Objective: To investigate the impact of extracurricular physical activity on heart rate variability (HRV) among primary and secondary school students in Chengdu City, so ao to provide references for scientific exercise prescription. Methods: Using a convenient sampling method, 1 323 primary and secondary students were enrolled from central Chengdu who underwent physical fitness assessments at Sichuan Provincial Institute of Sports Science from September 2020 to January 2022. According to the standards of the National Physical Fitness Monitoring Center, boys and girls were divided into groups with and without extracurricular physical exercise habits. HRV was monitored using the SA-3000P device. Key HRV parameters were evaluated separately by gender, including standard deviation of normal to normal intervals (SDNN), root mean square of successive differences (rMSSD), total power (TP), low frequency power (LF) and high frequency power (HF). Statistical analyses were employed by t-test, Mann-Whitney U-test and Chi square test. Results: lgSDNN, lgrMSSD, TP, LF and HF in the group without extracurricular physical exercise habit [boys:(1.67±0.13)ms, (1.59±0.20)ms, (7.34±0.73)ms 2, (6.11±0.74)ms 2, (6.05±0.87)ms 2; girls:(1.67± 0.13)ms , (1.59±0.19)ms, (7.35±0.60)ms 2, (6.06±0.69)ms 2, (6.12±0.87)ms 2] were lower than those in the group with extracurricular physical exercise habit [boys:(1.75±0.13)ms, (1.72±0.18)ms, (7.69±0.62)ms 2, (6.41±0.76)ms 2, (6.44±0.79)ms 2；girls:(1.73±0.13)ms, (1.68±0.20)ms, (7.60±0.65)ms 2, (6.26±0.86)ms 2, (6.36±0.90)ms 2] ( t =-8.24, -8.75, -6.54, -5.35 , -6.33；-5.10，-4.90，-4.47，-2.71，-2.93, all P ＜0.01). Only the group of boys without extracurricular physical exercise habits showed a decrease in lgLF/HF [0.04(-0.19,0.27)] compared to the group with extracurricular physical exercise habits [ -0.03 (-0.25,0.20)] ( Z=-2.01, P <0.05). When the score classes of autonomic nerve activity, stress index and fatigue index were compared between boys and girls groups without and with extracurricular physical exercise habits, the proportion of boys normal and above scores increased from 79.3%, 84.1%, 71.8% to 91.4%, 95.7%, 87.3%, respectively, and the differences were statistically significant ( χ 2=47.42, 63.66, 38.28); the proportion of girls normal score and above increased from 79.8%, 85.7%, 75.0% to 85.4%, 92.1%, 79.4%, and the differences were statistically significant ( χ 2=48.31, 22.18, 22.22) (all P <0.01). Conclusion The primary and secondary school students who have the habit of extracurricular physical exercise have enhanced compliance in indicators related to HRV, showing more complex heart rate variability.

