgical techniques and perioperative management over the past few decades, there have been improvements in islet cell function, insulin independence rate, and the survival rate of patients. This article summarizes the preoperative indications for TPAIT, the development of surgical operations, postoperative management and monitoring, and prognosis, so as to help clinicians learn more about TPAIT.
5.Reliability testing and clinical effectiveness evaluation of the scoring and classification system for osteoporotic thoracolumbar fracture
Qingda LI ; Jianan ZHANG ; Baorong HE ; Shiqing FENG ; Yanzheng GAO ; Jun SHU ; Hao WANG ; Dianming JIANG ; Wenyuan DING ; Yuan HE ; Junsong YANG ; Zhengping ZHANG ; Xinhua YIN ; Bolong ZHENG ; Yunfei HUANG ; Datong LI ; Rui GUO ; Hao AN ; Xiaohui WANG ; Tuanjiang LIU ; Dingjun HAO
Chinese Journal of Trauma 2023;39(11):980-990
Objective:To test and evaluate the reliability and clinical effectiveness of osteoporotic thoracolumbar fracture (OTLF) scoring and classification system.Methods:A multicenter retrospective case series study was conducted to analyze the clinical data of 530 OTLF patients admitted to 8 hospitals including Honghui Hospital Affiliated to Xi'an Jiaotong University from January 2021 to June 2022. There were 212 males and 318 females, aged 55-90 years [(72.6±10.8)years]. There were 4 patients with grade C and 18 with grade D according to American Spinal Injury Association (ASIA) classification. According to the osteoporotic thoracolumbar injury classification and severity (OTLICS) score, all patients had an OTLICS score over 4 points and required surgical treatment. Among them, 410 patients had acute symptomatic OTLF (ASOTLF), including 24 patients with type I, 159 type IIA, 47 type IIB, 31 type IIC, 136 type IIIA, 8 type IIIB, 2 type IV (absence of neurological symptoms) and 3 type IV (presence of neurological symptoms), and 120 patients had chronic symptomatic OTLF (CSOTLF), including 62 patients with type I, 21 type II, 17 type III, 3 type IV (reducible under general anesthesia), 9 type IV (not reducible under general anesthesia), 1 type V (reducible under general anesthesia), 5 type V (presence of neurological symptoms), and 2 type V (not reducible under general anesthesia). Surgical procedures included percutaneous vertebroplasty (PVP), positional repositioning plus PVP, percutaneous kyphoplasty (PKP), posterior open reduction combined with bone graft fusion and bone cement augmented screw internal fixation, posterior open reduction combined with decompression, bone graft fusion and bone cement augmented screw internal fixation, and posterior open reduction combined with osteotomy and orthopedics, bone graft fusion and bone cement augmented screw internal fixation. A weighted Kappa was used to test the interobserver and intraobserver reliability of the OTLICS score, the ASOTLF classification, and the CSOTLF classification. The visual analog scale (VAS), Oswestry disability index (ODI), ASIA classification were compared before, at 1 month after surgery and at the last follow-up. Incidence of postoperative complications was observed.Results:The percentage of mean interobserver agreement for OTLICS staging was 93.4%, with a mean confidence Kappa value of 0.86, and the percentage of mean intraobserver agreement was 93.0%, with a mean confidence kappa value of 0.86. The percentage of mean interobserver agreement for ASOTLF staging was 94.2%, with a mean confidence Kappa value of 0.84, and the percentage of mean intraobserver agreement was 92.5%, with a mean confidence Kappa value of 0.83. The percentage of mean interobserver agreement for CSOTLF subtyping was 91.9%, with a mean confidence Kappa value of 0.80, and the percentage of mean intraobserver agreement was 91.3%, with a mean confidence Kappa value of 0.81. All the patients were followed up for 6-12 months [(9.0±2.1)months]. The VAS and ODI scores were significantly lower in patients with ASOTLF and CSOTLF classifications at 1 month after surgery and at the last follow-up than those before surgery (all P<0.05). The VAS scores in patients with ASOTLF types IIA, IIB, IIC, IIIA, and IV were significantly lower at the last follow-up than that at 1 month after surgery; the ODI scores in patients with ASOTLF types I, IIA, IIB, IIIA, IIIB and IV were significantly lower at the last follow-up than those at 1 month after surgery. The VAS scores in patients with CSOTLF types II, III, IV, and V were significantly lower at the last follow-up than those at 1 month after surgery, and the ODI scores in patients with all CSOTLF types were significantly lower at the last follow-up than those at 1 month after surgery (all P<0.05). Two patients with ASIA grade C recovered to grade D, and the rest recovered to grade E at the last follow-up ( P<0.01). No major vessel or nerve injury or internal fixation failure was found during follow-up. There were 18 patients with cement leakage, none of whom showed relevant clinical symptoms. There were 35 patients with new vertebral fractures, all of whom recovered well after symptomatic treatment. Conclusions:The OTLICS score, ASOTLF classification and CSOTLF classification have a high degree of reliability. Application of stepwise treatment for patients with different levels of injury according to the scoring and classification system can reduce pain, promote recovery of the spinal function, and reduce complications, which is of some significance in guiding the selection of clinical treatment.
