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

Aim To investigate the effect of high-fat diet on the tight junction function injury of Sertoli cells through the NF-κB/NLRP3 signaling pathway in mice and to explore the underlying mechanism.Methods Male C57BL/6J mice were fed with high-fat or normal diet for five months.The body and gonadal organ weight of mice were measured,and their indices were calculated.The sperm concentration,the sperm viabili-ty,the testicular histomorphology and the expression levels of tight junction proteins ZO-1,Occludin and Claudin-11 were measured.TM4 cells were treated with palmitic acid(PA)for 24 h.Cell viability was detected by CCK-8 method.Then,TM4 cells were di-vided into different groups treated with PA(0,50,100,200 and 300 μmnol·L-1),and the expression lev-els of tight junction proteins ZO-1,Occludin and Clau-din-11 were detected by Western blot.The tight junc-tion permeability of TM4 cells were detected by transepithelial electrical resistance(TEER)and FITC-dextran.The expression levels of mRNA and proteins for the NF-κB/NLRP3 pathway-related factors were de-tected by RT-qPCR and Western blot.Results The results from animal experiments showed that high-fat diet increased body weight and seminal vesicle weight of mice,and decreased testicular index,epididymal in-dex,sperm concentration and sperm motility of mice.High-fat diet also caused testicular tissue structure damage and down-regulated the expression levels of tight junction proteins ZO-1 and Occludin,without af-fecting the expression of Claudin-11.In vitro,PA sig-nificantly down-regulated the expression levels of ZO-1,Occludin and Claudin-11 in TM4 cells,increased the cell permeability,as well as up-regulated the mRNA and protein expression levels of NLRP3/NF-κB signa-ling pathway-related factors in TM4 cells.Conclusions High-fat diet can impair the function of tight junction of testicualr Sertoli cells,and the machanism may be related to the activation of the NF-κB/NLRP3 signaling pathway,resulting in Sertoli cell inflammation in mice.

Aim To explore the protective effect of icariin on the damage of tight junctional function of Sertoli cells in naturally aging mice and the related mechanism.Methods 15-month-old C57BL/6J male mice were randomly divided into three groups:aging model group,low-dose and high-dose icariin treatment group(5 and 20 mg·kg-1).Another 1-month-old C57BL/6J male mice were considered as adult control group(n=10).The mice in adult control group and aging model group were given the vehicle(0.5％sodi-um carboxymethyl cellulose solution)by intragastric administration,while the mice in icariin-treated groups were given different concentrations of icariin,respec-tively.After continuous administration of icariin for three months,the testes and epididymis were immedi-ately removed,weighed,and the organ index was calcu-lated.Sperm viability and sperm concentration in epi-didymis were measured.The morphological changes of testes were observed by HE staining.The ultrastructur-al changes of tight junctions of Sertoli cells were ob-served by transmission electron microscopy.The ex-pression levels of tight junction-related proteins ZO-1,Occludin,and Claudin11 of testicular Sertoli cells were detected by Western blot.The expression and localiza-tion of ZO-1,Occludin,Raptor,Rictor,p-70S6K,and p-rps6 were detected by immunofluorescence.Results Compared with the aging model group,icariin signifi-cantly increased testicular weight and its index,and ep-ididymal index,improved sperm viability and increased sperm concentration in naturally aging mice.In addi-tion,icariin improved the degeneration of testicular morphology and the damage of ultrastructure of Sertoli cell tight junction with aging.Furthermore,Western blot results showed that icariin up-regulated the expres-sion of ZO-1 and Occludin,but had no significant effect on the expression of Claudin 11.Immunofluorescence assay showed that icariin up-regulated the expression of Rictor,and down-regulated the expression of p-70S6K,p-rps6 and Raptor.Conclusions Icariin improves the tight junction damage of Sertoli cells in naturally aging mice,and its mechanism may be related to restoring the balance between mTORC1 and mTORC2.

