Objective To design and synthesize derivatives of oleanolic acid and ursolic acid, and investigate their anti-hepatitis C virus （HCV） activity along with that of common triterpenoid acids. To explore the structure-activity relationship and provide a reference for the research of anti-HCV drugs derived from natural products through obtaining compounds with higher activity. Methods Oleanolic acid and ursolic acid were directly reacted with corresponding amines using PyBOP as a condensing agent in the presence of DIEA. Alternatively, the target compounds were prepared through PCC oxidation followed by the Baeyer-Villiger reaction catalyzed by m-CPBA. In vitro anti-HCV activity was tested using the HCVcc infection model. Molecular docking was performed by Autodock software to investigate the interaction between the active compounds and HCV NS5B. Results Oleanolic acid, glycyrrhetinic acid, ursolic acid, and asiatic acid all exhibited certain anti-HCV effects. Specifically, oleanolic acid derivatives OA2-OA4, OA6, and OA7, as well as ursolic acid derivatives UA1 and UA2, demonstrated superior anti-HCV activity compared to their parent compounds. Preliminary structure-activity relationship analysis revealed that introducing a bulky group to 28-COOH of oleanolic acid and ursolic acid enhanced their activity. Molecular docking results demonstrated that the active compounds could stably bind to HCV NS5B, thereby exhibiting antiviral activity. Conclusion Pentacyclic triterpenoids possessed anti-HCV effects, and their derivatives coud be synthesized to obtain more active compounds. The anti-HCV mechanism of these compounds may be associated with their inhibition of NS5B.

Objective:To investigate the application effect of discharge preparation service based on theory of goal attainment on patients with cervical spinal cord injury.Methods:A retrospective cohort study was conducted to analyze the clinic data of 60 patients with cervical spinal cord injury admitted to Zhengzhou Orthopedics Hospital from January 2017 to December 2022, including 49 males and 11 females, aged 23-79 years [(52.2±13.5)years]. Patients were all treated with cervical decompression fusion and internal fixation. Patients admitted from January 2017 to December 2019 were treated with conventional nursing intervention (conventional nursing group, n=30) and patients admitted from January 2020 to December 2022 were treated with discharge preparation service based on theory of goal attainment (discharge preparation service group, n=30). The readiness for hospital discharge of the two groups was compared using the Chinese version of Readiness for Hospital Discharge Scale (RHDS) at 4 hours before discharge. The degree of cervical spinal cord dysfunction of the two groups were compared using Japanese Orthopedic Association (JOA) score before intervention, at discharge and at 6 months after discharge. The complication and unplanned readmission rates of the two groups were compared at 6 months after discharge. Results:All the patients were followed up for 6 months. At 4 hours before discharge, the scores of the three parameters of RHDS containing personal status, adaptability and anticipatory support and the total score of the discharge preparation service group were (20.9±3.5)points, (35.9±2.2)points, (30.4±3.0)points and (87.1±7.8)points respectively, higher than those of the conventional nursing group [(16.2±1.7)points, (32.5±2.2)points, (26.3±2.1)points and (75.0±5.6)points respectively] ( P<0.01). There was no statistically significant difference in the JOA score of the two groups before intervention ( P>0.05). The JOA scores of the discharge preparation service group at discharge and at 6 months after discharge were (11.8±1.7)points and (13.8±1.5)points respectively, higher than those of the conventional nursing group [(10.3±1.8)points and (11.6±1.9)points respectively] ( P<0.01). At 6 months after discharge, the complication rate of the discharge preparation service group was 6.7% (2/30), lower than that of the conventional nursing group [36.7% (11/30)] ( P<0.05). The unplanned readmission rate of the discharge preparation service group was 3.3% (1/30), lower than that of the conventional nursing group [23.3% (7/30)] ( P<0.05). Conclusion:For patients with cervical spinal cord injury, discharge preparation service based on theory of goal attainment can improve the discharge readiness, promote spinal functional recovery and reduce the complication and unplanned readmission rates.

