BACKGROUND:Titanium elastic intramedullary nailing for the treatment of significantly displaced midshaft clavicle fractures has the characteristics of minimally invasive and elastic fixation.The displacement of the fracture is closely related to the later function.However,there are few studies on the three-dimensional displacement analysis of the fracture ends before surgery and after intramedullary fixation such as titanium elastic intramedullary nailing.OBJECTIVE:To explore the three-dimensional displacement of fracture ends after midshaft clavicle fracture and fixation with titanium elastic intramedullary nails,and to analyze the risk factors.METHODS:A total of 91 patients with midshaft clavicle fracture(fracture end shortening ≥15 mm)admitted to Wendeng Orthopedic Hospital of Shandong Province from April 2019 to April 2024 were selected,including 57 males and 34 females,aged(51.73±10.21)years old.All patients received closed reduction and internal fixation with titanium elastic intramedullary nail.CT scans of the affected clavicle were performed before and on the first day after surgery.The CT data were imported into Mimics software for modeling.The length of the clavicle,lateral displacement of the fracture end,and rotation of the distal end of the fracture along the X,Y,and Z axes were measured and recorded before and after surgery.Pearson correlation coefficient was used for correlation analysis of various parameters,and generalized linear regression was used to evaluate risk factors.RESULTS AND CONCLUSION:(1)Preoperatively,the variable that increased the risk of lateral displacement was the number of comminuted bone fragments,the variable that increased the risk of shortening displacement was male patients,and the variable that increased the risk of Z-axis rotation was the left limb.Shortening displacement was significantly positively correlated with lateral displacement(r=0.715,P＜0.001);shortening displacement was significantly positively correlated with X-axis rotation displacement and Y-axis rotation displacement(r=0.265,P=0.028;r=0.303,P=0.011);lateral displacement was significantly positively correlated with Y-axis rotation and Z-axis rotation(r=0.258,P=0.032;r=0.250,P=0.038);X-axis rotation was significantly positively correlated with Y-axis rotation(r=0.382,P=0.001),and Z-axis rotation was significantly positively correlated with Y-axis rotation(r=0.280,P=0.020).(2)Postoperatively:The number of scapula fractures and comminuted bone fragments were variables that increased the risk of postoperative shortening and lateral displacement:Preoperative X-,Y-,and Z-axis rotation displacements were risk variables that increased postoperative X-,Y-,and Z-axis rotation displacements,respectively.Postoperative lateral displacement was significantly positively correlated with postoperative shortening and displacement(r=0.584,P=0.000),and postoperative lateral displacement was also significantly positively correlated with postoperative Y axis rotation and Z axis rotation(r=0.360,P=0.002;r=0.250,P=0.038).Postoperative Y axis rotation was significantly positively correlated with postoperative Z axis rotation(r=0.248,P=0.040).(3)The results showed that the three-dimensional displacement of the clavicle end before and after surgery was affected by many factors,especially the number of comminuted bone fragments,scapula fractures,gender,and original rotation displacement.At the same time,there were complex correlations between various displacements,especially the correlation between shortening displacement and lateral displacement was the strongest.

