1.Progress in role of silent information regulator 3 in improving idiopathic pulmonary fibrosis by regulating mitochondrial dysfunction
Shusen YANG ; Yushan LIU ; Yilin ZHANG ; Yi HUI ; Jingtao LI ; Shuguang YAN
Chinese Journal of Pathophysiology 2024;40(2):358-364
Idiopathic pulmonary fibrosis(IPF)is a chronic progressive interstitial lung disease of unknown etiology,with a rapid disease course,poor prognosis,and the absence of effective therapeutic drugs.Mitochondrial dys-function is one of the crucial causes of inducing IPF.Silent information regulator 3(SIRT3)can restore mitochondrial ho-meostasis by inhibiting mitochondrial oxidative stress,repairing mitochondrial DNA damage,and ameliorating abnormal mitochondrial lipid metabolism.This paper summarizes the role and mechanism of SIRT3 in attenuating mitochondrial dys-function based on delineating the relationship between mitochondrial dysfunction and IPF,aiming to provide references for finding effective treatment methods for IPF.
2.Evaluating clinical significance of ductular reaction in liver transplantation
Xinhao HU ; Tianchen LAN ; Jian CHEN ; Zhetuo QI ; Fengqiang GAO ; Hao CHEN ; Libin DONG ; Xinyu YANG ; Shusen ZHENG ; Xiao XU
Chinese Journal of Organ Transplantation 2024;45(8):550-557
Objective:To explore the role of ductular reaction in assessing the efficacy of liver transplantation.Method:From January 2015 to December 2020, he relevant clinical data were retrospectively reviewed for 100 recipients and their corresponding donors at Shulan (Hangzhou) Hospital. They were assigned into two groups of hepatic steatosis (HS group, 65 cases) and non-hepatic steatosis (non-HS group, 35 cases) according to whether or not receiving steatosis donated liver. Furthermore, based upon the occurrence of early allograft dysfunction (EAD), the participants were categorized into two groups of EAD (33 cases) and non-EAD (67 cases). The degree of bile duct reaction ductular reaction was defined by the percentage of staining area occupied by cytokeratin 19 (CK19) -positive bile duct cells in immunohistochemical-stained specimens. Donor of ductular reaction were compared between HS/non-HS and EAD/non-EAD groups. The risk factors for EAD were identified by univariate and multivariate Logistic regression analysis. Subgroup analysis was conducted based upon the level of ductular reaction (DR number) in donors (DR=0.4 as a threshold) and whether or not donors exhibited steatosis. The impact of DR was examined on the incidence of EAD and survival post-liver transplantation in steatosis donors.Result:The level of DR was higher in steatosis donor than that in non-steatosis donor [ (0.59%±0.385%) vs. (0.32%±0.194%), P<0.01]. And it was higher in EAD group than that in non-EAD group [ (0.72%±0.449%) vs. (0.38%±0.226%), P<0.01]. Multivariate logistic regression analysis showed that a high level of ductular reaction was an independent risk factor for EAD post-liver transplantation in donor. Subgroup analysis revealed that receiving a steatosis donor with low ductular reaction (DR<0.4%) had comparable levels of EAD occurrence and overall survival rate to receiving a non-steatosis donor. Conclusion:Steatosis with low ductular reaction donor may be safely applied for liver transplantation. And assessing donor injury based upon ductular reaction can effectively expand the clinical application of steatosis donors.
3.Research Progress in Complement Receptor of the Immunoglobulin Superfamily in Regulating Liver Immunity
Shusen YANG ; Jingtao LI ; Shuguang YAN ; Junzhe JIAO
Acta Academiae Medicinae Sinicae 2024;46(4):603-609
Kupffer cells(KC),an important subset of immune cells in the liver,are essential for maintaining tissue homeostasis and responding quickly to liver damage.The complement receptor of the immuno-globulin superfamily(CRIg)is a receptor protein on the KC membrane.CRIg can not only capture pathogens in the blood flowing through the liver by complement binding but also mediate immune responses by regulating im-mune cells in the liver.Recent studies have confirmed the role of CRIg in regulating liver immunity.This article reviews the main modes of action of CRIg and the research progress of CRIg in regulating liver immunity.
