1.Lentivirus-modified hematopoietic stem cell gene therapy for advanced symptomatic juvenile metachromatic leukodystrophy: a long-term follow-up pilot study.
Zhao ZHANG ; Hua JIANG ; Li HUANG ; Sixi LIU ; Xiaoya ZHOU ; Yun CAI ; Ming LI ; Fei GAO ; Xiaoting LIANG ; Kam-Sze TSANG ; Guangfu CHEN ; Chui-Yan MA ; Yuet-Hung CHAI ; Hongsheng LIU ; Chen YANG ; Mo YANG ; Xiaoling ZHANG ; Shuo HAN ; Xin DU ; Ling CHEN ; Wuh-Liang HWU ; Jiacai ZHUO ; Qizhou LIAN
Protein & Cell 2025;16(1):16-27
Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans
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Leukodystrophy, Metachromatic/genetics*
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Pilot Projects
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Genetic Therapy/methods*
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Hematopoietic Stem Cell Transplantation
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Male
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Follow-Up Studies
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Female
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Lentivirus/genetics*
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Child
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Child, Preschool
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Hematopoietic Stem Cells/metabolism*
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Cerebroside-Sulfatase/metabolism*
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Adolescent
2.Risk factors for lymph node metastasis after RARP in high-risk prostate cancer patients and construction of a nomogram
Qi CAI ; Ziyan AN ; Zhoujie YE ; Jinpeng SHAO ; Kaipeng BI ; Zheng WANG ; Guanqiu CHEN ; Jie ZHU ; Guangfu CHEN ; Shaoxi NIU ; Baojun WANG ; Xin MA ; Jiangping GAO ; Weijun FU
Chinese Journal of Urology 2025;46(8):593-599
Objective:This study investigated the independent risk factors for lymph node metastasis(LNM)in high-risk prostate cancer(HRPCa)patients undergoing robot-assisted radical prostatectomy(RARP),and constructed a nomogram model based on clinical data to improve the accuracy and clinical practicality of preoperative prediction of LNM.Methods:A retrospective analysis was conducted on the clinical data of 218 HRPCa patients who received RARP treatment at the First Medical Center of the PLA General Hospital from January 2020 to March 2025 as the modeling group. The age of the modeling group was(66.91±6.94)years old. 75 cases(34.40%)had a history of smoking,and 48 cases(22.02%)had a history of drinking. There were a body mass index(BMI)of 25.55(23.58,27.00)kg/m 2,a total prostate-specific antigen(tPSA)of 20.59(10.42,30.61)ng/ml,a free prostate-specific antigen(fPSA)of 1.87(1.04,3.26)ng/ml,a prostate volume(PV)of(41.19±21.00)ml,a prostate-specific antigen density(PSAD)of 0.52(0.30,0.84)ng/ml 2. Among the patients,60 cases(27.52%)had a preoperative biopsy Gleason score >8,and the percentage of positive biopsy cores(PPBC)was 50%(31%,80%). Thirty-one patients(14.22%)were staged clinically as >T 2c. The diagnostic criteria for high-risk prostate cancer(HRPCa)were defined as meeting any one of the following:PSA >20 ng/ml,Gleason score on prostate biopsy ≥8,or clinical stage ≥T 3. Among the 218 patients in the modeling cohort,67 cases(30.73%)met two of the criteria,and 7 cases(3.21%)met all three criteria. All 218 patients underwent RARP,and based on postoperative pathology,they were divided into the LNM group and the non-LNM group. The relationship between the number of diagnostic criteria met and the occurrence of LNM was analyzed. An external validation cohort included 42 HRPCa patients who underwent RARP at the Third,Fifth Medical Centers of the PLA General Hospital between January 2023 and May 2025. Their mean age was(66.79±5.92)years. Eighteen patients(42.86%)had a smoking history,and nine(21.43%)had a history of alcohol consumption. The median BMI was 26.00(23.80,27.13)kg/m 2. The median tPSA level was 17.34(8.97,27.30)ng/ml. The median fPSA was 1.51(0.83,2.52)ng/ml,and the median PV was(35.57 ± 15.25)ml. The median PSAD was 0.57(0.23,0.87)ng/ml 2,and the median PPBC was 58%(36%,71%). Three patients(7.14%)had a clinical stage >T 2c,and 12 patients(28.57%)had a Gleason score >8 on preoperative biopsy. Univariate and multivariate binary logistic