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.

To clarify the structural characteristics of virus communities carried by primates in the Guangdong region,and evaluate the risk of the important zoonotic virus monkeypox virus(MPXV)being introduced into China through artificially do-mesticated primates,this study conducted metagenomic research on artificially domesticated primates and performed screening for MPXV.Primate samples were collected from 20 wildlife rescue centers or zoos in 14 prefecture level cities in Guangdong Province,and the structural characteristics of virus communities carried by artificially domesticated primates were identified through Illumina sequencing.Fluorescence quantitative PCR detection of MPXV excluded the risk of MPXV being introduced through artificially domesticated primates in Guangdong Prov-ince.A total of 489 oral and pharyngeal swabs and feces from primates were collected.High-throughput sequencing indicated that the viral group structure in the feces of artificially domesti-cated primates in the Guangdong region is complex and shows regional differences.Members of Alphaflexiviridae and Vir-gaviridae,followed by members of Parvoviridae and Genomo-viridae,had the highest abundance.Subsequently,fluorescence quantitative PCR results showed that all primates from wildlife rescue centers or zoos in Guangdong Province were MPXV neg-ative.This study provides the first description of the complex viral structure characteristics of artificially domesticated primates in the Guangdong region,and elucidates the differences in vi-ral communities among artificially domesticated primates in different regions.Our findings suggested that the risk of zoonotic diseases caused by artificially domesticated primates in Guangdong Province is extremely low,and the risk of MPXV being in-troduced into China through artificially domesticated primates in Guangdong Province is zero.

OBJECTIVE: To study epidemiological characteristics and hospitalization costs of female inpatients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Beijing. METHODS: A retrospective study was conducted to analyze electronic hospitalization summary reports of female inpatients with AECOPD in Beijing from 2013 to 2020. Clinical characteristics (age distribution and comorbidities), epidemiological characteristics (temporal and spatial distribution characteristics), hospi-talization times and costs of patients were described. RESULTS: A total of 57 911 subjects in 166 hospitals were included in this study, with a mean age of (78.84±8.59) years and the highest number of patients aged 80-89 years (49.06%), followed by patients aged 70-79 years (31.08%), and the lowest number of patients under 50 years (0.41%). The proportions of patients with coronary heart disease, hypertension and heart failure were 30.60%, 30.52% and 26.54% respectively. The median number of daily hospitalizations during the study period was 18 (IQR: 16). The number of daily hospitalizations for AECOPD showed an overall growth trend over the eight years from 2013 to 2020, starting to increase significantly in 2015 and continuing to increase until 2019, then followed by a decline in 2020. The proportion of inpatient admissions was higher in winter and spring (54.09%) than that in summer and autumn (45.91%). The top three districts in terms of the proportion of total inpatient admissions were Xicheng district (14.18%), Chaoyang district (14.12%) and Fengtai district (13.47%). The density of inpatients was relatively high in the western regions, central urban areas and northeastern regions of the city, while the density of inpatients was relatively low in the near suburbs. The median number of hospital days for female patients with AECOPD was 12 days, and the median hospital costs was CNY 20 648.37. Patients from urban areas had longer hospitalization times and higher hospitalization costs than those from suburban areas (P < 0.001). Western medicine expenses accounted for the largest proportion of total hospital expenses (33.32%). During the study period, hospitalization costs exhibited an overall pattern of initial growth, followed by subsequent decline, eventually stabilizing. The differences in hospitalization costs among the patients with different comorbidities were significant. CONCLUSION Female hospitalized patients with AECOPD in Beijing were older than 70 years, often complicated by cardiovascular disease. AECOPD occurred mainly in winter and spring, with regional differences. The hospitalization costs were closely associated with the patients' age, comorbidities, and the geographicical region.
Humans ; Female ; Aged ; Aged, 80 and over ; Inpatients ; Beijing ; Retrospective Studies ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Hospitalization

