1.Mechanism of action of the nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome and its regulation in liver injury.
Yifan LU ; Tianyu WANG ; Bo YU ; Kang XIA ; Jiayu GUO ; Yiting LIU ; Xiaoxiong MA ; Long ZHANG ; Jilin ZOU ; Zhongbao CHEN ; Jiangqiao ZHOU ; Tao QIU
Chinese Medical Journal 2025;138(9):1061-1071
Nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) is a cytosolic pattern recognition receptor that recognizes multiple pathogen-associated molecular patterns and damage-associated molecular patterns. It is a cytoplasmic immune factor that responds to cellular stress signals, and it is usually activated after infection or inflammation, forming an NLRP3 inflammasome to protect the body. Aberrant NLRP3 inflammasome activation is reportedly associated with some inflammatory diseases and metabolic diseases. Recently, there have been mounting indications that NLRP3 inflammasomes play an important role in liver injuries caused by a variety of diseases, specifically hepatic ischemia/reperfusion injury, hepatitis, and liver failure. Herein, we summarize new research pertaining to NLRP3 inflammasomes in hepatic injury, hepatitis, and liver failure. The review addresses the potential mechanisms of action of the NLRP3 inflammasome, and its regulation in these liver diseases.
Humans
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NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*
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Inflammasomes/physiology*
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Animals
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Liver Diseases/metabolism*
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Liver/metabolism*
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Reperfusion Injury/metabolism*
2.Electron microscopic evaluation of pre-transplant biopsies from deceased donor kidneys and preliminary study on graft outcome
Yujie ZHOU ; Fangcheng ZHANG ; Tao QIU ; Zeya JIN ; Long ZHANG ; Zhongbao CHEN ; Yang GUAN ; Jiangqiao ZHOU
Chinese Journal of Organ Transplantation 2025;46(7):497-503
Objective:To investigate the electron microscopic evaluation results of pre-transplant biopsies of deceased donor kidneys and the corresponding recovery of graft function in recipients after kidney transplantation.Methods:A retrospective analysis was conducted on the clinical data and donor kidney electron microscopy (EM) reports of 196 kidney transplant recipients who underwent pre-implantation kidney biopsies at Renmin Hospital of Wuhan University between October 2020 and June 2023. The ultrastructural pathological features assessed in the pre-transplant kidney biopsy included: the number of glomeruli, the presence of leukocytes and endothelial cells within the glomeruli, the arrangement of capillary loops, abnormalities in podocytes, mesangial cells, mesangial matrix and glomerular basement membrane (GBM), and multilayering of the peritubular capillary basement membrane. Referring to the Mayo Clinic/Renal Pathology Society Consensus Report on the pathological classification, diagnosis, and reporting of glomerulonephritis, the expert consensus on renal biopsy pathology reporting models, and the content of the 2019 Banff Transplant Pathology Meeting, a scoring system was established for ultrastructural pathology of donor kidneys. According to the scores, the recipients were divided into three groups: Group A (total score ≥ 8 points, 94 cases), Group B (total score between 6 and 8 points, 85 cases), and Group C (total score < 6 points, 17 cases). The serum creatinine, estimated glomerular filtration rate (eGFR), and proteinuria at postoperative day 1, day 7, month 1, month 3, month 6, and year 1 were compared among the three groups.Results:Among the 196 donor kidneys, EM examination before transplantation showed the following findings: 19 cases (9.7%) had prominent leukocyte infiltration within the glomeruli, 8 cases (4.1%) had mild leukocyte infiltration, and the remaining 169 cases (86.2%) showed no obvious increase in glomerular leukocytes. Glomerular capillary loop collapse or narrowing was seen in 19 cases (9.7%). Endothelial cell proliferation was observed in 32 cases (16.3%). Homogeneous thickening of the GBM (400-900 nm) was present in 82 cases (41.8%). Foot process effacement ranged from partial to diffuse. Podocyte vacuolar degeneration was seen in 62 cases (32.1%), and podocyte swelling in 10 cases (5.1%). Electron-dense deposits in the mesangial area were observed in 9 cases (4.6%). Mild tubular epithelial swelling was present in 6 cases (3.1%). Only 22 cases (11.2%) showed no multilayering of the peritubular capillary basement membrane, while 174 cases (88.8%) showed 2 to 5 layers of multilayering. All donor glomeruli showed irregular capillary loop arrangement, and the renal interstitium showed scattered inflammatory infiltration and varying degrees of collagen fiber deposition. Group C had significantly higher qualitative proteinuria levels at day 7 and month 1 post-transplantation compared with Groups A and B ( P=0.036, 0.004). There were no statistically significant differences in other renal function indicators among the groups (all P>0.05). Conclusions:Pre-transplant electron microscopy of donor kidneys helps in accurately assessing donor kidney quality and identifying subtle pre-existing pathological changes. It can serve as a reference tool for predicting post-transplant functional recovery. Mild ultrastructural abnormalities in donor kidneys have a relatively controllable impact on long-term graft outcomes.