Objective To investigate the relationship between pan-immune inflammation value(PIV)and the disease severity and outcome of acute respiratory distress syndrome(ARDS).Methods A total of 162 ARDS patients admitted to the hospital from February 2023 to February 2024 were selected as the study group,which were divided into mild group(n=52),moderate group(n=65)and severe group(n=45)ac-cording to the severity of the disease,and death group(n=37)and survival group(n=125)according to the 28 d disease outcome.Another 116 healthy people in the same hospital during the same period were selected as the control group.Neutrophil count(NEUT),platelet count(PLT),monocyte count(MONO)and lympho-cyte count(LYMPH)in peripheral blood of each group were detected,and PIV was calculated.Pearson corre-lation analysis was used to analyze the correlation between PIV and disease severity in ARDS patients.Receiv-er operating characteristic(ROC)curve was used to evaluate the diagnostic value of PIV for the disease out-come of ARDS patients.Binary Logistic stepwise regression analysis was used to analyze the related factors af-fecting the outcome of ARDS patients.Results Peripheral blood PIV in the study group was significantly higher than that in the control group(P<0.05).The severe group had a significantly higher peripheral blood PIV than the moderate disease and mild group(P<0.05),and the moderate group had a significantly higher peripheral blood PIV than the mild group(P<0.05).Pearson correlation analysis showed that PIV was nega-tively correlated with arterial partial pressure of oxygen/fraction of inspired oxygen(PaO2/FiO2)in ARDS patients(r=-0.452,P<0.001).Sequential organ failure assessment(SOFA)score,acute physiology and chronic health evaluation(APACHE)Ⅱ score,white blood cell count,C-reactive protein and PIV in the death group were significantly higher than those in the survival group(P<0.05),PaO2/FiO2 was significantly low-er than that in the survival group(P<0.05).ROC curve analysis showed that the area under the curve of PIV to diagnose the disease outcome of ARDS patients was 0.906(95%CI:0.865-0.956).Binary Logistic step-wise regression analysis showed that SOFA score>11.84 points(OR=2.591,95%CI:1.639-3.964),A-PACHEⅡ score>20.65 points(OR=3.367,95%CI:1.863-6.086),PaO2/FiO2>115.62 mmHg(OR=2.106,95%CI:1.521-2.916),PIV>465.52(OR=3.931,95%CI:2.075-7.448)were risk factors for the outcome of ARDS patients(P<0.05).Conclusion PIV is abnormally elevated in ARDS patients,and is closely related to the severity and outcome of the disease.It can be used as an effective indicator for early diag-nosis of the disease outcome in patients with ARDS.

Objective To retrospectively analyze the efficacy and safety of low-dose antithymocyte globulin(ATG)combined with low-dose post transplantation cyclophosphamide(PTCY)in prevention of graft versus host disease(GVHD)after haploidentical transplantation.Methods Clinical data of 90 patients receiving haplotype matched transplantation in No.920 Hospital of PLA Joint Logistic Support Force from January 2022 to February 2023 were collected,and they were divided into study group(n=47)and control group(n=43)according to different GVHD prevention programs.The patients of the study group were given low-dose ATG combined with low-dose PTCY,and those of the control group received standard dose of PTCY.The implantation status,occurrence of GVHD,survival status and other indicators were analyzed between the 2 groups.Results ① Both groups of patients were successfully implanted,the median duration for neutrophil implantation(11 vs 17 d,P＜0.05)and platelet implantation(12 vs 20 d,P＜0.05)was significantly shorter in the study group than the control group.The incidence of grade Ⅱ～Ⅳ aGVHD(12.8％vs 34.9％,P＜0.05)and grade Ⅲ～Ⅳ aGVHD(6.4％ vs 20.9％,P＜0.05)was significantly lower in the study group than the control group,so was the non-recurrent mortality rate(6.4％vs 20.9％,P＜0.05)and the incidence of hemorrhagic cystitis(12.8％ vs 34.9％,P＜0.05).② By the end of the study,there were no significant differences in the incidence of mild and moderate and severe cGVHD,recurrence rate,reactivation rates of EBV and CMV,overall survival rate or progression-free survival rate between the 2 groups.Conclusion For haploidentical transplantation,low-dose ATG combined with low-dose PTCY has the advantages of lower incidence of GVHD,non-recurrent mortality,incidence of hemorrhagic cystitis and faster implantation.

Objective To preliminarily explore the efficacy of chimeric antigen receptor T cells(CAR-T)targeting CD 123 in the treatment of acute myeloid leukemia(AML)and the role of dasatinib in the treatment of CD123 targeting CAR-T induced side effects.Methods Clinical data of 1 patient with relapsed AML admitted to No.920 Hospital of PLA Joint Logistic Support Force in September,2019 were collected.The patient relapsed after previous multi-line chemotherapy and was treated with CD123 targeting CAR-T therapy.The routine blood changes of the patient after treatment were observed.Dasatinib was used when agranulocytosis occurred,40 mg orally 3 times per day,and was stopped when agranulocytosis was relieved.Changes in blood cells,CAR-T amplification,and disease control were observed.The patient was followed up for over 1 year.Results Flow cytometry for bone marrow showed that minimal residual disease negative result was observed in 30 d after infusion.The patient remained disease-free for over 1 year.After CD 123 CAR-T cells infusion,significant expansion of CAR-T cells was observed,accompanied by granulocyte deficiency and cytokine release syndrome(CRS).After using dasatinib,inhibition of CAR-T cell expansion was observed,accompanied by blood cell recovery,and CRS symptoms were alleviated.After stop of dasatinib,CAR-T cells expanded again and blood cells decreased again.Conclusion CAR-T cells targeting CD 123 have certain efficacy in the treatment for relapsed AML.Dashatinib has a blocking effect on the amplification and function of CAR-T,which can alleviate bone marrow suppression caused by CD 123 targeting CAR-T and avoid severe CRS.

