Application of metagenomic next-generation sequencing in the detection of pathogenic bacteria in brain abscesses / 中国综合临床

Objective:To analyze the application value of metagenomic next-generation sequencing (mNGS) in the detection of pathogenic bacteria in brain abscesses.Methods:The data of patients with brain abscess in Tianjin Huanhu Hospital from January 2019 to December 2021 were retrospectively analyzed. All patients underwent stereotaxic abscess puncture and drainage. According to the different methods of pathogen detection, they were divided into bacterial culture group (bacterial culture only) and mNGS group (bacterial culture with mNGS). The clinical symptoms, abscess site, bacterial culture and mNGS results, antibiotic application protocol and prognosis of the patients were analyzed. The bacterial detection results of the two groups were analyzed, and the antibiotic application and prognosis were compared. χ 2 test, exact probability method and Mann Whitney test were used to compare the difference between the two groups. Results:A total of 43 patients with brain abscess were enrolled, including 21 cases in bacterial culture group and 22 cases in mNGS group. The positive rate of bacteria culture group was 42.9% (9/21), the positive rate of bacteria culture group was 45.5% (10/22), and the positive rate of mNGS detection was 100% (22/22). Only 3 cases in the bacterial culture group could have a clear bacterial source, while 17 cases in the mNGS group could have a clear bacterial source according to the bacterial results, showing a significant statistical difference between the two groups (χ 2=19.69, P<0.001). The return time of bacterial culture was 7.0 (4.0,7.0) days, and the average return time of mNGS was 1.5 (1.5,1.5) days, the difference of bacterial return time between the two groups was statistically significant ( Z=0.00, P<0.001). The cost of antibiotic use in bacterial culture group was 24.00 (5.60,31.00) thousands yuan, and the cost of antibiotic use in mNGS group was 12.00 (2.10, 20.00) thousands yuan, and there was significant statistical difference between them ( Z=5.22, P=0.026). Conclusions:MNGS can quickly and accurately identify the types and sources of brain abscess pathogens, guide the clinical application of antibiotics more targeted, reduce the cost of antibiotic use, and is an effective method for the detection of brain abscess pathogenic bacteria.

An epidemiological investigation on vaccine-hypervariable poliovirus in a case with acute flaccid paralysis in Zhejiang Province / 预防医学

Abstract@#Vaccine-hypervariable poliovirus type Ⅲ was detected in an acute flaccid paralysis infant at age of 6 months in Zhejiang Province in June, 2021, and the isolated and incubated virus had six nucleotide variations in the VP1 region as compared to the poliovirus Sabin vaccine strain. The infant had a history of three-dose poliovirus vaccination, and grade 2 muscle strength of the left upper limb upon onset. He was clinically diagnosed with cellulitis of the left shoulder, and recovered to normal following treatment. No abnormality was detected in the nervous system, and the infant was cured and discharged from hospital. No vaccine-hypervariable poliovirus was detected in subsequent infant' clinical samples or in close contacts, and no similar cases were identified during the active case detection by county/district medical institutions and among community populations. Since the infant did not present poliomyelitis-related clinical symptoms caused by vaccine-hypervariable poliovirus, poliomyelitis was excluded. The vaccine-hypervariable poliovirus was not spread because of timely identification and effective responses, suggesting the urgent need to maintain the sensitivity of the acute flaccid paralysis surveillance system and improve the coverage of poliovirus vaccination, so as to inhibit the transmission of poliovirus.

Enlightening from optimizing post-authorization safety monitoring system of SARS-CoV-2 vaccines in major economies worldwide / 中华预防医学杂志

Ongoing global pandemic of Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has promoted the unprecedented rapid development and large-scale rolling out of different platform-based COVID-19 vaccines worldwide. How to effectively respond to the expected scale increasing adverse events after vaccination campaign of COVID-19 vaccines is a common problem faced by the world. A lot of countries and regions around the world have arranged in advance at different levels, optimizing the original vaccine safety monitoring system from the perspectives of strengthening the foundation and capabilities, promoting internal and external cooperation, upgrading methods, as well as improving transparency and public communication, which has ensured the good and efficient operation of the system and can provide reference for the construction of relevant fields in China.