Objective:To evaluate the efficacy and feasibility of a domestically developed robotic surgical system based on fiber-optic dedicated line communication in cross-regional urological telesurgery.Methods:This was multicenter，single-arm，retrospective case series study. The data of patients who underwent urological telesurgeries using the telesurgical system between January 2023 and December 2024 were analyzed. The cohort included 59 patients from seven hospitals across China. Among the patients，47 were male（79.7%）and 12 were female（20.3%），with a median age of 63.0（56.0，68.0）years and a body mass index of（24.7 ± 3.0）kg/m 2. Surgical procedures included 32 radical prostatectomies，24 partial nephrectomies，one radical nephrectomy，one adrenalectomy，and one ureteral reconstruction. The perioperative indicators，pathological results and postoperative complications were analyzed. The network monitoring data were collected，and the perioperative data of patients，remote system monitoring data and costs were compared between the two communication modes of optical transport network（OTN）and cloud-connect network（CCN）. Results:All 59 remote surgeries were successfully completed，with a mean operative time of（138.0 ± 54.0）minutes，median intraoperative blood loss of 50.0（30.0，100.0）ml and a postoperative hospital stay of 5.0（4.0，6.0）days. No cases required reoperation，Clavien-Dindo grade ≥3 complications，or readmission. The geographical distance between the primary and remote surgical sites ranged from 450 to 2 800 km. Network monitoring revealed increased bidirectional latency with distance increasing：the shortest latency time（Hefei-Hangzhou，450 km）was（16.59 ± 0.80）ms，while the longest（Harbin-Hangzhou，2 200 km）latency time was（53.31 ± 0.31）ms. Average frame loss per procedure was 0?1.27 frames. The results of subgroup analysis comparing OTN and CCN communication modes showed no significant differences in operative time［（130.7 ± 70.5）minutes vs.（142.1 ± 42.9）minutes， P = 0.442］，postoperative hospitalization［6.0（4.0，8.0）d vs. 5.0（4.0，6.0）d， P = 0.581］，or readmission rates（0 vs. 0）. However，CCN demonstrated significant cost advantages with 500 RMB per operation vs. 3 000 RMB per operation for OTN. Conclusions:Urological telesurgery using fiber-optic communication is feasible. The CCN mode，with its cost-effectiveness，excellent usability，and multi-point interconnection flexibility，is currently the preferred communication model for telesurgical applications.

Objective To investigate the characteristics of changes in pain-anxiety-depression-fatigue symptom clusters and their possible associated factors in adolescents with acute lymphoblastic leukemia(ALL)during early chemotherapy.Methods A prospective longitudinal study was conducted from Nov 2019 to Oct 2021,enrolling newly diagnosed adolescent ALL patients from 5 tertiary or pediatric specialty hospitals in Shanghai,Zhejiang Province,Sichuan Province,Anhui Province and Guangdong Province.Patient-reported pain,anxiety,depression,and fatigue were collected at five time points within the first nine weeks of chemotherapy using the PROMIS Pediatric-25 instrument.Latent profile analysis(LPA)and latent transition analysis(LTA)were applied to explore the latent classes of symptom clusters,their transition probabilities over time,and possible risk or protective factors associated with class membership.Results A total of 134 ALL cases were enrolled,and symptom clusters at all the 5 time points(T1-T5)were consistently classified into three groups of mild,moderate and severe symptoms.The severe symptoms group accounted for the largest proportion at each time point(54.5%,59.7%,66.4%,49.3%,and 47.0%,respectively),while the mild and moderate symptoms groups showed an initial decline followed by an increase.Among participants,40.2%maintained the same symptom status,and 77.4%experienced at least one episode of severe symptom status during the trajectory.Religious affiliation(T5)and family monthly income>5 000 Yuan(T2,T4 and T5)served as protective factors against severe symptoms.Higher baseline fatigue(T1)was associated with membership in the severe symptoms group at subsequent time points.Conclusion Pain-anxiety-depression-fatigue symptoms in adolescents with ALL during early chemotherapy can be categorized into mild,moderate and severe symptoms with dynamic transitions over time.Higher baseline fatigue was associated with increased risk of severe symptoms,whereas higher family income and religious affiliation appeared protective effects.

