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

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.

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.

To explore the effects of different blood loss on liver and kidney function,blood lactic acid levels,and oxidative stress indexes after hemorrhagic shock resuscitation in dogs,10 healthy Chinese rural dogs were randomly divided into 1.5 h blood loss resuscitation group(HSRA group)and 3.5 h blood loss resuscitation group(HSRB group).The changes in liver and kidney function,blood lactic acid,and oxidative stress-related indexes were detected at 2,6,24,48 and 72 h after re-suscitation.The results showed that the liver function indexes of TBIL,ALT,and AST in the HSRB group were higher than those in the HSRA group at each time point after resuscitation.There was no significant change in renal function indexes between the two groups.The level of Lac in the HSRB group was significantly higher than that in the HSRA group at 2 and 6 h after resuscitation.CAT activity in the HSRB group was significantly lower than that in the HSRA group at 2 h after resuscitation.GSH-px activity in the HSRB group was significantly lower than that in the HSRA group at 2,6 and 24 h after resuscitation.SOD activity in the HSRB group was significantly lower than that in the HSRA group at 24 h after resuscitation.MDA content in the HSRB group was sig-nificantly higher than that in the HSRA group at 2,6,24 and 48 h after resuscitation.The results showed that HS could cause liver injury and oxidative stress after resuscitation,and the degree of liver injury and oxidative stress injury in dogs increased with the prolongation of blood loss.

Objective:To explore the molecular mechanism by which interferon regulatory factor 1 (IRF1) affects hepatic ischemia-reperfusion injury (HIRI) by regulating the polarization of Kupffer cells.Methods:Twelve male healthy C57BL/6 wild-type mice weighing 20-25 g and aged 6-8 weeks were divided into a sham operation group ( n=6) and a HIRI group ( n=6); Twelve male healthy C57BL/6 IRF1 gene knockout (IRF1 -/-) mice weighing 20-25 g and aged 6-8 weeks were divided into a sham operation IRF1 -/- group ( n=6) and a HIRI IRF1 -/- group ( n=6). The levels of serum alanine transaminase (ALT) and aspartate transaminase (AST) in mice were measured, and hematoxylin-eosin (HE) staining of liver tissues was performed for Suzuki scoring to evaluate liver injury. Fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to evaluate the mRNA levels of IRF1 and tumor necrosis factor α (TNFα) in liver tissues. Flow cytometry and qRT-PCR were used to detect the proportion and functional changes of M1/M2-type Kupffer cells in liver tissues. IRF1 was overexpressed or knocked down in the mononuclear macrophage cell line ANA1, and a co-culture and hypoxia-reoxygenation system with the hepatocyte cell line AML12 was established. Flow cytometry was used to detect the apoptosis of AML12 cells. Results:At 12 hours after hepatic ischemia-reperfusion in wild-type mice, the liver tissue injury was the most severe. Compared with the sham operation group, the levels of serum ALT [(8 073±83) U/L vs. (81±19) U/L, q=13.59] and AST [(11 170±2 890) U/L vs. (412±210) U/L, q=13.77] in the HIRI group were significantly higher, and the differences were statistically significant (both P<0.001). The Suzuki score reached 5-6 points. At 12 hours after hepatic ischemia-reperfusion in IRF1 gene knockout mice, the liver tissue injury was not obvious. There were no significant differences in the levels of serum ALT [668 (514, 2 344) U/L vs. 254 (147, 285) U/L, q=2.52, P=0.348] and AST [1 936 (1 262, 2 003) U/L vs. 628 (423, 759) U/L, q=1.22, P=0.824] between the HIRI IRF1 -/- group and the sham operation IRF1 -/- group. Compared with the HIRI group, the ratio of M1/M2-type Kupffer cells in the liver of the HIRI IRF1 -/- group decreased [(0.958±0.090) vs. (2.788±0.258), q=2.06, P<0.0001], and the mRNA expression of TNFα decreased [(4.363±0.393) vs. (12.900±5.504), q=5.59, P=0.018], and the differences between the two groups were statistically significant. In the co-culture and hypoxia-reoxygenation experiment using ANA1 cells overexpressing IRF1 and AML12 cells, the proportion of AML12 hepatocytes in late apoptosis was higher than that in the control group [(14.05±4.25) vs. (3.15±1.16), t=2.85, P=0.047], and the difference was statistically significant. In contrast, when the expression of IRF1 was knocked down, the proportion of apoptotic AML12 cells decreased [(9.26±3.04) vs. (13.36±4.64), t=2.15, P=0.098], but the difference was not statistically significant. Conclusion:The IRF1 protein can regulate the polarization of Kupffer cells into M1-type macrophages, promote the inflammatory injury of the liver tissue after ischemia-reperfusion, and increase the apoptosis of hepatocytes.

