Osteoarthritis (OA), the most prevalent joint disease of late life, is closely linked to cellular senescence. Previously, we found that the senescence of fibroblast-like synoviocytes (FLS) played an essential role in the degradation of cartilage. In this work, single-cell sequencing data further demonstrated that cartilage acidic protein 1 (CRTAC1) is a critical secreted factor of senescent FLS, which suppresses mitophagy and induces mitochondrial dysfunction by regulating SIRT3 expression. In vivo, deletion of SIRT3 in chondrocytes accelerated cartilage degradation and aggravated the progression of OA. Oppositely, intra-articular injection of adeno-associated virus expressing SIRT3 effectively alleviated OA progression in mice. Mechanistically, we demonstrated that elevated CRTAC1 could bind with NRF2 in chondrocytes, which subsequently suppresses the transcription of SIRT3 in vitro. In addition, SIRT3 reduction could promote the acetylation of FOXO3a and result in mitochondrial dysfunction, which finally contributes to the degradation of chondrocytes. To conclude, this work revealed the critical role and underlying mechanism of senescent FLSs-derived CRTAC1 in OA progression, which provided a potential strategy for the OA therapy.

Objective To explore whether hepatocyte Perilipin-2(Plin2)is involved in the development of fatty liver related to comparative gene identification-58(CGI-58)deficiency mice and compare the effects of Plin2 and Plin3 on lipid droplet formation and lipid accumulation.Methods Based on CGI-58Flox/Flox mice as animal model,the adeno-associated viruses targeting mouse liver,CGI-58 knockout and Plini2 knockdown were achieved by co-expression Cre protein and micro-RNA targeting Plin2(Mi-KD).Then CGI-58 deficiency mice were used as control(NC)to detect the differences in metabolic phenotype and liver pathology.AML-12 mouse hepatocytes were used as cellular model and interfered with siRNA to achieve Plin2/Plin3 knockdown in AML-12 cells.Lipid droplet formation and lipid accumulation were compared with Bodipy staining and enzyme colorimetry in basal condition or lipid-overloaded condition(OA inducement)after Plin2/Plin3 knockdown.Results Plin2 knockdown(Mi-KD)reduced PLIN2 protein level by＞99％in mouse livers.Mi-KD decreased hepatomegaly(P=0.019 5)and liver injury(P=0.000 4),while reduced the histological NAS score(P=0.000 2)and hepatic triglyceride content(P=0.016 6)in the CGI-58 deficiency female mice.Mi-KD prevented microvesicular hepatic steatosis in the CGI-58 deficient female mice.Plin3 knockdown significantly reduced the triglyceride content in basal condition of hepatocytes(P=0.001 4),and Plin2 knockdown just showed a decreased trend.Plin2 or Plin3 knockdown significantly reduced the triglyceride content separately in lipid-overloaded hepatocytes(P＜0.05).Conclusion Hepatocyte Plin2 is essential in the development of microvesicular hepatic steatosis caused by CGI-58 deficiency.Both Plin2 and Plin3 are involved in lipid droplet formation and lipid accumulation in hepatocytes,and Plin3 shows a stronger effect.