Aim To investigate the effect of high-fat diet on the tight junction function injury of Sertoli cells through the NF-κB/NLRP3 signaling pathway in mice and to explore the underlying mechanism.Methods Male C57BL/6J mice were fed with high-fat or normal diet for five months.The body and gonadal organ weight of mice were measured,and their indices were calculated.The sperm concentration,the sperm viabili-ty,the testicular histomorphology and the expression levels of tight junction proteins ZO-1,Occludin and Claudin-11 were measured.TM4 cells were treated with palmitic acid(PA)for 24 h.Cell viability was detected by CCK-8 method.Then,TM4 cells were di-vided into different groups treated with PA(0,50,100,200 and 300 μmnol·L-1),and the expression lev-els of tight junction proteins ZO-1,Occludin and Clau-din-11 were detected by Western blot.The tight junc-tion permeability of TM4 cells were detected by transepithelial electrical resistance(TEER)and FITC-dextran.The expression levels of mRNA and proteins for the NF-κB/NLRP3 pathway-related factors were de-tected by RT-qPCR and Western blot.Results The results from animal experiments showed that high-fat diet increased body weight and seminal vesicle weight of mice,and decreased testicular index,epididymal in-dex,sperm concentration and sperm motility of mice.High-fat diet also caused testicular tissue structure damage and down-regulated the expression levels of tight junction proteins ZO-1 and Occludin,without af-fecting the expression of Claudin-11.In vitro,PA sig-nificantly down-regulated the expression levels of ZO-1,Occludin and Claudin-11 in TM4 cells,increased the cell permeability,as well as up-regulated the mRNA and protein expression levels of NLRP3/NF-κB signa-ling pathway-related factors in TM4 cells.Conclusions High-fat diet can impair the function of tight junction of testicualr Sertoli cells,and the machanism may be related to the activation of the NF-κB/NLRP3 signaling pathway,resulting in Sertoli cell inflammation in mice.

Aim To explore the protective effect of icariin on the damage of tight junctional function of Sertoli cells in naturally aging mice and the related mechanism.Methods 15-month-old C57BL/6J male mice were randomly divided into three groups:aging model group,low-dose and high-dose icariin treatment group(5 and 20 mg·kg-1).Another 1-month-old C57BL/6J male mice were considered as adult control group(n=10).The mice in adult control group and aging model group were given the vehicle(0.5％sodi-um carboxymethyl cellulose solution)by intragastric administration,while the mice in icariin-treated groups were given different concentrations of icariin,respec-tively.After continuous administration of icariin for three months,the testes and epididymis were immedi-ately removed,weighed,and the organ index was calcu-lated.Sperm viability and sperm concentration in epi-didymis were measured.The morphological changes of testes were observed by HE staining.The ultrastructur-al changes of tight junctions of Sertoli cells were ob-served by transmission electron microscopy.The ex-pression levels of tight junction-related proteins ZO-1,Occludin,and Claudin11 of testicular Sertoli cells were detected by Western blot.The expression and localiza-tion of ZO-1,Occludin,Raptor,Rictor,p-70S6K,and p-rps6 were detected by immunofluorescence.Results Compared with the aging model group,icariin signifi-cantly increased testicular weight and its index,and ep-ididymal index,improved sperm viability and increased sperm concentration in naturally aging mice.In addi-tion,icariin improved the degeneration of testicular morphology and the damage of ultrastructure of Sertoli cell tight junction with aging.Furthermore,Western blot results showed that icariin up-regulated the expres-sion of ZO-1 and Occludin,but had no significant effect on the expression of Claudin 11.Immunofluorescence assay showed that icariin up-regulated the expression of Rictor,and down-regulated the expression of p-70S6K,p-rps6 and Raptor.Conclusions Icariin improves the tight junction damage of Sertoli cells in naturally aging mice,and its mechanism may be related to restoring the balance between mTORC1 and mTORC2.

Objective To investigate the characteristics of changes in pain-anxiety-depression-fatigue symptom clusters and their possible associated factors in adolescents with acute lymphoblastic leukemia(ALL)during early chemotherapy.Methods A prospective longitudinal study was conducted from Nov 2019 to Oct 2021,enrolling newly diagnosed adolescent ALL patients from 5 tertiary or pediatric specialty hospitals in Shanghai,Zhejiang Province,Sichuan Province,Anhui Province and Guangdong Province.Patient-reported pain,anxiety,depression,and fatigue were collected at five time points within the first nine weeks of chemotherapy using the PROMIS Pediatric-25 instrument.Latent profile analysis(LPA)and latent transition analysis(LTA)were applied to explore the latent classes of symptom clusters,their transition probabilities over time,and possible risk or protective factors associated with class membership.Results A total of 134 ALL cases were enrolled,and symptom clusters at all the 5 time points(T1-T5)were consistently classified into three groups of mild,moderate and severe symptoms.The severe symptoms group accounted for the largest proportion at each time point(54.5%,59.7%,66.4%,49.3%,and 47.0%,respectively),while the mild and moderate symptoms groups showed an initial decline followed by an increase.Among participants,40.2%maintained the same symptom status,and 77.4%experienced at least one episode of severe symptom status during the trajectory.Religious affiliation(T5)and family monthly income>5 000 Yuan(T2,T4 and T5)served as protective factors against severe symptoms.Higher baseline fatigue(T1)was associated with membership in the severe symptoms group at subsequent time points.Conclusion Pain-anxiety-depression-fatigue symptoms in adolescents with ALL during early chemotherapy can be categorized into mild,moderate and severe symptoms with dynamic transitions over time.Higher baseline fatigue was associated with increased risk of severe symptoms,whereas higher family income and religious affiliation appeared protective effects.