OBJECTIVE To evaluate the effects of ABCB1 genotypes on the efficacy and safety of taxanes in the treatment of breast cancer. METHODS By searching Embase，the Cochrane Library， PubMed， CNKI， and Wanfang databases， cohort studies and case-control studies about taxanes in the treatment of breast cancer were collected from the establishment of the database to July 2023. After screeningliterature， extracting data and evaluating quality， meta-analysis was performed by using RevMan 5.3 software. RESULTS A total of 11 studies were included， involving 1 321 patients. There was no correlation between the three genotypes and effective rate， the incidence of myelosuppression， the incidence of neurotoxicity （except for the allele and recessive model of ABCB1 C1236T）， and the incidence of hypersensitivity reactions （P＞0.05）. The subgroup analysis showed that there was a correlation between ABCB1 C1236T dominant model and effective rate when using anthracyclines+5-fluorouracil+cyclophosphamide+taxanes （P＜0.05）， there was a correlation between ABCB1 C3435T recessive model and effective rate when using taxanes+trastuzumab （P＜0.05）. ABCB1 C1236T allele model and recessive model were correlated with sample size ≥100 and using cyclophosphamide+epirubicin+5- fluorouracil+paclitaxel or cyclophosphamide+epirubicin+paclitaxel+trastuzumab or cyclophosphamide+epirubicin+5-fluorouracil+ trastuzumab+paclitaxel regimens； recessive model with sample size ＜100 and the African region were correlated with the incidence of peripheral neuropathy； recessive model was correlated with cutaneous adverse reactions （P＜0.05）. ABCB1 C3435T recessive model was correlated with the incidence of reduced neutrophil count with sample size ≥100； the incidence of white blood cell count reduction with sample size ＜100 and using docetaxel+epirubicin+cyclophosphamide was correlated with both the allele model and the dominant model； the incidence of infections was correlated with the dominant model （P＜0.05）. The incidence of neutrophil count reduction with the sample size ＜100 was correlated with allele model of ABCB1 G2677T/A； the incidence of edema with sample size ≥100 was correlated with allele model and recessive model； the incidence of infection was correlated with allele model and dominant model， especially in patients with neutrophil count complicated with fever （P＜0.05）. CONCLUSIONS ABCB1 genotypes are not correlated with effective rate of taxanes in the treatment of breast cancer， but ABCB1 C3435T genotype is associated with decreased neutrophil counts， decreased white blood cell counts and infections； ABCB1 C1236T genotype is associated with neurotoxicity and cutaneous adverse reactions； ABCB1 G2677T/A genotype is associated with decreased neutrophil counts， infections， and edema.

Objective:To analyze the clinical phenotype and genetic characteristics for a child with Canavan disease.Methods:A child who was admitted to the Children's Hospital Affiliated to Shandong University on April 9, 2021 for inability to uphold his head for 2 months and increased muscle tone for one week was subjected to whole exome sequencing, and candidate variants were verified by Sanger sequencing.Results:Genetic testing revealed that the child has harbored compound heterozygous variants of the ASPA gene, including a paternally derived c. 556_559dupGTTC (p. L187Rfs*5) and a maternally derived c.919delA (p. S307Vfs*24). Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+ PM2_Supporting+ PM3). Conclusion:The c. 556_559dupGTTC (p.L187Rfs*5) and c. 919delA (p.S307Vfs*24) compound heterozygous variants of the ASPA gene probably underlay the pathogenesis of Canavan disease in this child.

