ObjectiveTo investigate growth hormone secretagogue receptor （GHSR） rs2922126 gene polymorphisms and their association with genetic susceptibility to nonalcoholic fatty liver disease （NAFLD） in the Chinese Han population in Qingdao， China， and to provide a basis for diagnosis and treatment. MethodsA total of 220 patients who were admitted to Qingdao Municipal Hospital from June 2022 to June 2023 and were diagnosed with NAFLD based on radiological examination were enrolled as NAFLD group， and 167 healthy individuals during the same period of time were enrolled as control group. Fasting blood samples were collected from all subjects， and related biochemical parameters were measured. Whole blood DNA was extracted， and polymerase chain reaction and MALDI-TOF mass spectrometer were used for genotyping. The chi-square test was used for comparison of categorical data between groups， and the independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between groups. The binary logistic regression analysis was used to investigate the risk of NAFLD. ResultsCompared with the control group， the NAFLD group had significantly higher age， body mass index （BMI）， fasting plasma glucose， triglyceride， gamma-glutamyl transpeptidase， alkaline phosphatase， alanine aminotransferase， and aspartate aminotransferase， as well as a significantly lower level of high-density lipoprotein （all P0.05）. The distribution of GHSR rs2922126 genotypes was consistent with the Hardy-Weinberg equilibrium， suggesting population representativeness in the subjects enrolled （NAFLD group： P=0.106； control group： P=0.849）. There was no significant difference in the distribution of AA， TA， and TT genotypes at GHSR rs2922126 locus between the control group and the NAFLD group （P=0.099）， and there was also no significant difference in allele frequency between the two groups （P=0.063）. In the recessive model of A allele， there was a significant difference in the distribution of AA homozygote and TA+TT genotype between the NAFLD group and the control group （P=0.032）. The binary logistic regression analysis showed that in the recessive model of A allele， AA homozygote carriers had an increased risk of NAFLD compared with TA+TT genotype carriers （odds ratio ［OR］=1.712， 95% confidence interval ［CI］： 1.045 — 2.807， P=0.033）. There was still a significant difference after adjustment for sex， age， and BMI （OR=2.156， 95%CI： 1.221 — 3.808， P=0.008）. In the NAFLD group， AA genotype carriers had a significantly higher serum level of total cholesterol （TC） than TT+TA carriers （Z=-1.99，P=0.046）. ConclusionGHSR rs2922126 AA genotype may be associated with the increased risk of NAFLD in the Chinese Han population in Qingdao， and GHSR rs2922126 AA genotype is associated with the increase in TC in NAFLD patients.

Objective:To evaluate the clinical efficacy of rituximab injection combined with CHOP regimen (cyclophosphamide+doxorubicin+vincristine+prednisolone) in the treatment of diffuse large B-cell lymphoma (DLBCL).Methods:One hundred and twenty patients with DLBCL who treatment in the First Affiliated Hospital of Xinjiang Medical University from June 2019 to June 2022 were selected as the study object. They were randomly divided into the study group (60 cases) and the control group (60 cases). The control group was treated with CHOP regimen, and the study group was treated with rituximab injection on the basis of CHOP regimen. The clinical efficacy, inflammatory reaction, immune function and adverse reaction were evaluated after 6 courses of treatment.Results:After treatment, the total clinical effective rate in the study group was higher than that in the control group: 88.33%(53/60) vs. 70.00%(42/60), there was statistical difference ( χ2 = 6.11, P<0.05). Before treatment, the levels of serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the two groups had no significant differences ( P>0.05); after treatment, the levels of serum IL-6 and TNF-α were decreased, and the levels of serum IL-6 and TNF-α in the study group were lower than those in the control group: (223.56 ± 21.28) ng/L vs. (267.35 ± 25.36) ng/L, (9.34 ± 2.75) μg/L vs. (11.96 ± 3.83) μg/L, there were statistical differences ( P<0.05). Before treatment, the levels of serum immunoglobulin (Ig) A, IgM and IgG in the two groups had no significant differences ( P>0.05); after treatment, the levels of serum IgA, IgM and IgG were decreased, but the levels of serum IgA, IgM and IgG in the study group were higher than those in the control group: (1.83 ± 0.46) g/L vs. (1.34 ± 0.34) g/L, (1.15 ± 0.22) g/L vs. (0.83 ± 0.24) g/L, (10.67 ± 1.65) g/L vs. (8.02 ± 1.62) g/L, there were statistical differences ( P<0.05). After treatment, the incidence of thrombocytopenia, leucopenia, gastrointestinal reaction, bone marrow suppression and liver function injury in the study group were lower than those in the control group: 6.67%(4/60) vs. 20.00%(12/60), 15.00%(9/60) vs. 31.67%(19/60), 30.00%(18/60) vs. 58.33%(35/60), 5.00%(3/60) vs. 16.67%(10/60), 10.00%(6/60) vs. 25.00%(15/60), there were statistical differences ( χ2 = 4.62, 4.66, 9.77, 4.33, 4.88, P<0.05). Conclusions:The treatment effect of rituximab injection combined with CHOP regimen in DLBCL is significant, which can reduce the inflammatory reaction of the body, reduce the damage of immune function, and reduce the adverse reactions of chemotherapy.

