OBJECTIVE: To investigate the clinical features, treatment and prognosis of extranodal NK/T-cell lymphoma, nasal type (ENKTL) with skin lesions as initial symptom. METHODS: The clinical data of 11 ENKTL patients with skin lesions as initial symptom were retrospectively analyzed from August 2016 to January 2023 in Wuhan First Hospital and Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. RESULTS: Among the 11 patients, there were 6 males and 5 females, with a median age of 50(32-80) years. All patients had different forms of skin lesions as initial clinical symptom, including rash, ulcerative mass, painful skin nodules, infiltrating macula, etc. Most of the skin lesions were involved in the limbs and trunk but also appeared in the lower limbs alone. Five patients had hemophagocytic lymphohistiocytosis (HLH) at initial diagnosis, and 8 patients had B symptoms. All patients were diagnosed with advanced clinical staging (Lugano staging IV), and classified as high risk (PINK-E score ≥3). Immunohistochemical examination revealed that the positive rates of CD56 and EBER were both 100%, and the median Ki-67 index was 75%(50%-80%). Plasma EBV-DNA tests were all positive (≥5×10² copies/ml). Most of the induction chemotherapy regimens were combination chemotherapy (MESA, p-Gemox, SMILE) containing pegaspargase or L-asparaginase, or combined with PD-1 monoclonal immunotherapy, or HLH regimens (HLH-04 regimen, L-DEP). The median follow-up time and overall survival (OS) time were both 4.5(0.5-27) months. During the follow-up period, all 8 patients who did not receive autologous hematopoietic stem cell transplantation (ASCT) died, most of whom died of rapid disease progression. Three patients received ASCT, one died of central nervous system recurrence after transplantation, and two survived. The OS of three patients who underwent ASCT was 21, 27, and 19 months, and PFS was 11, 20, and 13 months, respectively. The plasma EBV-DNA copy number was monitored irregularly after transplantation, and the load of EBV was consistent with the changes of the disease. CONCLUSIONS Early clinical symptoms of ENKTL patients with skin lesions as initial symptom are more atypical, and early diagnosis is particularly difficult. The disease progresses rapidly and the prognosis is poor. There is still no uniform standard for the best treatment strategy. The survival of patients can be significantly prolonged by applying ASCT as soon as possible after complete remission obtained by high-dose induction chemotherapy.
Humans ; Male ; Female ; Lymphoma, Extranodal NK-T-Cell/diagnosis* ; Middle Aged ; Adult ; Retrospective Studies ; Aged ; Prognosis ; Aged, 80 and over

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.

Objective:To quantitatively evaluate the level of the three medical linkage in China from 2009 to 2022,explore the influencing factors and driving paths of the three medical linkage in China,and provide a new perspective for promoting the development of the three medical linkage.Methods:An optimized coupling coordination degree model was used to calculate the coupling coordination degree between the trinity healthcare systems and different binary systems within the systems in 31 provinces of China(excluding Hong Kong,Macao and Taiwan),and the Fuzzy-set Qualitative Comparative Analysis method was used to explore the condition configurations of multi-factor-driven three medical linkage.Results:From 2009 to 2022,the coupling coordination degree between the trinity healthcare systems in each province of China generally showed an increasing trend year by year.Among the binary systems,the overall coordinated development situation between the medical and medical insurance systems was the best and the regional development was the most balanced.The coupling coordination degree gap between the trinity healthcare system and the internal binary systems among provinces gradually widened,and the multi-polarization trend intensified.The paths to promote high-level three medical linkage can be summarized into two types:internal and external balanced development type(H1)and government-led type(H2,H3),among which the H1 path with per capita GDP and health expenditure as core conditions was the most common.Conclusion:It is suggested to enhance institutional and technological innovation,and integrate resources through a cross-departmental collaboration mechanism and digital technology.Provinces should select high-level optimization paths by leveraging regional endowments to narrow the regional development gap.Meanwhile,under the impetus of high-level policies,the protection and supervision system continues to improve,thereby promoting the three medical linkage.

