Analysis of risk factors and severity prediction of acute pancreatitis induced by pegaspargase in children / 中华实用儿科临床杂志

Objective:To analyze the risk factors for asparaginase-associated pancreatitis (AAP) in children with acute lymphoblastic leukemia (ALL) after treatment with pegaspargase and evaluate the predictive value of pediatric sequential organ failure assessment (SOFA) score, pediatric acute pancreatitis severity (PAPS) score, Ranson′s score and pediatric Ministry of Health, Labour and Welfare of Japan (JPN) score for severe AAP.Methods:Cross-sectional study.The clinical data of 328 children with ALL who received pegaspargase treatment in the Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University from January 2014 to August 2021, as well as their clinical manifestations, laboratory examinations, and imaging examinations were collected.The SOFA score at the time of AAP diagnosis, PAPS score and Ranson′s score at 48 hours after AAP diagnosis, and JPN score at 72 hours after AAP diagnosis were calculated, and their predictive value for severe AAP was evaluated by the receiver operating characteristic (ROC) curve.Results:A total of 6.7%(22/328) of children had AAP, with the median age of 6.62 years.AAP most commonly occurred in the induced remission phase (16/22, 72.7%). Three AAP children were re-exposed to asparaginase, and 2 of them developed a second AAP.Among the 22 AAP children, 16 presented with mild symptoms, and 6 with severe symptoms.The 6 children with severe AAP were all transferred to the Pediatric Intensive Care Unit (PICU). There were no significant differences in gender, white blood cell count at first diagnosis, immunophenotype, risk stratification, and single dose of pegaspargase between the AAP and non-AAP groups.The age at diagnosis of ALL in the AAP group was significantly higher than that in the non-AAP group ( t=2.385, P=0.018). The number of overweight or obese children in the AAP group was also higher than that in the non-AAP group ( χ2=4.507, P=0.034). The areas under the ROC curve of children′s JPN score, SOFA score, Ranson′s score, and PAPS score in predicting severe AAP were 0.919, 0.844, 0.731, and 0.606, respectively.The JPN score ( t=4.174, P=0.001) and the SOFA score ( t=3.181, P=0.005) showed statistically significant differences between mild and severe AAP. Conclusions:AAP is a serious complication in the treatment of ALL with combined pegaspargase and chemotherapy.Older age and overweight or obesity may be the risk factors for AAP.Pediatric JPN and SOFA scores have predictive value for severe AAP.

Mendelian randomization study on the correlation between gluten free diet and rheumatoid arthritis / 中华风湿病学杂志

Objective:To evaluate the relationship between gluten-free diet and rheumatoid arthritis (RA).Methods:Data were obtained from large-scale genome-wide association studies (GWAS), and genetic loci that are independent of gluten-free diet and RA of people of Europe2 were selected as instrumental variables. The gluten-free diet GWAS data included 64 949 individuals and 9 851 867 controls. Data were obtained from GWAS of 58 284 RA patients and 13 108 512 controls. The inverse variance weighted (IVW), MR Egger, weighted median method and weighted model were used to conduct two sample Mendelian randomization (MR) analysis. Cochran Q test and mendelian randomness pleiotropy residual sum and outlier (MR-PRESSO) were used to assess SNP heterogeneity. Applying the MR Egger intercept to test the level pleiotropy of SNP. The sensitivity analysis of the "leave one method" that evaluates whether MR studies were influenced by a single SNP. Results:After matching GFD and RA data, three SNPs were included as instrumental variables in the study. IVW showed that GFD could significantly reduce the risk of RA ( β=-60.83, s x=3.82, P<0.001). The weighted median method and weighted pattern also showed that the gluten free diet could reduce the risk of RA ( β=-57.97, s x=4.41, P<0.001; β=-55.81, s x=5.10, P=0.008). Sensitivity analysis of the correlation between GFD and RA showed that there might be heterogeneity between SNPs (Cochran Q test, Q=12.80, P=0.002). The MR-PRESSO results showed that no abnormal SNP was detected ( P=0.174). The forest map showed that SNPs was closely related to GFD and RA stability. The method comparison chart showed that the results of multiple testing methods were basically consistent. The funnel plot showed that SNPs were basically symmetrical, indicating that there was no pleiotropy in MR analysis. The MR Egger intercept test showed no horizontal pleiotropy in MR analysis (intercept value was-0.24, P=0.174). The sensitivity analysis of the "leave one method" is suggested that no single SNP had a significant impact on the overall results. Conclusion:Gluten free diet is related to the risk reduction of RA.