regression analyses were used to identify independent risk factors for LNM,and a nomogram model was constructed based on these factors. The predictive performance of the model was evaluated using receiver operating characteristic(ROC)curves and calibration plots,and the model was validated in the external cohort. Result:According to postoperative pathology,45 patients were classified into the LNM group,and 173 into the non-LNM group. The probability of LNM increased proportionally with the number of diagnostic criteria met for HRPCa(meeting two criteria: OR = 4.762,95% CI 2.323-9.761, P < 0.01;meeting three criteria: OR = 10.667,95% CI 2.187-52.025, P=0.003). Binary logistic regression analysis revealed that age( OR=0.913,95% CI 0.859-0.971, P = 0.004),tPSA( OR=1.039,95% CI 1.018-1.061, P<0.01),PPBC( OR = 5.656,95% CI 1.101-29.056, P = 0.038),and clinical T stage(T 2c stage: OR=2.945,95% CI 0.888-9.769, P=0.077;>T 2c stage OR = 18.351,95% CI 4.790-70.306, P < 0.01)were independent risk factors for postoperative LNM in HRPCa patients after RARP. The ROC curve of the nomogram model based on these factors showed an area under the curve(AUC)of 0.853(95% CI 0.790-0.917). In the external validation cohort,the nomogram achieved an AUC of 0.743(95% CI 0.556-0.929). The calibration plots demonstrated good agreement between the predicted probabilities and actual observations. Conclusions:Age,tPSA,PPBC,and clinical T stage were independent predictors of postoperative LNM in HRPCa patients undergoing RARP. The greater the number of HRPCa diagnostic criteria met,the higher the likelihood of postoperative LNM. The nomogram developed in this study could effectively predict the risk of LNM in HRPCa patients after RARP.
3.Study on the level changes and predictive value of coagulation and fibrinolytic indices in the treatment of patients with acute myeloid leukemia
Li GONG ; Jinying LUO ; Guoning CHEN ; Guangfu TONG ; Xiaogang WANG
China Modern Doctor 2025;63(27):19-22,92
Objective To investigate the changes in the levels of D-dimer(D-D),fibrin degradation product(FDP),thrombomodulin(TM),thrombin-antithrombin complex(TAT),tissue plasminogen activator-plasminogen activator inhibitor-1 complex(t-PAIC),and plasmin-alpha 2 plasmin inhibitor complex(PIC)during the treatment of patients with acute myeloid leukemia(AML)and their predictive value for efficacy and prognosis.Methods Thirty-one AML patients initially diagnosed at Guidong People's Hospital of Guangxi Zhuang Autonomous Region from January 2022 to December 2024 were collected as observation group,and 34 healthy medical checkupers were selected as control group.The changes in the levels of the indicators between two groups as well as before,during and after the treatment of observation group were compared,and observation group was divided into remission group and non-remission group according to the efficacy criteria,and the levels of the indicators between two groups were further compared.Risk factors for the efficacy and prognosis of AML patients were analyzed by using Logistic regression analysis.Results Before treatment,the levels of prothrombin time(PT),activated partial thromboplastin time(APTT),D-D,FDP,t-PAIC,PIC,TM and TAT in observation group were significantly higher than those in control group(P<0.05),whereas there was no significant difference in fibrinogen(Fib)compared with control group(P>0.05).During the treatment,the levels of t-PAIC and TM in observation group were higher than those before treatment(P<0.05);After treatment,the levels of PT,D-D,FDP,PIC and TAT in observation group were significantly lower than those before treatment(P<0.05).After treatment,the levels of PT,D-D,FDP,t-PAIC,PIC,TM and TAT were all lower than those during treatment(P<0.05).The D-D,FDP,t-PAIC,PIC,TAT and TM levels in non-remission group were all higher than those in remission group,with the t-PAIC and TM levels showing statistical significance(P<0.05).Binary Logistic regression analysis showed that t-PAIC was an independent risk factor affecting the efficacy and prognosis of AML patients(P<0.05,OR=1.205,95%CI:1.015-1.430).Conclusion Regular testing of D-D,FDP,TM,TAT,t-PAIC and PIC levels can help to assess the disease changes and efficacy prognosis of AML patients,and provide an important reference for clinical decision-making.
