1.Tranexamic acid-fatty alcohol polyoxyethylene ether conjugation/PVA foam for venous sclerotherapy via vascular damage and inhibiting plasmin system.
Jizhuang MA ; Keda ZHANG ; Wenhan LI ; Yu DING ; Yongfeng CHEN ; Xiaoyu HUANG ; Tong YU ; Di SONG ; Haoran NIU ; Huichao XIE ; Tianzhi YANG ; Xiaoyun ZHAO ; Xinggang YANG ; Pingtian DING
Acta Pharmaceutica Sinica B 2025;15(6):3291-3304
Venous system diseases mainly include varicose veins and venous malformations of lower limbs and the genital system. Most of them are chronic diseases that cause serious clinical symptoms to patients and affect their health and quality of life. Sclerotherapy has become the first-line therapy for venous system diseases. However, there are problems such as incomplete fibrosis and vascular recanalization after sclerotherapy, and improper operation will cause serious adverse consequences. Therefore, exploring a safe and effective sclerotherapy strategy is essential for developing clinically successful sclerotherapy. To solve the above problems, we proposed a new sclerotherapy strategy with a dual mechanism of "vascular damage and plasmin (PLA) system inhibition." We intended to construct a novel cationic surfactant (AEOx-TA) by reacting tranexamic acid (TA), a parent structure, with fatty alcohol polyoxyethylene ether (AEOx) by ester bonds. AEOx-TA could damage vascular endothelium and initiate a coagulation cascade effect to induce thrombus. Furthermore, AEOx-TA could be degraded by esterase and release the parent drug, TA, which could inhibit the PLA system to inhibit the degradation of thrombus and extracellular matrix and promote the process of vascular fibrosis. In addition, such surfactant-based sclerosants have foam-forming properties, and they can be blended with polyvinyl alcohol (PVA) to prepare a highly stable foam formulation (AEOx-TA/P), which can achieve a precise drug delivery and prolonged drug retention time, thereby improving drug efficacy and reducing the risk of ectopic embolism. Overall, the novel cationic surfactant AEOx-TA provides a new avenue to resolve the bottleneck: surfactant sclerosants' efficiency is relatively low in the current sclerotherapy.
2.Yiqi-Yangyin-Quyu prescription attenuates skeletal muscle injury and related metabolic disorders in mice with Sj?gren syndrome by targeting Hadhb
Ting ZHAO ; Yue SHEN ; Wenyue JIAO ; Xinyi YAO ; Dingqi LU ; Yating REN ; Liying CHEN ; Yihan WANG ; Wenhan HUANG ; Runrun ZHANG ; Xinchang WANG
Chinese Journal of Pathophysiology 2025;41(9):1793-1806
AIM:The aim of this study was to explore the effects of Yiqi-Yangyin-Quyu prescription(YP)on skeletal muscle injury and related metabolic disorders in mice with Sj?gren syndrome(SS),and to clarify the role of hy-droxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta(Hadhb)in mediating the effect of YP on skeletal muscle in SS.METHODS:The SS mice underwent YP treatment for 8 weeks.The morphological changes of the submandibular gland and muscle tissue were examined using hematoxylin-eosin staining.The mitochondrial status in mus-cle tissue was assessed through transmission electron microscopy.Additionally,combined transcriptome and proteome se-quencing was conducted on skeletal muscle samples.The omics sequencing results were validated by RT-qPCR.Immuno-fluorescence was used to confirm the levels of key proteins involved in the P53/peroxisome proliferator-activated receptor gamma(PPARG)signaling pathway.Immunohistochemistry and Western blot were employed to determine the levels of Hadhb key targets.RESULTS:Combined transcriptome and proteome analysis identified 1 523 differentially expressed genes(DEGs)and 182 differentially expressed proteins(DEPs)between the muscle tissue of SS mice(model group)and that of control animals(ICR group),12 of which showed co-differential expression at both transcriptomic and proteomic levels.Compared with model group,1 232 genes and 432 proteins were found to be differentially expressed in the muscle tissue of the mice in YP group.Among these,23 exhibited co-differential expression at both mRNA and protein levels.Gene Ontology(GO)analysis showed that the DEGs and DEPs between ICR and model groups were mainly involved in ener-gy metabolism and fatty acid oxidation,while the DEGs and DEPs between YP and model groups were primarily associated with sarcomere tissue and actin structure.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis indi-cated that the DEGs and DEPs between ICR and model groups and between model and YP groups were enriched in the com-plement and coagulation cascade and lipid and pyruvate metabolism.The RT-qPCR validation results were consistent with those of the transcriptome analysis.Furthermore,the protein expression of the tumor suppressor P53 was significantly de-creased in YP group compared with model group,whereas that of PPARG was significantly increased.Western blot analy-sis showed that compared with ICR group,Hadhb protein expression was significantly decreased in model group,whereas the opposite trend was detected in YP group.CONCLUSION:The SS-related skeletal muscle damage is closely related to amino acid metabolism disorder and fatty acid degradation.Treatment with YP modulates innate immune defenses,lipid metabolism and energy metabolism in SS,and Hadhb is the key target of YP in SS-related skeletal muscle.
