Background and purpose:Norcantharidin(NCTD)can inhibit the growth of tumors.In this study,we presented the chorioallantoci membrane(CAM)model to evaluate the effect of NTCD on angiogenesis and to study the anti-angiogenesis of NTCD in the chicken embro implant model of human breast carcinoma MCF-7 cells.Methods:The method was based on the implantation of gelatin sponges on top of growing CAM.The sponges were treated with various amounts of NCTD and 0.9% NaCl.Blood vessels surrounding CAM mesenchyme were counted.Then we established the MCF-7 chicken embryo implant model.The chicken embryo CAMs was treated with 0.9% NaCl,Various amounts of NCTD(72,36,18 ?g per 20 ?l)and the inhibition rates were calculated.Results:NCTD can inhibit the new capillary vessels growing into gelatin sponges placed on the CAM in a dose-dependent manner,and the inhibitory rates were 77.7%,62.9%,50.6% and 33.0% respectively.NCTD at the dosages of 72、36、18 ?g were able to inhibit capillary growth regardless of the angiogenic process induced by xenograft tumor and had a significant inhibition as compared with the control group,and the rates were 66.2%,39.3%,22.8% respectively.Conclusions:NCTD has an anti-angiogenic effect for targeting tumor angiogenesis.NCTD may be a potential therapeutic candidate for clinical application.

Objective:To investigate the protective effect of lactoferrin(Lf) on lung injury in mice exposed to irradiation.Methods:C57BL/6 J mice were randomly divided into control group, 15 Gy irradiation group (IR group) and lactoferrin combined 15 Gy irradiation group (Lf+ IR group), with 5 mice in each group. The mice in the Lf+ 15 Gy group drank lactoferrin solution (10 mg/ml) from 3 days before irradiation and contained the whole experiments. Then, single chest 15 Gyirradiation was performed both in the IR and Lf+ IR groups. The body weight and other characteristics were monitored during the experiment. The mice were killed at day 14 after irradiation. The lung histopathology was observed by HE staining. Serum inflammatory cytokine such as HMGB1, TNF-α, IL-1β and IL-6 was determined by ELISA method . The expression of inflammatory related protein in lung tissue including HMGB1, TLR4, MyD88 and NF-κB were performed by immune histochemistry and Western blot method.Results:Compared with the control group, lung weight was significantly increased ( t=3.20, P<0.05), pulmonary hyperemia and inflammatory cell infiltration was observed in the IR group. Exposure also significantly increased serum level of TNF-α[(291.80±5.49) vs.(332.25±22.18)pg/ml]( t=3.07, P<0.05), up-regulated the expression of inflammatory related protein in lung tissue ( t=4.04, 4.78, 3.77, 6.14, P<0.05). Lactoferrin intervention (Lf+ IR group) significantly decreased lung weight ( t=2.18, P<0.05), alleviated histopathologic changes, decrease serum levels of HMGB1, TNF-α and IL-1β ( t=4.67, 2.97, 3.49, P<0.05). On the other hand, lactoferrin intervention decreased the positive cell number of HMGB1 and NF-κB, and down-regulated the protein expression of HMGB1, TLR4, MyD88 and NF-κB in lung tissues, with significant difference with the IR group ( t=8.06, 9.80, 3.07, 5.56, P<0.05). Conclusions:Lactoferrin plays the protective effect of radiation-induced lung injury through the downregulation of inflammatory response, such as HMGB1/TLR4/MyD88/NF-κB signaling pathway.

Diabetic cardiomyopathy(DCM)is a serious cardiovascular complication of diabetes.Mitochondrial dysfunction constitutes an important pathological basis of diabetic cardiomyopathy.Since DCM usually coexists with dysfunction of mitophagy, elucidating the relationship between them will help find new therapeutic targets for DCM.Mitochondrial autophagy includes two processes, the initiation of autophagy and degradation, and can selectively remove damaged mitochondria to achieve a balance in myocardial homeostasis and metabolic regulation in diabetes.Therefore, it is necessary to understand the role of mitochondrial autophagy in the pathophysiology underlying DCM, the influence of diabetes on mitochondria autophagy in cardiomyocytes and related molecular mechanisms.