Multiple portions enteral nutrition and chyme reinfusion of a blunt bowel injury patient with hyperbilirubinemia undergoing open abdomen: A case report / 中华创伤杂志(英文版)

Blunt bowel injury (BBI) is relatively rare but life-threatening when delayed in surgical repair or anastomosis. Providing enteral nutrition (EN) in BBI patients with open abdomen after damage control surgery is challenging, especially for those with discontinuity of the bowel. Here, we report a 47-year-old male driver who was involved in a motor vehicle collision and developed ascites on post-trauma day 3. Emergency exploratory laparotomy at a local hospital revealed a complete rupture of the jejunum and then primary anastomosis was performed. Postoperatively, the patient was transferred to our trauma center for septic shock and hyperbilirubinemia. Following salvage resuscitation, damage control laparotomy with open abdomen was performed for abdominal sepsis, and a temporary double enterostomy (TDE) was created where the anastomosis was ruptured. Given the TDE and high risk of malnutrition, multiple portions EN were performed, including a proximal portion EN support through a nasogastric tube and a distal portion EN via a jejunal feeding tube. Besides, chyme delivered from the proximal portion of TDE was injected into the distal portion of TDE via a jejunal feeding tube. Hyperbilirubinemia was alleviated with the increase in chyme reinfusion. After 6 months of home EN and chyme reinfusion, the patient finally underwent TDE reversal and abdominal wall reconstruction and was discharged with a regular diet. For BBI patients with postoperative hyperbilirubinemia who underwent open abdomen, the combination of multiple portions EN and chyme reinfusion may be a feasible and safe option.

Wnt/b-Catenin Promotes the Osteoblastic Potential of BMP9 Through Down-Regulating Cyp26b1 in Mesenchymal Stem Cells

BACKGROUND@#All-trans retinoic acid (ATRA) promotes the osteogenic differentiation induced by bone morphogenetic protein 9 (BMP9), but the intrinsic relationship between BMP9 and ATRA keeps unknown. Herein, we investigated the effect of Cyp26b1, a critical enzyme of ATRA degradation, on the BMP9-induced osteogenic differentiation in mesenchymal stem cells (MSCs), and unveiled possible mechanism through which BMP9 regulates the expression of Cyp26b1. @*METHODS@#ATRA content was detected with ELISA and HPLC–MS/MS. PCR, Western blot, and histochemical staining were used to assay the osteogenic markers. Fetal limbs culture, cranial defect repair model, and micro–computed tomographic were used to evaluate the quality of bone formation. IP and ChIP assay were used to explore possible mechanism. @*RESULTS@#We found that the protein level of Cyp26b1 was increased with age, whereas the ATRA content decreased. The osteogenic markers induced by BMP9 were increased by inhibiting or silencing Cyp26b1 but reduced by exogenous Cyp26b1. The BMP9-induced bone formation was enhanced by inhibiting Cyp26b1. The cranial defect repair was promoted by BMP9, which was strengthened by silencing Cyp26b1 and reduced by exogenous Cyp26b1. Mechanically, Cyp26b1 was reduced by BMP9, which was enhanced by activating Wnt/b-catenin, and reduced by inhibiting this pathway. b-catenin interacts with Smad1/5/9, and both were recruited at the promoter of Cyp26b1. @*CONCLUSIONS@#Our findings suggested the BMP9-induced osteoblastic differentiation was mediated by activating retinoic acid signalling, viadown-regulating Cyp26b1. Meanwhile, Cyp26b1 may be a novel potential therapeutic target for the treatment of bone-related diseases or accelerating bone-tissue engineering.

Evaluating the real-world vaccine effectiveness using a regression discontinuity design / 中华流行病学杂志

Estimating the actual real-world effectiveness of the vaccine is an essential part of the post-marketing evaluation. This regression discontinuity design (RDD) using observational data is designed to quantify the effect of an intervention when eligibility for the intervention is based on a defined cutoff as age, making it suited to estimate vaccine effects. This approach can avoid the high cost and ethical issues; overcome difficulties in the organization and practice process in randomized controlled trials, which leads to a higher level of causal inference evidence and more realistic results. Here, we describe key features of RDD in general, and then specific scenarios, with examples, to illustrate that RDD are an essential tool for advancing our understanding of vaccine effects.