Objective:To compare the efficacy of closed reduction and internal fixation combined with percutaneous kyphoplasty (PKP) and non-operative treatment for intertrochanteric fracture combined with osteoporotic vertebral compression fracture (OVCF) in the elderly.Methods:A retrospective cohort study was conducted to analyze the clinical data of 59 patients with intertrochanteric fracture combined with OVCF admitted to Tianjin Hospital from June 2020 to June 2023, including 16 males and 43 females, aged 66-91 years [(80.2±6.8)years]. The injured vertebral segments included T 10 in 3 patients, T 11 in 9, T 12 in 18, L 1 in 17, L 2 in 8, and L 3 in 4. According to the Genant semi-quantitative classification of vertebral fracture, 42 patients were scaled into grade 1 and 17 into grade 2. Based on the AO classification of intertrochanteric fracture, 33 patients were classified as type A1, 21 type A2, and 5 type A3. All the patients underwent closed reduction and internal fixation for intertrochanteric fractures, among whom 26 patients received PKP after the internal fixation of OVCF (PKP group) and 33 patients received non-surgical treatment after the internal fixation of OVCF (non-surgical group). The healing of the hip incision at 2 weeks after internal fixation and the healing of intertrochanteric fractures at 6 months after surgery were observed in both groups. The visual analogue scale (VAS) for low back pain was compared between the two groups before PKP, immediately after PKP, at 3 months after PKP, and at the last follow-up. The Oswestry disability index (ODI), anterior vertebral height ratio, and Cobb angle of the injured vertebrae were compared between the two groups before PKP, at 3 months after PKP, and at the last follow-up. The Harris hip function score was compared between the two groups at 3 months after internal fixation and at the last follow-up. Cement leakage was observed. The incidence of deep vein thrombosis (DVT) in the lower extremities after internal fixation were compared between the two groups. Results:All the patients were followed up for 10-46 months [(25.5±9.9)months]. The hip incisions of both groups all healed by first intention at 2 weeks after internal fixation, and the intertrochanteric fracture in both groups had bony union at 6 months after surgery. There were no significant differences between the two groups in VAS or ODI before PKP ( P>0.05). Immediately after PKP, at 3 months after PKP, and at the last follow-up, the VAS scores for low back pain were (2.6±0.6)points, (2.4±0.9)points, and (1.5±0.5)points in the PKP group, which were lower than those in the non-surgical group [(8.2±0.8)points, (3.7±1.2)points, and (3.3±0.6)points] ( P<0.01). At 3 months after PKP and at the last follow-up, the ODI values were (21.4±6.9)% and (16.2±6.3)% in the PKP group, which were lower than (38.6±11.6)% and (32.7±12.0)% in the non-surgical group ( P<0.01). The VAS for low back pain and ODI in both groups were gradually improved at each time point after PKP compared with those before PKP ( P<0.05 or 0.01). There were no significant differences in the anterior vertebral height ratio or Cobb angle of the injured vertebrae in the two groups before PKP ( P>0.05). At 3 months after PKP and at the last follow-up, the anterior vertebral height ratio was (79.8±9.6)% and (79.3±9.4)% in the PKP group, which were higher than (73.4±9.3)% and (62.0±10.4)% in the non-surgical group ( P<0.05 or 0.01); the values of the Cobb angle of the injured vertebrae were (12.6±3.6)° and (12.0±3.3)°in the PKP group, which were lower than (15.5±2.6)° and (20.4±4.9)° in the non-surgical group ( P<0.01). There were no significant differences in the anterior vertebral height ratio and Cobb angle of the injured vertebrae in the PKP group before PKP and at each time point after PKP ( P>0.05) while in the non-surgical group, the anterior vertebral height ratio at each time point after PKP was lower than that before PKP and the Cobb angle of the injured vertebrae was increased compared with that before PKP ( P<0.01). At 3 months after internal fixation and at the last follow-up, the Harris hip function scores in the PKP group were (76.4±3.4)points and (87.7±4.5)points, which were higher than (57.0±6.8)points and (76.3±8.9)points in the non-surgical group ( P<0.01). The Harris hip function scores in both groups were improved at the last follow-up, compared with those at 3 months after internal fixation. Five patients had cement leakage in the PKP group, all of which were lateral leakage.There was no occurrence of radiating pain in the lower extremities. The incidence of DVT at 1 month after internal fixation was 19.2% (5/26) in the PKP group, which was lower than 57.6% (19/33) in the non-surgical group ( P<0.01). Conclusion:Compared with non-operative treatment after the closed reduction and internal fixation, PKP after internal fixation can significantly relieve low back pain in the early stage, improve the functional restoration of the vertebral column, maintain vertebral height, prevent kyphosis, promote the recovery of the hip joint function, and reduce the occurrence of DVT in the lower extremities in the treatment of intertrochanteric fracture combined with OVCF.

