Objective:To explore the risk factors associated with the clinical progression of COVID-19 infection in kidney transplant(KT)recipients during the spread of Omicron variant and evaluate the effectiveness of anti-RNA virus agents in blocking the clinical progression of COVID-19 in these recipients.Methods:Retrospective analysis was conducted for the clinical data on COVID-19 infection in 232 KT recipients followed up from December 4, 2022 to January 31, 2023 at Department of Renal Transplantation, Organ Transplantation Center, Beijing Tsinghua Changgung Hospital.Inclusion criteria were age ≥18 years and stable kidney function without renal replacement therapy.The follow-up time was 30 days after COVID-19 infection.Based upon whether or not there was an infection of COVID-19, KT recipients were divided into two groups of infection(181 cases)and non-infection(51 cases). In infection group, recipients were further assigned into two sub-groups of disease progression(n=23)and stable(158 cases)according to whether or not there was a progression to severe disease.Various factors such as gender, age, body mass index(BMI), time after transplantation, underlying diseases(history of hypertension, diabetes mellitus, coronary heart disease & chronic lung disease), smoking history and dosing of anti-RNA virus agents were collected.Pearson χ2 test or Fisher's exact probability method was utilized for examining enumeration data while Mann-Whitney U test for measurement data.Univariate Logistic regression analysis was conducted and variables with P<0.05 were included into multifactorial Logistic regression analysis to identify independent risk factors for clinical progression of COVID-19 infection in KT recipients. Results:Among 232 KT recipients, infection rate of COVID-19 was 78.0%(181/232). The clinical classification was mild(112 cases), moderate(46 cases), severe(21 cases)and critical(n=2 cases). The severe rate was 12.7%(23/181). After infection with COVID-19, the proportion of KT recipients aged ≥65 years progressing from mild/moderate to severe was higher than those aged<65 years[38.5%(5/13)vs 10.7%(18/168)]. The difference was statistically significant( P=0.014); The proportion of diabetic KT recipients progressing from mild/moderate to severe was higher than those without diabetes[19.1%(13/68)vs 8.8%(10/113)]. The difference was statistically significant( P=0.045). Univariate Logistic analysis showed similar results.Age≥65 years( OR=5.21, 95% CI: 1.54-17.64, P=0.008)or diabetes mellitus( OR=2.44, 95% CI: 1.003-5.911, P=0.049)were the risk factors for COVID-19 infection recipients progressing from mild/moderate to severe disease.Multivariate Logistic analysis revealed that age ≥65 years( OR=4.03, 95% CI: 1.14-14.34, P=0.031)was an independent risk factor for COVID-19 infection recipients progressing from mild/moderate to severe.Among 181 cases of COVID-19 mild/medium infected patients, 18 cases received nimativir/ritonavir and 10 cases had azvudine for anti-RNA virus treatment.However, none of them progressed to severe; 153 cases did not use anti-RNA virus drugs and 23 cases(15.0%)progressed to severe disease and the difference was statistically significant( P=0.028). Among 23 severe cases, 14 cases received nirmatrelvir/ritonavir and 2 cases had azivudine for anti-RNA virus treatment.The former did not progress to critical disease while 1 case in the latter progressed to critical illness and death; 1/7 recipients not using anti-RNA virus agents progressed to critical illness and died while another 6 cases did not progress to critical illness. Conclusions:KT recipients aged ≥65 years or diabetes mellitus have a greater risk of progression from mild/moderate to severe disease after COVID-19 infection.Among them, age ≥65 years is an independent risk factor for patients with COVID-19 infection to progress from mild/moderate to severe.Antiviral treatment with nirmatrelvir/ritonavir or azivudine in KT recipients during mild/moderate stage of COVID-19 infection can significantly reduce the rate of severe disease.Treatment with Nirmatrelvir/Ritonavir is still effective in the severe stage.