4.Effectiveness of tibial transverse transport combined with modified neurolysis in treatment of diabetic foot ulcers.
Shusen CHANG ; Wei YANG ; Hehua SONG ; Wei CHEN ; Jian ZHOU ; Fang ZHANG ; Xueping YAN ; Xiaojin MO ; Kaiyu NIE ; Chengliang DENG ; Zairong WEI
Chinese Journal of Reparative and Reconstructive Surgery 2023;37(11):1410-1417
OBJECTIVE:
To investigate the effectiveness of tibial transverse transport (TTT) combined with modified neurolysis in treatment of diabetic foot ulcer (DFU) through a prospective randomized controlled study.
METHODS:
The patients with DFU and diabetic peripheral neuropathy, who were admitted between February 2020 and February 2022, were selected as the research objects, of which 31 cases met the selection criteria and were included in the study. The patients were divided into two groups by random number table method. The 15 patients in the trial group were treated with TTT combined with modified neurolysis, and the 16 patients in the control group received treatment with TTT alone. There was no significant difference in gender, age, duration of DFU, ulcer area, Wagner classification, as well as preoperative foot skin temperature, visual analogue scale (VAS) score, ankle-brachial index (ABI), motor nerve conduction velocity (MNCV) of the common peroneal nerve, MNCV of the tibial nerve, MNCV of the deep peroneal nerve, two-point discrimination (2-PD) of heel, and cross-sectional area (CSA) of the common peroneal nerve between the two groups ( P>0.05). The time for ulcer healing, foot skin temperature, VAS scores, ABI, 2-PD of heel, and CSA of the common peroneal nerve before operation and at 6 and 12 months after operation were recorded and compared between groups. The differences in MNCV of the common peroneal nerve, MNCV of the tibial nerve, and MNCV of the deep peroneal nerve between pre-operation and 12 months after operation were calculated.
RESULTS:
All patients in both groups were followed up 12-24 months (mean, 13.9 months). The surgical incisions in both groups healed by first intention and no needle tract infections occurred during the bone transport phase. Ulcer wounds in both groups healed successfully, and there was no significant difference in the healing time ( P>0.05). During the follow-up, there was no ulcer recurrences. At 12 months after operation, the MNCV of the common peroneal nerve, the MNCV of the tibial nerve, and the MNCV of the deep peroneal nerve in both groups accelerated when compared to preoperative values ( P<0.05). Furthermore, the trial group exhibited a greater acceleration in MNCV compared to the control group, and the difference was significant ( P<0.05). The foot skin temperature, VAS score, ABI, 2-PD of heel, and CSA of the common peroneal nerve at 6 and 12 months after operation significantly improved when compared with those before operation in both groups ( P<0.05). The 2-PD gradually improved over time, showing significant difference ( P<0.05). The 2-PD of heel and VAS score of the trial group were superior to the control group, and the differences were significant ( P<0.05). There was no significant difference in ABI, foot skin temperature, and CSA of the common peroneal nerve between groups after operation ( P>0.05).
CONCLUSION
Compared with TTT alone, the TTT combined with modified neurolysis for DFU can simultaneously solve both microcirculatory disorders and nerve compression, improve the quality of nerve function recovery, and enhance the patient's quality of life.
