1.Deep learning-based radiomics allows for a more accurate assessment of sarcopenia as a prognostic factor in hepatocellular carcinoma.
Zhikun LIU ; Yichao WU ; Abid Ali KHAN ; L U LUN ; Jianguo WANG ; Jun CHEN ; Ningyang JIA ; Shusen ZHENG ; Xiao XU
Journal of Zhejiang University. Science. B 2024;25(1):83-90
Hepatocellular carcinoma (HCC) is one of the most common malignancies and is a major cause of cancer-related mortalities worldwide (Forner et al., 2018; He et al., 2023). Sarcopenia is a syndrome characterized by an accelerated loss of skeletal muscle (SM) mass that may be age-related or the result of malnutrition in cancer patients (Cruz-Jentoft and Sayer, 2019). Preoperative sarcopenia in HCC patients treated with hepatectomy or liver transplantation is an independent risk factor for poor survival (Voron et al., 2015; van Vugt et al., 2016). Previous studies have used various criteria to define sarcopenia, including muscle area and density. However, the lack of standardized diagnostic methods for sarcopenia limits their clinical use. In 2018, the European Working Group on Sarcopenia in Older People (EWGSOP) renewed a consensus on the definition of sarcopenia: low muscle strength, loss of muscle quantity, and poor physical performance (Cruz-Jentoft et al., 2019). Radiological imaging-based measurement of muscle quantity or mass is most commonly used to evaluate the degree of sarcopenia. The gold standard is to measure the SM and/or psoas muscle (PM) area using abdominal computed tomography (CT) at the third lumbar vertebra (L3), as it is linearly correlated to whole-body SM mass (van Vugt et al., 2016). According to a "North American Expert Opinion Statement on Sarcopenia," SM index (SMI) is the preferred measure of sarcopenia (Carey et al., 2019). The variability between morphometric muscle indexes revealed that they have different clinical relevance and are generally not applicable to broader populations (Esser et al., 2019).
Humans
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Aged
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Sarcopenia/diagnostic imaging*
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Carcinoma, Hepatocellular/diagnostic imaging*
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Muscle, Skeletal/diagnostic imaging*
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Deep Learning
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Prognosis
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Radiomics
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Liver Neoplasms/diagnostic imaging*
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Retrospective Studies
2.Preliminary application of foldable pedicled latissimus dorsi myocutaneous flap for repairing soft tissue defects in shoulder and back.
Jian ZHOU ; Yucen ZHENG ; Shune XIAO ; Zairong WEI ; Kaiyu NIE ; Zhiyuan LIU ; Shusen CHANG ; Wenhu JIN ; Wei CHEN ; Fang ZHANG
Chinese Journal of Reparative and Reconstructive Surgery 2024;38(1):69-73
OBJECTIVE:
To explore the feasibility and effectiveness of a foldable pedicled latissimus dorsi myocutaneous flap to repair soft tissue defects in the shoulder and back.
METHODS:
Between August 2018 and January 2023, the foldable pedicled latissimus dorsi myocutaneous flaps were used to repair soft tissue defects in the shoulder and back of 8 patients. There were 5 males and 3 females with the age ranged from 21 to 56 years (mean, 35.4 years). Wounds were located in the shoulder in 2 cases and in the shoulder and back in 6 cases. The causes of injury were chronic infection of skin and bone exposure in 2 cases, secondary wound after extensive resection of skin and soft tissue tumor in 4 cases, and wound formation caused by traffic accident in 2 cases. Skin defect areas ranged from 14 cm×13 cm to 20 cm×16 cm. The disease duration ranged from 12 days to 1 year (median, 6.6 months). A pedicled latissimus dorsi myocutaneous flap was designed and harvested. The flap was divided into A/B flap and then were folded to repair the wound, with the donor area of the flap being pulled and sutured in one stage.
RESULTS:
All 7 flaps survived, with primary wound healing. One patient suffered from distal flap necrosis and delayed healing was achieved after dressing change. The incisions of all donor sites healed by first intention. All patients were followed up 6 months to 4 years (mean, 24.7 months). The skin flap has a good appearance with no swelling in the pedicle. At last follow-up, 6 patients had no significant difference in bilateral shoulder joint motion, and 2 patients had a slight decrease in abduction range of motion compared with the healthy side. The patients' daily life were not affected, and linear scar was left in the donor site.
CONCLUSION
The foldable pedicled latissimus dorsi myocutaneous flap is an ideal method to repair the soft tissue defect of shoulder and back with simple operation, less damage to the donor site, and quick recovery after operation.
Male
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Female
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Humans
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Young Adult
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Adult
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Middle Aged
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Plastic Surgery Procedures
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Myocutaneous Flap/surgery*
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Shoulder/surgery*
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Skin Transplantation
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Superficial Back Muscles/transplantation*
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Soft Tissue Injuries/surgery*
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Wound Healing
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Treatment Outcome
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Perforator Flap
3.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.
