Copper death-related factors can modulate mitochondrial function, chemotherapy sensitivity, and reshape the immune microenvironment, playing important roles in the development of hepatocellular carcinoma (HCC). Copper chelators, copper ionophores, and combination with immune checkpoint inhibitors all have significant antitumor effects. Multi-omics analysis reveals that copper death-related genes and cuproptosis-related long non-coding RNAs can serve as prognostic biomarkers and therapeutic targets. This article focused on copper metabolism and copper-induced cell death, reviewing the theoretical foundations of precision therapy for HCC. It delineates the molecular mechanisms by which dysregulated copper homeostasis drives hepatocarcinogenesis and elucidates the translational directions necessary for future research.

Copper death-related factors can modulate mitochondrial function, chemotherapy sensitivity, and reshape the immune microenvironment, playing important roles in the development of hepatocellular carcinoma (HCC). Copper chelators, copper ionophores, and combination with immune checkpoint inhibitors all have significant antitumor effects. Multi-omics analysis reveals that copper death-related genes and cuproptosis-related long non-coding RNAs can serve as prognostic biomarkers and therapeutic targets. This article focused on copper metabolism and copper-induced cell death, reviewing the theoretical foundations of precision therapy for HCC. It delineates the molecular mechanisms by which dysregulated copper homeostasis drives hepatocarcinogenesis and elucidates the translational directions necessary for future research.

Objective To investigate the method of modeling, finite element modeling and AnyBody musculoskeletal multi-body dynamics simulation technique analyze the biomechanics of clinical orthopaedic surgery. Methods The AnyBody software was used to establish the musculoskeletal motor model of the individualized upper limbs according to the height, weight and CT data of the volunteers. The flexion motion of the elbow in normal people was simulated, and the muscle force, joint force, torque, constraint condition of the humerus during the flexion movement were derived and used as the boundary conditions of finite element analysis.Then, the 3D reconstruction was conducted in the MIMICS software based on CT data. In the Geomagic Studio software, the humeral curved surface and position coordinate matching were completed, and grid division and material assignment were done in the HyperMesh software. Finally, the 3D reconstruction for finite element model of the humerus was introduced into ABAQUS software. The boundary condition data derived from the AnyBody software were applied and the stress calculation analysis was performed. Results The results of the stress and displacement of the humerus during elbow flexion motion were calculated in the ABAQUS software. The maximum stress and displacement of the humerus were 0.76 MPa and 20 μm when flexion of the elbow joint was about 90°. Conclusions A continuous dynamic analysis of humeral stress and displacement during elbow flexion motion was realized, which was more consistent with the requirements of human physiological anatomy and could provide an efficient analysis platform and a new way for studying clinical orthopedic problems.

Objective: To explore the most economically feasible cervical cancer screening strategies in urban China. Methods: A series of Markov models were constructed to evaluate health and economic outcomes of different screening strategies. There were 24 screening strategies including four screening methods: liquid-based cytology (LBC), human papillomavirus (HPV) DNA genotyping, HPV DNA genotyping with LBC triage (HPV DNA+ LBC), HPV DNA genotyping and LBC co-testing (HPV DNA-LBC), along with three intervals (every 1, 3 or 5 years) and two starting age for screening (30 or 35 years old) were compared. Models parameters were obtained from a cervical cancer screening study in urban China and literature reviews. Results: The cumulative incidence and mortality risk of cervical cancer declined over 69% and 82% respectively for each screening strategy as compared with the no screening scenario. LBC every five years starting from 35 years old strategy cost the least (RMB 690 per capita) and could save life years compared with no screening. The cost effectiveness ratios of 24 strategies ranged from -10 903 to 117 992 RMB per life year saved. All strategies were cost-effective compared to no screening. In the incremental cost-effectiveness analysis, LBC every 5 years starting from 30 strategy, HPV DNA genotyping every 3 years starting from 30 strategy, LBC every 3 years starting from 30 strategy and LBC every year starting from 30 strategy were dominant strategies. Conclusions Screening can effectively prevent cervical cancer. In urban Chinese areas with insufficient socioeconomic resources, LBC every 5 years from 35 years old strategy is recommended. In relatively more affluent areas, LBC every 5 years from 30 years old strategy, LBC every 3 years from 30 years old strategy, HPV DNA genotyping every 3 years from 30 years old strategy, and LBC every year from 30 years old strategy are recommended successively.