Extracellular vesicles(EVs)are small vesicles secreted by cells,widely present in various body fluids,and they play important biological roles.In recent years,EVs have garnered significant attention as novel diagnostic and thera-peutic tools in multiple ocular diseases.Glaucoma,as a common cause of irreversible blindness,is primarily caused by optic nerve damage associated with pathologically elevated intraocular pressure.Emerging evidence indicates that EVs hold considerable therapeutic potential in glaucoma management,particularly in modulating aqueous humor circulation and pro-viding retinal neuroprotection.This review summarizes the latest research progress on EVs in the treatment of glaucoma.

Objective To investigate the effect of Modified Renshen Wumei Decoction on the TLR4/MyD88/pNF-κBp65 signaling pathway and elucidate the potential mechanism by which this formula repairs the intestinal mucosal barrier in diarrheal rats.Methods Twelve rats were randomly selected from a total of 48 rats to serve as the blank control group(CK),while the remaining 36 rats were used to establish a disease model via a compound method.After 14 days of model preparation,the rats were randomly divided into three groups:the model group(MC),the western medicine group(MV),and the traditional Chinese medicine group(MRWD).Each of the four groups(including CK)received corresponding interventions for 7 days.The concentrations of serum diamine oxidase(DAO),D-lactic acid(D-Lac),interleukin-1β(IL-1β),IL-6,IL-10,tumor necrosis factor-α(TNF-α),mucin 2(MUC2),MUC4,MUC6,and colonic homogenate secretory immunoglobulin A(SIgA)were measured using ELISA.Additionally,the protein and gene expressions of colonic toll-like receptor 4(TLR4),myeloid differentiation primary response 88(MyD88),phosphorylated nuclear factor kappa-light-chain-enhancer of activated B cells p65(pNF-κBp65),occludin,claudin-1,and zonula occludens-1(ZO-1)were analyzed by Western blot and RT-PCR.Results(1)Intestinal mucosal injury markers:Compared with the blank group,the serum levels of DAO and D-Lac in the model group were significantly increased(P<0.05).Compared with the model group,both the Chinese medicine group and Western medicine group significantly decreased the serum levels of DAO(P<0.001),while the traditional Chinese medicine group also significantly reduced the serum levels of D-Lac(P<0.05).There was no significant difference in the changes of DAO and D-Lac serum levels between the Chinese medicine group and Western medicine group(P>0.05).(2)Inflammatory indicators:Compared with the blank group,the model group exhibited significant upregulation of TLR4,MyD88,pNF-κ Bp65 protein and gene expression,as well as serum levels of IL-1β,IL-6,and TNF-α(P<0.05),along with a significant decrease in IL-10 serum levels(P<0.05).Compared with the model group,both the Chinese medicine group and Western medicine group significantly downregulated TLR4,MyD88,pNF-κBp65 protein and gene expression,as well as serum levels of IL-1β,IL-6,and TNF-α(P<0.05),and significantly upregulated IL-10 serum levels(P<0.05).There was no significant difference in serum levels of TLR4,MyD88,pNF-κBp65 protein,gene expression,and IL-1β,IL-6,IL-10,and TNF-α between the Chinese medicine group and Western medicine group(P>0.05).(3)Intestinal mucosal barrier factors:Compared with the blank group,the model group exhibited significant downregulation in MUC2,MUC6,SIgA content,as well as Claudin-1,ZO-1 protein and gene expression,and Occludin protein expression(P<0.05).Compared with the model group,both Chinese and Western medicine groups significantly upregulated the content of MUC2 and SIgA,as well as the protein and gene expression of Claudin-1 and ZO-1(P<0.05).The traditional Chinese medicine group also significantly increased the content of MUC6 and Occludin protein expression(P<0.05).No significant differ-ences were observed between the Chinese and Western medicine groups in terms of MUC2,MUC6,SIgA serum content,and Claudin-1 and ZO-1 gene expression(P>0.05).However,the Western medicine group showed better Claudin-1 protein expression than the Chinese medicine group(P<0.05),while the ZO-1 protein expression was higher in the traditional Chinese medicine group compared to the Western medicine group(P<0.05).Conclusion Modified Renshen Wumei Decoction exerts an intestinal mucosal barrier repair effect in diarrhea rats by modulating the TLR4/MyD88/pNF-κBp65 signaling pathway.