4.Construction and characterization of monoclonal antibodies against the native H11 protein of Haemonchus contortus
Feng LIU ; Simin WU ; Yao ZHANG ; Shusen LIAO ; Liurong FANG ; Min HU ; Chunqun WANG
Chinese Journal of Veterinary Science 2024;44(6):1204-1212
To construct monoclonal antibodies against Haemonchus contortus native H11 protein.In this study,five 4-6 weeks female BALB/c mice were immunized with native H11 protein extrac-ted from adult worms by Concanavalin A lectin.Spleen cells were isolated and fused with SP2/0 cells after 3 times of immunization.Two hybridoma cell lines,named A1E3 and A10E1,which could stably secrete monoclonal antibodies against H11 protein were obtained.The subtype identi-fication and immunological analysis showed that the heavy chain of the two monoclonal antibodies belonged to IgG1 and the light chain was κ type,and both monoclonal antibodies recognized the natural antigen H11.Immunohistochemical localization and larval developmental inhibition test in vitro showed that the mAb A1E3 could be localized to the intestinal microvilli of the adult worm,and that the antibody can inhibit the growth of the fourth-stage larvae.The successful production of two monoclonal antibodies not only lays the foundation for the study of protective antigenic epitopes of the H11 protein and the development of epitope vaccines,but also provides a potential application of the monoclonal antibody for the treatment of haemonchusis in animals.
5.Changes in FOXO1 expression in β-cells during the progression of type 2 diabetes mellitus and aging
Rui LIANG ; Tengli LIU ; Jiaqi ZOU ; Boya ZHANG ; Shusen WANG ; Na LIU
Chinese Journal of Endocrinology and Metabolism 2024;40(5):414-419
Objective:To investigate the changes of β-cell dedifferentiation in type 2 diabetes mellitus(T2DM) and aging subjects.Methods:Using pancreatic samples from 12 prediabetic individuals, 21 type 2 diabetic patients, and 27 control, the level of β-cell dedifferentiation was assessed by immunofluorescence staining for FOXO1 and insulin expression. Correlation analyses were performed between β-cell dedifferentiation levels and hemoglobin A 1C(HbA 1C) level in 60 human pancreatic samples. Correlation analyses were performed between β-cell dedifferentiation levels and age in non-diabetic and T2DM. Results:FOXO1 was mainly expressed in the cytoplasm of human islet β-cells. The proportion of FOXO1 -INS + /INS + cells in T2DM significantly increased compared with control and pre-diabetes, and positively correlated with HbA 1C level( r=0.623, P<0.001). The proportion of FOXO1 -INS + /INS + cells in the young group of T2DM was significantly higher than that in the non-diabetic young and elderly groups, and further significantly increased in elderly group. In T2DM, the proportion of FOXO1 -INS + /INS + cells was positively correlated with age( r=-0.53, P<0.05). Conclusion:Hyperglycemia and aging lead to an increased level of β-cell dedifferentiation in T2DM.
6.JNK inhibitor SP600125 inhibits interleukin-1β induced pyroptosis in βTC-6 cells
Wenmiao MA ; Tengli LIU ; Rui LIANG ; Na LIU ; Le WANG ; Shusen WANG ; Rongxiu ZHENG
Chinese Journal of Endocrinology and Metabolism 2023;39(5):430-434
Objective:To investigate whether interleukin(IL)-1β is involved in pyroptosis which leads to mouse islet β cell line βTC-6 cell damage, and to explore the role of JNK inhibitor SP600125 in inhibiting IL-1β induced βTC-6 cell pyroptosis.Methods:βTC-6 cell line and mouse islets were incubated with IL-1β for 48 h or intervened with both JNK inhibitor SP600125 and IL-1R antagonist IL-1Ra, then GSDMD expression and β cell pyroptosis morphology were detected by immunofluorescence staining of GSDMD and DAPI. The expression levels of Gsdmd, IL-1β and IL-18 mRNAs were detected by real time fluorescence PCR, and apoptosis was examined by Annexin-V/7-AAD staining combined with flow cytometry.Results:βTC-6 cell pyroptotic body was significantly increased in the IL-1β treated group compared with the control group, and the expressions of pyroptosis related genes Gsdmd, IL-1β, and IL-18 mRNA were significantly higher( P<0.05), and apoptosis was increased, suggesting that IL-1β effectively induced the βTC-6 cell pyroptosis, IL-1Ra prevented IL-1β induced βTC-6 cell pyroptosis. In the presence of JNK inhibitor SP600125, IL-1β treatment failed to induce the expressions of Gsdmd and IL-18 mRNA, markers of pyroptosis, and reduced the rate of apoptosis, indicating that SP600125 suppressed IL-1β induced βTC-6 cell pyroptosis. Conclusion:Pyroptosis is one of the mechanisms of βTC-6 cell impairment caused by IL-1β, and SP600125, a JNK inhibitor, can block the IL-1β induced pyroptosis pathway and has a potential role in inhibiting βTC-6 cell pyroptosis.