4.Ferroptosis and osteoporosis
Cheng YANG ; Weimin LI ; Dongcheng RAN ; Jiamu XU ; Wangxiang WU ; Jiafu XU ; Jingjing CHEN ; Guangfu JIANG ; Chunqing WANG
Chinese Journal of Tissue Engineering Research 2025;29(3):554-562
BACKGROUND:It has also been confirmed that ferroptosis is closely related to a variety of musculoskeletal diseases,such as rheumatoid arthritis,osteosarcoma,and osteoporosis.The pathophysiological mechanisms of ferroptosis and osteoporosis need to be further studied and elucidated to broaden our understanding of iron metabolism and osteoporosis.It will provide research ideas for the future elucidation of new mechanisms of osteoporosis and the development of new technologies and drugs for the treatment of osteoporosis. OBJECTIVE:To provide an overview of the current status of research on ferroptosis in osteoporosis,to provide a new direction for future research on the specific molecular mechanisms of osteoporosis,and to provide more effective and better options for osteoporosis treatment strategies. METHODS:The first author used the computer to search the literature published from 2000 to 2024 in CNKI,WanFang,VIP,and PubMed databases with search terms"ferroptosis,iron metabolism,osteoporosis,osteoblast,osteoclast,bone metabolism,signal pathway,musculoskeletal,review"in Chinese and English.A total of 68 articles were finally included according to the selection criteria. RESULTS AND CONCLUSION:(1)Ferroptosis is a new type of cell death discovered in recent years,which is usually accompanied by a large amount of iron accumulation and lipid peroxidation during cell death,and its occurrence is iron-dependent.This is distinctly different from several types of cell death that are currently being hotly studied(e.g.,cellular pyroptosis,necrotic apoptosis,cuproptosis,and autophagy).(2)Intracellular iron homeostasis is manifested as a balance between iron uptake,export,utilization,and storage.The body's iron regulatory system includes systemic and intracellular regulation.The main factor of systemic regulation is hepcidin produced by hepatic secretion,and cellular regulation depends on the iron regulatory protein/iron response element system.Of course,intracellular iron homeostasis can be controlled by other factors,such as hypoxia,cytokines,and hormones.(3)Lipid peroxidation causes oxidative damage to biological membranes(plasma membrane and internal organelle membranes),lipoproteins,and other lipid-containing molecules.Polyunsaturated fatty acid-containing phospholipids are important targets of lipid peroxidation.Free polyunsaturated fatty acid is an important substrate for lipid oxidation and can bind to the phospholipid bilayer,leading to over-oxidation and thus triggering lipid apoptosis.(4)Several studies have shown that osteoblasts are overloaded with iron in different ways,resulting in the accumulation of unstable ferrous iron and the generation of reactive oxygen species and lipid peroxides,causing ferroptosis of osteoblasts and ultimately a decrease in bone formation,affecting bone homeostasis and the development of osteoporosis.(5)Osteoclasts are large multinucleated cells formed by the fusion of mononuclear macrophage cell lines or bone marrow mesenchymal stem cells induced by nuclear factor-κB ligand receptor activator,and they have the function of bone resorption.Iron ions can promote osteoclast differentiation and bone resorption through the production of intracellular lipid reactive oxygen species,while iron chelators can inhibit osteoclast formation in vitro and thus affect the occurrence and development of osteoporosis.