Objective To explore the efficacy of middle and high (mid-high) flow intracranial-external vascular bypass in treatment of complex intracranial aneurysms and selection of grafts. Methods The clinical data of 79 patients with complicated intracranial aneurysms treated by mid-high flow extracranial-intracranial bypass in our hospital from August 2010 to October 2017 were collected retrospectively. The grafts were radial artery (n=21), saphenous vein of the calf segment (n=29) or thigh saphenous vein segment (n=29). The efficacy was determined based on Glasgow outcome scale (GOS) scores at discharge and modified Rankin scale (mRS) scores at follow-up, and the differences of occlusion in different types of grafts were analyzed. Results CTA showed patency of the grafts in all patients one d after surgery. There were 6 patients having vascular occlusion: 2 patients (the grafts at saphenous vein of the calf segment ) were occluded 3 and 4 d after surgery, without symptom; 2 patients (the grafts at the radial artery), with decreased limb muscle strength, were occluded 5 and 25 d after procedure; 2 patients ( the grafts at the saphenous veins of the calf segment) were occluded 6 months after procedure without any symptom. There were 4 patients developed cerebral ischemia after operation: one had cerebral infarction and three had vasospasm. GOS scores at discharge and mRS scores at follow-up showed that 78 patients had improved symptoms and good prognosis; one patient showed no improvement in symptoms and plant survival. Conclusion Mid-high flow extracranial-intracranial bypass for treatment of complex intracranial aneurysms is effective; the graft should be individually selected based on preoperative assessment results.

Objective:To investigate the value of monitoring on serum silent information regulator-related enzyme 3 (SIRT3), glucagon-like peptide-1 (GLP-1) and angiopoietin-like protein 4 (ANGPTL4) in patients with acute ischemic stroke (AIS).Methods:Eighty patients with AIS who treatment in Qiongzhong Li and Miao Autonomous County People′s Hospital from May 2019 to April 2022 were selected retrospectively as the observation group, and 60 healthy volunteers who underwent physical examination during the same period were selected as the normal control group. The levels of serum SIRT3, GLP-1, and ANGPTL4 between the two groups were compared. The neurological deficit degree of AIS patients was evaluated by National Institutes of Health Stroke Scale(NIHSS) and the correlation of SIRT3, GLP-1 and ANGPTL4 with neurological deficit degree were analyzed. The levels of serum SIRT3, GLP-1 and ANGPTL4 before and after treatment and their difference value were compared between different clinical outcome of AIS patients, the risk factors for poor clinical outcome of AIS patients were analyzed by Logistic regression analysis, the value of prediction was analyzed by receiver operating characteristic (ROC) curve.Results:The level of serum GLP-1 in the observation group was lower than that in the normal control group: (50.37 ± 5.69) nmol/L vs. (34.89 ± 4.26) nmol/L; and the levels of serum SIRT3 and ANGPTL4 in the observation group were higher than those in the normal control group: (50.37 ± 5.69) ng/L vs. (34.89 ± 4.26) ng/L, (15.07 ± 3.12) μg/L vs. (11.15 ± 2.63) μg/L, there were statistical differences ( P<0.05). The results of correlation analysis showed that the levels of serum SIRT3 and ANGPTL4 were positively correlated with the degree of neurological impairment in AIS patients( r = 0.631, 0.776, P<0.05), and the level of serum GLP-1 was negatively correlated with the degree of neurological impairment in AIS patients ( r = - 0.693, P<0.05). After treatment, 66 patients obtained good clinical outcome, the good outcome rate was 82.50%(66/80). The levels of serum SIRT3 and ANGPTL4 in the poor clinical outcome patients were higher than those in the good clinical outcome patients: (41.33 ± 4.74) ng/L vs. (37.82 ± 4.05) ng/L, (12.98 ± 2.17) μg/L vs. (11.69 ± 2.06) μg/L; the level of serum GLP-1 in the poor clinical outcome patients was lower than that in the good clinical outcome patients: (592.33 ± 98.44) nmol/L vs. (709.41 ± 125.31) nmol/L; the difference value of SIRT3, GLP-1 and ANGPTL4 before and after treatment in the poor clinical outcome patients were lower than those in the good clinical outcome patients: (10.22 ± 2.05) ng/L vs. (12.31 ± 2.94) ng/L, (268.21 ± 70.12) nmol/L vs. (379.92 ± 85.33) nmol/L, (2.18 ± 0.65) μg/L vs. (3.36 ± 0.94) μg/L, there were statistical differences ( P<0.05). The results of Logistic regression analysis showed that differences value of SIRT3, GLP-1 and ANGPTL4 before and after treatment were all independent influencing factors of poor clinical outcome in patients with AIS ( P<0.05). The results of ROC curve analysis showed that the area under the curve (AUC) of differences value of SIRT3, GLP-1 and ANGPTL4 before and after treatment in predicting poor clinical outcome were 0.701, 0.758 and 0.844, respectively, and had certain predictive value, the AUC of joint evaluation was the largest (0.912). Conclusions:The levels of serum SIRT3 and ANGPTL4 in patients with AIS are increased, and the level of serum GLP-1 is decreased, and they are related to the degree of neurological deficit. Clinical monitoring of their level changes is helpful for clinical evaluation of the clinical outcome of patients with AIS.

