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.

Neonatal diabetes mellitus （NDM） is a rare monogenic disorder primarily caused by insufficient insulin secretion resulting from mutations in the KCNJ11 and ABCC8 genes. Sulfonylureas， represented by glibenclamide， have become the standard therapy for this type of NDM by precisely closing the mutated ATP-sensitive potassium channels in pancreatic β cells， thereby restoring insulin secretion. Clinical studies confirm that sulfonylureas enable over 90% of patients to successfully transition from insulin to oral treatment， achieving long-term stable glycemic control and improving neurological outcomes to a certain extent. In terms of safety， severe hypoglycemia induced by sulfonylureas is relatively rare and gastrointestinal reactions are mild； moreover， sulfonylureas show good long-term tolerability， and have no adverse effects on child growth and development. In the future， by further refining the full-chain management pathway of “rapid genetic diagnosis-early intervention-specialized dosage forms-long-term follow-up”， the clinical application of sulfonylureas is expected to provide NDM patients with an optimized treatment regimen and maximize their health benefits.

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 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.

To analyze the disease burden, temporal trends, and attributable risk factors of early-onset female breast cancer (EOBC) in China and globally from 1990 to 2021.

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.

Objective To investigate the prognostic value of optic nerve sheath diameter(ONSD)measured by critical care ultrasound combined with serum biomarkers[S100 calcium-binding protein β(S100β)and neuron-specific enolase(NSE)]in patients with severe traumatic brain injury.Methods A total of 103 adult severe traumatic brain injury patients admitted to the intensive care unit of this hospital from A-pril 1,2023,to April 1,2024 were enrolled.All patients underwent invasive intracranial pressure monitoring after admission,alongside bedside critical care ultrasound measurement of ONSD at 3 mm behind the globe and serum biomarker testing.Baseline data and Glasgow outcome scale(GOS)scores at 90 days after dis-charge were recorded.Patients were divided into the survival and the non-survival groups based on GOS scores.Receiver operating characteristic(ROC)curve analysis and area under the curve(AUC)were used to evaluate the predictive performance of ONSD and serum biomarkers for poor prognosis in severe traumatic brain injury patients.Results Ninety-six patients were ultimately included,with 52(54.1％)in the survival group and 44(45.9％)in the non-survival group.Significant differences were observed in blood glucose,Glas-gow coma scale(GCS)score,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score,ONSD,NSE,and S100β levels(P＜0.05)between the two groups.Multivariate analysis identified ONSD(OR=4.962,95％CI:3.473-6.254),NSE(OR=2.704,95％CI:1.987-3.033),S100β(OR=2.983,95％CI:1.843-4.571),and APACHE Ⅱ score(OR=3.726,95％CI:2.837-4.592)as independent predictors of mortality in severe traumatic brain injury patients(P＜0.05).The combination of ONSD,NSE,and S100β yielded an AUC of 0.840 for predicting poor prognosis,with a specificity of 88.3％and sensitivity of 98.6％.Conclusion ONSD and serum brain injury biomarkers(NSE,S100β)are associated with in-hospital prognosis in severe traumatic brain injury patients.Their combined detection can effectively predict a poor outcome.

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.