1.Necroptosis-related diagnostic biomarkers of bronchopulmonary dysplasia and their relationships with immune microenvironment
Haixia TU ; Changjiang FANG ; Ping GAN ; Nana PENG ; Yunyun GU ; Honghua JIANG ; Weiwei HOU ; Guihua SHU
Journal of Clinical Medicine in Practice 2025;29(14):80-87
Objective To investigate necroptosis-related diagnostic biomarkers of bronchopulmo-nary dysplasia(BPD)and their relationships with the immune microenvironment through the analysis of necroptosis-related genes(NRGs)in BPD.Methods The dataset GSE32472 was downloaded from the Gene Expression Omnibus(GEO)database,and NRGs were obtained from the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway and Gene Cards databases.Differentially expressed necroptosis-related genes(DE-NRGs)were screened,and their biological functions and pathways were explored through functional enrichment analysis.Machine learning algorithms,inclu-ding least absolute shrinkage and selection operator(LASSO)and support vector machine-recursive feature elimination(SVM-RFE),were applied to screen feature genes.The Cell-type Ⅰdentification By Estimating Relative Subsets of RNA Transcripts(CIBERSORT)algorithm and the Estimation of Stromal and Immune Cells in Malignant Tumor Tissues using Expression Data(ESTIMATE)algo-rithm were used to explore the immune infiltration characteristics of BPD.Spearman correlation anal-ysis between feature genes and immune cells was performed using the"corrplot"package in R lan-guage.Results A total of 19 DE-NRGs were identified.The main biological functions and path-ways of DE-NRGs included the regulation of necroptosis and inflammatory responses.Three feature genes,namely flotillin-2(FLOT2),CASP8 and FADD-like apoptosis regulators(CFLAR),and charged multivesicular body protein 7(CHMP7),were further screened to construct a nomogram.In the validation sets GSE8586 and GSE188944,the area under the curve(AUC)values were all greater than 0.7.CIBERSORT analysis revealed that BPD group presented a higher proportion of naive B cells,neutrophils,eosinophils and resting mast cells compared to control group(P<0.05).Meanwhile,the proportion of CD8+T cells,CD4+naive T cells,CD4+resting memory T cells,regulatory T cells,resting natural killer(NK)cells,M0 macrophages,M2 macrophages and activated dendritic cells was lower than that in the control group(P<0.05).ESTIMATE analysis showed that the stromal score in the BPD group was higher than that in the control group,while the immune score was lower,with statistically significant differences(P<0.05).Correlation analysis between the three feature genes and ESTIMATE scores indicated that FLOT2 and CFLAR were posi-tively correlated with the stromal score and negatively correlated with the immune score,whereas CHMP7 was positively correlated with the immune score and negatively correlated with the stromal score.Conclusion The three necroptosis-related feature genes can serve as diagnostic biomarkers for BPD-related necroptosis,with high diagnostic efficacy.They may play an important roles through immune mechanisms,providing new insights and theoretical references for the early diagnosis and immune intervention of BPD.
