Objective To evaluate the prevalence of full thickness rotator cuff tear in patients with proximal humeral fractures,and the relationships between different risk factors.Methods Data of 113 patients with proximal humeral fractures from January 2014 to January 2016 who underwent surgical treatment were retrospectively analyzed.The general characteristics of patients (age,sex,cause of injury) were recorded and the rotator cuff was evaluated preoperatively on MRI and explored intra-operatively.We calculated and compared the incidence rate of age,sex in patients with and without rotator cuff tear.And the incidence rate of rotator cuff tear in different types of fracture according to Neer classification was calculated.Results The full thickness ro tator cuff tear were indentified in 28 patients (24.8％),and 21 of them had been confirmed by MRI preoperatively.Statistical significant difference was found between patients with rotator cuff tear group (average of 75.11± 10.89 years old) and without rotator cuff tear group (64.68± 13.43) for the age of the patient.Full thickness rotator cuff tear was most common in Neer 3 GT fracture (33.3％,8/54),followed by Neer 2 GT (26.67％,4/15) and Neer 2 SN (17.65,6/34),however,no full thickness rotator was found in Neer 4 type fracture.There were 4 patients with total rotator cuff tear who had symptom of shoulder before the operation.The other 24 patients had no symptom of shoulder.Conclusion Patient age was found as a risk factor for full thickness rotator cuff tear in humeral proximal fractures with the rate of 24.8％.Full thickness rotator cuff tear was most common in Neer 3 GT fracture.

Objective To study the diagnostic value of endoscopic ultrasound guided fine needle aspiration (EUS-FNA) combined with the new category of papanicolaou society of cytopathology in solid pancreatic lesions (SPL) rapid on-site evaluation (ROSE).Methods From February 2011 to October 2014,225 patients with SPL who underwent EUS-FNA and obtained the cytological diagnosis were enrolled.The lesions were finally diagnosed according to pathological results,imaging and follow-up data,and then the sensitivity,specificity,and accuracy of EUS-FNA in the diagnosis of SPL were calculated based on the new papanicolaou society of cytopathology terminology.Logistic stepwise regression analysis was performed to analyze the risk factors.Results Among 225 patients with SPL,96 cases (42.7％)had uncertain cytological diagnosis,17.3％ (39/225) could not be diagnosed,8.0％ (18/225) were atypical lesions,and 17.3％ (39/225) were suspicious malignant carcinomas.Among 129 cases (57.3％)with certain cytological diagnosis,15.1％ (34/225) were benign lesions,14.7％ (33/225) were tumors (benign or others) and 27.6％ (62/225) were malignant tumors.When atypical lesions were added into non-tumor lesions or tumor lesions,the sensitivity,specificity and accuracy of diagnosis were 87.3 ％,91.7％,88.2％,and 94.7％,72.2％,90.3％,respectively.Serum CA125≥14 kU/L (odds ratio (OR) =7.13,95％ confidence interval (CI) 2.02 to 25.22,P=0.002) and history of biliary disease (OR=3.85,95％CI 1.22 to 12.51,P=0.022) were two independent risk factors of pancreatic tumors.Conclusions Despite of a high percentage of uncertain cytological diagnosis,EUS-FNA still has high diagnostic value in SPL when combined with the new papanicolaou society of cytopathology terminology.Furthermore,serum CA125≥14 kU/L and history of biliary disease may help to diagnose pancreatic tumors.

