Hilar cholangiocarcinoma is insidious in onset and often causes obstructive jaundice due to bile stasis,leading to impaired liver function.For tumors with malignant obstructive jaundice,biliary drainage is often performed before surgery in clinical practice.Currently,the commonly used drainage methods are percutaneous transhepatic biliary drainage(PTBD)and endoscopic retrograde biliary drain-age(ERBD),but there are controversies over the advantages and disadvantages of the two drainage methods.PTBD drainage can often lead to tumor implantation metastasis,but the underlying mechanism remains unclear.We detected tumor cells in PTBD and ERBD bile samples from hilar cholangiocarcino-ma patients,subsequently explored their tumorigenicity and mechanisms through tumorsphere assay in vitro and xenograft tumor models in vivo.The experiments included benign gallstones group(30 cases)as a negative control,PTBD group(14 cases)and ERBD group(13 cases).Tumorsphere formation was i-dentified in 3 cases(23％)among the 13 cases of ERBD group,in 6 cases(42％)among the 14 cases of PTBD group,but there were no tumor cells or formed tumorspheres in the 30 cases of benign gallstone group.The tumor sphere formation ability of cells in the PTBD group was significantly higher than that in ERBD group.Subcutaneous xenograft tumor assays showed that tumor growth in the PTBD group was sig-nificantly higher than that in the ERBD group.Tumor cells in PTBD bile possessed stronger tumorigenici-ty compared with the ERBD group.Mechanically,stem cell transcription factor Nanog mRNA levels were significantly higher in the PTBD group compared to the ERBD group.Both tumorsphere formation and xenograft tumor growth were reduced by Nanog knockdown in three cases of the PTBD group,indicating the important roles of Nanog in tumorigenicity of PTBD group tumor cells.The half-life of Nanog mRNA was longer in PTBD group cells than in ERBD group cells,suggesting potential post-transcriptional regu-lation on Nanog mRNA.The Nanog m6A level was higher in PTBD group tumor cells compared to the ERBD group.Analysis of methyltransferases and demethylases,ALKBH5(α-ketoglutarate dependent dioxygenase alkb family homolog 5)mRNA levels were lower in the PTBD group than in the ERBD group and significantly correlated with the m6A level of Nanog.ALKBH5 knockdown led to an increase in the m6A level of Nanog,while ALKBH5 overexpression decreased the m6A level of Nanog.Dual-luciferase activity assays demonstrated that ALKBH5 knockdown significantly enhanced luciferase activity,whereas ALKBH5 overexpression reduced it.Further studies confirmed that ALKBH5 knockdown upregulated both the mRNA and protein levels of Nanog,whereas overexpressing ALKBH5 downregulated them.ALKBH5 mediated the demethylation modification of Nanog mRNA,and the lower levels of ALKBH5 expression in the PTBD group promoted Nanog's m6A modification.Overexpressing ALKBH5 decreased tumorsphere growth,while ALKBH5 knockdown increased it,which was subsequently reduced by the simultaneous Nanog knockdown again.In sum,tumor cells in PTBD and ERBD drainage bile from hilar cholangiocar-cinoma patients exhibited tumorigenicity.Compared to the ERBD group,tumor cells in PTBD bile with lower ALKBH5 expression levels enhanced Nanog's m6A modification to upregulate Nanog expression levels,resulting in stronger tumorigenicity.These findings are significant for elucidating propensity to tumor implantation metastasis from PTBD drainage.