2.The relationship between thyroid antibody level and early renal injury in patients with type 2 diabetes mellitus and Hashimoto's thyroiditis with normal thyroid function
Ruirui FU ; Jingjing CHEN ; Yao FANG ; Yuchun LU ; Xiaoyan ZHOU ; Changjiang YING
Chinese Journal of Diabetes 2024;32(9):657-661
Objective To explore the correlation between thyroid antibody levels and early renal injury in patients with type 2 diabetes mellitus(T2DM)combined with Hashimoto's thyroiditis(HT).Methods A total of 375 T2DM patients hospitalized in The Affiliated Hospital of Xuzhou Medical University from January 2018 to December 2022 were selectedas the study subjects,and 197 healthy people were selected as the control subjects.The patients with T2DM were divided into simple T2DM group(n=191)and T2DM combined with HT group(HT,n=184).According to the urinary albumin/creatinine ratio(UACR)level,T2DM patients with HT were divided into microalbuminuria subgroup(MUAlb,30≤UACR≤300 mg/g,n=70)and normal albuminuria subgroup(NUAlb,UACR<30 mg/g,n=114).According to whether the thyroid antibody was positive,they were divided into thyroid peroxides antibody[TPOAb(+)]subgroup(n=56),thyroglobulin antibody[TGAb(+)]subgroup(n=40)and TGAb and TPOAb double antibody positive subgroup(n=88).Results Compared with the NC group,the smoking,drinking,urinary creatinine,alpha 1-microglobulin,UACR,FPG,HbA1c,LDL-C,TC,and TG in the HT and T2DM groups increased(P<0.05),while HDL-C decreased(P<0.05).Compared with the NUAlb subgroup,the MUAlb subgroup showed age,DM duration,FPG,HbA1c,TGAb,TPOAb,thyroid stimulating hormone(TSH)increased(P<0.05),while FT3 and eGFR decreased(P<0.05).Spearman correlation analysis showed that UACR was positively correlated with age,HbA1c,TPOAb,TGAb,TSH(P<0.01),and negatively correlated with FT3(P<0.01).The UACR of the TGAb(+)+TPOAb(+)subgroup was higher than that of the TGAb(+)and TPOAb(+)subgroups(P<0.05).Logistic regression analysis showed that TSH,TGAb,TPOAb,and HbA1c were risk factors for MUAlb,while FT3 was a protective factor for MUAlb.Conclusions In T2DM with HT patients with normal thyroid function,TPOAb and TGAb are closely related to the occurrence of early renal injury.
3.Influencing factors of liver regeneration after full-size split liver transplantation
Yuhao DU ; Yuying SHAN ; Shuqi MAO ; Changjiang LU ; Shengdong WU ; Jing HUANG ; Jiongze FANG ; Caide LU
Chinese Journal of General Surgery 2024;39(9):692-697
Objective:To investigate the factors influencing recipient liver regeneration after full-size split liver transplantation (fSLT).Methods:The clinical data of patients undergoing split liver transplantation in the Affiliated Li Huili Hospital of Ningbo University from May 2019 to Sep 2023 were retrospectively collected. Graft volume (GV) and initial graft volume (IGV) at (30±7) days after operation were measured, and postoperative liver regeneration rate (LRR) was calculated. The patients undergoing fSLT were divided into high regeneration group and low regeneration group with LRR=30% as boundary. The differences of donor and recipient data and perioperative data between the two groups were compared.Results:A total of 52 patients were included. The low fSLT regeneration group (16 cases) was compared with the high fSLT regeneration group (36 cases), and in high fSLT regeneration group donor age was lower, the donor liver steatosis was less, GRWR was lower, the incidence of hepatitis B virus-related liver disease was lower, the postoperative diagnosis of malignant liver disease was lower, the intraoperative blood loss was less, and the postoperative platelet count was higher. The levels of liver enzyme and total bilirubin (TBiL) were higher than those in high regeneration group ( P<0.05). Conclusions:Donor age, donor liver steatosis, GRWR, hepatitis B virus associated liver disease, and recipient pathogenesis are important factors affecting liver regeneration after fSLT. Postoperative platelet and liver enzyme levels are important indicators for monitoring liver regeneration after fSLT.
4.Acute-on-chronic liver failure treated by split liver transplantation:a single-center experience on 9 cases
Wei JIANG ; Yuying SHAN ; Shuqi MAO ; Xi YU ; Shengdong WU ; Jiongze FANG ; Jing HUANG ; Changjiang LU ; Caide LU
Chinese Journal of General Surgery 2023;38(6):423-428
Objective:To evaluate the short-term efficacy of split liver transplantation (SLT) in patients with acute-on-chronic liver failure (ACLF).Methods:The clinical data of 9 ACLF patients receiving SLT in our center from Mar 2021 to May 2022 were retrospectively analyzed to evaluate its safety and efficacy.Results:The preoperative APASL ACLF Research consortium (AARC) score of the 9 ACLF patients was 8 points in 1 case, 9 points in 3 cases, 10 points in 3 cases, 11 points in 1 case and 12 points in 1 case, 7 cases were in AARC-ACLF grade 2, and 2 cases in grade 3.In-situ liver splitting was performed in 9 deceased donors, including 4 classical split cases, 5 full size split cases. Among these 9 ACLF patients, 2 received left half liver transplantation, 3 received right half liver transplantation, and 4 received extended right lobe liver transplantation. After transplantation, all 9 recipients were discharged fully recovered, 1 case developed Clavien grade Ⅳa complication and 2 cases developed Clavien grade Ⅲb complication.After SLT treatment the median postoperative hospital stay was 27 days, the 1-year survival rate was 100%, and the organ survival rate was 88.9%.Conclusion:Split liver transplantation is a safe and feasible treatment method for ACLF patients.