Objective:To explore the efficacy of stage I modified posterior vertebral column resection (mPVCR) in the treatment of postoperative infection after percutaneous vertebroplasty (PVP) for osteoporotic vertebral compression fracture (OVCF).Methods:A retrospective case series study was conducted to analyze the clinical data of 11 OVCF patients with post-PVP infection who were admitted to Zhengzhou Orthopedics Hospital from January 2016 to June 2022, including 4 males and 7 females, aged 61-81 years [(70.2±6.4)years]. Injured segments included T 9 in 1 patient, T 11 in 2, T 12 in 3, L 1 in 1, L 2 in 2, T 11-T 12 in 1, and T 12-L 1 in 1. American Spinal Injury Association (ASIA) grading was grade D in 5 patients and grade E in 6. All the patients were treated with stage I mPVCR. The operation time and intraoperative bleeding volume were recorded. The values of Visual Analogue Scale (VAS), Oswestry Dysfunction Index (ODI), and Cobb angle of the lesion segments before, at 2 weeks, 3 months after surgery, and at the last follow-up were compared. The loss of Cobb angle of the lesion segments at 2 weeks after surgery and at the last follow-up were compared, and the ASIA grading at the last follow-up was recorded. The infection control, bone healing, and the incidence of complications were observed at the last follow-up. Results:All the patients were followed up for 12-44 months [(26.0±9.4)months]. The operation time and intraoperative bleeding volume were 230-330 minutes [(279.2±28.6)minutes] and 500-1 100 ml [(840.9±184.1)ml] respectively. At 2 weeks, 3 months after surgery and at the last follow-up, the VAS scores were (4.0±0.8)points, (2.7±0.9)points, and (2.4±0.7)points respectively, which were all lower than that before surgery [(8.1±1.2)points] ( P<0.01); the ODI was (45.5±5.1)%, (30.0±6.5)%, and (18.5±3.6)% respectively, which were all lower than that before surgery [(78.7±6.2)%] ( P<0.01); the Cobb angle of the lesion segments were (7.9±1.4)°, (8.5±1.4)°, and (9.2±1.5)° respectively, which were lower than that before surgery [(25.5±9.2)°] ( P<0.01). The VAS and ODI were both improved at 3 months after surgery compared with those at 2 weeks after surgery ( P<0.05), while there was no significant difference in Cobb angle of the lesion segments ( P>0.05). The ODI was further improved at the last follow-up compared with that at 3 months after surgery ( P<0.05), while there were no significant differences in VAS or Cobb angle of the lesion segments ( P>0.05). The loss of Cobb angle correction of the lesion segment at the last follow-up was 0.96 (0.69, 1.45)° compared with that at 2 weeks after surgery and the rate of loss of Cobb angle correction of the lesion segment was 4.4(2.2, 7.4)%. At the last follow-up, the ASIA grading was grade E for all the patients, who were able to walk normally independently. The infection was all cured and good bony fusion was observed in the operated area at the last follow-up. Two patients had pleural effusion and pulmonary atelectasis, 1 incision fat liquefaction, and 1 pneumonia after the surgery. None of the patients had internal fixation failure and serious complications such as worsening neurological symptoms or death. Conclusion:Stage I mPVCR for the treatment of post-PVP infection in patients with OVCF is proved to attain significant pain relief and functional improvement, good correction results, effective reconstruction of spinal stability, complete removal of infected lesions, and few serious complications.