3.Yiqi-Yangyin-Quyu prescription attenuates skeletal muscle injury and related metabolic disorders in mice with Sj?gren syndrome by targeting Hadhb
Ting ZHAO ; Yue SHEN ; Wenyue JIAO ; Xinyi YAO ; Dingqi LU ; Yating REN ; Liying CHEN ; Yihan WANG ; Wenhan HUANG ; Runrun ZHANG ; Xinchang WANG
Chinese Journal of Pathophysiology 2025;41(9):1793-1806
AIM:The aim of this study was to explore the effects of Yiqi-Yangyin-Quyu prescription(YP)on skeletal muscle injury and related metabolic disorders in mice with Sj?gren syndrome(SS),and to clarify the role of hy-droxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta(Hadhb)in mediating the effect of YP on skeletal muscle in SS.METHODS:The SS mice underwent YP treatment for 8 weeks.The morphological changes of the submandibular gland and muscle tissue were examined using hematoxylin-eosin staining.The mitochondrial status in mus-cle tissue was assessed through transmission electron microscopy.Additionally,combined transcriptome and proteome se-quencing was conducted on skeletal muscle samples.The omics sequencing results were validated by RT-qPCR.Immuno-fluorescence was used to confirm the levels of key proteins involved in the P53/peroxisome proliferator-activated receptor gamma(PPARG)signaling pathway.Immunohistochemistry and Western blot were employed to determine the levels of Hadhb key targets.RESULTS:Combined transcriptome and proteome analysis identified 1 523 differentially expressed genes(DEGs)and 182 differentially expressed proteins(DEPs)between the muscle tissue of SS mice(model group)and that of control animals(ICR group),12 of which showed co-differential expression at both transcriptomic and proteomic levels.Compared with model group,1 232 genes and 432 proteins were found to be differentially expressed in the muscle tissue of the mice in YP group.Among these,23 exhibited co-differential expression at both mRNA and protein levels.Gene Ontology(GO)analysis showed that the DEGs and DEPs between ICR and model groups were mainly involved in ener-gy metabolism and fatty acid oxidation,while the DEGs and DEPs between YP and model groups were primarily associated with sarcomere tissue and actin structure.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis indi-cated that the DEGs and DEPs between ICR and model groups and between model and YP groups were enriched in the com-plement and coagulation cascade and lipid and pyruvate metabolism.The RT-qPCR validation results were consistent with those of the transcriptome analysis.Furthermore,the protein expression of the tumor suppressor P53 was significantly de-creased in YP group compared with model group,whereas that of PPARG was significantly increased.Western blot analy-sis showed that compared with ICR group,Hadhb protein expression was significantly decreased in model group,whereas the opposite trend was detected in YP group.CONCLUSION:The SS-related skeletal muscle damage is closely related to amino acid metabolism disorder and fatty acid degradation.Treatment with YP modulates innate immune defenses,lipid metabolism and energy metabolism in SS,and Hadhb is the key target of YP in SS-related skeletal muscle.