5.Patients with perihilar cholangiocarcinoma resection combined with portal vein resection and reconstruction
Caide LU ; Shengdong WU ; Jiongze FANG ; Jing HUANG ; Changjiang LU ; Sheng YE ; Wei JIANG ; Shuqi MAO
Chinese Journal of Hepatobiliary Surgery 2022;28(5):356-361
Objective:To study the safety and efficacy of combining portal vein resection and reconstruction (PVR) with resection of perihilar cholangiocarcinoma (PHC).Methods:A total of 104 patients with PHC who underwent hepatectomies for either biliary resection alone or biliary resection combined with PVR from October 2006 to December 2019 at the Department of Hepatopancreatobiliary, Ningbo Medical Center of Lihuili Hospital entered into this study. There were 63 males and 41 females, with the age of (64.4±10.4) years. The control group consisted of 75 patients who underwent biliary resection alone, while the PVR group consisted 29 patients with biliary resection combined with PVR. The patient characteristics and the follow-up outcomes of the two groups were analyzed and compared. Survival analyses were performed using the Kaplan Meier method with the log-rank test.Results:Wedge resection of portal vein, side to side anastomosis in 2 cases, segmental resection and end to end anastomosis in 27 cases. The time taken for PVR and portal vein resection were (12.7±2.9)(range 8 to 18)min and (20.7±7.3)(range 8 to 38) mm, respectively. The estimated blood loss for the PVR group was significantly more than the control group [ M( Q1, Q3)] 800.0 (600.0, 1 500.0) ml vs. 600.0(500.0, 1 000.0) ml ( P<0.05). Based on postoperative pathological studies, the proportion of lymph node metastasis was significantly higher in the PVR group than the control group (58.6% vs. 32.0%, P<0.05). Clavien-Dindo grade Ⅲ and above complications were 30.7%(23/75) and 34.5%(10/29) in the control and PVR groups, respectively ( P>0.05). The re-operation and postoperative 90 days mortality rates were 9.3%(7/75) and 2.7%(2/75) in the control group, compared with 3.4%(1/29) and 0 in the PVR group, respectively (both P>0.05). The 1-, 3- and 5-year survival rates were 81.1%, 44.8% and 36.4% respectively for the control group and 78.1%, 35.9% and 31.4% for the PVR group (χ 2=0.33, P=0.570). Conclusion:When compared to biliary resection alone, biliary resection combined with PVR did not significantly increase postoperative complication and mortality rates, but with comparable long-term survival outcomes. Combined biliary resection with PVR was safe and improved the resection rate in selected patients with locally advanced PHC.