OBJECTIVE: To investigate the feasibility and effectiveness of "tail compression fixation+suture bridge" technology under shoulder arthroscopy for treating primary tear in medial enthesis of rotator cuff. METHODS: The clinical data of 11 patients with primary tear in medial enthesis of rotator cuff who met the selection criteria between October 2020 and October 2022 were retrospectively analyzed, including 3 males and 8 females, aged 39-79 years, with an average of 61.0 years. Rotator cuff injury was caused by traumatic fall in 8 cases, and the time from injury to admission was 1-4 months, with an average of 2.0 months; the remaining 3 cases had no obvious inducement. The active range of motion of the affected shoulder was limited, with an active forward flexion range of motion of (64.1±10.9)°, abduction of (78.1±6.4)°, internal rotation of (48.2±6.6)°, and external rotation of (41.8±10.5)°; 5 cases had shoulder stiffness. The preoperative visual analogue scale (VAS) score was 7.8±0.8 and the American Society of Shoulder and Elbow Surgeons (ASES) score was 23.9±6.4. The patients were treated with "tail compression fixation+suture bridge" technology under shoulder arthroscopy, and the pain and functional recovery were evaluated by VAS score, ASES score, and active range of motion of shoulder joint at last follow-up; MRI was performed after operation, and the integrity of rotator cuff was evaluated by Sugaya classification system. RESULTS: All the 11 patients were followed up 2-22 months, with an average of 13.5 months. All incisions healed by first intention, and there was no complication such as infection, rotator cuff re-tear, and anchor falling off. At last follow-up, the VAS score was 0.8±0.7 and the ASES score was 93.5±4.2, which significantly improved when compared with those before operation ( P<0.05). All 11 patients had no significant swelling in the shoulders, and the active range of motion was (165.1±8.8)° in flexion, (75.3±8.4)° in abduction, (56.6±5.5)° in internal rotation, and (51.8±4.0)° in external rotation, which significantly improved when compared with those before operation ( P<0.05). Shoulder MRI showed adequate tendon thickness and good continuity in 9 cases, including 4 cases with partial high signal area; and 2 cases with inadequate tendon thickness but high continuity and partial high signal area. According to Sugaya classification system, there were 4 cases of type 1 (36.4%), 5 cases of type 2 (45.5%), and 2 cases of type 3 (18.1%). CONCLUSION For the patients with primary tear in medial enthesis of rotator cuff, the "tail compression fixation+suture bridge" technology under shoulder arthroscopy is simple and effective.
Male ; Female ; Humans ; Rotator Cuff/surgery* ; Shoulder ; Arthroscopy ; Retrospective Studies ; Treatment Outcome ; Rotator Cuff Injuries/surgery* ; Rupture ; Shoulder Joint/surgery* ; Sutures ; Range of Motion, Articular

Objective    To explore the application value of machine learning models in predicting postoperative survival of patients with thoracic squamous esophageal cancer. Methods    The clinical data of 369 patients with thoracic esophageal squamous carcinoma who underwent radical esophageal cancer surgery at the Department of Thoracic Surgery of Northern Jiangsu People's Hospital from January 2014 to September 2015 were retrospectively analyzed. There were 279 (75.6%) males and 90 (24.4%) females aged 41-78 years. The patients were randomly divided into a training set (259 patients) and a test set (110 patients) with a ratio of 7 : 3. Variable screening was performed by selecting the best subset of features. Six machine learning models were constructed on this basis and validated in an independent test set. The  performance of the models' predictions was evaluated by area under the curve (AUC), accuracy and logarithmic loss, and the fit of the models was reflected by calibration curves. The best model was selected as the final model. Risk stratification was performed using X-tile, and survival analysis was performed using the Kaplan-Meier method with log-rank test. Results    The 5-year postoperative survival rate of the patients was 67.5%. All clinicopathological characteristics of patients between the two groups in the training and test sets were not statistically different (P>0.05). A total of seven variables, including hypertension, history of smoking, history of alcohol consumption, degree of tissue differentiation, pN stage, vascular invasion and nerve invasion, were included for modelling. The AUC values for each model in the independent test set were: decision tree (AUC=0.796), support vector machine (AUC=0.829), random forest (AUC=0.831), logistic regression (AUC=0.838), gradient boosting machine (AUC=0.846), and XGBoost (AUC=0.853). The XGBoost model was finally selected as the best model, and risk stratification was performed on the training and test sets. Patients in the training and test sets were divided into a low risk group, an intermediate risk group and a high risk group, respectively. In both data sets, the differences in surgical prognosis among three groups were statistically significant (P<0.001). Conclusion    Machine learning models have high value in predicting postoperative prognosis of thoracic squamous esophageal cancer. The XGBoost model outperforms common machine learning methods in predicting 5-year survival of patients with thoracic squamous esophageal cancer, and it has high utility and reliability.