3.Screening and identification of African swine fever virus M1249L interacting fac-tors based on yeast two-hybrid system
Shuai CUI ; Yang WANG ; Shiyu CHEN ; Yajun JIANG ; Lichun FANG ; Zhongbao PANG ; Xiaoyu GUO ; Hong JIA ; Hongfei ZHU
Chinese Journal of Veterinary Science 2025;45(11):2301-2308
To explore the interaction between ASFV capsid protein M1249L and host from the host cellular perspective,M1249L was selected for constructing the bait plasmid(pGBKT7-M1249L)to screen the bone marrow-derived macrophages(BMDMs)cDNA library.After again co-transform and sequence alignment,20 candidate interacting host proteins were screened,such as IL-1β,CTSB and DNAJA3.And then,co-immunoprecipitation assay was performed to verify the interaction be-tween M1249L and host proteins.GO ontology(GO)and KEGG pathway enrichment analyses re-vealed that biological regulation,cellular communication and response to stimulus and others were enriched in biological processes.And these host proteins could share some pathways,including toll-like receptor signaling pathway and Nod-like receptor signaling pathway.Therefore,the results provides the theoretical basis for further research on the mechanism of ASFV M1249L in viral in-fection and immune regulation.
4.Screening and identification of African swine fever virus M1249L interacting fac-tors based on yeast two-hybrid system
Shuai CUI ; Yang WANG ; Shiyu CHEN ; Yajun JIANG ; Lichun FANG ; Zhongbao PANG ; Xiaoyu GUO ; Hong JIA ; Hongfei ZHU
Chinese Journal of Veterinary Science 2025;45(11):2301-2308
To explore the interaction between ASFV capsid protein M1249L and host from the host cellular perspective,M1249L was selected for constructing the bait plasmid(pGBKT7-M1249L)to screen the bone marrow-derived macrophages(BMDMs)cDNA library.After again co-transform and sequence alignment,20 candidate interacting host proteins were screened,such as IL-1β,CTSB and DNAJA3.And then,co-immunoprecipitation assay was performed to verify the interaction be-tween M1249L and host proteins.GO ontology(GO)and KEGG pathway enrichment analyses re-vealed that biological regulation,cellular communication and response to stimulus and others were enriched in biological processes.And these host proteins could share some pathways,including toll-like receptor signaling pathway and Nod-like receptor signaling pathway.Therefore,the results provides the theoretical basis for further research on the mechanism of ASFV M1249L in viral in-fection and immune regulation.
