Objective To analyze the predictive value of serum levels of procalcitonin(PCT)and cytokines on the prognosis of patients with COVID-19 at admission.Methods From November 2022 to February 2023,patients diagnosed with COVID-19 who were admitted to Beijing Chest Hospital were enrolled.Chemiluminescence was used to detect serum PCT levels,and flow microsphere array was used to detect serum cytokines IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17A,IL-17F,IL-22,TNF-α,TNF-β,IFN-γ level.ICU admission,mechanical ventilation and in-hospital death were defined as poor prognosis.After excluding patients with bacterial infection,the relationship between serum PCT and cytokine levels at admission and the prognosis of COVID-19 patients was analyzed.After excluding patients with bacterial infection,the relationship between serum PCT and cytokine levels at admission and the prognosis of COVID-19 patients was analyzed.Results A total of 176 patients with complete data were included,including 134 in the PCT-normal group and 42 in the PCT-elevated group,with a median age of 71.50 years and 71.59%males.Patients in the PCT elevated-group had significantly higher rates of ICU admission(38.41%vs.13.11%,P<0.05),mechanical ventilation(76.92%vs.24.59%,P<0.001)and in-hospital mortality(38.46%vs.6.56%,P<0.001)were significantly higher than those in the PCT-normal group.Serum levels of cytokines IL-6(7.40 pg/mL vs.4.78 pg/mL,P = 0.033 4)and IL-8(10.97 pg/mL vs.5.92 pg/mL,P<0.001)were significantly higher in patients with poor prognosis than in those with good prognosis.The area under the curve for PCT,IL-6,and IL-8 to predict poor prognosis in COVID-19 patients was 0.687,0.660,and 0.746,respectively;sensitivity was 52.78%,55.17%,and 72.41%,respectively;and specificity was 81.58%,74.19%,and 74.19%,respectively,as calculated from the ROC curve.When PCT,IL-6 and IL-8 jointly predict the prognosis of COVID-19 patients,the area under the curve is 0.764,the sensitivity is 70.00%,and the specificity is 80.00%.Conclusion Serum PCT and cytokines IL-6 and IL-8 could be used as predictive markers for poor prognosis in patients with COVID-19.

Objective:To analyze the efficacy and feasibility of performing a new surgical procedure, tunnel esophagogastrostomy, to perform proximal gastrectomy.Methods:The study cohort comprised 10 consecutive patients who had undergone esophagogastrostomy by the tunnel technique in Jiangsu Cancer Hospital between October 2019 and July 2022. All patients were male. Their average age was (64.2±8.1) years and body mass index (25.5±3.2) kg/m2. Nine had upper gastric body adenocarcinoma, the remaining one having signet ring cell carcinoma. TNM staging of the tumors showed that seven were Stage IA, one Stage IB, one Stage IIA, and one Stage IIIA. Briefly, tunnel esophagogastrostomy is performed as follows: After performing a proximal gastrectomy, a rectangular seromuscular flap (3.0 cm × 3.5 cm) is created. The posterior esophageal wall is sutured to the gastric wall at the orad end of the seromuscular flap 5 cm from the stump with three to four stitches. Next, the stump of the esophagus is opened, the posterior esophageal wall is sutured to the gastric mucosa and submucosa, and the anterior esophageal wall is sutured to the full layer of the stomach. Finally, the caudad end of the seromuscular flap is closed. Data on surgical safety, postoperative morbidity, and postoperative reflux esophagitis were analyzed. All enrolled patients completed endoscopic follow-up 1 year and 2 years after surgery.Results:All procedures were completed. They comprised four cases of laparoscopic assisted surgery, four of DaVinci robotic surgery, and two of open surgery. The mean operation time was 212.7±33.2 mins, mean anastomosis time (51.6±5.3) minutes, mean tunnel preparation time (20.0±3.5) minutes, and mean operative blood loss (90.0±51.6) mL. The time to first postoperative passage of flatus was (64.8±11.5) hours. The mean hospital stay after surgery was (9.2±1.7) days. There were no postoperative complications above Clavien-Dindo Grade II. The mean preoperative Reflux Disease Questionnaire score was (3.3± 0.4) before the surgery, (3.8±1.0) 1 month postoperatively, and (3.3±0.4) 12 months postoperatively. All patients underwent endoscopic follow-up; no anastomotic stenoses were found. However, one patient had Grade A reflux esophagitis 1 year after surgery and another Grade B reflux esophagitis 2 years after surgery.Conclusion:Esophagogastrostomy by the tunnel technique is a safe and feasible means of performing proximal gastrectomy.

