Objective To mine the adverse drug event(ADE)signals of galcanezumab based on U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)to provide reference for clinical drug safety.Methods The data from the FAERS database from the third quarter of 2018 to the fourth quarter of 2023 were extracted.After data cleaning and standardization,the duplicate data was removed using structured query language,ADE reports with galcanezumab as the main suspected drug were screened.ADE reports were standardized and categorized using the Medical Dictionary for Drug Regulatory Activities.The reporting odds ratio(ROR)method and information component(IC)method were applied for signal detection.Results A total of 60 ADE signals were detected after screening,11 system organ classes were involved,mainly general disorders and administration site conditions.The ADE signals that occurred most frequently were a variety of discomfort reactions at the injection site,consistent with the most common ADEs documented in the drug insert.The top 3 new ADE signals in order of occurrence frequency were alopecia,weight increased and constipation,and in order of ROR and IC values were injection site pustule,vertebral artery dissection and Raynaud's phenomenon.Conclusion ADE related to galcanezumab mainly involve systemic diseases and various reactions at the site of administration,among which vertebral artery dissection and Raynaud's phenomenon are stronger signals and newer ADEs.The patient's disease progression should be closely monitored during the treatment period to avoid serious consequences.

Objective To compare rotational techniques used by Chinese and world elite men’s shot put athletes, so as to provide scientific references for Chinese male shot putters to improve their sports performance and results in international competitions. Methods Three-dimensional (3D) kinematics data from Chinese male shot putters in actual competitions were obtained, and kinematic parameters of Chinese and world elite men’s shot put athletes were calculated and compared. Namely, shot velocities and hip-shoulder separation angles at five critical instants of rotational techniques: right foot off, left foot off, right foot touchdown, left foot touchdown and release, as well as phase durations and shot travel distances during four critical phases: first single support, air-born flight, second single support and final delivery. ResultsCompared with world elite athletes, Chinese male shot putters using rotational techniques had significantly lower vertical release velocity, longer air-borne duration, smaller hip-shoulder separation angles at left foot off and touchdown instant, and longer shot travel distance during air-borne flight, but shorter shot travel distance during final shot delivery. Conclusions The difference in lower extremity strength is a primary casue leading to different sports performance between Chinese and world elite male shot putters. The technique differences in Chinese and world elite male shot putters mainly lie in different phase timing and shot travel distances during different techinique phases.

Objective: To investigate the role of CD11b agonist leukadherin-1 (LA1) in the development of intestinal inflammation and colitis disease in a mouse model of dextran sulfate sodium (DSS)-induced colitis. Methods: The mouse model of experimental colitis was induced by DSS. Body weight changes and survival status were monitored every day. The length of colons was measured at day 7. Colon tissue sections were stained with hematoxylin and eosin (HE) and observed under an optical microscope for pathological analysis. The percentages of apoptotic cells in colon tissues were observed by TUNEL staining. Myeloperoxidase (MPO) activity was measured with MPO activity detection kit. IL-1β and TNF-α levels were detected by ELISA. Macrophages and TNF-α in colon tissues were observed using immunofluorescence staining and confocal microscopy. Flow cytometry was performed to detect the changes in TLR4 expression on macrophages after stimulating mice with LA1 for 0, 3, 6 and 12 h. Moreover, TLR4 expression was also measured by Western blot after treating bone marrow-derived macrophages (BMDMs) with LA1 for 0, 3, 6 and 12 h. Unpaired t-test was used for statistical analysis. Results: Compared with the DSS group, the LA1+ DSS group presented lower mortality rate, greater body weight and longer colon and the differences between the two groups were statistically significant. Moreover, the LA1+ DSS group showed lighter pathological damages, decreased percentage of apoptotic cells and suppressed MPO activity as compared with those of the DSS group. The number of macrophages and the relative concentrations of IL-1β and TNF-α in colon tissues were lower in the LA1+ DSS group than in the DSS group, and the differences between the two groups were statistically significant. There was no significant difference in the total expression of TLR4 on macrophages before and after LA1 treatment. However, the mean flourscence indensity (MFI) of TLR4 was weaker on the LA1-treated macrophages than on the untreated macrophages. Conclusions LA1 could alleviate the DSS-induced experimental colitis in mice through suppressing the activation of TLR4 pathway on macrophages. This study provided a new insight and theoretical reference for understanding the pathogenesis of inflammatory bowel diseases.