6. Optimization strategy of antibiotic dosing regimen in intensive care unit patients with augmented renal clearance
Zilong DANG ; Wenyuan CHENG ; Yuhui WEI ; Xin'an WU ; Zilong DANG ; Haiyang LIU ; Yangfan ZHANG ; Jinfeng LIU ; Tianwei ZHANG ; Xin'an WU ; Bin LI ; Hong GUO ; Xiaohui XU ; Yile LI ; Xin'an WU
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(5):561-571
The incidence of augmented renal clearance (ARC) in intensive care patients (ICU) is exceptionally high, and these patients are often co-morbid with infection. The occurrence of ARC will significantly increase the clearance rate of antibiotics, making it difficult for conventional doses to reach effective therapeutic concentrations and affect the patient's anti-infective treatment effect and prognosis. It can be seen that it is crucial to formulate a reasonable dosing regimen for ICU patients with ARC. Regrettably, few reports in China about the adjustment strategy of antibiotic dosing regimens for ARC patients. Therefore, this article reviews the domestic and foreign literature for reference to provide evidence for medical personnel to adjust the dose of antibacterial drugs for such patients.
7.Chaperone-mediated Autophagy Regulates Cell Growth by Targeting SMAD3 in Glioma.
Hanqun LIU ; Yuxuan YONG ; Xingjian LI ; Panghai YE ; Kai TAO ; Guoyou PENG ; Mingshu MO ; Wenyuan GUO ; Xiang CHEN ; Yangfu LUO ; Yuwan LIN ; Jiewen QIU ; Zhiling ZHANG ; Liuyan DING ; Miaomiao ZHOU ; Xinling YANG ; Lin LU ; Qian YANG ; Pingyi XU
Neuroscience Bulletin 2022;38(6):637-651
Previous studies suggest that the reduction of SMAD3 (mothers against decapentaplegic homolog 3) has a great impact on tumor development, but its exact pathological function remains unclear. In this study, we found that the protein level of SMAD3 was greatly reduced in human-grade IV glioblastoma tissues, in which LAMP2A (lysosome-associated membrane protein type 2A) was significantly up-regulated. LAMP2A is a key rate-limiting protein of chaperone-mediated autophagy (CMA), a lysosome pathway of protein degradation that is activated in glioma. We carefully analyzed the amino-acid sequence of SMAD3 and found that it contained a pentapeptide motif biochemically related to KFERQ, which has been proposed to be a targeting sequence for CMA. In vitro, we confirmed that SMAD3 was degraded in either serum-free or KFERQ motif deleted condition, which was regulated by LAMP2A and interacted with HSC70 (heat shock cognate 71 kDa protein). Using isolated lysosomes, amino-acid residues 75 and 128 of SMAD3 were found to be of importance for this process, which affected the CMA pathway in which SMAD3 was involved. Similarly, down-regulating SMAD3 or up-regulating LAMP2A in cultured glioma cells enhanced their proliferation and invasion. Taken together, these results suggest that excessive activation of CMA regulates glioma cell growth by promoting the degradation of SMAD3. Therefore, targeting the SMAD3-LAMP2A-mediated CMA-lysosome pathway may be a promising approach in anti-cancer therapy.
8.CHCHD2 maintains mitochondrial contact site and cristae organizing system stability and protects against mitochondrial dysfunction in an experimental model of Parkinson’s disease
Lin LU ; Hengxu MAO ; Miaomiao ZHOU ; Yuwan LIN ; Wei DAI ; Jiewen QIU ; Yousheng XIAO ; Mingshu MO ; Xiaoqin ZHU ; Zhuohua WU ; Zhong PEI ; Wenyuan GUO ; Pingyi XU ; Xiang CHEN
Chinese Medical Journal 2022;135(13):1588-1596
Background::Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s dementia. Mitochondrial dysfunction is involved in the pathology of PD. Coiled-coil-helix-coiled-coil-helix domain-containing 2 (CHCHD2) was identified as associated with autosomal dominant PD. However, the mechanism of CHCHD2 in PD remains unclear.Methods::Short hairpin RNA (ShRNA)-mediated CHCHD2 knockdown or lentivirus-mediated CHCHD2 overexpression was performed to investigate the impact of CHCHD2 on mitochondrial morphology and function in neuronal tumor cell lines represented with human neuroblastoma (SHSY5Y) and HeLa cells. Blue-native polyacrylamide gel electrophoresis (PAGE) and two-dimensional sodium dodecyl sulfate-PAGE analysis were used to illustrate the role of CHCHD2 in mitochondrial contact site and cristae organizing system (MICOS). Co-immunoprecipitation and immunoblotting were used to address the interaction between CHCHD2 and Mic10. Serotype injection of adeno-associated vector-mediated CHCHD2 and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration were used to examine the influence of CHCHD2 in vivo.Results::We found that the overexpression of CHCHD2 can protect against methyl-4-phenylpyridinium (MPP+)-induced mitochondrial dysfunction and inhibit the loss of dopaminergic neurons in the MPTP-induced mouse model. Furthermore, we identified that CHCHD2 interacted with Mic10, and overexpression of CHCHD2 can protect against MPP +-induced MICOS impairment, while knockdown of CHCHD2 impaired the stability of MICOS. Conclusion::This study indicated that CHCHD2 could interact with Mic10 and maintain the stability of the MICOS complex, which contributes to protecting mitochondrial function in PD.
