Analysis of 10 cases of monkeypox in Changning District， Shanghai / 上海预防医学

ObjectiveTo analyze the clinical and epidemiological characteristics of confirmed cases of human monkeypox infection in Changning District， Shanghai， and to explore their clinical and epidemiological characteristics. MethodsClinical data from 10 reported cases of monkeypox in individuals residing in Changning District or identified by local medical institutions between July 20 and September 30， 2023， were collected. Epidemiological case investigations were conducted， and throat swabs， anal swabs， and rash swabs were collected by the treating medical institutions. Real-time fluorescence quantitative PCR was used for monkeypox virus nucleic acid testing， and descriptive epidemiological analysis was applied to analyze the epidemiological characteristics of the cases. ResultsAll 10 confirmed cases of human monkeypox infection were all young males with an average age of 35.4 years， all of whom belonged to the men who have sex with men （MSM） population， with no occupational clustering. The primary clinical symptoms included fever， rash， enlarged inguinal lymph nodes， and muscle soreness. Nine cases presented with a rash， and seven cases experienced fever symptoms. Among the 10 cases， one experienced fever， rash， enlarged lymph nodes， and muscle soreness； two had fever， rash， and enlarged lymph nodes； two had fever， rash， and systemic soreness； two had only a rash； one had fever or rash； and one was asymptomatic. Among the nine cases with a rash， the rash was mainly localized to the genital or anal area， with fewer cases presenting rashes on the limbs or trunk simultaneously. All cases reported a history of non-exclusive MSM behavior within 21 days before the onset of the disease. The interval between the last suspected high-risk exposure and the onset of symptoms was 4 to 10 days， with an average interval of 6.9 days. The time from the onset of fever to the appearance of a rash was 0 to 5 days， with an average of 1.87 days. ConclusionThe main clinical manifestations of human infection with monkeypox are fever， rash， and enlarged inguinal lymph nodes. The MSM population is a high-risk group for monkeypox infection， and its source of infection may be associated with MSM exposure. Early-stage symptoms are mild， leading to potential underdiagnosis. Additionally， patients may conceal information during the investigation process， which increases the difficulty of epidemic prevention and control.

A comparative study to measure the sagittal condylar inclination using mechanical articulator, virtual articulator and jaw tracking device

PURPOSE@#. To compare the sagittal condylar inclination (SCI) in dentate individuals measured by the different methods with mechanical articulator (MA), virtual articulator (VA), and a jaw tracking device (JTD) system. @*MATERIALS AND METHODS@#. A total of 22 healthy dentate participants were enrolled in this study. For MA workflow, the SCI was obtained by a semi-adjustable articulator with protrusive interocclusal records. The SCI was also set on a VA by aligning intraoral scan (IOS) with cone beam computed tomography (CBCT) and facial scan (FS), respectively. These virtual workflows were conducted in a dental design software, namely VAIOS-CBCT and VAIOS-FS . Meanwhile, a JTD system was also utilized to perform the measurement. Intraclass correlation was used to assess the repeatability within workflows. The bilateral SCI values were compared by Wilcoxon matched-pairs signed rank test for each workflow, and Kruskal-Wallis test and post hoc p-value Bonferroni correction were used to compare the differences among four workflows. The agreement of VAIOS-CBCT , VAIOS-FS , and JTD compared with MA was evaluated by Bland-Altman analysis. @*RESULTS@#. Intraclass correlation of the SCI revealed a high degree of repeatability for each workflow. There were no significant differences between the left and right sides (P > .05), except for VAIOS-CBCT (P = .028). Significant differences were not found between MA and VAIOS-FS (P > .05). Bland-Altman plots indicated VAIOS-CBCT , VAIOS-FS , and JTD were considered to substitute MA with high 95% limits of agreement. @*CONCLUSION@#. The workflow of VAIOS-FS provided an alternative approach to measure the SCI compared with MA.

Clinical characteristics of choledocholithiasis combined with periampullary diverticulum and influencing factor analysis for difficult cannulation of endoscopic retrograde cholangiopan-creatography: a report of 1 920 cases / 中华消化外科杂志

