Nasopharyngeal carcinoma （NPC） is a malignant tumor originating from the mucosal epithelium of the nasopharynx. In recent years， its incidence and mortality rates have shown a continuous upward trend， and there is still a lack of therapeutic regimens with both favorable efficacy and safety in clinical practice. Mitogen-activated protein kinase （MAPK） signaling pathway plays a key regulatory role in biological processes such as cell proliferation， differentiation， apoptosis and invasion. It is widely involved in the occurrence and progression of NPC， and serves as an important target in the research field of anti-NPC therapy. This article systematically elaborates on the mechanism of action of the MAPK signaling pathway in NPC， and reviews the research status regarding the anti-NPC effect of active components of traditional Chinese medicine （TCM） and TCM compound prescriptions by regulating this signaling pathway. The results show that TCM active components， including flavonoids （luteolin， maackiain， baicalein， etc.）， alkaloids （picrasidine Ⅰ， tetrandrine， etc.）， terpenoids （bakuchiol， cantharidic acid）， as well as traditional Chinese medicine compound formulas （such as Biyan jiedu capsules and Yiqi jiedu formula） can exert effects including inducing autophagy and apoptosis of NPC cells， promoting pyroptosis， reversing drug resistance， blocking epithelial-mesenchymal transition， weakening cell stemness and arresting cell cycle progression by regulating the MAPK signaling pathway， thereby inhibiting the occurrence and development of NPC through multiple pathways.

OBJECTIVE: To summarize the clinical features and management of two brothers affected with X-linked inhibitor of apoptosis protein (XIAP) deficiency. METHODS: This study retrospectively analyzed the clinical presentations, treatment, and follow-up of two brothers with XIAP deficiency diagnosed at Shanghai Children's Hospital in 2020, and summarized similar cases recorded in databases such as PubMed, Wanfang, Chinese Medical Association Journals, and WIP from January 2006 to November 2024. This study was approved by the Medical Ethics Committee of our hospital (Ethics No.: 2025R128-E01). RESULTS: Patient 1 was the younger brother, who presented at 8 years of age with growth retardation, folliculitis, erythema nodosum, and perineal abscess. Sequencing revealed that he has carried a hemizygous c.566T>C (p.Leu189Pro) variant of the XIAP gene, which was inherited from his mother. He was allergic to infliximab treatment and underwent allogeneic stem cell transplantation (HSCT) in January 2021. During a follow-up of 3 years and 10 months post-transplantation, he showed no gastrointestinal symptoms and had a good outcome. Patient 2 was the elder brother, who presented at 10 years and 6 months of age with growth retardation, rash, and anal fistula. Genetic testing revealed the same variant. He was treated with oral azathioprine but did not have regular follow-ups. At 14-years-and-6-months of age, he had developed severe gastrointestinal infection and hemophagocytic lymphohistiocytosis, which was alleviated after treatment with antibiotics, glucocorticoids, immunoglobulin, and rituximab. He is currently being prepared for HSCT. A total of 13 publications were retrieved, which involved 64 patients from 23 families, with 23 different variants identified. The main clinical manifestations included splenomegaly (34 cases, 53.1%), hemophagocytic lymphohistiocytosis (27 cases, 42.2%), and inflammatory bowel disease or colitis (20 cases, 31.8%). There were significant phenotypic differences among patients from the same family. Thirteen patients (20.3%) underwent HSCT, with a survival rate of 61.5%. CONCLUSION For male children with early onset, poor treatment response, especially those with unexplained splenomegaly and IBD-like symptoms, early genetic testing is recommended. HSCT is a safe and effective treatment for XIAP deficiency. For patients with developmental delay, early onset, and severe IBD phenotype, early transplantation is recommended.