Objective:To investigate the efficacy of one-stage posterior-anterior combined operation for the treatment of abnormal fusion after facet joint dislocation in the subaxial cervical spine.Methods:A retrospective study of case series was conducted to analyze the clinical data of 10 patients with abnormal fusion after facet joint dislocation in the subaxial cervical spine who had been admitted to Department of Spine Surgery, Zhengzhou Orthopedic Hospital from January 2015 to May 2023. There were 7 males and 3 females with an age of (41.2±3.1) years. Preoperative American Spinal Injury Association (ASIA) grading: 5 cases of grade A, 4 cases of grade B, and 1 cases of grade C. All the patients were treated with one-stage posterior-anterior combined operation. The surgical time and intraoperative bleeding volume were recorded. The ASIA grading was used to evaluate the improvements in nerve function of the spinal cord 3 months after surgery. The VAS scores, cervical intervertebral heights, and Cobb angles were compared between pre-surgery, 3 months after surgery, and the last follow-up. The fusion of intervertebral bone graft was evaluated 3 months after surgery using the Bridgell intervertebral fusion criteria. Complications were observed.Results:All patients were followed up for 15.5 (13.8, 20.5) months. The surgical time was (119.5±3.6) minutes, and the intraoperative bleeding volume (141.6±25.6) mL. Significant improvements in VAS score, cervical intervertebral height, and Cobb angle were observed at 3 months after surgery and the last follow-up compared with the pre-surgery values ( P<0.05), but there was no statistically significant difference between 3 months after surgery and the last follow-up ( P>0.05). ASIA grading 3 months after surgery: 4 cases of grade A, 4 cases of grade B, and 2 cases of grade C. By the Bridgell intervertebral fusion criteria at 3 months after surgery: 9 cases of grade Ⅰ and 1 cases of grade Ⅱ, showing good intervertebral fusion. Surgery went on well for all patients, showing no postoperative complications such as aggravation of nerve lesion or vascular injury. Conclusion:In the treatment of abnormal fusion after facet joint dislocation in the subaxial cervical spine, the efficacy of one-stage posterior-anterior combined operation is definite because it can effectively reduce pain, restore the height and physiological curvature of the cervical intervertebral space, and achieve good intervertebral fusion.

Objective To investigate the role of delta/notch-like epidermal growth factor-related receptor(DNER)in gastric cancer and its regulatory mechanism.Methods The mRNA and protein levels of DNER in gastric cancer tissues and cells were detected with quantitative real time polymerase chain reaction(qRT-PCR)and Western blot.Gastric cancer cell line SGC7901 with silenced DNER expression was constructed,and cells were treated with mitochondrial dynamin-related protein 1(DRP1)inhibitor Mdivi-1.CCK-8 assay,Transwell assay,and flow cytometry were used to detect cell viability,invasion ability and apoptosis,respectively.Western blot was used to detect DNER protein levels,apoptosis-associated proteins[Cysteinyl aspartate-specific proteinase-3(Caspase-3),Bcl-2 Associated X(Bax)],autophagy associated proteins[microtubule-associated protein 1 light chain 3-Ⅱ/Ⅰ,LC3 Ⅱ/Ⅰ),p62,PTEN induced putative kinase 1(PINK1)and Parkin],and mitochondrial fission and fusion protein[DRP1,mitochondrial fission factor(MFF),mitochondrial fission protein 1(FIS1),Optic Atrophy 1(OPA1),mitofusin 1(MFN1)and MFN2]levels.Results The expression levels of DNER mRNA and protein in gastric cancer tissues were higher than those in adjacent normal tissues(t=-52.485,-46.955),while expression levels of DNER mRNA and protein in gastric cancer cells were higher than those in normal gastric epithelial cells(F=60.551,60.652),and the differences were significant(P＜0.001).Silencing DNER inhibited the proliferation and invasion of SGC7901 cells,induced apoptosis,and increased the expression of apoptosis-related proteins,with significant differences(t=8.026～25.903,all P＜0.05).Silenced DNER increased LC3 Ⅱ/Ⅰ ratio(t=18.086),decreased p62 protein level(t=6.747),promoted the aggregation of PINK1 and Parkin proteins in mitochondria(t=15.630,18.171),inhibited the expression of mitochondrial fusion proteins OPA1,MFN1 and MFN2(t=12.835,8.963,9.732),and promoted the expression of mitochondrial fission proteins DRP1,MFF and FIS1(t=16.034,16.939,15.971),with significant differences(all P＜0.05).Mdivi-1 treatment could counteract the effects of silencing DNER on mitochondrial autophagy,proliferation,invasion and apoptosis of gastric cancer cells.Conclusion DNER can reduce mitochondrial autophagy by inhibiting mitochondrial dynamic imbalance,promote cell proliferation and invasion,and inhibit cell apoptosis,thus promoting the progression of gastric cancer.