Objective To examine the feasibility and early effects of unilateral pedicle screw fixation in combination with contralateral translaminar facet screw fixation plus interbody fusion through the channel-assisted muscle-splitting approach for the treatment of degenerative lumbar spine diseases in elderly patients.Methods A total of 82 elderly patients with degenerative lumbar spine diseases received treatment between January 2015 and June 2016.Of these patients,25 had lumbar spinal stenosis,42 had degenerative lumbar instability,13 had giant lumbar disc herniation,and two had recurrent lumbar disc herniation;There were 69 cases of single segment and 13 cases of double segment lesions.Perioperative evaluation,imaging evaluation,and clinical evaluation were performed,and surgical complications were analyzed.Results The average length of incision was (2.6 ± 0.4) cm in cases of single segment lesions and (4.4±0.5) cm in cases of two segment lesions.The mean operation time was (98.3±19.6) minutes and peri-operation blood loss was (232.2±25.8) ml.The post-operation height of the intervertebral disc space significantly increased at the last follow-up(P ＜ 0.05);the height of the intervertebral disc space was restored and well maintained with internal fixation showing no loosening,breakage or Cage shift.The post-operation lumbar coronal Cobb angle decreased(P＜0.05)while the sagittal Cobb angle increased(P＜0.05)at the last follow-up.There was no significant difference in the area and grade of the multifidus muscle on MRI 12 months after operation.Seventy-two patients were followed up for 12-18 months (mean =16.8 months),and there were 67 cases of intervertebral fusion (93.1％).The last follow-up showed a Japanese Orthopaedic Association(JOA) score of (25.8 ± 1.7),which was significantly higher than the pre-operation score (10.6±1.3),with an excellence rate of 88.9 ％.The Oswestry Disability Index score was significantly reduced,from (50.9±21.6) at pre-operation to (9.6± 4.8) at the last follow-up.There were 78 patients with primary wound healing,three cases of superficial wound necrosis,one case of dural tear,and one case of nerve root injury.No cardiovascular or cerebrovascular incident was observed during or after operation.Conclusions Combined pedicle/facet screw fixation plus interbody fusion through the channel-assisted muscle-splitting approach shows satisfactory short-term effects when used for the treatment of degenerative lumbar spine diseases in the elderly and possesses advantages such as minimal invasiveness,limited bleeding,quick recovery,high fusion rates and significantly improved clinical outcomes.However,further clinical studies are required to assess its medium-and long-term efficacy.

Objective To analyze the clinical value of immature granulocytes in peripheral blood for prediction of persistent systemic inflammatory response syndrome (SIRS) in patients with acute pancreatitis (AP). Methods 1 973 patients with AP in Hunan People's Hospital from 2012 to 2017 were retrospectively enrolled and divided by SIRS duration into the persistent SIRS group, temporary SIRS group and non-SIRS group. The independent risk factor for persistent SIRS in AP patients was evaluated by Logistic regression analysis, and predictive value of immature granulocytes for persistent SIRS in AP patients was analyzed by the receiver operating characteristic (ROC) curve. Results These 1 973 AP patients (1 165 males, 59.0%) with an average age of 49 (40, 60) years old, including 288 persistent SIRS, 189 temporary SIRS and 1 496 non-SIRS cases. There was no significant difference in gender, age and etiology among three groups. Compared with non-SIRS group, more severe symptoms were observed in the temporary and persistent SIRS groups. Moreover, The acute physiology and chronic health evaluation Ⅱ(APACHEⅡ), CT severity index (CTSI), multiple organ failure (MOF) and acute respiratory distress syndrome (ARDS) incidence, mortality and C-reactive protein (CRP), white blood cell count (WBC), procalcitonin (PCT) and immature granulocytes in persistent SIRS group were further higher than those in the temporary SIRS group [APACHEⅡ: 9 (6, 12) vs. 5 (3, 7), CTSI: 6 (4, 6) vs. 4 (3, 6), MOF incidence: 92.0% vs. 32.8%, ARDS incidence: 39.9% vs. 10.1%, morbidity: 11.1% vs. 4.2%, CRP (mg/L): 25.00 (0.80, 212.25) vs. 0.80 (0.80, 123.50), WBC (×109/L): 15.17±6.78 vs. 14.84±5.86, PCT (μg/L): 0.23 (0.10, 1.76) vs. 0.10 (0.10, 0.31), immature granulocytes: 1.95 (0.90, 4.95) % vs. 0.80 (0.40, 2.10) %, all P < 0.05]. Logistic regression analysis showed that besides pancreatic necrosis, WBC and CRP, immature granulocyte was an independent risk factor for persistent SIRS associated with AP [odds ratio (OR) = 1.844, 95% confidence interval (95%CI) = 1.372-2.220]. ROC curve showed that immature granulocytes had better predictive value for persistent SIRS, the area under the curve (AUC) was 0.806, which was significantly higher than the APACHEⅡ (AUC = 0.783), CTSI (AUC = 0.752), PCT (AUC = 0.676), CRP (AUC = 0.677), WBC (AUC = 0.644). The cut-off value of immature granulocyte was 0.65%, the sensitivity was 84.0%, the specificity was 66.3%, the positive predictive value was 62.4%, and the negative predictive value was 76.3%. Conclusion Immature granulocyte in peripheral blood is a potential indicator for persistent SIRS in AP patients.