5.Risk factors for lymph node metastasis after RARP in high-risk prostate cancer patients and construction of a nomogram
Qi CAI ; Ziyan AN ; Zhoujie YE ; Jinpeng SHAO ; Kaipeng BI ; Zheng WANG ; Guanqiu CHEN ; Jie ZHU ; Guangfu CHEN ; Shaoxi NIU ; Baojun WANG ; Xin MA ; Jiangping GAO ; Weijun FU
Chinese Journal of Urology 2025;46(8):593-599
Objective:This study investigated the independent risk factors for lymph node metastasis(LNM)in high-risk prostate cancer(HRPCa)patients undergoing robot-assisted radical prostatectomy(RARP),and constructed a nomogram model based on clinical data to improve the accuracy and clinical practicality of preoperative prediction of LNM.Methods:A retrospective analysis was conducted on the clinical data of 218 HRPCa patients who received RARP treatment at the First Medical Center of the PLA General Hospital from January 2020 to March 2025 as the modeling group. The age of the modeling group was(66.91±6.94)years old. 75 cases(34.40%)had a history of smoking,and 48 cases(22.02%)had a history of drinking. There were a body mass index(BMI)of 25.55(23.58,27.00)kg/m 2,a total prostate-specific antigen(tPSA)of 20.59(10.42,30.61)ng/ml,a free prostate-specific antigen(fPSA)of 1.87(1.04,3.26)ng/ml,a prostate volume(PV)of(41.19±21.00)ml,a prostate-specific antigen density(PSAD)of 0.52(0.30,0.84)ng/ml 2. Among the patients,60 cases(27.52%)had a preoperative biopsy Gleason score >8,and the percentage of positive biopsy cores(PPBC)was 50%(31%,80%). Thirty-one patients(14.22%)were staged clinically as >T 2c. The diagnostic criteria for high-risk prostate cancer(HRPCa)were defined as meeting any one of the following:PSA >20 ng/ml,Gleason score on prostate biopsy ≥8,or clinical stage ≥T 3. Among the 218 patients in the modeling cohort,67 cases(30.73%)met two of the criteria,and 7 cases(3.21%)met all three criteria. All 218 patients underwent RARP,and based on postoperative pathology,they were divided into the LNM group and the non-LNM group. The relationship between the number of diagnostic criteria met and the occurrence of LNM was analyzed. An external validation cohort included 42 HRPCa patients who underwent RARP at the Third,Fifth Medical Centers of the PLA General Hospital between January 2023 and May 2025. Their mean age was(66.79±5.92)years. Eighteen patients(42.86%)had a smoking history,and nine(21.43%)had a history of alcohol consumption. The median BMI was 26.00(23.80,27.13)kg/m 2. The median tPSA level was 17.34(8.97,27.30)ng/ml. The median fPSA was 1.51(0.83,2.52)ng/ml,and the median PV was(35.57 ± 15.25)ml. The median PSAD was 0.57(0.23,0.87)ng/ml 2,and the median PPBC was 58%(36%,71%). Three patients(7.14%)had a clinical stage >T 2c,and 12 patients(28.57%)had a Gleason score >8 on preoperative biopsy. Univariate and multivariate binary logistic regression analyses were used to identify independent risk factors for LNM,and a nomogram model was constructed based on these factors. The predictive performance of the model was evaluated using receiver operating characteristic(ROC)curves and calibration plots,and the model was validated in the external cohort. Result:According to postoperative pathology,45 patients were classified into the LNM group,and 173 into the non-LNM group. The probability of LNM increased proportionally with the number of diagnostic criteria met for HRPCa(meeting two criteria: OR = 4.762,95% CI 2.323-9.761, P < 0.01;meeting three criteria: OR = 10.667,95% CI 2.187-52.025, P=0.003). Binary logistic regression analysis revealed that age( OR=0.913,95% CI 0.859-0.971, P = 0.004),tPSA( OR=1.039,95% CI 1.018-1.061, P<0.01),PPBC( OR = 5.656,95% CI 1.101-29.056, P = 0.038),and clinical T stage(T 2c stage: OR=2.945,95% CI 0.888-9.769, P=0.077;>T 2c stage OR = 18.351,95% CI 4.790-70.306, P < 0.01)were independent risk factors for postoperative LNM in HRPCa patients after RARP. The ROC curve of the nomogram model based on these factors showed an area under the curve(AUC)of 0.853(95% CI 0.790-0.917). In the external validation cohort,the nomogram achieved an AUC of 0.743(95% CI 0.556-0.929). The calibration plots demonstrated good agreement between the predicted probabilities and actual observations. Conclusions:Age,tPSA,PPBC,and clinical T stage were independent predictors of postoperative LNM in HRPCa patients undergoing RARP. The greater the number of HRPCa diagnostic criteria met,the higher the likelihood of postoperative LNM. The nomogram developed in this study could effectively predict the risk of LNM in HRPCa patients after RARP.
