Objective:To summarize the clinical and genetic characteristics of pseudoachondroplasia and multiple epiphyseal dysplasia caused by COMP gene variants in pediatric patients.Methods:This retrospective study concluded 15 pediatric patients with COMP-related pseudoachondroplasia and multiple epiphyseal dysplasia at Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine from July 2013 to August 2024. This paper analyzed clinical manifestations, laboratory findings and genetic testing.Results:This cohort comprised 15 pediatric patients (8 males and 7 females) with a diagnostic age of 5.3 (1.8,9.3) years. The major clinical presentations included abnormal gait (15/15), brachydactyly (11/15), genu varum (12/15), irregular metaphyseal changes (14/14) and epiphyseal dysplasia (14/14). Genetic analysis revealed 13 cases of pseudoachondroplasia and 2 multiple epiphyseal dysplasias cases associated with COMP gene variants. Fifteen variants were identified (8 pathogenic and 7 likely pathogenic), including 2 novel variants (c.1223A>G, c.1378G>C). Thirteen of these patients had variations clustered in exons 8-14 encoding the calmodulin-like domains, with c.1414_1419dupGACGAC emerging as a hotspot variant.Conclusions:COMP-related pseudoachondroplasia and multiple epiphyseal dysplasia predominantly manifest with gait abnormalities and skeletal deformities. COMP gene pathogenic variations were mainly located in calmodulin-like domains.

Objective To investigate the occurrence of hemodialysis events in patients who received maintenance hemodialysis in outpatient setting in Liangshan Yi Autonomous Prefecture of Sichuan Province,and provide basis for the formulation of infection prevention and control strategies in this area.Methods Based on the standards from Center for Disease Control and Prevention-National Healthcare Safety Network(CDC-NHSN)as well as the WS/T 312-2023 standards,four public hospitals(two secondary and two tertiary hospitals)in three counties and one city of Liangshan Yi Autonomous Prefecture were selected,and prospective surveillance method was adopted.A total of 826 patients(n=8 675 cases)who received maintenance hemodialysis on the first two working day of each month from March 2024 to March 2025 were surveilled.Data were collected with standardized form by infection control teams in dialysis centers.Statistical analysis was conducted.Results During the surveillance period,the incidence of hemodialysis events was 5.15％(447/8 675).The incidence(16.67％,36/216)and mortality(10.00％,4/40)of hemodialysis events in patients with non-tunneled catheters were the highest among patients with all types of ac-cess.Patients with tunneled-catheters had the highest hospitalization rate(42.86％).Systemic use of antimicrobial agents accounted for 82.33％(368/447).Upper respiratory tract infection was the main infection(38.32％).In-fection at the puncture site of vascular access accounted for 16.78％(75/447).Four cases(0.89％,4/447)had positive blood culture.Conclusion Systemic antimicrobial use and infection at vascular access puncture site is the most frequent events in patients who receive maintenance hemodialysis in outpatient setting in Liangshan Yi Autono-mous Prefecture of Sichuan Province.Patients with non-tunneled catheters have the highest rate of hemodialysis events.

Objective To investigate the occurrence of hemodialysis events in patients who received maintenance hemodialysis in outpatient setting in Liangshan Yi Autonomous Prefecture of Sichuan Province,and provide basis for the formulation of infection prevention and control strategies in this area.Methods Based on the standards from Center for Disease Control and Prevention-National Healthcare Safety Network(CDC-NHSN)as well as the WS/T 312-2023 standards,four public hospitals(two secondary and two tertiary hospitals)in three counties and one city of Liangshan Yi Autonomous Prefecture were selected,and prospective surveillance method was adopted.A total of 826 patients(n=8 675 cases)who received maintenance hemodialysis on the first two working day of each month from March 2024 to March 2025 were surveilled.Data were collected with standardized form by infection control teams in dialysis centers.Statistical analysis was conducted.Results During the surveillance period,the incidence of hemodialysis events was 5.15％(447/8 675).The incidence(16.67％,36/216)and mortality(10.00％,4/40)of hemodialysis events in patients with non-tunneled catheters were the highest among patients with all types of ac-cess.Patients with tunneled-catheters had the highest hospitalization rate(42.86％).Systemic use of antimicrobial agents accounted for 82.33％(368/447).Upper respiratory tract infection was the main infection(38.32％).In-fection at the puncture site of vascular access accounted for 16.78％(75/447).Four cases(0.89％,4/447)had positive blood culture.Conclusion Systemic antimicrobial use and infection at vascular access puncture site is the most frequent events in patients who receive maintenance hemodialysis in outpatient setting in Liangshan Yi Autono-mous Prefecture of Sichuan Province.Patients with non-tunneled catheters have the highest rate of hemodialysis events.