4.Clinical characteristics and outcomes of hospitalized kidney transplant recipients with COVID-19 infection in China during the Omicron wave:a single-center cohort study
LV DUO ; XIE XISHAO ; YANG QINYUN ; CHEN ZHIMIN ; LIU GUANGJUN ; PENG WENHAN ; WANG RENDING ; HUANG HONGFENG ; CHEN JIANGHUA ; WU JIANYONG
Journal of Zhejiang University. Science. B 2024;25(6):529-540,后插1-后插2
Background:Following the short-term outbreak of coronavirus disease 2019(COVID-19)in December 2022 in China,clinical data on kidney transplant recipients(KTRs)with COVID-19 are lacking.Methods:We conducted a single-center retrospective study to describe the clinical features,complications,and mortality rates of hospitalized KTRs infected with COVID-19 between Dec.16,2022 and Jan.31,2023.The patients were followed up until Mar.31,2023.Results:A total of 324 KTRs with COVID-19 were included.The median age was 49 years.The median time between the onset of symptoms and admission was 13 d.Molnupiravir,azvudine,and nirmatrelvir/ritonavir were administered to 67(20.7%),11(3.4%),and 148(45.7%)patients,respectively.Twenty-nine(9.0%)patients were treated with more than one antiviral agent.Forty-eight(14.8%)patients were treated with tocilizumab and 53(16.4%)patients received baricitinib therapy.The acute kidney injury(AKI)occurred in 81(25.0%)patients and 39(12.0%)patients were admitted to intensive care units.Fungal infections were observed in 55(17.0%)patients.Fifty(15.4%)patients lost their graft.The 28-d mortality rate of patients was 9.0%and 42(13.0%)patients died by the end of follow-up.Multivariate Cox regression analysis identified that cerebrovascular disease,AKI incidence,interleukin(IL)-6 level of>6.8 pg/mL,daily dose of corticosteroids of>50 mg,and fungal infection were all associated with an increased risk of death for hospitalized patients.Conclusions:Our findings demonstrate that hospitalized KTRs with COVID-19 are at high risk of mortality.The administration of immunomodulators or the late application of antiviral drugs does not improve patient survival,while higher doses of corticosteroids may increase the death risk.
5.Association between physical exercise, exercise motivation with mental health among vocational college students
TIAN Yong, WEN Zhen, MA Wenhan, HUANG Jingting, SUN Xinlong, LU Wenwen, ZHOU Fuyuan, ZHANG Lu
Chinese Journal of School Health 2024;45(9):1300-1303
Objective:
To explore mental health status of vocational college students and its association with physical exercise and exercise motivation, so as to provide data support for the promotion of physical exercise, exercise motivation theory and the protection of mental health among vocational college students.
Methods:
From June 2 to July 2, 2023, a convenience sampling method was used to select 1 763 college students from three vocational colleges in Sichuan, Chongqing, and Guizhou for the survey. Physical Activity Rating Scale (PARS-3), Motives for Physical Activities Measure-Revised (MPAM-R), Patient Health Questionnaire-9 (PHQ-9) and Flourishing Scale (FS) were used to assess physical exercise, exercise motivation, depressive symptoms and flourishing levels of vocational college students. Multiple linear regression analysis was conducted to examine the relationship between physical exercise, exercise motivation, depression as the negative indicator of mental health and flourishing as the positive indicator of mental health.
Results:
There were negative correlations between physical exercise, exercise motivation and their five factors with depression scores among vocational college students ( r=-0.162--0.133, P <0.01). Physical exercise, health motivation and pleasure motivation were positively correlated with flourishing and its eight factors among vocational college students ( r= 0.054 -0.099, P <0.05). Depression scores and flourishing scores varied significantly across students with different levels of physical exercise and exercise motivation ( F=11.18-15.69, 2.80-16.05, P <0.05). Multiple linear regression analysis indicated that physical exercise, health motivation, and total exercise motivation scores were negatively correlated with depressive symptoms ( β = -0.02 , -0.11, -0.35), and physical exercise, health motivation, pleasure motivation, and total exercise motivation scores were positively correlated with flourishing ( β =0.31, 0.32, 0.50, 0.30) ( P <0.05).
Conclusions
Physical exercise and exercise motivation are significantly associated with mental health of vocational college students. Enhancing physical exercise and increasing exercise motivation in aspects of health and pleasure can promote mental health of vocational college students.