Objective:To investigate the clinical characteristics of choledocholithiasis com-bined with periampullary diverticulum and influencing factor for difficult cannulation of endoscopic retrograde cholangiopancreatography (ERCP).Methods:The retrospective case-control study was conducted. The clinical data of 1 920 patients who underwent ERCP for choledocholithiasis in 15 medical centers, including the First Hospital of Lanzhou University, et al, from July 2015 to December 2017 were collected. There were 915 males and 1 005 females, aged (63±16)years. Of 1 920 patients, there were 228 cases with periampullary diverticulum and 1 692 cases without periampullary diverticulum. Observation indicators: (1) clinical characteristics of patients with choledocholithiasis; (2) intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis; (3) influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and com-parison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Logistic regression model was used for univariate and multivariate analyses. Results:(1) Clinical characteristics of patients with choledocholithiasis. Age, body mass index, cases with complications as chronic obstructive pulmonary disease, diameter of common bile duct, cases with diameter of common bile duct as <8 mm, 8?12 mm, >12 mm, diameter of stone, cases with number of stones as single and multiple were (69±12)years, (23.3±3.0)kg/m 2, 16, (14±4)mm, 11, 95, 122, (12±4)mm, 89, 139 in patients with choledocholithiasis combined with periampullary diverticulum, versus (62±16)years, (23.8±2.8)kg/m 2, 67, (12±4)mm, 159, 892, 641, (10±4)mm, 817, 875 in patients with choledocholithiasis not combined with periampullary diver-ticulum, showing significant differences in the above indicators between the two groups ( t=?7.55, 2.45, χ2=4.54, t=?4.92, Z=4.66, t=?7.31, χ2=6.90, P<0.05). (2) Intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis. The balloon expansion diameter, cases with intraoperative bleeding, cases with hemorrhage management of submucosal injection, hemostatic clip, spray hemostasis, electrocoagulation hemostasis and other treatment, cases with endoscopic plastic stent placement, cases with endoscopic nasal bile duct drainage, cases with mechanical lithotripsy, cases with stone complete clearing, cases with difficult cannulation, cases with delayed intubation, cases undergoing >5 times of cannulation attempts, cannulation time, X-ray exposure time, operation time were 10.0(range, 8.5?12.0)mm, 56, 6, 5, 43, 1, 1, 52, 177, 67, 201, 74, 38, 74, (7.4±3.1)minutes, (6±3)minutes, (46±19)minutes in patients with choledocholithiasis combined with periampullary diverticulum, versus 9.0(range, 8.0?11.0)mm, 243, 35, 14, 109, 73, 12, 230, 1 457, 167, 1 565, 395, 171, 395, (6.6±2.9)minutes, (6±5)minutes, (41±17)minutes in patients with choledocholithiasis not combined with periampullary diverticulum, showing significant differences in the above indicators between the two groups ( Z=6.31, χ2=15.90, 26.02, 13.61, 11.40, 71.51, 5.12, 9.04, 8.92, 9.04, t=?3.89, 2.67, ?3.61, P<0.05). (3) Influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Results of multivariate analysis showed total bilirubin >30 umol/L, number of stones >1, combined with periampullary diverticulum were indepen-dent risk factors for difficult cannulation in patients with periampullary diverticulum who underwent ERCP for choledocholithiasis ( odds ratio=1.31, 1.48, 1.44, 95% confidence interval as 1.06?1.61, 1.20?1.84, 1.06?1.95, P<0.05). Results of further analysis showed that, of 1 920 patients undergoing ERCP for choledocholithiasis, the incidence of postoperative pancreatitis was 17.271%(81/469) and 8.132%(118/1 451) in the 469 cases with difficult cannulation and 1 451 cases without difficult cannula-tion, respectively, showing a significant difference between them ( χ2=31.86, P<0.05). In the 1 692 patients with choledocholithiasis not combined with periampullary diverticulum, the incidence of postopera-tive pancreatitis was 17.722%(70/395) and 8.250%(107/1 297) in 395 cases with difficult cannula-tion and 1 297 cases without difficult cannulation, respectively, showing a significant difference between them ( χ2=29.00, P<0.05). In the 228 patients with choledocholithiasis combined with peri-ampullary diverticulum, the incidence of postoperative pancreatitis was 14.865%(11/74) and 7.143%(11/154) in 74 cases with difficult cannulation and 154 cases without difficult cannulation, respectively, showing no significant difference between them ( χ2=3.42, P>0.05). Conclusions:Compared with patients with choledocholithiasis not combined with periampullary divertioulum, periampullary divertioulum often occurs in choledocholithiasis patients of elderly and low body mass index. The proportion of chronic obstructive pulmonary disease is high in choledocholithiasis patients with periampullary diverticulum, and the diameter of stone is large, the number of stone is more in these patients. Combined with periampullary diverticulum will increase the difficult of cannulation and the ratio of patient with mechanical lithotripsy, and reduce the ratio of patient with stone complete clearing without increasing postoperative complications of choledocholithiasis patients undergoing ERCP. Total bilirubin >30 μmol/L, number of stones >1, combined with periampullary diverticulum are independent risk factors for difficult cannulation in patients of periampullary diverticulum who underwent ERCP for choledocholithiasis.

Whole-cell biosynthesis of cytarabine by an unnecessary protein-reduced Escherichia coli that coexpresses purine and uracil phosphorylase.

Currently, whole-cell catalysts face challenges due to the complexity of reaction systems, although they have a cost advantage over pure enzymes. In this study, cytarabine was synthesized by purified purine phosphorylase 1 (PNP1) and uracil phosphorylase (UP), and the conversion of cytarabine from adenine arabinoside reached 72.3 ± 4.3%. However, the synthesis was unsuccessful by whole-cell catalysis due to interference from unnecessary proteins (UNPs) in cells. Thus, we carried out a large-scale gene editing involving 377 genes in the genome of Escherichia coli to reduce the negative effect of UNPs on substrate conversion and cytarabine production. Finally, the PNP1 and UP activities of the obtained mutant were increased significantly compared with the parental strain, and more importantly, the conversion rate of cytarabine by whole-cell catalysis reached 67.4 ± 2.5%. The lack of 148 proteins and downregulation of 783 proteins caused by gene editing were equivalent to partial purification of the enzymes within cells, and thus, we provided inspiration to solve the problem caused by UNP interference, which is ubiquitous in the field of whole-cell catalysis.

Efficient Neutralization of SARS-CoV-2 Omicron and Other VOCs by a Broad Spectrum Antibody 8G3

Numerous mutations in the spike protein of SARS-CoV-2 B.1.1.529 Omicron variant pose a crisis for antibody-based immunotherapies. The efficacy of emergency use authorized (EUA) antibodies that developed in early SARS-CoV-2 pandemic seems to be in flounder. We tested the Omicron neutralization efficacy of an early B cell antibody repertoire as well as several EUA antibodies in pseudovirus and authentic virus systems. More than half of the antibodies in the repertoire that showed good activity against WA1/2020 previously had completely lost neutralizing activity against Omicron, while antibody 8G3 displayed non-regressive activity. EUA antibodies Etesevimab, Casirivimab, Imdevimab and Bamlanivimab were entirely desensitized by Omicron. Only Sotrovimab targeting the non-ACE2 overlap epitope showed a dramatic decrease activity. Antibody 8G3 efficiently neutralized Omicron in pseudovirus and authentic virus systems. The in vivo results showed that Omicron virus was less virulent than the WA1/2020 strain, but still caused deterioration of health and even death in mice. Treatment with 8G3 quickly cleared virus load of mice. Antibody 8G3 also showed excellent activity against other variants of concern (VOCs), especially more efficient against authentic Delta plus virus. Collectively, our results suggest that neutralizing antibodies with breadth remains broad neutralizing activity in tackling SARS-CoV-2 infection despite the universal evasion from EUA antibodies by Omicron variant.

