Objective: To examine the causal association and potential mechanisms between bone mineral density in different age groups and primary malignant bone tumor based on two sample Mendelian randomization (MR), so as to provide a reference for the prevention and treatment of primary malignant bone tumor. Methods: The genome-wide association study (GWAS) of bone mineral density was obtained from the GEFOS database,which included 66 628 subjects divided into five age groups (0-15, 15-30, 30-45, 45-60, and >60 years) based on the phases of human bone development. The GWAS of primary malignant bone tumor was sourced from the FinnGen database, including 648 cases and 378 749 controls. Using bone mineral density of five age groups as the exposure and primary malignant bone tumor as the outcome, an MR analysis was performed with the inverse-variance weighted (IVW) method. Sensitivity analysis were conducted using Cochran's Q test, MR-Egger regression, MR-PRESSO test and MR Steiger test. The potential mechanisms underlying the causal association between bone density and primary malignant bone tumors were explored using Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Results: The MR analysis results showed that there was a negative causal association between bone density and primary malignant bone tumors in the 30-45 age group (OR=0.301, 95%CI: 0.126-0.721). No statistically significant associations between bone density and primary malignant bone tumors were found in the 0-15, 15-30, 45-60, and >60 age groups (all P>0.05). Sensitivity analysis did not detect heterogeneity, pleiotropy (all P>0.05) and reverse causality. KEGG enrichment analysis revealed that genes highly associated with bone density and primary malignant bone tumors were enriched in the mTOR signaling pathway and the Wnt signaling pathway, among which Low Density lipoprotein Receptor Related protein 5 and Wnt Family Member 16 are key regulatory genes. Conclusion The decrease in bone mineral density among individuals aged 30-45 may increase the risk of primary malignant bone tumors through the mTOR signaling pathway and the Wnt signaling pathway.

Objective:To investigate the characteristics and distribution of plaque of patients with mild middle cerebral artery(MCA)stenosis by using three dimensional(3D)high-resolution magnetic resonance imaging(3D HR-MRI),and the correlation between that and the occurrence of ischemic stroke.Methods:The clinical data of 64 patients with mild MCA stenosis who admitted to Beijing Huairou hospital from March 2020 to March 2022 were retrospectively analyzed.They were divided into symptomatic group(n=30)and asymptomatic group(n=34)according to whether occurred transient ischemic cerebral attack or ischemic cerebral stroke.The degree and distribution of plaque enhancement between the two groups were assessed and analyzed,and the correlation of plaque features in HR-MRI and ischemic stroke was analyzed.Results:There were a total of 71 plaques in 64 patients,including 30 responsible plaques and 41 non-responsible plaques.The enhancement degree of responsible plaques was significantly stronger than that of non-responsible plaques,and the difference was statistically significant(Z=5.645,P<0.05).Compared with non-responsible plaques,the responsible plaques more concentrated at the dorsal and upper walls of MCA,and the probability of occurring positive remodeling of responsible plaques was greater than that of non-responsible plaques,with statistical significance(x2=7.658,P<0.05).Conclusion:In patients with mild MCA stenosis,the degree enhancement and distribution location of plaque,and positively remodeling index of vessel are closely related to the occurrence of ischemic cerebral stroke.

Objective:To assess the enhancement characteristics of responsibility plaque of patients with intracranial artery stenosis(ICAS)and explore the correlation between that and stroke by using three dimensional high-resolution magnetic resonance imaging(3D-HR-MRI).Methods:A total of 72 ICAS patients who admitted to Beijing Huairou Hospital from April 2019 to April 2022 were retrospectively selected as the study objects,with a total of 96 atherosclerotic stenosis plaques.The plaques were divided into mild to moderate stenosis group(33 cases)and severe stenosis group(63 cases)according to the results of whole brain digital subtraction angiography.They were also were divided into sub-acute/acute plaque group(within 1 month)(47 cases)and non-acute plaque group(including chronic and non-responsible plaques)(49 cases)according to the time of occurring plaque.The imaging characteristics of the 3D-HR-MRI results were assessed by two radiologists.The degrees of plaque enhancement referred to the degrees of pituitary enhancement,and the degrees of plaque enhancement were divided into significant enhancement group(52 cases)and non-significant enhancement group that included moderate enhancement group and non-enhancement group(44 cases).The relationships between ICAS,degree of plaque enhancement and stroke were analyzed.Results:A total of 96 atherosclerotic stenosis plaques were confirmed in 72 patients.The statistical analysis of Kruskal-Wallis H test of multiple samples showed that there was a significant correlation between the time of occurring plaque and the degree of plaque enhancement(H=3.294,P＜0.05).Univariate Logistic regression analysis indicated that the difference between the acute plaque group and the non-acute plaque group was respectively significant correlations with ICAS degree[P＜0.05,OR(95%CI)=1.0(0.3-2.6)]and degree of plaque enhancement[P＜0.05,OR(95%CI)=1.0(0.4-2.0)].The multivariate Logistic regression analysis demonstrated that both severe arterial stenosis[P＜0.05,OR(95%CI)=1.0(0.3-1.9)]and significant enhancement of plaque[P＜0.05,OR(95%CI)=1.0(0.4-2.1)]were independent risk factors of stroke.Conclusion:Severe ICAS and significant plaque enhancement are the independent risk factors of stroke,which can provide effective basis for clinical prevention,diagnosis and treatment of stroke.