6.Study on the level changes and predictive value of coagulation and fibrinolytic indices in the treatment of patients with acute myeloid leukemia
Li GONG ; Jinying LUO ; Guoning CHEN ; Guangfu TONG ; Xiaogang WANG
China Modern Doctor 2025;63(27):19-22,92
Objective To investigate the changes in the levels of D-dimer(D-D),fibrin degradation product(FDP),thrombomodulin(TM),thrombin-antithrombin complex(TAT),tissue plasminogen activator-plasminogen activator inhibitor-1 complex(t-PAIC),and plasmin-alpha 2 plasmin inhibitor complex(PIC)during the treatment of patients with acute myeloid leukemia(AML)and their predictive value for efficacy and prognosis.Methods Thirty-one AML patients initially diagnosed at Guidong People's Hospital of Guangxi Zhuang Autonomous Region from January 2022 to December 2024 were collected as observation group,and 34 healthy medical checkupers were selected as control group.The changes in the levels of the indicators between two groups as well as before,during and after the treatment of observation group were compared,and observation group was divided into remission group and non-remission group according to the efficacy criteria,and the levels of the indicators between two groups were further compared.Risk factors for the efficacy and prognosis of AML patients were analyzed by using Logistic regression analysis.Results Before treatment,the levels of prothrombin time(PT),activated partial thromboplastin time(APTT),D-D,FDP,t-PAIC,PIC,TM and TAT in observation group were significantly higher than those in control group(P<0.05),whereas there was no significant difference in fibrinogen(Fib)compared with control group(P>0.05).During the treatment,the levels of t-PAIC and TM in observation group were higher than those before treatment(P<0.05);After treatment,the levels of PT,D-D,FDP,PIC and TAT in observation group were significantly lower than those before treatment(P<0.05).After treatment,the levels of PT,D-D,FDP,t-PAIC,PIC,TM and TAT were all lower than those during treatment(P<0.05).The D-D,FDP,t-PAIC,PIC,TAT and TM levels in non-remission group were all higher than those in remission group,with the t-PAIC and TM levels showing statistical significance(P<0.05).Binary Logistic regression analysis showed that t-PAIC was an independent risk factor affecting the efficacy and prognosis of AML patients(P<0.05,OR=1.205,95%CI:1.015-1.430).Conclusion Regular testing of D-D,FDP,TM,TAT,t-PAIC and PIC levels can help to assess the disease changes and efficacy prognosis of AML patients,and provide an important reference for clinical decision-making.
