Vitamin C is an essential micronutrient for human and its deficiency will lead to scurvy.In recent years,as a new therapeutic strategy,high dose intravenous vitamin C(HDIVC)has been widely studied in critical cared diseases.In this review,we summarized the progress of HDIVC in sepsis,including its research history,rationality of usage,controversy and prospect,problems and outlook.The application of HDIVC in critical cared diseases underwent three periods:early,preheating and outbreaking period.Given the reduction of vitamin C in critical diseases,it requires rapid intravenous supplementation.We confirmed the therapeutic efficacy of HDIVC in COVID-19 and severe acute pancreatitis respectively.It is well known that HDIVC has effect of suppressing inflammatory responses,stabilizing the circulation and improving the immunity.But the application of HDIVC in critical cared diseases is still controversial,for the opposing findings in multiple large-scale randomized controlled trials.Future studies should be better to pay further attention on the dose and time of vitamin C and vitamin C plasma concentration monitoring.

In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease (PD). However, difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1. Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains. CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology. Importantly, PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival. Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.

Objective:To analyze the clinical characteristics and pathogen distributions of the patients with bone and joint infection.Methods:The clinical data and etiological results of 225 patients with bone and joint infection from January 2008 to October 2020 in Huashan Hospital, Fudan University were retrospectively analyzed.Statistical analysis was conducted by chi-square test.Results:Of the 225 cases with bone and joint infection, 75.6%(170/225) were extremities and other osteomyelitis, 16.0%(36/225) were suppurative arthritis, 8.4%(19/225) were spinal osteomyelitis. Non-implants related infection accounted for 80.4%(181/225) of the cases, while 19.6%(44/225) of the cases were implants related infection. The main clinical manifestations were localized pain (48.4%(109/225)), dyskinesia (47.6%(107/225)), localized swelling (28.9%(65/225)), fever (28.0%(63/225)), and increased purulent exudation (24.9%(56/225)). The proportions of localized pain (55.8%(101/181)) and fever (31.5%(57/181)) of non-implants infection were higher than those of implants infection (18.2%(8/44) and 13.6%(6/44), respectively), while the proportion of increased purulent exudation in implants infection (50.0%(22/44)) was higher than that in non-implants infection (18.8%(34/181)). There were all significant differences between the two groups ( χ2=15.49, 5.60 and 18.45, respectively, all P<0.050). Of the 225 cases, 63 cases(28.0%) had complications with other site infection, especially soft tissue infection and bloodstream infection. A total of 106 strains of pathogens were isolated from 225 specimens, 58.5%(62/106) of them were Gram positive bacterium.Among them, 34.0%(36/106) were Staphylococcus aureus, with the rate of methicillin resistant Staphylococcus aureus (MRSA) isolation accounting for 11.3%(12/106). Laboratory tests showed that 40.4%(91/225) of the patients had elevated erythrocyte sedimentation rate (ESR), 32.9%(74/225) patients had elevated C-reactive protein (CRP). Proportions of patients with elevated ESR (43.6%(79/181)) and CRP (37.6%(68/181)) in non-implants infection were significantly higher than those in implants infection (27.3%(12/44) and 13.6%(6/44), respectively). There were significant differences between the two groups ( χ2=3.94 and 9.19, respectively, P=0.047 and 0.002, respectively). Conclusions:The main clinical manifestations of bone and joint infection are localized pain, dyskinesia, localized swelling, fever and increased purulent exudation. Patients with bone and joint infection are easy to be complicated with soft tissue infection and bloodstream infection, and often accompanied by increased ESR and CRP levels. Gram positive bacterium are the main pathogens.

