ObjectiveTo investigate the relationship of physical activity (PA) and cognitive function to sleep quality in older adults with cognitive impairment based on resting electroencephalogram (EEG), and to explore the mediating role of specific EEG markers in the relationship between PA and sleep quality. MethodsFrom March to May, 2024, 137 older adults were recruited from Chenfu Jiayuan and Qiangwei Jiuli in Songjiang district, and Luyan communities in Jinshan district, Shanghai. The assessments included Montreal Cognitive Assessment (MoCA), International Physical Activity Questionnaire-Short Form (IPAQ-SF) and Pittsburgh Sleep Quality Index (PSQI), along with a five-minute EEG recording. ResultsThere was significant difference in sleep quality among older adults with different levels of cognitive impairment (t = -7.400, P < 0.001). The PSQI total score was negatively correlated with MoCA scores (r = -0.412, P < 0.001) and total physical activity level (PAL) (r = -0.363, P < 0.001). The θ power in the frontal areas (F3, F4) was significantly correlated with both PSQI scores and PAL (P < 0.01). The θ power in F3 + F4 exhibited a significant partial (effect size = -0.0004, 95%CI -0.0007 to -0.0002) mediating effect between PA and sleep quality in older adults with cognitive impairment. ConclusionOlder adults with more severe cognitive impairment tend to have poorer sleep quality, whereas higher PAL is associated with better sleep quality. PA can indirectly influence sleep quality in older adults with cognitive impairment by affecting θ power (F3 + F4).

Objective To explore the characteristics of intestinal flora in the chronic insomnia population in northern Shandong Province， China， and to provide a theoretical basis for further analysis of the connection between intestinal flora and insomnia. Methods This study included 30 chronic insomnia patients （18-65 years） presented to the Department of Neurology， Binzhou Medical University Hospital from January to July 2022. The control group included 33 healthy individuals. All subjects met strict inclusion and exclusion criteria. There was no significant difference in BMI between the two groups （P>0.05）. Fecal samples of all subjects were collected using sterile instruments. Bacterial DNA was extracted using a DNA assay kit. PCR amplification was performed on multiple amplicon libraries covering the V3-V4 region of the 16S rDNA gene. Results （1） The α-diversity analysis indicated that the ACE， Chao1， Shannon， and Simpson's indices were significantly higher in the chronic insomnia group than in the normal group. The β-diversity analysis showed significant differences in species composition between the chronic insomnia group and the normal group. LEfSe analysis showed significant differences in the relative abundance of bacterial phyla such as Fusobacteriota and Firmicutes between the chronic insomnia group and the normal group. （2） Random forest analysis showed the largest difference in Lachnospiraceae between the chronic insomnia group and the normal group. Conclusion The gut microbial diversity alters in the chronic insomnia population in northern Shandong Province. Lachnospiraceae may be a potential biomarker of insomnia.

OBJECTIVE: To analyze the clinical features and genetic variants in four neonates with very long chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency. METHODS: Neonates with a tetradecenoylcarnitine (C14:1) concentration at above 0.4 μmol/L in newborn screening were recalled for re-testing. Four neonates were diagnosed with VLCAD deficiency by MS-MS and genetic testing, and their clinical features and genotypes were analyzed. RESULTS: All cases had elevated blood C14:1, and the values of first recalls were all lower than the initial test. In 2 cases, the C14:1 had dropped to the normal range. 1 case has remained at above 1 μmol/L after the reduction, and the remainder one case was slightly decreased. In total eight variants of the ADACVL genes were detected among the four neonates, which included 5 missense variants and 3 novel variants (p.Met344Val, p.Ala416Val, c.1077+6T>A). No neonate showed salient clinical manifestations. CONCLUSION Above findings have enriched the spectrum of ADACVL gene mutations and provided a valuable reference for the screening and diagnosis of VLCAD deficiency.
Acyl-CoA Dehydrogenase/genetics* ; Acyl-CoA Dehydrogenase, Long-Chain ; Congenital Bone Marrow Failure Syndromes ; Genetic Testing ; Humans ; Infant, Newborn ; Lipid Metabolism, Inborn Errors ; Mitochondrial Diseases ; Muscular Diseases ; Tandem Mass Spectrometry