7.Improvement effect of velvet antler polypeptide in osteoporosis model rats and its effect on SIRT1/FOXO1 signaling pathway
Xueting CHI ; Xiaowei HUANG ; Fangyuan CHEN ; Gaofeng ZHOU ; Jinji WANG ; Guangfu LYU ; Zhe LIN ; Qing GONG
Journal of Jilin University(Medicine Edition) 2024;50(1):120-127
Objective:To discuss the protective effect of velvet antler peptide(VAP)in the osteoporosis(OP)model rats,and to clarify the possible mechanism.Methods:Sixty 12-week-old SD rats were randomly divided into control group,model group,positive drug group(treated with 1 mg·kg-1·d-1 of alendronate sodium by gavage),low dose of VAP group(treated with 100 mg·kg-1·d-1 VAP),medium dose of VAP group(treated with 200 mg·kg-1·d-1 VAP),and high dose of VAP group(treated with 300 mg·kg-1·d-1 VAP),and there were ten rats in each group.Except for control group,the rats in the other groups were injected with dexamethasone(2 mg·kg-1)to replicate the OP rat model,while the rats in control group were injected with the equivalent volume of saline twice a week for 11 consecutive weeks.Dual-energy X-ray absorptiometry was used to detect the bone mineral density(BMD)of femur tissue of the rats in various groups;enzyme-linked immunosorbent assay(ELISA)method was used to detect the levels of serum calcium(Ca2+),phosphate(P),osteoprotegerin(OPG),alkaline phosphatase(ALP),and osteocalcin(OCN)in serum of the rats in various groups;biochemical method was used to detect the malondialdehyde(MDA)level and superoxide dismutase(SOD)activity in serum of the rats in various groups;HE staining was used to observe the pathomorphology of bone tissue of the rats in various groups;Western blotting method was used to detect the expression levels of silent information regulator 1(SIRT1),catalase(CAT),Runt-related transcription factor 2(RUNX2),and forkhead box protein O1(FOXO1)proteins in bone tissue of the rats in various groups.Results:Compared with control group,the BMD of femoral tissue of the rats in model group was decreased(P<0.05);compared with model group,the BMD of femur tissue of the rats in positive drug group,medium dose of VAP group,and high dose of VAP group were increased(P<0.05 or P<0.01).Compared with control group,the levels of Ca2+,P,OPG,and SOD activities in serum of the rats in model group were decreased(P<0.05),and the levels of ALP,OCN,and MDA were increased(P<0.05);compared with model group,the level of OPG in serum of the rats in low dose of VAP group was significantly increased(P<0.05),the levels of Ca2+,P,OPG,and activities of SOD in serum of the rats in positive drug group,medium dose of VAP group,and high dose of VAP group were significantly increased(P<0.05 or P<0.01),and the levels of ALP,OCN,and MDA in serum of the rats in positive drug group and different doses of VAP groups were decreased(P<0.05 or P<0.01).The HE staining results showed that compared with control group,the rats in model group had fewer bone cells and disordered arrangements in the bone tissue,thinner bone trabeculae with large fractures,and an expanded marrow cavity;compared with model group,the rats in positive drug group,medium dose of VAP group,and high dose of VAP group had thicker bone trabeculae arranged more tightly.The Western blotting results showed that compared with control group,the expression levels of SIRT1,CAT,RUNX2,and FOXO1 proteins in bone tissue of the rats in model group were decreased(P<0.05);compared with model group,the expression levels of SIRT1,CAT,RUNX2,and FOXO1 proteins in bone tissue of the rats in positive drug group,medium dose of VAP group,and high dose of VAP group were significantly increased(P<0.05 or P<0.01).Conclusion:VAP has the protective effect against OP in the rats,and its mechanism may be related to mediating the antioxidant stress action through the SIRT1/FOXO1 signaling pathway.