Objective:To summarize the clinical and genetic characteristics of pseudoachondroplasia and multiple epiphyseal dysplasia caused by COMP gene variants in pediatric patients.Methods:This retrospective study concluded 15 pediatric patients with COMP-related pseudoachondroplasia and multiple epiphyseal dysplasia at Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine from July 2013 to August 2024. This paper analyzed clinical manifestations, laboratory findings and genetic testing.Results:This cohort comprised 15 pediatric patients (8 males and 7 females) with a diagnostic age of 5.3 (1.8,9.3) years. The major clinical presentations included abnormal gait (15/15), brachydactyly (11/15), genu varum (12/15), irregular metaphyseal changes (14/14) and epiphyseal dysplasia (14/14). Genetic analysis revealed 13 cases of pseudoachondroplasia and 2 multiple epiphyseal dysplasias cases associated with COMP gene variants. Fifteen variants were identified (8 pathogenic and 7 likely pathogenic), including 2 novel variants (c.1223A>G, c.1378G>C). Thirteen of these patients had variations clustered in exons 8-14 encoding the calmodulin-like domains, with c.1414_1419dupGACGAC emerging as a hotspot variant.Conclusions:COMP-related pseudoachondroplasia and multiple epiphyseal dysplasia predominantly manifest with gait abnormalities and skeletal deformities. COMP gene pathogenic variations were mainly located in calmodulin-like domains.

Objective:To explore the method of constructing an early mortality risk prediction model for patients with sepsis-induced cardiorenal syndrome by machine learning algorithm, so as to provide a basis for early clinical identification of high-risk patients and accurate treatment.Methods:Patients with sepsis-induced cardiorenal syndrome from January 1, 2015 to May 31, 2019 in Tongji Hospital, Tongji University were enrolled. Basic characteristics, laboratory indexes, hospitality treatment and other relevant baseline data were collected. Thirty-day mortality was defined as the primary end-point event after the enrolled patients were diagnosed. Python software was applied to establish different machine learning models, and the area under the receiver -operating characteristic curve ( AUC) was used to evaluate the predictive value of models. Disease-related risk factors were selected according to the most optimal model. Importantly, visualized decision tree and semi-naive Bayesian (sNB) models were established to further explore the interrelationship between these risk factors. Results:A total of 340 patients were included, of whom 114 patients (33.5%) died within 30 days after diagnosis. The AUC of support vector machine (SVM), random forest (RF), gradient boosting decision tree (GBDT), extreme gradient boosting (XGBoost), and light gradient boosting machine (LGBM) prediction models were 0.652, 0.868, 0.870, 0.754, and 0.852, respectively. The AUC of GBDT model had the most efficiency to predict end-point events, and the prediction AUC value was better. According to the feature ranking of GBDT model, the relevant influencing factors were selected, including total sequential organ failure assessment (SOFA) score, neural SOFA score, vasoactive drug application, cardiac troponin I (cTNI), age, myoglobin, circulation system SOFA score, chronic kidney disease, heart rate and baseline serum creatinine. Visualized decision tree model had 4 layers, 15 nodes and 8 terminal nodes as evidenced by total SOFA score, myoglobin, baseline serum creatinine and age. The total SOFA score, change rate of myoglobin, serum creatinine and age were included into the visualized decision model. The AUC value of the model for predicting end-point event was 0.690. sNB model revealed complex correlation between the risk factors, in which neural SOFA score was related to total SOFA score, vasoactive drug application was related to total SOFA score, and cTNI was related to baseline serum creatinine. Conclusions:A risk prediction model for patients with sepsis-induced cardiorenal syndrome is established and the model showes that high SOFA score remains the primary risk factor for patients with sepsis-induced cardiorenal syndrome based machine learning. Visualized decision tree and sNB models help clinicians to further identify the dependence and logic relationship among these risk factors clearly and provide a novel method to predict mortality risk for patients with sepsis-induced cardiorenal syndrome.