Objective:To establish a decision tree model of pediatric complicated appendicitis (CA) based on Pediatric Appendicitis Score (PAS) combined with inflammatory indicators, and to evaluate its clinical application efficacy in pediatrics.Methods:The clinical data of 544 children diagnosed with appendicitis in Children′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2018 to December 2021 was retrospectively analyzed. According to postoperative pathology, the children were divided into uncomplicated appendicitis group and CA group. The independent risk factors of CA were screened by univariate and multivariate logistic regression analysis, and these parameters were included to establish the decision tree model. The accuracy of the decision tree model was verified by receiver operating characteristic (ROC) curve.Results:Binary logistic regression analysis indicated that the PAS, C-reactive protein (CRP) and neutrophil to lymphocyte ratio (NLR) were identified as independent risk factors for complicated appendicitis in children (all P<0.05). PAS, CRP and NLR were included as covariables to construct the decision tree model and binary logistic regression model for predicting CA. The decision tree demonstrated an overall accuracy of 79.2% with a sensitivity of 86.7% and specificity of 71.9%, and achieved an area under curve (AUC) of 0.821(95% CI: 0.786-0.857). The binary logistic regression model had a sensitivity of 79.6% and specificity of 69.1%, with an overall accuracy of 75.1% and achieved an AUC of 0.808(95% CI: 0.770-0.845). Conclusions:The decision tree model based on PAS score combined with CRP, NLR is a simple, intuitive and effective tool , which can provide pediatric emergency physicians a reliable basis for diagnosis of pediatric CA.

Objective:This paper briefly reviewed the literature related to skin flaps published in Chinese Journal of Plastic Surgery ( CJPS) and Plastic and Reconstructive Surgery ( PRS) in recent five years (from January 2016 to December 2020) to compare the similarities and differences between these two journals and to direct future research. Methods:In May of 2021, literature with "flap" as the keyword in the titles and abstracts published in CJPS and PRS in recent five years were searched. Related literature published by CJPS were searched by Wanfang Data and CNKI database, and that of PRS were searched by PubMed and Scopus database. After removing the repetitive literature, the titles and abstracts were read to exclude the non-flap studies and non-original articles. By reading the full text and using bibliometrics, the total number of papers published, the number of papers on flap research, the level of evidence-based medicine evidence, the nationality and organization distribution of the authors, the type of flaps, the application of flaps, and new technologies were comprehensively analyzed. Results:The total number of papers published by CJPS in recent five years was 1 116, and 244 were included in this study. The total number of articles published in PRS in the same period was 4 562, and 268 were included in this study. Most of the articles published in PRS are from American authors. The number of articles published by Chinese authors is in the second place. In the past five years, authors from the mainland of China published 21 papers in PRS. Most of the articles published by CJPS are about the pedicle flap, while PRS is about the free flap. CJPS published more articles about the traditional flaps than perforator flaps, and PRS did the opposite. CJPS published articles mainly on the local flap, anterolateral thigh flap, and peroneal artery perforator flap, while PRS focused on the inferior epigastric artery perforator fibula bone or osteocutaneous flap, and anterolateral thigh flap. The indication of flap surgery reported by CJPS is the reconstruction of various defects, while the flaps reported by PRS are mainly used in breast reconstruction and other fields. In addition, computer-aided imaging, indocyanine green angiography, propeller flap, multilobed flap, and other new technologies and concepts have been widely reported in the literature related to skin flaps published in CPJS and PRS. Conclusions:In the recent five years, the flap research in China has been at the leading international level and has certain competitiveness. However, the study in China is limited to reporting clinical experience, and the level of evidence-based medicine is relatively low, so there is still a certain gap with the international frontier research.