Objective:To establish venetoclax-resistant acute myeloid leukemia(AML)cell lines,assess the sensitivity of venetoclax-resistant cell lines to the BCL-2 protein family,and investigate their resistance mechanisms.Methods:CCK-8 method was used to screen AML cell lines(MV4-11,MOLM13,OCI-AML2)that were relatively sensitive to venetoclax.Low concentrations of venetoclax continuously induced drug-resistance development in the cell lines.Changes in cell viability and apoptosis rate before and after resistance development were measured using the CCK-8 method and flow cytometry.BH3 profiling assay was performed to anayze the transform of mitochondrion-dependent apoptosis pathway as well as the sensitivity of resistant cell lines to BCL-2 family proteins and small molecule inhibitors.Real-time fluorescence quantitative PCR(RT-qPCR)was utilized to examine changes in the expression levels of BCL-2 protein family members in both venetoclax-resistant cell lines and multidrug-resistant patients.Results:Venetoclax-resistant cell lines of MV4-11,MOLM13,and OCI-AML2 were successfully established,with IC50 values exceeding 10-fold.Under the same concentration of venetoclax,the apoptosis rate of resistant cells decreased significantly(P＜0.05).BH3 profiling assay revealed that the drug-resistant cell lines showed increased sensitivity to many pro-apoptotic proteins(such as BIM,BID and NOXA).RT-qPCR showed significantly upregulated MCL1 and downregulated NOXA1 were detected in drug-resistant cell lines.Expression changes in MCL1 and NOXA1 in venetoclax-resistant patients were consistent with our established drug-resistant cell line results.Conclusion:The venetoclax-resistant AML cell lines were successfully established through continuous induction with low concentrations of venetoclax.The venetoclax resistance resulted in alterations in the mitochondrial apoptosis pathway of the cells and an increased sensitivity of cells to pro-apoptotic proteins BIM,BID,and NOXA,which may be associated with the upregulation of MCL1 expression and downregulation of NOXA1 expression in the drug-resistant cells.

Objective:To compare the efficacy of O-arm navigation versus C-arm guidance for anterior internal fixation in the management of Anderson-D′Alonzo type II odontoid fractures.Methods:A retrospective cohort study was conducted to analyze the clinical data of 58 patients with Anderson-D′Alonzo type II odontoid fractures admitted to Zhengzhou Orthopedic Hospital between January 2017 and September 2024, including 35 males and 23 females, aged 18-57 years [(39.3±9.0)years]. Anderson-D′Alonzo type II fractures were further classified as type IIA in 25 patients and type IIB in 33. Twenty-seven patients underwent O-arm assisted anterior internal fixation (O-arm navigation group), while 31 received C-arm guided anterior internal fixation (C-arm guidance group). The two groups were compared in terms of the operative duration, intraoperative blood loss, success rate for one-time guidewire placement, and intraoperative radiation exposure (anteroposterior and lateral views). At 3 days postoperatively, screw placement accuracy was evaluated via CT in both groups. Additionally, neck disability index (NDI) and visual analogue scale (VAS) scores were assessed preoperatively, at 1 week, 3 months postoperatively, and at the last follow-up. Bone union time and complication rate were also analyzed.Results:All the patients were followed up for 6-20 months [(13.1±3.4)months]. The O-arm navigation group exhibited significantly shorter operative duration [(91.1± 8.9)minutes] and less intraoperative blood loss [(38.9±8.2)ml], compared with (103.3±14.5)minutes and (47.3±9.1)ml in the C-arm guidance group ( P<0.01). The success rate for one-time guidewire placement was 100% (27/27) in the O-arm navigation group, significantly higher than 52% (16/31) in the C-arm