Comprehensive Evaluation of ACE2-Fc Combination with Neutralization Antibody on Broad Protection against SARS-CoV-2 and Its Variants

Emerging SARS-CoV-2 variants are threatening the efficacy of antibody therapies. Combination treatments including ACE2-Fc have been developed to overcome the evasion of neutralizing antibodies (NAbs) in individual cases. Here we conducted a comprehensive evaluation of this strategy by combining ACE2-Fc with NAbs of diverse epitopes on the RBD. NAb+ACE2-Fc combinations efficiently neutralized HIV-based pseudovirus carrying the spike protein of the Delta or Omicron variants, achieving a balance between efficacy and breadth. In an antibody escape assay using replication-competent VSV-SARS-CoV-2-S, all the combinations had no escape after fifteen passages. By comparison, all the NAbs without combo with ACE2-Fc had escaped within six passages. Further, the VSV-S variants escaped from NAbs were neutralized by ACE2-Fc, revealing the mechanism of NAb+ACE2-Fc combinations survived after fifteen passages. We finally examined ACE2-Fc neutralization against pseudovirus variants that were resistant to the therapeutic antibodies currently in clinic. Our results suggest ACE2-Fc is a universal combination partner to combat SARS-CoV-2 variants including Delta and Omicron.

Clinical efficacy of posterolateral approach combined with anteromedial approach in treatment of trimalleolus fracture / 中华创伤骨科杂志

Objective:To investigate the clinical efficacy of posterolateral approach combined with anteromedial approach in the treatment of trimalleolus fracture.Methods:A retrospective analysis was performed of the 20 patients who had been admitted to The Second Department of Orthopedics, The First People's Hospital of Tianshui for trimalleolus fractures from January 2016 to August 2020. They were 16 men and 4 women, aged from 20 to 70 years (average, 49.6 years). The lateral malleolus, posterior malleolus and medial malleolus were treated with reduction and internal fixation using the posterolateral approach combined with the anteromedial approach. Postoperative complications were observed, and the foot function was assessed using the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and pain visual analog scale (VAS).Results:In this cohort, the operation time ranged from 85 to 115 minutes, averaging 88.4 minutes and the intraoperative blood loss from 50 to 600 mL, averaging 120 mL. All patients were followed up for 12 to 20 months (mean, 14.5 months). The fracture healing time ranged from 3.2 to 5.4 months, averaging 3.8 months. Follow-ups observed no such complications as infection or necrosis of surgical incision, failure of internal fixation, nonunion, or malunion. The AOFAS ankle-hindfoot score at 12 months after operation (87.8±6.4) was significantly higher than that before operation (32.3±4.9) ( t=29.454, P<0.001); as for VAS, one case scored 0, 13 cases 1 to 3 points and 6 cases 4 points. Conclusion:In the treatment of trimalleolus fracture, a combination of posterolateral approach and anteromedial approach can lead to definitely positive efficacy because of a significant reduction in operation time, intraoperative bleeding and postoperative complications.

Outcomes and safety of phacoemulsification combined with intraocular lens implantation plus goniosynechialysis and goniotomy for advanced primary angle-closure glaucoma / 中华实验眼科杂志

Objective:To evaluate the effectiveness and safety of phacoemulsification cataract extraction combined with intraocular lens implantation (PEI) plus goniosynechilysis (GSL) and goniotomy (GT) for advanced primary angle-closure glaucoma (PACG).Methods:An observational case series study was performed.Fifty eyes of 50 patients with advanced PACG were enrolled in Zhongshan Ophthalmic Center from August 2020 to June 2021.All the patients received PEI+ GSL+ GT and were followed up for over 6 months, with a mean follow-up of 7.5 (6, 10) months.Intraocular pressure (IOP) was measured with a Goldmann applanation tonometer.Best corrected visual acuity (BCVA) was examined with an ETDRS chart and converted to logarithm of the minimum angle of resolution (LogMAR) units for analysis.Types and number of anti-glaucoma medications applied before and after surgery, and the surgical complications were collected.Success rate of surgery was calculated.Complete surgical success was defined as an IOP of 5-18 mmHg (1 mmHg=0.133 kPa) with a reduction of 20% from baseline without anti-glaucoma medication, no vision-threatening complications, no loss of light perception, and no reoperation.Qualified success was defined as an IOP of 5-18 mmHg with a reduction of 20% from baseline with or without anti-glaucoma medication, no vision-threatening complications, no loss of light perception, and no reoperation.This study adhered to the Declaration of Helsinki.This research protocol was approved by an Ethics Committee of Zhongshan Ophthalmic Center (No.2021KYPJ177). Written informed consent was obtained from each subject before entering the cohort.Results:The mean preoperative IOP was (28.81±7.81)mmHg, and the IOP at the end of follow-up was (13.41±4.10)mmHg, showing a statistically significant decrease ( t=12.260, P<0.001). The postoperative IOP was decreased by 13.80 (9.10, 19.40)mmHg, with a percentage decrease of 51.1% (38.6%, 67.1%). The mean preoperative and postoperative BCVA was (0.92±0.11) LogMAR and (0.88±0.10) LogMAR, respectively, and no significant difference was found ( t=-0.560, P=0.580). The number of anti-glaucoma medications was reduced from 2 (1, 3) before operation to 0 (0, 0) after operation.The complete success rate of surgery was 80% (40/50), and the qualified success rate was 94% (47/50). Surgical complications mainly included hyphema in 7 eyes, IOP spike in 7 eyes, and corneal edema in 3 eyes.No vision-threatening complication occurred. Conclusions:PEI+ GSL+ GT is preliminarily effective and safe for advanced PACG by reducing IOP and application of anti-glaucoma medications with few complications.