BACKGROUND:Titanium elastic intramedullary nailing for the treatment of significantly displaced midshaft clavicle fractures has the characteristics of minimally invasive and elastic fixation.The displacement of the fracture is closely related to the later function.However,there are few studies on the three-dimensional displacement analysis of the fracture ends before surgery and after intramedullary fixation such as titanium elastic intramedullary nailing.OBJECTIVE:To explore the three-dimensional displacement of fracture ends after midshaft clavicle fracture and fixation with titanium elastic intramedullary nails,and to analyze the risk factors.METHODS:A total of 91 patients with midshaft clavicle fracture(fracture end shortening ≥15 mm)admitted to Wendeng Orthopedic Hospital of Shandong Province from April 2019 to April 2024 were selected,including 57 males and 34 females,aged(51.73±10.21)years old.All patients received closed reduction and internal fixation with titanium elastic intramedullary nail.CT scans of the affected clavicle were performed before and on the first day after surgery.The CT data were imported into Mimics software for modeling.The length of the clavicle,lateral displacement of the fracture end,and rotation of the distal end of the fracture along the X,Y,and Z axes were measured and recorded before and after surgery.Pearson correlation coefficient was used for correlation analysis of various parameters,and generalized linear regression was used to evaluate risk factors.RESULTS AND CONCLUSION:(1)Preoperatively,the variable that increased the risk of lateral displacement was the number of comminuted bone fragments,the variable that increased the risk of shortening displacement was male patients,and the variable that increased the risk of Z-axis rotation was the left limb.Shortening displacement was significantly positively correlated with lateral displacement(r=0.715,P＜0.001);shortening displacement was significantly positively correlated with X-axis rotation displacement and Y-axis rotation displacement(r=0.265,P=0.028;r=0.303,P=0.011);lateral displacement was significantly positively correlated with Y-axis rotation and Z-axis rotation(r=0.258,P=0.032;r=0.250,P=0.038);X-axis rotation was significantly positively correlated with Y-axis rotation(r=0.382,P=0.001),and Z-axis rotation was significantly positively correlated with Y-axis rotation(r=0.280,P=0.020).(2)Postoperatively:The number of scapula fractures and comminuted bone fragments were variables that increased the risk of postoperative shortening and lateral displacement:Preoperative X-,Y-,and Z-axis rotation displacements were risk variables that increased postoperative X-,Y-,and Z-axis rotation displacements,respectively.Postoperative lateral displacement was significantly positively correlated with postoperative shortening and displacement(r=0.584,P=0.000),and postoperative lateral displacement was also significantly positively correlated with postoperative Y axis rotation and Z axis rotation(r=0.360,P=0.002;r=0.250,P=0.038).Postoperative Y axis rotation was significantly positively correlated with postoperative Z axis rotation(r=0.248,P=0.040).(3)The results showed that the three-dimensional displacement of the clavicle end before and after surgery was affected by many factors,especially the number of comminuted bone fragments,scapula fractures,gender,and original rotation displacement.At the same time,there were complex correlations between various displacements,especially the correlation between shortening displacement and lateral displacement was the strongest.

ObjectiveTo evaluate the clinical efficacy and safety of Tengshen Granules in the treatment of grade 1 hypertension with the syndrome of severe liver heat and hyperactive Yang combined with mild kidney Yin deficiency. MethodsA total of 120 patients with grade 1 hypertension presenting with severe liver heat and hyperactive Yang combined with mild kidney Yin deficiency were enrolled in a randomized， double-blind， placebo-controlled， parallel-group clinical trial. Patients were randomly assigned to the observation group （Tengshen granules） and the control group （placebo）， with 60 cases in each group. On the basis of lifestyle intervention， treatment was administered for 8 weeks followed by a 2-month follow-up. During the study period， traditional Chinese medicine （TCM） syndrome scores， blood pressure， antihypertensive efficacy， blood pressure control rate， and other indicators were recorded and analyzed， and safety was evaluated. ResultsA total of 114 patients completed the trial， including 57 in the control group and 57 in the observation group. Compared with baseline， TCM syndrome scores， systolic blood pressure， and diastolic blood pressure in the observation group were significantly reduced after treatment （P<0.01）. Compared with the control group after treatment， systolic blood pressure in the observation group was lower from week 4 of medication （P<0.05）， and this difference persisted until 2 months after drug discontinuation. For diastolic blood pressure， the observation group was superior to the control group at week 8 （P<0.01）， with no statistically significant differences at other time points. Regarding syndrome improvement， the TCM syndrome scores for severe liver heat and hyperactive Yang combined with mild kidney Yin deficiency showed significant improvement at weeks 6 and 8 of treatment， with the observation group superior to the control group （P<0.05）. During the 1-month follow-up after drug discontinuation， the syndrome scores in the observation group remained lower than those in the control group （P<0.01）. The total effective rate of antihypertensive efficacy in the observation group was higher than that in the control group （χ²=11.389， P<0.05）. In addition， the level of urinary microalbumin in the observation group was lower after treatment than before treatment （P<0.05）. ConclusionTengshen granules demonstrate significant clinical efficacy and good safety in the treatment of grade 1 hypertension with severe liver heat and hyperactive Yang combined with mild kidney Yin deficiency. They can effectively reduce blood pressure and improve related TCM syndrome manifestations.

