OBJECTIVE:The main clinical manifestations of knee osteoarthritis are pain,swelling,stiffness,and limited activity,which have a serious impact on the life of patients.Exercise therapy can effectively improve the related symptoms of patients with knee osteoarthritis.This paper uses the method of network meta-analysis to compare the efficacy of different exercise types in the treatment of knee osteoarthritis. METHODS:CNKI,WanFang,PubMed,Embase,Cochrane Library,Web of Science,Scopus,Ebsco,SinoMed,and UpToDate were searched with Chinese search terms"knee osteoarthritis,exercise therapy"and English search terms"knee osteoarthritis,exercise".Randomized controlled trials on the application of different exercise types in patients with knee osteoarthritis from October 2013 to October 2023 were collected.The outcome measures included visual analog scale,Western Ontario and McMaster Universities Osteoarthritis Index score,Timed Up and Go test,and 36-item short form health survey.Literature quality analysis was performed using the Cochrane Manual recommended tool for risk assessment of bias in randomized controlled trials.Two researchers independently completed the data collection,collation,extraction and analysis.RevMan 5.4 and Stata 18.0 software were used to analyze and plot the obtained data. RESULTS:A total of 29 articles with acceptable quality were included,involving 1 633 patients with knee osteoarthritis.The studies involved four types of exercise:aerobic training,strength training,flexibility/skill training,and mindfulness relaxation training.(1)The results of network meta-analysis showed that compared with routine care/health education,aerobic training could significantly improve pain symptoms(SMD=-3.26,95%CI:-6.33 to-0.19,P<0.05);strength training(SMD=-0.79,95%CI:-1.34 to-0.23,P<0.05)and mindfulness relaxation training(SMD=-0.79,95%CI:-1.23 to-0.34,P<0.05)could significantly improve the function of patients.Aerobic training(SMD=-1.37,95%CI:-2.24 to-0.51,P<0.05)and mindfulness relaxation training(SMD=-0.41,95%CI:-0.80 to-0.02,P<0.05)could significantly improve the functional mobility of patients.Mindfulness relaxation training(SMD=0.70,95%CI:0.21-1.18,P<0.05)and strength training(SMD=0.42,95%CI:0.03-0.81,P<0.05)could significantly improve the quality of life of patients.(2)The cumulative probability ranking results were as follows:pain:aerobic training(86.6%)>flexibility/skill training(60.1%)>strength training(56.8%)>mindfulness relaxation training(34.7%)>routine care/health education(11.7%);Knee function:strength training(73.7%)>mindfulness relaxation training(73.1%)>flexibility/skill training(56.1%)>aerobic training(39.9%)>usual care/health education(7.6%);Functional mobility:aerobic training(94.7%)>mindfulness relaxation training(65.5%)>strength training(45.1%)>flexibility/skill training(41.6%)>routine care/health education(3.2%);Quality of life:mindfulness relaxation training(91.3%)>strength training(68.0%)>flexibility/skill training(44.3%)>aerobic training(34.0%)>usual care/health education(12.3%). CONCLUSION:(1)Exercise therapy is effective in the treatment of knee osteoarthritis,among which aerobic training has the best effect on relieving pain and improving functional mobility.Strength training and mindfulness relaxation training has the best effect on improving patients'function.Mindfulness relaxation training has the best effect on improving the quality of life of patients.(2)Limited by the quality and quantity of the included literature,more high-quality studies are needed to verify it.

Objective:By analyzing the characteristics, diagnosis, and treatment process of anti-synthetase syndrome complicated by interstitial pneumonia and cardiac dysfunction, we aim to enhance general practitioners' understanding and diagnosis of this disease, thereby improving their level of diagnosis and treatment and reducing misdiagnoses and missed diagnoses.Methods:A patient with anti-synthase syndrome complicated by interstitial pneumonia and cardiac dysfunction, who was admitted to The First Affiliated Hospital of Xi'an Medical University in February 2020 due to limb weakness accompanied by paroxysmal cough for 2 years and aggravated symptoms for 10 days, was included in this study. The patient's clinical symptoms, physical signs, laboratory examination results, diagnosis and treatment process, and follow-up were retrospectively analyzed based on previous literature.Results:Through the general practitioner's SOAP consultation, physical examination, and imaging examination, the patient was diagnosed with anti-synthase syndrome complicated by interstitial pneumonia and cardiac dysfunction. Then rheumatology and immunology experts, respiratory medicine experts, and cardiovascular experts collaborated to provide a specialist diagnosis and treatment plan for the patient. Subsequently, the patient was referred to the department of rheumatology and immunology for specialized disease management. Finally, the patient was followed up in the general clinic. After the patient's condition stabilized, she gradually resumed her health.Conclusion:The multidisciplinary diagnosis and treatment scheme for anti-synthase syndrome can enhance general practitioners' understanding of the disease, make the diagnosis of the disease, and fully leverage the advantages of multi-disciplinary consultation and primary diagnosis in general medicine.