Protein Engineering is a core compulsory course of biotechnology major, which is the first-class undergraduate major being constructed in Shanxi Province. In view of the problems of single teaching mode of Protein Engineering, such as insufficient students' participation, short teaching time, and expensive experiment cost, the course team carried out the reform and practice of teaching mode for this course, and put forward a new teaching strategy. Under the guidance of the "Golden Course" standard for advancement, innovation and challenge, the course team developed the materials for massive open online courses (MOOC), and carried out the online and offline mixed teaching of Protein Engineering based on BOPPPS+flipped classroom by using the Chao-Xing Fan-Ya network teaching platform. Through this, a comprehensive, systematic and dynamic new teaching system of Protein Engineering was developed. Using the teaching mode based on BOPPPS+flipped classroom, the offline classroom teaching was combined with students' online self-study and homework completion, chapter test and discussion, and this mixed teaching mode was fully integrated into the flipped classroom. After three rounds of teaching practice, the course team had developed a complete, reproducible, scientific and reasonable online and offline mixed teaching mode, which included course materials preparation, exploring experiment guidance, classroom discussion design and course performance evaluation. The online and offline mixed teaching mode of Protein Engineering based on BOPPPS+flipped classroom was helpful for students to improve their autonomous learning ability, to be deeply engaged in the whole teaching process, and to develop a comprehensive and profound understanding of Protein Engineering. This teaching mode improved the teaching quality of Protein Engineering, and facilitated students to learn other follow-up professional courses. Moreover, it provides a reference for the course teaching reform.
Humans ; Learning ; Students

Background::The pharmacokinetic and clinical behaviors of many proton pump inhibitors (PPIs) in peptic ulcer treatment are altered by CYP2C19 genetic polymorphisms. This non-inferiority study evaluated the efficacy and safety of the novel PPI anaprazole compared with rabeprazole. We also explored the influence of Helicobacter pylori ( H. pylori) infection status and CYP2C19 polymorphism on anaprazole. Methods::In this multicenter, randomized, double-blind, double-dummy, positive-drug parallel-controlled, phase III study, Chinese patients with duodenal ulcers were randomized 1:1 to receive rabeprazole 10 mg + anaprazole placebo or rabeprazole placebo + anaprazole 20 mg once daily for 4 weeks. The primary efficacy endpoint was the 4-week ulcer healing rate assessed by blinded independent review. Secondary endpoints were the proportion of patients with improved overall and individual duodenal ulcer symptoms at 4 weeks. Furthermore, exploratory subgroup analysis of the primary endpoint by H. pylori status and CYP2C19 polymorphism was conducted. Adverse events were monitored for safety. Non-inferiority analysis was conducted for the primary endpoint. Results::The study enrolled 448 patients (anaprazole, n = 225; rabeprazole, n = 223). The 4-week healing rates were 90.9% and 93.7% for anaprazole and rabeprazole, respectively (difference, -2.8% [95% confidence interval, -7.7%, 2.2%]), demonstrating non-inferiority of anaprazole to rabeprazole. Overall duodenal ulcer symptoms improved in 90.9% and 92.5% of patients, respectively. Improvement rates of individual symptoms were similar between the groups. Healing rates did not significantly differ by H. pylori status or CYP2C19 genotype for either treatment group. The incidence of treatment-emergent adverse events was similar for anaprazole (72/220, 32.7%) and rabeprazole (84/219, 38.4%). Conclusions::The efficacy of anaprazole is non-inferior to that of rabeprazole in Chinese patients with duodenal ulcers.Registration::ClinicalTrials.gov, NCT04215653.