ObjectiveTo evaluate the clinical efficacy and safety of Tengshen Granules in the treatment of grade 1 hypertension with the syndrome of severe liver heat and hyperactive Yang combined with mild kidney Yin deficiency. MethodsA total of 120 patients with grade 1 hypertension presenting with severe liver heat and hyperactive Yang combined with mild kidney Yin deficiency were enrolled in a randomized， double-blind， placebo-controlled， parallel-group clinical trial. Patients were randomly assigned to the observation group （Tengshen granules） and the control group （placebo）， with 60 cases in each group. On the basis of lifestyle intervention， treatment was administered for 8 weeks followed by a 2-month follow-up. During the study period， traditional Chinese medicine （TCM） syndrome scores， blood pressure， antihypertensive efficacy， blood pressure control rate， and other indicators were recorded and analyzed， and safety was evaluated. ResultsA total of 114 patients completed the trial， including 57 in the control group and 57 in the observation group. Compared with baseline， TCM syndrome scores， systolic blood pressure， and diastolic blood pressure in the observation group were significantly reduced after treatment （P<0.01）. Compared with the control group after treatment， systolic blood pressure in the observation group was lower from week 4 of medication （P<0.05）， and this difference persisted until 2 months after drug discontinuation. For diastolic blood pressure， the observation group was superior to the control group at week 8 （P<0.01）， with no statistically significant differences at other time points. Regarding syndrome improvement， the TCM syndrome scores for severe liver heat and hyperactive Yang combined with mild kidney Yin deficiency showed significant improvement at weeks 6 and 8 of treatment， with the observation group superior to the control group （P<0.05）. During the 1-month follow-up after drug discontinuation， the syndrome scores in the observation group remained lower than those in the control group （P<0.01）. The total effective rate of antihypertensive efficacy in the observation group was higher than that in the control group （χ²=11.389， P<0.05）. In addition， the level of urinary microalbumin in the observation group was lower after treatment than before treatment （P<0.05）. ConclusionTengshen granules demonstrate significant clinical efficacy and good safety in the treatment of grade 1 hypertension with severe liver heat and hyperactive Yang combined with mild kidney Yin deficiency. They can effectively reduce blood pressure and improve related TCM syndrome manifestations.

Objective To explore the effect of low-frequency repetitive transcranial magnetic stimulation(rTMS)combined with unilateral upper limb mirror training on contralateral limb strength in patients with hemiplegia after ischemic stroke.Methods A total of 196 patients with hemiplegia after ischemic stroke were selected.All patients were divided into study group and control group via a random number table method,with 98 patients in each group.The control group received mirror training,while the study group received low-frequency rTMS treatment in addition to the control group.The neuroelectrophysiology,neurological function,limb motor function,and clinical efficacy of all patients were observed before and after treatment,and all patients were performed the resting-state functional MRI examination.A generalized estimating equation(GEE)model were used to analyze the improvement of contralateral limb strength.Results After treatment,the seed points in the study group showed a significant enhancement in connectivity with the whole brain function.The overall efficiency of the study group was significantly better than that of the control group.After treatment,the central motor conduction time(CMCT),neuron specific enolase(NSE),cortical latency(CL),and S100β of the two groups of patients were significantly reduced compared with before treatment,while the neurotrophin-3(NT-3),nerve growth factor(NGF),Fugl-Meyer assessment upper extremities(FMA-UE),Wolf motor function test(WMFT),modified Barthel index(MBI),and Berg balance scale(BBS)scores were significantly increased.Moreover,the study group showed a more significant improvement compared to the control group(P＜0.05).The GEE model analysis results showed that the improvement of contralateral limb strength in the study group was significantly better than that in the control group.Conclusion Low-frequency rTMS combined with unilateral upper limb mirror training can improve cortical excitability and upper limb motor function in hemiplegic patients after ischemic stroke,with good therapeutic effects.