Objective To compare the stability of multi-rod structures with double-headed screws and traditional connectors in posterior three-column osteotomy of the spine using finite element analysis.Methods A finite element model of the T3-L4 thoracolumbar spine was constructed based on postoperative computed tomography(CT)data of patients with severe kyphosis.Based on the patient's standard two-rod model(2R),a double-headed screw multi-rod structure model(4R-DHS)and a traditional connector multi-rod structure model(4R-TC)were constructed.The two models were evaluated under 300 N follower load and 7.5 N-m moment load,and the stability,maximum von Mises stresses on the main rods,and stress distributions of the two multi-rod structures were analyzed.Results There was little difference in the stability between the two multi-rod structures.Compared with 4R-TC,4R-DHS showed a decrease in the maximum von Mises stresses on the main rods during all motions(the stress decreased by 7.2％,8.8％,8.7％,18.5％,and 16.9％during flexion,left lateral bending,right lateral bending,left axial rotation,and right axial rotation,respectively)and more uniform stress distribution,except for a slight increase in the maximum von Mises stresses on the main rods during post-extension.Conclusions The double-headed screw multi-rod structure can reduce the maximum stress on the main rod compared with the traditional connector multi-rod structure,and there is no problem with stress concentration on the main rod near the connector,which can more effectively reduce the risk of internal fixation failure.

Objective:To investigate the efficacy and safety of combined catheter-directed thrombolysis and anticoagulation for acute pulmonary embolism combined with lower limb deep vein thrombosis.Methods:A retrospective analysis was conducted using a case-control study approach on the clinical data of 58 patients with acute pulmonary embolism who received treatment at the Inner Mongolia Autonomous Region People's Hospital from August 2021 to August 2023. These patients were categorized into two groups based on whether they had lower-limb deep vein thrombosis or not. The group with pulmonary embolism alone ( n = 14) underwent targeted catheter thrombolysis in combination with anticoagulation treatment using low molecular-weight heparin. The group with both pulmonary embolism and deep vein thrombosis in the lower limbs (combined group, n = 44) received inferior vena cava filter placement, along with targeted catheter thrombolysis and anticoagulation treatment with low-molecular weight heparin. The improvement in pulmonary circulation was observed before and after the surgical interventions in both groups. A comparison was made regarding the improvement in indicators including arterial oxygen pressure, fingertip oxygen saturation, the proportion of pulmonary artery trunk thrombosis area to pulmonary artery trunk area, and respiratory rate, both before and after pulmonary artery catheterization and thrombolysis in both groups. Results:The surgery was successful for all patients. The symptom of shortness of breath was obviously relieved after surgery. After surgery, in the pulmonary embolism alone group, the respiratory rate was (22.75 ± 4.38) beats/min, the mean pulmonary artery pressure was (32.53 ± 3.63) mmHg (1 mmHg = 0.133 kPa), the arterial oxygen partial pressure was (81.46 ± 7.24) mmHg, and the fingertip oxygen saturation was (90.53 ± 4.57)%, respectively. In the combined group, the respiratory rate, mean pulmonary artery pressure, arterial oxygen partial pressure, and fingertip oxygen saturation were (23.35 ± 5.8) beats/min, (31.34 ± 4.53) mmHg, (82.34 ± 4.62) mmHg, and (92.57 ± 3.45)%, respectively. After surgery, the respiratory rate, pulmonary artery pressure, arterial oxygen partial pressure, and fingertip oxygen saturation in each group were significantly higher compared with the corresponding levels before surgery ( t = 6.33, 12.12, 17.32, 8.13, 6.86, 13.02, 15.52, 7.20, all P < 0.001). The proportion of pulmonary artery trunk thrombosis area to pulmonary artery trunk area in the group with pulmonary embolism alone was (19.56 ± 7.53)%, while in the combined group, it was (20.63 ± 4.83)%. After surgery, the proportion of pulmonary artery trunk thrombosis area to pulmonary artery trunk area in each group decreased compared with the corresponding value before surgery ( t = 19.36, 18.23, both P < 0.001). Conclusion:The surgical method combining catheter-directed thrombolysis with inferior vena cava filter placement is effective and safe for the treatment of acute pulmonary embolism combined with deep vein thrombosis in the lower limbs.