Objective:To analyze the clinic effects of arthroscopic partial trapeziectomy and suture button suspensionplasty in the treatment of first carpometacarpal joint (CMCJ) Eaton stage II/III arthrosis.Methods:A retrospective study was conducted on a total of 15 cases (16 hands) of patients including 5 males (1 bilateral) and 10 females with CMCJ stage II/III arthrosis who underwent surgical treatment at the first affiliated hospital of Shenzhen university from January 2020 to June 2022, with mean age of 56.7±6.4 years (range, 46-75 years). The duration from pain to treatment was 7.8±3.2 months (range, 4-14 months). X-ray showed narrowing of CMCJ with osteophytes and distal radial subluxation. All the patients were treated with arthroscopic partial trapeziectomy and suture button suspensionplasty. The preoperative and last postoperative follow-up radiographs, visual analogue scale (VAS), thumb's Kapandji scores, disabilies of the arm, shoulder, and hand (DASH) scores, grip and pinch strength and time to return to work were compared.Results:All cases were followed up for 19.6±6.3 months (range, 11-36 months). The postoperative X-ray showed all the CMCJs were reduced with a normal height of first metacarpal. The mean time for patients to return to their daily activities was 18.69±3.70 d and the mean time to return to work was 24.63±4.91 d. The average VAS score decreased from 6.56±1.15 preoperatively to 1.00 (0.75, 1.25). The preoperative Kapandji's score was 8.00±0.82 and the postoperative Kapandji's score was 8.00 (7.25, 9.00). The average DASH values improved from 24.06±3.19 to 4.00 (3.00, 5.00). The were significant differences except for Kapandji score ( Z=-4.905, P<0.001; Z=-0.121, P=0.905; Z=-4.846, P<0.001). The mean grip and pinch strength showed improvement from an average of 16.4 (14.13, 18.68) kg and 1.70±0.35 kg to 26.14±3.27 kg and 3.58±0.91 kg with significant difference ( Z=-4.617, P<0.001; t=-7.669, P<0.001). Conclusion:Arthroscopic partial trapeziectomy and suture button suspensionplasty is a minimally invasive surgery for the treatment of first CMCJ Eaton stage II/III arthrosis. By this technique, the patients' existing instability and pain problems can be solved.

Objectives: . The annual prevalence of chronic rhinosinusitis (CRS) is increasing, and the lack of effective treatments imposes a substantial burden on both patients and society. The formation of nasal polyps in patients with CRS is closely related to tissue remodeling, which is largely driven by the epithelial-mesenchymal transition (EMT). MicroRNA (miRNA) plays a pivotal role in the pathogenesis of numerous diseases through the miRNA-mRNA regulatory network; however, the specific mechanism of the miRNAs involved in the formation of nasal polyps remains unclear. Methods: . The expression of EMT markers and Smad3 were detected using western blots, quantitative real-time polymerase chain reaction, and immunohistochemical and immunofluorescence staining. Differentially expressed genes in nasal polyps and normal tissues were screened through the Gene Expression Omnibus database. To predict the target genes of miR-145-5p, three different miRNA target prediction databases were used. The migratory ability of cells was evaluated using cell migration assay and wound healing assays. Results: . miR-145-5p was associated with the EMT process and was significantly downregulated in nasal polyp tissues. In vitro experiments revealed that the downregulation of miR-145-5p promoted EMT. Conversely, increasing miR-145-5p levels reversed the EMT induced by transforming growth factor-β1. Bioinformatics analysis suggested that miR-145-5p targets Smad3. Subsequent experiments confirmed that miR-145-5p inhibits Smad3 expression. Conclusion . Overall, miR-145-5p is a promising target to inhibit nasal polyp formation, and the findings of this study provide a theoretical basis for nanoparticle-mediated miR-145-5p delivery for the treatment of nasal polyps.