Objective:To explore the protective efficacy of sulforaphane (SFN) in alleviating intestinal mucosal injury after resuscitation in pigs and its possible mechanism.Methods:This experiment was performed in the laboratory animal center, Zhejiang university. Using a random number table, twenty-four domestic healthy male white pigs were randomly divided into the Sham group, cardiopulmonary resuscitation (CPR) group, and SFN group, in which the Sham group had 6 pigs, and the other two groups had 9 pigs, respectively. The experimental parameters of 10 min of cardiac arrest and 6 min of CPR were chosen to establish the porcine model of CPR in the CPR and SFN groups. At 5 min after resuscitation, a dose of 2 mg/kg of SFN was infused via the femoral vein within 10 min in the SFN group. At 1 h, 2 h, 4 h, and 24 h after resuscitation, vein samples were collected, and then the levels of intestinal fatty acid binding protein (IFABP) and diamine oxidase (DAO) in serum were measured by ELISA. Subsequently, 6 pigs were chosen to be euthanized in each group, and then tissue samples were harvested from distal ileum to measure the level of cell apoptosis by TUNEL, the activities of superoxide dismutase (SOD) and catalase (CAT) and the contents of glutathione (GSH) and malondialdehyde (MDA) by biochemical method, the contents of 4-hydroxy-2-nonenal (4-HNE) by ELISA, the fluorescence intensity of reactive oxygen species (ROS) by immunofluorescence staining, and the expression levels of zonula occluden-1 (ZO-1), occludin, nuclear factor E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) by Western blot. Continuous variables were compared with one way analysis of variance among the three groups, and Bonferroni test was used for further pairwise comparison.Results:During the observation period after resuscitation, the serum levels of biomarkers of intestinal mucosal injury including IFABP and DAO were significantly higher in the CPR and SFN groups than in the Sham group (all P<0.05). However, the serum levels of IFABP at 2 h, 4 h, and 24 h after resuscitation and the serum levels of DAO at 1 h, 2 h, 4 h, and 24 h after resuscitation were significantly lower in the SFN group than in the CPR group (all P<0.05). At 24 h after resuscitation, apoptotic index was significantly increased, SOD and CAT activities and GSH contents were significantly decreased, MDA and 4-HNE contents and ROS production were significantly increased, ZO-1 and occludin expression were significantly down-regulated, and Nrf2 and HO-1 expression were significantly up-regulated in the CPR and SFN groups when compared with the Sham group (all P<0.05). However, apoptotic index was significantly decreased, SOD and CAT activities and GSH contents were significantly increased, MDA and 4-HNE contents and ROS production were significantly decreased, and ZO-1, occludin, Nrf2, and HO-1 expression were significantly up-regulated in the SFN group when compared to the CPR group (all P<0.05). Conclusion:SFN could effectively protect against intestinal mucosal injury after resuscitation in pigs, and its mechanism was possibly related to the inhibition of oxidative stress and cell apoptosis via the activation of Nrf2/HO-1 pathway.