Objective:To analyze the efficacy and safety of CLAG regimen (cladribine, cytarabine, granulocyte colony-stimulating factor) in treatment of relapsed/refractory acute myeloid leukemia (AML).Methods:The clinical data of 30 patients with relapsed/refractory AML who were admitted to Suzhou Hongci Blood Disease Hospital from January 2018 to February 2021 were retrospectively analyzed, and the efficacy and adverse reactions were observed.Results:Among 30 patients, 1 patient was not evaluated for efficacy due to treatment-related death. Among the 29 evaluable patients, 17 patients (58.6%) achieved complete remission (CR), 5 patients (17.3%) achieved partial remission (PR) and 7 patients (24.1%) had no remission (NR). One patient in low-medium-risk group achieved CR; the CR rate in medium-risk group was higher than that in high-risk group [68.8% (11/16) vs. 41.7% (5/12)], but the difference was not statistically significant ( P = 0.250). Seven patients with M 5 achieved CR. Five patients with positive MLL gene rearrangement achieved CR. Among 6 patients with extramedullary invasion of leukemia cells, 4 patients achieved CR, and among them 3 patients with central nervous system invasion achieved CR. Among 6 patients with cladribine 3.5 mg·m -2·d -1×5 d, 1 patient died of infection after chemotherapy, 1 patient had NR, and the rest achieved CR. Among 24 patients with cladribine 5 mg·m -2·d -1×5 d, the CR rate in patients with cytarabine 2 g·m -2·d -1×5 d was higher than that in patients with cytarabine 1 g·m -2·d -1×5 d [70.0% (7/10) vs. 42.9% (6/14)], but the difference was not statistically significant ( P = 0.240). All patients developed grade Ⅳ myelosuppression after chemotherapy. 12 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CR, and 9 patients were still alive. Conclusions:CLAG regimen is effective and well tolerated in the treatment of relapsed/refractory AML. In order to improve the prognosis, allo-HSCT should be performed as soon as possible after CR.

Objective:To compare the efficacy and safety of transurethral thulium laser enucleation of prostate for benign prostatic hyperplasia (BPH) with laser controller and sheath.Methods:The clinical data of 128 BPH patients who underwent transurethral thulium laser enucleation of prostate (THuLEP) in our hospital from January to June 2020 were retrospectively analyzed. Prostatic enucleation by laser controller was performed in 66 patients (LC-THuLEP group). The prostatic urethral mucosa was cut into Ω shape at 0.5 cm in front of the verumontanum to expose the prostate capsule, and then the fiber was retracted into the laser controller. Push the gland directly between the prostate gland and the prostate surgical capsule and expand along the capsule by the laser controller. In case of bleeding or prostate adhesive cord, the fiber was extended to coagulate or cut off, and the prostate was eventually en bloc removed. THuLEP by sheath was performed in 62 cases (THuLEP group). The ages of patients in LC-THuLEP group and THuLEP group were (71.00±8.72) years and (70.32±7.80) years, respectively. The prostate volumes were (74.80±40.88) ml and (73.14±36.31) ml, respectively. Prostate specific antigen (PSA) was (4.67±4.99) ng/ml and (4.89±4.59) ng/ml, International Prostate Symptom Score (IPSS) was (19.48±5.30) points and (18.50±5.05) points, respectively. The quality of life (QOL) scores were (4.17 ± 0.78) points and (4.18± 0.67) points, the maximum urine flow rate (Q max) was (9.82± 2.58) ml /s and (9.98± 2.91) ml/s, respectively. Postvoid residual (PVR) was (60.20±39.19) ml and (61.11±52.83) ml, respectively. The international index of erectile function (IIEF-5) score was (5.58±4.50) and (5.60±4.16), respectively.There was no significant difference in preoperative baseline data between 2 groups ( P>0.05). The operation time, the reduced level of hemoglobin, the weight of removed tissue, The time to postoperative bladder irrigation, the time to indwelling catheter and complications were compared between the two groups. IPSS, QOL score, Q max, PVR, and complications were compared between the two groups at 1, 3 and 6 months after surgery, while IIEF-5 score were compared only at 6 months after surgery. Results:The operative time of LC-THuLEP group and THuLEP group was (71.85±25.68) min and (80.65±29.64) min, respectively, and the decrease of postoperative hemoglobin was (6.42±9.89) g/L and (9.47±10.79) g/L, respectively, the weight of the removed tissue was (56.73±31.21) g and (48.11±24.50) g, respectively, and the time to postoperative bladder irrigation was (14.73±2.71) h and (16.06±2.71) h, respectively, the time to indwelling catheter was (4.41±1.92)d and (4.31±1.66)d, respectively, with no statistically significant differences between the two groups. IPSS scores of LC-THuLEP group were (6.52±2.46) points, (5.83±2.43) points and (5.30±2.49) points at 1, 3 and 6 months after surgery, respectively. QOL scores were (2.36±0.85) points, (2.27±1.02) points and (1.98±0.77) points, Q max were (22.89±2.41) ml/s, (23.61±2.62) ml/s and (23.83±3.53) ml/s, respectively. In THuLEP group, IPSS were (7.60±1.89) points, (6.86±1.81) points and (6.44±1.78) points at 1, 3 and 6 months after surgery, and QOL scores were (2.68±0.67) points, (2.74±1.01) points and (2.35±0.68) points, respectively. Q max were (21.31±2.52) ml/s, (22.13±2.51) ml/s and (22.11±2.49) ml/s, respectively. Those indexes (except Qmax at 6 months)were better in LC-ThuLEP group than THuLEP group, and the differences were statistically significant ( P<0.05). PVR of LC-THuLEP group were (15.95±12.31) ml, (14.83±12.19) ml and (13.67±15.03) ml, respectively, PVR of THuLEP group were (21.89±21.14) ml, (20.03±21.51) ml and (19.69±21.19) ml, respectively, and there were no significant differences. There was no bladder injury, severe bleeding, blood transfusion or secondary operation. The incidence of urinary incontinence 1 month after surgery was 6.1% (4/66) in the LC-THuLEP group and 19.4% (12/62) in the THuLEP group, the difference was statistically significant ( P<0.05). There was no significant difference at 3 months (3/66 vs. 4/62) and 6 months (1/66 vs. 2/62) after surgery ( P>0.05). There were no significant differences in the incidence of epididymitis, urethral stricture and bladder neck contracture between the two groups ( P>0.05). Conclusion:Compared by sheath, THuLEP by laser controller could be a safe and effective surgical method with better curative effect and lower complication rate.