The effect of national tertiary public hospital performance assessment on the functional orientation of provincial public hospitals / 中华医院管理杂志

Objective:To analyze the impact of the national tertiary public hospital performance assessment(hereinafter referred to as the national examination) on the functional orientation of the provincial public hospitals in Zhejiang province, for reference to improve the allocation of provincial medical resources and high-quality development of public hospitals.Methods:The data came from the hospital financial data of 17 provincial tertiary public hospitals in Zhejiang province from 2012 to 2021 and the DRG quality performance analysis report of the tertiary hospitals in Zhejiang province from 2020 to 2021. The information of the number of employees and actual number of beds at the end of the period, etc., were extracted to analyze the overall operation of the hospital. The ratio of outpatient times to discharged times and the proportion of discharged patients undergoing surgery, as well as the proportion of discharged patients′ day surgery and level-4 surgery in hospital and in province were took as evaluation indicators to analyze the functional positioning of tertiary public hospitals.Results:Compared with 2012 to 2018, the average number of employees at the end of the period and actual number of beds in 17 hospitals from 2019 to 2021 increased by 761 and 303 respectively, and the average number of hospitalization days decreased by 2.26 days. The average ratio of outpatient times to discharged times in the hospital decreased from 175.76 in 2012 to 67.51 in 2021. The average proportion of discharged patients undergoing surgery in general hospitals increased from 0.39 in 2012 to 0.46 in 2021, and that in non-general hospitals decreased from 0.67 to 0.43. The average proportion of discharged patients undergoing day surgery in hospital and in province increased from 0.20 and 0.03 in 2020 to 0.23 and 0.04 in 2021 respectively, and the average proportion of discharged patients undergoing level-4 surgery in province increased from 0.04 to 0.05.Conclusions:The national examination could be conducive to strengthening the functional orientation of public hospitals. After the national examination, the ratio of outpatient times to discharged times in the provincial tertiary public hospitals in Zhejiang province had declined as a whole, the proportion of discharged patients in general hospitals had increased, but the proportion of level-4 surgery in hospitals needs to be further improved. The author suggested that we should continue to strengthen the operation mechanism of functional positioning of provincial public hospitals, improve the service capacity of hospitals for difficult and critical diseases, and improve the performance evaluation system of tertiary public hospitals.

Comparison of safety and efficacy of laparoscopy and laparotomy for 5-10 cm intermediate-risk primary gastric stromal tumors / 中华消化内镜杂志

Objective:To compare the safety and efficacy of laparoscopy and laparotomy for 5-10 cm intermediate-risk gastric stromal tumor, and to evaluate whether there was evident benefits of postoperative adjuvant treatment with imatinib.Methods:A retrospective study was conducted on 72 patients with moderate risk gastric stromal tumors (5-10 cm in diameter) who received operation in Nanjing Drum Tower Hospital from January 2010 to July 2020. There were 28 cases in the laparoscopy group and 44 cases in the laparotomy group. The clinical features, pathological data, perioperative results and hospitalization costs were compared between the two groups. The survival rates of postoperative adjuvant therapy with or without imatinib were analyzed and compared.Results:There was no significant difference in clinicopathological features between the two groups ( P>0.05). The incidences of postoperative complications in the laparoscopy group and the laparotomy group were 32.1% (9/28) and 52.3% (23/44) respectively, showing no significant difference ( P=0.094). Compared with the laparotomy group, both the hospital stay (12.5±3.2 days VS 15.0±3.5 days, P=0.004) and the median postoperative hospital stay (7.5 days VS 9.0 days, P=0.006) in the laparoscopy group were significantly shorter, and the first exhaust time was significantly shorter ( P=0.003). During the median follow-up period of 58 months (13-129 months), there was no tumor-related death. Two cases died of breast cancer and heart disease in the laparotomy group, and 1 case died irrelevant to gastric stromal tumor in the laparoscopy group. Of the 72 patients, 40 received postoperative imatinib adjuvant therapy, 22 cases (50.0%) in the laparotomy group and 18 cases (64.3%) in the laparoscopy group, with no significant difference in the proportion ( χ2=1.414, P=0.234). There was significant difference in the overall survival rate between the group treated with imatinib and the group without imatinib ( P=0.015). Conclusion:Laparoscopic resection is safe and effective for intermediate-risk gastric stromal tumor of 5-10 cm. Taking imatinib adjuvant treatment does not increase overall survival rate of patients with intermediate-risk gastric stromal tumors (5-10 cm), and there is no tumor-related death, recurrence or metastasis for those who did not accept imatinib adjuvant treatment after R0 resection.

Broad ultra-potent neutralization of SARS-CoV-2 variants by monoclonal antibodies specific to the tip of RBD

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) continue to wreak havoc across the globe. Higher transmissibility and immunologic resistance of VOCs bring unprecedented challenges to epidemic extinguishment. Here we describe a monoclonal antibody, 2G1, that neutralizes all current VOCs and has surprising tolerance to mutations adjacent to or within its interaction epitope. Cryo-electron microscopy structure showed that 2G1 bound to the tip of receptor binding domain (RBD) of spike protein with small contact interface but strong hydrophobic effect, which resulted in nanomolar to sub-nanomolar affinities to spike proteins. The epitope of 2G1 on RBD partially overlaps with ACE2 interface, which gives 2G1 ability to block interaction between RBD and ACE2. The narrow binding epitope but high affinity bestow outstanding therapeutic efficacy upon 2G1 that neutralized VOCs with sub-nanomolar IC50 in vitro. In SARS-CoV-2 and Beta- and Delta-variant-challenged transgenic mice and rhesus macaque models, 2G1 protected animals from clinical illness and eliminated viral burden, without serious impact to animal safety. Mutagenesis experiments suggest that 2G1 could be potentially capable of dealing with emerging SARS-CoV-2 variants in future. This report characterized the therapeutic antibodies specific to the tip of spike against SARS-CoV-2 variants and highlights the potential clinical applications as well as for developing vaccine and cocktail therapy.