guidance group ( P<0.01). Intraoperative radiation exposure for patients in the O-arm navigation group was lower in both anteroposterior view [(11 612.6±1 603.6)μSv] and lateral views [(29 738.2±6 602.5)μSv], compared with (40 638.0±9 431.9)μSv and (47 152.0±11 759.3)μSv in the C-arm guidance group ( P<0.01). CT scans at 3 days postoperatively revealed a 100% (27/27) screw placement accuracy in the O-arm navigation group, compared with 65% (20/31) in the C-arm guidance group ( P<0.01). Before operation, at 1 weeks and 3 months postoperatively, and at the last follow-up, NDI scores were (48.4±7.8)%, (21.0±3.1)%, (14.4±2.4)%, and (13.9±2.3)% in the O-arm navigation group, while they were (47.4±7.6)%, (20.9±3.2)%, (14.1±2.0)%, and (13.8±1.4)% in the C-arm guidance group ( P>0.05); VAS scores were 6.0(6.0, 7.0)points, 4.0(3.0, 4.0)points, 2.0(1.0, 2.0)points, and 2.0(1.0, 2.0)points in the O-arm navigation group, while they were 7.0(6.0, 7.0)points, 4.0(3.0, 5.0)points, 2.0(1.0, 3.0)points, and 2.0(2.0, 2.0)points in the C-arm guidance group ( P>0.05). The NDI and VAS scores in both groups were significantly improved at 1 weeks and 3 months postoperatively, and at the last follow-up compared to those preoperatively ( P<0.05), and were furtherly improved at 3 months postoperatively and at the last follow-up compared to those at 1 weeks postoperatively ( P<0.05), with no significant differences between those at 3 months postoperatively and at the last follow-up ( P>0.05). No significant difference was found in bone union time between the two groups ( P>0.05). The complication rate in the O-arm navigation group was 4% (1/27), lower than 29% (9/31) in the C-arm guidance group ( P<0.05). Conclusions:Compared with C-arm guidance, O-arm assisted anterior internal fixation for Anderson-D′Alonzo type II odontoid fractures can reduce operative duration and intraoperative blood loss, improve the success rate for one-time guidewire placement and screw accuracy, and decrease radiation exposure and complication rate.

Aim Mouse model of myocardial hypertro-phy was established via intraperitoneal injection of iso-proterenol(ISO)in mice.This approach allows for an in-depth investigation into the pharmacological effects and mechanisms of action of emodin,offering novel in-sights and directions for the improvement of myocardial hypertrophy.Methods The mice were randomly di-vided into the following groups:control group(CON),emodin group(EMO),MAPK activator control group(EMO+Ani),model group(ISO),treatment group(ISO+EMO),and activator intervention group(ISO+EMO+Ani).After treatment with emodin and inter-vention with MAPK activator,the heart weight ratio and cardiac size of each group were observed.Hematoxy-lin-eosin(HE)staining was used to observe the patho-logical changes in cardiac tissue,and kits were utilized to measure the levels of GSH,LDH,and MDA in the serum.Western blot was employed to detect the protein expression levels of inflammatory and oxidative factors,as well as p-p38,p-ERK,p38,and ERK in cardiac tis-sue.Results Emodin can significantly inhibit the production of myocardial inflammatory and oxidative factors induced by ISO,thereby effectively alleviating the degree of myocardial hypertrophy and fibrosis.Af-ter the p38/ERK signaling pathway was specifically ac-tivated by farnesol,the improvement effect of emodin on myocardial hypertrophy was weakened.Further comparison revealed that,compared with the myocardi-al hypertrophy pathological model group,the pathologi-cal protein expression levels in the farnesol-treated group showed no significant difference,and were even higher in some indicators.Conclusion Emodin can effectively inhibit the release of inflammatory factors and improve the state of oxidative stress by modulating the p38/ERK signaling pathway,thereby exerting an ameliorative effect on myocardial hypertrophy.