Humans
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Diabetic Foot/surgery*
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Microcirculation
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Prospective Studies
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Quality of Life
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Treatment Outcome
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Diabetes Mellitus
5.Mechanism of Nrf2 in the treatment of ulcerative colitis via regulating macrophage polarization
Yilin ZHANG ; Yushan LIU ; Shusen YANG ; Shuguang YAN
Journal of Central South University(Medical Sciences) 2023;48(11):1746-1752
Ulcerative colitis(UC)is an inflammatory bowel disease induced by multiple factors,which causes abnormal activation of intestinal immune cells and excessive release of antibodies and inflammatory factors,repeatedly damaging the intestinal mucosa.Macrophages,as innate intestinal immune cells,often maintain the balance of M1/M2 macrophages polarization to normalize the regression inflammation,and the imbalance of their polarization will cause repeated damage of intestinal mucosa and persistent inflammation,which is a main cause of UC.Nuclear factor E2-related factor 2(Nrf2),as an important regulator of antioxidant and anti-inflammatory,is often used as a target for the treatment of autoimmune diseases.Nrf2 alleviates intestinal high oxidative stress and inflammatory factors by balancing macrophage polarization,which may be of great significance for the prevention and treatment of UC.Summarizing the mechanism of macrophage polarization imbalance on the course of UC and the possible regulatory mechanism of Nrf2 may provide basis for the development of UC targeted therapeutic drugs.
6.Clinical effects of antibiotic bone cement combined with free anterolateral thigh flap in sequential treatment of diabetic foot ulcer
Wei CHEN ; Shusen CHANG ; Jian ZHOU ; Fang ZHANG ; Chenglan YANG ; Kaiyu NIE ; Chengliang DENG ; Zairong WEI
Chinese Journal of Burns 2023;39(4):319-324
Objective:To investigate the clinical effects of antibiotic bone cement combined with free anterolateral thigh flap in sequential treatment of diabetic foot ulcer (DFU) wounds.Methods:A retrospective observational study was conducted. From August 2018 to August 2021, 15 patients with DFU who met the inclusion criteria were admitted to the Affiliated Hospital of Zunyi Medical University, including 12 males and 3 females, aged 42-65 years, with a history of type 2 diabetes for 5-19 years. All the wounds of patients were complicated with local bone, muscle, or tendon defects or exposure. The wounds were covered with antibiotic bone cement after debridement in stage Ⅰ+free anterolateral thigh chimeric perforator flap (perforator flap+muscle flap) or simple free anterolateral thigh flap grafting in stage Ⅱ. The defect area of the wound after bone cement removal and debridement was 9.0 cm×5.0 cm-20.0 cm×7.0 cm, the incision area of the flap was 10.0 cm×5.0 cm-22.0 cm×7.0 cm, and the incision area of the muscle flap was 5.0 cm×3.0 cm-8.0 cm×4.0 cm. The donor sites of flaps were sutured directly. During follow-up, the situations of donor site healing and flap survival were observed. At the last follow-up, the texture and shape of the flap, the presence of new ulcers on both limbs, and the walking ability of the patient were observed.Results:During the follow-up of 8 to 21 months after operation in stage Ⅱ, the donor sites healed well with only residual linear scar; flaps in 14 patients survived completely, and the flap in 1 patient developed partial necrosis at 3 weeks after stage Ⅱ surgery, which was healed after debridement and skin grafting. At the last follow-up, the flaps were good in texture and appearance, there were no new ulcers in the affected limb or opposite limb, and the patients had no obvious impairment in daily walking function.Conclusions:To repair DFU wounds with antibiotic bone cement combined with free anterolateral thigh flap can rapidly control the infection, achieving a high survival rate of flap after operation with no obvious impairment in daily walking function of patients.
