Objective To explore the effect of calycosin(CAL)on neuronal autophagy and apoptosis in rats with spinal cord injury(SCI)by regulating PI3K/Akt signaling pathway and its mechanism.Methods A total of 32 male or female adult SD rats were randomly divided into the sham group,the SCI group,the CAL low(20 mg/kg)dose group and the CAL high(40 mg/kg)dose group with 8 rats in each group.The rat model of moderate SCI was established by modified Allen's method.After successful modeling,rats were injected intraperitoneally immediately with different dosage of CAL or equal amount of saline once a day for 7 consecutive days.Basso,Beattie and Bresnahan(BBB)scores were used to evaluate the recovery of motor function of rats at 1,3 and 7 d after surgery.At 7 d after surgery,Nissl staining was used to detect the surviving number of motor neurons in anterior horn of spinal cord.Western blot assay was used to assess expression levels of p62,Beclin-1,microtubule-associated protein 1 light chain 3(LC3B),phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway,Cleaved-Caspase-3,B-cell lymphoma-2(Bcl-2)and Bcl-2-associated X protein(Bax)proteins.Immunofluorescence staining was used to measure the expression of LC3B in anterior neurons of spinal cord.Results Compared with the sham group,BBB scores,the surviving number of motor neurons and levels of Bcl-2,Bcl-2/Bax,p-PI3K,p-PI3K/PI3K,p-Akt and p-Akt/Akt were significantly decreased(P＜0.05),and levels of p62,Beclin-1,LC3B Ⅱ,LC3BⅡ/Ⅰ,Cleaved-Caspase-3 and Bax were significantly increased in the SCI group(P＜0.05).Compared with the SCI group,BBB scores,the survival of anterior horn motor neurons and levels of LC3B Ⅱ,LC3B Ⅱ/Ⅰ,Bcl-2,Bcl-2/Bax,p-PI3K,p-PI3K/PI3K,p-Akt and p-Akt/Akt were increased in the CAL low dose group and CAL high dose group,and levels of p62,Cleaved-Caspase-3 and Baxcould were significantly decreased(P＜0.05).Conclusion CAL could promote autophagy and inhibit apoptosis of neurons through activating PI3K/Akt signaling pathway,thereby conferring a protective role following SCI in rats.

Objective:To explore the clinical effect and safety of extended debridement combined with BAM bone-induced artificial bone repair in the treatment of Cierny-Mader type IV osteomyelitis.Methods:From January 2021 to December 2022, 106 patients with Cierny-Mader type IV osteomyelitis who were treated with allogeneic bone mixed with autologous bone in department of orthopedics of Sichuan Orthopedic Hospital were retrospectively selected as the study subjects. Among them, 54 patients who were combined with BAM bone-induced artificial bone mixed with autologous bone repair were included in observation group, and 52 patients who only received allogeneic bone mixed with autologous bone repair were enrolled as control group. The clinical related indicators (bone healing time, fracture healing time), clinical efficacy (Johner-Wruh tibial shaft fracture evaluation standard) at 1 year after surgery, inflammatory factors (white blood cell count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin), limb function (American Orthopedic Foot and Ankle Society Ankle-Hindfoot Scale (AOFAS-AH)) and bone healing degree before surgery and at 1 year after surgery were compared between both groups. Chi-square test was used to compare the enumeration data between groups, and the independent sample t test was performed to compare the measurement data with normal distribution between groups.Results:At 1 year after surgery, the clinical healing indicators of bone healing time and fracture healing time and inflammatory factors such as WBC, ESR, CRP and procalcitonin with (21.19±2.16) weeks, (11.35±1.01) weeks, (6.15±0.73)×10 9/L, (9.10±1.05) mm/h, (8.09±1.11) mg/L and (0.05±0.01) μg/L in observation group were significantly shorter or lower than (24.32±2.39) weeks, (12.29±1.27) weeks, (7.86±0.89)×10 9/L, (10.10±1.32) mm/h, (9.26±1.23) mg/L and (0.08±0.01) μg/L in control group,and the differences were statistically significant ( t values were 7.08, 4.23, 10.83, 4.33, 5.15, and 15.44, respectively; all P<0.001). The clinical effective rate (85.19%(46/54)), AOFAS-AH score((84.83±12.17) points) and bone healing probability (94.44%(51/54)) were higher than (67.31%(35/52)), (79.17±11.25) points and 80.77% (42/52) in control group,with statistically significant differences (statistical values were χ2=4.70, t=2.48, and χ2=4.60, respectively; P values were 0.030, 0.015, and 0.032, respectively). Conclusion:Expanded debridement combined with BAM bone-induced artificial bone repair can effectively promote the bone tissue healing in patients with Cierny-Mader type IV osteomyelitis, relieve the inflammatory response, and improve the limb function, and it has good clinical efficacy and high safety.

