Objective:To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis.Methods:Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups.Results:Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old ( OR=0.54,95% CI 0.30-0.93), tumor lysis syndrome before chemotherapy ( OR=0.48,95% CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy ( OR=0.55,95% CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions:The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.

Background and Objective Accurate diagnosis of mucous cystic lesion(PCL)remains a clinical difficult.Both Carcinoembryonic antigen(CEA)and glucose(GLU)are reported to have ability to distinguish mucinous PCL from non-mucinous PCL,but the accuracy was limited.The objective of this study was to evaluate the value of cystic CEA combined with GLU in the diagnosis of mucinous PCL.Methods PCL patients who underwent pancreatic surgery and endoscopic ultrasonography guided fine-needle aspiration(EUS-FNA)were retrospectively collected from the First Affiliated Hospital of Naval Medical University.Clinical data and cystic fluid analysis of included PCLs patients were analyzed using receiver operator(ROC)curves.ROC analysis,sensitivity and specificity analyses were used to evaluate the value of CEA combined with GLU in the diagnosis of mucinous PCL.Results From January 2015 to December 2021,a total of 84 patients underwent cyst fluid CEA and GLU analysis,of whom 44(52.4％)had mucinous PCL and 40(47.6％)had non-mucinous PCL.The AUC for distinguishing mucinous from non-mucinous PCL by CEA was 0.82[(95％confidence interval(CI):0.72-0.92)].When 192 ng/mL was used as the cutoff level,the diagnostic sensitivity and specificity were 50％and 93％,respectively.Using 20 ng/mL as cutoff level,the diagnostic sensitivity increased to 80％and the specificity decreased to 68％.The AUC for the cystic GLU to distinguish mucinous from non-mucinous PCL was 0.73(95％CI:0.99-0.87),and the diagnostic sensitivity and specificity were 100％and 60％,respectively.When the cutoff level of CEA was 192 ng/mL,the AUC of CEA combined with GLU in the diagnosis of mucinous PCLs was 0.94(95％Cl:0.86-0.99),while when the cutoff level of CEA was 20 ng/mL,the AUC of CEA combined with Glu in the diagnosis of mucinous PCLs was 0.94(95％CI:0.85-0.99).The AUCs were significantly higher than the AUC with single diagnostic indicators.Conclusion When using the cutoff level of 192 ng/mL,cyst fluid CEA combined with GLU has high sensitivity and specificity in differentiating mucinous PCL from non-mucinous PCL,so it can be considered for clinical application.Lower CEA cutoff level(20 ng/mL)can improve the sensitivity of diagnosis.

Objective To explore the effect of applying comprehensive interventions on promoting pathogen detec-tion before antimicrobial therapy in hospitalized patients.Methods Hospitalized patients who received therapeutic use of antimicrobial agents in a tertiary first-class hospital from January 2020 to December 2021 were selected as the research subjects.Comprehensive intervention measures were implemented from January 2021.The pathogen detec-tion rates,detection classification,and detection rates of key monitored departments before antimicrobial therapy were compared between the pre-intervention group(January-December 2020)and the post-intervention group(Janu-ary-December 2021).Results A total of 10 239 hospitalized patients who received therapeutic use of antimicrobial agents were included in analysis,4 526 cases were in the pre-intervention group and 5 713 cases in the post-interven-tion group.The pathogen detection rates before antimicrobial therapy,before restricted grade antimicrobial therapy,and before special grade antimicrobial therapy after intervention were 94.56％,94.72％,and 96.03％,respective-ly,which were higher than 83.74％,84.47％,and 84.95％before intervention,with statistical significance(all P＜0.05).The detection rate of targeted pathogens after intervention was 64.87％,higher than that before interven-tion(28.04％),with statistically significant difference(P＜0.05).The pathogen detection rates before therapeutic use of antimicrobial agents in departments of critical care medicine,pulmonary and critical care medicine,pediatrics,neurosurgery,and general surgery after intervention were 93.20％,91.17％,92.20％,94.12％,and 91.15％,re-spectively,higher than the rates before intervention,namely 85.00％,82.19％,83.20％,83.33％,and 83.03％,respectively,with statistical significance(all P＜0.05).Conclusion The application of comprehensive intervention measures can improve the pathogen detection rate before antimicrobial therapy of hospitalized patients.Close atten-tion should be paid to the pathogen detection indicators related to healthcare-associated infection diagnosis and for the detection of sterile body fluid.