7.Prognosis and influencing factors of liver transplantation for hepatocellular carcinoma using steatotic donor liver: a multicenter study
Mengfan YANG ; Rui WANG ; Binhua PAN ; Renyi SU ; Siyi DONG ; Xiao XU ; Shusen ZHENG ; Xuyong WEI
Chinese Journal of Digestive Surgery 2022;21(2):237-248
Objective:To investigate the prognosis and influencing factors of liver transplantation (LT) for hepatocellular carcinoma (HCC) using steatotic donor liver.Methods:The retrospective cohort study was conducted. The clinicopathological data of 152 pairs of donors and the corresponding recipients undergoing LT for HCC in the two medical centers [89 pairs in Shulan (Hangzhou) Hospital and 63 pairs in the First Affiliated Hospital of Zhejiang University School of Medicine] from January 2015 to December 2019 were collected. Of 152 donors, there were 131 males and 21 females, aged (48±12)years, and there were 130 cases with liver mild steatosis and 22 cases with liver moderate steatosis. Of 152 recipients, there were 138 males and 14 females, aged (52±9)years. Observation indicators: (1) follow-up, overall survival and tumor recurrence free survival of recipients; (2) influencing factors for overall survival and tumor recurrence free survival of recipients; (3) construction and validation of nomogram prediction model for overall survival and tumor recurrence free survival of recipients. Follow-up was conducted using outpatient examination and telephone interview to detect survival and tumor recurrence of recipients up to December 2020. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( IQR). Count data were described as absolute numbers. The Kaplan-Meier method was used to calculate the survival time and draw survival curve, and the Log-Rank test was used for survival analysis. The COX regression model was used for univariate and multivariate analysis. The independent risk factors were brought into the R 3.6.2 software to construct nomogram prediction model and draw the receiver operating characteristic (ROC) curve. The accuracy and discrimination of the nomogram prediction model were evaluated using the area under curve (AUC) and the calibration curve. Results:(1) Follow-up, overall survival and tumor recurrence free survival of recipients. All the 152 recipients undergoing LT for HCC using steatotic donor liver were followed up for 45.8(27.6)months, with the overall survival time and tumor recurrence free survival time of 36.5(32.3)months and 30.4(34.6)months. The 1-year, 3-year overall survival rates and tumor recurrence free rates of the 152 recipients were 73.4%, 55.8% and 62.2%, 43.4%, respectively. (2) Influencing factors for overall survival and tumor recurrence free survival of recipients. Results of univariate analysis showed that the donor liver cold ischemia time (CIT), the donor liver warm ischemia time (WIT), graft-to-recipient weight ratio (GRWR), ABO compatibility, recipient body mass index (BMI), recipient tumor diameter, recipient tumor number, recipient tumor differentiation degree, recipient preoperative alpha fetoprotein (AFP) were related factors influencing the overall survival of recipients ( hazard ratio=6.26, 1.90, 2.47, 4.08, 0.55, 5.16, 3.62, 5.28, 2.65, 95% confidence interval as 3.01?13.03, 1.07?3.38, 1.36?4.49, 2.07?8.03, 0.31?0.98, 2.56?10.42, 1.95?6.72, 1.60?17.42, 1.48?5.01, P<0.05) and the donor liver CIT, GRWR, ABO compatibility, recipient tumor diameter, recipient tumor number, recipient tumor differentiation degree, recipient preoperative AFP were related factors influencing the tumor recurrence free survival of recipients ( hazard ratio=4.24, 2.53, 4.05, 3.39, 3.10, 5.19, 2.63, 95% confidence interval as 2.50?7.21, 1.54?4.17, 2.12?7.72, 2.04?5.62, 1.91?5.03, 2.04?13.18, 1.61?4.30, P<0.05). Results of multivariate analysis showed that donor liver CIT ≥8 hours, GRWR ≥2.5%, recipient tumor diameter ≥8 cm and recipient preoperative AFP ≥400 μg/L were independent risk factors influencing the