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.

Objective:To analysis the Mimotopes of the peptide mimics to PGN using online softwares.Methods: Mimotopes of PGN were screened from 12-mers linear phage display peptide library by using anti-PGN McAb and the antigenicity of selected clones was identified by ELISA.The B cell epitopes,T cell epitopes of ′GRWxHxVxWAGL′ were estimated by DNAstar and online softwares.Results: 16 phage clones that bound with anti-PGN McAb were screened from 12-mers linear phage display peptide library.Among these positive clones,phage clones No.39 shared the conserved sequence:WxHx……AGL found in previous clone No.31(ATWxHxLxSAGL),which provoked an effective protective immunity against infection with S.aureus.To enhance the stability of the conformation as well as adding biotin on the N-ter-minal as a tag,the sequences ′39′ were redesigned and synthesized by adding S(serine)A(alanine) and GG(glycine)on the C-terminal of origin sequence(named SP39).Next,we estimated or predicted antigenic epitopes,T cell epitopes and scores binding to MHC of these peptides by using DNASTAR and online softwares(http://bio.dfci.harvard.edu/Tools/antigenic.pl,www.syfpeithi.de,http://www.darrenflower.info/mhcpred),indicating that SP39 contains sites bound both mice and human MHC.The sequences ′WxHxVxW-′ may be antigenic epitope as SP39,which contains a T cell epitope.Our results showed that both SP39 could bind to both anti-PGN McAb and a polyclonal antibody against S.aureus.Moreover PGN could inhibit the binding of SP39 to the anti-PGN McAb.These data indicated that SP39 mimic to epitopes on PGN.Conclusion: SP39(GRWxHxVxWAGLAGGS) probably display the mimotopes of PGN.

Objective This study was performed to investigate the levels of HSP70 in tissue in pemphigus as a possible new theoretical basis for further elucidate the pathogenesis of pemphigus.Methods The expression of HSP70 in 62 patients with pemphigus was determined by immunohistochemistry,and the normal skin was taken as control.Results The results showed that the positive cells of HSP70＞75 ％ in the blisters of pemphigus vulgaris and the positive cells of HSP70＞50％ in the inflammatory cells near the blisters,and the expression of HSP70 was significantly higher than that in normal skin,which was statistically significant(Z=5.42,4.73,P＜0.01).Conclusion The abnormal expression of HSP70 in inflammatory cells and psoriasis of pemphigus patients showed that HSP70 is involved in the pemphigus.

Objective To study the accuracy of collapsed cone convolution ( CCC) and anisotropic analytical algorithm ( AAA) in dosimetric calculation on the air cavity interface. Methods A BEAMnrc/EGSnrc Monte Carlo ( MC ) simulation was performed on a Varian Trilogy linear accelerator. The IBA Dosimetry “blue phantom” 3D scanning system was used to verify the accuracy and reliability of the MC simulation. Central axis depth dose distribution and lateral dose profile in a water?equivalent phantom with variously sized air cavities were calculated by CCC and AAA. The obtained depth dose distribution and lateral dose profile were compared with those by MC simulation and EBT2 film, respectively. Results Both CCC and AAA overestimated the dose on the air cavity interface. In spite of some errors, CCC had a higher accuracy than AAA. The errors were mainly related to computational grid, field size, photon energy, cavity size, and the number of fields. Conclusion Electronic disequilibrium on the air cavity interface should be taken into account when CCC and AAA are used for dosimetric calculation in treatment planning system.

Objective:To evaluate immune response of murine peritoneal macrophage challenging by methicillin-resistant S.aureus(MRSA)after pretreatment with Pam3Csk4(TLR2 agonist).Methods: Murine peritoneal macrophage was pretreated with Pam3Csk4(1 μg/ml).Following pretreatment 12 h later,heat-killed MRSA( HK-MRSA) was added and incubated for another 2 or 6 hours.The protein and mRNA level of TNF-α, IL-6 and IL-1 were determined by ELISA and Q-PCR, respectively.To estimate phagocytosis of macrophage,HK-MRSA/MSSA labeled with FITC( FITC-HK-MRSA/MSSA) were added to well and incubated for 30 min.After washing 5 times with PBS,intracellular FITC-HK-MRSA was detected by flow cytometry.To estimate antimicrobal activity of macrophage,live MRSA and MSSA were added to well and incubated at indication time,the CFU of s.aureus was estimated via a 10-fold serial dilution on agar media.cDNA was further quantitative assessed using primers for mouse FCR-Ⅰ,FCR-Ⅲ,CR-1,CR-3,iNOS and LL37 by Q-PCR .Results: Compared with saline-pretreated cell, the protein and mRNA level of TNF-α, IL-6 and IL-1 were markely reduced, respectively.However, both the phagocytosis and antimicrobal activity to S.aureus were significantly increased in macrophages pretreated with Pam3Csk4.Further study found that the macrophages had higher FCR-Ⅰ,FCR-Ⅲ,CR-1,CR-3,iNOS and LL37 expression at 6 h and 12 h post-stimulation Pam3Csk4.Conclusion: The results suggest that Pam3Csk4 could activate murine antimicrobal activity of peritoneal macrophage challenging by methicillin-resistant Saureus via increasing opsonophagocytosis in depended antibodies, complements manners.The results suggest Pam3Csk4 probably be a novel immunotherapy candidate against MRSA.