Magnesium and its alloys have been widely studied in the field of orthopaedics for their desirable mechanical properties, biodegradability and biocompatibility. However, the rapid degradation rate of magnesium and its alloys cannot match the healing process of bone itself, and may adversely affect the adhesion, growth and differentiation of surrounding cells, resulting in early loosening of implants, thus limiting their wide clinical application. Surface coating modification is a feasible and promising anti-corrosion solution to solve the problem of uncontrollable corrosion rate of magnesium implants. The surface coating modification technology can optimize the integration of the bone-implant interface by improving the bone induction ability of the implant surface (such as the bio-mimetic coating based on phosphate ceramics) or improving the corrosion resistance (such as the micro-arc oxidation coating with wear resistance and corrosion resistance, and the phytic acid coating with self-healing potential). While optimizing the degradation rate of magnesium implant, it can also realize multiple functions such as promoting osseointegration, drug delivery and photothermal therapy through composite component modification. In this paper, the advantages and disadvantages of different coating modification method on the surface of orthopaedic magnesium implants are comprehensively illustrated, and the key technologies in each preparation process are summarized and the composite modification methods are further discussed, so as to provide references for the preparation of multifunctional magnesium implants that meet the requirements of orthopaedic applications.

Objective To explore the value of deep learning models in predicting axillary lymph node(ALN)metastasis of breast cancer based on intratumoral and peritumoral dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI).Methods A retrospective analysis was conducted on cases from Tianjin Medical University Cancer Hospital and Laoshan Branch of Affiliated Hospital of Qingdao University,involving a total of 850 lesions in 850 patients.The region of interest within the tumor was delineated at the largest area of the lesion on the first enhancement images and automatically expanded by 3 mm and 6 mm in a conformal fashion.Deep learning prediction models based on ResNet50 were developed via intratumoral,peritumoral,and intratumoral combined peritumoral models,respectively,and a comprehensive prediction model was developed by integrating semantic features of imaging reports.Cases from Tianjin Medical University Cancer Hospital were randomly divided into training and test cohorts in a 7∶3 ratio,while cases from Laoshan Branch of Affiliated Hospital of Qingdao University served as the external validation cohort.The area under the curve(AUC),accuracy,sensitivity,specificity,F1-score,and Brier-score were calculated,respectively.Results The model incorporating intratumoral,peritumoral(3 mm),and semantic features demonstrated the highest performance,with AUC of 0.801[95％confidence interval(CI)0.765-0.845],0.781(95％CI 0.745-0.817),and 0.752(95％CI 0.700-0.793)in the training cohort,test cohort,and external validation cohort,respectively,and there was no significant difference in AUC between combined model and intratumoral/peritumoral model,respectively,but it demonstrated the higher sensitivity and F1-score,and the lower Brier-score.Conclusion Incorporating peritumoral images into the conventional model based on intratumoral images enhanced the predictive ability of ALN metastasis in breast cancer.

Proteolysis targeting chimera (PROTAC) refers to heterobifunctional small molecules that can simultaneously bind an E3 ubiquitin ligase and a target protein, enabling specific degradation of the target protein with the aid of the ubiquitin proteasome system. At present, most PROTAC drugs are in the clinical trial stage, and the ligands are mainly non-covalent compounds. PROTAC drugs have the advantage of overcoming drug resistance and degrading "undruggable" target proteins, but non-covalent ligands could lead to the hook effect that undermines drug efficacy. With its own advantages, covalent ligands can avoid the occurrence of this phenomenon, which is of great help to the development of PROTAC. This review summarizes the progress in preclinical and clinical research and application of PROTAC molecules targeting three different classes of protein targets, including intranuclear, transmembrane, and cytosolic proteins. We also offer perspective discussions to provide research ideas and references for the future development of PROTAC.
Proteolysis ; Proteolysis Targeting Chimera ; Proteasome Endopeptidase Complex/metabolism* ; Ubiquitin-Protein Ligases/metabolism* ; Proteins/metabolism* ; Ligands

