OBJECTIVES: To observe the therapeutic effect of spermine in neonatal mouse models of severe hand, foot and mouth disease (HFMD) caused by enterovirus 71 (EV71) infection and explore its therapeutic mechanism in light of regulation of macrophage GBP5/NLRP3 inflammasome pathway. METHODS: Neonatal BALB/c mice (3-5 days old) were divided into control group, EV71 infection group and Spermine treatment group. The mice in the latter two groups received an intraperitoneal injection of 50 μL EV71 suspension (1×10⁶ TCID50 of EV71), followed 3 days later by intraperitoneal injection of 50 μL PBS or 100 μmol/L spermine. GBP5, NLRP3, CXCL10, and TNFSF10 expressions in heart, liver, lung and kidney tissues of the mice were detected using Western blotting and qPCR, and tissue pathologies and macrophage infiltration were assessed with HE staining and immunohistochemistry. In cultured THP-1 and RAW264.7 cells, the effects of EV71 infection, GBP5 siRNA transfection and treatment with spermine or eflornithine on GBP5, NLRP3, CXCL10, and TNFSF10 mRNA expressions were investigated using qPCR. RESULTS: In the neonatal mice, EV71 infection resulted in multiple organ damage, macrophage infiltration and activation of the GBP5/NLRP3 pathway, and spermine treatment significantly improved tissue injuries, reduced macrophage infiltration, and down-regulated the expressions of GBP5, NLRP3 and the inflammatory factors in the infected mice. In THP-1 and RAW264.7 cells, EV71 infection caused significant upregulation of GBP5, NLRP3, CXCL10, and TNFSF10 expressions, which were obviously lowered by spermine treatment. In THP-1 cells, treatment with eflornithine significantly suppressed the reduction of GBP5, NLRP3, CXCL10, and TNFSF10 expressions induced by GBP5 siRNA transfection. CONCLUSIONS Spermine suppressed EV71 infection-induced inflammatory responses by inhibiting GBP5-mediated NLRP3 inflammasome activation, suggesting a new strategy for treatment of severe HFMD.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein ; Mice ; Macrophages/metabolism* ; Enterovirus A, Human ; Mice, Inbred BALB C ; Inflammasomes/metabolism* ; Spermine/therapeutic use* ; Animals, Newborn ; Humans ; Enterovirus Infections ; Hand, Foot and Mouth Disease/drug therapy* ; RAW 264.7 Cells ; Chemokine CXCL10/metabolism*

Objective To explore the effectiveness of a hospital-to-home transitional health management program for caregivers of children with severe encephalitis,aiming to provide a reference for optimizing transitional care models for these patients.Methods A convenience sampling method was used to select 84 children with severe encephalitis and their caregivers admitted to the neurology department of a tertiary hospital in Zhengzhou between March 2023 and June 2024.According to the admission time,they were divided into an experimental group and a control group,with 42 cases in each group.The experimental group received a hospital-to-home transitional health management program in addition to routine care,while the control group received standard care and discharge instructions.Differences in caregivers' perceived benefits,caregiver burden,disease management ability,and post-intervention outcomes of the children were compared between the 2 groups before and after the intervention.Results All 42 participants in both groups completed the study.After the intervention,the experimental group reported higher perceived benefits of(91.29±9.76)compared to(84.81±12.86)in the control group,lower caregiver burden of(48.55±7.15)compared to(54.71±11.23)in the control group,greater disease management ability of(41.83±4.97)than(37.79±5.23)in the control group,and lower difficulty in disease management of(31.52±7.82)compared to(34.55±3.96)in the control group,with all differences being statistically significant(P＜0.05).No statistically significant difference was found in the prognosis of the children between the 2 groups(P=0.500).Conclusion The hospital-to-home transitional health management program can effectively enhance caregivers'perceived benefits and disease management capabilities,reduce their caregiving burden,and provide scientific evidence for optimizing transitional care for children with severe encephalitis.