Objective: To analyze the clinical efficacy and prognostic factors of patients with early-stage diffuse large B-cell lymphoma of Waldeyer′s ring (WR-DLBCL) treated with CHOP-based chemotherapy. Methods: A total of 137 patients diagnosed with WR-DLBCL admitted to our hospitalfrom 2006 to 2018 were enrolled, including 22 patients with stage Ⅰ and 115 patients with stage Ⅱ WR-DLBCL. All patients received CHOP-based chemotherapy, of whom 62 receiving rituximab and 87 receiving involved-field radiotherapy. The overall survival (OS), progression-free survival (PFS) and local recurrence-free survival (LRRFS) were calculated by Kaplan-Meier method. Log-rank test, was conducted for univariate analysis and Cox’s regression model was performed for multivariate analysis. Results: The 5-year OS, PFS, and LRFFS in the whole group were 78.6%, 69.5% and 83.2%, and 87.5%, 80.2%, 90.9% in the comprehensive treatment group, and 64.2%, 53.6% 72.9% in the chemotherapy group, respectively. Univariate analysis showed that lactate dehydrogenase (LDH), international prognostic index score, large mass, rituximab, chemotherapy cycle and comprehensive treatment were the prognostic factors of OS and PFS. In addition, LDH, large mass and comprehensive treatment were the prognostic factors associated with LRFFS. Multivariate analysis demonstrated that LDH, comprehensive treatment mode and rituximab were the prognostic factors of OS. LDH and comprehensive treatment mode were the prognostic factors associated with PFS. LDH was a prognostic factor of LRFFS. Conclusion Patients with early-stage WR-BLBCL obtain excellent clinical prognosis. In the era of rituximab treatment, chemotherapy combined with radiotherapy remains an efficacious treatment of early-stage WR-BLBCL.

Objective To investigate the clinical therapy of early internal fixation combined with perforator flap for forearm open fractures of Gustilo types Ⅲ B & Ⅲ C.Methods A retrospective study was conducted of the 45 patients with forearm open fracture of Gustilo type ⅢB or Ⅲ C who had been treated from July 2012 to October 2016 at Department of Traumatic Orthopaedics,The Ninth People's Hospital of Wuxi.They were 26 men and 19 women,aged from 20 to 61 years (average,41 years).Twenty cases were Gustilo type ⅢB and 25 Gustilo type ⅢC.By AO classification,8 cases were type A,21 ones type B,and 16 ones type C.The wound size ranged from 4 cm × 3 cm to 36 cm × 8 cm.Thirty-three patients were treated by primary internal fixation plus secondary transfer with a perforator flap,12 ones by secondary internal fixation plus transfer with a perforator flap.The period from injury to secondary flap transfer ranged from 5 to 20 days (average,12 days).In this series,36 anterolateral thigh perforator flaps,5 latissimus dorsal muscular flaps and 4 lateral arm flaps were transferred.Results All the 45 free flaps survived with no deep infection or osteomyelitis.Partial necrosis happened at the distal ends of 2 latissimus dorsal muscular flaps which were cured by skin graft.Postoperative circulatory crisis happened after transfer of an anterolateral thigh perforator flap which survived with 5 cm skin necrosis at the distal end after successful surgical exploration.Superficial wound infection happened in 12 patients with no deep or bone infection.All the patients were followed up for 12 to 36 months (average,18.5 months).All the flaps were soft in texture,with varying degrees of pigmentation.The sensory recovery was S2 in 8 flaps,S3 in 29 flaps,and S4 in 8 flaps.Obvious scar hyperplasis was observed at the donor site in 5 cases while no obvious scar hyperplasis was observed in the other 40 ones.All the fractures got united after 4 to 14 months (average,8.6 months).Nonunion happened in 2 patients who were treated with autologous iliac graft 8 months after operation.By Anderson criteria,the curative efficacy was assessed as excellent in 15 cases,as good in 21,as fair in 7 and as poor in 2,yielding an excellent to good rate of 80.0％.Conclusion Early internal fixation combined with perforator flap transfe is an effective strategy for treatment of forearm open fractures with soft tissue defects of Gustilo types Ⅲ B &Ⅲ C,due to its advantages of shortened treatment period,possibility for early rehabilitation,decreased complications and satisfactory functional recovery.