Objective:To optimize the stimulation and activation system of mouse CD3 + T cells in vitro and explore the optimal infection time of CD3 + T cells to establish mouse CD19 chimeric antigen receptor T cells (mCD19 CAR-T) , and to also verify its killing effect in vivo and in vitro. Method:Splenic CD3 +T cells were isolated and purified using magnetic beads, and the cells were cultured in Soluble anti-CD3/CD28, PMA+Ionomycin, and Plated anti-CD3/CD28. Cell activation and apoptosis were assessed by flow cytometry after 8, 24, 48, and 72 hours. ScFv plasmid of mouse CD19 antibody was transfected to plat-E cells to package retrovirus. Activated CD3 + T cells were infected to construct mouse-specific CD19 chimeric antigen receptor T cells (mCD19 CAR-T) , and mCD19 CAR-T cells were co-cultured with B-cell lymphoma cell line A20 in vitro. The specific toxicity of A20 was detected by flow cytometry, and mCD19 CAR-T cells were infused into the lymphoma mouse model to detect its killing effect and distribution. Results:The activation effect of Plated anti-CD3/CD28 on CD3 + T cells was superior, with the cells exhibiting good viability 24–48 hours after stimulation. Established mCD19 CAR-T cells with stable efficiency[ (32.27±7.56) % ] were specifically able to kill A20 tumor cells (The apoptosis rate was 24.3% at 48 h) . In vivo detection showed a non-significant decrease in the percentage[ (1.83±0.58) % ] of splenic CD19 + cells 6 days after mCD19 CAR-T cell infusion. A marked clearance in bone marrow and spleen appeared on day 12 compared with the A20 group, and this difference was statistically significant[spleen: (0.36±0.04) % vs (47.00±13.46) % , P<0.001; bone marrow: (1.82±0.29) % vs (37.30±1.44) % , P<0.0001]. Moreover, mCD19 CAR-T cells were distributed in high proportions in the peripheral blood, spleen, and bone marrow[ (2.90±1.12) % , (4.96±0.80) % , (13.55±1.56) % ]. Conclusion:This study demonstrated an optimized activation system and the optimal infection time of CD3 + T cells. Furthermore, stable constructed mCD19 CAR-T cells showed a remarkable killing ability in vitro and in vivo.

Ewing sarcoma is a member of the Ewing sarcoma family tumor(ESFT), which is commonly from bones and soft tissues, while it is rare for penis. In this thesis, a case of 21-year-old Ewing sarcomas on the left side of the penis was reported. After the penis mass excision, the pathological diagnosis was Ewing sarcoma and positive margin, then he underwent penis total hysterectomy. After the surgery, he received chemotherapy for 14 cycles without radiation. With 8 months’ reexamination and follow-up, there was no local recurrence or metastasis.

Coronary angiography is the core technology in the diagnosis and treatment of coronary heart disease. The left main coronary artery (LMCA), which supplies most of the left ventricular myocardium, is the key segment of the coronary network, but because of its special anatomical characteristics, it limits the value of coronary angiography in the diagnosis. Intravascular ultrasound, as an invasive tomographic technique, has been widely used in clinic to assist coronary angiography, and its value in diagnosis and treatment of left main artery disease has been recognized by most studies.

Objective: To evaluate the prognostic value of the preoperative Geriatric Nutritional Risk Index (GNRI) in patients with esophageal squamous cell carcinoma after radical resection. Methods: Clinicopathological and laboratory data of 315 elderly patients with esophageal squamous cell carcinoma who were older than 60 years and underwent radical resection in Tianjin Medical University Cancer Institute and Hospital from January 2008 to December 2012 were retrospectively analyzed. The GNRI formula was as follows:1.489×serum albumin (g/L)+41.7×(current body weight/ideal body weight). According to the GNRI, patients were divided into the normal and abnormal GNRI groups. The χ2 test was used to analyze the relationship between the GNRI and the clinicopathological char-acteristics of patients. The Kaplan-Meier method was used to analyze the survival rate, and survival analysis was conducted using the Log-rank test. Multivariate survival analysis was conducted using the Cox proportional risk regression model. Results: There were 259 patients in the normal GNRI group (GNRI>98) and 56 patients in the abnormal GNRI group (GNRI≤98). The GNRI was closely correlated with age, tumor location, tumor diameter, serum albumin level, body mass index (BMI), and lymph node metastasis (all P<0.05). The 5-year survival rates in the normal and abnormal GNRI groups were 41.2% and 27.0%, respectively, with statistical significance (P=0.002). Univariate analysis showed that age, tumor diameter, serum albumin level, BMI, GNRI, platelet-lymphocyte ratio, tumor invasion depth, and lymph node metastasis were risk factors for the prognosis of patients with esophageal squamous cell carcinoma (all P<0.05). Multivariate analysis showed that the preoperative GNRI (hazard ratio=0.687, 95% confidence interval: 0.487-0.968, P=0.032) was an independent factor affecting the prognosis of patients with esophageal squamous cell carcinoma. Subgroup analysis showed that the survival rates in the normal GNRI group were significantly higher than those in the abnormal GNRI group (P=0.036 and 0.010, respectively), regardless of lymph node metastasis. Conclusions: The preoperative GNRI is associated with malignant biological behav-ior in elderly patients with esophageal squamous cell carcinoma and can be used as a useful indicator for predicting survival after radi-cal resection.