Humans ; Male ; X-Linked Inhibitor of Apoptosis Protein/deficiency* ; Child ; Genetic Diseases, X-Linked/therapy* ; Phenotype ; Siblings ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation

The frequent extreme climatic events post multifaceted impacts on the distribution of Oncomelania hupensis, the intermediate host of Schistosoma japonicum in the context of global climate change. This article systematically reviews the effects of four types of extreme climatic events, including floods, droughts, heat waves, and cold waves, on the survival, reproduction, and distribution of Oncomelania hupensis. Floods may expand suitable snail habitats, and increase both emerging and re-emerging snail habitats; however, the impact of floods on O. hupensis density is characterized by a lag effect of a decline followed by a rise. Droughts may cause fragmentation of suitable O. hupensis snail habitats, reduced O. hupensis snail egg production rates, and increased O. hupensis snail mortality, and heat waves may cause an increase in O. hupensis snail mortality, a reduction in numbers of O. hupensis snail populations and shrinking of O. hupensis snail distribution, while cold waves may cause a reduction in O. hupensis snail density and a rise in O. hupensis snail mortality. Extreme climate events pose both shortand long-term effects on the distribution of O. hupensis. Intensified surveillance of O. hupensis snails is required in high-risk environments.

BACKGROUND:Upper lumbar spinal stenosis is a multifactorial degenerative disorder of the spine.For narrowing of the spinal canal in the upper lumbar region(L1-L4),surgical decision-making is particularly complex.Existing minimally invasive surgeries each have their own advantages and limitations.Currently,there are few reports on biomechanical comparison and finite element analysis of different surgical methods for the treatment of high lumbar spinal stenosis.OBJECTIVE:To analyze the biomechanical impact of endoscopic unilateral laminotomy for bilateral decompression,transforaminal endoscopic lumbar decompression,and cross-overtop decompression in the treatment of upper lumbar spinal stenosis using endoscopy,and to verify the reliability and effectiveness of these three surgical techniques in treating upper lumbar spinal stenosis,providing a biomechanical basis for clinical decision-making.METHODS:The CT images of the lumbar spine of a healthy volunteer were selected,and the finite element model M0 of the normal lumbar L1-L5 segments was established using Mimics,Geomagic,Solid works,and Ansys software.The L2-L3 segment,representing upper lumbar characteristics,was chosen.Based on this model,the surgical models for endoscopic unilateral laminotomy for bilateral decompression(M1),transforaminal endoscopic lumbar decompression(M2),and cross-overtop decompression(M3)were established.Using software,the changes in the range of motion of the entire lumbar segment and the maximum Von Mises stress of the intervertebral discs were simulated and evaluated for each group of models under six loading conditions:flexion,extension,left lateral bending,right lateral bending,left rotation,and right rotation.RESULTS AND CONCLUSION:(1)Compared with model MO,the range of motion in M1,M2,and M3 increased under all six conditions,with M1 showing a greater increase.(2)M1 and M2 demonstrated significant increases in range of motion under forward bending,extension,and right rotation,while the increase under other conditions remained below 7％.(3)Compared with model M3,model M1 exhibited slightly increased overall joint range of motion during extension and left bending,while no significant changes were observed in other aspects,and the L1-L5 lumbar segments did not reach an unstable state.(4)In model M1,the maximum Von Mises stress of the intervertebral discs increased most significantly under flexion and extension loading conditions.However,under left lateral bending,right lateral bending,left rotation,and right rotation loading conditions,the increase did not exceed 5％.(5)These findings suggest that due to the sagittal anatomical characteristics of the facet joints,the unilateral laminotomy for bilateral decompression technique,while decompressing,involves resection of more facet joints,which impacts overall segmental stability.The transforaminal endoscopic lumbar decompression technique is suitable for patients with foraminal stenosis but cannot achieve complete decompression for those with severe ventral central stenosis.The Cross-Overtop technique effectively enlarges the volume of the central canal and lateral recess,optimizing decompression,and shows unique advantages in treating upper lumbar spinal stenosis.