Objective:To explore the clinical application value of dynamic contrast-enhanced MRI (DCE) time-signal intensity curve (TIC) combined with diffusion weighted imaging (DWI) in the diagnosis of benign and malignant breast lesions.Methods:This study was a retrospective study. 95 patients with suspected breast cancer who were diagnosed and treated in the Beijing Huairou Hospital from October 2018 to October 2021 were taken as the study subjects. All patients received DCE-TIC and DCE-DWI examinations, and then underwent needle biopsy after imaging examination. We evaluated the diagnostic efficacy of DCE-TIC and DCE-DWI alone and in combination in benign and malignant breast lesions by collecting general clinical data and apparent diffusion coefficient (ADC) values of patients, using pathological examination results as the " gold standard" .Results:A total of 95 patients with suspected breast cancer were diagnosed as benign lesions in 25 cases and malignant lesions in 70 cases after biopsy. Compared with benign lesions, the tumor diameter and ADC value of malignant lesions were significantly different (all P<0.05). The eceiver operating characteristic (ROC) curve of subjects was drawn, and the area under the curve (AUC) of DCE-DWI diagnosis of breast cancer was 0.826. 95 suspected breast cancer patients were diagnosed by DCE-TIC in 28 cases of type Ⅰ, 27 cases of type Ⅱ, and 40 cases of type Ⅲ. With the pathological diagnosis results as the " gold standard", the accuracy, sensitivity, and negative predictive value of DCE-TIC combined with DCE-DWI in the diagnosis of breast cancer were higher than those of a single diagnosis, with a statistically significant difference (all P<0.05); The specificity and positive predictive value of combined diagnosis were not statistically significant compared to single diagnosis (all P>0.05). Conclusions:Both DCE-TIC and DCE-DWI can differentiate benign and malignant breast lesions, and the accuracy, sensitivity, and positive predictive value of combined diagnosis are higher than those of single diagnosis. The combination of DCE-TIC and DCE-DWI can help improve the differential efficiency of breast lesion properties.

Objective:To evaluate the clinical efficacy of modified all-arthroscopic reconstruction of medial patella femoral ligament (MPFL) for the treatment of recurrent patellar dislocation.Methods:A retrospective case series study was conducted to analyze the clinical data of 38 patients (46 knees) with recurrent patellar dislocation, who were treated at First Affiliated Hospital of Shenzhen University from January 2017 to January 2020. The patients included 12 males (12 knees) and 26 females (34 knees), aged 14-40 years [(24.6±5.4)years]. All patients underwent the modified all-arthroscopic MPFL reconstruction procedure. The femoral tunnel locations were assessed by 3D-CT immediately after surgery. The MRI was performed at 6 and 12 months after operation to assess the healing morphology of the reconstructed MPFL. The Lysholm score and Kujala score were used to assess the knee function before operation, at 6 months after operation, at 12 months after operation and at the last follow-up. The time to return to sports as well as complications were observed.Results:All patients were followed up for 26-48 months [(32.4±8.6)months]. Postoperative 3D-CT examination showed that the femoral tunnels were located in the groove area of the medial epicondyle of the femur and the adductor tubercle. At 6 and 12 months after operation, MRI T2 images showed that the reconstructed MPFL had a low signal and well tensioned ligament tissue, indicating that the MPFL was healed well. The Lysholm scores at 6 and 12 months postoperatively and at the last follow-up were (81.1±12.0)points, (91.2±3.8)points, and (92.2±9.8)points, respectively, being significantly higher than the preoperative (52.4±10.6)points (all P<0.01). The Kujala scores at 6 and 12 months postoperatively and at the last follow-up were (85.4±3.9)points, (91.4±3.6)points, and (93.1±8.5)points, respectively, being significantly higher than the preoperative (55.2±6.8)points (all P<0.01). Compared with 6 months postoperatively, the Lysholm score and Kujala score were significantly improved at 12 months postoperatively and at the last follow-up (all P<0.05). All patients returned to sports, with the time to return to sports for 3-12 months [(8.7±2.3)months] after operation. One patient had poor wound healing but was healed after dressing changes. No wound infection, nerve injury, joint stiffness, patella re-dislocation or other complications occurred. Conclusion:For recurrent patellar dislocation, the modified all-arthroscopic MPFL reconstruction has advantages of accurate bone tunnel positioning, good ligament healing, good function recovery, early return to sports, and less postoperative complications.