Objective To construct a clinical-radiological nomo-gram model for severe mycoplasma pneumoniae pneumonia coinfec-tion with other pathogens(Co-SMPP)in children.Methods The clinical and radiological data of children with severe mycoplasma pneumoniae pneumonia(SMPP)who underwent nucleic acid testing or bronchoalveolar lavage(BAL)were analyzed retrospectively.The data analysis were performed by using SPSS 27.0 software.The group comparison between simple SMPP and Co-SMPP children was conducted by using t-tests,Mann-Whitney U tests,or chi-square tests.Nomogram analysis was performed by using R software and rms packages.The predictive performance of the model was evaluated by using the receiver operating characteristic(ROC)curve.Results A total of 194 SMPP children were included in the study,including 136 cases(70.1％)with simple SMPP,58 cases(29.9％)with Co-SMPP.The fibrinogen and albumin levels were lower in Co-SMPP children[(3.53±0.85)g/L,41.00(39.03,43.68)g/L]than in simple SMPP children[(3.79±0.80)g/L,42.80(41.00,44.40)g/L],with P values of 0.047 and 0.036,respec-tively.The probability of bronchial stenosis and grid shadow were higher in Co-SMPP children than in simple SMPP children,and there were significant differences between the two groups(P＜0.001,P=0.010).The odds ratio of bronchial stenosis in predicting Co-SMPP children was 14.085.The clinical-radiological nomogram model had an area under the curve(AUC)of 0.840,with sensi-tivity and specificity of 0.756 and 0.848,respectively.Conclusion The nomogram model based on clinical-radiological features can effectively predict Co-SMPP.

Objective:To investigate the feasibility and clinical efficacy of percutaneous vertebroplasty (PVP) with measured saturated bone cement injection in the treatment of elderly patients with stage Ⅱ Kümmell's disease.Methods:A retrospective analysis was conducted to analyze the clinical data of the 41 elderly patients with stage Ⅱ Kümmell's disease who had been treated at Department of Spinal Orthopedics, Zhengzhou Orthopedic Hospital from June 2017 to June 2023 by PVP with bone cement injection into the intravertebral vacuum cleft. According to the amount of bone cement injected, the patients were divided into a saturated volume group (bone cement injection metered ≥ 150% of the cleft volume preoperatively measured) in which there were 21 cases, 4 males and 17 females, aged (78.4±5.2) years and a conventional volume group (bone cement injection metered was 100% to 120% of the cleft volume preoperatively measured) in which there were 20 cases, 6 males and 14 females, aged (79.5±7.4) years. The operative time, vacuum cleft volume measured, actual volume of bone cement injected, and percentage of bone cement injected were compared between the 2 groups. Visual analogue scale (VAS) for pain and Oswestry disability index (ODI) were compared between preoperation, postoperative 3 days, and the final follow-up in the 2 groups, as well as between the 2 groups. Cement leakage and other complications were documented.Results:The differences in the preoperative general data were not statistically significant between the 2 groups, indicating comparability ( P>0.05). All the 41 elderly patients successfully completed their surgery. Follow-up time was (18.1±3.3) months. The operative time [(39.7±7.5) min], actual volume of bone cement injected [(5.6±0.9) mL], and percentage of bone cement injected (1.8%±0.3%) in the saturated volume group were all significantly greater than those in the conventional volume group [(35.5±4.9) min, (4.4±1.0) mL, and 1.2%±0.1%] ( P<0.05). Postoperatively, the incisions healed completely in all patients, with no such complications as cement-related adverse reactions. Cement leakage occurred in 2 patients in the conventional volume group, leading to lumbar pain or discomfort after activity, which was relieved by cement reinforcement and nail-rod internal fixation. VAS pain scores and ODIs at 3 d postoperatively and at the final follow-up were significantly improved in all patients compared with preoperation ( P<0.05). At the final follow-up, both VAS pain score and ODI in the saturated volume group improved significantly greater than those in the conventional volume group ( P<0.05). None of the patients had complications like cement displacement at the final follow-up. Conclusion:PVP with measured saturated bone cement injection into the intravertebral vacuum clefts is a safe and effective treatment for stage Ⅱ Kümmell's disease in elderly patients, offering a new minimally invasive option.