The unilateral biportal endoscopic technique is defined as posterior unilateral of two small incision with established percutaneous observation channel and endoscopic observation channel in monitoring field. The operation tools were placed within the channel for each operation inside and outside vertebral canal. The characteristics of dual channel intervention make this technology different from coaxial endoscopic technology. This technique has a clear vision for flexible and convenient operation with the advantages of relatively simple surgical instrument requirements. In recent years, the use of unilateral dual channel endoscopic surgery in treating spinal diseases was gradually increasing, especially in the removal of nucleus including lumbar intervertebral disc protrusion and lumbar spinal stenosis disease decompression, and in endoscopic space-occupying lesions such as vertebral fusion and spinal canal between inside and outside. It was also applied in cervical and thoracic diseases with good clinical effects. Its advantages include less surgical trauma and faster recovery process. In addition, it has a large surgical field of vision under the microscope for easy identification of structures and surgery and with relatively gentle learning curve. Thus, it is conducive to beginners' mastery. However, complications such as nerve injury and postoperative lower limb numbness are still frequently reported. Some factors have to be considered, including insufficient understanding of the new technology, the local anatomy of the dual-channel endoscope, the operation of the spinal canal under the microscope. The successful application of the technique in treating various lumbar diseases needs understanding the operation process of the technique and local anatomy under the microscope.