6.Clinical diagnosis and treatment guidelines for long-term systemic complications in kidney transplant recipients in China
Branch of Organ Transplantation of Chinese Medical Association ; Youzan LI ; Meng YANG ; Wenhan QIN ; Weili WANG ; Yajun SONG ; Chibing HUANG ; Hongwen ZHAO
Organ Transplantation 2024;15(4):479-496
In order to further standardize the diagnosis and treatment of long-term systemic complications in kidney transplant recipients,Branch of Organ Transplantation of Chinese Medical Association initiated the formulation of"Clinical Diagnosis and Treatment Guidelines for Long-term Systemic Complications in Kidney Transplant Recipients in China".Experts on organ transplantation were organized to summarize and integrate the latest progress in this field based on existing clinical guidelines,systematic evaluations,case studies,expert consensus.The guideline was formed after multiple rounds of discussion and reaching a consensus which included complications of hematological system,central nervous system,cardiovascular system,ocular,cutaneous and osteoporosis disorders.The full text focuses on 27 clinical problems and forms 40 recommendations,mainly involving the risk factors,classification,diagnosis,treatment and prevention of various complications.This guideline graded the quality of evidence and the strength of recommendation for each clinical issue using 2009 Oxford Centre for Evidence-Based Medicine(OCEBM)Grading and Strength of Recommendation criteria,so as to provide reference for the diagnosis and treatment of late complications,comprehensively improve the management capacity of clinicians to benefit kidney transplant recipients.
7.Outcomes of allograft from donor kidney microthrombi and secondary recipient thrombotic microangiopathy: should we consider loosening the belt?
Yamei CHENG ; Luying GUO ; Xue REN ; Zhenzhen YANG ; Junhao LV ; Huiping WANG ; Wenhan PENG ; Hongfeng HUANG ; Jianyong WU ; Jianghua CHEN ; Rending WANG
Journal of Zhejiang University. Science. B 2023;24(6):524-529
There is currently a huge worldwide demand for donor kidneys for organ transplantation. Consequently, numerous marginal donor kidneys, such as kidneys with microthrombi, are used to save patients' lives. While some studies have shown an association between the presence of microthrombi in donor kidneys and an increased risk for delayed graft function (DGF) (McCall et al., 2003; Gao et al., 2019), other studies have demonstrated that microthrombi negatively impact the rate of DGF (Batra et al., 2016; Hansen et al., 2018), but not graft survival rate (McCall et al., 2003; Batra et al., 2016; Gao et al., 2019). In contrast, Hansen et al. (2018) concluded that fibrin thrombi were not only associated with reduced graft function six months post-transplantation but also with increased graft loss within the first year of transplantation. On the other hand, Batra et al. (2016) found no significant differences in the DGF rate or one-year graft function between recipients in diffuse and focal microthrombi groups. To date, however, the overall influence of donor kidney microthrombi and the degree of influence on prognosis remain controversial, necessitating further research.
Humans
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Thrombotic Microangiopathies
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Transplantation, Homologous
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Tissue Donors
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Kidney
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Allografts
8.Influencing factors and outcomes of acute rejection within one year after pediatric kidney transplantation
Wenqi CONG ; Qinghang WU ; Yu CUI ; Hongfeng HUANG ; Rending WANG ; Wenhan PENG ; Jianghua CHEN ; Jianyong WU
Chinese Journal of Organ Transplantation 2023;44(2):94-101
Objective:To explore the influencing factors of acute rejection (AR) within one year after pediatric kidney transplantation (KT) and the effect of AR onset time on prognosis.Methods:From January 2011 to October 2021, a total of 112 patients aged under 18 years at the time of transplantation were selected.After excluding 6 of them with early renal non-function caused by non-rejection, 106 cases were examined.There were 63 males and 43 females with the age of 15(12, 16) years.The donors were living related (n=26) and deceased (n=80).According to the presence/absence and onset time of AR, they were assigned into three groups of AR within one year, AR after one year and non-AR.The relevant clinical data of donor/recipient, influencing factors of AR and therapeutic outcomes of AR were retrospectively compared.One-way ANOVA or Kruskal-Wallis test was utilized for comparing 1-year renal function after the occurrence of AR among three groups.With graft-function loss as an end-point event of follow-up, the effects of AR within one year and AR after one year on survival rate and function of graft-kidney were analyzed by Kaplan-Meier survival curve.Results:The median follow-up period of 106 pediatric KT recipients was 35 months.During follow-ups, 19 episodes of AR occurred in 17(16.0%) patients and 89 recipients exhibited no AR episode by the end of follow-up (non-AR group).As for initial AR, 9 episodes of AR occurred within one year (AR within one year group) and 8 episodes of AR after one year (AR after one year group).After anti-rejection treatment, 8 patients (47.1%) achieved full recovery and 6 patients (35.3%) failed to completely normalize and 3 patients (17.6%) developed graft failure.Univariate analysis indicated that, as compared with non-AR group, female recipients, donors aged under 8 years and early postoperative infection with parvovirus B19 were risk factors of AR within one year ( P=0.032, P=0.039, P=0.047).Kaplan-Meier survival analysis revealed that the incidence rates of AR within one year in patients with donors aged under 8 years and early postoperative parvoviral infection were 14.5%(8/55) and 30.0%(3/10) respectively.They were significantly higher than 2.0%(1/51) and 6.3%(6/96) of patients with donors aged above 8 years and those without parvoviral infection ( P=0.012, P=0.004).With graft-function loss as an end-point event of follow-up, Kaplan-Meier survival analysis showed that 10-year kidney graft survival rate in AR within one year and AR after one year groups were 88.9% and 65.6%.Both were significantly lower than that in non-AR group (98.9%).And the inter-group differences were statistically significant ( χ2=4.286, P=0.038; χ2=7.787, P=0.005).However, no significant difference existed in survival rate between AR within one year and AR after one year groups ( P=0.689).One-way ANOVA and Kruskal-Wallis test indicated that estimated glomerular filtration rates at 3/6/12 months after an onset of AR in AR within one year group were (76.8±51.6), (80.6±56.6) and (85.6±40.2) ml·min -1·1.73 m -2.The values of 3/6 months were lower than (125.3±39.2) and (124.7±38.2) ml·min -1·1.73 m -2 in AR after one year group.And the inter-group differences were statistically significant ( P=0.021, P=0.039).The values of 3/6/12 months were lower than (112.2±34.2), (115.3±33.2) and (117.4±30.2) ml·min -1·1.73 m -2 in non-AR group.And the inter-group differences were also statistically significant ( P=0.019, P=0.020, P=0.020). Conclusions:Female recipients, donors aged under 8 years and early postoperative infection with parvovirus B19 may elevate the risks of AR in children within one year of KT.AR within one year affects the survival rate of graft-kidney and renal function.
9.Clinical efficacy of immunotherapy combined with chemotherapy sequential surgery for locally advanced esophageal cancer
Xinglin LONG ; Songping XIE ; Gaoli LIU ; Wenhan ZHANG ; Jie HUANG
Journal of Clinical Surgery 2023;31(11):1040-1043
Objective To explore the safety and efficiency of sequential operation of Tirelizumab combined with chemotherapy in neoadjuvant therapy for locally advanced esophageal cancer.Methods A retrospective analysis was conducted on 60 patients with locally advanced esophageal cancer admitted to Renmin Hospital of Wuhan University from August 2018 to June 2022.The immunotherapy combined with chemotherapy sequential surgery patients were selected as the observation group(29 cases)and the chemotherapy sequential surgery patients were selected as the control group(31 cases)according to the treatment method.The study aimed to analyze whether there were differences in efficacy and safety between the two groups.Results There are 28 patients with R0 resection in the observation group,and 14 case reached ORR.In the control group,29 cases were resected with R0,and 7 cases reached ORR.The proportion of ORR patients in the observation group was significantly higher than that in the control group,which was statistically significant(P<0.05).There were 9 patients with pCR in the observation group and 2 patients with pCR in the control group,and the proportion of pCR patients in the two groups was significantly different(P<0.05).There were no significant differences between the two groups for preoperative and postoperative adverse events.Conclusion Immune checkpoint inhibitors combined with chemotherapy sequential surgery are safe and reliable in patients with locally advanced esophageal cancer,with significant short-term efficacy,and long-term efficacy remains to be observed.
10.Surgical treatment of upper gastrointestinal cancer after esophagectomy
Wenhan ZHANG ; Songping XIE ; Gaoli LIU ; Xinglin LONG ; Jie HUANG
Journal of Clinical Surgery 2023;31(12):1141-1143
Objective To summarize the clinical experience in the treatment of postoperative upper gastrointestinal cancer of esophageal cancer.Methods The clinical data of 16 patients with postoperative upper gastrointestinal malignancies treated in our hospital from January 2018 to June 2022 were retrospectively analyzed.Results All the 16 patients successfully completed the operation,and no perioperative death occurred.The cumulative length of hospitalization was 18-38 days.After operation,2 cases of pulmonary infection,1 case of respiratory failure,and 1 case of cervical anastomotic fistula were cured after conservative treatment.All patients could eat normally during postoperative follow-up,and no tumor recurrence and metastasis was found.Conclusion For patients with recurrent upper gastrointestinal cancer after esophageal cancer surgery,if the lesion is relatively limited,surgical treatment is reliable and an optional treatment plan.


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