Objective:To explore the efficacy and safety of daratumumab in late antibody-mediated rejection (late AMR) after kidney transplantation (KT).Methods:From December 2020 to December 2021, the relevant clinical data were reviewed for 8 patients with late AMR after receiving daratumumab at Affiliated Tongji Hospital. In intensive phase, the combination of plasma exchange (PP)/intravenous immunoglobulin (IVIG) and daratumumab were dosed once a week; in maintenance phase, once every 2 to 4 weeks. The levels of donor-specific antibody (DSA) and renal function were compared pre-treatment and Month 3/12 post-treatment. The treatment-related toxicities were observed. Independent sample T test was utilized for inter-group comparison.Results:The median treatment course during intensive period was 9(4-17) sessions. Maintenance treatment lasted for 5 to 19 months and 2 cases withdrew after 5 to 6 treatments for achieving antibody clearance. A total of 11 DSAs were detected in 8 recipients. At Month 3/12, mean fluorescent intensity (MFI) of DSA was 6 016±4 775 and 6 438±3 668. Both were significantly lower than 11 944±5 237 pre-treatment and the difference was statistically significant ( P=0.012, 0.004). Seven recipients achieved stable renal function during treatment and one recipient resumed hemodialysis at Month 18 due to acute rejection. Glomerular filtration rate of 7 recipients was (40.6±20.1), (53.6±20.9) and (49.0±17.2) ml·min -1· (1.73 m 2) -1 pre-treatment and Month 3/12 and no significant differences existed among different timepoints. During follow-ups, 2 cases developed mild nasal congestion during an early stage of daratumumab infusion while the remainders had no obvious discomfort during infusion and tolerance was decent. Conclusion:Early combination of daratumumab with PP/IVIG, followed by a course of daratumumab has demonstrated an excellent antibody reduction effect on late AMR. During treatment, renal function remains generally stable.

Objective:To investigate the efficacy of different conversion therapies for colorectal cancer with unresectable simultaneous liver metastasis.Methods:A total of 170 patients of colorectal cancer complicated with liver metastasis who were admitted to the First Affiliated Hospital of Nanchang University from Jan 2015 to Dec 2020 were included in the study. Patients were divided into an initial resectable group (42 cases) and an initial non-resectable group (128 cases).Results:There were no significant differences in OS and PFS between patients with CRLM (colorectal cancer with liver metastasis) who were resected initially and those successfully underwent transformation therapy ( P>0.05). The median OS was 36 months in the group with successful transformation, while it was 21 months in the group with simple primary tumor resection and no liver metastasis resection ( P=0.014), HR=0.48 (0.27-0.86). The median PFS was 28 months in the successful conversion group, while it was 10 months in the primary tumor resection only and no liver metastasis resection ( P=0.005), HR=0.43 (0.24-0.77). The OS difference between the group with simple primary tumor resection and no resected liver metastasis and the group with neither primary tumor nor liver metastasis resection was statistically significant: (21 months vs.13 months), HR=0.52 (0.32-0.86) ( P=0.01), while the PFS between the two groups was not statistically significant, ( P>0.05). Conclusions:Chemotherapy combined with targeted therapy has the best effect among the conversion therapies, and can improve the resection rate and survival rate of patients undergoing R 0 surgery. Resection of the primary lesion alone can also prolong the patient's survival.