5.Electron microscopic evaluation of pre-transplant biopsies from deceased donor kidneys and preliminary study on graft outcome
Yujie ZHOU ; Fangcheng ZHANG ; Tao QIU ; Zeya JIN ; Long ZHANG ; Zhongbao CHEN ; Yang GUAN ; Jiangqiao ZHOU
Chinese Journal of Organ Transplantation 2025;46(7):497-503
Objective:To investigate the electron microscopic evaluation results of pre-transplant biopsies of deceased donor kidneys and the corresponding recovery of graft function in recipients after kidney transplantation.Methods:A retrospective analysis was conducted on the clinical data and donor kidney electron microscopy (EM) reports of 196 kidney transplant recipients who underwent pre-implantation kidney biopsies at Renmin Hospital of Wuhan University between October 2020 and June 2023. The ultrastructural pathological features assessed in the pre-transplant kidney biopsy included: the number of glomeruli, the presence of leukocytes and endothelial cells within the glomeruli, the arrangement of capillary loops, abnormalities in podocytes, mesangial cells, mesangial matrix and glomerular basement membrane (GBM), and multilayering of the peritubular capillary basement membrane. Referring to the Mayo Clinic/Renal Pathology Society Consensus Report on the pathological classification, diagnosis, and reporting of glomerulonephritis, the expert consensus on renal biopsy pathology reporting models, and the content of the 2019 Banff Transplant Pathology Meeting, a scoring system was established for ultrastructural pathology of donor kidneys. According to the scores, the recipients were divided into three groups: Group A (total score ≥ 8 points, 94 cases), Group B (total score between 6 and 8 points, 85 cases), and Group C (total score < 6 points, 17 cases). The serum creatinine, estimated glomerular filtration rate (eGFR), and proteinuria at postoperative day 1, day 7, month 1, month 3, month 6, and year 1 were compared among the three groups.Results:Among the 196 donor kidneys, EM examination before transplantation showed the following findings: 19 cases (9.7%) had prominent leukocyte infiltration within the glomeruli, 8 cases (4.1%) had mild leukocyte infiltration, and the remaining 169 cases (86.2%) showed no obvious increase in glomerular leukocytes. Glomerular capillary loop collapse or narrowing was seen in 19 cases (9.7%). Endothelial cell proliferation was observed in 32 cases (16.3%). Homogeneous thickening of the GBM (400-900 nm) was present in 82 cases (41.8%). Foot process effacement ranged from partial to diffuse. Podocyte vacuolar degeneration was seen in 62 cases (32.1%), and podocyte swelling in 10 cases (5.1%). Electron-dense deposits in the mesangial area were observed in 9 cases (4.6%). Mild tubular epithelial swelling was present in 6 cases (3.1%). Only 22 cases (11.2%) showed no multilayering of the peritubular capillary basement membrane, while 174 cases (88.8%) showed 2 to 5 layers of multilayering. All donor glomeruli showed irregular capillary loop arrangement, and the renal interstitium showed scattered inflammatory infiltration and varying degrees of collagen fiber deposition. Group C had significantly higher qualitative proteinuria levels at day 7 and month 1 post-transplantation compared with Groups A and B ( P=0.036, 0.004). There were no statistically significant differences in other renal function indicators among the groups (all P>0.05). Conclusions:Pre-transplant electron microscopy of donor kidneys helps in accurately assessing donor kidney quality and identifying subtle pre-existing pathological changes. It can serve as a reference tool for predicting post-transplant functional recovery. Mild ultrastructural abnormalities in donor kidneys have a relatively controllable impact on long-term graft outcomes.
6.Early implementation of group rehabilitation exercise improves quality of life in patients with Parkinson's disease
Yang YANG ; Tianyu JIANG ; Lifeng CHEN ; Jiarui YAO ; Na WANG ; Dandan LIU ; Dongmei LI ; Dan LIU ; Weiping WU ; Zhongbao GAO ; Zhenfu WANG
Chinese Journal of Geriatrics 2023;42(6):645-649
Objective:To investigate the impact of group-based rehabilitation exercise on motor and non-movement symptoms of Parkinson's disease(PD).Methods:A total of 88 patients from out-patient and in-patient services at our hospital were randomly assigned to an early exercise group(E-EG), a late exercise group(L-EG), and a control group(CG)using a randomized delayed-start design.Patients in the E-EG carried out a rigorous, formal group exercise program, one hour per session, twice per week, for 18 months(May 2018-November 2019). Patients in the L-EG took part in the exercise program in the final 6-12 months of the study.We assessed outcomes using the Unified Parkinson's Disease Rating Scale(UPDRS), Parkinson's disease questionnaire-39(PDQ-39 Q), trail-making test part A & B, nine-hole peg test(9-HPT), 30 second sit to stand test(30s SST), 10 m walk test(10 m W), mini-balance evaluation systems test(Mini-BEST), Fullerton Advanced Balance(FAB)Scale and time up and go(TUG)test.Results:Compared with pre-exercise levels, patients with PD in the E-EG had lower performance in UPDRS(17.5±8.3 vs.20.0±8.6, t=-2.2, P=0.02)and lower performance in PDQ-39(27.2±2.1 vs.29.0±9.8, t=-2.6, P=0.001)after exercise.Moreover, compared with pre-exercise levels, patients with PD in the E-EG showed decreased post-exercise performance in trail-making test part B(114.2±25.5 vs.129.8±28.4, t=-2.3, P=0.02)and in 9-HPT(33.7±7.3 vs.39.6±9.3, t=-2.6, P=0.001). Conclusions:The practice of group-based rehabilitation exercise can improve movement abilities and quality of life in PD patients, especially if implemented early.Targeted rehabilitation exercise should be taken as part of the treatment strategy for PD patients as early as possible to deliver the best benefits.