Objective:To quantitatively evaluate the level of the three medical linkage in China from 2009 to 2022,explore the influencing factors and driving paths of the three medical linkage in China,and provide a new perspective for promoting the development of the three medical linkage.Methods:An optimized coupling coordination degree model was used to calculate the coupling coordination degree between the trinity healthcare systems and different binary systems within the systems in 31 provinces of China(excluding Hong Kong,Macao and Taiwan),and the Fuzzy-set Qualitative Comparative Analysis method was used to explore the condition configurations of multi-factor-driven three medical linkage.Results:From 2009 to 2022,the coupling coordination degree between the trinity healthcare systems in each province of China generally showed an increasing trend year by year.Among the binary systems,the overall coordinated development situation between the medical and medical insurance systems was the best and the regional development was the most balanced.The coupling coordination degree gap between the trinity healthcare system and the internal binary systems among provinces gradually widened,and the multi-polarization trend intensified.The paths to promote high-level three medical linkage can be summarized into two types:internal and external balanced development type(H1)and government-led type(H2,H3),among which the H1 path with per capita GDP and health expenditure as core conditions was the most common.Conclusion:It is suggested to enhance institutional and technological innovation,and integrate resources through a cross-departmental collaboration mechanism and digital technology.Provinces should select high-level optimization paths by leveraging regional endowments to narrow the regional development gap.Meanwhile,under the impetus of high-level policies,the protection and supervision system continues to improve,thereby promoting the three medical linkage.

Extracellular vesicles(EVs)are small vesicles secreted by cells,widely present in various body fluids,and they play important biological roles.In recent years,EVs have garnered significant attention as novel diagnostic and thera-peutic tools in multiple ocular diseases.Glaucoma,as a common cause of irreversible blindness,is primarily caused by optic nerve damage associated with pathologically elevated intraocular pressure.Emerging evidence indicates that EVs hold considerable therapeutic potential in glaucoma management,particularly in modulating aqueous humor circulation and pro-viding retinal neuroprotection.This review summarizes the latest research progress on EVs in the treatment of glaucoma.

Objective To investigate the effect of Modified Renshen Wumei Decoction on the TLR4/MyD88/pNF-κBp65 signaling pathway and elucidate the potential mechanism by which this formula repairs the intestinal mucosal barrier in diarrheal rats.Methods Twelve rats were randomly selected from a total of 48 rats to serve as the blank control group(CK),while the remaining 36 rats were used to establish a disease model via a compound method.After 14 days of model preparation,the rats were randomly divided into three groups:the model group(MC),the western medicine group(MV),and the traditional Chinese medicine group(MRWD).Each of the four groups(including CK)received corresponding interventions for 7 days.The concentrations of serum diamine oxidase(DAO),D-lactic acid(D-Lac),interleukin-1β(IL-1β),IL-6,IL-10,tumor necrosis factor-α(TNF-α),mucin 2(MUC2),MUC4,MUC6,and colonic homogenate secretory immunoglobulin A(SIgA)were measured using ELISA.Additionally,the protein and gene expressions of colonic toll-like receptor 4(TLR4),myeloid differentiation primary response 88(MyD88),phosphorylated nuclear factor kappa-light-chain-enhancer of activated B cells p65(pNF-κBp65),occludin,claudin-1,and zonula occludens-1(ZO-1)were analyzed by Western blot and RT-PCR.Results(1)Intestinal mucosal injury markers:Compared with the blank group,the serum levels of DAO and D-Lac in the model group were significantly increased(P<0.05).Compared with the model group,both the Chinese medicine group and Western medicine group significantly decreased the serum levels of DAO(P<0.001),while the traditional Chinese medicine group also significantly reduced the serum levels of D-Lac(P<0.05).There was no significant difference in the changes of DAO and D-Lac serum levels between the Chinese medicine group and Western medicine group(P>0.05).(2)Inflammatory indicators:Compared with the blank group,the model group exhibited significant upregulation of TLR4,MyD88,pNF-κ Bp65 protein and gene expression,as well as serum levels of IL-1β,IL-6,and TNF-α(P<0.05),along with a significant decrease in IL-10 serum levels(P<0.05).Compared with the model group,both the Chinese medicine group and Western medicine group significantly downregulated TLR4,MyD88,pNF-κBp65 protein and gene expression,as well as serum levels of IL-1β,IL-6,and TNF-α(P<0.05),and significantly upregulated IL-10 serum levels(P<0.05).There was no significant difference in serum levels of TLR4,MyD88,pNF-κBp65 protein,gene expression,and IL-1β,IL-6,IL-10,and TNF-α between the Chinese medicine group and Western medicine group(P>0.05).(3)Intestinal mucosal barrier factors:Compared with the blank group,the model group exhibited significant downregulation in MUC2,MUC6,SIgA content,as well as Claudin-1,ZO-1 protein and gene expression,and Occludin protein expression(P<0.05).Compared with the model group,both Chinese and Western medicine groups significantly upregulated the content of MUC2 and SIgA,as well as the protein and gene expression of Claudin-1 and ZO-1(P<0.05).The traditional Chinese medicine group also significantly increased the content of MUC6 and Occludin protein expression(P<0.05).No significant differ-ences were observed between the Chinese and Western medicine groups in terms of MUC2,MUC6,SIgA serum content,and Claudin-1 and ZO-1 gene expression(P>0.05).However,the Western medicine group showed better Claudin-1 protein expression than the Chinese medicine group(P<0.05),while the ZO-1 protein expression was higher in the traditional Chinese medicine group compared to the Western medicine group(P<0.05).Conclusion Modified Renshen Wumei Decoction exerts an intestinal mucosal barrier repair effect in diarrhea rats by modulating the TLR4/MyD88/pNF-κBp65 signaling pathway.