overall survival of recipients ( hazard ratio=4.21, 2.58, 4.10, 2.27, 95% confidence interval as 1.98?8.96, 1.24?5.35, 1.35?12.43, 1.13?4.56, P<0.05) and donor liver CIT ≥8 hours, GRWR ≥2.5%, recipient tumor diameter ≥8 cm, recipient tumor number ≥3 and recipient preoperative AFP ≥400 μg/L were independent risk factors influencing the tumor recurrence free survival of recipients ( hazard ratio=3.37, 2.63, 2.42, 2.12, 2.22, 95% confidence interval as 1.70?6.67, 1.40?4.96, 1.04?5.66, 1.08?4.18, 1.26?3.90, P<0.05). (3) Construction and validation of nomogram prediction model for overall survival and tumor recurrence free survival of recipients. The donor live CIT, GRWR, recipient tumor diameter, recipient preoperative AFP were used to construct nomogram prediction model for overall survival of recipients and the donor liver CIT, GRWR, recipient tumor diameter, recipient tumor number, recipient preoperative AFP were used to construct nomogram prediction model for tumor recurrence free survival of recipients. The ROC curve showed that the AUC of the nomogram prediction model for overall survival of recipients was 0.84 (95% confidence interval as 0.76?0.92, P<0.05), with the optimal diagnostic value as 7.3 and the specificity and sensitivity as 87.6% and 70.0%. The AUC of the nomogram prediction model for tumor recurrence free survival of recipients was 0.79 (95% confidence interval as 0.71?0.87, P<0.05), with the optimal diagnostic value as 5.8 and the specificity and sensitivity as 97.4% and 52.5%. The calibration curve showed that the nomogram prediction model had good distinction for high risk recipients in overall survival and tumor recurrence free survival. Conclusion:Donor liver CIT ≥8 hours, GRWR ≥2.5%, recipient tumor diameter ≥8 cm and recipient preoperative AFP ≥400 μg/L are independent risk factors influencing the overall survival of recipients who underwent LT for HCC using steatotic donor liver and donor liver CIT ≥8 hours, GRWR ≥2.5%, recipient tumor diameter ≥8 cm, recipient tumor number ≥ 3 and recipient preoperative AFP ≥400 μg/L are independent risk factors influencing the tumor recurrence free survival of recipients.
8.Preliminary evaluation of immune checkpoint inhibitors as a salvage treatment of tumor recurrence after liver transplantation for hepatocellular carcinoma
Jingqi SUN ; Zhe YANG ; Jianpeng LIU ; Qijian YU ; Zhaoxin SHANG ; Shuo WANG ; Li ZHUANG ; Xiao XU ; Shusen ZHENG
Chinese Journal of Organ Transplantation 2022;43(7):396-399
Objective:To explore the safety and efficacy of immune checkpoint inhibitors(ICI)for patients with tumor recurrence after liver transplantation(LT).Methods:A single-center retrospective study was conducted for 6 recipients of tumor recurrence after LT on a therapy of ICI admitted into Shulan(Hang Zhou)Hospital from September 2015 to June 2018.The authors examined the occurrences of graft rejection and clinical outcomes of overall response rate, progression-free survival and overall survival after dosing of PD-1/PD-L1 inhibitors.Results:Six patients enrolled with tumor recurrence on a therapy of ICI undergoing LT due to hepatocellular carcinoma (HCC). Nivolumab (n=4) and duvalizumab (n=2) were administrated.The median session of treatment was 8.3(2-31) cycles.The disease outcomes were stable (3/6, 50%) and progressive (3/6, 50%), The progression-free survival time of 3 disease-controlled patients was 1.5, 16.2 and 18 months and the median survival time after recurrence was 19.75(10.8-37.8) months.Rejection occurred in 1 patients (1/6, 16.7%) and the occurring time of rejection was 28 days after PD-1 inhibitor dosing.After acute rejection, high-dose corticosteroids and immunoglobulin were ineffective and the patient died from acute rejection related liver failure.Conclusions:ICI may be employed as a salvage treatment for tumor recurrence after LT for HCC.Due to a possibility of severe acute rejection, usage should be cautious under close monitoring of liver function.