Development of a grading diagnostic model for schistosomiasis-induced liver fibrosis based on radiomics and clinical laboratory indicators / 中国血吸虫病防治杂志

Objective To investigate the feasibility of developing a grading diagnostic model for schistosomiasis-induced liver fibrosis based on B-mode ultrasonographic images and clinical laboratory indicators. Methods Ultrasound images and clinical laboratory testing data were captured from schistosomiasis patients admitted to the Second People’s Hospital of Duchang County, Jiangxi Province from 2018 to 2022. Patients with grade I schistosomiasis-induced liver fibrosis were enrolled in Group 1, and patients with grade II and III schistosomiasis-induced liver fibrosis were enrolled in Group 2. The machine learning binary classification tasks were created based on patients’radiomics and clinical laboratory data from 2018 to 2021 as the training set, and patients’radiomics and clinical laboratory data in 2022 as the validation set. The features of ultrasonographic images were labeled with the ITK-SNAP software, and the features of ultrasonographic images were extracted using the Python 3.7 package and PyRadiomics toolkit. The difference in the features of ultrasonographic images was compared between groups with t test or Mann-Whitney U test, and the key imaging features were selected with the least absolute shrinkage and selection operator (LASSO) regression algorithm. Four machine learning models were created using the Scikit-learn repository, including the support vector machine (SVM), random forest (RF), linear regression (LR) and extreme gradient boosting (XGBoost). The optimal machine learning model was screened with the receiver operating characteristic curve (ROC), and features with the greatest contributions to the differentiation features of ultrasound images in machine learning models with the SHapley Additive exPlanations (SHAP) method. Results The ultrasonographic imaging data and clinical laboratory testing data from 491 schistosomiasis patients from 2019 to 2022 were included in the study, and a total of 851 radiomics features and 54 clinical laboratory indicators were captured. Following statistical tests (t = −5.98 to 4.80, U = 6 550 to 20 994, all P values < 0.05) and screening of key features with LASSO regression, 44 features or indicators were included for the subsequent modeling. The areas under ROC curve (AUCs) were 0.763 and 0.611 for the training and validation sets of the SVM model based on clinical laboratory indicators, 0.951 and 0.892 for the training and validation sets of the SVM model based on radiomics, and 0.960 and 0.913 for the training and validation sets of the multimodal SVM model. The 10 greatest contributing features or indicators in machine learning models included 2 clinical laboratory indicators and 8 radiomics features. Conclusions The multimodal machine learning models created based on ultrasound-based radiomics and clinical laboratory indicators are feasible for intelligent identification of schistosomiasis-induced liver fibrosis, and are effective to improve the classification effect of one-class data models.

Diagnosis and individualized drug therapy for the rejection with hyperglycemia after liver Transplantation / 中国临床药理学与治疗学

AIM: To establish individualized drug therapy strategy for patients with rejection and hyperglycemia after liver transplantation. METHODS: Clinical pharmacist collaborated with the surgeons and participated in the diagnosis and treatment of rejection and hyperglycemia after liver transplantation. Taking together liver function, therapeutic drug monitoring, drug-drug interactions between tacrolimus and wuzhi capsule, individualized drug therapy was adapted to improve the prognosis. RESULTS: The patient recovered well and survived in good health till now. CONCLUSION: It is highly suggested that clinical pharmacists actively involved in treatment of more severe and difficult-to-treat disease and design the individualized dosing regimens. This will largely contribute in reduced adverse drug reaction, improved safety and effectiveness in drug use as well as the quality of life in the "post-transplantation era".