BACKGROUND:Upper lumbar spinal stenosis is a multifactorial degenerative disorder of the spine.For narrowing of the spinal canal in the upper lumbar region(L1-L4),surgical decision-making is particularly complex.Existing minimally invasive surgeries each have their own advantages and limitations.Currently,there are few reports on biomechanical comparison and finite element analysis of different surgical methods for the treatment of high lumbar spinal stenosis.OBJECTIVE:To analyze the biomechanical impact of endoscopic unilateral laminotomy for bilateral decompression,transforaminal endoscopic lumbar decompression,and cross-overtop decompression in the treatment of upper lumbar spinal stenosis using endoscopy,and to verify the reliability and effectiveness of these three surgical techniques in treating upper lumbar spinal stenosis,providing a biomechanical basis for clinical decision-making.METHODS:The CT images of the lumbar spine of a healthy volunteer were selected,and the finite element model M0 of the normal lumbar L1-L5 segments was established using Mimics,Geomagic,Solid works,and Ansys software.The L2-L3 segment,representing upper lumbar characteristics,was chosen.Based on this model,the surgical models for endoscopic unilateral laminotomy for bilateral decompression(M1),transforaminal endoscopic lumbar decompression(M2),and cross-overtop decompression(M3)were established.Using software,the changes in the range of motion of the entire lumbar segment and the maximum Von Mises stress of the intervertebral discs were simulated and evaluated for each group of models under six loading conditions:flexion,extension,left lateral bending,right lateral bending,left rotation,and right rotation.RESULTS AND CONCLUSION:(1)Compared with model MO,the range of motion in M1,M2,and M3 increased under all six conditions,with M1 showing a greater increase.(2)M1 and M2 demonstrated significant increases in range of motion under forward bending,extension,and right rotation,while the increase under other conditions remained below 7％.(3)Compared with model M3,model M1 exhibited slightly increased overall joint range of motion during extension and left bending,while no significant changes were observed in other aspects,and the L1-L5 lumbar segments did not reach an unstable state.(4)In model M1,the maximum Von Mises stress of the intervertebral discs increased most significantly under flexion and extension loading conditions.However,under left lateral bending,right lateral bending,left rotation,and right rotation loading conditions,the increase did not exceed 5％.(5)These findings suggest that due to the sagittal anatomical characteristics of the facet joints,the unilateral laminotomy for bilateral decompression technique,while decompressing,involves resection of more facet joints,which impacts overall segmental stability.The transforaminal endoscopic lumbar decompression technique is suitable for patients with foraminal stenosis but cannot achieve complete decompression for those with severe ventral central stenosis.The Cross-Overtop technique effectively enlarges the volume of the central canal and lateral recess,optimizing decompression,and shows unique advantages in treating upper lumbar spinal stenosis.

Objective To summarize the clinical characteristics and analyze prognostic factors of neuroblastoma (NB) in infants (≤12 months) at a single center. Methods A retrospective analysis was conducted on the clinical data of infant patients (≤12 months) diagnosed with NB and treated between January 2014 and December 2022. Clinical features were analyzed, and comparisons between two sample rates were performed using the χ² test. Univariate prognostic analysis was conducted using the log-rank test, and survival outcomes were analyzed using the Kaplan-Meier method. Results A total of 42 infants (≤12 months) with NB were enrolled. Low-risk patients underwent surgical resection alone; intermediate-risk patients received surgery combined with chemotherapy with or without maintenance therapy; high-risk patients were treated with surgery and chemotherapy with or without maintenance therapy or radiotherapy. The 5-year event-free survival (EFS) rate was (92.7±4.9)%, and the 5-year overall survival rate was (95.2±3.6)%. Only two patients died because of tumor recurrence or progression. Univariate analysis identified MYCN amplification and the initial lactate dehydrogenase (LDH) level ≥ five times the upper limit of the normal were significantly associated with poor prognosis (5-year EFS: 33.3% vs. 97.4% and 60.0% vs. 97.3%, P<0.0001 and P=0.0035). Conclusion Infant NB has a favorable overall prognosis. MYCN amplification and markedly elevated initial LDH are associated with poor outcomes.