Studies on the level of neutralizing antibodies produced by inactivated COVID-19 vaccines in the real world

BackgroundAlthough effective vaccines have been developed against COVID-19, the level of neutralizing antibodies (Nabs) induced after vaccination in the real world is still unknown. To evaluate the level and persistence of NAbs induced by two inactivated COVID-19 vaccines in China. Methods and findingsSerum samples were collected from 1,335 people aged 18 and over who were vaccinated with COVID-19 inactivated vaccine in Peking University Peoples Hospital from January 19 to June 23, 2021, for detection of COVID-19 antibodies. The WHO standard of SARS-CoV-2 NAbs was detected. The coefficients of variation between the detection results and the true values of the NAbs detected by the WHO standard were all lower than the WHO international standard 3% after the dilution of the original and the dilution of the theoretical concentrations of 500 IU/mL, 250 IU/mL, 125 IU/mL, 72.5 IU/mL, 36.25 IU/mL and 18.125 IU/mL. On day 11-70, the positive rate of NAbs against COVID-19 was 82% to 100%; From day 71 to 332, the positive rate of NAbs decreased to 27%. The level of NAbs was significantly higher at 3-8 Weeks than at 0-3 Weeks. There was a high linear correlation between NAbs and IgG antibodies in 1335 vaccinated patients. NAbs levels were decreased in 31 of 38 people (81.6%) at two time points after the second dose of vaccine. There was no significant difference in age between the group with increased and decreased neutralizing antibody levels ({chi}2 =-0.034, P>0.05). The positive rate of NAbs in the two-dose vaccine group (77.3%) was significantly higher than that in the one-dose group (18.1%), with statistical difference ({chi}2=312.590, P<0.001). A total of 206 people who were 11-70 days after receiving the second dose were tested and divided into three groups: 18-40 years old, 41-60 years old and >60 years old. The positive rates of NAbs in three groups (18-40 years old, 41-60 years old and >60 years old) were 95.14%, 78.43% and 81.8%, respectively. The positive rate of NAbs was significantly higher in 18-40 years old than in 41-60 years old ({chi}2=12.547, P <0.01). The titer of NAbs in 18-40 years old group was significantly higher than that in 41-60 years old group (t=-0.222, P <0.01). The positive rate of NAbs in male group (89.32%) was lower than in female (91.26%), but there was no significant difference ({chi}2=0.222, P >0.05). ConclusionsThe positive rate of NAbs was the highest from 10 to 70 days after the second dose of vaccine, and the positive rate gradually decreased as time went by. There was a high linear correlation between COVID-19 NAbs and IgM/IgG antibodies in vaccinators, suggesting that in cases where NAbs cannot be detected, IgM/IgG antibodies can be detected instead. The level of NAbs produced after vaccination was affected by age, but not by gender. The highest levels of NAbs were produced between shots 21 to 56 days apart, suggesting that 21 to 56 days between shots is suitable for vaccination. Author summaryO_ST_ABSWhy was this study done?C_ST_ABSO_LIAt present, the inactivated vaccines that have been approved to market in China have passed clinical trials to prove their effectiveness and safety. But the level of neutralizing antibodies induced by vaccination in the real world remains unclear. C_LIO_LISerological testing for neutralizing antibodies against COVID-19 is important for assessing vaccine and treatment responses and comparing multiple drug candidates. We assessed the levels of neutralizing antibodies produced in populations receiving inactivated vaccines and assessed the persistence of these vaccines in producing COVID-19 neutralizing antibodies in healthy adults. C_LI What did the researchers do and find?O_LIWe collected serum samples from 1,335 people aged 18 and above who had received COVID-19 vaccine in Peking University Peoples Hospital, and divided them into two groups according to one dose of inactivated vaccine and two doses of inactivated vaccine. C_LIO_LIOur study found that the positive rate of NAbs was 66.2% in adults who received one or two doses of inactivated vaccine and 77.3% in adults who received two doses of inactivated vaccine in the real world. C_LIO_LIFrom 11 to 70 days after the second dose of vaccine, the positive rate of neutralizing antibodies against COVID-19 was 82-100%; On days 71-332, the positive rate of neutralizing antibodies decreased to 27%. C_LIO_LIThe titer and the positive rate of NAbs in 18-40 years old group were significantly higher than that in 41-60 years old group. C_LI What do these findings mean?O_LIWhat is novel is we observed that in the real world, the positive rate of neutralization antibody was the highest at 10 to 70 days after the second vaccination, and with the extension of the vaccination time, the positive rate of antibody gradually decreased. Therefore, we recommend that the third dose of vaccine be administered at day 61 to day 70 for COVID-19 neutralizing antibodies levels. C_LIO_LIWe observed that there was a high linear correlation between COVID-19 neutralization antibodies and COVID-19 IgM/IgG antibodies in vaccinators, suggesting that in cases where NAbs cannot be detected, COVID-19 IgM/IgG antibodies can be detected instead. C_LIO_LIIn our manuscript, we found that the titer and positive rate of neutralizing antibodies in 18-40 years old group were higher than those in 41-60 years old group. The level of neutralizing antibodies produced after vaccination was affected by age, but not by gender. C_LIO_LIWe also observed that the highest levels of NAbs were produced between shots 21 to 35 days apart, suggesting that 21 to 35 days between shots is suitable for vaccination. C_LI

