Objective: To explore the mediating effects of psychological flexibility and exercise self-efficacy between frailty and social isolation among elderly patients with type 2 diabetes mellitus (T2DM), so as to provide the basis for alleviating social isolation in this population. Methods: From July to November 2024, elderly patients with T2DM aged ≥65 years were selected by using the convenience sampling method from the endocrinology and geriatrics departments of a tertiary hospital in Shanxi Province. Demographic and clinical data were collected using structured questionnaires. Frailty was assessed using the FRAIL Scale, psychological flexibility was measured with the Acceptance and Action Questionnaire-II (AAQ-II), exercise self-efficacy was evaluated via the Chinese version of the Exercise Self-Efficacy Scale, and social isolation was quantified employing the General Alienation Scale. The mediating effects of psychological flexibility and exercise self-efficacy between frailty and social isolation were analyzed using the Process macro program. Results: A total of 300 elderly patients with T2DM were included, with a mean age of (71.16±4.88) years. There are 167 males (55.67%) and 133 females (44.33%). The mean scores for frailty, psychological flexibility, exercise self-efficacy, and social isolation were (2.82±1.59), (28.32±6.95), (5.69±1.20), and (39.27±9.24). Mediation analysis revealed that frailty positively affected social isolation (β=0.227, 95%CI: 0.132-0.323). It also indirectly positively influenced social isolation through psychological flexibility (β=0.165, 95%CI: 0.105-0.234) and exercise self-efficacy (β=0.150, 95%CI: 0.093-0.217), and the chained mediating effect of psychological flexibility and exercise self-efficacy (β=0.066, 95%CI: 0.038-0.100). Conclusion Frailty exacerbates social isolation by diminishing psychological flexibility and exercise self-efficacy among elderly patients with T2DM.

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.

Hepatocellular carcinoma(HCC)is one of the most common tumor types and remains a major clinical challenge.Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC.However,few mitophagy inhibitors have been approved for clinical use in humans.Pyrimethamine(Pyr)is used to treat infections caused by protozoan parasites.Recent studies have reported that Pyr may be beneficial in the treatment of various tumors.However,its mechanism of action is still not clearly defined.Here,we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis.Mechanistically,Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells.In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29(SNAP29)-vesicle-associated membrane protein 8(VAMP8)interaction.Moreover,Pyr acted synergistically with sorafenib(Sora)to induce apoptosis and inhibit HCC proliferation in vitro and in vivo.Pyr enhances the sensitivity of HCC cells to Sora,a common chemotherapeutic,by inhibiting mitophagy.Thus,these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor.Notably,Pyr and Sora combination therapy could be a promising treatment for malignant HCC.

Fetal STR typing of aborted tissue has long been a major problem in forensic DNA.Especially for the first trimester abortion tissue,it is difficult to isolate the embryonic components by histomorphological means,resulting in the inability to accurately obtain the STR typing of the fetus.The mixed STR typing results of mother and fetus can provide a key basis for the identification of suspects in cases of rape-induced pregnancy.In this study,next generation sequencing was used to successfully detect mixed STR typing of mother and suspected fetus or single STR typing of suspected fetus in 4 rape-induced early pregnancy abortion tissues.Combined with Y-STR and flank sequence information,it provides a more comprehensive and reliable genetic basis for the identification of suspects.

Objective:To explore the mechanism of social support and self-efficacy in rehabilitation exercise in the relationship between psychological resilience and kinesiophobia in hip fracture patients.Methods:Totally 284 hip fracture patients treated at the Department of Trauma and Orthopedics, Binzhou Medical University Hospital from May 2022 to April 2023 were selected by convenience sampling. Data were collected using the general information questionnaire, the Connor-Davidson Resilience Scale (CD-RISC), the Social Support Rating Scale (SSRS), the Self-Efficacy Rehabilitation Outcome Scale (SER), and the Tampa Scale for Kinesiophobia (TSK). Process 4.1 was used for chain mediation effect analysis.Results:The scores for the 284 hip fracture patients were as follows: CD-RISC (58.72±7.77), SSRS (29.70±5.11), SER (91.23±8.41), and TSK (38.07±3.65). Psychological resilience, social support, self-efficacy in rehabilitation exercise, and kinesiophobia were all significantly correlated pairwise (all P<0.01). Social support and self-efficacy in rehabilitation exercise had a chain mediation effect between psychological resilience and kinesiophobia, with mediation effect values of -0.020 and -0.079, accounting for 17.52% and 67.70% of the total effect, respectively. Conclusions:Psychological resilience directly influences the level of kinesiophobia in hip fracture patients and has an indirect effect through the chain mediation of social support and self-efficacy in rehabilitation exercise.

Objective A sterile golden hamster model was established by cesarean section purification.Methods SPF-grade donor female golden hamsters were selected,and males and females were mated 1∶1 and separated after mating.The cage time of the surrogate mothers was 1 week earlier than that of the donor mothers.Parturient golden hamsters underwent hysterectomy on a sterilized workbench,and the uteruses were transferred into isolation kits and stripped.To obtain sterile milk for milk replacement,sterile ICR mice and sterile SD rats were used.After successful separation,the hamsters were transferred to isolation kits to prepare for feeding.The sterility status of the feeding isolation kits was tested monthly.Results Three caesarean sections were performed,but the first and second lactations failed.The third milk replacement was successful,and 18 young hamsters were obtained with survival rates of 88%and 66%after weaning.All hamsters were quality tested by GB/T 14926.41-2001.Conclusions Using a cesarean section purification technique and sterile ICR mice and SD rats for microbial-free milk replacement,a sterile golden hamster model was obtained.