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Objective:To investigate the mid-term efficacy of prostatic artery embolization (PAE) for the treatment of lower urinary tract symptoms (LUTS), urinary retention (UR) or hematuria secondary to benign prostatic hyperplasia (BPH).Methods:This was a retrospective study conducted from February 2014 to December 2018 in 140 patients who underwent PAE for LUTS, UR or hematuria secondary to BPH, including 85 patients with LUTS (60 patients with LUTS and 25 LUTS combined with hematuria), 52 patients with UR (50 patients with UR and 2 UR combined with hematuria) and 3 patients with hematuria. All patients were followed up for 24 months. Clinical success rates were evaluated. Friedman test was performed to compare the differences in International Prostate Symptom Score (IPSS), quality of life (QoL) score, and prostatic volume (PV) between baseline and follow-up time points (3, 6, 12 and 24 months). A post hoc test was performed by the Bonferroni method.Results:Significant differences in IPSS, QoL score and PV between baseline and follow-up time points were observed in 85 patients with LUTS ( P<0.001 for all), and clinical success rates at 3, 6, 12, 24 months after PAE were 95.3% (81/85), 91.8% (78/85), 87.1%(74/85), 83.5%(71/85). The success rate of extubation in patients with UR within 1 month after PAE was 98.1% (51/52). The average interval from PAE to catheter-independence was (6.8±3.7) days, and clinical success rates were 94.1% (48/51), 92.2% (47/51), 88.2% (45/51), 84.3% (43/51), respectively. The interval from PAE to the resolution of hematuria was (3.4±2.5) days, and clinical success rates were 90.0%(27/30), 90.0%(27/30), 83.3%(25/30), 80.0%(24/30), respectively. Conclusions:PAE was an effective treatment option for symptoms secondary to BPH in mid-term follow up.

Objective: To investigate the current basic situation of ultrasound machines of ultrasound departments in Shanghai medical institutions, and to provide the basis for making management policy in order to promote medical quality. Methods: Questionnaire surveys about ultrasound machines and service ability including producing countries of ultrasound machines, the number of ultrasound machines, using years of ultrasound machines, yearly workload and the yearly number of patients that each ultrasound machine accepted were made in 2013 and 2018, respectively. Statistical results were compared between the two surveys. Results: Compared with 2013, the share of imported ultrasound machines declined in 2018 (82% vs 91%). Compared with 2013, the number of ultrasound machines in Shanghai medical institutions had increased by 31% in 2018 (2 123 vs 1 617). The occupancy rate of ultrasound machines in tertiary hospitals was the highest (tertiary hospitals 40%, secondary hospitals 25%, primary grade hospitals 20%, and private hospitals 15%). Compared with 2013, the proportion of ultrasound machines that have been used for more than 10 years increased (9% vs 4%), the yearly workload of ultrasound examination had increased by 46% (19.82 million person-time vs 13.59 million person-time). Tertiary hospitals bored the highest proportion of the workload (tertiary hospitals 51%, secondary hospitals 35%, primary grade hospitals 4%, and private hospitals 10%). Currently, the number of ultrasound machines per 10, 000 people in Shanghai was 1.14. The yearly number of patients that each ultrasound machine accepted had increased by 11% (9300 person-time vs 8400 person-time in 2018). Conclusions The scale of ultrasound departments in Shanghai medical institutions has been developing. Brand localization of ultrasound machines is improving. However, the renewal ability of ultrasound machines still needs to be improved. The workload of ultrasound department is getting heavier. Hierarchical diagnosis and treatment is unbalanced.

Objective:To establish an analytical method for the simultaneous determination of five fat-soluble vitamins in serum using isotope dilution ultra high performance liquid chromatography-tandem mass spectrometry (ID-UPLC-MSMS).Methods:Fat-soluble vitamins were obtained from serum samples which collected from Shanghai Tenth People′s Hospital between April 2019 and August 2019 by the extraction method, and were detected by ID-UPLC-MSMS. The performance of the method was verified by referring to the relevant documents of the Clinical and Laboratory Standards Institute (CLSI).Results:The ID-UPLC-MSMS method for the rapid detection of various fat-soluble vitamins in serum was proposed and successfully verified. The linear range of the method: vitamin A: 25-2 500 μg/L, 25(OH)D 2: 2-200 μg/L, 25(OH)D 3: 2-200 μg/L, vitamin E: 0.25-50 mg/L, vitamin K1: 0.1-20 μg/L. The intra- and inter-assay precision standard deviations of the five analytes were within ± 15%, and the accuracy of the test results of the 25(OH)D 2 and 25(OH)D 3 standards was 96.44%-102.37%. Conclusion:The performance of ID-UPLC-MSMS method for the simultaneous determination of five fat-soluble vitamins is satisying, and the result is accurate and reliable, which suggested it can be used for the clinical sample.