Objective:To explore the predictive value of peripheral blood cytokine models on organ functional impairment after chimeric antigen receptor T(CAR-T) cell therapy in children with B-lineage lymphocytic leukemia.Methods:The clinical data of 44 children with acute B-lineage lymphoblastic leukemia who received CAR-T cell therapy at Children′s Hospital of Soochow University from September 2018 to October 2020 were retrospectively analyzed.Peripheral blood cytokines, including interleukin(IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-α, interferon(IFN)-γ and IL-17A, were measured daily for 14 days after receiving CAR-T cell therapy.The trend of peripheral blood cytokine levels was analyzed at the endpoint of organ function recovery or death within 14 days after CAR-T cell treatment.Receiver operating characteristic curve was used to establish a mathematical prediction model to predict the occurrence of organ damage in the children.Results:Of the 44 children, 31 cases were boys and 13 cases were girls, with a median age of 7.96 (5.19, 11.48)years.Cytokine release syndrome(CRS) response occurred in 95.5% (42/44) children, with 88.1% (37/42) had a grade 1-3 CRS response, and 16.7% (7/42) had a severe grade 4-5 CRS response.Using IL-6>3 892.95 pg/mL as cut-off value, the area under the curve(AUC) for predicting acute respiratory failure was 0.818, with a sensitivity of 0.8 and a specificity of 0.735, while combining IFN-γ>414.4 pg/mL, IL-6>3 892.95 pg/mL and IL-2>27.05 pg/mL were the three cut-off values, with an AUC of 0.741, sensitivity of 0.6 and specificity of 0.912 for predicting acute respiratory failure. Using IFN-γ>1 699.5 pg/mL as cut-off value, the AUC for predicting shock was 0.908, with a sensitivity of 0.722 and a specificity of 1.With IL-6>4 607.3 pg/mL as cut-off value, the AUC for predicting liver injury was 0.964, with a sensitivity of 1 and a specificity of 0.906, while combining both IL-6>4 607.3 pg/mL and IFN-γ>1 446.2 pg/mL as cut-off values, the AUC for predicting liver injury was 0.977, with a sensitivity of 1 and a specificity of 0.906.Combining both IL-6>6 972.2 pg/mL and IFN-γ>3 981.5 pg/mL predicted a positive predictive value of 62.5% and a negative predictive value of 94.4% for grade 4-5 CRS response, with an AUC of 0.846, a predictive sensitivity of 0.714 and a specificity of 0.838, and all children had a combination of two or more organ function injuries.Conclusion:The combination of IL-6 and IFN-γ can effectively predict the incidence of liver injury and cytokine release syndrome.The combination of peripheral blood cytokines IFN-γ, IL-6 and IL-2 can be used to predict the incidence of acute respiratory failure after the treatment of CAR-T cells in children with acute B-lineage lymphoblastic leukaemia.IFN-γ single index can be used to predict the incidence of shock.The combination of IL-6 and IFN-γ can be used to predict the incidence of liver injury and the severity of CRS.