7.Application of plantar medial thin skin flaps preserving plantar fascia with its superficial fascia tissue to repair skin defects in hands and feet.
Jian ZHOU ; Yucen ZHENG ; Shune XIAO ; Zairong WEI ; Kaiyu NIE ; Zhiyuan LIU ; Shusen CHANG ; Wenhu JIN ; Wei CHEN
Chinese Journal of Reparative and Reconstructive Surgery 2023;37(12):1501-1504
OBJECTIVE:
To explore the feasibility and effectiveness of plantar medial thin skin flaps preserving plantar fascia with its superficial fascia tissue to repair skin defects in hands and feet.
METHODS:
Between July 2017 and January 2023, 35 cases of hand and foot defects were repaired with plantar medial thin skin flaps preserving plantar fascia with its superficial fascia tissue (13 pedicled flaps and 22 free flaps). There were 18 males and 17 females, with an average age of 38.8 years (range, 8-56 years). Thirty cases of defects were caused by trauma, and the interval between injury and admission ranged from 2 to 6 hours (mean, 3.3 hours). Three cases were ulcer wounds with a course of 3.0, 3.8, and 7.0 months, respectively. Two cases were malignant melanoma. Eight cases of wounds located in the fingers, 13 cases in the palm, 12 cases in the heel, and 2 cases in the distal foot. The size of skin defects ranged from 4.0 cm×3.5 cm to 12.0 cm×10.0 cm, and the size of flap ranged from 5.0 cm×4.5 cm to 13.0 cm×11.0 cm. The donor sites were repaired with skin grafts.
RESULTS:
All flaps were survived and the wounds healed by first intention after operation. The partial necrosis at the edge of the skin graft occurred in 1 case, which healed after dressing change; the other skin grafts survived successfully. All patients were followed up 6-24 months (mean, 18 months). The flaps exhibited similar color and thickness to the surrounding hand and foot skin. Two-point discrimination ranged from 7 to 10 mm in the flaps with an average of 8 mm. The donor sites had no painful scars or sensory abnormalities. Foot and ankle functions were good and gaits were normal.
CONCLUSION
Application of plantar medial thin skin flaps preserving plantar fascia with its superficial fascia tissue to repair skin defects in hands and feet had good flap shape, high survival rate of skin graft at the donor site, and no obvious complications.
Male
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Female
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Humans
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Adult
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Plastic Surgery Procedures
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Subcutaneous Tissue/surgery*
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Soft Tissue Injuries/surgery*
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Skin Transplantation
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Fascia
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Free Tissue Flaps
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Treatment Outcome
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Perforator Flap
8.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.
9.ALDH1A3 + INS + cells in non-diabetic subjects and risk for type 2 diabetes: Analysis of cross-sectional data
Tengli LIU ; Rui LIANG ; Peng SUN ; Le WANG ; Na LIU ; Jiaqi ZOU ; Yaojuan LIU ; Xuejie DING ; Shusen WANG
Chinese Journal of Endocrinology and Metabolism 2022;38(3):219-224
Objective:To investigate the correlations of β cell dedifferentiation in non-diabetic subjects with risk factors for type 2 diabetes mellitus(T2DM).Methods:Immunofluorescence staining with insulin and β cell dedifferentiated marker ALDH1A3 was used to evaluate the β cell dedifferentiation levels in 38 non-diabetic and 23 T2DM. Correlation analyses were performed between β cell dedifferentiation levels and available clinical parameters including age, body mass index, HbA 1C level, triglycerides, and cholesterol levels in non-diabetic subjects. Results:β cell dedifferentiation level defined by the positive expression of ALDH1A3 in β cells(ALDH1A3 + INS + cell proportion) was significantly elevated in T2DM subjects( P<0.001). In PreD subjects, ALDH1A3 + INS + cells proportion were decreased( P=0.050) and negatively correlated with HbA 1C( r=-0.44, P=0.006), but not with age and body mass index. The analysis of correlation with lipidemic parameters showed that ALDH1A3 + INS + cells proportion was positively correlated with plasma total cholesterol level( r=0.39, P=0.045), but not plasma total triglyceride. Conclusion:ALDH1A3 + INS + cells were found to be decreased in prediabetes, suggesting that there may be enhanced β-cell identity in prediabetes to compensate for insulin secretion requirements; ALDH1A3 + INS + cells were elevated in people with high plasma total cholesterol levels, suggesting that total cholesterol may be one of the factors that induce β-cell dedifferentiation.
10.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.

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