Objective: To account the direct cost of uterine cervix carcinoma treatment in China and to explore the related factors which influence the direct financial burden of the disease. Methods: Data was collected through the medical record system and telephone interviews in 14 county-level hospitals and 9 provincial and municipal hospitals from 14 provinces/municipalities enrolled in the Chinese National Health Industry Research Project in 2015. The direct financial burden of uterine cervix carcinoma treatment consisted of the direct medical cost and the direct non-medical cost of treatment in different pathological cervical cancer stages and precancerous lesions. Multiple liner regression method was used to analyze the factors affecting the costs. Results: The age of the 3 246 patients was (46.40±10.43) years, including 2 423 patients from provincial and municipal hospitals and 823 patients from county-level hospitals. The direct financial burden for one patient of pathological uterine cervix carcinoma stage or precancerous lesion ranged from 10 156.3 yuan to 75 716.4 yuan in provincial and municipal hospitals, and for patients from county-level hospitals, the cost was between 4 927.9 yuan and 47 524.8 yuan per person. There was a wide gap between the direct financial burden of patients in different disease stages. The direct financial burden of patients with precancerous lesions ranged from 4 927.9 yuan per person to 11 243.0 yuan per person, as for patients of pathological uterine cervix carcinoma stages, the direct financial burden was between 29 274.6 yuan and 75 716.4 yuan per person. The factors which influence direct financial burden would include: the levels of the hospital, pathological period, medicare reimbursement, days of treatment, and the methods of treatment (P<0.001). Conclusion The direct financial burden of diseases in patients with pathological uterine cervix carcinoma stage or precancerous lesion differed in different levels of hospital and pathological periods. In addition, medicare reimbursement, days of treatment, and the methods of treatment all had impact on it.

Objective To explore the feasibility and effectiveness of channel-assisted spatium intermusculare approach interbody fusion for treating lumbar vertebra diseases.Methods A total of 81 patients with lumbar vertebra diseases were treated from June 2012 to December 2013,including 35 males and 46 females between 29 and 76 years old with an average age of 54.6.There were 36 cases of lumbar disc degeneration,10 cases of recurrence in situ after lumbar disc herniation surgery,6 cases of huge lumbar disc herniation,11 cases of lumbar disc herniation with spinal canal stenosis,5 cases of extreme lateral lumbar disc herniation and 13 cases of lumbar degenerative spondylolisthesis.There were 67 cases of single segment lesion and 14 cases of two segment lesions.Lesion sites contained L1,2 in 1 case,L3,4 in 4 cases,L4,5 in 50 cases,L5S1 in 12 cases,L3,4 and L4,5 in 8 cases,and L4,5 and L5S1 in 6 cases.Results The length of incision was 2.42±0.45 cm in cases of single segment lesion and 4.28±0.38 cm in cases of two segment lesions.The operation time was 96.00±21.53 minutes and intraoperative blood loss was 347.50± 241.62 ml.During the operation,one case suffered from dural laceration,cerebrospinal fluid leakage and ipsilateral nerve root injury.Two cases suffered from pedicle fractures.Eight cases experienced epidermal necrosis of the incision.One case had poor wound healing.Three cases suffered from nerve injury.A total of 76 patients were followed up for 12-30 months,averagely 20.5 months.Intervertebral height of lesion segments was apparently recovered after surgery,and maintained in good condition during the final follow-up.No significant difference in the changes of area and grade of multifidus was detected 12 months after surgery and before surgery.Except 4 cases,the remaining had interbody fusion with a fusion rate of 94.7％.The balance between the coronal plane and sagittal plane of the lumbar spine was evidently improved.Average Japanese Orthopaedic Association score increased from 12.66±1.88 points preoperatively to 26.4±1.92 points during the final follow-up,which showed significant differences.Conclusion The method of channel-assisted spatium intermusculare approach interbody fusion has some advantages for treating lumbar vertebra such as small incision,fewer traumas,less bleeding,fast recovery,and high fusion rate.However,there is a long time of operation in the early stage and high occurrence rate of complications.