This study investigated the mechanisms and targets of Shenfu Injection in the intervention in chronic heart failure(CHF) through the NOD-like receptor thermal protein domain associated protein 3(NLRP3)/caspase-1 signaling pathway. A CHF model was induced in rats by subcutaneous injection of isoproterenol. Model rats were randomly divided into a model group, a Shenfu Injection group, and a MCC950(NLRP3 inhibitor) group, and a blank group was also set up as a control. After 15 days of treatment, echocardiography was performed to measure cardiac function parameters [left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS)]. Enzyme-linked immunosorbent assay(ELISA) was used to measure serum levels of N-terminal pro-brain natriuretic peptide(NT-proBNP), interleukin(IL)-1β, and IL-18. Hematoxylin-eosin(HE) and Masson staining were used to observe morphological changes in myocardial tissues, and Western blot was used to measure the expression levels of NLRP3/caspase-1 pathway-related proteins [NLRP3, caspase-1, apoptosis-associated speck-like protein containing a CARD(ASC), gasdermin D(GSDMD), IL-1β, and IL-18]. The study found that isoproterenol-induced CHF in rats resulted in decreased cardiac function, worsened myocardial fibrosis, increased expression levels of NLRP3, ASC, caspase-1, GSDMD-N, IL-1β, and IL-18 in myocardial tissues, elevated serum inflammatory factors, and induced myocardial cell pyroptosis. Following Shenfu Injection intervention, the Shenfu Injection group showed significantly improved LVEF and LVFS, a significant decrease in NT-proBNP, a marked downregulation of NLRP3, ASC, caspase-1, GSDMD-N, IL-1β, and IL-18 protein expression levels, reduced serum inflammatory factors IL-1β and IL-18 expression in CHF rats, and a decrease in the rate of TUNEL-positive cells. Shenfu Injection can significantly improve cardiac function in CHF, inhibit myocardial fibrosis, and alleviate the progression of myocardial cell pyroptosis through the inhibition of the NLRP3/caspase-1 pathway.
Rats ; Animals ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Pyroptosis ; Interleukin-18/metabolism* ; Caspase 1/metabolism* ; Stroke Volume ; Isoproterenol ; Ventricular Function, Left ; Heart Failure/drug therapy* ; Fibrosis ; Drugs, Chinese Herbal

OBJECTIVE: To investigate a family with congenital dysfibrinogenemia, and analyze the risk of hemorrhage and thrombosis and blood transfusion strategies. METHODS: Prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) of the proband and her family members were detected by automatic coagulometer, fibrinogen (Fg) activity and antigen were detected by Clauss method and PT algorithm respectively. Meanwhile, thromboelastometry was analyzed for proband and her family members. Then, peripheral blood samples of the proband and her family members were collected, and all exons of FGA, FGB and FGG and their flanks were amplified by PCR and sequenced to search for gene mutations. RESULTS: The proband had normal APTT and PT, slightly prolonged TT, reduced level of Fg activity (Clauss method). The Fg of the proband's aunt, son and daughter all decreased to varying degrees. The results of thromboelastogram indicated that Fg function of the proband and her family members (except her son) was basically normal. Gene analysis showed that there were 6233 G/A (p.AαArg35His) heterozygous mutations in exon 2 of FGA gene in the proband, her children and aunt. In addition, 2 polymorphic loci were found in the family, they were FGA gene g.9308A/G (p.AαThr331Ala) and FGB gene g.12628G/A (p.BβArg478Iys) polymorphism, respectively. The proband was injected with 10 units of cryoprecipitate 2 hours before delivery to prevent bleeding, and no obvious bleeding occurred during and after delivery. CONCLUSION Heterozygous mutation of 6233G/A (p.AαArg35His) of FGA gene is the biogenetic basis of the disease in this family with congenital dysfibrinogenemia.
Humans ; Child ; Female ; Fibrinogen/genetics* ; Pedigree ; Afibrinogenemia/genetics* ; Mutation ; Blood Transfusion