Self-assessment of COVID-19 vaccination efficacy using a simple POCT for SARS-CoV-2 S1 protein antibody IgG-IgM

BackgroundMore than ten novel COVID-19 vaccines have been approved with protections against SARS-CoV-2 infections ranges between 52-95%. It is of great interest to the vaccinees who have received the COVID-19 vaccines, vaccine developers and authorities to identify the non-responders in a timely manner so intervention can take place by either giving additional boosts of the same vaccine or switching to a different vaccine to improve the protection against the SARS-CoV-2 infections. A robust correlation was seen between binding antibody titer and efficacy (p=0.93) in the clinic studies of 7 COVID-19 vaccines, so it is of urgency to develop a simple POCT for vaccinees to self-assess their immune response at home. MethodsUsing CHO cell-expressed full length SARS-CoV2 S1 protein as coating antigen on colloidal gold particles, a SARS-CoV-2 S1 IgG-IgM antibody lateral flow test kit (POCT) was developed. The test was validated with negative human sera collected prior to the COVID-19 outbreaks, and blood samples from human subjects prior, during, and post-immunization of COVID-19 vaccines. ResultsThe specificity of the POCT was 99.0%, as examined against 947 normal human sera and 20 whole blood samples collected pre-immunization. The limit of detection was 50 IU/mL of pseudovirus neutralizing titer (PVNT) using human anti-SARS-2 neutralizing standards from convalescent sera. The sensitivity of POCT for SARS-CoV-2 S1 protein antibody IgG-IgM was compared with SARS-CoV-2 RBD antibody ELISA and determined to be 100% using 23 blood samples from vaccinated human subjects and 10 samples from non-vaccinated ones. Whole blood samples were collected from 119 human subjects (ages between 22-61 years) prior to, during, and post-vaccination of five different COVID-19 vaccines. Among them, 115 people tested positive for SARS-CoV-2 S1 antibodies (showing positive at least once) and 4 people tested negative (tested negative at least twice on different days), demonstrating 96.64% of seroconversion after full-vaccination. 92.3% (36/39) of the human subjects who were younger than 45 achieved seroconversion within 2 weeks while only 57.1% (4/7) of subjects older than 45 tested positive for S1 antibodies, suggesting that younger people develop protection much faster than older ones. Even though the S1 antibody level in 88% of human subjects vaccinated with inactivated virus dropped below 50 IU/mL two months later, one boost could quickly raise the S1 antibody titer above 50 IU/mL of PVNT, indicates that the initial vaccination was successful and immunization memory was developed. ConclusionUsing the lateral flow tests of SARS-CoV2 S1 IgG+IgM, vaccinated human subjects can easily self-assess the efficacy of their vaccination at home. The vaccine developer could quickly identify those non-responders and give them an additional boost to improve the efficacy of their vaccines. Vaccinees who failed in response could switch to different types of COVID-19 vaccines since there are more than 10 COVID-19 vaccines approved using three different platform technologies. HighlightsO_LIMore than ten novel COVID-19 vaccines have been approved with protections against SARS-CoV-2 infections ranges between 52-95%. It is of great interest to the vaccinees who have received the COVID-19 vaccines, vaccine developers and authorities to identify the non-responders in a timely manner. C_LIO_LIA highly specific and very simple lateral flow test kit for measurement of SARS-CoV-2 S1IgG+IgM antibodies post-immunization of COVID-19 vaccine using peripheral blood was developed as a home-test assay with a limit of detection (LOD) at 50 IU/mL of pseudovirus neutralizing titer (PVNT). C_LIO_LIAfter full vaccinations with COVID-19 vaccines, 96.6% of the volunteers successfully achieved the seroconversion of SARS-CoV-2 S1 IgG+IgM antibody. C_LIO_LI92.3% (36/39) of the human subjects who were younger than 45 achieved seroconversion within 2 weeks while only 57.1% (4/7) of subjects older than 45 tested positive for S1 antibodies, suggesting that younger people develop protection much faster than older ones. C_LIO_LIEven though the S1 antibody level in 88% of human subjects vaccinated with inactivated virus dropped below the detection 2-6 months later, one boost could quickly raise the S1 antibody titer above 50 IU/mL of PVNT, indicating that the initial vaccination was successful and immunization memory was developed. C_LI

Acute gallstone pancreatitis caused by duodenal papillary impacted stone: a study on its risk factors based on ERCP findings / 中华肝胆外科杂志

Objective:To study the risk factors of acute gallstone pancreatitis (AGP) caused by impaction of duodenal papilla stones based on ERCP findings to provide evidence on prevention of AGP caused by stone impaction.Methods:The data of 304 patients with duodenal papilla stone impaction who were treated by ERCP at the Integrated Chinese and Western Medicine Hospital of Tianjin University from January 2009 to December 2020 were analyzed retrospectively. There were 177 males and 127 females, with a median age of 65.0 years. These patients were divided into the AGP group ( n=174) and the non-AGP group ( n=130) according to whether they developed acute pancreatitis before hospitalization. The analysis was performed on perioperative data. Multivariate logistic regression analysis was used to detect risk factors of AGP in patients with duodenal papillary stone impaction. Results:Multivariate logistic analysis showed that acute cholangitis ( OR=2.114, 95% CI: 1.279-3.494, P<0.05) and impacted stones ≤5 mm ( OR=1.738, 95% CI: 1.064-2.840, P<0.05) were independent risk factors of duodenal papillary stone impaction complicated with AGP. No perforation and death related to ERCP treatment occurred in both groups. The symptom alleviating time of patients in the AGP versus the non-AGP groups was (2.67±1.19) versus (1.88±0.88) d respectively ( t=-6.321, P<0.001). Conclusion:Among patients with duodenal papilla impacted stones, acute cholangitis and impacted stones ≤5 mm were risk factors of developing AGP, and ERCP should be carried out as early as possible.