To investigate the therapeutic effect and mechanism of Qingwen Baiduyin on acute lung injury （ALI） in mice induced by lipopolysaccharide （LPS）. MethodA total of 144 C57BL/6 mice were randomly divided into the following groups： a normal group， a model group （LPS， 5 mg·kg^-1）， a dexamethasone group （5 mg·kg^-1）， and low-， medium-， and high-dose Qingwen Baiduyin groups （14.105， 28.21， 56.42 g·kg^-1）. The mice were treated once daily for 5 days. One hour after the final administration， the ALI model was established by intratracheal instillation of LPS， and samples were collected at 6 h and 24 h after modeling. The arterial blood gas index of mice was analyzed. The total protein content， total cell count， Evans blue dye （EBD） content， and lung tissue wet-to-dry weight ratio （W/D） of bronchoalveolar lavage fluid （BALF） were measured. Hematoxylin-eosin （HE） staining was performed to assess the pathological changes in mouse lung tissue. Western blot was used to detect the expression levels of key proteins in the Janus kinase 1/signal transducer and activator of transcription 1/interferon regulatory factor 1 （JAK1/STAT1/IRF1） signaling pathway in lung tissue. ResultCompared with the normal group， the model group showed reduced arterial oxygen pressure （pO₂）， oxygen saturation （SO₂）， and lung tissue W/D （P<0.05， P<0.01）， increased carbon dioxide pressure （pCO₂）， total protein content， total cell count， EBD content， interferon-γ （IFN-γ）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， chemokine CXC ligand 1 （CXCL1）， chemokine CXC ligand 2 （CXCL2）， chemokine CXC ligand 9 （CXCL9）， and chemokine CXC ligand 10 （CXCL10） content （P<0.05， P<0.01）， thickening of the alveolar walls， fusion of alveolar cavities， and infiltration of inflammatory cells in lung tissue， increased proportion of M1 macrophage polarization and lung cell apoptosis （P<0.05）， and increased protein expression levels of JAK1， phosphorylated JAK1 （p-JAK1）， inducible nitric oxide synthase （iNOS）， STAT1， phosphorylated STAT1 （p-STAT1）， IRF1， gasdermin D （GSDMD）， and mixed lineage kinase domain-like protein （MLKL） （P<0.05， P<0.01）. Compared with the model group， Qingwen Baiduyin significantly increased pO₂， SO₂， and lung tissue W/D （P<0.05， P<0.01）， improved the pathological changes in lung tissue， and reduced pCO₂， total protein content， total cell count， EBD content， IFN-γ， TNF-α， IL-1β， CXCL1， CXCL2， CXCL9， and CXCL10 content， proportion of M1 macrophage polarization， and protein expression levels of JAK1， p-JAK1， iNOS， STAT1， p-STAT1， IRF1， GSDMD， and MLKL （P<0.05， P<0.01）. ConclusionQingwen Baiduyin can improve the lung inflammatory response and reduce lung cell apoptosis in mice with ALI by inhibiting the JAK1/STAT1/IRF1 signaling pathway， thereby exerting a lung-protective effect.

ObjectiveTo explore the effect and mechanism of Zuojinwan （ZJW） in the treatment of ulcerative colitis （UC） through network pharmacology and experimental validation. MethodUsing network pharmacology and molecular docking， the active components and potential mechanism of ZJW in treating UC were preliminarily identified. Forty-eight male C57BL/6J mice were randomly divided into a normal group， a model group， a sulfasalazine group （300 mg·kg^-1）， and low-， medium-， and high-dose ZJW groups （1.82， 3.64， 7.28 g·kg^-1）. The UC model was induced by dextran sulfate sodium （DSS）， and oral administration of drugs began on the third day of modeling， lasting for 7 days. The general condition of mice was observed daily， and the disease activity index （DAI） was evaluated. Hematoxylin-eosin （HE） staining was performed to observe histopathological changes in colon tissue. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of tumor necrosis factor （TNF）-α， interleukin （IL）-6， and IL-10 in mouse serum. The molecular mechanism was validated using Western blot. ResultNetwork pharmacology predicted that the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway might be a key pathway in the regulation of UC by ZJW. Molecular docking results showed good binding ability between the key components of ZJW and core targets. Animal experiment results showed that compared with the normal group， the model group had shortened colon length （P<0.01）， increased DAI scores， spleen index， colon tissue pathology scores， and levels of TNF-α and IL-6 in serum （P<0.05， P<0.01）， increased PI3K， phosphorylated Akt （p-Akt）， and B-cell lymphoma-2 （Bcl-2）-associated X protein （Bax） expression in colon tissue （P<0.05， P<0.01）， and decreased serum IL-10 levels and colon tissue Bcl-2 protein expression （P<0.01）. Compared with the model group， the ZJW groups showed significant improvement in UC symptoms， relieved colon tissue pathological damage， downregulated levels of inflammatory cytokines TNF-α and IL-6 in serum （P<0.01）， inhibited expression of PI3K， p-Akt， and Bax proteins in colon tissue （P<0.05， P<0.01）， and increased serum IL-10 levels and colon tissue Bcl-2 protein expression （P<0.01）， with the high-dose group showing the best effect. ConclusionZJW effectively alleviates DSS-induced UC， and its mechanism may be related to the inhibition of the PI3K/Akt signaling pathway and regulation of apoptosis-related protein expression.