In this paper, the causes of dimethylacetamide poisoning in a small and micro enterprise were analyzed through on-site occupational health investigation, clinical data summary of poisoned patients and occupational hazard factors detection results. The incident was a group poisoning incident caused by exposure to dimethylacetamide, resulting in different degrees of toxic liver disease in 6 workers. Although the concentration of dimethylacetamide in the air in the workplace was excessive, percutaneous absorption may be the main cause of poisoning. The characteristics of percutaneous absorption of dimethylacetamide need to be paid great attention to, which can be used for reference to prevent similar incidents in the future.

Objective:To evaluate the efficacy of an etoposide (Vp16) -intensified conditioning regimen in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of relapsed/refractory acute myeloid leukemia (AML).Method:A retrospective analysis was conducted on the clinical data of 27 recipients with relapsed/refractory AML who underwent allo-HSCT using a Vp16-intensified conditioning regimen at Aerospace Center Hospital from January 2019 to January 2022. Transplantation-related complications and treatment outcomes were observed. Kaplan-Meier survival analysis was used to assess the overall survival (OS) and disease-free survival (DFS) rates.Result:Among the 27 recipients, there were 14 males and 13 females, with a median age of 41 years (range: 12~55 years). Except for one recipient who experienced primary graft failure, the remaining 26 recipients achieved hematopoietic reconstitution. The median neutrophil and platelet engraftment times were 13 days (range: 9~20 days) and 13.5 days (range: 11~33 days), respectively. Regimen-related toxicity (RRT) was mainly gastrointestinal toxicity and oral mucositis, and no deaths were attributed to RRT. A total of 12 recipients (44.44%) developed acute graft-versus-host disease (aGVHD), of whom 3 cases (11.11%) had grade III~IV aGVHD. Chronic GVHD (cGVHD) occurred in 13 recipients (48.15%), including 8 cases (29.63%) of extensive cGVHD. The median follow-up time after transplantation was 17 months (range: 1~48 months). Fifteen recipients (55.56%) survived without disease, while 12 recipients (44.44%) died— 9 due to relapse and 3 due to transplant-related complications. The 1-year overall survival and DFS rates were 74.07% and 59.26%, respectively; the 2-year overall survival and DFS rates were 59.26% and 55.56%, respectively. The 2-year relapse rate and transplant-related mortality (TRM) were 33.33% and 11.11%, respectively.Conclusion:The Vp16-intensified conditioning regimen in allo-HSCT appears to be a viable treatment option for patients with relapsed/refractory AML, offering favorable efficacy and manageable safety.