OBJECTIVE: To testify the spatial relationship between the subscapularis muscle splitting window and the axillary nerve in modified arthroscopic Latarjet procedure, which could provide anatomical basis for the modification of the subscapularis muscle splitting. METHODS: A total of 29 adult cadaveric shoulder specimens were dissected layer by layer, and the axillary nerve was finally confirmed to walk on the front surface of the subscapularis muscle. Keeping the shoulder joint in a neutral position, the Kirschner wire was passed through the subscapularis muscle from back to front at the 4 : 00 position of the right glenoid circle (7 : 00 position of the left glenoid circle), and the anterior exit point (point A, the point of splitting subscapularis muscle during Latarjet procedure) was recorded. The vertical and horizontal distances between point A and the axillary nerve were measured respectively. RESULTS: In the neutral position of the shoulder joint, the distance between the point A and the axillary nerve was 27.37 (19.80, 34.55) mm in the horizontal plane and 16.67 (12.85, 20.35) mm in the vertical plane. CONCLUSION In the neutral position of the shoulder joint, the possibility of axillary nerve injury will be relatively reduced when radiofrequency is taken from the 4 : 00 position of the right glenoid (7 : 00 position of the left glenoid circle), passing through the subscapularis muscle posteriorly and anteriorly and splitting outward.
Adult ; Humans ; Shoulder ; Rotator Cuff/surgery* ; Arthroscopy/methods* ; Scapula/surgery* ; Shoulder Joint/surgery* ; Cadaver ; Joint Instability/surgery*

Objective:To summarize the clinical characteristics and treatment of cytomegalovirus(CMV)infection in pediatric kidney transplant patients.Methods:From May 2014 to July 2021, a total of 9 cases(8.65%)of 104 pediatric kidney transplant recipients were diagnosed with CMV infection in our centre.Retrospective data was collected for these 9 paediatric recipients.The clinical characteristics of the disease, treatment data and outcomes were summarized.Results:The median age of the 9 children was 10 years(0.25-15 years), 6 of whom were treated with polyclonal antibody for immunity induction.CMV IgG was negative in 4 children before renal transplantation.Only one patient received anti-CMV prophylaxis.The median time from transplant to the diagnosis of CMV infection was 22(7-15)days.Among the 9 children, 7 had fever, pneumonia and diarrhea, 2 had no typical symptoms, three patients were complicated with viral, bacterial or fungal infections.Acute rejection occurred in 3 patients at the same time as CMV infection or after CMV DNA turned negative.Nine patients were cured and discharged after ganciclovir or valganciclovir treatment.Median time of CMV DNA negative transformation was 32(17-90)days.Conclusions:Pediatric transplant recipients are at particularly elevated risk of CMV disease.Antiviral prophylaxis should be initiated early after transplantation.

Abivertinib, a third-generation tyrosine kinase inhibitor, is originally designed to target epidermal growth factor receptor (EGFR)-activating mutations. Previous studies have shown that abivertinib has promising antitumor activity and a well-tolerated safety profile in patients with non-small-cell lung cancer. However, abivertinib also exhibited high inhibitory activity against Bruton's tyrosine kinase and Janus kinase 3. Given that these kinases play some roles in the progression of megakaryopoiesis, we speculate that abivertinib can affect megakaryocyte (MK) differentiation and platelet biogenesis. We treated cord blood CD34⁺ hematopoietic stem cells, Meg-01 cells, and C57BL/6 mice with abivertinib and observed megakaryopoiesis to determine the biological effect of abivertinib on MK differentiation and platelet biogenesis. Our in vitro results showed that abivertinib impaired the CFU-MK formation, proliferation of CD34⁺ HSC-derived MK progenitor cells, and differentiation and functions of MKs and inhibited Meg-01-derived MK differentiation. These results suggested that megakaryopoiesis was inhibited by abivertinib. We also demonstrated in vivo that abivertinib decreased the number of MKs in bone marrow and platelet counts in mice, which suggested that thrombopoiesis was also inhibited. Thus, these preclinical data collectively suggested that abivertinib could inhibit MK differentiation and platelet biogenesis and might be an agent for thrombocythemia.
Acrylamides/pharmacology* ; Animals ; Blood Platelets/drug effects* ; Cell Differentiation ; Megakaryocytes/drug effects* ; Mice ; Mice, Inbred C57BL ; Piperazines/pharmacology* ; Pyrimidines/pharmacology*