Objective Polyinosinic-polycytidylic acid (poly IC) plays an important role in the central nervous system damage and repair.This study was to investigate the effect of poly IC on inflammatory response after spinal cord ischemia-reperfusion injury (SCIRI) in rats.Methods A total of 72 healthy adult male SD rats were equally randomized into a sham-operation, an ischemia-reperfusion (IR), and a poly IC group.The abdominal cavities of the rats were cut open and closed again in the sham-operation group and SCIRI models were established in the IR and poly IC groups by clamping the abdominal aorta, followed by reperfusion 60 minutes later and intraperitoneal injection of saline (0.1 mL) and poly IC (1.25 μg/g), respectively.At 6, 24, and 48 hours after modeling, BBB scores were obtained and the contents of TNFα, IL-1β and IFN-β were measured by ELISA.At 48 hours, the expressions of NF-κB and IL-10 were determined by immunohistochemistry, the area of ischemic necrosis in the spinal cord tissue was calculated by TTC staining, and its morphological changes were observed under the optical microscope.Results At 48 hours after modeling, the BBB scores were significantly lower in the IR and poly IC groups than in the sham-operation group (3.80±0.75 and 9.40±0.49 vs 20.00±0.00, P<0.01), though higher in the poly IC than in the IR group (P<0.01).The rats of the IR group showed extensive degenerated neurons in the gray substance of the spinal cord, with scattered foci of bleeding and blood coagulation, while those of the poly IC group exhibited fewer necrotic neurons and basically normal nuclear morphology, though with a few swelling cells.The ischemic necrosis area of the spinal cord tissue was significantly reduced.The expression of NF-κB was decreased while that of IL-10 increased markedly.Compared with the IR group, the poly IC group showed a significant increase in the expression of IFNβ (117.23±6.06 vs 55.65±4.02, P<0.01) and a remarkably decrease in the expressions of TNFα (190.45±4.16 vs 201.82±2.18, P<0.01) and IL-1β (39.27±2.48 vs 50.59±1.47, P<0.01) at 48 hours.Conclusion Poly IC can protect the spinal cord and reduce inflammatory response after spinal cord ischemia-reperfusion injury.

Objective To evaluate the feasibility and efficacy of twin grasper combined with endoloops on closing acute stomach perforation.Methods Two experimental porcines of stomach perforation underwent endoscopic closure by twin grasper combined with endoloops.Survival conditions and closure of perforating were observed.Results Mild infection and abdominal adhesions were observed in one week after operation.The nylon rope fell off and an ulcer-like lesion was presented in the closed position.The methylene blue leak test was negative.Histologic examination revealed chronic inflammatory cells infiltration,granulation,fibroplasias,and regenerative mucous membrane crawling toward the center of perforation.Conclusion The technique of twin grasper combined with nylon ropes in closing the acute stomach perforation is feasible and effective.

BACKGROUND:Three-dimensional finite element studies found that the instal ation location of the hip prosthesis is closely related to the effects of hip replacement, but studies on different anteversion and abduction angle of the hip prosthesis mounting position on the effects of hip biomechanics are not much. OBJECTIVE:To analyze the biomechanical characteristics of different prosthetic positions in hip arthroplasty using three-dimensional finite element analysis. METHODS:One healthy volunteer was selected and data of pelvis and femur were col ected. Three-dimensional geometric model of this volunteer was established and received finite element network partitioning. CT scan was used to obtain prosthesis model data and accurate prosthesis model was established. 16 kinds of different prosthesis position model of hip replacement were established. Vertical y downward force of 780 N was applied on the top of sacroiliac joint and pubic symphysis. The acetabular stress peak, femoral stress peaks, polyethylene liner peak stress and polyethylene liner damage zone volume of 16 kinds of model were observed. RESULTS AND CONCLUSION:(1) The acetabular stress peak, femoral stress peaks, polyethylene liner peak stress and polyethylene liner damage zone volume of 16 kinds of different prosthesis position model of hip replacement, anteversion angle 10° abduction angle 50° got the best results. The acetabular stress peak was 51.23 MPa;femoral stress peak was 26.34 MPa. Polyethylene liner peak stress was 5.288 MPa and polyethylene liner damage zone volume was 2.239×10-7 m3. (2) These results indicated that anteversion angle 10° abduction angle 50° is the ideal hip replacement degree. The peak stresses of acetabulum, femur, and polyethylene liner at this instal ation angle are minimum;polyethylene liner damage zone volume is also minimum. This can provide data for clinical reference.