Objective:This paper briefly reviewed the literature related to skin flaps published in Chinese Journal of Plastic Surgery ( CJPS) and Plastic and Reconstructive Surgery ( PRS) in recent five years (from January 2016 to December 2020) to compare the similarities and differences between these two journals and to direct future research. Methods:In May of 2021, literature with "flap" as the keyword in the titles and abstracts published in CJPS and PRS in recent five years were searched. Related literature published by CJPS were searched by Wanfang Data and CNKI database, and that of PRS were searched by PubMed and Scopus database. After removing the repetitive literature, the titles and abstracts were read to exclude the non-flap studies and non-original articles. By reading the full text and using bibliometrics, the total number of papers published, the number of papers on flap research, the level of evidence-based medicine evidence, the nationality and organization distribution of the authors, the type of flaps, the application of flaps, and new technologies were comprehensively analyzed. Results:The total number of papers published by CJPS in recent five years was 1 116, and 244 were included in this study. The total number of articles published in PRS in the same period was 4 562, and 268 were included in this study. Most of the articles published in PRS are from American authors. The number of articles published by Chinese authors is in the second place. In the past five years, authors from the mainland of China published 21 papers in PRS. Most of the articles published by CJPS are about the pedicle flap, while PRS is about the free flap. CJPS published more articles about the traditional flaps than perforator flaps, and PRS did the opposite. CJPS published articles mainly on the local flap, anterolateral thigh flap, and peroneal artery perforator flap, while PRS focused on the inferior epigastric artery perforator fibula bone or osteocutaneous flap, and anterolateral thigh flap. The indication of flap surgery reported by CJPS is the reconstruction of various defects, while the flaps reported by PRS are mainly used in breast reconstruction and other fields. In addition, computer-aided imaging, indocyanine green angiography, propeller flap, multilobed flap, and other new technologies and concepts have been widely reported in the literature related to skin flaps published in CPJS and PRS. Conclusions:In the recent five years, the flap research in China has been at the leading international level and has certain competitiveness. However, the study in China is limited to reporting clinical experience, and the level of evidence-based medicine is relatively low, so there is still a certain gap with the international frontier research.

Objective: To investigate the clinical efficacy of arthroscopic irrigation combined with surgical debridement in the treatment of shoulder infection after arthroscopic rotator cuff repair. Methods: Data of 4 post-operative infected patients [(male 3 cases, female 1 case; 55 years (51-61 years)] after arthroscopic rotator cuff repair who underwent arthroscopic irrigation combined with surgical debridement from January 2016 to June 2019 were retrospectively analyzed. Less than 1 month after surgery, swelling, pain in the surgical area occurred and all patients had fever, abscess and sinus. Hematology and radiology were conducted immediately after admission. Antibiotic treatment was applied, and adjusted according to the culture results timely. All patients underwent arthroscopic irrigation combined with surgical debridement. Antibiotics continued accordingly after the operation. Blood routine, erythrocyte sedimentation rate, C-reactive protein, X-ray, etc. were rechecked regularly to evaluate the symptomatic relief of the infection and prognosis. Visual analogue scale (VAS) and American Shoulder and Elbow Surgeons (ASES) score were used to evaluate shoulder function during the pre-operative and post-operative follow-up period. Results: The surgery was successfully completed in all 4 patients. One was treated with VSD for vacuum suction and the wound was closed one week later. The results of microbial culture showed that 2 cases were Mycobacterium tuberculosis positive, 1 case Pseudomonas aeruginosa positive, and 1 case was Staphylococcus aureus positive. After treatment, the shoulder sinuses of all patients were healed, without swelling, pain, etc. The follow-up time was 3, 4, 32, and 33 months, respectively. There was no recurrence of infection until the latest follow-up. The joint mobility and scores were better than the situation of preoperative. The VAS score and ASES score of 2 patients with early debridement (< 1 month duration of infected symptoms) were respectively improved significantly from 5 and 40, 6 and 23 before operation to 1 and 80, 1 and 73 respectively at the latest follow up. The VAS score and ASES score of other 2 patients (> 6 months duration of infected symptoms) were respectively improved from 6 and 28, 6 and 32 to 1 and 62, 2 and 65 respectively. All patients were satisfied with the results. Conclusion Early arthroscopic irrigation combined with surgical debridement is an effective method to treat the post-operative infections after arthroscopic rotator cuff repair.