7.Management of vascular complications after kidney transplantation caused by donor derived infection: a report of 6 cases
Long ZHANG ; Jiangqiao ZHOU ; Tao QIU ; Zhongbao CHEN ; Jilin ZOU ; Xiaoxiong MA ; Zeya JIN ; Yu XU ; Xiuheng LIU
Chinese Journal of Organ Transplantation 2022;43(6):340-345
Objective:To summarize the institutional experiences of treating vascular complications caused by donor-derived infection(DDI)after kidney transplantation(KT).Methods:From January 1, 2015 to December 31, 2020, clinical data were retrospectively reviewed for 6 cases of vascular complications caused by DDI.Age, gender, surgical approaches, immunity induction therapy, immune suppression therapy, infection prevention, onset time of complication, type of complications, infection pathogens, therapeutic protocols and prognoses were summarized.Results:Six patients developed vascular complications caused by DDI in 997 KT recipients with an overall morbidity rate of 0.6%.In 3 cases, carbapenem resistant Klebsiella pneumoniae were positive in culture of secretion and blood samples.And Candida albicans was detected by blood cultures and pathological examinations.One case of antibiotic resistant Staphylococcus aureus was detected by blood culture.Among 3 cases of transplant kidney artery pseudoaneurysm on interventional therapy, there were curing(1 case)and immediate recurrent infection(2 cases). The latter two eventually died by cardiac complications.In 2 cases of arterial hemorrhage, graft nephrectomy was followed by hemodialysis.One case of transplanted renal artery stenosis was successfully cured by artery stenting and survived with normal graft function so far.Conclusions:Interventional endovascular therapy and open surgery are indicated for vascular complications caused by DDI post-KT.Interventional therapy may boost the odds of rescuing transplant kidney.However, clinicians should watch out for the risk of recurrent infection.Open surgery is an effective tool of eliminating infected focus.Preserving transplant kidney or nephrectomy may be adopted on the basis of specific conditions.
8. The report of two cases infection with novel coronavirus (2019-ncov) after kidney transplantation and the association literature analyzation
Tao QIU ; Jingyue WANG ; Jiangqiao ZHOU ; Jilin ZOU ; Zhongbao CHEN ; Xiaoxiong MA ; Long ZHANG
Chinese Journal of Organ Transplantation 2020;41(0):E004-E004
Objective:
To investigate the clinical experience of patients with novel coronavirus (2019-ncov) infection after kidney transplantation.
Method:
Clinical data of two patients with 2019-nCoV infection after renal transplantationin Jan 2020 Renmin Hospital of Wuhan Universiyt were retrospectively analyzed.Case 1 was a 48-year-old male with CMV pneumonia secondary to 2019-nCoV infection at 4 months after transplantation. CT imaging showed multiple patchy ground-glass images of both lungs. Case 2 was a 59-year-old male, who was screened positive for 2019-nCoV nucleic acid due to fever at 9 days after renal transplantation and showed no clinical manifestations of pneumonia. After diagnosis, case 1 was transferred to a designated hospital for isolation. Treatment regimens: cefoperazone sulbactam sodium + linezolid to resist infection, gamma globulin to enhance immunity function, methylprednisolone to control inflammatory response, antiviral regimens including arbidol tablets + lopina-velitonavir tablets. Case 2 was treated with isolated treatment in a single room. The treatment plan included anti-infection (cefoperazone sulbactam sodium), enhancing immunity function (gamma globulin), antivirus therapy with arbidol and other symptomatic treatment.
Result:
Follow up with 3 weeks, case 1 recovered with renal dysfunction, nucleic acid test with nasopharyngeal swabs turned negative, and pulmonary imaging improved. Case 2 showed no obvious clinical symptoms, and the nucleic acid test of nasopharyngeal swabs turned negative for 3 times.
Conclusion
Renal transplant recipients should receive fine protection to avoid exposure to high-risk environments. Diagnosis should be defined with combination of clinical manifestations, nucleic acid test and pulmonary imaging. At present, there are no antiviral drugs and symptomatic treatment is the main choice.