Advances in research of interchangeable immunization with live attenuated Japanese encephalitis vaccines and inactivated vaccines / 中华预防医学杂志

Japanese encephalitis (JE) virus is the leading cause of vaccine-preventable encephalitis in Asia and the Western Pacific, which mainly invades central nervous system. Vaccination is the most important strategy to prevent JE. Currently, both live attenuated Japanese encephalitis vaccines (JE-L) and inactivated vaccines (JE-I) are in use. Due to the supply of vaccines and the personal choice of recipients, there will be a demand for interchangeable immunization of these two vaccines. However, relevant research is limited. By reviewing domestic and foreign research evidence, this article summarizes the current situation of the interchangeable use of JE-L and JE-I, and makes recommendations when the interchangeable immunization is in urgent need, so as to provide reference for practical vaccination and policymaking in China.

Epidemiological characteristics and spatiotemporal clustering of hepatitis A in Zhejiang Province from 2010 to 2019 / 中华预防医学杂志

Objective: To analyze the epidemiological characteristics and spatiotemporal clustering of hepatitis A in Zhejiang Province from 2010 to 2019. Methods: The data of hepatitis A incidence in Zhejiang Province from 2010 to 2019 were collected from the infectious disease surveillance system of China Information System for Disease Control and Prevention. ArcGIS 10.7 software was used for spatial autocorrelation analysis. SaTScan 9.6 software was used for spatiotemporal scanning analysis. SPSS 25.0 software was used for additional analysis. Results: Zhejiang Province has reported 5 465 cases of hepatitis A in 2010-2019 years, with an average annual incidence rate of 1.00/100 000, and periodicity and seasonality are not obvious. The incidence of male was higher than that of female (P=0.023), and the highest incidence rate was 50-59 years old. Spatial autocorrelation analysis showed that there was a positive spatial correlation between the incidence of hepatitis A in Zhejiang Province from 2010 to 2017, with the weakest correlation in 2010 (Moran's I =0.103, Z=1.769, P=0.049), and the strongest correlation in 2016 (Moran's I=0.328, Z=4.979, P=0.001). Spatiotemporal scanning analysis showed that there was spatial aggregation of hepatitis A in Zhejiang Province from 2010 to 2019, with a total of three aggregation areas identified. Among them, the mostly aggregation area was concentrated in Xiangshan county of Ningbo city, which covered 10 counties (cities and districts), including Ninghai county and Yinzhou district, and appeared from January 1 to June 30, 2012. Conclusion: The incidence level of hepatitis A in Zhejiang Province shows a stable fluctuation trend from 2010 to 2019, and the seasonal regularity is not obvious. The population group aged 50-59 years old is the key population. There is spatial aggregation in the epidemic situation of hepatitis A. Targeted prevention and control measures of hepatitis A should be done based on the law of spatiotemporal aggregation and local incidence.

The Use of Lipoprotein-Associated Phospholipase A2 in a Chinese Population to Predict Cardiovascular Events / 生物医学与环境科学（英文）

Objective@#To explore associations between lipoprotein-associated phospholipase A2 (Lp-PLA2) and the risk of cardiovascular events in a Chinese population, with a long-term follow-up.@*Methods@#A random sample of 2,031 participants (73.6% males, mean age = 60.4 years) was derived from the Asymptomatic Polyvascular Abnormalities Community study (APAC) from 2010 to 2011. Serum Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay (ELISA). The composite endpoint was a combination of first-ever stroke, myocardial infarction (MI) or all-cause death. Lp-PLA2 associations with outcomes were assessed using Cox models.@*Results@#The median Lp-PLA2 level was 141.0 ng/mL. Over a median follow-up of 9.1 years, we identified 389 events (19.2%), including 137 stroke incidents, 43 MIs, and 244 all-cause deaths. Using multivariate Cox regression, when compared with the lowest Lp-PLA2 quartile, the hazard ratios with 95% confidence intervals for developing composite endpoints, stroke, major adverse cardiovascular events, and all-cause death were 1.77 (1.24-2.54), 1.92 (1.03-3.60), 1.69 (1.003-2.84), and 1.94 (1.18-3.18) in the highest quartile, respectively. Composite endpoints in 145 (28.6%) patients occurred in the highest quartile where Lp-PLA2 (159.0 ng/mL) was much lower than the American Association of Clinical Endocrinologists recommended cut-off point, 200 ng/mL.@*Conclusion@#Higher Lp-PLA2 levels were associated with an increased risk of cardiovascular event/death in a middle-aged Chinese population. The Lp-PLA2 cut-off point may be lower in the Chinese population when predicting cardiovascular events.