Acid-base dissociation constant (pK_a) is a key physicochemical parameter in chemical science, especially in organic synthesis and drug discovery. Current methodologies for pK_a prediction still suffer from limited applicability domain and lack of chemical insight. Here we present MF-SuP-pK_a (multi-fidelity modeling with subgraph pooling for pK_a prediction), a novel pK_a prediction model that utilizes subgraph pooling, multi-fidelity learning and data augmentation. In our model, a knowledge-aware subgraph pooling strategy was designed to capture the local and global environments around the ionization sites for micro-pK_a prediction. To overcome the scarcity of accurate pK_a data, low-fidelity data (computational pK_a) was used to fit the high-fidelity data (experimental pK_a) through transfer learning. The final MF-SuP-pK_a model was constructed by pre-training on the augmented ChEMBL data set and fine-tuning on the DataWarrior data set. Extensive evaluation on the DataWarrior data set and three benchmark data sets shows that MF-SuP-pK_a achieves superior performances to the state-of-the-art pK_a prediction models while requires much less high-fidelity training data. Compared with Attentive FP, MF-SuP-pK_a achieves 23.83% and 20.12% improvement in terms of mean absolute error (MAE) on the acidic and basic sets, respectively.

Prediction of the interactions between small molecules and their targets play important roles in various applications of drug development, such as lead discovery, drug repurposing and elucidation of potential drug side effects. Therefore, a variety of machine learning-based models have been developed to predict these interactions. In this study, a model called auxiliary multi-task graph isomorphism network with uncertainty weighting (AMGU) was developed to predict the inhibitory activities of small molecules against 204 different kinases based on the multi-task Graph Isomorphism Network (MT-GIN) with the auxiliary learning and uncertainty weighting strategy. The calculation results illustrate that the AMGU model outperformed the descriptor-based models and state-of-the-art graph neural networks (GNN) models on the internal test set. Furthermore, it also exhibited much better performance on two external test sets, suggesting that the AMGU model has enhanced generalizability due to its great transfer learning capacity. Then, a naïve model-agnostic interpretable method for GNN called edges masking was devised to explain the underlying predictive mechanisms, and the consistency of the interpretability results for 5 typical epidermal growth factor receptor (EGFR) inhibitors with their structure‒activity relationships could be observed. Finally, a free online web server called KIP was developed to predict the kinome-wide polypharmacology effects of small molecules (http://cadd.zju.edu.cn/kip).

Protein neddylation is catalyzed by a three-enzyme cascade, namely an E1 NEDD8-activating enzyme (NAE), one of two E2 NEDD8 conjugation enzymes and one of several E3 NEDD8 ligases. The physiological substrates of neddylation are the family members of cullin, the scaffold component of cullin RING ligases (CRLs). Currently, a potent E1 inhibitor, MLN4924, also known as pevonedistat, is in several clinical trials for anti-cancer therapy. Here we report the discovery, through virtual screening and structural modifications, of a small molecule compound HA-1141 that directly binds to NAE in both

Chaperone-mediated autophagy (CMA) is a lysosome-dependent selective degradation pathway implicated in the pathogenesis of cancer and neurodegenerative diseases. However, the mechanisms that regulate CMA are not fully understood. Here, using unbiased drug screening approaches, we discover Metformin, a drug that is commonly the first medication prescribed for type 2 diabetes, can induce CMA. We delineate the mechanism of CMA induction by Metformin to be via activation of TAK1-IKKα/β signaling that leads to phosphorylation of Ser85 of the key mediator of CMA, Hsc70, and its activation. Notably, we find that amyloid-beta precursor protein (APP) is a CMA substrate and that it binds to Hsc70 in an IKKα/β-dependent manner. The inhibition of CMA-mediated degradation of APP enhances its cytotoxicity. Importantly, we find that in the APP/PS1 mouse model of Alzheimer's disease (AD), activation of CMA by Hsc70 overexpression or Metformin potently reduces the accumulated brain Aβ plaque levels and reverses the molecular and behavioral AD phenotypes. Our study elucidates a novel mechanism of CMA regulation via Metformin-TAK1-IKKα/β-Hsc70 signaling and suggests Metformin as a new activator of CMA for diseases, such as AD, where such therapeutic intervention could be beneficial.