6.Gene-phenotype correlation analysis of 226 cases of sporadic thoracic aortic diseases in southern China
Ying LI ; Miaoxian FANG ; Changjiang YU ; Chuangwen ZHANG ; Qiuji WANG ; Jue YANG ; Xin LI ; Tucheng SUN ; Ruixin FAN
Chinese Journal of Thoracic and Cardiovascular Surgery 2022;38(6):348-356
Objective:To identify the causative genes of sporadic thoracic aortic aneurysm or dissection (TAAD) and their correlation with clinical phenotype in the southern Chinese.Methods:We analyzed 11 core genes of TAAD probands without specific family history of 226 cases by next-generation sequencing technology, and performed sanger sequencing for their close relatives. Clinical data of each patient, including age of onset, syndromic phenotypes, involvement of aortic root, aortic maximum diameter and D-dimer were collected. And statistical software SPSS was used to evaluate the correlation between clinical phenotypes and gene mutations.Results:A total of 106 variants were detected in 226 probands with gene-positive frequency of 44.69%, consist of 16 pathogenic (P) variants, 18 likely pathogenic (LP) variants and 71 variants of uncertain significance (VUS). More than half of the mutations were from the non-syndromic TAAD, in which the FBN1 still was the most common causative gene. Earlier age of onset, an increase of women, larger diameter of aorta, Stanford B dissection and severe aortic regurgitation were likely to occur on carriers of P/LP, while thoracic aortic aneurysm occurs on carriers of VUS. Phenotype of both syndrome and dissection with aneurysm could increase the likelihood of carrying gene mutation, but D-dimer and involvement of aortic root couldn’t.Conclusion:Patients with sporadic aortic diseases in southern China have significant genetic heterogeneity and specific correlation between their clinical phenotype and gene mutation, especially in non-syndromic population. Earlier age of onset in carriers of FBN1 or ACTA2 genes, and larger maximum diameters of aorta in carrier of P/LP.
7.Modification and innovation of in-situ full-left/full-right liver splitting technique
Shengdong WU ; Jiongze FANG ; Jing HUANG ; Yangke HU ; Shuqi MAO ; Yuying SHAN ; Hongda ZHU ; Ke WANG ; Changjiang LU ; Caide LU
Chinese Journal of Organ Transplantation 2022;43(12):749-757
Objective:To explore the feasibility of technological modification and innovation of full-left/full-right liver splitting in situ for donors and examine the safety of clinical application for liver transplantation (LT).Methods:From March 2021 to June 2022, clinical and surgical data are retrospectively reviewed for 27 donors undergoing full-left/full-right liver splitting in situ and the corresponding 49 recipients undergoing full-left/full-right LT.According to the split liver technique used in donor liver surgery, they are divided into conventional split group(group A, 13 cases)and innovative split group(group B, 14 cases). The corresponding recipients are divided into two groups of recipient C(25 cases)and recipient D(24 cases). General profiles, intraoperative findings, type of vascular allocation and short-term outcomes in two groups are compared.After full-size split liver transplantation(fSLT), follow-ups continued until the end of September 2022.Results:There are 23 males and 4 females in donors.The causes of mortality for donors are traumatic head injury(12 cases)cerebrovascular accident(13 cases)and anoxia encephalopathy(2 cases). Baseline characteristics of two groups indicate that body weight and body mass index(BMI)are higher in group B and blood sodium level is lower than that in group A( P<0.05). No statistical differences exist for the others.Liver splitting time is significantly shorter in group B than that in group A(175 vs.230 min, P=0.022). No significant inter-group difference exists in type of vascular allocation.Retrohepatic inferior vena cava(IVC)is split in one case in group A and 10 cases in group B( P=0.001). Among 20 cases of right hemiliver requiring a reconstruction of segment Ⅴ/Ⅷ venous outflow, 12 cases in group A and 3 cases in group B are reconstructed with conventional independent bridging method(independent type)while another 5 cases in group B reconstruct with innovated technique by bridging Ⅴ/Ⅷ vein for splitting IVC with iliac vessel and molding all outflows as one for anastomosis(combined typ e). There is significant inter-group difference( P=0.004). No significant differences exist in operative duration, anhepatic phase or blood loss between groups C and B, except for T tube retaining in 7 cases of group A and 14 cases of group D( P=0.032). Twelve cases developed a total of 26 instances of≥Clavien-Dindo grade Ⅲ complications.Of which, 7 cases in group C and 5 cases in group D show no significant difference in postoperative morbidity.However, for serious biliary complications(≥Clavien Dindo grade Ⅲ), there are 6 cases in group C versus none in group D( P=0.016). Two cases died from postoperative complication with a postoperative mortality rate of 4.1%.Postoperative hospital stay is similar in two groups.And accumulates 6/12-month survivals were 95.9% and 87.7% for grafts and 95.9% and 92.4% for recipients respectively. Conclusions:Operative duration of full-left/full-right liver splitting in situ tends to shorten with an accumulation of a certain amount of cases.Technological modification and innovation in IVC splitting and segment Ⅴ/Ⅷ vein reconstruction should be further validated as both feasible and safe by short-term outcomes of the corresponding recipients.