Objective:To evaluate the application of digital visualization in preoperative planning for surgical clearance of vertebral infection lesions following percutaneous vertebroplasty (PVP).Methods:A retrospective study was conducted to analyze the 13 patients with infectious spondylitis following PVP who had undergone one-stage posterior debridement and interbody bone grafting combined with instrumentation at Department of Spinal Surgery, Zhengzhou Orthopaedics Hospital from January 2016 to December 2022. They were 4 males and 9 females with an age of (71.4±6.5) years. Before surgery, the CT raw data of the patients were imported into software Mimics to reconstruct a three-dimensional model of the spine. After the distribution of bone cement in the model and its relationships with the vertebral plate, pedicle, articular process, and spinal cord were observed, a safe area for spinal canal surgery was designed. Intraoperative operations were carried out according to the preoperative planning. Surgical time, intraoperative blood loss, improvements in American Spinal Injury Association (ASIA) grading, and postoperative complications were recorded. The therapeutic efficacy was evaluated by comparisons of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), visual analogue scale (VAS), and Oswestry disability index (ODI) between preoperation, 2 weeks and 3 months postoperation, and the last follow-up.Results:Surgery went on successfully in all the 13 patients according to the preoperative planning. The surgical time was (275.9±28.3) min and the intraoperative blood loss (865.4±183.0) mL. All patients were followed up for (24.7±9.4) months. The levels of ESR, CRP, VAS, and ODI at 2 weeks, 3 months and the last follow-up were significantly lower than those before surgery ( P<0.05). At the last follow-up, X-ray and CT examinations showed good positions of internal fixation and sufficient bone graft fusion. The ASIA grading recovered from preoperative D to E in 5 patients. No incision infection, sinus formation, worsening of neurological symptoms, loosening or rupture of internal fixation, or worsening of neurological dysfunction were found. Conclusion:With the assistance of 3D visualization, the spinal cord, bone cement, and debridement area can be visualized directly to reduce nerve injury complications so that a safe and effective preoperative planning can be made for surgical clearance of vertebral infection lesions following PVP.

Objective:To explore the clinicopathological and genetic characteristics of sporadic medullary thyroid carcinoma (MTC) and new therapeutic targets for sporadic MTC.Methods:Based on family and personal disease history, we identified 32 sporadic MTC who underwent surgical resection from Jan 2010 to Dec 2022. Clinicopathological and immunohistochemical features were analyzed in all patients, while 6 of them were subject to the whole exome sequencing (WES).Results:Compared with those of low-grade sporadic MTC, patients with high-grade tumors were more likely to have lymph node metastasis at presentation ( χ2=4.428, P=0.040); less likely to be cured by biochemical treatment ( χ2=4.072, P=0.044). Pathological grading scheme, biochemical cure, and TNM stage were independent risk factors of disease free survival. WES was performed on 6 pairs of normal tissues. We screened RET and RAS as driver mutations, and the mutation ratio was 3/6 respectively. Patients with RET or RAS mutations had no recurrence. In addition, we detected PDGFRA somatic mutation, with a mutation ratio of 1/6. Conclusions:For sporadic MTC cases, the pathological grading system has important prognostic value, and RET and RAS somatic mutations are the main driver mutations. PDGFRA are potential therapeutic targets for sporadic MTC.