8.Improvement effect of velvet antler polypeptide on postmenopausal osteoporosis in rats and its mechanism
Xueting CHI ; Fangyuan CHEN ; Zifeng PI ; Guangfu LYU ; Yuchen WANG ; Yinqing LI ; Xiaowei HUANG ; Zhe LIN
Journal of Jilin University(Medicine Edition) 2024;50(4):963-969
Objective:To discuss the protective effect of velvet antler peptide(VAP)on the postmenopausal osteoporosis(PMOP)model rats,and to clarify its possible mechanism.Methods:A total of 60 twelve-week-old female SD rats were randomly divided into sham operation group,model group,alendronate sodium group(1 mg·kg 1·d-1 alendronate sodium administered via gavage),low dose of VAP group(100 mg·kg·d-1 VAP administered via gavage),medium dose of VAP group(200 mg·kg 1·d-1 VAP administered via gavage),and high dose of VAP group(300 mg·kg1·d-1 VAP administered via gavage),and there were 10 rats in each group.Except for the sham operation group,the rats in the other groups underwent bilateral ovariectomy to establish the PMOP rat models.Dual-energy X-ray absorptiometry was used to detect the femur bone mineral density(BMD)of the rats in various groups;enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of serum calcium(Ca2+),serum phosphorus(P),bone alkaline phosphatase(BALP),and procollagen type Ⅰ N-terminal propeptide(PINP)of the rats in various groups;Kits were used to detect the activities of superoxide dismutase(SOD)and the levels of malondialdehyde(MDA)of the rats in various groups;HE staining was used to observe the pathomorphology of bone tissue of the rats in various groups;Western blotting method was used to detect the expression levels of phosphatidylinositol 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(AKT),and phosphorylated AKT(p-AKT)proteins in bone tissue of the rats in various groups.Results:Compared with sham operation group,the BMD in femur of the rats in model group was decreased(P<0.01);compared with model group,the BMD in femur of the rats in alendronate sodium group,medium dose of VAP group,and high dose of VAP group was increased(P<0.05 or P<0.01).Compared with sham operation group,the levels of Ca2+,P,BALP,PINP,and SOD activity in serum of the rats in model group were decreased(P<0.05 or P<0.01),and the MDA level was increased(P<0.01);compared with model group,the level of P in serum of the rats in medium dose of VAP group was increased(P<0.01),and the levels of Ca2+,P,BALP,PINP and the activities of SOD in serum of the rats in alendronate sodium group and high dose of VAP group were increased(P<0.05 or P<0.01),and the level of MDA in serum was decreased(P<0.05).The HE staining results showed that compared with sham operation group,the bone trabeculae in bone tissue of the rats in model group were thin and fractured,and the medullary cavity was enlarged;compared with model group,the bone trabeculae in bone tissue of the rats in alendronate sodium group,medium dose of VAP group,and high dose of VAP group were thick and tightly arranged,and had more osteocytes.The Western blotting results showed that compared with sham operation group,the ratios of p-PI3K/PI3K and p-AKT/AKT in bone tissue of the rats in model group were decreased(P<0.01);compared with model group,the ratios of p-PI3K/PI3K in bone tissue of rats in different doses of VAP groups were increased(P<0.05 or P<0.01),and the ratios of p-AKT/AKT of the rats in alendronate sodium group and high dose of VAP group was increased(P<0.01).Conclusion:VAP can improve PMOP in the rats,and its mechanisms may be related to the regulation of the PI3K/AKT signaling pathway and the reduction of oxidative stress in bone tissue by VAP.
9.Five-year survival analysis of gastric cancer from population-based cancer registration data in Zhejiang province, China
Huizhang LI ; Hongting ZHU ; Yaoyao CHEN ; Rongshou ZHENG ; Guangfu JIN ; Lingbin DU ; Xiangdong CHENG
Chinese Journal of Oncology 2024;46(9):862-870
Objective:To analyze epidemiology of gastric cancer five-year survival distribution in Zhejiang population-based cancer registration.Methods:The follow-up data of registrated gastric cancer cases diagnosed from 2008 to 2019 in 22 national cancer registry areas of Zhejiang Province were collected and divided into three diagnostic periods: 2008-2011, 2012-2015 and 2016-2019 to calculate five-year observed survival rates (OSRs), five-year relative survival rates (RSRs) and five-year age-standardized relative survival rates (ARSRs). The distribution of population characteristics (including gender, urban/rural, age group and occupation) and clinical characteristics (including the highest diagnostic institution, sub-site, pathological type and degree of differentiation) of gastric cancer survival rates in each period