Construction of an evaluation index system for the capability of comprehensive control of mountain - type zoonotic visceral leishmaniasis based on the One Health concept / 中国血吸虫病防治杂志

Objective To construct an evaluation index system for the capability of comprehensive control of mountain-type zoonotic visceral leishmaniasis based on the One Health concept, so as to provide insights into the control and elimination of mountain-type zoonotic visceral leishmaniasis using the One Health approach. Methods A preliminary evaluation index system was constructed based on literature review, panel discussions and field surveys. Thirty-three experts were selected from 7 provincial disease control and prevention centers in Beijing Municipality, Hebei Province, Shanxi Province, Henan Province, Sichuan Province, Shaanxi Province and Gansu Province where mountain-type zoonotic visceral leishmaniasis was endemic, and two rounds of expert consultations were conducted to screen the indicators. The positive coefficient, degree of concentration, degree of coordination, and authority of the experts were calculated, and the normalized weights of each index were calculated with the analytic hierarchy process. Results The response rates of questionnaires during two rounds of expert consultation were both 100.00% (33/33), and the authority coefficients of the experts were 0.86 and 0.88, respectively. The coefficients of coordination among experts on the rationality, importance, and operability of the indicators were 0.392, 0.437, 0.258, and 0.364, 0.335, 0.263, respectively (all P values < 0.05). Following screening, the final evaluation index system included 3 primary indicators, 17 secondary indicators, and 50 tertiary indicators. The normalized weights of primary indicators “external environment”, “internal support” and “comprehensive control” were 16.98%, 38.73% and 44.29%, respectively. Among the secondary indicators of the primary indicator “external environment”, the highest weight was seen for natural environment (66.67%), and among the secondary indicators of the primary indicator “internal support”, the lowest weight was seen for the scientific research for visceral leishmaniasis control (8.26%), while other indicators had weights of 12.42% to 13.38%. Among the secondary indicators of the primary indicator “comprehensive control”, the weight was 16.67% for each indicator. Conclusions An evaluation index system has been constructed for the capability of comprehensive control of mountain-type zoonotic visceral leishmaniasis based on the One Health concept. In addition to assessment of the effect of conventional mountain-type zoonotic visceral leishmaniasis control measures, this index system integrates the importance of top-level design, organizational management, and implementation of control measures, and includes indicators related to multi-sectoral cooperation.

METTL14 is a chromatin regulator independent of its RNA N6-methyladenosine methyltransferase activity

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.

Cerebral venous sinus thrombosis caused by pegasparaginase: a clinical analysis of 8 cases / 中华神经医学杂志

Objective:To investigate the risk factors and prognoses of cerebral venous sinus thrombosis (CVST) caused by pegasparaginase (PEG-Asp).Methods:A total of 252 children with acute lymphoblastic leukemia (ALL) were treated with PEG-Asp chemotherapy in our hospital from December 2016 to July 2021, including 8 children with CVST. The clinical manifestations, laboratory and imaging features, treatments and prognoses of these children with CVST caused by PEG-Asp were analyzed retrospectively.Results:(1) CVST occurred during induction chemotherapy in 4 children, during re-induction chemotherapy in 3 children, and during consolidation stage in one child. CVST occurred in two children who received PEG-ASP chemotherapy once, in one child who received PEG-Asp chemotherapy twice, and 5 children who received PEG-Asp chemotherapy more than twice. The median time between CVST occurrence and last treatment of PEG-Asp was 20.5 d. (2) The clinical manifestations included paroxysmal headache ( n=4), nausea or vomiting ( n=3), convulsions ( n=2) and persistent blurred vision ( n=1). (3) CVST appeared at the sigmoid sinus ( n=6), transverse sinus ( n=4) and superior sagittal sinus ( n=4), of which one child was complicated with hemorrhage in left frontal parietal and right parietal cortex, and one with reversible posterior encephalopathy syndrome; 8 children were not complicated with thrombus in other parts. (4) Some of the children were complicated with abnormal blood coagulation. When CVST occurred, fibrinogen level decreased in 3 children, anti-thrombin III level decreased in 2 children, and D-dimer level increased in 3 children. (5) Six children were treated with low molecular weight heparin (LMWH), of which, 4 were treated with rivasaban and one with warfarin sequentially. The total course of anticoagulation was 56 d. (6) The symptoms of 6 children disappeared after anticoagulation; Magnetic resonance venography (MRV) showed disappeared thrombus in 4 children and reduced thrombus range in 2 children. One child with intracranial hemorrhage did not use PEG-Asp anymore; 7 accepted PEG-Asp further during follow-up chemotherapy, of which one had CVST recurrence and the range of thrombus was reduced after anticoagulant therapy. Conclusions:When children with ALL develop unexplained neurological symptoms during PEG-Asp chemotherapy, CVST should be highly vigilant. Enhanced MRI and MRV should be performed for early diagnosis. Some children are complicated with abnormal blood coagulation, and LMWH, warfarin and rivasaban are effective. The prognosis is good and there are no sequelae. Most children accepted PEG-Asp again will not have CVST again.