Objective:To investigate the efficacy of the classified reduction based on CT two-dimensional images for the surgical treatment of single segment facet joint dislocation in subaxial cervical spine.Methods:A retrospective case series study was made on 105 patients with single segment facet joint dislocation in subaxial cervical spine admitted to Zhengzhou Orthopedic Hospital from January 2015 to October 2022. There were 63 males and 42 females, with the age range of 22-78 years [(47.5±3.6)years]. Preoperative American Spinal Cord Injury Association (ASIA) classification was grade A in 23 patients, grade B in 45, grade C in 22, grade D in 15 and grade E in 0. The classification of surgical approach was based on the presence or not of continuity between anterior and posterior subaxial cervical structures and the movability of the posterior cervical facet joint on CT two-dimensional images, including anterior cervical surgery if both were presented and posterior facet joint resection plus anterior cervical surgery if there was discontinuity between anterior and posterior subaxial cervical structures or posterior facet joint fusion. Reduction procedures were applied in accordance with the type of facet joint dislocation classified based on the position of the lower upper corner of facet joint, including skull traction or manipulative reduction for the dislocation locating at the dorsal side (type A), intraoperative skull traction and leverage technique for the dislocation locating at the top (type B) and intraoperative skull traction and leverage technique with boosting for the dislocation locating at the ventral side (type C). If the dislocation of two facet joints in the same patient was different, the priority of management followed the order of type C, type B and type A. The reduction success rate, operation time and intraoperative blood loss were recorded. The cervical physiological curvature was evaluated by comparing the intervertebral space height and Cobb angle before operation, at 3 months after operation and at the last follow-up. The fusion rate of intervertebral bone grafting was evaluated by Lenke grading at 3 months after operation. The spinal cord nerve injury was assessed with ASIA classification before operation and at 3 months after operation. Japanese Orthopedic Association (JOA) score was applied to measure the degree of cervical spinal cord dysfunction before operation and at 3 months after operation, and the final follow-up score was used to calculate the rate of spinal cord functional recovery. The occurrence of complications was observed.Results:All patients were followed up for 3-9 months [(6.0±2.5)months]. The reduction success rate was 100%. The operation time was 40-95 minutes [(58.6±9.3)minutes]. The intraoperative blood loss was 40 to 120 ml [(55.7±6.8)ml]. The intervertebral space height was (4.7±0.3)mm and (4.7±0.2)mm at 3 months after operation and at the last follow-up, significantly decreased from preoperative (3.1±0.5)mm (all P<0.01), but there was no significant difference in intervertebral space height at 3 months after operation and at the last follow-up ( P>0.05). The Cobb angle was (6.5±1.3)° and (6.3±1.2)° at 3 months after operation and at the last follow-up, significantly increased from preoperative (-5.4±2.2)° (all P<0.01), but there was no significant difference in Cobb angle at 3 months after operation and at the last follow-up ( P>0.05). The fusion rate of intervertebral bone grafting evaluated by Lenke grading was 100% at 3 months after operation. The ASIA grading was grade A in 15 patients, grade B in 42, grade C in 29, grade D in 12 and grade E in 7 at 3 months after operation. The patients showed varying degrees of improvement in postoperative ASIA grade except that 15 patients with preoperative ASIA grade A had partial recovery of limb sensation but no improvement in ASIA grade. The JOA score was (13.3±0.6)points and (13.1±0.6)points at 3 months after operation and at the last follow-up, significantly improved from preoperative (6.8±1.4)points (all P<0.01), but there was no significant difference in JOA score at 3 months after operation and at the last follow-up ( P>0.05). The rate of spinal cord functional recovery was (66.3±2.5)% at the last follow-up. All patients had no complications such as increased nerve damage or vascular damage. Conclusion:The classified reduction based on CT two-dimensional images for the surgical treatment of single segment facet joint dislocation in subaxial cervical spine has advantages of reduced facet joint dislocation, recovered intervertebral space height and physiological curvature, good intervertebral fusion and improved spinal cord function.