8.Evaluations of total hilar en bloc resection and reconstruction in comparison with portal vein resection and reconstruction in treatment of perihilar cholangiocarcinoma
Caide LU ; Jing HUANG ; Shengdong WU ; Jiongze FANG ; Yongfei HUA ; Changjiang LU ; Gaoqing WANG ; Yuying SHAN
Chinese Journal of Surgery 2021;59(1):32-39
Objective:To evaluate the feasibility and efficacy of total hilar en bloc resection and reconstruction(THERR) and portal vein resection and reconstruction(PVRR) in treatment of perihilar cholangiocarcinoma(PHC).Methods:Data of a total of 101 consecutive patients with PHC who underwent bile duct resection with various types of hepatectomies from June 2013 to December 2019 at Department of Hepatopancreatobiliary,Lihuili Hospital were retrospectively analyzed. Patients who underwent PHC resection combined with THERR or PVRR were identified and grouped accordingly. Fourteen patients(6 males, 8 females, aged (64.3±9.7)years old) underwent hepatectomy combined with THERR, 19 patients(11 males, 8 females, aged (63.8±8.6)years old) underwent hepatectomy combined with PVRR. Indications and surgical procedures of THERR and PVRR were reported. The clinicopathological characteristics and operation data, as well as the short and long-term outcomes of patients of the two groups were compared by Student′s t-test and the χ 2 test or Fisher exact test, respectively. The actual survivals rates were calculated by using the Kaplan-Meier method, and compared using the Log-rank test. Results:There were no statistically significant differences between the two groups in respect to age,sex and whether they had preoperative biliary drainage or not. The types of combined hepatectomy carried out predominately between the two groups were statistically different with the left side being predominant in the THERR group(10/14, P=0.010) and right side in PVRR group(12/19, P=0.001). There were no significant differences between the two groups in respect to whether they received preoperative portal vein embolization,intraoperative blood loss,curative degree,number of lymph node dissections, and whether there was lymphatic metastasis or not. However, both the times of operation and continuous Pringle maneuver were statistically longer in the THERR group((586±158)minutes and (32.5±7.3)minutes)than those in the PVRR group((453±88)minutes and (12.4±3.8)minutes),respectively( t=3.087, P=0.004; t=10.325, P<0.01). One patient in the THERR group died of liver failure 9 days postoperative, the cumulative 1-, 3- and 5-year survival rates were 84.9%, 57.1% and 37.0% for the THERR group and 81.9%, 37.8% and 30.2% for the PVRR group, respectively. There was no statistically significant differences between the two groups(χ2=0.150, P=0.698). Conclusions:Compared to the role of PVRR in the treatment of PHC, THERR is a novel and technically demanding procedure that is feasible in selected patients for the treatment of advanced PHC with invasion of both the hepatic artery and portal vein. However,due to the small size of this primary study,the value of THERR needs further evaluation.