Construction of a path for optimizing the health management of HBV infections among pregnant and lying-in women based on a Delphi method / 预防医学

Objective@#To establish an optimized path for health management of HBV infections among pregnant and lying-in women based on a Delphi method, so as to provide the evidence for intensifying the interruption of the mother-to-child transmission of HBV.@*Methods@#Based on literature review and previous studies, the preliminary framework and contents of the optimized path for health management of HBV infections were constructed. Experts from epidemiology, clinical medicine and maternal and children healthcare were invited to participate in two-round Delphi consultations, and the preliminarily designed indicators were screened and revised. The score for feasibility of each indicator was calculated, and the weight of each indicator was estimated using a proportional distribution method.@*Results@#Sixteen experts participated in the consultation, including 13 women. The participants had a mean age of (45.69±5.71) years, and a mean employment duration of (23.06±7.05) years. All participants had a degree of bachelor and above, and there were 14 experts with vice senior professional titles. The mean positive coefficient was 96.88% and the mean authority coefficient was 0.790 during the two-round expert consultations. There were significant differences in the coordination coefficient of importance, necessity and feasibility of indicators at all levels (P<0.05), and the coefficient of variation of the feasibility was all less than 0.250. The final optimized path for health management of HBV infections among pregnant and lying-in women included 6 primary indicators, 17 secondary indictors and 73 tertiary indicators. Among the primary indicators, delivery management (0.173 4), screening and evaluation (0.172 8) and pregnancy management (0.172 7) had a high weight.@*Conclusion@#A scientific and reliable optimized path is created for health management of HBV infections among pregnant and lying-in women, which has a potential value for improving the interruption of mother-to-child transmission of HBV.

Serum anti-measles antibody levels among residents in Zhejiang Province / 预防医学

Objective@#To investigate the serum levels of anti-measles antibody among residents in Zhejiang Province in 2018, so as to provide insights into measles control.@*Methods@#Permanent residents aged 0 to 59 years were recruited using the stratified multistage random sampling method in Zhejiang Province in 2018, and subjects' demographic features, medical history of measles and history of immunization with measles-containing vaccine (MCV) were collected using a questionnaire survey. The serum level of anti-measles IgG antibody was detected, and the geometric mean concentration (GMC) of anti-measles IgG antibody was estimated. The seroprevalence, protective rate and GMC of anti-measles IgG antibody were compared among residents at different age groups and regions.@*Results@#A total of 4 189 residents were enrolled, including 1 939 males and 2 250 females, with a male to female ratio of 1∶1.16. There were 3 858 residents positive for anti-measles IgG antibody, with seroprevalence of 92.10%, and there were 2 072 residents with protective antibodies against measles, with a protective rate of 49.46%. The median GMC of anti-measles IgG antibody was 798.33 (interquartile range, 1 024.06) mIU/mL, and the protective rate of anti-measles IgG antibody appeared a tendency towards a decline with age ( χ2trend=18.067, P<0.001 ). There were significant differences in the seroprevalence ( χ2=45.090, P<0.001 ), protective rate ( χ2=57.432, P<0.001 ) and GMC of anti-measles IgG antibody (χ2=88.624, P<0.001 ) among residents at different regions, with the lowest seroprevalence of anti-measles IgG antibody in Ningbo City ( 85.19% ), the lowest antibody-protective rate (38.98%) and the lowest GMC [632.89 ( 909.04 ) mIU/mL] in Zhoushan City, the highest seroprevalence ( 95.16% ), antibody-protective rate (58.48%) and GMC [1 035.84 ( 1 301.77 ) mIU/mL] in Huzhou City.@*Conclusions@# The protective rate of anti-measles antibody was low and appeared a tendency towards a decline among residents in Zhejiang Province in 2018. There was a region-specific serum level of anti-measles antibody in Zhejiang Province in 2018.

Clinical study on Shaoyao-Bawei Decoction combined with moxibustion in the treatment of spleen stomach weakness syndrome of chronic atrophic gastritis / 国际中医中药杂志