Objective:To explore the clinical and genetic features of two Chinese pedigrees affected with Autosomal dominant intellectual developmental disorder 49 (MRD49).Methods:Two MRD49 pedigrees which were admitted to the Children′s Hospital Affiliated to Shandong University respectively on January 28, 2021 and November 10, 2022 were selected as the study subjects. Clinical data of the two pedigrees were collected and analyzed. Genomic DNA was extracted from peripheral blood samples of the probands and their family members. The probands were subjected to mutational analysis by high-throughput sequencing. Candidate variants were validated using real-time fluorescence quantitative PCR (q-PCR) or Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethics Committee of the Children′s Hospital Affiliated to Shandong University (No. SDFE-IRB/T-2022002).Results:Proband 1 had presented with language delay, motor retardation and intellectual disability, and his maternal grandmother, mother, aunt and cousin all had various degrees of intellectual disability. Sequencing results showed that proband 1 had deletion of exons 3 ~ 7 of the TRIP12 gene. q-PCR verification showed that his mother, aunt, maternal grandmother and cousin had all harbored the same deletion. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PVS1+ PM2_Supporting+ PP1). Proband 2, who had mainly presented with language delay, motor retardation and intellectual disability, and was found to harbor a heterozygous c.3010C>T (p.Arg1004*) variant of the TRIP12 gene, which was verified to be de novo in origin. Based on the guidelines from the ACMG, the variant was classified as pathogenic (PVS1+ PS2+ PM2_Supporting). Conclusion:This study had diagnosed two MRD49 families through high-throughput sequencing. Above findings have enriched the phenotypic and mutational spectrum of MRD49 in China, which has also facilitated genetic counseling for the two pedigrees.

Objective To explore the sufentanil by adjusting the adenosine monosodium phosphate activa-ted protein kinase(AMPK)/thioredoxin interacting proteins(TXNIP)/nucleotide-binding oligomerization do-main-like receptor protein 3(NLRP3)signaling pathways of the alveolar epithelial cells induced by lipopo-lysaccharide to the dead.Methods Human alveolar epithelial type Ⅱ cell(AECⅡ)were cultured to logarith-mic phase.Then they were divided into control group(normal glucose culture),lipopolysaccharide group(li-popolysaccharide induced injury by 50 μg/mL),low concentration sufentanil group(20 μmol/L),high concen-tration sufentanil group(40 μmol/L),high concentration sufentanil(40 μmol/L)+AMPK-IN-3 group(50μmol/L AMPK inhibitors).MTT assay was used to detect cell proliferation.Pyroptosis was detected by Ho-echst 33342 and propidium iodide(PI)double staining.The levels of interleukin(IL)-1β,IL-18 and tumor nec-rosis factor-α(TNF-α)in cell supernatant were detected by enzyme-linked immunosorbent assay.Quantitative real-time PCR was used to detect the mRNA expression of focal death related factors cysteinyl proteinase-1(Caspase-1),apoptosis-associated speck-like protein(ASC),and gasdermin D(GSDMD).The protein expres-sion of AMPK,phosphorylated adenosine monosodium phosphate activated protein kinase(p-AMPK),TXNIP and NLRP3 were detected by Western blot.Results Compared with the control group,the survival rate of AEC Ⅱ cells in the lipopolysaccharide group decreased,the number of PI+positive cells increased,the release of inflammatory factors IL-1β,IL-18 and TNF-α increased,the expression of Caspase-1,ASC and GSDMD mR-NA increased,the expression of p-AMPK/AMPK decreased,and the expression of TXNIP and NLRP3 in-creased(P＜0.05).Compared with the lipopolysaccharide group,the survival rate of AEC Ⅱ cells in the low concentration sufentanil group and the high concentration sufentanil group increased,PI+positive cells de-creased,the release of inflammatory factors IL-1β,IL-18 and TNF-α decreased,the expression of Caspase-1,ASC and GSDMD mRNA decreased,the expression of p-AMPK/AMPK increased,and the expression of TX-NIP and NLRP3 decreased(P＜0.05).Compared with the high concentration sufentanil group,the survival rate of AEC Ⅱ cells in the high concentration sufentanil+AMPK-IN-3 group decreased,the number of PI+positive cells increased,the release of inflammatory factors IL-1β,IL-18 and TNF-α increased,the expression of Caspase-1,ASC and GSDMD mRNA increased,the expression of p-AMPK/AMPK decreased,and the ex-pression of TXNIP and NLRP3 increased(P＜0.05).Conclusion Sufentanil may improve lipopolysaccharide induced alveolar epithelial cell pyroptosis by regulating AMPK/TXNIP/NLRP3 signaling pathway.