Objective:To explore the incidence and risk factors of preoperative deep vein thrombosis (DVT) of elective total joint arthroplasty (TJA).Methods:Data of 500 patients before TJA from March 2015 to August 2016 who underwent ultrasound surveillance were retrospectively analyzed. All patients were divided into DVT group and non-DVT group according to results of ultrasound. Parameters including demographic data, basic medical history, and surgical information and laboratory indexes were collected. Risk factors were assessed via univariate, multivariate and logistic regression analysis.Results:Preoperative DVT was detected in 23 cases (4.6%, 23/500), all of which occurred in the intermuscular vein with no symptom, and among them there were 16 cases (5.6%, 16/285) before total knee arthroplasty and 7 cases (3.3%, 7/215) before total hip arthroplasty. Univariate analysis showed that age ( t=2.266, P=0.024), female patients ( χ2=4.028, P=0.045), history of hypertension ( χ2=7.907, P=0.005), D-dimer ≥0.5 μg/ml ( χ2=13.171, P < 0.001) were significantly higher than those in non-DVT group, and the differences were statistically significant. Multivariate analysis showed that D-dimer ≥0.5 μg/ml [ OR=6.655, 95% CI (1.929, 22.960), P=0.003] and history of hypertension [ OR=2.715, 95% CI (1.017, 7.250), P=0.046] were independent risk factors for preoperative DVT. Among them, the thrombus of 14 cases located in the operation side, 6 cases in non-operation side, and 3 cases in bilateral sides. Postoperative ultrasound showed that newly DVT occurred in 9 patients of whom 5 cases located in the contralateral muscular veins and 4 cases in the nearby muscular veins. After discharge, 22 patients (95.7%) with preoperative DVT were further evaluated by ultrasound. The average follow-up time was 3.0 months (range from 6 weeks to 9 months). The results showed that thrombus of 7 cases were completely dissolved, 13 cases were partially dissolved, and 2 cases remained unchanged. Thrombus extensions to proximal veins or symptomatic PE were not found. Conclusion:The incidence of preoperative DVT in patients with elective joint replacement was about 4.6%, among which D-dimer ≥0.5 μg/ml and history of hypertension were the risk factors for preoperative thrombosis.

OBJECTIVE：To prov ide referen ce for clinical safe and rational use of belimumab by mining the risk signals of adverse drug event （ADE）. METHODS ：ADE reports related to belimumab were collected from FDA adverse event reporting system（FAERS）from the first quarter of 2015 to the first quarter of 2021. The reporting odds ratio （ROR）method and the Medicines and Healthcare Products Regulatory Agency （MHRA）method were adopted to mine the ADE risk signals related to belimumab，setting the threshold as the number of reports ＞3 and the lower limit of 95％ CI ＞1（ROR method ）and the proportional reporting ratio （PRR）＞2，and χ2 ＞4（MHRA method ）. ADEs were counted and classified by using the preferred system organ class （SOC）and preferred term （PT）of Medical Dictionary for Regulatory Activities （MedDRA）. RESULTS & CONCLUSIONS：A total of 3 529 ADE reports with belimumab as the primary suspicious drug were screened ，in which female patients（90.31％）were much more than male patients （6.15％）；age distribution was concentrated in 18-59 years old （41.80％）. There were 1 234 cases（34.97％）of severe ADE reports ，mainly involving hospital or prolonged hospital stay. Most of the reporters were consumers or other non-medical professionals （81.84％）. North America reported the most （70.39％）and the main reporting country was the United States （2 029 reports）. A total of 180 PTs were mined from 3 529 reports，in addition to PTs associated with primary disease （systemic lupus erythematosus ，pain，arthralgia，pyrexia，weight decreased ，swelling，oropharyngeal pain ， etc.），PTs related to medication error （product dose omission ，inappropriate schedule of product administration ，underdose， product availability issue ，etc.）and PTs related to infection （influenza，urinary tract infection ，infection，sinusitis，etc.）were reported in a large number of cases. Twenty-six SOCs were involved ，the top 10 SOC in ADE reports were all kinds of injuries ， poisoning and surgical complications （2 225 reports），infections and infectious diseases （1 247 reports），general disorders and administration site conditions （1 196 reports），musculoskeletal and connective tissue disorders （1 195 reports），surgical and medical procedures（515 reports），etc. PTs in SOC in the first place （all kinds of injuries ，poisoning and surgical complications ）of ADE reports were all related to medication error ；herpes zoster ，kidney infection and cellulitis in SOC in the second place （infections and infectious diseases ）of ADE reports were not included in the drug instruction of belimumab ；most PTs in SOCs such as various nervous system diseases ，immune system diseases ，mental diseases ，benign，malignant and unknown tumors （including cystic and polypoid）which were taken attention in clinic were not included in the drug instruction of belimumab. It is suggested to avoid medication errors as far as possible in clinical use of belimumab ，and to guard against adverse reactions such as herpes zoster ， kidney infection ，cellulitis and various nervous system diseases ，immune system diseases and mental diseases. In addition ，the patients with malignant tumor or related history should use belizumab carefully.