9.Association of interleukin-12 pathway-related gene single nucleotide polymorphisms with psoriasis vulgaris and their interaction with HLA-Cw*0602 in populations of Mongolian and Han nationalities in Inner Mongolia
Wenyuan DING ; Zhiqiang SUN ; Yanping HUANG ; Xin LI ; Yan GUO ; Xueli ZHANG ; Xinxiang LYU ; Jianwen HAN
Chinese Journal of Dermatology 2021;54(5):414-420
Objective:To investigate the genetic correlation of interleukin-12 (IL-12) pathway-related gene single nucleotide polymorphisms (SNPs) with psoriasis vulgaris and their interaction with HLA-Cw*0602 in populations of Mongolian and Han nationalities in Inner Mongolia.Methods:From December 2012 to March 2018, 1 409 inpatients with psoriasis vulgaris (1 030 of Han nationality and 379 of Mongo-lian nationality) and 1 483 healthy controls (965 of Han nationality and 518 of Mongolian nationality) were collected from the Affiliated Hospital of Inner Mongolia Medical University, and served as patient group and control group respectively. Five milliliters of peripheral venous blood samples were collected from these subjects, and DNA was extracted. Nine SNPs located in the coding regions of IL-12 pathway-related genes were selected, including IL-12B (rs2082412, rs2288831, rs3212227, rs3213094, rs7709212) , IL-23R (rs11209026, rs2201841, rs7530511) and IL-28RA (rs4649203) genes, and detected by next-generation sequencing. HLA-Cw*0602 was genotyped by polymerase chain reaction with sequence-specific primers (PCR-SSP) . Statistical analysis was carried out with PLINK1.07 software, Chi-square test was used to compare allele frequencies between the 2 groups, relative risk estimates of alleles were calculated by using odds ratio ( OR) , and chi-square test for R × C contingency tables was used for haplotype analysis. Results:The allele frequencies of rs2082412, rs2288831, rs3212227, rs3213094 and rs7709212 in the IL-12B gene were significantly lower in the patients with psoriasis vulgaris of Han nationality than in the controls of Han nationality (all P < 0.005) ; the allele frequency of rs3213094 in the IL-12B gene was significantly lower in the patients of Mongolian nationality than in the controls of Mongolian nationality ( P < 0.005) . The prevalence of HLA-Cw*0602 was significantly lower in the patients with psoriasis vulgaris of Han and Mongolian nationalities than in the controls of corresponding nationalities (both P < 0.005) . As stratification analysis showed, the allele frequencies of rs2082412, rs2288831, rs3212227, rs3213094 and rs7709212 in the IL-12B gene were significantly lower in HLA-Cw*0602-positive patients of Han nationality than in HLA-Cw*0602-positive controls of Han nationality (all P < 0.005) , while there was no significant difference between HLA-Cw*0602-negative patients of Han nationality and HLA-Cw*0602-negative controls of Han nationality (all P > 0.05) . Among the HLA-Cw*0602-positive or negative populations of Mongolian nationality, no significant difference was observed in the allele frequencies between the patients and controls (all P > 0.005) . Haplotypes were constructed using 5 SNPs in the IL-12B gene, and there was no significant difference in the frequencies of 6 haplotypes between the patients and controls of Mongolian or Han nationality (all P > 0.005) ; stratification analysis showed that there was no significant difference in the frequencies of 7 haplotypes between HLA-Cw*0602-positive/negative patients and controls of Mongolian or Han nationality (all P > 0.005) . Conclusion:IL-12 pathway-related gene polymorphisms are associated with psoriasis vulgaris in the populations of Mongolian and Han nationalities in Inner Mongolia, and there may be interaction between IL-12B and HLA-Cw*0602 in the occurrence of psoriasis vulgaris.
10.Present status and enlightenment of the US naval continuing medical education
Fei TENG ; Jiaxi MAO ; Qian CHEN ; Cong LIU ; Guoshan DING ; Wenyuan GUO
Chinese Journal of Medical Education Research 2020;19(11):1258-1262
The US naval continuing medical education is in a leading position all over the world, and to study the US naval continuing medical education plays an important reference role in the development of naval continuing medical education in China. This article expounds the characteristics, organization setting, curriculum setting, medical training and independent escort training of the US naval continuing medical education, and analyzes its enlightenments to the naval continuing medical education of China. We need to learn from the experience of the US naval continuing medical education, combined with the actual characteristics of our navy, improve the training system of continuing medical education, adopt diversified educational technologies, create a scientific education management system, and optimize curriculum reform, thus constantly improving the quality and effectiveness of naval continuing medical education in China.

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