9.Evaluations of total hilar en bloc resection and reconstruction in comparison with portal vein resection and reconstruction in treatment of perihilar cholangiocarcinoma
Caide LU ; Jing HUANG ; Shengdong WU ; Jiongze FANG ; Yongfei HUA ; Changjiang LU ; Gaoqing WANG ; Yuying SHAN
Chinese Journal of Surgery 2021;59(1):32-39
Objective:To evaluate the feasibility and efficacy of total hilar en bloc resection and reconstruction(THERR) and portal vein resection and reconstruction(PVRR) in treatment of perihilar cholangiocarcinoma(PHC).Methods:Data of a total of 101 consecutive patients with PHC who underwent bile duct resection with various types of hepatectomies from June 2013 to December 2019 at Department of Hepatopancreatobiliary,Lihuili Hospital were retrospectively analyzed. Patients who underwent PHC resection combined with THERR or PVRR were identified and grouped accordingly. Fourteen patients(6 males, 8 females, aged (64.3±9.7)years old) underwent hepatectomy combined with THERR, 19 patients(11 males, 8 females, aged (63.8±8.6)years old) underwent hepatectomy combined with PVRR. Indications and surgical procedures of THERR and PVRR were reported. The clinicopathological characteristics and operation data, as well as the short and long-term outcomes of patients of the two groups were compared by Student′s t-test and the χ 2 test or Fisher exact test, respectively. The actual survivals rates were calculated by using the Kaplan-Meier method, and compared using the Log-rank test. Results:There were no statistically significant differences between the two groups in respect to age,sex and whether they had preoperative biliary drainage or not. The types of combined hepatectomy carried out predominately between the two groups were statistically different with the left side being predominant in the THERR group(10/14, P=0.010) and right side in PVRR group(12/19, P=0.001). There were no significant differences between the two groups in respect to whether they received preoperative portal vein embolization,intraoperative blood loss,curative degree,number of lymph node dissections, and whether there was lymphatic metastasis or not. However, both the times of operation and continuous Pringle maneuver were statistically longer in the THERR group((586±158)minutes and (32.5±7.3)minutes)than those in the PVRR group((453±88)minutes and (12.4±3.8)minutes),respectively( t=3.087, P=0.004; t=10.325, P<0.01). One patient in the THERR group died of liver failure 9 days postoperative, the cumulative 1-, 3- and 5-year survival rates were 84.9%, 57.1% and 37.0% for the THERR group and 81.9%, 37.8% and 30.2% for the PVRR group, respectively. There was no statistically significant differences between the two groups(χ2=0.150, P=0.698). Conclusions:Compared to the role of PVRR in the treatment of PHC, THERR is a novel and technically demanding procedure that is feasible in selected patients for the treatment of advanced PHC with invasion of both the hepatic artery and portal vein. However,due to the small size of this primary study,the value of THERR needs further evaluation.
10. Expert consensus on emergency surgery management for traumatic orthopedics under prevention and control of novel coronavirus pneumonia
Jing LIU ; Hui LI ; Wu ZHOU ; Guohui LIU ; Yingze ZHANG ; Baoguo JIANG ; Peifu TANG ; Guodong LIU ; Xinbao WU ; Zhi YUAN ; Fang ZHOU ; Tianbing WANG ; Zhongguo FU ; Zhiyong HOU ; Jiacan SU ; Bin YU ; Zengwu SHAO ; Tian XIA ; Liming XIONG ; Yue FANG ; Guanglin WANG ; Peng LIN ; Yanxi CHEN ; Jiangdong NI ; Lei YANG ; Dongliang WANG ; Chengjian HE ; Ximing LIU ; Biao CHE ; Yaming LI ; Junwen WANG ; Ming CHEN ; Meng ZHAO ; Faqi CAO ; Yun SUN ; Bobin MI ; Mengfei LIU ; Yuan XIONG ; Hang XUE ; Liangcong HU ; Yiqiang HU ; Lang CHEN ; Chenchen YAN
Chinese Journal of Trauma 2020;36(2):111-116
Since December 2019, novel coronavirus pneumonia (NCP) has been reported in Wuhan, Hubei Province, and spreads rapidly to all through Hubei Province and even to the whole country. The virus is 2019 novel coronavirus (2019-nCoV), never been seen previously in human, but all the population is generally susceptible. The virus spreads through many ways and is highly infectious, which brings great difficulties to the prevention and control of NCP. Based on the needs of orthopedic trauma patients for emergency surgery and review of the latest NCP diagnosis and treatment strategy and the latest principles and principles of evidence-based medicine in traumatic orthopedics, the authors put forward this expert consensus to systematically standardize the clinical pathway and protective measures of emergency surgery for orthopedic trauma patients during prevention and control of NCP and provide reference for the emergency surgical treatment of orthopedic trauma patients in hospitals at all levels.

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