Objective    To compare the 5-year survival rates between two different follow-up patterns of postoperative stage Ⅰ-ⅢA non-small cell lung cancer (NSCLC) patients. Methods    Pathological stage Ⅰ-ⅢA NSCLC 11 958 patients who underwent surgical resection and received follow-up within 6 months after initial diagnosis through telephone follow-up system were included in nine hospitals from July 2014 to July 2020. The patients were divided into two groups including a proactive follow-up group (n=3 825) and a passive follow-up group (n=8 133) according to the way of following-up. There were 6 939 males and 5 019 females aged 59.8±9.5 years. The Kaplan-Meier and Cox proportional hazards regression model were used. Results    The median follow-up frequency was 8.0 times in the proactive follow-up group and 7.0 times in the passive follow-up group. The median call duration was 3.77 minutes in the proactive follow-up group and 3.58 minutes in the passive follow-up group. The 5-year survival rate was 81.8% and 74.2% (HR=0.60, 95CI 0.53-0.67, P<0.001) in the proactive follow-up group and the passive follow-up group, respectively. Multivariate analysis showed that follow-up pattern, age, gender and operation mode were independent prognostic factors, and the results were consistent in all subgroups stratified by clinical stages. Conclusion    The proactive follow-up leads to better overall survival for resected stage Ⅰ-ⅢA NSCLC patients, especially in the stage ⅢA.

Objective:To summarize the clinical characteristics and therapeutic drug selection of post-transplantation diabetes mellitus(PTDM)after kidney transplantation in children.Methods:From May 2014 to March 2021, a total of 5 cases(5.38%)of 93 paediatric kidney transplant recipients with a median follow-up period of 34 months were diagnosed with PTDM in our centre.Retrospective data analysis was performed for these 5 paediatric recipients.The characteristics of the disease, treatment data and outcomes were summarized.Among the five paediatric recipients, one was male and four patients were female, ranging the age from 12 to 17 years.All recipients received a tacrolimus-based immunosuppressive regimen with prednisone discontinued no later than 3 months after kidney transplant.Results:The onset of PTDM ranged from 1 month to 46 months(median: 17 months)after transplantation.The blood glucose of two children returned to normal gradually after tacrolimus conversion to cyclosporine, with one of them was given insulin temporarily.Three children received oral hypoglycaemic agents, including one received acarbose, one received metformin, and one received metformin combined with acarbose.After a median follow-up of 6 months, the levels of blood glucose in five children were stable, and there was no significant change in serum creatinine and urine protein.Conclusions:The treatment of PTDM in children should be individualized with considering of age, gender and immunosuppressive regimen. Switch from tacrolimus to cyclosporine is effective. Metformin or other hypoglycemic agentsis helpful when tacrolimus is maintained.

Objective:To observe the changes in acromiaohumeral distance(AHD) in patients undergoing the modified arthroscopic double-button Latarjet procedure for recurrent anterior shoulder dislocation complicated with glenoid bone defect.Methods:A retrospective study was performed of the 52 patients who had undergone the modified arthroscopic double-button Latarjet procedure from October 2014 to October 2016 at Department of Sports Medicine, The First Affiliated Hospital to Shenzhen University for recurrent anterior shoulder dislocation complicated with glenoid bone defect. They were 33 males and 19 females, having 30 left and 22 right shoulders affected. Their ages ranged from 19 to 45 years(mean, 29.6 years). Their glenoid bone defects ranged from 17% to 30%(mean, 23.4%). CT scans were performed on the surgery side to observe the healing and reshaping of the bone grafts and to measure the AHDs of healthy shoulder, immediately, 6, 18 and 36 months after operation. Their American Shoulder and Elbow Surgeons(ASES), Rowe and Walch-Duplay scores were recorded before operation and at the final follow-up for comparison.Results:The follow-up time for this series ranged from 37 to 44 months (mean, 40.6 months). The AHDs at immediate postoperation(9.6 mm ± 0.7 mm), 6 months postoperation(8.6 mm ± 0.9 mm), 18 months postoperation (8.0 cm ± 0.8 cm) and 36 months postoperation(7.9 cm ± 0.8 cm) were significantly wider than the healthy side value (7.8 mm ± 0.8 mm)( P<0.05). The ASES, Rowe and Walch-Duplay scores at the final follow-up (93.9±3.2, 94.5±2.7 and 95.7±3.6) were significantly improved than the preoperative values (67.3±9.1, 40.1±4.2 and 63.5±9.0) ( P<0.05). The final follow-ups observed no symptoms or signs of chronic shoulder pain, rotator cuff injury or acromion impingement. Conclusion:As the AHD becomes wider rather than narrower after arthroscopic double-button Latarjet procedure for recurrent anterior shoulder dislocation complicated with glenoid bone defect, no subsequent rotator cuff injury may happen due to the uplift of the humeral head after the modified arthroscopic double-button Latarjet procedure.