Objective:To examine the impact of sleep quality on cognitive function in older adults with mild cognitive impairment(MCI)and explore the potential mediating role of depression.Methods:Using a cross-sectional design, we conducted an on-site questionnaire survey among 310 elderly individuals with MCI in Haishu District, Ningbo City from April to June 2021.Out of the 310 questionnaires collected, 299 were deemed valid.The survey encompassed gathering basic demographic information of the participants, as well as administering the Montreal Cognitive Assessment Scale, Patient Health Questionnaire Depression Scale, and Pittsburgh Sleep Quality Index Scale.Results:The cognitive functions of patients with MCI were found to be positively related to their education level( F=3.89, P<0.05).The correlation analysis indicated that sleep quality was positively correlated with depression( r=0.40, P<0.01)and negatively correlated with cognitive function( r=-0.22, P<0.01).Furthermore, a significant negative correlation was observed between depression and cognitive function( r=-0.20, P<0.01).The mediation analysis revealed that depression played a role in mediating the influence of sleep quality on cognitive function, with a mediation effect of -0.02(95% CI: -0.03--0.01). Conclusions:The cognitive function of elderly individuals with MCI can be significantly affected by sleep quality, with depression playing a mediating role.

OBJECTIVE: To explore the clinical and genetic characteristics of two children with developmental delay. METHODS: Two children who had presented at the Children's Hospital Affiliated to Shandong University on August 18, 2021 were enrolled as the study subjects. Clinical and laboratory examination, chromosomal karyotyping and high-throughput sequencing were carried out for both children. RESULTS: Both children had a 46,XX karyotype. High-throughput sequencing showed that they have respectively carried a c.489delG (p.Q165Rfs*14) and a c.1157_1158delAT (p.Y386Cfs*22) frameshifting variant of the CTCF gene, both had a de novo origin and were unreported previously. CONCLUSION The CTCF gene variants probably underlay the development delay in the two children. Above discovery has enriched the mutational spectrum of the CTCF gene and has important implications for revealing the genotype-phenotype correlation for similar patients.
Child ; Humans ; Developmental Disabilities/genetics* ; High-Throughput Nucleotide Sequencing ; Intellectual Disability/genetics* ; Karyotyping ; Mutation

OBJECTIVE: To explore the genetic etiology of a child with Hypomagnesemia, epilepsy and mental retardation syndrome (HSMR). METHODS: A child who was admitted to the Children's Hospital of Shandong University on July 9, 2021 due to repeated convulsions for 2 months was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his pedigree members were collected for the extraction of genomic DNA. Whole exome sequencing was carried out, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 1-year-and-7-month-old male, had presented with epilepsy and global developmental delay. Serological testing revealed that he has low serum magnesium. Genetic testing showed that the child has harbored a heterozygous c.1448delT (p.Val483GlyfsTer29) variant of the CNNM2 gene, which was de novo in origin. The variant has caused substitution of the Valine at position 483 by Glycine and formation of a termination codon after 29 amino acids at downstream. As predicted by Swiss-Model online software, the variant may alter the protein structure, resulting in a truncation. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1448delT (p.Val483GlyfsTer29) was predicted as a pathogenic variant (PVS1+PS2+PM2_Supporting+PP4). CONCLUSION The heterozygous c.1448delT variant of the CNNM2 gene probably underlay the HSMR in this child. Above finding has enriched the phenotype-genotype spectrum of the CNNM2 gene.
Humans ; Male ; Cation Transport Proteins ; Computational Biology ; Ethnicity ; Intellectual Disability/genetics* ; Magnesium ; Mutation ; Seizures/genetics* ; Infant

OBJECTIVE: To explore the clinical and genetic characteristics of a very early-onset inflammatory bowel disease (VEO-IBD) type 28 child with atypical clinical manifestations. METHODS: A VEO-IBD type 28 child with atypical clinical manifestations admitted to the Department of Neonatology, Children's Hospital Affiliated to Shandong University on November 5, 2021 was selected as the study subject. Clinical data of the child was collected. Peripheral venous blood samples of the child and his parents were collected for high-throughput sequencing. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 50-day-old male, had manifested bronchitis, ulcerative stomatitis, eczema and slightly loose stool. High-throughput sequencing revealed that he has harbored compound heterozygous variants of the IL-10RA gene, namely c.299T>G (p.V100G) and c.301C>T (p.R101W), which were inherited from his father and mother, respectively. Bioinformatic analysis showed that both variants have been recorded in the HGMD database, though the c.299T>G variant has not been included in the gnomAD, 1000 Genomes, ExAC and ESP6500 databases, while the c.301C>T variant has a low population frequency. Both variants were predicted to be deleterious by the online software including SIFT, PolyPhen-2 and Mutation Taster. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PS3+PM2_Supporting+PP3). CONCLUSION The c.299T>G and c.301C>T variants of the IL-10RA gene probably underlay the VEO-IBD type 28 in this child. Above finding has expanded the phenotypic spectrum of VEO-IBD type 28 due to variants of the IL-10RA gene and provided a reference for the clinical diagnosis of this disease.
Humans ; Child ; Male ; Computational Biology ; Diarrhea ; Gene Frequency ; Inflammatory Bowel Diseases/genetics* ; Mutation