Objective To observe the feasibility and safety of CT-guided fine-needle assisted localization for puncturing difficult lung or liver lesions.Methods Data of 30 patients with single difficult lung or liver lesion,i.e.lesion located at difficult part for puncturing or deep lesion with diameter of 0.5-2.0 cm who underwent CT-guided 22G needle assisted localization before puncturing were retrospectively analyzed.The success rate of fine-needle assisted localization,the success rate of the first-time puncturing and the occurrence of complications were recorded.Results Among 30 difficult lesions,there were 27 lung lesions and 3 hepatic lesions,with a mean diameter of(1.0±0.4)cm.Assisted localization of difficult lesions were successfully performed with 22G needle under CT guidance at the edge of lesion,1 cm adjacent to lesion or at the puncture path,with success rate of fine-needle assisted localization of 100%,and no obvious complication happened.The followed operations included preoperative localization of 14 lung nodules,biopsy of 10 lung nodules and 3 liver nodules,as well as microwave ablation of 3 liver nodules,with the success rate of the first-time puncturing of 100%.Mild pneumothorax was observed in 3 cases(3/27,11.11%)of difficult lung lesions after biopy.No other obvious complication occurred.Conclusion CT-guided fine-needle assisted localization for percutaneous puncturing difficult lung or liver lesions was feasible and safe.

Objective To explore the association between R611H(G/A,rs734312)variation of WFS1 gene and early-onset type 2 diabetes mellitus(T2DM).Methods A total of 181 Chinese patients with early-onset T2DM(T2DM group)and 196 non-diabetic controls(NC group)were enrolled in this study.The rs734312 variation was detected by PCR-direct sequencing.Genotypic and allelic frequencies of rs734312 and clinical variables were compared and analyzed between the two groups.Results Compared with the NC group,the frequencies of AA genotype and A allele in R611H(G→A)variation were significantly elevated in the early-onset T2DM group,AA vs GA+GG(OR 1.720,95%CI 1.100～2.680,P<0.05).A vs G(OR 1.500,95%CI 1.020～2.220,P<0.05).The remarkable differences of frequencies of genotype and allele in rs734312(G/A)were observed between Asians(China,Japan and Korea)and Caucasians(Denmark,Britain,Spain,France and Russia,P<0.01 for each).Compared with AA genotype,fasting and 2 hours postprandial insulin(FIns and 2 hIns)as well as HOMA-β were significantly rise in GG+GA genotype carriers of early-onset T2DM group(P<0.05).Conclusions The a allele of rs734312 in WFS1 may be a risk factor for early-onset T2DM in Chinese population,and the variation might be a potential genetic marker for predicting the islet β-cell dysfunction in early-onset T2DM in Chinese population.

Objective To investigate the improvement effect and mechanism of marmesin on cognitive impairment in Alzheimer's disease(AD)mice.Methods Fifty mice were randomly divided into five groups:blank group,model group,low-and high-dose marmesin groups and donepezil(positive drug)group,with 10 mice in each group.After 21 days of continuous administration,except for the blank group,the mice in other groups were given intraperitoneal injection of scopolamine to establish the AD model.Network pharmacology was used to construct the protein-protein interaction(PPI)network of common targets of marmesin in the treatment of AD,and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed to provide further research direction.The cognitive function of AD model mice was evaluated by Morris water maze,open field test and new object recognition test.Nissl staining was used to observe the damage of hippocampal neurons.The levels of acetylcholine(Ach),acetylcholine transferase(ChAT),acetylcholinesterase(AChE),reactive oxygen species(ROS),malondialdehyde(MDA)and catalase(CAT)in hippocampus of mice were detected by kit.The protein expression levels of interleukin 6(IL-6),interleukin 1β(IL-1 β),tumor necrosis factor α(TNF-α),nuclear factor E2-related factor 2(NRF2),silent information regulator homologous protein 3(SIRT3),Kelch-like ECH-associated protein 1(KEAP1),quinone oxidoreductase 1(NQO1)and heme oxygenase 1(HO-1)in hippocampus were detected by Western Blot.Results Compared with the model group,the latency of Morris water maze test was significantly shortened in the high-dose marmesin group,the time of entering the target area in the open field new object test and the movement distance in the central area of the open field were prolonged,the number of neurons in the hippocampal CA1 and CA3 regions was significantly increased,the levels of ChAT and Ach in the hippocampus were significantly increased,AChE level was significantly decreased,CAT level was significantly increased,ROS and MDA levels were significantly decreased,TNF-α expression level was decreased,SIRT3 and HO-1 expression levels were increased,and KE AP1 protein expression level was decreased,the differences being statistically significant(P＜0.05 or P＜0.01 or P＜0.001).Conclusion Marmesin can effectively improve the learning and memory impairment of AD mice,and its mechanism may be related to the activation of NRF2/SIRT3 signaling pathway,thereby alleviating oxidative stress level and neuroinflammation,and repairing cholinergic neuron function.