Clinical value of endoscopic ultrasonography in preoperative endoscopic retrograde cholangiopancreatography for undetermined common bile duct stones / 中华消化内镜杂志

Objective:To study the clinical value of endoscopic ultrasonography (EUS) before endoscopic retrograde cholangiopancreatography (ERCP) in patients with non-deterministic choledocholithiasis.Methods:Data of 132 patients with unconfirmed common bile duct calculi diagnosed in Tianjin Nankai Hospital from January 2017 to December 2019, whose clinical manifestations were not consistent with magnetic resonance cholangiopancreatography (MRCP) results, were retrospectively analyzed. Patients were divided into two groups: group A showed calculi under MRCP with no suspicious clinical manifestations, while group B showed no calculi under MRCP with suspected clinical manifestations. All patients underwent EUS. Necessity of ERCP was determined according to EUS results, and the diagnostic accuracy of EUS was analyzed compared with ERCP results and follow-up results as the gold standard.Results:Of the 132 patients, 87 were confirmed as choledocholithiasis, and 45 had no common bile duct calculi by the golden standard. Forty-four (33.3%) cases were negative in EUS and were confirmed free of calculi by follow-up. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of EUS for choledocholithiasis were 95.40% (83/87), 97.78% (44/45), 96.21% (127/132), 98.81% (83/84) and 91.67% (44/48), respectively.The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of MRCP for choledocholithiasis were 66.67% (58/87), 82.22% (37/45), 71.97% (95/132), 87.88% (58/66) and 56.06% (37/66), respectively. There were significant differences in the sensitivity, accuracy, positive predictive value or negative predictive value between EUS and ERCP (all P<0.05). There was significant consistency between the EUS results and the final diagnosis ( Kappa=0.917, P<0.001), and good consistency between MRCP results and the final diagnosis ( Kappa=0.439, P<0.001). The detection rate of false positive MRCP in group A was higher than that of false negative MRCP in group B [8/8 VS 89.66% (26/29), P<0.001] under EUS. Conclusion:EUS is superior to MRCP in the diagnosis of uncertain choledocholithiasis, and EUS prior to ERCP can reduce unnecessary ERCP operations and avoid missing stones.

Application of Renaissance spinal surgical robot in middle and upper thoracic fractures / 中华骨科杂志

Objective:To explore the safety and effectiveness of the Renaissance spine surgery robot in the middle and upper thoracic spine fractures.Methods:62 patients with middle and upper thoracic vertebra fractures from March 2015 to March 2019 were prospectively analyzed. These patients were randomly divided into robot group (Renaissance robot-assisted nailing) and free hand group (unarmed nailing under perspective). There were 32 patients in robot group, including 25 males and 7 females with an average age of 43.1±8.91 years (range, 18-65 years). Body mass index (BMI) was 26.15±3.97 kg/m 2 (range, 16.3-41.7 kg/m 2). The preoperative Cobb angle was 20.9 °±2.83° (range, 10.7 °-33.9°). In the free hand group, there were 30 cases, including 24 males and 6 females; Age 44.2±9.10 years (range, 20-67 years), BMI 25.97±4.02 kg/m 2 (range, 17.1-43.2 kg/m 2); The preoperative Cobb angle was 21.3°±3.01° (range, 11.6°-35.1°). The 2 groups were compared in terms of accuracy of screw placement, one-time success rate of screw placement, completion time of screw placement, time of total operation and penetration rate of anterior vertebral margin. The robot group also compared the consistency of screw placement angle with preoperative planning. Results:All patients completed the operation successfully. The number of fractured vertebrae in the robot group was 37; the screw placement time was 16.11±5.82 min; the total number of screws was 230, of which 227 were successfully placed at one time, with a success rate of 98.70% (227/230); 1 screw was inserted through the anterior edge of the vertebral body, and the penetration rate was 0.43% (1/230). The number of fractured vertebrae in the free hand group was 35; the nail placement time was 21.09±7.31 min; the total number of screws was 216, of which 195 were successfully placed at one time, with a success rate of 90.28% (195/216); 12 screws was inserted through the anterior edge of the vertebral body, and the penetration rate was 5.56% (12/216). There were significant differences in the time, success rate and penetration rate between the two groups. There was no significant difference in the total operation time between the robot group and the unarmed nail group 137.23±12.68 min and 140.23±13.13 min, respectively. There was no significant difference in the angle of screw placement between pre-operative planning image and post-operative CT scan in the robot group.Conclusion:Renaissance spinal surgery robot in the treatment of middle and upper thoracic vertebra fractures has the advantages of high accuracy, low intraoperative risk, high safety and satisfactory effect of pedicle screw placement.