Drug resistance is one of the key factors affecting the effectiveness of cancer treatment methods, including chemotherapy, radiotherapy, and immunotherapy. Its occurrence is related to factors such as mRNA expression and methylation within cancer cells. If drug resistance in patients can be accurately identified early, doctors can devise more effective treatment plans, which is of great significance for improving patients' survival rates and quality of life. Cancer drug resistance prediction based on artificial intelligence (AI) technology has emerged as a current research hotspot, demonstrating promising application prospects in guiding clinical individualized and precise medication for cancer patients. This review aims to comprehensively summarize the research progress in utilizing AI algorithms to analyze multi-omics data including genomics, transcriptomics, epigenomics, proteomics, metabolomics, radiomics, and histopathology, for predicting cancer drug resistance. It provides a detailed exposition of the processes involved in data processing and model construction, examines the current challenges faced in this field and future development directions, with the aim of better advancing the progress of precision medicine.

In the 1950s and 1960s,Japan's implementation of policies prioritizing economic develop-ment caused a lack of effective supervision over the discharge of industrial wastewater and exhaust gases,which led to the occurrence of the"Four Major Pollution Diseases",including Minamata disease,causing serious social and public health problems.To more effectively address public nuisances and pro-vide compensation to victims,the Japanese government gradually established an environmental damage compensation system with administrative relief characteristics since the 1970s.Through long-term prac-tice and system optimization,this system has evolved into a mature institutional framework with a clear division of labor and efficient collaboration.This paper systematically reviews the development process of Japan's environmental damage compensation system and deeply analyzes its legal frame-work and supporting policies,aiming to provide useful references for the construction and improve-ment of China's environmental damage compensation system.Meanwhile,through the case analysis of Minamata disease,the paper explores the specific mechanisms and effects in the compensation practices,further revealing the system's operational characteristics and implications,and providing a reference ba-sis for the construction of China's environmental governance legal system.

Objective:To compare the efficacy of O-arm navigation versus C-arm guidance for anterior internal fixation in the management of Anderson-D′Alonzo type II odontoid fractures.Methods:A retrospective cohort study was conducted to analyze the clinical data of 58 patients with Anderson-D′Alonzo type II odontoid fractures admitted to Zhengzhou Orthopedic Hospital between January 2017 and September 2024, including 35 males and 23 females, aged 18-57 years [(39.3±9.0)years]. Anderson-D′Alonzo type II fractures were further classified as type IIA in 25 patients and type IIB in 33. Twenty-seven patients underwent O-arm assisted anterior internal fixation (O-arm navigation group), while 31 received C-arm guided anterior internal fixation (C-arm guidance group). The two groups were compared in terms of the operative duration, intraoperative blood loss, success rate for one-time guidewire placement, and intraoperative radiation exposure (anteroposterior and lateral views). At 3 days postoperatively, screw placement accuracy was evaluated via CT in both groups. Additionally, neck disability index (NDI) and visual analogue scale (VAS) scores were assessed preoperatively, at 1 week, 3 months postoperatively, and at the last follow-up. Bone union time and complication rate were also analyzed.Results:All the patients were followed up for 6-20 months [(13.1±3.4)months]. The O-arm navigation group exhibited significantly shorter operative duration [(91.1± 8.9)minutes] and less intraoperative blood loss [(38.9±8.2)ml], compared with (103.3±14.5)minutes and (47.3±9.1)ml in the C-arm guidance group ( P<0.01). The success rate for one-time guidewire placement was 100% (27/27) in the O-arm navigation group, significantly higher than 