Objective:To investigate knowledge, attitude and practice intention of medical students on advance care planning (ACP) and to analyze the relevant influencing factors.Methods:This study was a cross-sectional study. From April to May 2019, the convenience sampling method was used to select medical students who were interning in 3 medical schools and affiliated hospitals in Guangdong Province as the research objects. General information questionnaire and self-designed ACP Knowledge, Attitude and Practice Intention Questionnaires were uesd to investigate. Multiple linear regression analysis was used to influencing factors. A total of 276 questionnaires were recovered in this survey, of which 274 were valid, the effective response rate was 99.3%.Results:The average accuracy rate of the ACP Knowledge Questionnaire for medical students was 48.75%. The average score of items of the ACP Attitude Questionnaire was (4.00±0.53) . The average score of items of the ACP Practice Intention Questionnaire for medical students was (3.94±0.59) . The results of multiple linear regression analysis showed that the attitude toward the major they studied, whether they had the part-time social experience, whether they heard of ACP and whether they received ACP training or courses were influencing factors of ACP knowledge for medical students ( P<0.05) . Whether they had clinical practice and whether they had the treatment experience of patients' death were the influencing factors of ACP attitude of medical students ( P<0.05) . Attitudes towards the major they learned and whether they had any experience in the treatment of patients' death were the influencing factors of ACP practice intention of medical students ( P<0.05) . Conclusions:Medical students have a certain acceptance of ACP, but the awareness rate of ACP is generally low. Consideration should be given to improving the relevant education methods and content to prepare for the role adaptation of medical students in future clinical work, improving the humanistic care literacy of medical students and promotion of ACP in the clinical practice.

Objective:To compared theclinic effectiveness ofBikini incision with that of traditional incisionbased on a short-term following and provide a suggesting reference for surgeons.Methods:The data of patients who accepted total hip arthroplasty (THA) through direct anterior approach (DAA) from January to November in 2019 were collected, male 13 and female 73, age 67.5±11.8 years (42-90 years). Forty-three patients were recruited to analyzeas one retrospective study in each group. Bikini incision: male 5 and female 38; age 69.7±10.8 years (51-90 years), following up 5.7 months (3.0-8.5 months). Traditional incision: male 8 and female 35; age 66.1±10.6 years (42-90 years), following up 6.5 months (3.0-10.0 months). The length area of incision, duration of operation, intraoperative blood loss, the rate of infection, lateral femoral cutaneous nerve (LFCN) deficits, and the Harris score were analyzed between those two groups. The scars were evaluated according toPatients Scar Assessment Scale and Vancouver Scar Scale.Results:There were no significant difference in age, sex, BMI and diseases distribution between Bikini and traditional incision group. The length of incision, duration of operation, analgesic drugs dosage and hip Harris score wereanalysed no significant difference between those two groups. No patients in those twogroupssuffered from infection of incision. As to LFCN deficits, Bikini group had lower than traditional group (11.6% vs 32.6%, P=0.019). The scar area of Bikini group 1.0±0.4 cm 2 wasmeasured smaller rate than that of traditional group 16.5±28.7 cm 2. As to the Patients Scar Assessment Scale and Vancouver Scar Scale, Bikini group was 8.2±3.2 and 2.4±1.8, which was better than traditional group which was 17.0±5.8 and 4.2±3.0. Conclusion:Compared to traditional incision, Bikini incision was evaluated having significant lower rate of LFCN deficits and smaller scar,good cosmetic appearance and clinical application value.