Objective To summarize the best evidence of early rehabilitation management of hand function in patients with hand burn,and provide basis for medical personnel to carry out early rehabilitation management of hand burn.Methods According to the 5S model,all evidence on early rehabilitation management of hand function in patients with hand burns was retrieved from databases and websites including UpToDate,BMJ Best Practice,NICE,RNAO,GIN,and so on.The retrieved evidence included clinical decisions,guidelines,evidence summaries,expert consensuses,systematic reviews,Meta analysis.The search period of the summary of best evidence,expert concensus and guidelines are from the establishment of the database to December 20,2024,and the search period of the systematic reviews is from January 1,2019 to December 20,2024.Quality evaluation of literature,evidence extraction and summary were conducted.The evidence was graded according to JBI evidence pre-grading system 2014.Results Totally 17 pieces of the literature were included,including 1 clinical decision,4 guidelines,6 evidence summaries,3 expert consensus articles,and 3 systematic reviews.Totally pieces of best evidence were summarized,including 7 aspects of assessment,hand positioning,treatment of edema,dressing,use of orthotics,joint mobility training,and health education.Conclusion This study summarized the best evidence of early rehabilitation management of hand function in patients with hand burn,and provided evidence-based evidence for clinical rehabilitation management plan.According to the clinical situation,the medical staff can apply the evidence to clinical practice,so as to improve the hand function and quality of life of patients.

Objective To explore the effectiveness of a hospital-to-home transitional health management program for caregivers of children with severe encephalitis,aiming to provide a reference for optimizing transitional care models for these patients.Methods A convenience sampling method was used to select 84 children with severe encephalitis and their caregivers admitted to the neurology department of a tertiary hospital in Zhengzhou between March 2023 and June 2024.According to the admission time,they were divided into an experimental group and a control group,with 42 cases in each group.The experimental group received a hospital-to-home transitional health management program in addition to routine care,while the control group received standard care and discharge instructions.Differences in caregivers' perceived benefits,caregiver burden,disease management ability,and post-intervention outcomes of the children were compared between the 2 groups before and after the intervention.Results All 42 participants in both groups completed the study.After the intervention,the experimental group reported higher perceived benefits of(91.29±9.76)compared to(84.81±12.86)in the control group,lower caregiver burden of(48.55±7.15)compared to(54.71±11.23)in the control group,greater disease management ability of(41.83±4.97)than(37.79±5.23)in the control group,and lower difficulty in disease management of(31.52±7.82)compared to(34.55±3.96)in the control group,with all differences being statistically significant(P＜0.05).No statistically significant difference was found in the prognosis of the children between the 2 groups(P=0.500).Conclusion The hospital-to-home transitional health management program can effectively enhance caregivers'perceived benefits and disease management capabilities,reduce their caregiving burden,and provide scientific evidence for optimizing transitional care for children with severe encephalitis.

Objective To summarize the best evidence of early rehabilitation management of hand function in patients with hand burn,and provide basis for medical personnel to carry out early rehabilitation management of hand burn.Methods According to the 5S model,all evidence on early rehabilitation management of hand function in patients with hand burns was retrieved from databases and websites including UpToDate,BMJ Best Practice,NICE,RNAO,GIN,and so on.The retrieved evidence included clinical decisions,guidelines,evidence summaries,expert consensuses,systematic reviews,Meta analysis.The search period of the summary of best evidence,expert concensus and guidelines are from the establishment of the database to December 20,2024,and the search period of the systematic reviews is from January 1,2019 to December 20,2024.Quality evaluation of literature,evidence extraction and summary were conducted.The evidence was graded according to JBI evidence pre-grading system 2014.Results Totally 17 pieces of the literature were included,including 1 clinical decision,4 guidelines,6 evidence summaries,3 expert consensus articles,and 3 systematic reviews.Totally pieces of best evidence were summarized,including 7 aspects of assessment,hand positioning,treatment of edema,dressing,use of orthotics,joint mobility training,and health education.Conclusion This study summarized the best evidence of early rehabilitation management of hand function in patients with hand burn,and provided evidence-based evidence for clinical rehabilitation management plan.According to the clinical situation,the medical staff can apply the evidence to clinical practice,so as to improve the hand function and quality of life of patients.