ObjectiveTo compare the clinical results of pedicle screw fixation via the injured vertebra versus across the injured vertebra for thoracolumbar spine fracture.MethodsThe study reviewed 56 patients (41 males and 15 females,at age range of 21-66 years,mean 41.5 years) with thoracolumbar spine fractures managed with the two fixation methods from June 2005 to December 2008.The fracture segment included T12 in 13 patients,L1 in 27 and L2 in 16.According to the AO classification,there were six patients with type A1.2,29 with type A3.1,nine with type A3.2 and 12 with type A3.3.McCormack load score was 5-8 points (average 6.3 points). The spinal cord injury was classified as grade A in three patients,grade B in four,grade C in eight,grade D in 17 and grade E in 24 according to Frankel scale.The patients were divided into two groups,ie,across vertebral fixation group (27 patients) and via the vertebral fixation group (29 patients).All patients were selectively treated with monosegment bone graft simultaneously.The Cobb' s angle,restoration of the anterior height of the injured vertebra,improvement of spinal canal stenosis rate and Denis scale in local pain and work status were compared between the two groups.The bone graft fusion and spinal cord recovery of both groups were observed during follow-up.ResultsAll patients were followed up for 12-48 months (average 25.8 months).Implantation loosening occurred in one patient 1.5 month after operation in across vertebral fixation group.There were no significant differences in aspects of correction of Cobb' s angle,restoration of the anteriorheight of injured vertebra and improvement of spinal canal stenosis rate postoperatively as well as in aspects of restoration of anterior height of injured vertebra and improvement of spinal canal stenosis rate at the latest follow-up between the two groups ( P ＞ 0.05).The postoperative loss of correction rate of Cobb's angle of both groups existed,with significant difference (P ＜0.05). The differences of the Cobb's angle at the latest follow-up and after operation were significant in the across vertebral fixation group ( P ＜ 0.05) but insignificant in the via vertebral fixation group (P ＞ 0.05 ).Bone graft fusion occurred in 21 patients (78％) in the across vertebral fixation group and in 27 patients (93％) in the via vertebral fixation group ( P ＜ 0.05 ).Denis scale indicated a better recovery in the local pain of via vertebral fixation group compared with the across vertebral fixation group ( P ＜ 0.05 ),but showed no significant differenc e in work status between the two groups ( P ＞ 0.05 ).ConclusionsCompared with across vertebral fixation,the pedicle screw fixation via the vertebra has the advantages of higher fusion rate and better correction rate of Cobb' s angle and is a better choice for thoracolumbar spine fracture with posterior approach.

ObjectiveTo investigate safety and efficacy of one-stage pedicle screw fixation plus 360° spinal canal decompression and reconstruction in treatment of severe thoracolumbar burst fractures.MethodsThe study reviewed 11 patients (8 males and 3 females, at age range of 19-59 years, mean 34.4 years) with severe thoracolumbar burst fracture, who underwent one-stage posterior pedicle screw fixation, 360° spinal canal decompression and reconstruction. The injury location was at T12 in one patient, at L1 in three, at L2 in two, at L3 in three and at L4 in two. According to AO classification, all patients were with type A 3.3 fractures. McCormack load score was 7-9 points ( average 8.2 points). Based on the Frankel' s scale, the spinal cord function was classified as grade A in one patient, grade B in one,grade C in five and grade D in four. ResultsAll the operations accomplished successfully, with operation duration for 3.5-4.5 hours ( mean 4.1 hours) , blood loss for 900-2 800 ml ( mean 1 750 ml) and allogeneic blood transfusion for 400-1 200 ml ( average 760 ml). There was no complication either during or after operation. The loss rate of the anterior vertebrae column height was 48％ -85％ ( average 64.2％ )before operation and recovered to 95％ -100％ (average 98.6％ ) of the normal. The kyphotic Cobb angle was at -12°-35 ° ( average 12.1 ° ) before operation and recovered to - 30°-7 ° ( average - 8.1 ° ) after operation. The spinal canal stenosis rate was improved remarkably. The patients were followed up for 10-18 months (average 14. 5 months), which showed solid bone fusion, with no implant failure. The spinal cord function was improved Ⅰ to Ⅲ degrees in all patients except for one patient at grade A. One patient had mild lower back pain.ConclusionsOne-stage pedicle screw fixation plus 360° spinal canal decompression and reconstruction is a good alternative for severe thoracolumbar burst fracture, but it is essential for choosing strictly the surgical indications.