52% (16/31) in the C-arm guidance group ( P<0.01). Intraoperative radiation exposure for patients in the O-arm navigation group was lower in both anteroposterior view [(11 612.6±1 603.6)μSv] and lateral views [(29 738.2±6 602.5)μSv], compared with (40 638.0±9 431.9)μSv and (47 152.0±11 759.3)μSv in the C-arm guidance group ( P<0.01). CT scans at 3 days postoperatively revealed a 100% (27/27) screw placement accuracy in the O-arm navigation group, compared with 65% (20/31) in the C-arm guidance group ( P<0.01). Before operation, at 1 weeks and 3 months postoperatively, and at the last follow-up, NDI scores were (48.4±7.8)%, (21.0±3.1)%, (14.4±2.4)%, and (13.9±2.3)% in the O-arm navigation group, while they were (47.4±7.6)%, (20.9±3.2)%, (14.1±2.0)%, and (13.8±1.4)% in the C-arm guidance group ( P>0.05); VAS scores were 6.0(6.0, 7.0)points, 4.0(3.0, 4.0)points, 2.0(1.0, 2.0)points, and 2.0(1.0, 2.0)points in the O-arm navigation group, while they were 7.0(6.0, 7.0)points, 4.0(3.0, 5.0)points, 2.0(1.0, 3.0)points, and 2.0(2.0, 2.0)points in the C-arm guidance group ( P>0.05). The NDI and VAS scores in both groups were significantly improved at 1 weeks and 3 months postoperatively, and at the last follow-up compared to those preoperatively ( P<0.05), and were furtherly improved at 3 months postoperatively and at the last follow-up compared to those at 1 weeks postoperatively ( P<0.05), with no significant differences between those at 3 months postoperatively and at the last follow-up ( P>0.05). No significant difference was found in bone union time between the two groups ( P>0.05). The complication rate in the O-arm navigation group was 4% (1/27), lower than 29% (9/31) in the C-arm guidance group ( P<0.05). Conclusions:Compared with C-arm guidance, O-arm assisted anterior internal fixation for Anderson-D′Alonzo type II odontoid fractures can reduce operative duration and intraoperative blood loss, improve the success rate for one-time guidewire placement and screw accuracy, and decrease radiation exposure and complication rate.

Objective:To analyze the clinical efficacy of asymmetric T 1 transpedicular wedge resection Smith-Petersen osteotomy (T 1 SPO) in the treatment of stiff cervical thoracic lateral kyphosis deformity. Methods:This is a retrospective case series study. The clinical data of nine patients with stiff cervical thoracic kyphosis who underwent asymmetric T 1 SPO corrective treatment from June 2012 to October 2022 were collected. There were 7 males and 2 females, aged 45 to 68 years. The surgery time, intraoperative blood loss, and complications were recorded. The chin brow vertical angle (CBVA), cervical thoracic kyphosis Cobb angle, cervical thoracic scoliosis Cobb angle, and cervical thoracic sagittal axis (C 2-T 1 sagittal vertical axis, SVA) before surgery, after surgery, and at the last follow-up were measured and the correction rates were calculate. Results:All 9 patients successfully completed the surgery. The operation time ranged from 245 to 320 minutes, and the intraoperative blood loss was 1 400 to 2 200 ml. All patients were followed up for 24 to 48 months. The preoperative CBVA was 93.7° to 112.0°, which improved to 25.2° to 31.7° at the last follow-up, with an correction rate of 73.4%. The preoperative cervicothoracic kyphosis Cobb angle was -57.0° to -16.6°, which improved to 10.3° to 18.5° at the last follow-up, with an correction rate of 166.7%. The preoperative scoliosis Cobb angle was 13.0° to 16.5°, which improved to 2.2° to 3.8° at the last follow-up, with an correction rate of 84.9%. The preoperative SVA was 7.8 to 12.5 cm, which improved to 4.5 to 6.8 cm at the last follow-up, with an correction rate of 42.3%. One patient experienced numbness and weakness in the left hand after surgery, which recovered after 3 months. One patient had poor healing of the surgical incision, which healed after symptomatic treatment. During the follow-up, the coronal and sagittal balance of all patients was maintained, and no other neurological complications occurred. There were no cases of screw loosening, broken screws, or broken rods, or other internal fixation failures.Conclusion:The application of asymmetric T 1 SPO technique in the treatment of stiff cervical thoracic lateral kyphosis deformity can achieve relatively satisfactory correction effects.