Objective:To establish a rapid quantitative PCR (qPCR) technique for Mycobacterium marinum skin infections, and to analyze its clinical diagnostic efficiency. Methods:DNA was extracted from Mycobacterium marinum colonies and serially diluted (10 -1 to 10 -8). Twelve pairs of previously reported primers and probes, as well as 6 pairs of newly designed primers and probes in this study, were used for qPCR amplification to identify the most sensitive primers and probes for the detection of Mycobacterium marinum. Skin lesion tissues were collected from 72 patients with confirmed Mycobacterium marinum infections (experimental group) and 68 with other mycobacterial infections (control group) at Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences in 2021. These skin tissues were subjected to qPCR amplification, interferon-gamma release assay (IGRA), acid-fast staining, and tissue culture to evaluate the diagnostic efficacy. Results:The newly designed primers and probes targeting the mycobacterial enhanced infection locus 2 (Mel2) demonstrated the highest sensitivity, with a detection limit of 0.86 copies/μl (cycle threshold value = 37) ; the qPCR amplification with the Mel2 primers/probes did not yield positive results when used for the detection of other mycobacteria (including Mycobacterium leprae and Staphylococcus spp) . Among the 72 patients in the experimental group, 44 were positive for qPCR with a sensitivity of 61.1% (95% CI: 49.6% - 71.5%), and 47 were positive for culture with a sensitivity of 65.2% (95% CI: 53.8% - 75.3%) ; all the 68 controls were negative for both qPCR and culture, with their specificities both being 100%. Among 65 patients subjected to IGRA, 31 were positive with a sensitivity of 47.7% (95% CI: 36.0% - 59.6%), while 16 out of 25 controls were negative for IGRA with a specificity of 64.0% (95% CI: 44.5% - 79.8%). Among 58 patients subjected to acid-fast staining, 37 were positive with a sensitivity of 63.8% (95% CI: 50.9% - 74.9%), and 52 out of 66 controls were negative for acid-fast staining with a specificity of 78.8% (95% CI: 67.5% - 86.9%). The combination of qPCR and culture resulted in a sensitivity of 93% and a specificity of 100% for the detection of Mycobacterium marinum. Conclusion:In this study, a highly sensitive qPCR assay was developed for the detection of Mycobacterium marinum, and its combination with culture could further improve the detection sensitivity.

"Chinese model" of organ donation and transplantation in China has won acclaims from all over the world. Current contradictions between unbalanced and inadequate development of organ donation and transplantation and surging public demands for transplant services remain serious. And an acute shortage of donated organs is still the greatest difficulty. Improving organ donation rate per million population (PMP) and organ utilization rate has been a great challenge for organ donation teams in China. This review summarized the relevant experiences of Second Affiliated Hospital of Guangxi Medical University in fostering organ donation culture atmosphere and connotation to accelerate the high-quality development of organ donation. It was intended to provide references for disciplined construction of other organ donation management teams and promote the development of organ donation and transplantation in China.

Objective To establish a reference interval for the pepsinogen(PG)Ⅰ,PGⅡ and PGⅠ/PGⅡ in healthy adult subjects in Zhejiang Province.Methods The data of 45 504 healthy adult subjects were collected,and the levels of serum PGⅠ and PG Ⅱ were detected by chemiluminescence microparticle immunoassay.The reference range of PGs were determined according to the CLSI-C28-A3 file.Results The median serum PGⅠ concentration in male was 132.62μg/L,PGⅡ concentration was 8.10μg/L,and PGⅠ/PGⅡ was 15.9.For females,they were 107.44μg/L,6.96μg/L and 15.0,respectively.PGI,PGⅡ concentration and PGⅠ/PGⅡ ratio were significantly higher in males than in females(P<0.001).The levels of PGⅠ and PGⅡ increased with age(P<0.001).Serum PGⅠ reference interval for male:59.79-234.97μg/L for 19-39 years old,63.33-294.62μg/L for 40-59 years old,64.25-333.61μg/L for≥60 years old,PGⅡ reference interval:3.33-22.60μg/L for 19-39 years of age,3.79-33.89μg/L for 40-59 years of age,4.15-42.08μg/L for≥60 years of age,PGⅠ/PGⅡ reference interval:those aged 19-39 years ranged from 7.3 to 31.4,those aged 40-59 years ranged from 5.8 to 30.9,and those aged≥60 years ranged from 3.9 to 30.7.The reference intervals of female PGⅠ were 48.79-215.68μg/L,52.10-276.01μg/L,and 64.34-317.20μg/L,respectively.The reference intervals of female PgⅡwere:2.87-23.93μg/L,3.41-33.31μg/L and 3.88-39.16μg/L,respectively.The reference intervals of of female PGⅠ/PGⅡ are 6.6-28.1,5.2-27.9 and 3.6-26.2.Conclusion This study determined the reference range of serum PGs deficiency in healthy subjects of different sex and age in Zhejiang Province.