were analysed.Results:51 663 new cases of gastric cancer in 2008-2019 in the cancer registration area of Zhejiang Province were included in the analysis, and the ARSR of gastric cancer in 2008-2011, 2012-2015 and 2016-2019 showed an increasing trend (39.2%, 41.3% and 44.7%, respectively). In 2016-2019, the ARSR was similar across gender and urban and rural areas (44.4% for men and 45.7% for women; 44.9% in urban areas and 44.2% in rural areas); Among people with different occupations, the ARSR was highest among business and service workers (55.3%), the agriculture, forestry, animal husbandry and fisheries, water conservancy production workers and domestic workers were lower (41.5% and 43.2%, respectively). The highest diagnostic institution was the provincial hospital with a higher gastric cancer survival rate (47.0%) than the municipal (43.4%) and district (43.6%) levels. The ARSR for gastric cancer was relatively high in the lesser curvature (59.7%), pylorus (50.4%), antrum (49.3%), and greater curvature (48.7%), and lowest in cardia (38.9%). Among the major pathological types, adenocarcinoma (NOS) had an ARSR of 48.1%, mucinous adenocarcinoma 41.3%, imprinted cell carcinoma 39.4%, and squamous carcinoma 33.4%. The ARSR for highly differentiated, moderately differentiated, poorly differentiated and undifferentiated gastric cancers were 80.6%, 57.9%, 43.2% and 36.8%, respectively.Conclusion:The 5-year survival rate of gastric cancer in Zhejiang Province is high and on the rise, with similar survival rates in different genders, urban and rural areas, and significant differences in the survival rates of gastric cancer patients with different occupational groups, highest diagnostic institutions, tumour sub-sites, pathological types and differentiation degrees.
10.Five-year survival analysis of gastric cancer from population-based cancer registration data in Zhejiang province, China
Huizhang LI ; Hongting ZHU ; Yaoyao CHEN ; Rongshou ZHENG ; Guangfu JIN ; Lingbin DU ; Xiangdong CHENG
Chinese Journal of Oncology 2024;46(9):862-870
Objective:To analyze epidemiology of gastric cancer five-year survival distribution in Zhejiang population-based cancer registration.Methods:The follow-up data of registrated gastric cancer cases diagnosed from 2008 to 2019 in 22 national cancer registry areas of Zhejiang Province were collected and divided into three diagnostic periods: 2008-2011, 2012-2015 and 2016-2019 to calculate five-year observed survival rates (OSRs), five-year relative survival rates (RSRs) and five-year age-standardized relative survival rates (ARSRs). The distribution of population characteristics (including gender, urban/rural, age group and occupation) and clinical characteristics (including the highest diagnostic institution, sub-site, pathological type and degree of differentiation) of gastric cancer survival rates in each period were analysed.Results:51 663 new cases of gastric cancer in 2008-2019 in the cancer registration area of Zhejiang Province were included in the analysis, and the ARSR of gastric cancer in 2008-2011, 2012-2015 and 2016-2019 showed an increasing trend (39.2%, 41.3% and 44.7%, respectively). In 2016-2019, the ARSR was similar across gender and urban and rural areas (44.4% for men and 45.7% for women; 44.9% in urban areas and 44.2% in rural areas); Among people with different occupations, the ARSR was highest among business and service workers (55.3%), the agriculture, forestry, animal husbandry and fisheries, water conservancy production workers and domestic workers were lower (41.5% and 43.2%, respectively). The highest diagnostic institution was the provincial hospital with a higher gastric cancer survival rate (47.0%) than the municipal (43.4%) and district (43.6%) levels. The ARSR for gastric cancer was relatively high in the lesser curvature (59.7%), pylorus (50.4%), antrum (49.3%), and greater curvature (48.7%), and lowest in cardia (38.9%). Among the major pathological types, adenocarcinoma (NOS) had an ARSR of 48.1%, mucinous adenocarcinoma 41.3%, imprinted cell carcinoma 39.4%, and squamous carcinoma 33.4%. The ARSR for highly differentiated, moderately differentiated, poorly differentiated and undifferentiated gastric cancers were 80.6%, 57.9%, 43.2% and 36.8%, respectively.Conclusion:The 5-year survival rate of gastric cancer in Zhejiang Province is high and on the rise, with similar survival rates in different genders, urban and rural areas, and significant differences in the survival rates of gastric cancer patients with different occupational groups, highest diagnostic institutions, tumour sub-sites, pathological types and differentiation degrees.

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