Objective:To evaluate the clinical efficacy of Shaoyao-Bawei Decoction combined with moxibustion in the treatment of spleen stomach weakness syndrome of chronic atrophic gastritis (CAG). Methods:The 98 CAG patients admitted to the Zhaoqing Gaoyao District People’s Hospital from January 2019 to January 2021 who met the selection criteria were divided into 2 groups according to the random number table method, with 49 in each group. The control group received conventional western medicine treatment, and the observation group was treated with Shaoyao-Bawei Decoction combined with moxibustion on the basis of the control group. TCM symptom scores were performed before and after treatment, the levels of IL-6, IL-8 and TNF-α were detected by ELISA, and the levels of serum motilin (MLT), gastrin-17 (G17) and gastrin (gas) were detected by radioimmunoassay, the safety of medication was observed and the clinical efficacy was evaluated. Results:The total effective rate was 93.9% (46/49) in the observation group and 71.4% (35/49) in the control group. There was significant difference between the two groups ( χ2=8.611, P=0.043). After treatment, the scores of epigastric burning, fullness in stomach, dull appetite, dry mouth and bitter mouth, shortness of breath and unwillingness to speak, general lassitude, pale tongue, small and weak pulse in the observation group were significantly lower than those in the control group ( t=12.061, 7.331, 6.869, 5.975, 5.208, 10.567, 8.738, 8.631, respectively, all Ps<0.01), and the levels of serum IL-6, IL-8 and TNF-α were significantly lower than those in the control group ( t=8.573,13.423,12.099, respectively, all Ps <0.01). After treatment, the level of serum MLT (154.52 ± 26.25 ng/L vs. 180.26 ± 28.13 ng/L, t=4.488) in the observation group was lower than that of the control group ( P<0.01); the levels of G17 (14.28 ± 1.75 pmol/L vs. 10.28 ± 1.06 pmol/L, t=-7.966) and GAS (24.73 ± 3.42 ng/L vs. 19.02 ± 3.38 ng/L, t=-13.115) in the observation group were significantly higher than those in the control group ( t=-7.966 and -13.115, respectively, all Ps<0.01). During the treatment, the incidence of adverse reactions was 8.16% (4/49) in the observation group and 6.12% (3/49) in the control group, and there was no significant difference between the two groups ( χ2=0.152, P=0.695). Conclusion:Shaoyao-Bawei Decoction combined with moxibustion can alleviate the clinical symptoms of CAG patients with spleen stomach weakness syndrome, regulate the level of inflammatory cytokines, promote the recovery of gastrointestinal function and improve the clinical curative effect.

Preparation of hydrophilic Indigo Naturalis based on polyethylene glycol( PEG) surface film-forming method and evaluation / 中国中药杂志

Polyethylene glycol (PEG) surface film-forming method was used to prepare hydrophilic Indigo Naturalis decoction pieces with stable effect.The preparation process of modified Indigo Naturalis was optimized and its microscopic properties,hydrophilicity,antipyretic efficacy,and safety were systematically evaluated.With equilibrium contact angle as assessment index,the influence of modifier type,modifier dosage,dispersant dosage,and co-grinding time on water solubility of Indigo Naturalis was investigated by single factor test.The results showed that the optimal preparation process was as follows.The 6%PEG6000 is dissolved in 10%anhydrous ethanol solution by sonification and then the mixture is ground with Indigo Naturalis for 2 min.The resultant product is dried on a square tray in an oven at 60℃to remove ethanol and thereby the PEG-modified hydrophilic Indigo Naturalis decoction pieces are yielded.The morphological observation under scanning electron microscope (SEM) indicated that the modified Indigo Naturalis had smoother surface than Indigo Naturalis,and energy spectrometer measurement showed that the nitrogen (N),calcium(Ca),oxygen (O),and silicon (Si) on the surface of modified Indigo Naturalis powder were less than those of Indigo Naturalis powder.Modified Indigo Naturalis had the equilibrium contact angle 18.96°smaller,polar component 22.222 m J·m~(-2)more,and nonpolar component 7.277 m J·m~(-2)smaller than the Indigo Naturalis powder.Multiple light scattering technique was employed to evaluate the dispersion in water and the result demonstrated that the transmittance of Indigo Naturalis and modified Indigo Naturalis was about85%and 75%,respectively,suggesting the higher dispersity of modified Indigo Naturalis.The suspension rate of modified Indigo Naturalis in water was determined by reflux treatment.The result showed that 57%of Indigo Naturalis was not wetted after refluxing for1 h,while the modified Indigo Naturalis was all wetted and dispersed into water.The dissolution of indigo and indirubin of modified Indigo Naturalis increased and the process was more stable.Then,rats were randomized into the blank group,model group,acetaminophen group,Indigo Naturalis group,and hydrophilic Indigo Naturalis group.The temperature changes of rats were observed after administration and the concentration of IL-1βand TNF-αin serum and IL-1βand PGE_2in hypothalamus was measured.The results indicated that the temperature of Indigo Naturalis group and hydrophilic Indigo Naturalis group dropped and the IL-1βlevel of the hydrophilic Indigo Naturalis group decreased (P<0.05) as compared with those in the model group.Thus,both Indigo Naturalis and hydrophilic Indigo Naturalis had antipyretic effect,particularly the hydrophilic Indigo Naturalis.The acute toxicity test of hydrophilic Indigo Naturalis verified that it had no toxicity to rats.In this study,the hydrophilic Indigo Naturalis decoction pieces were prepared with the PEG surface film-forming method,and the antipyretic efficacy and safety were evaluated,which expanded the technological means of powder modification for Chinese medicine and provided a method for clinical use of Chinese medicine.