Objective:To identify the possible pathogenesis of a neonate with carnitine palmitoyltransferase 1A (CPT1A) deficiency by analyzing genetic variants.Methods:Potential variants were detected with an Ion Torrent semiconductor sequencer using a gene panel for inherited diseases, and candidate variants were verified by Sanger sequencing.Results:Genetic testing indicated that the neonate has carried c. 1895T>A(p.Leu632X) and c. 1153G>A(p.Ala385Thr) compound heterozygous variants of the CPT1A gene, which were inherited from his father and mother, respectively. Both variants were verified as novel through the retrieval of HGMD database, ClinVar database and literature. According to the standards and guidelines of the American College of Medical Genetics and Genomics, the c. 1895T>A variant was predicted as pathogenic(PVS1+ PM2+ PP4) and c. 1153G>A as likely pathogenic (PM1+ PM2+ PM3+ PP3). Conclusion:The c. 1895T>A and c. 1153G>A compound heterozygous variants of the CPT1A gene might underlie the pathogenesis in this child. Above results have provided a basis for clinical diagnosis and genetic counseling, and enriched the variant spectrum of the CPT1 deficiency.

Model informed precision dosing (MIPD) is a new concept to guide precision dosing for individual patient by modeling and simulation based on the available information about the individual patient, medications and the disease. Compared to the empirical dosing, MIPD could improve the efficacy, safety, economics and adherence of the pharmacotherapy according to the individual's pathophysiology, genotyping and disease progression. This consensus report provides a brief account of the concept, methodology and implementation of MIPD as well as clinical decision supporting systems for MIPD. The status and future advancing of MIPD was also discussed to facilitate the appropriate application and development of MIPD in China.

Objective:To investigate the pathological change mechanism of patients with chronic active Epstein-Barr virus infection (CAEBV).Methods:The clinical manifestations, laboratory examinations, diagnosis and treatment of one CAEBV patient in Suzhou Hongci Hematology Hospital of Jiangsu Province were retrospectively analyzed with review of related literature.Results:Combined with the results of laboratory, lymph node biopsy and bone marrow tests in different periods, the patient initially showed lymphoproliferative disease, and gradually transformed into lymphoma with the diagnosis results of EB virus-related lymphocyte clones in different periods. The patient received the corresponding treatment plan in different periods, but eventually died due to hemophagocytic syndrome and rapid progress of the disease.Conclusion:CAEBV may cause lymphocytes to gradually evolve from polyclonal to monoclonal state.

Objective:To analysis the characteristics and trends of non-martial and non-commercial heterosexual transmission of HIV/AIDS cases in Henan province between 2015 and 2020.Methods:Information of newly reported HIV/AIDS through non-martial and non-commercial heterosexual transmission was collected from National Comprehensive HIV/AIDS Information system, using SPSS 22.0 to analyze the characteristics and tend of cases.Results:During 2015-2020, a total of 10 877 HIV/AIDS cases infected by non-martial and non-commercial heterosexual transmission were newly reported in Henan province. This mode of infection increased from 32.6% in 2015 to 35.5% in 2020 (trend χ2=81.880, P<0.01). The male to female ratio was 1.9∶1 (7 105∶3 772). The mean age was (45.5±15.8) years, increasing annually ( F=5.184, P<0.01). For female cases, the proportion of aged 15-50 years group was decreased annually (trend χ2=69.888, P<0.01). Most HIV/AIDS cases were distributed in the early HIV epidemic areas and Zhengzhou city, the same as the cases of the first CD4 +T cells counts (CD4) below 200 cells/μl. The median ( P 25, P 75) first CD4 count was 298 (143, 462) cells/μl. The proportion of the first CD4<200 cells/μl was no significant change annually, while the proportion of the first CD4≥500 cells/μl was decreasing annually (trend χ2=18.961, P<0.01). Conclusions:The reported cases through non-martial and non-commercial heterosexual transmission increased, with most of them were male, married, junior, farmer, migrant laborer, and aged 40-59 years. It is needed to focus on the rural district and the middle-aged population, combined with biological and social factors to control the prevalence of AIDS through comprehensive prevention and control measures.

With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.