Objective To explore the feasibility and efficacy of transcatheter closure of ventricular septal defect (VSD) through radial artery combined femoral vein approach. Methods A total of 11 patients with congenital VSD, who were admitted to authors' hospital during the period from June 2017 to November2017, were enrolled in this study. The patterns of lesion included intracristal type (n=3) and perimembranous type (n=8), and in 3 patients the VSD was associated with concant ventricular septal aneurysm. Transcatheter closure of VSD via radial approach was carried out in all patients. The mean age of the patients was (37.82±12.44) years old, and the average body weight was (62.79±14.95) kg. The transthoracic echocardiography (TTE) showed that the mean diameter of VSD was (5.87±1.91)mm. The effect of transcatheter closure therapy was assessed by intraoperative TTE and left ventriculography. All patients were followed up with electrocardiogram and TTE at 24 hours and one, 3, 6 months after transcatheter closure therapy. Results Successful closure was achieved in 10 patients, and one patient had to be transferred to surgery because the catheter could not pass through the defect. The mean diameter of the implanted occluders was (7.50±3.60)mm, the average procedural time and fluoroscopy time were (47.20±5.45) min and (13.00±3.65) min respectively. The postoperative average in-bed time was (99.00±11.97) min. Two patients developed radial artery spasm during the operation. During the follow-up period lasting for a mean of (3.50±1.90) months, no serious complications, such as dropping of occluder, residual shunt, atrioventricular block, aortic regurgitation, radial artery occlusion, etc. occurred in the 10 patients. Conclusion For the treatment of VSD, transcatheter closure through radial artery combined with femoral vein approach is safe and effective. Therefore, this technique is worthy of clinical application.

We investigated serotype and resistance of Salmonella during pig slaughtering in Shandong Province,China,providing basic data for the risk assessment of Salmonella and for guiding the clinical medication.We used rapid classification kit to identify Salmonella serotype,adopted broth microdilution method to detect the resistance of 13 kinds drugs belong to 8 categories.Result showed that the identified 9 kinds of serotype were mainly S.derby and S.typhimurium.The resistance to 13 kinds drugs of 298 Salmonella were different.The higher percentage of tetracycline drugs as Doxycycline(DOX) and Tetracycline(TE) were 97.99％ and 80.20％,respectively,which was most sensitive to Colistine E.The resistant rate was only 2.01 ％,following by Amoxicillin/Clavulanic acid and Ofloxacin which were 2.35 ％ and 4.03％,and the multiple resistant rate was 81.88％.TE-DOX was the regnant drug-resistant spectrum.In conclusion,the predominant serotype of Salmonella in links of pig slaughtering in Shandong Province is S.derby,and resistance is different to the different drugs.The drug resistance of different slaughter links exist significant differences,multiple drug resistance is serious,and drug-resistant spectrum are varied.

Objective To discuss the method of implantation that Medtronic 3830 pacemaker electrode and how to deal with the situations which association with the surgery.Methods Select 200 patients who receive the treatment of Medtronic 3830 pacemaker electrode. Al of them conform to the clinical diagnostic criteria, folow-up visit, colect the complications after the implantation surgery of pacemaker electrode.Results Al patients recovered wel after pacemaker implantation or replacement, primary disease was cured, and quality life was improved.Conclusion By the data of colating and analysis, it shows that patients can get a good recovery by sufficient equipment and perioperative preparation, operate strictly and appropriate operation selection.