Objective:To evaluate the efficacy and feasibility of a domestically developed robotic surgical system based on fiber-optic dedicated line communication in cross-regional urological telesurgery.Methods:This was multicenter，single-arm，retrospective case series study. The data of patients who underwent urological telesurgeries using the telesurgical system between January 2023 and December 2024 were analyzed. The cohort included 59 patients from seven hospitals across China. Among the patients，47 were male（79.7%）and 12 were female（20.3%），with a median age of 63.0（56.0，68.0）years and a body mass index of（24.7 ± 3.0）kg/m 2. Surgical procedures included 32 radical prostatectomies，24 partial nephrectomies，one radical nephrectomy，one adrenalectomy，and one ureteral reconstruction. The perioperative indicators，pathological results and postoperative complications were analyzed. The network monitoring data were collected，and the perioperative data of patients，remote system monitoring data and costs were compared between the two communication modes of optical transport network（OTN）and cloud-connect network（CCN）. Results:All 59 remote surgeries were successfully completed，with a mean operative time of（138.0 ± 54.0）minutes，median intraoperative blood loss of 50.0（30.0，100.0）ml and a postoperative hospital stay of 5.0（4.0，6.0）days. No cases required reoperation，Clavien-Dindo grade ≥3 complications，or readmission. The geographical distance between the primary and remote surgical sites ranged from 450 to 2 800 km. Network monitoring revealed increased bidirectional latency with distance increasing：the shortest latency time（Hefei-Hangzhou，450 km）was（16.59 ± 0.80）ms，while the longest（Harbin-Hangzhou，2 200 km）latency time was（53.31 ± 0.31）ms. Average frame loss per procedure was 0?1.27 frames. The results of subgroup analysis comparing OTN and CCN communication modes showed no significant differences in operative time［（130.7 ± 70.5）minutes vs.（142.1 ± 42.9）minutes， P = 0.442］，postoperative hospitalization［6.0（4.0，8.0）d vs. 5.0（4.0，6.0）d， P = 0.581］，or readmission rates（0 vs. 0）. However，CCN demonstrated significant cost advantages with 500 RMB per operation vs. 3 000 RMB per operation for OTN. Conclusions:Urological telesurgery using fiber-optic communication is feasible. The CCN mode，with its cost-effectiveness，excellent usability，and multi-point interconnection flexibility，is currently the preferred communication model for telesurgical applications.

OBJECTIVE: To examine the association of handgrip strength with aortic stenosis incidence among adults aged 60 years and older. METHODS: We conducted a cohort study using the UK Biobank data to assess the relationship between handgrip strength and incident aortic stenosis in individuals aged 60 years and older. Handgrip strength was measured using a Jamar J00105 hydraulic hand dynamometer. Adjusted Cox proportional hazards regression models were conducted to assess the association between handgrip strength and incident aortic stenosis. RESULTS: We included 157,097 UK Biobank participants (78,151 women and 78,946 men) in our study, with mean age of 64 ± 2.9 years. During a median follow-up of 8.1 (7.4-8.8) years, 1543 (1.0%) participants developed incident aortic stenosis. Compared with those with the lowest handgrip strength (tertile 1), the adjusted hazard ratios (95% confidence interval) of incident aortic stenosis in the middle (tertile 2) and the highest (tertile 3) were 0.86 (0.77-0.97) and 0.76 (0.67-0.87), respectively. CONCLUSIONS Higher handgrip strength was associated with lower risk of developing aortic stenosis in older adults. Future studies warrant preventive strategies for older adults with lower handgrip strength.