Objective:To develop a unilateral biportal endoscopic technique and investigate the clinical efficacy of unilateral biportal endoscopic technique in the treatment of lumbar disc herniation and lumbar spinal stenosis.Methods:Between July 2018 and June 2019, 60 patients with lumbar disc herniation or spinal stenosis were treated by unilateral biportal endoscopic technique. According to the inclusion and exclusion criteria, 51 patients were included in the study. There were 25 cases of prolapsed lumbar disc herniation, 26 cases of degenerative lumbar spinal stenosis, all of which were treated with posterior lumbar decompression by unilateral biportal endoscopic laminectomy, and contralateral stealth decompression by unilateral approach was performed on the patients with bilateral stenosis. Endoscopic interbody fusion and percutaneous pedicle screw fixation were performed in 5 patients with instability. Operation time, length of incision, hospital stay and complications were recorded. Visual analogue scale (VAS) for low back pain and leg pain, Oswestry dysfunction index (ODI) and the modified Macnab scale were used to evaluate the clinical efficacy.Results:All operations were completed successfully, and no cases were transferred to open surgery. The operative time was 70.29±19.55 min (44-151 min), while the length of incision was 1.79±0.34 cm (1.4-3.0 cm). Postoperative CT suggested complete decompression with intact contralateral structure. All patients got out of bed 1-3 d after surgery, and the postoperative hospital stay was 3.49±2.76 d (1-14 d). The postoperative follow-up time was 13.59±2.80 months (10-21 months). Forty-six patients returned to work or normal activities within 3 weeks and 5 patients with interbody fusion returned to normal activities within 4 weeks. According to the modified Macnab criteria, the final outcome was excellent in 43 cases, good in 6 cases, and fair in 2 cases. There were 3 cases of dural sac tear during operation and 2 cases of transient numbness of lower limbs after surgery and they all recovered after conservative treatment. The VAS score of low back pain of 26 patients with lumbar spinal stenosis was reduced from 6.69±1.44 before surgery to 3.27±1.43 at postoperative 1 month, 2.69±1.57 at postoperative 3 months, 2.31±1.16 at postoperative 6 months and 2.23±1.28 at the last follow-up, respectively, and the difference was statistically significant ( F=128.534, P<0.005). The VAS scoreof leg pain was reduced from 6.77±1.34 before surgery to 3.27±1.37 at postoperative 1 month, 2.88±1.48 at postoperative 3 months, 2.85±1.52 at postoperative 6 months and 2.54±1.53 at the last follow-up, and the difference was statistically significant ( F=146.951, P<0.005). The ODI score was reduced from 64.18%±8.23% before surgery to 37.53%±4.45% at postoperative 1 month, 27.51%±3.83% at postoperative 3 months, 19.91%±5.27% at postoperative 6 months and 6.84%±2.74% at the last follow-up, and the difference was statistically significant ( F=783.966, P<0.005). The VAS score of low back pain of 25 patients with lumbar disc herniation was reduced from 5.60±1.38 before surgery to 3.04±1.54 at postoperative 1 month, 2.84±1.75 at postoperative 3 months, 3.12±1.86 at postoperative 6 months and 3.44±1.69 at the last follow-up, respectively, and the difference was statistically significant ( F=22.357, P<0.005). The VAS scoreof leg pain was reduced from 5.48±1.45 before surgery to 2.88±1.64 at postoperative 1 month, 2.52±1.83 at postoperative 3 months, 2.76±1.83 at postoperative 6 months and 3.00±1.92 at the last follow-up, and the difference was statistically significant ( F=29.445, P<0.005). The ODI score was reduced from 53.59%±6.87% before surgery to 32.46%±3.78% at postoperative 1 month, 23.39%±2.78% at postoperative 3 months, 16.49%±3.49% at postoperative 6 months and 7.23%±3.15% at the last follow-up, and the difference was statistically significant ( F=790.985, P<0.005). Conclusion:Unilateral biportal endoscopic technique has the advantages of clear and wide field of vision, large operating space, relatively simple surgical instrument need and convenient and flexible operation procedure. It has excellent clinical effects in the treatment of lumbar disc herniation and lumbar spinal stenosis.

A change in the metabolic flux of glucose from mitochondrial oxidative phosphorylation (OXPHOS) to aerobic glycolysis is regarded as one hallmark of cancer. However, the mechanisms underlying the metabolic switch between aerobic glycolysis and OXPHOS are unclear. Here we show that the M2 isoform of pyruvate kinase (PKM2), one of the rate-limiting enzymes in glycolysis, interacts with mitofusin 2 (MFN2), a key regulator of mitochondrial fusion, to promote mitochondrial fusion and OXPHOS, and attenuate glycolysis. mTOR increases the PKM2:MFN2 interaction by phosphorylating MFN2 and thereby modulates the effect of PKM2:MFN2 on glycolysis, mitochondrial fusion and OXPHOS. Thus, an mTOR-MFN2-PKM2 signaling axis couples glycolysis and OXPHOS to modulate cancer cell growth.

Animals ; Fasting ; metabolism ; Membrane Proteins ; metabolism ; Mice ; Sterol Regulatory Element Binding Protein 1 ; metabolism ; Transcription Factors ; deficiency ; metabolism

Tinnitus is recognized as a refractory disease, which is common in clinic, and always treated from the liver and kidney. We treat tinnitus mainly by heart based on syndrome differentiation. It often works well when the leftpulse is abnormal. Referring to ancient literature, we find that the heart is related to ears by meridians, and the kidney and heart govern ears. The normal function of heart and kidney means normal hearing. The heart secretes atrial natriuretic polypeptins (ANP), whose receptor is widely distributed in ears and can increase the cochlear blood flow. In this paper we explore the relationship between the heart and the ears so as to provide theories of treatment by heart for tinnitus.