Comparative analysis of output factor of high-energy photon small field between measurements with or without correction of IAEA-483 report and Monte-Carlo simulation / 中华放射肿瘤学杂志

Objective:To evaluate the accuracy of measurement of the output factor of high-energy photon small field (Scp) using commercial semi-diodes and ionization chambers in small fields in accordance with the IAEA-483 report, which has been proposed that all kinds of detectors should be revised for small field Scp measurement in clinical practice.Methods:EGSnrc of Monte Carlo (MC) software was utilized to simulate the treatment head of Varian Novalis Tx linear accelerator, and the profile curve and relative dose value were generated by simulation in DOSXYZnrc based on derived phase space file. Measurement of PDD and Profiles was used to adjust and validate the simulation mode. Detectors including ionization chambers A16, A14 sL, CC01, CC13, PFD and EFD and semi-diodes PFD, EFD and Razor under different radiation field settings (0.5 cm to 10.0 cm) were employed to measure the profile curves and Scp of FWHM equivalent rectangular fields, which were compared with data of Monte-Carlo simulation. The measurement of Scp was revised by data given in the IAEA-483 report. The data with or without correction were compared with the data of MC simulation.Results:A curve deviation o F<2.0% between MC simulation and PFD measurement was accepted. MC simulated Profiles were consistent with PFD, EFD and Razor measurements, when the field was<3.0 cm. Razor response in the out-field region was 2.3% higher than those of MC and PFD, and it increased with the increment of field and was 3.0% at 10.0 cm. The maximum 20.0%-80.0% penumbra width was detected as 3.0 mm for CC13 at 10.0 cm rectangular field. With the decrease of the radiation field, the deviation relative to MC simulation was increased as for Scp mean values of 7 detectors before correction. The standard deviation (SD) of the measured value was increased rapidly when it was close to 1.0 cm, ranging from 0.009-0.014 for the field of 5.0 cm-1.5 cm to 0.030-0.089 for the field of 1.0 cm-0.5 cm. The mean value of SD for the whole measurement before correction was 0.030. The mean SD of Scp measured by the six probes was 0.008, 0.013 at 0.8 cm and 0.021 at 0.6 cm after correction. When the equivalent field was ≥1.0 cm, the corrected Scp and MC simulation deviation was ranged from -3.6% to -0.5%. The error was between -6.9% and -1.3% when the radiation field was<1.0 cm. Conclusion:The SD of Scp measured by different detectors after correction in accordance to the IAEA-483 report is small, which is in good agreement with the data of MC simulation, suggesting that it could be applied in clinical dosimetry.

Clinical effect of pantoprazole combined with traditional Chinese medicine in the treatment of gastroesophageal reflux / 中华消化内镜杂志

To investigate the clinical effect of pantoprazole combined with traditional Chinese medicine for gastroesophageal reflux. A total of 50 cases of gastroesophageal reflux selected from January 2019 to December 2019 in Aviation General Hospital were randomly divided into the control group and the observation group. The control group was given pantoprazole, and the observation group was given traditional Chinese medicine combined with pantoprazole. Both groups were treated for 28 days. The recovery of clinical symptoms, status of esophageal mucosa by endoscopy and the incidence of adverse reactions were compared between the two groups. The clinical symptoms and status of esophageal mucosa in both group were obviously improved. Efficiency of the observation group was significantly higher than that of the control group( P<0.05). No serious adverse reactions happened during treatment. Pantoprazole combined with traditional Chinese medicine has definite clinical effects in the treatment of gastroesophageal reflux, which can improve the clinical symptoms and the recovery of esophageal mucosa of patients with high safety.

Endoscopic ultrasonographic performance of common bile duct adenomas / 中华消化内镜杂志

Objective:To investigate the features of common bile duct adenoma under endoscopic ultrasonography (EUS).Methods:Clinical data of 15 patients with common bile duct adenomas confirmed by pathology from January 2015 to January 2020 in Tianjin Nankai Hospital were analyzed retrospectively. The patients′ EUS features were summarized.Results:The common bile duct adenoma was characterized by homogeneous soft tissue mass with medium or low echo and clear boundary, floating in the bile duct with no movement under EUS. EUS diagnosis of 14 out of 15 patients was consitent with the pathology, and the diagnostic consistency was 93.3%. One patient with a movable lesion was misdiagnosed as cholestasis by EUS. One patient had two solitary adenomas, located in the middle and lower part of the common bile duct, and 14 others had single adenoma. There were 9 adenomas in the lower part, 4 in the ampulla, 2 in the upper part, and 1 in the middle of the common bile duct. The pathological findings were 7 cases of villous adenoma with high-grade intraepithelial neoplasia, 4 cases of local malignant changes; 6 villous tubular adenoma with high-grade intraepithelial neoplasia, 3 local malignant changes; 2 villous tubular adenoma with low-grade intraepithelial neoplasia; and 1 papillary adenoma.Conclusion:EUS, helpful for the qualitative diagnosis, can be used as an important technique to improve the diagnosis of common bile duct adenoma.

Impacts of COVID-19 pandemic on public hospitals operation and the countermeasures: public hospitals in Wenzhou as an example / 中华医院管理杂志

Objective:To provide countermeasures and suggestions for the current operation and management of public hospitals by analyzing the impacts of COVID-19 on public hospitals′ operation.Methods:Collection of operation data of 44 public hospitals in Wenzhou from January to March in both 2019 and 2020. By means of descriptive analysis and financial analysis, we analyzed the impacts of the pandemic on the hospitals′ business, revenue and expenditure structure.Results:As of April 2020, even the outpatients visits and inpatient at Wenzhou public hospitals had significantly rebounded, and the downrange for the same periods of 2019 was as high as 23.12% and 17.37% respectively. April witnessed the total medical service revenue of 44 hospitals business totaled 17.44 billion yuan, down 15.43%from the previous year and up 17 percentage points compared to the decline in the first quarter(at 32.54%). As the pandemic moves into a normalized state for epidemic prevention and control, the recovery of medical business was slow, while expenditure of manpower costs and epidemic prevention costs had increased instead. Capital pressure would be the biggest pressure for most hospitals.Conclusions:The hospitals need to further strengthen their operation of fine management and cost control, for sustainable development. It is suggested that government departments should continue to increase effective investment in public health, reduce hospitals′ social insurance premiums in stages, further promote the implementation of online medical service pricing policies, especially Internet hospitals, and relax hospitals′ working capital loan access to ensure liquidity turnover.