Objective:To investigate the computed tomography(CT)and magnetic resonance imaging(MRI)features of retroperitoneal ded-ifferentiated liposarcoma(DDL),and improve the understanding of DDL and the accuracy of preoperative diagnosis.Methods:Clinical and imaging features of 25 patients with retroperitoneal DDL from Tianjin Medical University Cancer Institute&Hospital,confirmed by patho-logy from January 2012 to June 2022,were retrospectively analyzed.Results:Among 25 cases of retroperitoneal DDL,19 and 6 had single and multiple tumors,respectively and 10 and 15 were oval and irregular shaped tumors,respectively.Most lesions had unclear boundaries,with 15 cases invading the surrounding tissues and organs.Small vessel shadows were visible in 15 cases,while calcifications or ossifications were observed in 7 cases,and cystic necrosis was observed in only 3 cases.Enhanced scanning exhibits a centripetal and progressive con-tinuous augmentation characteristic defined as"slow in and slow out."According to its manifestations in CT and MRI,it can be divided into two types:type I(soft tissue mass type),where the tumor has a soft tissue component with no fat content(14 cases);and type Ⅱ(fat con-taining),where the tumors exhibit both soft tissue and adipose components,most of which are clearly defined and rarely present in a mosa-ic shape.In abnormal fat areas,cord-like fibrous septa can be seen.Among them,the intratumoral fat composition<50%was Ⅱa type(10 cases).Intratumor fat composition≥50%was type Ⅱb(1 case).Conclusions:Combined with imaging classification,a comprehensive ana-lysis of the CT and MRI imaging characteristics of retroperitoneal DDL is of great value for its preoperative qualitative diagnosis.

Objective:To observe the effect of enriched rehabilitation training on cognitive function, plasma mir-146a-5p microRNA precursor levels and inflammatory factors in persons with post-stroke cognitive impairment (PSCI).Methods:Fifty-eight persons with PSCI were randomly divided into an observation group and a control group, each of 29. The observation group was given enriched rehabilitation training, while the control group was provided with conventional cognitive rehabilitation training. The Montreal Cognitive Assessment Scale (MoCA), the Digit Span Test (DST), parts A and B of the Trail Making Test (TMT A-B) and the Modified Barthel Index (MBI) were used to assess the subjects′ cognitive functioning and their ability in the activities of daily living (ADL). Plasma levels of mir-146a-5p, IL-6 and TNF-α were detected before and after the treatment.Results:After treatment, the average MOCA, DST and MBI scores, as well as the average TMT A-B times had improved significantly for both groups. However, the observation group′s averages were significantly better than those of the control group on all three tests. After the treatment, the average plasma expression of miR-146a-5p had increased significantly in both groups, but the increase in the observation group was significantly greater. Plasma IL-6 and TNF-α levels were significantly lower than before the treatment, with the average TNF-α level in the observation group significantly lower than that of the control group.Conclusions:Enriched rehabilitation training can improve the cognition of stroke survivors more effectively than conventional cognitive rehabilitation training. That may be related to the up-regulation of plasma miR-146a-5p and reducing inflammation.

Objective:To investigate the value of logistic regression model based on the features of cone-beam breast CT (CBBCT) for the identification of benign and malignant masses in dense breast.Methods:The data of 106 patients (130 masses) with dense breast who underwent contrast-enhanced CBBCT examination and obtained pathological results from May 2011 to August 2020 were retrospectively analyzed as the training set. From August 2020, the data of 49 patients (54 masses) who met the same criteria were prospectively and consecutively collected and used as the validation set. Taking pathological results as the gold standard, the training set was divided into benign and malignant groups. The t-test, χ 2 test and Fisher′s exact test were used to compare the differences in CBBCT image characteristics between the two groups in the training set. A binary logistic regression model was established by multivariate analysis. ROC curves were used to assess the diagnostic efficacy of the model as a whole in the training and validation sets and the diagnostic efficacy of each feature in the model, and the cut-off value of the intensity (ΔCT) value was determined. The H-L method was used to test the goodness of fit of the model. Decision curve analysis (DCA) was drawn to validate the clinical power of the model. Results:Univariate analysis showed that the breast parenchymal background enhancement (BPE), shape, margin, lobulation, spiculation, density, calcifications, ΔCT value, enhancement pattern, non-mass enhancement, ipsilateral increased vascularity (IIV), and peripheral vascular signs had statistical difference between benign group and malignant group ( P<0.05). BPE, margin, ΔCT value and IIV were included in the multivariate analysis, the equation was logit( P′)=-8.510+0.830×BPE+0.822×margin+1.919× ΔCT+1.896 × IIV. The are a under curve of the model in the training set was 0.879 ( P<0.001) and in the validation set was 0.851 ( P=0.001). The are a under curve of BPE, margin, ΔCT value, and IIV in the diagnosis of malignant mass were 0.645, 0.711, 0.712, 0.775 (all P<0.05); the best cut-off value of ΔCT was 50.38 HU. The fit of this model was good ( P = 0.776). The DCA curve showed that when the risk threshold was 0.05-0.97, the net benefit rate was>0, and this model had some clinical value. Conclusion:The logistic regression model based on the features of CBBCT is helpful to distinguish benign and malignant masses in dense breasts.