Bacterial stress response, physiological metabolism and antimicrobial tolerance and the control strategies / 生物工程学报

Overuse of antibiotics in medical care and animal husbandry has led to the development of bacterial antimicrobial resistance, causing increasingly more health concern. In addition to genetic mutations and the formation of resistance, the various stresses bacteria encountered in the natural environment trigger their stress responses, which not only protect them from these stresses, but also change their tolerance to antimicrobials. The emergence of antimicrobial tolerance will inevitably affect the physiological metabolism of bacteria. However, bacteria can restore their sensitivity to drugs by regulating their own metabolism. This article reviews recent studies on the relationship between bacterial stress responses or the physiological metabolism and antimicrobial tolerance, intending to take more effective measures to control the occurrence and spread of antimicrobial resistance.

Radiosensitivity of connexin 43(CX43) on S24-GBMSCs based brain tumor in nude mice / 中华放射肿瘤学杂志

Objective:To investigate the impact of connexin 43(CX43) on the connection of S24 glioblastoma multiforme (S24-GBM) cellular network and to explore its role on radio-resistance.Methods:Specific lentiviral vectors were used to knockout CX43 in S24-GBM stem cells (S24-GBMSCs). Alternatively, carbenoxolone (CBX) was used to block transmission of CX43. Subsequently, the animal subjects grafted with S24-GBMSCs were monitored under a multiphoton laser scanning microscope (MPLSM). Dynamic changes of tumor microtubes (TMs) and transmission of Ca 2+ and SR101 in the cellular network were recorded. To study the radiosenstivity of S24-GBM before and after CX43 inhibition, MRI scanning of the brains was taken before and after radiation to assess the tumor sizes. Survival time of each subject was also recorded. Results:In comparison with control group, knockout of CX43 in S24-GBMSCs led to shorter TMs, less TM connected cells, lower Ca 2+ synchronicity and SR101 fluorescence, as well as decreased tumor sizes and prolonged survival time (all P<0.01), which were independent from radiation. However, CBX only demonstrated inhibition on the growth of tumors and the diffussion of Ca 2+ and SR101, without affecting TMs formation. These above-mentioned alterations could be enhanced by the combination of gap43 knockout in S24-GBMSCs with blockage of CX43 by CBX (all P<0.05). Conclusion:CX43 plays a critical role in the radioresistance of S24-GBM by influencing the formation of S24-GBM cellular network and the transmission of important signaling molecules including Ca 2+ and SR101.

Dose constraints of optic nerves and chiasm in locally advanced nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy / 中华放射肿瘤学杂志

Objective To investigate the tolerated dose of the optic nerves and chiasm in patients with locally advanced nasopharyngeal carcinoma(NPC)treated with intensity-modulated radiotherapy (IMRT). Methods A retrospective analysis was performed on dose characteristics and the incidence of radiation optic neuropathy in 108 patients with locally advanced NPC treated with IMRT at D 2>55 Gy in the optic nerves and chiasm in our hospital between May 2009 and December 2013. The Common Terminology Criteria for Adverse Events(CTCAE)Version 3.0 grading criteria were used for evaluating adverse reactions of the optic nerves and optic chiasm.A logistic regression analysis was performed to assess the risk factors for the development of radiation-induced optic neuropathy(RION). Results No patient had severe RION (grade 3-5),although 7 of the 108 patients had mild optic nerve disorder(grade 1-2). No patient-or treatment-related factors were found to be associated with the development of RION(P>0.05). With a median follow-up of 46 months(range,13-91 months),the 3-year estimated overall survival,local recurrence-free survival,and distant metastasis-free survival rates were 90.0%,94.5%,and 86.4%, respectively. Conclusions The dose constraint of<55 Gy derived for optic nerves and chiasm from conventional radiotherapy does not seem to apply to IMRT. For advanced NPC patients treated with IMRT, the dose constraints of optic nerves and chiasm might be relaxed in order to improve target coverage.