The quality of traditional Chinese medicine has a direct impact on the effectiveness and safety of its use, and is the premise necessary to ensure the healthy development of the traditional Chinese medicine industry. Comprehensive and accurate control and evaluation of the quality of medicinal materials is of great significance to the traditional Chinese medicine industry, but the complexity and dynamics of the chemical composition of medicinal materials makes their quality evaluation a challenge. Plant metabolomics provides an integrated and comprehensive analysis that is consistent with the holistic approach of traditional Chinese medicine. Chemical information therein promotes the establishment of a traceable system and provides new ideas and methods for the quality evaluation of medicinal materials. Plant metabolomics in the quality evaluation of medicinal materials is gradually increasing, and the core is the screening and identification of differential metabolites or specific marker compounds by means of stoichiometry. This study focused on the main factors that affect the quality of medicinal materials, such as origin, environmental adversity, varieties, harvest time, commercial specification and TCM processing. We describe the research progress in plant metabolomics combined with chemometrics analysis for the quality control and evaluation of medicinal materials, summarize existing problems, identify trends, and propose future research directions. Metabolomics plays an increasingly important role in the quality evaluation of medicinal materials, but the absolute qualitative and quantitative information of metabolomics needs to be further developed, and a single 'omics' technique is not sufficient for an in-depth analysis of medicinal value. In the future, standardization of plant metabolomics methods and a more complete database should be actively promoted, and plant metabolomics should be integrated into quality marker exploration. Plant metabolomics will need to be integrated with other 'omics' methods to improve the quality and evaluation system of medicinal materials.

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.

OBJECTIVE: Through analysis of ABO blood group gene typing technology, to assist in the identification of difficult clinical serological specimens. METHODS: A total of 10 forwardreverse typing ambiguous samples were collected from January 2021 to August 2021 in our hospital.ABO genotypes were analysed by gene sequencing. RESULTS: The genotypes of 10 ABO ambiguous blood group samples were A102/BW11, A102/BW12, O02/O02, A102/B303, A102/B101, BW11/O02, B101/O04, BW11/O01, BW11/O01, A101/O02, respectively. The genotype results of 6 cases was consistent with the serological phenotype, and the serological phenotype of 4 cases were different from the geno sequencing. CONCLUSION ABO blood groups genotyping technology combined with serological typing can be used for accurate typing of ambiguous blood group, and better ensure the safety of blood transfusion.
ABO Blood-Group System/genetics* ; Alleles ; Blood Grouping and Crossmatching ; Exons ; Genotype ; Phenotype

The vagina contains at least a billion microbial cells,dominated by lactobacilli.Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age,as well as cervical,fecal,and salivary samples from a second cohort of 632 women.Factors such as pregnancy history,delivery history,cesarean section,and breastfeeding were all more important than menstrual cycle in shaping the microbiome,and such information would be necessary before trying to interpret differences between vagino-cervical micro-biome data.Greater proportion of Bifidobacterium breve was seen with older age at sexual debut.The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history.Potential markers for lack of menstrual regularity,heavy flow,dysmenor-rhea,and contraceptives were also identified.Lactobacilli were rare during breastfeeding or post-menopause.Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome.Gut and salivary microbiomes,plasma vitamins,metals,amino acids,and hormones showed associations with the vagino-cervical microbiome.Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.

OBJECTIVE: To observe the therapeutic effect between acupuncture combined with medication and simple medication on migraine and cerebral hemodynamics. METHODS: A total of 120 patients with migraine were randomized into an acupuncture plus medication group (60 cases, 3 cases dropped off) and a medication group (60 cases, 6 cases dropped off). In the medication group, flunarizine hydrochloride capsule was given orally before sleep, 10 mg a day. On the basis of the treatment in the medication group, acupuncture was applied at Sizhukong (TE 23), Shuaigu (GB 8), Taiyang (EX-HN 5), Fengchi (GB 20) and etc. in the acupuncture plus medication group, 30 min each time, once a day. Treatment for 4 weeks was required in both groups. Before and after treatment, the visual analogue scale (VAS) score, indexes of cerebral hemodynamic [blood flow velocity of anterior cerebral artery (ACA), middle cerebral artery (MCA), posterior cerebral artery (PCA), vertebral artery (VA) and basilar artery (BA)] and total TCM syndrome score were observed, and the clinical therapeutic effect and the incidence of the adverse events were evaluated in both groups. RESULTS: Compared before treatment, the VAS scores, the blood flow velocity of ACA, MCA, PCA, VA, BA and the total TCM syndrome scores were decreased in both groups ( CONCLUSION Acupuncture combined with flunarizine hydrochloride capsule can effectively relieve the pain in patients with migraine, reduce the cerebral blood flow velocity, the efficacy is superior to simple flunarizine hydrochloride capsule.
Acupuncture Points ; Acupuncture Therapy ; Hemodynamics ; Humans ; Migraine Disorders/therapy* ; Pain ; Treatment Outcome