9.Chinese consensus on surgical treatment of traumatic rib fractures (2021)
Lingwen KONG ; Guangbin HUANG ; Yunfeng YI ; Dingyuan DU ; Baoguo JIANG ; Jinmou GAO ; Lianyang ZHANG ; Jianxin JIANG ; Xiangjun BAI ; Tianbing WANG ; Xingji ZHAO ; Xingbo DANG ; Zhanfei LI ; Feng XU ; Zhongmin LIU ; Ruwen WANG ; Yingbin XIAO ; Qingchen WU ; Chun WU ; Liming CHENG ; Bin YU ; Shusen CUI ; Jinglan WU ; Gongliang DU ; Jin DENG ; Ping HU ; Jun YANG ; Xiaofeng YANG ; Jun ZENG ; Haidong WANG ; Jigang DAI ; Yong FU ; Lijun HOU ; Guiyou LIANG ; Yidan LIN ; Qunyou TAN ; Yan SHEN ; Peiyang HU ; Ning TAO ; Cheng WANG ; Dali WANG ; Xu WU ; Yongfu ZHONG ; Anyong YU ; Dongbo ZHU ; Renju XIAO ; Biao SHAO
Chinese Journal of Trauma 2021;37(10):865-875
Traumatic rib fractures are the most common injury in thoracic trauma. Previously,the patients with traumatic rib fractures were mostly treated non-surgically,of which 50%,especially those combined with flail chest presented chronic pain or chest wall deformities and over 30% had long-term disabilities,being unable to retain a full-time job. In the past two decades,thanks to the development of internal fixation material technology,the surgical treatment of rib fractures has achieved good outcomes. However,there are still some problems in clinical treatment,including inconsistency in surgical treatment and quality control in medical services. The current consensuses on the management of regional traumatic rib fractures published at home and abroad mainly focus on the guidance of the overall treatment decisions and plans,and relevant clinical guidelines abroad lacks progress in surgical treatment of rib fractures in recent years. Therefore,the Chinese Society of Traumatology affiliated to Chinese Medical Association and Chinese College of Trauma Surgeons affiliated to Chinese Medical Doctor Association,in conjunction with national multidisciplinary experts,formulate the Chinese Consensus for Surgical Treatment of Traumatic Rib Fractures(2021)following the principle of evidence-based medicine,scientific nature and practicality. This expert consensus puts forward some clear,applicable,and graded recommendations from aspects of preoperative imaging evaluation,surgical indications,timing of surgery,surgical methods,rib fracture sites for surgical fixation,internal fixation methods and material selections,treatment of combined injuries in rib fractures,in order to provide references for surgical treatment of traumatic rib fractures.
10.Predictive effect of liver fibrosis score and other factors on the prognosis of liver transplantation for liver cancer
Binhua PAN ; Xuyong WEI ; Zhikun LIU ; Li ZHUANG ; Jianhui LI ; Mengfan YANG ; Zhisheng ZHOU ; Shusen ZHENG ; Xiao XU
Chinese Journal of Organ Transplantation 2021;42(3):131-135
Objective:To explore the value of aspartate aminotransferase(AST)and platelet (PLT)ratio index(APRI)in the prognosis of liver transplantation(LT)for hepatocellular carcinoma and establish a nomogram model for evaluating its clinical application potential.Methods:From January 2015 to December 2019, retrospective review was conducted for clinical data of LT for hepatocellular carcinoma(HCC)at First Affiliated Hospital of Zhejiang University School of Medicine and Shulan(Hangzhou)Hospital(601 cases). They were randomized into two groups of modeling (399 cases)and validation(202 cases)and then divided into low and high APRI groups according to the APRI value at Month 1 post-transplantation. The independent risk factors of recurrence and prognosis post-LT were screened in modeling group using univariate and multivariate Cox regression analyses and were further used for constructing a nomogram prediction model. The receiver operating characteristic curve(ROC)and survival curve were utilized for verifying the accuracy of nomogram prediction model.Results:Univariate and multivariate Cox regression analyses revealed that independent risk factors for the prognosis of HCC-LT included cold ischemic time(CIT) >8 h, beyond Hangzhou criteria, surgical bleeding volume >1 000 ml and APRI >1.5. The AUC of HCC-LT recurrence prediction model was 0.734(95%CI: 0.681~0.787)and 0.749(95%CI: 0.671~0.817)in modeling and validation groups; the AUC of HCC-LT mortality prediction model was 0.735(95%CI: 0.679~0.790)and 0.758(95%CI: 0.682~0.834)in modeling and validation groups.Conclusions:APRI>1.5 is an independent risk factor for postoperative recurrence and mortality after HCC-LT. The nomogram prediction model based upon CIT, Hangzhou criteria, intraoperative bleeding volume and APRI can effectively predict the recurrence and overall survival of LT for HCC.

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