The rational use of medical consumables in clinical practice is of great significance for improving medical quality and controlling medical costs. In June 2023, a tertiary hospital established a management organization system, formulated a list of key monitored medical consumables, built supporting information system and database, and established a warning mechanism, to explore the rationality evaluation path for clinical use of medical consumables through in-depth analysis of the entire hospital-department-disease-surgical procedure. This evaluation path achieved good results. Taking absorbable hemostatic gauze as an example, through implementing this evaluation path, problems with the clinical use of this consumable were promptly identified, and targeted improvements were made. After rectification, the number of absorbable hemostatic gauze used in the third quarter of 2023 (209.0 pieces) had decreased compared to the second quarter of the same year (254.0 pieces), and clinical use was more reasonable and standardized. This evaluation path achieved refined control over key monitored medical consumables, which could provide references for other hospitals to carry out the management of clinical rational use of medical consumables.

Objective To evaluate the efficacy and safety of eravacycline in the treatment of complicated intra-abdominal infection(cIAI)in Chinese adult patients.Methods In this multicenter,randomized,double-blind phase Ⅲ study,cIAI patients were randomly assigned to receive either eravacycline(1.0 mg/kg,q12h)or ertapenem(1 g,q24h)by intravenous infusion for 5 to 14 days.The primary and secondary efficacy endpoints included the clinical efficacy and microbiological efficacy in different populations,including modified intention-to-treat(MITT)population,clinically evaluable(CE)population,and microbiologically evaluable(ME)population,at different time points after treatment.Clinical cure rates at specific visits were summarized and compared between treatment groups in different populations.The microbial eradication rate was calculated for the patients with baseline pathogens.The incidence of adverse events(AE)and drug-related treatment emergent adverse event(TEAE)was analyzed by treatment group.Results A total of 144 patients with cIAI who received at least one dose of the study drug were included in the MITT population.The clinical cure rate was 77.8％(56/72)in eravacycline-treated patients and 90.3％(65/72)in ertapenem-treated patients at 25-31 days after the first dose(TOC visit).When the patients who received insufficient treatment(＜72 hours)were excluded,the clinical cure rate was 83.6％(56/67)in eravacycline group and 90.3％(65/72)in ertapenem.For CE and ME patients,the clinical cure rate at TOC visit was 91.1％(51/56)and 83.3％(25/30)in eravacycline group,95.3％(61/64)and 90.9％(30/33)in ertapenem group.Eravacycline treatment achieved microbiological eradication rate of 91.3％(21/23)against Escherichia coli at TOC visit in micro-MITT population while ertapenem treatment resulted in a microbiological eradication rate of 96.2％(25/26).The microbiological efficacy of eravacycline and ertapenem against Klebsiella pneumoniae was 4/5 and 3/3,respectively.The incidence of TEAE was similar in eravacycline and ertapenem groups(75.0％vs.70.8％),most of which were mild or moderate.The AEs associated with eravacycline were mainly infusion site phlebitis(9.7％,7/72)and infusion site pain(8.3％,6/72).Conclusions Similar to ertapenem,eravacycline has good clinical and microbiological efficacy in treating cIAI.It is also safe and well-tolerated in the patients.