Investigation on immunization program coverage rate and its safety in children with tuberous sclerosis / 中华儿科杂志

Objective@#To investigate the status of immunization of National Immunization Program (NIP) and its adverse reaction rate in children with tuberous sclerosis.@*Method@#Questionnaire survey was adopted to identify the vaccination coverage and its adverse events; 72 cases of children with tuberous sclerosis and 78 normal controls (healthy children completing age-appropriate NIP) admitted to Chinese People′s Liberation Army General Hospital from December 2014 to November 2015 were involved into this study.@*Result@#The age-appropriate NIP coverage rate of tuberous sclerosis was 36%(26/72). The coverage rate of bacillus calmette-guerin (BCG), hepatitis B vaccine 1st to 3rd doses (HepB1-3), oral poliovaccine 1st dose (OPV1), diphtheria, pertussis and tetanus 1st dose (DPT1), DPT1-3, meningococcal polysaccharide vaccine group A (MPVA), measles amd rubella vaccine/measles vaccine 1st dose (MRV/MCV1), and Japanese encephalitis vaccine 1st dose (JEV1) were 100%(72 cases), 75%(51 cases), 97%(66 cases), 91%(62 cases), 82%(56 cases), 66%(45 cases), 69%(42 cases), and 61%(37 cases) respectively. The reasons why the children did not complete the vaccination plan were that parents were concerned about vaccination-induced seizures or seizures had not been controlled. Among 72 children with TSC, the rate of adverse events or suspected adverse events after vaccination was 17% (12 cases), which was higher than the normal control children (2 cases, 3%) (χ2=8.799, P<0.05). The main adverse events were seizure events, which accounted for 92%(11 cases).@*Conclusion@#The age-appropriate NIP coverage rate among children with tuberous sclerosis is low. The high incidence of adverse events may be associated with a fact that there are some nervous system abnormalities in cases with tuberous sclerosis. TSC children vaccination is relatively safe, with no serious adverse events.

Standardized management and effects for hospital′s humanistic nursing care / 中华医院管理杂志

Objective To explore the methods of the standardized management used in humanistic nursing care and to assess its effects.Methods Measures of the standardized management began to be used in such care at the hospital since January 2013.Questionnaires of patient satisfaction with nursing care for inpatients and those discharged were used to assess the effects of the standardized management measures periodically and synthetically.Results The patient satisfaction with humanistic nursing care keeps increasing year by year from 2013 to 201 5.The differences among three sets of data are statistically significant(P < 0.05 ).Conclusions Humanistic nursing care calls for promotion of standardized management.It is high time to build such a standardized management system at the hospitals.

A clinical analysis of 33 cases of Kimura's disease / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To improve the diagnosis and treatment of Kimura's disease (KD) by investigating its clinical characteristics, pathological features and complications.@*METHOD@#The clinical data of 33 cases of KD were analyzed retrospectively.@*RESULT@#Of 33 cases, 22 showed the mass on head and neck, while in the other cases, the mass distributed in the region of groin, axillary fossa, hilum of lung and mesentery. Regional lymph nodes were involved in 21 cases and major salivary glands were invaded in 8 cases. Twenty-three cases had typical peripheral eosinophilia, although only in 2 patients the quantity of serum total IgE increased markedly. Urine abnormalities happened to 7 cases, such as massive proteinuria (3 cases) and hematuria (2 cases). Among 6 cases which underwent bone marrow aspiration, 2 showed eosinophilia. Two cases were complicated with nephritic syndrome. Six cases were combined with local inflammation on head and neck and 2 cases were combined with malignant tumor.@*CONCLUSION@#Mass on the head and neck is the typical clinical manifestation in KD, with regional lymph nodes and major salivary glands involved most. Serum total IgE and histopathologic examination should always be done to confirm KD, especially in the cases with unknown eosinophilia increasing.

The different-dose simvastatin's effect on the platelet activity after the elderly patients' treatment by PCI / 中国实用内科杂志

Objective To observe the serum level of the CD62p,CD63 which indicates the platelet activity of the elderly patients treated by different-dose simvastatin after PCI.Methods Sixty-eight patients with acute coronary syndrome post PCI were randomly divided into 20 mg/d simvastatin group(36 patients)and 40 mg/d simvastatin group(32 patients).We examined the patient's blood CD62p,CD63 levels on the day before the treatment of PCI in both groups.Then all of the patients in both groups received different-dose simvastatin treatment(20mg/d or 40 mg/d qn po);we observed the results again after four weeks in both groups,and compared the results.Results The patients' blood CD62p,CD63 levels decreased significantly after the treatment of simvastatin in both groups(P