Background: Immunochemotherapy has demonstrated a promising efficacy for a variety of B-cell lymphoma but has limited efficacy for Epstein–Barr virus-positive (EBV +) diffuse large B-cell lymphoma (DLBCL) that is refractory or relapsed to conventional chemotherapy regimens. Considering higher programmed death-ligand 1 (PD-L1) expres‑ sion in the subset of patients with DLBCL with positive EBV, we speculated that PD-1 inhibitors plus chemotherapy may be an alternative regimen in patients with refractory/relapsed EBV + DLBCL. Methods: This retrospective study included six adult patients diagnosed with refractory EBV + DLBCL resistant to first-line immunochemotherapy regimens (R-CHOP). These patients received PD-1 inhibitors plus chemotherapy as second-line treatment. Results: The final analysis included six patients (four men and two women (median age, 50 years; range, 39–83 years)). Four patients were diagnosed with Epstein–Barr virus (EBV) + DLBCL, and two had DLBCL associated with chronic inflammation. Over a median follow-up of 20 months (range, 2–31 months), the objective response rate was 83% (5/6) and the complete remission rate was 67% (4/6). No severe immune-related adverse reactions occurred, and only a mild rash was reported, which did not necessitate the discontinuation of therapy. Conclusion The combination of PD-1 inhibitors and chemotherapy offers promising results as a second-line treat‑ ment for patients with refractory EBV + DLBCL that is resistant to first-line immunochemotherapy regimens. These preliminary findings warrant further investigation in larger clinical trials to validate the efficacy and safety of this therapeutic approach.

Objective To examine the relationship between the expressions of mismatch repair proteins,MutS homolog 2(MSH2)and MutS homolog 6(MSH6),and villin and the pathological features in patients with colon cancer.Methods A total of 310 cases of colon cancer patients who were treated at our hospital between January 2017 and September 2021 were selected.The diagnosis of colon cancer of all patients was verified by pathological evaluation.Immunohistochemistry was used to determine the protein expressions of MSH2,MSH6,and villin.The correlation between the expressions of MSH2,MSH6,and villin and the clinicopathological parameters in patients with colon cancer was analyzed accordingly.Multivariate logistic regression was used to analyze the correlation between the expressions of MSH2,MSH6,and villin and the clinicopathological parameters of colon cancer.Kaplan-Meier survival curve was used to compare the 2-year survival rates of colon cancer patients with different expression levels of the proteins.Results Among the 310 patients with colon cancer,the negative expression rates of MSH2,MSH6,and villin proteins in cancer tissues were 8.71％(27/310),9.35％(29/310),and 46.13％(143/310),respectively.The negative expression rates of the three proteins in tissues adjacent to cancer were 3.23％(10/310),4.19％(13/310),and 9.68％(30/310),respectively.The negative expression rates of the three proteins in cancer tissues were all higher than those in adjacent tissues(P＜0.05).Regression analysis showed that the expression of MSH2 and MSH6 in cancer tissues was correlated with the age,the location of tumor lesions,tumor differentiation degree,and lymph node metastasis in colon cancer patients(P＜0.05).The expression of villin in the cancer tissue is correlated with the depth of tumor infiltration,lymph node metastasis,distant metastasis,and clinical staging status in colon cancer patients(P＜0.05).The 2-year survival rates of patients with negative expressions of MSH2 and MSH6 were 51.85％and 44.83％,respectively,which were lower than those of patients with positive expression of MSH2 and MSH6(79.51％and 80.43％,P＜0.05).Thirteen patients(4.1％)had negative expression of MSH2,MSH6,and villin(referred to as"triple negative expressions")in the cancer tissues,and their 2-year survival rate was 30.77％,which was lower than that of colon cancer patients who did not meet the criteria for triple negative expressions(79.12％[235/297],P＜0.05).Conclusion The expressions of MSH2,MSH6,and villin are closely correlated with the pathological features of colon cancer patients.Evaluating the expression of the three proteins may assist in the clinical diagnosis,treatment,and prognosis evaluation of colon cancer.