Objective:To analyze the efficacy and feasibility of performing a new surgical procedure, tunnel esophagogastrostomy, to perform proximal gastrectomy.Methods:The study cohort comprised 10 consecutive patients who had undergone esophagogastrostomy by the tunnel technique in Jiangsu Cancer Hospital between October 2019 and July 2022. All patients were male. Their average age was (64.2±8.1) years and body mass index (25.5±3.2) kg/m2. Nine had upper gastric body adenocarcinoma, the remaining one having signet ring cell carcinoma. TNM staging of the tumors showed that seven were Stage IA, one Stage IB, one Stage IIA, and one Stage IIIA. Briefly, tunnel esophagogastrostomy is performed as follows: After performing a proximal gastrectomy, a rectangular seromuscular flap (3.0 cm × 3.5 cm) is created. The posterior esophageal wall is sutured to the gastric wall at the orad end of the seromuscular flap 5 cm from the stump with three to four stitches. Next, the stump of the esophagus is opened, the posterior esophageal wall is sutured to the gastric mucosa and submucosa, and the anterior esophageal wall is sutured to the full layer of the stomach. Finally, the caudad end of the seromuscular flap is closed. Data on surgical safety, postoperative morbidity, and postoperative reflux esophagitis were analyzed. All enrolled patients completed endoscopic follow-up 1 year and 2 years after surgery.Results:All procedures were completed. They comprised four cases of laparoscopic assisted surgery, four of DaVinci robotic surgery, and two of open surgery. The mean operation time was 212.7±33.2 mins, mean anastomosis time (51.6±5.3) minutes, mean tunnel preparation time (20.0±3.5) minutes, and mean operative blood loss (90.0±51.6) mL. The time to first postoperative passage of flatus was (64.8±11.5) hours. The mean hospital stay after surgery was (9.2±1.7) days. There were no postoperative complications above Clavien-Dindo Grade II. The mean preoperative Reflux Disease Questionnaire score was (3.3± 0.4) before the surgery, (3.8±1.0) 1 month postoperatively, and (3.3±0.4) 12 months postoperatively. All patients underwent endoscopic follow-up; no anastomotic stenoses were found. However, one patient had Grade A reflux esophagitis 1 year after surgery and another Grade B reflux esophagitis 2 years after surgery.Conclusion:Esophagogastrostomy by the tunnel technique is a safe and feasible means of performing proximal gastrectomy.

Objective:To explore the correlation between glycated hemoglobin variability index (HGI) and carotid artery plaque in patients with type 2 diabetic kidney disease (DKD).Methods:This cross-sectional study included 620 DKD patients admitted to the Department of Endocrinology in the First Affiliated Hospital of Nanjing Medical University from June 2019 to June 2022. Basic demographic and laboratory data, including age, disease duration, body mass index (BMI), blood pressure, fasting blood glucose (FBG), glycated hemoglobin (HbA 1c), lipid profile, and urinary albumin excretion rate (UAER), were collected for all participants. A linear regression equation was developed based on FPG and HbA 1c to calculate the HGI level of each patient. The patients were divided into low HGI group, medium HGI group, and high HGI group based on the tertiles of HGI. The detection rate of carotid artery plaque in the three HGI groups was analyzed. The patients were further divided into the non-plaque group (254 cases) and plaque group (366 cases) based on the presence or absence of carotid artery plaque. Binary logistic regression analysis was used to identify the risk factors for carotid artery plaque in DKD patients. Results:Among the DKD patients, the detection rate of carotid artery plaque was 59%. Compared with the non-plaque group, the patients in the plaque group had older age (60.52 years, t=-7.71), longer disease duration (10 years, Z=-4.17), higher systolic blood pressure (141.9 mmHg, t=-3.29), higher HbA 1c (9.2%, Z=-2.17), higher HGI (-0.20%, Z=-3.43), higher urea nitrogen (6.87 μmol/L, Z=-3.96), higher creatinine (77 mmol/L, Z=-4.05), and higher UAER (234.25 mg/24 h, Z=-5.59) (all P<0.05). The detection rate of carotid artery plaque in the low HGI group, medium HGI group and high HGI group was 50.5%, 57.9% and 68.5%, respectively, with a statistically significant difference among the three groups (χ 2=14.15, P=0.001). Age, UAER, and HGI were identified as risk factors for carotid artery plaque ( OR=1.051, 2.775 and 1.474, all P<0.05). The risk of carotid artery plaque in the high HGI group was 2.142 times of that in the low HGI group. After adjusting for confounding factors such as age, gender, disease duration, BMI, blood pressure, lipid profile and UAER, the risk of carotid artery plaque in the high HGI group was 2.558 times of that in the low HGI group. Conclusion:HGI is significantly elevated in DKD patients with carotid artery plaque, and the detection rate of carotid artery plaque increases with HGI level. Elevated HGI is an independent risk factor for carotid artery plaque in DKD patients.