Objective To investigate the clinical characteristics of DCD donor-derived CRKP infection and bleeding in kidney transplantation,and to summarize the experience of diagnosis,treatment and prevention.Methods A retrospective analysis was carried out from July 2016 to December 2017 in hospital,containing clinical data of 4 cases of CRKP-infected DCD donors and 7 cases of kidney transplantation recipients.Results In the CRKP culture of 4 cases of DCD donors,1 case was positive for blood culture,1 case was positive for urine culture,1 case was positive for sputum culture,and 1 case was negative for blood,urine and sputum culture.The corresponding 7 recipients were all positive for blood culture after renal transplantation,4 cases were positive for urine culture,3 cases were positive for sputum culture,and 5 cases were positive for perirenal drainage.Of the 7 patients,4 cases had renal artery hemorrhage,1 of them was died.The average bleeding time was 17.75 days after operation (14-19 days).In 7 patients with renal transplantation,CRP increasd.And in 3 cases of deaths,CRP was stably higher than normal.Meanwhile,CRP in 4 surviving patients gradually decreased to the normal range after effective anti-infection treatment.All 7 patients were treated with carbapenems;2 patients were dead without avibactam therapy;and 5 cases were treated with avibactam and carbapenems and survived,1 case died and 1 case had good renal function recovery.Conclusion Positive CRKP in blood,urine and sputum of DCD donors can lead to CRKP infection in kidney transplant recipients.Even if the body fluids of donors are all negative,the false negative results could not be excluded.Persistent or increased high-level CRP after operation is an early warning on CRKP infection.And CRP can be used as an indicator for evaluating the effectiveness of anti CRKP therapy.The combination of avibactam and carbapenem antibiotics is an effective regimen in the treatment of DCD donor-derived CRKP.

BJ-DRGs grouping process was cited as an example, to describe the factors affecting the grouping process, grouping results and assessment results, and the solutions in transferring homepages into WJT form 4-1 for inpatient medical record homepages (WJT form 4-1 for short).Authors analyzed how to better information acquisition quality of such homepages by unifying the data interface standard of WJT form 4-1, for the purposes of enhancing BJ-DRGs grouping efficiency, and expanding its functions as a tool for medical quality management and that for medical insurance payment management.

AIM:To observe the effects of granulocyte colony-stimulating factor (G-CSF) on calcium, sodium and potassium ion channel currents of the ischemic atrial myocytes in guinea pig by whole-cell patch clamp technique.METHODS:The guinea pig atrial myocytes were obtained by enzymolysis.Under ischemia and hypoxia condition, whole-cell patch clamp was used to observe the effects of G-CSF at various concentrations on the changes of the I-V curve, activation curve and availability of L-type calcium channel current (ICa,L) and voltage-dependent sodium channel current (INa), as well as I-V curve of delayed rectifier potassium channel current (IK).RESULTS:Under ischemic condition, the I-V curves of ICa,L were changed by acute G-CSF intervention in a dose-dependent fashion.Except for G-CSF at dose of 300 μg/kg, the other concentrations of G-CSF did not change the activation curve and availability of ICa,L, indicating that the effects of G-CSF on ICa,L were in a voltage-independent fashion.The I-V curves of ICa,L under ischemic condition were gradually approaching the normal levels by the higher dose of G-CSF, while the effect of 300 μg/kg G-CSF on ICa,L was similar to 100 μg/kg G-CSF.Acute G-CSF intervention at different doses did not change I-V curve, activation curve, and availability or steady-state availability of INa.As a part of IK, the rapid activating component (IKr) was improved by 100 μg/kg and 300 μg/kg G-CSF intervention with the similar effects, while the slowly activating component (IKs) was not changed by G-CSF.CONCLUSION:G-CSF affects ion channel electrophysiological properties of ischemic atrial myocytes in a voltage-independent but concentration-dependent manner, thus reducing the incidence of atrial arrhythmia.