Economic evaluation on strategy for preventing mother-to-child transmission of hepatitis B in Zhejiang Province / 中华预防医学杂志

Objective@#To evaluate the cost-benefit and cost-effectiveness of current strategy for preventing mother-to-child transmission (PMTCT) of hepatitis B virus.@*Methods@#A decision tree model with the Markov process was developed and simulated over the lifetime of a birth cohort in Zhejiang Province in 2016. The current PMTCT strategy was compared with universal vaccination and non-vaccination. Costs were assessed from social perspective. Benefits were the savings from reduced costs associated with disease and effectiveness were measured by quality-adjusted of life-years (QALY) gained. The net present value (NPV), cost-benefit ratio (BCR) and incremental cost-effectiveness ratio (ICER) were calculated. Univariate and Probabilistic Sensitivity Analyses (PSA) were performed to assess parameter uncertainties. The parameters of costs and utilities value of hepatitis B-related disease came from the results of the field survey, which were obtained by face-to-face questionnaire survey combined with inpatient medical records, including eight county and municipal hospitals in Jinhua, Jiaxing and Taizhou. A total of 626 outpatients and 523 inpatient patients were investigated. The annual total costs of infection was calculated by combining the costs of outpatient and inpatient.@*Results@#The PMTCT strategy showed a net-gain as 38 323.78 CNY per person, with BCR as 21.10, which was higher than 36 357.80 CNY per person and 13.58 respectively of universal vaccination. Compared with universal vaccination, the PMTCT strategy would save 2 787.07 CNY per additional QALY gained for every person, indicating that PMTCT would be cost-saving. The most important parameters that could affect BCR and ICER were the vaccine coverage rate and costs of hepatitis B related diseases respectively. The PSA showed the PMTCT strategy was preferable as it would gain more QALY and save costs.@*Conclusions@#The PMTCT strategy appeared as highly cost-beneficial and highly cost-effective. High vaccination rate was a key factor of high economic value.

Mutational profile of myeloproliferative neoplasms detected by a customized NGS-based gene panel / 中华检验医学杂志

Objective By a sequencing panel consisting of 50 targeted genes, aiming at depicting the molecular landscape of ET, PV, and PMF, which are three major subtypes of MPN, to provide valuable information in the diagnosis and prognosis of MPN.Methods A retrospective study was conducted of 53 patients from Huashan hospital and Changhai hospital. All patients were diagnosed in accordance with the 2016 WHO diagnostic criteria for MPN, including 31 cases of ET(11 males, 20 females, median age 55 years), 17 cases of PV(12 males, 5 females, median age 65 years), and 5 cases of PMF(4 males, 1 females, median age 67 years), and underwent next-generation of DNA sequencing of their bone marrow or blood samples. The genetic analyses were performed on bone marrow or peripheral blood. Referring to COSMIC, dbSNP, Clinvar and other public databases, we analyzed the sequencing data, and elucidated the mutation profile of MPN patients, combining with their clinic information. Results In addition to the typical JAK2, CALR, and MPL mutations, pathogenic mutations in other 11 genes were detected, as well as 4 SNPs that confer individual susceptibility to MPNs (rs4858647, rs9376092, rs58270997, rs621940). The average rate of mutated genes was 2.3 genes per patient. In all patients (53 cases), the mutated genes detected were TET2, EZH2, ASXL1, MIR662, SF3B1, BARD1, DNMT3A, KIT, RUNX1, TP53, NRAS according to their mutational frequency. Conclusions Applying next-generation sequencing technology, multi-gene sequencing of a bunch of typical BCR-ABL-negative MPN patients can be performed at one time within 2 working days, and pathogenic mutations other than JAK2, CALR, MPL can be found, which has a bright prospection in clinic.