Objective:To investigate the clinical efficacy of wrist arthroscopic transosseous footprint repair technique for treating triangular fibrocartilage complex (TFCC) injury.Methods:A retrospective case series study was conducted to analyze the clinical data of 56 patients with TFCC injury admitted to Shenzhen Second People′s Hospital from July 2017 to September 2020, including 38 males and 18 females, aged 17-45 years [(33.5±3.6)years]. All patients had unilateral injury. Physical examination showed instability of the distal radioulnar joint, and MRI and arthroscopy confirmed deep ligament injury of TFCC. All patients underwent repair of deep insertion of the TFCC by using wrist arthroscopic transosseous footprint. The operation time, intraoperative blood loss, wound healing and postoperative complications were recorded. The flexion and extension range of motion of the wrist, radial and ulnal deviation of the wrist, rotation range of motion of the forearm, patient related wrist evaluation (PRWE) score, modified Mayo wrist score, visual analogue scale (VAS), and percentage of grip strength between the affected side and unaffected side were compared preoperatively, at 3 months postoperatively and at 1 year postoperatively.Results:All patients were followed up for 12-18 months [(13.4±5.2)months]. The operation time was (61.3±8.9)minutes, with the intraoperative blood loss of (2.4±1.2)ml. All wounds were healed by first intension. There was no wound infection or ulnar nerve irritation symptom after operation. Four patients experienced clicking on the ulnar side of the wrist in a short period of time post-operation, with spontaneous disappearance of the symptom. At 3 months postoperatively, the radial and ulnar deviation of the wrist was decreased from (52.5±5.9)° preoperatively to (42.6±5.9)°, and rotation range of motion of the forearm was decreased from (94.9±8.4)°preoperatively to (84.6±5.9)° (all P<0.01). The flexion and extension range of motion of the wrist was (93.1±17.4)° preoperatively, with insignificant difference compared with (89.4±5.8)° at 3 months postoperatively ( P>0.05). At 1 year postoperatively, the flexion and extension range of motion of the wrist, radial and ulnar deviation range of motion of the wrist, and rotation range of motion of the forearm were significantly increased to (101.3±13.6)°, (52.4±6.6)°, and (116.4±16.4)° when compared with those at 3 months postoperatively (all P<0.01). At 3 months postoperatively, the PRWE score was increased to (17.1±3.8)points from (10.6±3.2)points preoperatively ( P<0.01), modified Mayo wrist score was decreased to (70.3±6.7) points from (78.1±12.7)points preoperatively ( P<0.01), VAS was decreased to (4.4±1.7)points from (6.2±1.5)points preoperatively ( P>0.05), and percentage of grip strength between the affected side and unaffected side was decreased to (55.7±8.7)% from (74.4±15.2)% preoperatively ( P<0.01). At 1 year postoperatively, the PRWE score was increased to (2.0±0.9)points, modified Mayo wrist score was increased to (94.8±3.3)points, VAS was decreased to (2.1±1.1)points, and percentage of grip strength between the affected side and unaffected side was increased to (93.2±8.7)% when compared with those at 3 months postoperatively (all P<0.01). Conclusion:Wrist arthroscopic transosseous footprint repair technique can effectively treat deep ligament injury of TFCC, with advantages of significantly improving postoperative joint range of motion and functional score, relieving the pain on the ulnar side of the wrist and enhancing grip strength.