AIM:To investigate whether Xibining Ⅱ(XBN Ⅱ)attenuates cartilage damage in rats with knee osteoarthritis(KOA)by modulating glycolysis via the AMP-activated protein kinase(AMPK)/peroxisome proliferator-acti-vated receptor γ coactivator 1α(PGC1α)signaling pathway.METHODS:Thirty-two SD rats were randomly divided into sham group,KOA group,XBN Ⅱ group and metformin(AMPK activator)group,with 8 rats in each group.The rats in KOA group were subjected to the anterior cruciate ligament transection procedure to establish the KOA model.Starting from the 14th day after modeling,the rats in XBN Ⅱ group received a daily dose of XBN Ⅱ via gavage once a day,and those in metformin group were administered metformin via intraperitoneal injection once a day for 4 weeks.Subsequently,the histopathological changes of the cartilage were examined by HE and safranin O-fast green staining with matching Mankin and OARSI scores.The protein levels of phosphorylated AMPK(p-AMPK)and PGC1α in cartilage were quanti-fied through immunohistochemistry.In addition,RT-qPCR and Western blot were conducted to measure the mRNA and protein expression levels of glycolysis-related factors,including glucose transporter 1,hexokinase 2 and lactate dehydroge-nase A,biomarkers related to cartilage synthesis and catabolism,such as collagen type Ⅱ,aggrecan,matrix metallopro-teinase 13 and a disintegrin and metalloproteinase with thrombospondin motifs 5,and AMPK/PGC1α signaling pathway-re-lated indicators.RESULTS:Lactate levels in cartilage and serum were higher in KOA group compared with sham group(P<0.05).Similarly,the cartilage in KOA group exhibited significant surface abrasion and structural damage,with faint-stained matrix and significantly higher Mankin and OARSI scores compared with sham group(P<0.05).Further analysis revealed significant decreases in the mRNA and protein expression levels of factors related to cartilage anabolism and AMPK/PGC1α signaling pathway in KOA group compared with sham group(P<0.05).In contrast,there were marked in-creases in the mRNA and protein expression levels of factors related to cartilage catabolism and glycolysis(P<0.05).No-tably,XBN Ⅱ and metformin treatments significantly improved the cartilage morphology,reduced Mankin and OARSI scores,and reversed the changes in mRNA and protein levels of the aforementioned indexes(P<0.05).CONCLU-SION:Treatment with XBN Ⅱ can alleviate cartilage damage in KOA rats by inhibiting glycolysis,through a mechanism involving activation of the AMPK/PGC1α signaling pathway.

OBJECTIVE To explore the effectiveness and possible mechanism of Shangke Lengtong Patch in treating knee osteo-arthritis with cold-dampness arthralgia obstruction.METHODS A total of 70 patients who met the inclusion criteria of knee osteoar-thritis with cold-dampness arthralgia obstruction in the Orthopedics Department of Affiliated Hospital of Nanjing University of Chinese Medicine from November to December 2024 were randomly divided into an experimental group and a control group,with 35 cases in each group.During the treatment,1 case dropped out of the experimental group,3 cases dropped out of the control group,and 1 case was discontinued.The experimental group was treated with Shangke Lengtong Patch,and the control group was treated with Compound Nanxing Zhitong Ointment.The WOMAC scores and TCM syndrome scores of the two groups before and after treatment were compared to comprehensively evaluate the clinical efficacy.The changes in the expression levels of CGRP,substance P,HMGB1,IL-1β,CX-CL12,and CXCR4 in the serum of the two groups were detected by ELISA.RESULTS After 3,7,and 14 d of treatment,the WOMAC scores and TCM syndrome scores of the two groups were significantly reduced(P<0.05,P<0.01),and the score of aggrava-ted cold in the experimental group was better than that in the control group at 7 d of treatment(P<0.05);after 14 d of treatment,the expression levels of CGRP,substance P,HMGB1,IL-1β,CXCL12,and CXCR4 in the serum of the two groups were significantly re-duced(P<0.05),and there was no statistical difference between the two groups.CONCLUSION Shangke Lengtong Patch can sig-nificantly relieve the pain symptoms of knee osteoarthritis patients with cold-dampness arthralgia obstruction and improve the joint func-tion of patients.It may improve synovial inflammation by inhibiting the HMGB1/CXCL12/CXCR4 pathway,thereby exerting a thera-peutic effect.