9.Two cases infected with novel coronavirus (2019-nCoV) after kidney transplantation and a review of related literature
Tao QIU ; Jingyue WANG ; Jiangqiao ZHOU ; Jilin ZOU ; Zhongbao CHEN ; Xiaoxiong MA ; Long ZHANG
Chinese Journal of Organ Transplantation 2020;41(3):140-143
Objective:To summarize the clinical experiences of managing patients with novel coronavirus(2019-nCoV) infection after kidney transplantation.Methods:Clinical data were retrospectively analyzed for two patients with 2019-nCoV infection after renal transplantation in January 2020. Case 1 was a 48-year-old male with CMV pneumonia secondary to 2019-nCoV infection at 4 months post-transplantation. CT imaging showed multiple patchy ground-glass opacities of both lungs. Case 2 was a 59-year-old male who screened positive for 2019-nCoV nucleic acid due to fever at 9 days post-transplantation and he showed no clinical manifestations of pneumonia. After a definite diagnosis, case 1 was transferred to a designated hospital for isolation. Treatment regimens: cefoperazone sulbactam sodium plus linezolid for anti-infection, gamma globulin for enhancing immunity, methylprednisolone for controlling inflammatory responses and antiviral regimens of arbidol tablets plus lopina-velitonavir tablets. Case 2 was isolated in a single room. The treatment plan included cefoperazone sulbactam sodium for anti-infection, gamma globulin for enhancing immunity, arbidol for antiviral therapy and other symptomatic measures.Results:During a follow-up period of 3 weeks, case 1 recovered with renal dysfunction, nucleic acid test of nasopharyngeal swab turned negative and pulmonary imaging improved. Case 2 showed no obvious clinical symptoms and nucleic acid test of nasopharyngeal swab turned negative thrice.Conclusions:Renal transplant recipients should take precautions to avoid exposure to high-risk environments. A definite diagnosis should be made on the basis of clinical manifestations and results of nucleic acid test and pulmonary imaging. Currently there is no effective antiviral agent and symptomatic treatment is a major option.
10.Analysis of thinprep cytologic test and human papillomavirus infection in 7646 women in Anhui
Hong YE ; Zhongbao CHANG ; Lin TONG ; Juanping YU ; Shuang ZHANG ; Qianqian WANG ; Chen CAO ; Qinghua XU ; Xiaohua LI
Chinese Journal of Experimental and Clinical Virology 2020;34(5):562-566
Objective:To investigate the types of cervical epithelial cells and the Human Papillomavirus (HPV) infection subtypes of 7 646 women specimens in Anhui province, and provide evidence for cervical cancer prevention.Methods:Thinprep cytologic test (TCT) and flow fluorescence hybridization technique were used to detect cervical epithelial lesions and HPV subtypes.Results:The total positive rate for TCT was 20.25%, and the positive rate was the highest in ≥ 60 age group (28.41%), followed by 10 to ≤ 19 age group (26.32%). The atypical squamous cells-undetermined significance (ASC-US), cannot exclude high-grade squamous intraepithelial lesion (ASC-H) and HSIL positive rates were the highest in the ≥60 age group, and the low-grade squamous intraepithelial lesions (LSIL) positive rate was highest in the 10-19 age group. The proportion of patients with 40-49 age group was the highest, and that of ≥60 age group was the highest. The single infection rate of different cervical epithelial cell lesions was higher than that of multiple infection rates. As the deepening degree of the lesion, the high-risk single infection rate of HPV showed a increasing trend from ASCUS, LSIL, ASC-H to high-grade squamous intraepithelial lesions (HSIL); The common subtypes of HPV infection in negative for intraepithelial lesion or malignancy (NILM) are 52, 16, 58, 53 and 6. The common subtypes of ASCUS are 52, 16, 53, 58 and 51. The common subtypes of ASC-H are 18, 58 and16. LSIL common subtypes are 16, 52, 56, 58, 53 and 66, HSIL common subtypes are16, 58, 33, 52 and 59 type.Conclusions:The high risk and single genotypes of infection were dominant in different cervical epithelial cell lesions in Anhui. Women who aged ≥60 should pay attention and regularly undergo HPV testing and cervical cancer screening. The HPV infection subtypes of different cervical epithelial cell lesions are different, and the common subtypes are HPV52, 16, 58, 53, among which types 16, 58 and 33 are common infection subtypes detected in different lesions.

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