Objective To evaluate the characteristics of the mass balance and pharmacokinetics of[14 C]birociclib in Chinese male healthy volunteers after a single oral administration.Methods This study used a 14 C labeled method to investigate the mass balance and biological transformation of birociclib in human.Subjects were given a single oral dose of 360 mg/50 pCi of[14 C]birociclib suspension after meals.The blood,urine,and fecal samples were collected at specified time points/intervals after administration.The radiation levels of 14 C labeled birociclib-related compounds in the blood,plasma,urine,and feces were analyzed using liquid scintillation counting.In addition,a combination of high-performance liquid chromatography and on-line/off-line isotope detectors was used to obtain radioactive isotope metabolite spectra of plasma,urine,and fecal samples,and high-resolution mass spectrometry was used to identify the main metabolites.Results A total of 6 healthy male subjects were enrolled in this study.The median peak time of radioactive components in plasma was 5.00 h and the average terminal elimination half-life was 43.70 h after administration.The radioactive components were basically excreted and cleared from the body within 288.00 hours after administration,and average cumulative recovery rate of radioactive drugs was(94.10±8.19)％.The radioactive drugs were mainly excreted through feces,accounting for(84.60±7.10)％of the dose of radioactive drugs administered.Urine was the secondary excretory pathway,accounting for 9.41％of the dose of radioactive drugs administered.Metabolic analysis indicated that the prototype drug was the main radioactive components in plasma samples.The main metabolites in plasma were RM4(XZP-5286),RM6(XZP-3584),and RM7(XZP-5736).The drugs were mainly cleared from the body in the form of prototype drugs and metabolites.In addition to prototype drugs,a total of 9 metabolites were identified and analyzed in plasma,urine,and fecal samples,all of which were phase 1 metabolites.The main metabolic and clearance pathways of drugs in the body were deethylation,diisopropylat ion,oxidation,etc.Conclusion After a single oral administration of[14C]birociclib suspension to healthy subjects,it was mainly cleared from the body in the form of prototype drugs and metabolites,with feces as the main excretory pathway and urine as the secondary excretory pathway.Drugs mainly undergo metabolic reactions in the body,such as deethylation,diisopropylation,and oxidation.The subjects were well tolerance after administration.

Excessive nitrite can cause serious harm to human health.In this work,gold nanoparticles/zeolitic imidazolate framework-67(AuNPs/ZIF-67)nanocomposite with three-dimensional structure was designed and synthesized on carbon cloth(CC),and a AuNPs/ZIF-67 modified CC electrode was then prepared for detection of nitrite.The interleaved foliated ZIF-67 nanosheets were synthesized on CC,and then coral-like AuNPs were coated on ZIF-67 modified CC by electrodeposition.The morphology,composition and surface area of AuNPs/ZIF-67/CC were characterized by scanning electron microscopy(SEM),X-ray photoelectron spectroscopy(XPS),X-ray diffraction(XRD)and N2 adsorption-desorption test.The prepared electrode combined the high catalytic performance of AuNPs with the morphology of ZIF-67,significantly increasing the surface area and electrocatalytic activity of the electrode.The oxidation potential of NO2-on AuNPs/ZIF-67/CC electrode decreased significantly,and the oxidation current increased significantly,showing excellent response performance.Cyclic voltammetry(CV)was used to detect NO2-with linear ranges of 0.005-5.0 mmol/L and 5.0-24.0 mmol/L,and limit of detection(LOD,3σ/S)of 1.26 μmol/L.Chronoamperometry(i-t)was also used to detect NO2-,with linear ranges of 1-800 μmol/L and 800-1800 μmol/L,and LOD(3σ/S)of 0.08 μmol/L.In addition,AuNPs/ZIF-67/CC prepared here showed good anti-interference,repeatability and stability,and could be used to detect NO2-in real samples.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

Objectives It was a preliminary exploration on rare disease management of comprehensive hospital based on the"Center-Multidisciplinary Team"structure.Methods By applying interrupted time series analysis,the characteristics and related medical service of rare disease patients discharged from sample hospitals from 2021 to 2023 were measured.Results The results showed that the hospital served 19 825 rare disease patients from 2021 to 2023.The proportion of patients whose main diagnosis were rare diseases was approximately 27％.The interrupted time series technique indicated that the expected proportion of rare disease patients increased instantly by 1.89 thousand points.The capability to diagnose has significantly improved,with a growing trend on volume of bioinformatics analysis services for rare diseases patients.Conclusion The rare disease management based on the"Center-Team"structure can increase the attention of medical staff to rare diseases,strengthen the diagnostic capacity of rare diseases,and make patient management more continuous and disciplinary co-operation more efficient without significantly increasing the input burden on hospitals.