Objective To assess the survival vulnerability of Oncomelania hupensis in Jiangxi Province under future climate scenarios, and to identify low-vulnerability areas for its survival in this province. Methods Village-level O. hupensis snail survey and O. hupensis snail control with chemical treatments in Jiangxi Province from 2016 to 2024 were captured from the Parasitic Disease Prevention and Control Information Management System of China Disease Prevention and Control Information System. Climatic data were primarily sourced from the Resource and Environmental Science Data Platform, Chinese Academy of Sciences (http://www.resdc.cn/), including annual average temperature, annual average precipitation, annual accumulated temperature above 10 °C, annual accumulated temperature above 0 °C, annual maximum temperature, annual minimum temperature, and annual average relative humidity, and nineteen bioclimatic variables were downloaded from the WorldClim website (https://www.worldclim.org/), including mean diurnal range, isothermality, temperature seasonality, and so on. Elevation and normalized difference vegetation index were catprued from the Resource and Environmental Science Data Platform, Chinese Academy of Sciences (http://www.resdc.cn/), and distance to rivers was downloaded from the WorldPop website (http://www.worldpop.org), and land use and land cover (LULC) data were downloaded from the Big Earth Data Center, Chinese Academy of Sciences (https://data.casearth.cn/), and nature reserve data were obtained from the China Nature Reserve Specimen Resource Sharing Platform (http://www.papc.cn/). Three Shared Socioeconomic Pathways (SSPs) from the Beijing Climate Center-Climate System Model version 2-Medium Resolution (BCC-CSM2-MR) global climate model were employed as future climate scenarios, including SSP126, SSP245, SSP585, and the biomod2 ensemble model in R package was used to simulate suitable habitats for O. hupensis snails in Jiangxi Province in 2050 and 2070 under these scenarios. A snail survival vulnerability index was constructed based on the area of suitable snail habitats, area covered by snail control through chemical treatment, area covered by nature reserves, and changes in snail habitat fragmentation, and a map of snail survival vulnerability distribution was plotted. Results The real area of snail habitats ranged from 78 486.76 to 85 309.47 hm², and the area of snail control with chemical treatment ranged from 10 138.98 to 13 240.16 hm² in Jiangxi Province from 2016 to 2024. There were 429 to 531 villages detected with snails during the nine-year period, and the number of actually snail-infested villages ranged from 645 to 686. A total of 818 snail-present points and 1 996 snail-absent points were obtained from snail survey records. The best performance of the biomod2 ensemble model was achieved if a weighted mean approach was used as the ensemble strategy, with a true skill statistic value of 0.799 and an area under the receiver operating characteristic curve of 0.957, and modeling identified annual average relative humidity and annual average precipitation as two most influencing climatic variables for snail distribution. Relative to the current areas of suitable snail habitats under present climate conditions, the area of suitable snail habitats was projected to expand by 24.49% to 46.28% in Jiangxi Province under future climate scenarios, and the proportion of nature reserves areas in the areas of suitable snail habitats was projected to decrease slightly from the current 2.77% to approximately 2.52%, while the proportion of areas of snail control through chemical treatment in areas of suitable snail habitats varied from 0.64% to 19.57%, and the percentage of changes in snail habitat fragmentation ranged from 3.86% to 12.23%. Based on these four indicators, the snail survival vulnerability index was estimated to range from –1.96 to 0.62 in Jiangxi Province. The arithmetic mean of the snail survival vulnerability index differed under three SSP scenarios (SSP126, SSP245 and SSP585), with the highest mean value (–0.69) in 2070 under SSP126, and the lowest mean value (–0.78) in 2070 under SSP585. Conclusions The snail survival vulnerability index ranges from –1.96 to 0.62 in Jiangxi Province under future climate scenarios, and the suitable habitats for O. hupensis snails appear an overall tendency towards expansion. Low-vulnerability snail habitats are mainly distributed along the shores of Poyang Lake and the Yangtze River in Jiangxi Province, partially overlapping with nature reserves. Intensified surveillance of O. hupensis snails is recommended in these areas in the future.