Objective:To investigate the efficacy of 3D-printed quantitative bone implants assisting second-stage Masquelet technique for the treatment of long-segment bone defect following Gustilo type IIIB and IIIC tibial fractures.Methods:A retrospective case series analysis was made on 26 patients with long-segment bone defect following Gustilo type IIIB and IIIC tibial fractures treated in Wuxi Ninth People′s Hospital from July 2015 to December 2020, including 20 males and 6 females; aged 19-63 years [(46.5±4.5)years]. Gustilo classification was type IIIB in 23 patients and type IIIC in 3. In the first stage, all patients had thoroughly emergent debridement, removal of all free bone pieces, restoration of the length and force line plus externally fixion, and vacuum sealing drainage (VSD) of the residual wound. After 2-7 days, the external fixation was removed and replaced by internal fixation, with the bone cement filling in the defect area and the free flap covering the wound. The length of tibial bone defect was 5-14 cm [(6.3±0.4)cm], and the tibial defect volume was 12.2-73.1 cm 3 [(33.6±9.2)cm 3]. In the second stage (6-19 weeks after injury), the bone cement was removed, followed by autologous bone grafting. Prior to bone grafting, digital technology was used to accurately calculate the bone defect volume, and an equal volume of bone harvesting area was designe to produce the 3D printed osteotomy template. Bone grafting was conducted after bone removal according to the osteotomy template during operation. The success rate of one-time iliac bone extraction, bone harvesting time, and bleeding volume were recorded. Pain in the bone extraction area was evaluated by visual analogue score (VAS) at 1 day and 1 month after operation and at the last follow-up. Wound healing, complications, and bone healing were observed. Life quality was evaluated by health survey brief form (SF-36) including scores of physical component summary (PCS) and mental component summary (MCS) before bone grafting and at the last follow-up. Results:All the patients were followed up for 13-53 months [(32.3±12.5)months]. One-time iliac bone extraction was successful in all the patients. Bone harvesting time was 15-30 minutes [(21.0±2.5)minutes]. The bleeding volume was 50-120 ml [(62.3±29.0)ml]. The VAS was 1-4 points [(1.2±0.9)points] at 1 day after operation, higher than these (0.0±0.0)points at 1 month after operation and at the last follow-up (all P<0.01). Totally, 25 patients obtained wound healing after operation, except for 1 patient with superficial wound infection after bone grafting that was healed by dressing change. There was 1 patient with bone infection after 3 months of bone grafting that was healed by repeated surgery with Masquelet technique in the first and second stage. Besides, 2 patients had symptoms of cutaneous nerve injury in the iliac donor area. The time of bone healing was 4-7 months [(5.8±0.8)months]. The scores of PCS and MCS in SF-36 at the last follow-up were (73.6±12.8)points and (83.6±13.2)points, significantly higher than those before bone grafting [(46.8±0.5)points, (60.7±2.0)points] (all P<0.01). Conclusion:Second-stage Masquelet technique with 3D printed quantitative bone implants for the treatment of long-segment bone defect following Gustilo type IIIB and IIIC tibial fractures is associated with shortened bone harvesting time, attenuated pain, reduced complications, accelerated bone healing and improved function.

Objective: This study’s objective is to assess the efficacy and safety of Pulsed Magnetic Therapy System (PMTS) in improving insomnia disorder. Methods: Participants with insomnia disorder were randomly assigned to receive either PMTS or sham treatment for four weeks (n= 153; PMTS: 76, sham: 77). Primary outcomes are the Insomnia Severity Index (ISI) scores at week 0 (baseline), 1, 2, 3, 4 (treatment), and 5 (follow-up). Secondary outcomes are the Pittsburgh Sleep Quality Index at baseline and week 4, and weekly sleep diary-derived values for sleep latency, sleep efficiency, real sleep time, waking after sleep onset, and sleep duration. Results: The ISI scores of the PMTS group and the sham group were 7.13±0.50, 11.07±0.51 at week 4, respectively. There was a significant group×time interaction for ISI (F3.214, 485.271=24.25, p<0.001, ηp 2=0.138). Only the PMTS group experienced continuous improvement throughout the study; in contrast, the sham group only experienced a modest improvement after the first week of therapy. At the end of the treatment and one week after it, the response of the PMTS group were 69.7% (95% confidence interval [CI]: 58.6%–79.0%), 75.0% (95% CI: 64.1%–83.4%), respectively, which were higher than the response of the sham group (p<0.001). For each of the secondary outcomes, similar group×time interactions were discovered. The effects of the treatment persisted for at least a week. Conclusion PMTS is safe and effective in improving insomnia disorders.