Background and Objectives: To investigate the role of exosomes from periodontal ligament cells (PDLCs) in bone marrow mesenchymal stem cell (BMSC) migration. Methods: and Results: Human PDLCs were applied cyclic tension stretching. Exosomes were extracted from cultured PDLCs by ultracentrifugation, then characterized for their size, morphology and protein markers by NTA, TEM and western blotting. The process that PKH26-labeled exosomes taken up by BMSCs was assessed by confocal microscope.BMSC migration was examined by Transwell assay. Exosomes derived from PDLCs were identified. Cyclic tension stretch application on PDLCs can enhance the migration ability of BMSCs through exosomes. The exosomal miRNA expression profiles of unstretched and stretched PDLCs were tested by miRNA microarray. Four miRNAs (miR-4633-5p, miR-30c-5p, miR-371a-3p and let-7b-3p) were upregulated and six (miR-4689, miR-8485, miR-4655-3p, miR-4672, miR-3180-5p and miR-4476) were downregulated in the exosomes after stretching. Sixteen hub proteins were found in the miRNA-mRNA network. Gene Ontology and KEGG pathway analyses demonstrated that the target genes of differentially expressed exosomal miRNAs closely related to the PI3K pathway and vesicle transmission. Conclusions The exosomes derived from cyclic tension-stretched PDLCs can promote the migration of BMSCs. Alternation of microRNA profiles provides a basis for further research on the regulatory function of the exosomal miRNAs of PDLCs during orthodontic tooth movement.

Objective:To explore the application effect of "blended learning + flipped classroom" in public elective courses for medical students, and provide reference for the blended construction of related courses.Methods:Totally 229 medical students were selected as research participants, who were taught by "blended learning + flipped classroom". After the courses, the curriculum evaluation questionnaires and focus group interview were used to collect students' evaluation of this course. SPSS 22.0 statistical software was used to make descriptive statistics on the questionnaire data.Results:Totally 98.5% students preferred "blended learning + flipped classroom" teaching mode, and more than 93% students thought this teaching method could improve their learning interest, empathy, understanding and application of knowledge. The results of the qualitative survey extracted two themes, namely "improving learning autonomy" and "expanding comprehensive quality".Conclusion:Perfecting the "blended learning + flipped classroom" teaching mode of the medical public elective courses plays a positive role in improving the learning autonomy and comprehensive quality of medical students and optimizing the learning effect.

Taking the Department of Obstetrics and Gynecology as an example, this paper expounds a series of practices of online education, in the process from pre-course training, platform selection, curriculum design, to student evaluation, etc. From that, we can provide a reference for carrying out online teaching in response to the epidemic for clinical medical colleges which have not been exposed to the online course. Furthermore, it is a new attempt to explore a way to make a change of the traditional teaching method and deepen the reform of clinical teaching in our hospital after the epidemic, not only in professional medical education, but also in the popularization of medical knowledge.

Model informed precision dosing (MIPD) is a new concept to guide precision dosing for individual patient by modeling and simulation based on the available information about the individual patient, medications and the disease. Compared to the empirical dosing, MIPD could improve the efficacy, safety, economics and adherence of the pharmacotherapy according to the individual's pathophysiology, genotyping and disease progression. This consensus report provides a brief account of the concept, methodology and implementation of MIPD as well as clinical decision supporting systems for MIPD. The status and future advancing of MIPD was also discussed to facilitate the appropriate application and development of MIPD in China.

With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.