OBJECTIVE To provide direction and reference for the adjustment of the discount rate （DR） in China’s pharmacoeconomic guidelines. METHODS Search was conducted on the official websites of the International Society for Pharmacoeconomics and Outcomes Research， health technology assessment agencies in various countries/regions， as well as relevant websites of other upper-middle-income or high-income countries/regions. The recommended DR， adjustment trends， and setting rationales in pharmacoeconomic evaluation guidelines across different countries/regions were then summarized and compared. Based on theoretical derivation and literature analysis， the effects of different DR on the incremental cost-effectiveness ratio （ICER） were examined. RESULTS & CONCLUSIONS Among the 40 included guidelines， the base-case DR ranged from 1.5% to 5%， with 5% being the most common value； the range for sensitivity analysis was 0 to 12%. Thirty-six countries/regions applied the same DR to both costs and health outcomes， while in the Netherlands， Belgium， Poland and Czech Republic， DR for costs was higher than for health outcomes. In recent years， Korea， France and Ireland had lowered their DR in response to economic changes， whereas the Netherlands and Czech Republic had raised their DR for cost. The setting of the DR was primarily based on the public project investment interest rate or referred to recommendations from internationally authoritative institutions and other relevant guidelines. The direction and magnitude of the impact of different DR on the ICER largely depended on the distribution of costs and health outcomes between the intervention and reference measure. The setting and adjustment of DR were closely associated with the economic environment. Based on international experience, the DR in China can be lowered by 0.5% to 1.5%， and localized empirical research can be conducted using internationally common estimation methods.

Objective : To explore the effect and mechanism of CD151 on vascular permeability by regulating vesicle internalization and recycling. Methods: Wild-type mice and CD151 knockout mice were divided into WT-con group, WT-model group, KO-con group and KO-model group, with 6 mice in each group. WT-model group and KO-model group were intraperitoneally injected with LPS to prepare sepsis ALI model, and WT-con group and KO-con group were intraperitoneally injected with phosphate buffer saline(PBS) as a control. 24 h after modeling, pulmonary vascular permeability was measured by Miles test. The siRNA silencing CD151 expression(si-CD151) and negative control si-NC were transfected into EA.hy 926 cells. The permeability of endothelial cell layer to FITC-dextran at different time points was observed under basic conditions and vascular endothelial growth factor-A(VEGF-A) stimulation conditions. Transcriptome sequencing of endothelial cells in si-CD151 group and si-NC group; the distribution and internalization of CD151 in each group were measured using immunofluorescence. Western blot and real-time quantitative RT-qPCR were used to detect the expression of VE-cadherin in si-CD151 groupand other groups. The distribution and internalization of VE-cadherin in each group were measured using immunofluorescence. Results : Miles experiment results indicated that dye exudation in lung tissue of WT-model group was significantly higher than that of WT-con group(P<0.01). The dye exudation in the lung tissue of KO-model group increased compared with WT-model group(P<0.05). The results of endothelial cell layer permeability test showed that the permeability of FITC-dextran in si-CD151 group was significantly higher than that in control group after VEGF-A stimulation for 30, 60 and 120 min(P<0.05). Transcriptome sequencing results suggested that CD151 in endothelial cells was closely related to vesicle-mediated transport. Compared with other groups, protein and mRNA levels of VE-cadherin in CD151 knockdown endothelial cells was significantly lower(allP<0.01). The immunofluorescence assay demonstrated that after VEGF-A stimulation, the decrease of CD151 expression significantly impaired the expression of VE-cadherin at cell-cell contacts and reduced the CD151-VE-cadherin colocalization in the perinuclear region compared with other groups. Conclusion The absence of CD151 affects the internalization and recycling of endothelial cell vesicles, affects the expression and internalization of VE-cadherin, and then influences vascular permeability.