Objective:To test whether the constructed intervention model of advance care planning (ACP) for patients with advanced cancer can be successfully implemented and the preliminary intervention effect, which provides reference for empirical research.Methods:32 cases of advanced cancer patients and 25 cases of their families at the Fifth Affiliated Hospital of Zunyi Medical University, Zhuhai were selected. The patients were subdivided into the experimental group and the control group by random number table method. The control group received routine nursing, while the experimental group adopted the intervention model of "VIP for future care" on the basis of customary nursing. We measured the main outcome indicators: enrollment rate, consent rate, completion rate and loss of follow-up rate and secondary outcome indicators: decision-making certainty, end-of-life care preference and post-intervention satisfaction of patients and their families, within 1 week and 1 month after intervention.Results:The enrollment rate, consent rate and loss of follow-up rate were 74.6% (206/276), 36.9% (76/151)and 15.6% (5/32), respectively. After intervention, the completion rates of the experimental group and the control group were 16/16 and 15/16 within one week, and 14/16 and 13/16 within one month. All of the family members were conducted during the follow-up period. The intervention mode of "VIP for future care" had a statistically significant difference in decision-making certainty between the two groups of patients ( β=0.63, 95% CI 0.08-1.18, P<0.05), no statistically significant difference in end-of-life care preference between the two groups of patients and their families ( P>0.05), and had a statistically significant difference in "whether to recommend this project to others" between the two groups ( χ2 value was 4.167 , P<0.05). Conclusions:On the premise of sufficient preparation, the "VIP for future care" intervention mode can be successfully implemented in advanced cancer patients in mainland China, can improve the decision-making certainty of patients and the satisfaction of patients and their families, and it is recommended. And should be applied to ACP intervention for patients with advanced cancer.

Objective To evaluate the feasibility of anticoagulant therapy for acute proximal deep vein thrombosis without inferior vena cava filter placement for femoral neck patients before hip arthroplasty.Methods From January 2013 to August 2017,9 femoral neck fractures patients with acute proximal deep vein thrombosis before hip arthroplasty were enrolled into this study.There were 3 men and 6 women.The average age was 76.44±5.39 years old (range,69 to 83 years old).The average injured time before admission was 4.00±4.06 days.All patients received anticoagulant therapy without placement of inferior vena cava filter before hip arthroplasty.Four patients received Rivaroxaban 10mg,two times per day,while two patients received Enoxaparin 0.4 ml,two times per day;3 cases received Batroxobin 0.5 ml,every other day combined with Rivaroxaban 10 mg one time per day or Enoxaparin 0.4 ml,one time per day.The size of thrombus before and after treatment,changes of coagulation markers,the outcome of thrombosis before surgery,during surgery,postoperatively and during follow-up,the related complications were recorded.Results The diagnosis time for proximal DVT was 3.89±3.01 days after admission.8 patients showed proximal DVT combined with distal thrombus and 1 patient showed isolated proximal DVT.The average length of proximal thrombus was 10.78±6.10 cm (range,4.0-20.0 cm).The mean duration of treatment was 14.22±7.03 days.The results showed 5 proximal DVTs have complete disappeared,3 cases significantly improved,and 1 case had no change but showed stable.After treatment,the length of the proximal thrombus was significantly decreased (10.77±6.10 cm vs.4.39±6.50 cm),there were statistically significant between two groups (t=3.429,P=0.009);D-dimer was significantly lower after treatment (10.47±4.87 μg/ml vs.2.59± 1.60 μg/ml) with statistical difference (t=4.970,P=O.O01).However,no statistical significance was found in other coagulation parameters such as plasma prothrombin time,the international normalized ratio,activated partial thromboplastin time,thrombin time,fibrinogen.Incision exudate occurred in one patient and anticoagulant therapy was paused,however,two days later,DVT recurred and then the patient received continuous therapy with drug anticoagulation.The average time for postoperative follow-up was 8.3±7.6 months.At the latest follow-up,4 cases had thoroughly recovered with the thrombi fully resolved;4 cases had significantly improved including three thrombi partly locating in the muscular veins and one partly locating in the infra-popliteal vein.One case became more severe after discharge and received continuous anticoagulant therapy.No death,symptomatic pulmonary embolism,bleeding and other adverse events occurred.Conclusion Inferior vena cava filter placement for femoral neck fracture patients with acute proximal venous thrombosis before hip arthroplasty may not be potent.Anticoagulant therapy which make the proximal thrombus completely dissolved or stabilized before surgery may be effective.