Objective:To evaluate the outcomes of minimally invasive therapy for aortic arch pathology after ascending aortic replacement.Methods:A retrospective analysis was conducted at the Department of Cardiovascular Surgery, West China Hospital of Sichuan University from 2016 to 2024. After multidisciplinary discussion, these included patients were evaluated to be at high risk for traditional open surgery. Various minimally invasive repair techniques were employed, including Ⅳb hybrid technique, physician-modified endograft and novel unibody endograft. The study outcomes were technical success, in-hospital and follow-up mortality, stroke, endoleak, and the patency of the supra-aortic vessels.Results:A total of 40 patients(32 males and 8 females) with a median age of 60 years old were included in this study. The technique success rate was 100%, with no deaths or strokes reported. The patency of the supra-aortic vessels was 100%. 10 patients underwent Type Ⅳb hybrid surgery without any endoleaks occurring. Among the 22 patients who received physician-modified endograft, endoleaks were observed in 2 cases. One of these type Ⅰc endoleaks persisted and underwent reintervention. One patient underwent femoral artery replacement due to vascular injury. For the 8 patients who received novel unibody endograft, one case required reintervention due to persistent type Ⅰc endoleaks.Conclusion:With the development of different endovascular techniques and novel branched endograft, patients with aortic arch pathology who are at high risk for redo open surgery can achieve favorable outcomes with various minimal invasive techniques. However, long-term and large-sample follow-up studies are needed for further evaluation.

Allergic rhinitis (AR), a globally prevalent immune-mediated inflammatory condition, is still an incurable disease. In the present study, we have validated the impact of the Kelch-like ECH associated protein 1 (Keap1)-related oxidative stress and inflammatory response in clinical AR patient peripheral blood and nasal swab samples, emphasizing the biological relevance of Keap1 and AR. Targeting Keap1 -nuclear factor erythroid 2-related factor 2 (Nrf2) related anti-oxidative stress may be effective for AR intervention. Drawing inspiration from the Keap1 homodimerization and the E3 ligase characteristics, we herein present a design of novel bivalent molecules for chemical knockdown of Keap1. For the first time, we characterized ternary complexes of Keap1 dimer and one molecule of bivalent compounds. The best bivalent molecule 8 encompasses robust capacity to degrade Keap1 as a homoPROTAC^KEAP1. It efficaciously suppresses inflammatory cytokines in extensively different cells, including human nasal epithelial cells. Moreover, in an AR mouse model, we confirmed that the chemical degradation induced by homoPROTAC^KEAP1 led to therapeutic benefits in managing AR symptoms, oxidative stress and inflammation. In summary, our findings underscore the efficacy of targeting the Keap1 system through the homoPROTAC-ing technology as an innovative and promising treatment strategy for the incurable allergic disorders.

Objective To study anti-inflammatory activities of oridonin derivatives without Michael fragment. Methods Two oridonin sulfonylureas were designed and synthesized by a photocatalysis reaction and a scaffold hopping strategy. The inhibitory rate of IL-1β was selected for anti-inflammatory activity evaluation. Results Both compound ZM658 and ZM659 revealed potent anti-inflammatory activities with the values of 69.3% and 59.7% in THP-1 cells, respectively. Moreover, two compounds also showed dose-dependent and low cytotoxicity. Conclusion The result indicated that Michael receptor fragment of oridonin could be substituted with sulfonylurea group.