BACKGROUND: Anterior cervical decompression and fusion has been widely used in the treatment of multi-level cervical spondylotic myelopathy, but accompanied with lots of complications.OBJECTIVE: To investigate the efficacy of zero-profile interboby fixation system for multi-level cervical spondylotic myelopathy.METHODS: Seventy-one patients with multi-level cervical spondylotic myelopathy were randomly divided into two groups, and the patients in group A accepted zero-profile interboby fixation system, and group B accepted cage interboby fixation system. The Japanese Orthopaedic Association score, fusion rate, as well as the incidence of dysphagia and esophageal fistula were detected to compare the efficacy between two groups.RESULTS AND CONCLUSION: (1) All cases were followed-up for 3-34 months, average of 17.5 months. The excellent and good rate at the last follow-up showed no significant difference between two groups. (2) The final fusion rate did not differ significantly between two groups, but the fusion rate in the group A was significantly higher than that in the group B at 6 and 9 months postoperatively (P < 0.05). (3) There was one patient with mild dysphagia in the group A (3％), three mild, five medium, and two severe dysphagia in the group B (29％), which showed significant difference between two groups (P < 0.05). No internal fixation loosening occurred in the group A, but three cases in the group B. The blood loss, operation time and radiology times in the group A were significantly lower than those in the group B (P < 0.05). (4) These results suggest that the effect of these two surgical methods in promoting functional recovery of spinal cord and final fusion rate show no significant differences; however, the zero-profile interboby fixation system exhibits better postoperative stability and interim fusion rate, with lower incidence of dysphagia.

Objective:Using the macrophage cell lines RAW264.7 stably expressing Rab5a and its dominant negative mutant Rab5aN133I as models to analyze the effect and the mechanism of Rab 5a,Rab5aN133I on CpG-induced production of pro-inflammatory cytokines and type Ⅰ IFN.Methods: The eukaryotic expression vectors of Rab5a and Rab5aN133I were transfected into RAW264.7 cells by liposome,and screened with G418.The G418-resistant colonies were obtained and amplified.The transformed cell lines were i-dentified by RT-PCR,Real time-PCR and Western blot.The production of cytokines were measured after transformed cell lines of Rab5a and Rab5aN133I was stimulation with CpG for 8 h.Results: Rab5a expression in transfected cells was significantly higher than the control cell group (P<0.05).Overexpression of Rab5a significantly promoted the production of TNF -α,IL1-β(P<0.01) and IFN-β( P<0.05) in CpG stimulated RAW264.7.The production of cytokines was restored in Rab 5aN133I transfected cell line.Conclusion:Rab 5a promotes CpG-induced pro-inflammatory cytokines and typeⅠIFN in macrophages,it may be act as a positive regulator in TLR9 signaling pathway.

BACKGROUND: The mechanisms of spinal cord ischemia-reperfusion injury are the result of the combined effects of multiple factors, but there is no effective treatment.
OBJECTIVE: To investigate the effect of lipoxin receptor agonist BML-111 on inflammatory factor and apoptosis in rats with spinal cord ischemia-reperfusion injury.
METHODS: A total of 72 healthy adult male Sprague-Dawley rats were randomly divided into sham surgery group, ischemia-reperfusion group and BML-111 group. Rat models of spinal cord ischemia-reperfusion injury were established by clamping the abdominal aorta in the later two groups. Rats in the ischemia-reperfusion group and BML-111 group were injected with 0.1 mL of saline and 1 mg/kg BML-111 through caudal vein at 30 minutes after model establishment.
RESULTS AND CONCLUSION: Compared with ischemia-reperfusion group, BBB scores were significantly improved, pathological injury of spinal cord tissue significantly reduced, the number of apoptotic cel s, tumor necrosis factor α and interleukin-1β expression, myeloperoxidase oxide activity and malondialdehyde content decreased in the BML-111 group. These findings indicate that lipoxin receptor agonist BML-111 can inhibit neuronal apoptosis and inflammation so as to reduce spinal cord injury.

AIM: To observe the therapeutic effect of modified Bushen Huoxue granules (MBHG) on ovariec-tomized osteoporosis rats.METHODS: Female SD rats were randomly given sham operation (n =10) and ovariectomy, and then the model rats were further randomly divided into model group, MBHG treatment groups at doses of 200 mg/kg, 100 mg/kg and 50 mg/kg respectively, and positive control (estradiol valerate) group, with 10 rats in each group by intra-gastric administration for 12 weeks.The morphology, area, thickness, spacing and area percentage of trabecular bone in the rats were observed.The serum levels of calcium (Ca), phosphorus (P) and alkaline phosphatase (ALP) were mea-sured by automatic analyzer.Bone mineral density (BMD) was analyzed.Serum estradiol (E2 ), osteocalcin (BGP), os-teoprotegerin (OPG), receptor activator of nuclear factor-κB (RANK) and receptor activator of nuclear factor κB ligand (RANKL) levels were detected by ELISA.RESULTS: Compared with model group, trabecular bone significantly widened in all treatment groups with large number, and net-like structure restored partially.The thickness, area and area percenta-ges of trabecular bone in treatments groups were higher than those in model group,and trabecular spacing was less than that in model group (P <0.05).The serum Ca, P, E2 and OPG, and femoral BMD were significantly higher in treatment groups than those in model group, and the levels of ALP, BGP, RANK and RANKL were significantly lower than those in model group (P <0.01).CONCLUSION: MBHG has a significant therapeutic effect on ovariectomized osteoporosis rats. The mechanism may be related to the regulation of OPG and inhibition of RANKL secretion.