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.

Objective:To investigate the value of immunoglobulin heavy chain(IgH)gene rearrangement in monitoring minimal residual disease(MRD)in multiple myeloma(MM)received autologous hematopoietic stem cell transplantation(auto-HSCT).Methods:The clinical data of 26 MM patients who received auto-HSCT in the Department of Hematology,Wuhan First Hospital from 2018 to 2022 were collected.IgH rearrangement was detected by multiplex PCR combined with capillary electrophoresis fragment analysis to evaluate minimal residual disease(MRD),and the outcome of the disease was analyzed statistically.Results:Among the 26 MM patients,18 were males and 8 were females,with a median age of 59(41-70)years.The median follow-up time after transplantation was 33(7-52)months.Compared with the IgH rearrangement negative group(n=17),the proportion of CR and sCR of patients with IgH rearrangement positive in bone marrow samples before auto-HSCT at 3 months after transplantation was lower(1/9 vs 14/17),and the duration of remission(DOR)after transplantation was shorter(10.78±4.35 vs 15.88±5.22 months),with statistically significant difference in DOR between the two groups(P＜0.05).Compared with IgH rearrangement negative group(n=21),the proportion of CR and sCR of patients with positive IgH rearrangement results from peripheral blood stem cell collection at 3 months after transplantation was lower(0/5 vs 15/21),the duration of remission(DOR)after transplantation was shorter(9.60±4.83 vs 15.19±5.11 months),and the difference in DOR between the two groups was statistically significant(P＜0.05).During the follow-up period,5 patients(5/9)with positive IgH rearrangement results in bone marrow specimens died,and all patients with negative IgH rearrangement results survived.Four patients(4/5)with positive IgH rearrangement results by peripheral blood stem cell samples died,while one patient(1/21)with negative IgH rearrangement results died.In both bone marrow and peripheral blood stem cell samples,the survival time of IgH rearrangement-positive patients after transplantation was shorter than that of IgH rearrangement-negative patients(P＜0.05).Logistic regression analysis showed that gender,disease stage,the proportion of bone marrow smear plasma cells at initial diagnosis,stem cell mobilization plan,efficacy evaluation before transplantation(≥ CR and＜CR),and CD34+cell count had no effect on IgH rearrangement results of stem cell collection(P＞0.05).Conclusion:By detecting IgH rearrangement of MM patients receiving auto-HSCT,the depth of MRD can be further evaluated,which has a certain guiding significance for the efficacy and prognosis of the disease.