A fast adaptive active contour model based on local gray difference for parotid duct / 南方医科大学学报

OBJECTIVE@#To establish a fast adaptive active contour model based on local gray difference for parotid duct image segmentation.@*METHODS@#On the basis of the LBF model, we added the mean difference of the local gray scale inside and outside the contour as the energy term of the driving evolution curve, and the local gray-scale variance difference was used to replace and as the control term of the energy parameter value. Two local similarity factors of different neighborhood sizes were introduced to correct the effects of image gray unevenness and boundary blur to improve the segmentation efficiency.@*RESULTS@#During image segmentation, this algorithm allowed for adaptive adjustment of the evolution direction, velocity and the energy weight of the internal and external regions according to the difference of gray mean and variance between the internal and external regions. This algorithm was also capable of detecting the actual boundary in a complex gradient boundary region, thus enabling the evolution curve to approach the target boundary quickly and accurately.@*CONCLUSIONS@#The proposed algorithm is superior to the existing segmentation algorithms and allows fast and accurate segmentation of the parotid duct with well-preserved image details.

Economic evaluation of different chickenpox vaccination strategies / 浙江大学学报·医学版

OBJECTIVE@#To evaluate the cost/benefit of different vaccination strategies related to chickenpox vaccine.@*METHODS@#The direct economic cost and indirect economic cost caused by chickenpox were obtained through questionnaire survey. The epidemic characteristics of chickenpox in Zhejiang province were studied by literature review. Dynamic model was set up by Matlab software based on the parameters of chickenpox, to predict the incidence trends of chickenpox with different immunization strategies (no vaccination, 1-dose vaccination, 2-dose vaccination) in future 40 years (2017-2056). A cost-benefit analysis was conducted, and the sensitivities of the main parameters were analyzed.@*RESULTS@#Through the questionnaire survey of 105 cases, the direct and indirect economic cost per case was 506.84 Yuan and 1045.39 Yuan respectively, with the total of 1552.23 Yuan. During the prediction period (40 years), there would be 7.0908 million cases in strategy 2, which was 59.71% less than strategy 1 (17.5989 million cases). Total vaccination costs in strategy 2 were 2.366 billion Yuan, with a total economic gain of 33.741 billion Yuan and benefit/cost ratio (BCR) of 14.26:1. If strategy 3 was adopted, 2.7249 million chickenpox cases would occur, with a decrease of 84.52% compared with strategy 1. Total vaccination costs in strategy 3 was 4.495 billion Yuan, with a total economic gain of 44.309 billion Yuan and BCR of 9.86:1. Analysis showed that the vaccine price was the most sensitive variable, followed by the incidence of chickenpox in the absence of vaccine.@*CONCLUSIONS@#In Zhejiang province, one-dose strategy and two-dose strategy were both cost effective. It is suggested that the chickenpox vaccination should be included in the immunization program in Zhejiang province.

Influencing factors for high level measles antibodies among 6-15 year-old children in Zhejiang province / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To determine measles antibody levels and influencing factors among children aged 6 to 15 years in Zhejiang province.</p><p><b>METHODS</b>Blood samples were collected from 2069 children aged 6 to 15 years in Changxing county (Huzhou) and Liandu district (Lishui) of Zhejiang province. Serum level of measles IgG antibody was measured using ELISA, and 800 mIU/mL was applied as the cut-off point of high antibody level. Chi-square or trend Chi-square test was used to analyze difference in positive rates of high antibody level among children with different characters, and the factors related to high antibody level in the vaccinated children were analyzed using multivariate logistic regression.</p><p><b>RESULTS</b>Among 2069 subjects, positive rate of high measles antibody level was 36.06% (746/2069). Multivariate logistic regression showed that the high measles antibody level was significantly associated with age of children and the age of first measles vaccine inoculation. The positive rate of high measles antibody level decreased with age(=0.866, 95%:0.830-0.904, <0.01), and the positive rate in children whose first vaccination at ≥ 12 months of age was higher than those whose first vaccination at 8 months of age(=0.633, 95%:0.498-0.805, <0.01).</p><p><b>CONCLUSIONS</b>In order to obtain high measles antibody level and to maintain high levels of population immune barrier, it is suggested that first dose of vaccination can be appropriately delayed in low epidemic areas, and elder children should have timely catch-up vaccination.</p>