Objective:To analyze and explore the common radiomics features of radiation pneumonitis (RP) in patients with lung cancer and esophageal cancer, and then establish a prediction model that can predict the occurrence of RP in two types of cancer after radiotherapy.Methods:Clinical data of 100 patients with stage Ⅲ lung cancer and 100 patients with stage Ⅲ esophageal cancer who received radical radiotherapy were retrospectively analyzed. The RP was graded by imaging data and clinical information during follow-up, and the planning CT images were collected. The whole lung was used as the volume of interest to extract radiomics features. The radiomics features, clinical and dosimetric parameters related to RP were analyzed, and the model was constructed by machine learning.Results:A total of 1691 radiomics features were extracted from CT images. After ANOVA and LASSO dimensionality reduction in lung cancer and esophageal cancer patients, 8 and 6 radiomics features associated with RP were identified, and 5 of them were the same. Using the random forest to construct the prediction model, lung cancer and esophageal cancer were alternately used as the training and validation sets. The AUC values of esophageal cancer and lung cancer as the independent validation set were 0.662 and 0.645.Conclusions:It is feasible to construct a common prediction model of RP in patients with lung cancer and esophageal cancer. Nevertheless, it is necessary to further expand the sample size and include clinical and dosimetric parameters to increase its accuracy, stability and generalization ability.

Objective To evaluate the accuracy of cone?beam breast CT (CBBCT) on tumor sizing in patients with invasive breast carcinoma and analyze the influence factors. Methods The preoperative CBBCT images of 82 female patients (85 breast lesions) with invasive breast carcinoma confirmed by pathology from November, 2011 to December, 2017 in Tianjin Medical University Cancer Hospital were included in this retrospective study. All the patients underwent the pathology and immunohistochemical test after operation. Tumor size estimation were performed on preoperative CBBCT images. Referring to tumor size measurement on pathology, all the lesions were divided into two groups. Concordance was defined as the discrepancy in diameter less than 0.5 cm, and the discordance was more than 0.5 cm. Pathology examination was performed after resection, and estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2(HER?2) and Ki?67 result were recorded. All the lesions were classified into molecular subtype, including 14 Luminal A, 50 Luminal B, 11 HER?2?enriched and 10 triple?negative. Intraclass correlation coefficient (ICC) and Pearson correlation coefficient were used to analyze the reliability of CBBCT on tumor sizing. CBBCT?pathology discordance was analyzed based on the clinical, histopathology and CBBCT features by using t test, Chi?square and Fisher exact test. ROC curve was used to analyze the cut?off value between tumor size and CBBCT?pathology discordance. Results The agreement between CBBCT (2.155 ± 0.799) cm and pathology (1.986 ± 0.933) cm measurement was on moderate degree based on the ICC value (ICC=0.781, P<0.01) and had positive correlation (r=0.803, P<0.01). CBBCT?pathology concordance was found in 71 lesions, and discordance in 14 lesions. The factors of family history, symptom, pathology type, molecular subtypes, histological grade, surrounding fat invasion, lymphatic invasion, axillary lymph node metastasis, HER?2 positive and Ki?67 high expression had no significant difference between two groups. ER or PR positive had significant difference, suggesting that the accuracy of evaluation on ER or PR negative lesions could be reduced. The cut?off value of ROC curve between tumor size and CBBCT?pathology discordance was 2.08 cm, and the area under curve was 0.70. In 85 lesions. 66 of 75 mass lesions and 5 of 10 non?mass lesions were consistent. The lesion type had significant difference between two groups (χ2=6.705, P=0.010), which suggested the CBBCT evaluation on non?mass could have discrepancy with pathology. Conclusion CBBCT has high accuracy on tumor size evaluation on invasive carcinoma. ER or PR negative, large lesions or non?tumor lesions should be alert to the impact of CBBCT?pathology discordance before surgery which may cause the alteration of surgical protocols.