Antibody persistence following on different vaccination strategies of domestic measles, mumps and rubella combined attenuated live vaccine: a 3-year follow-up study / 中华预防医学杂志

Objective@#To assess the 3-year antibody persistence after vaccination of domestic measles, mumps and rubella combined attenuated live vaccine (MMR) with different program.@*Methods@#Children from three different vaccination strategies (Group 8 m MR: 8 months and 18 months vaccinated with measles-rubella combined attenuated live vaccine and domestic MMR,respectively; Group 8 m MMR: 8 months and 18 months both vaccinated with domestic MMR; Group 12 m MMR: 12 months and 22 months both vaccinated with domestic MMR ) were followed up in Zhejiang province in July 2015. There were 170 participants in Group 8 m MR, 171 participants in Group 8 m MMR and 173 participants in Group 12 m MMR selected by simple random sampling method .Blood samples (venous blood 2-3 ml) were collected 1 month after the first dose vaccination of MMR (only in Group 8 m MMR and Group 12 m MMR) and 3 years (36-38 months) after the last dose vaccination of MMR and tested for antibody IgG against Measles, Mumps and Rubella using ELISA. Seropostive rate and Geometric mean concentration (GMC) were calculated and compared among different groups by Chi-square test or Fisher exact test and Kruskal-Wallis H test.@*Results@#A total of 514 participants (8 m MR: 170; 8 m MMR:171; 12 m MMR:173) were enrolled. The overall seropositivity rate of measles, mumps and rubella was 98.1% (504), 93.4% (480) and 88.1% (453), respectively, with corresponding GMC was 1 012.33 mU/ml, 502.87 U/ml and 50.53 U/ml respectively. There was no significant difference of seropositivity rate for measles among three groups (all groups were>97%). The highest seropositivity rate for mumps was found in the Group 12 m MMR with the rate of 98.8% (171/173), followed by Group 8 m MMR and Group 8 m MR with 93.0% (159/171) and 88.2%(150/170) respectively (Fisher exact test, P<0.001). The highest seropositivity rate for rubella was also found in the Group 12 m MMR with the rate of 94.8% (164/173), followed by Group 8 m MMR and Group 8 m MR with 86.6%(148/171) and 82.9%(141/170) respectively (Fisher exact test, P=0.002). The highest GMC of antibody against measles, mumps and rubella were all found in Group 12 m MMR, with 1 217.30 (1 119.35-1 323.82) mU/ml, 717.07 (643.83-798.65) U/ml and 62.54(56.21-69.58) U/ml respectively. The lowest GMC of antibody against measles and mumps were both in Group 12 m MR with 812.01 (734.52-897.67) mU/ml and 363.28 (305.42-432.11) U/ml respectively. The lowest GMC of antibody against rubella was in Group 8 m MMR with 44.10 (39.08-49.76) U/ml. These differences of GMCs among three groups were all reach significant means (P<0.05).@*Conclusion@#High level seropostive rates and GMCs were exist against measles and rubella after 3-year vaccination of domestic MMR among different program. Higher antibody level against mumps were found in those children with two doses vaccination of MMR.

Economic evaluation on new strategy for preventing poliomyelitis in Zhejiang Province / 预防医学

Objective To evaluate the economic effect of new strategy for preventing poliomyelitis in Zhejiang Province. Methods Based on the population of Zhejiang Province in 2016, cost-effectiveness ratio (CER) , benefit-cost ratio (BCR), and net benefit (NB) were applied to calculate the health economic difference for the new strategy and the original strategy as compared to no vaccination strategy. Univariate sensitivity analysis was used to assess the robustness of results with main parameters; including burdens of poliomyelitis, cost of vaccines, and the vaccination program itself, and the discount rate. Results CERdisease, CERdeath, BCR and NB for the new strategy were 1:52700 RMB Yuan per case, 1:1813700 RMB Yuan per case, 12.26 and 796.6622 million and CERdisease, CERdeath, BCR and NB for the original strategy were 1 :32900 RMB Yuan per case, 1 :1133900 RMB Yuan per case, 19.58 and 823.1753 million, respectively. The results of the univariate sensitivity analysis with main parameters were robust. Conclusion The new strategy for preventing poliomyelitis is necessary for this period of the global polio eradication. Though the new strategy appears not as good as the original strategy on economic evaluation, its health economic benefit is significant.