Objective:To evaluate the effect of combining contralateral high-frequency transcranial magnetic stimulation (rTMS) with biofeedback-controlled empty swallowing training on dysphagia among stroke survivors.Methods:Eighty dysphagic stroke survivors were divided at random into a control group, a biofeedback group, an rTMS group and a combined treatment group, each of 20. In addition to routine dysphagia rehabilitation, the biofeedback group and the rTMS group received empty swallowing training based on biofeedback or high-frequency rTMS applied to the healthy motor cortex as appropriate. The combined treatment group was given both. The treatment was administered once daily, 5 days a week for 3 consecutive weeks. Before and after the treatment, all of the subjects′ swallowing was evaluated using the penetration aspiration scale (PAS), functional oral intake scale (FOIS) and a standardized swallowing assessment (SSA). The latency and amplitude of the mylohyoid muscle′s motor evoked potentials (MEPs) were also recorded before and after the treatment.Results:After the treatment, significant improvement was observed in the average PAS, FOIS and SSA scores as well as in the latency and amplitude of the MEPs in the four groups. The average results in the combined treatment group were significantly better than in the other 3 groups. The latency of the mylohyoid muscle′s MEP was significantly shorter in the combined group than in the control and biofeedback groups on average, while the amplitude was significantly greater than in the control group.Conclusion:Combining contralateral high frequency rTMS with empty swallowing training based on biofeedback can better improve the swallowing of dysphagic stroke survivors.

Objective To systematically evaluate the experiences of drug self-management in elderly patients with multiple chronic illnesses,so as to provide references for the development of personalized drug self-management intervention programs.Methods Qualitative research on drug self-management experiences of elderly patients with multiple chronic diseases was retrieved from PubMed,Cochrane Library,Embase,CINAHL,Web of Science,Scopus,CNKI,Wanfang,VIP and SinoMed.The retrieval time limit is from the establishment of the databases to November 2023.The qualitative research quality evaluation criteria of the Joanna Briggs Institute Evidence-based Health Care Center in Australia was used to evaluate quality of studies.The results were integrated by meta-integration method.Results A total of 9 studies were included,and 33 research results were extracted,and 4 integrated results and 12 categories were synthesized.The integration results included the objective dilemmas and challenges of drug self-management,the low level of drug literacy,willingness to engage in positive behavior attempts,need of multi-party assistance.Conclusion The objective dilemmas of drug self-management and low level of drug literacy in elderly patients with multimorbidity will seriously affect their health outcomes.Medical staffs should pay attention to the different experiences of patients in the process of drug self-management,identify the needs of patients,formulate targeted intervention support strategies,and improve the level of drug self-management in elderly patients.

Objective:To explore the application value of contrast-enhanced ultrasound (CEUS) combined with transvaginal ultrasound features and quantitative parameters in evaluating high-risk endometrial cancer (EC).Methods:Retrospective analysis was made on 69 EC patients who received CEUS examination and were confirmed by surgery and pathology in Beijing Shijitan Hospital, Capital Medical University from December 2017 to September 2022. According to postoperative pathology, the patients were divided into low-risk group ( n=38) and high-risk group ( n=31). The differences in CEUS, transvaginal ultrasound features and quantitative parameters between the two groups were compared, relevant parameters that with predictive value for high-risk EC were screened, and these parameters were scored. Results:①There were differences in lesion size (thick diameter, long diameter), vascular morphology, and color blood flow score between high and low risk ECs (all P<0.05). ②There were differences in CEUS parameters [perfusion mode, enhancement intensity, area under curve(AUC)] between high and low risk EC groups (all P<0.05). ③The areas under the ROC curve for diagnosing high-risk EC were 0.79, 0.69, 0.69, and 0.62, respectively, based on the critical values of lesion thickness diameter ≥1.85 cm, lesion length diameter ≥2.05 cm, ultrasound contrast quantification parameter AUC ≥859 au, and enhancement intensity ≥29.4 dB. ④Using statistically significant parameters for scoring, the sensitivity and specificity for diagnosing high-risk EC with the score ≥5, were 70.97% and 89.47%, respectively. Conclusions:The combination of CEUS and transvaginal ultrasound is a feasible method for predicting high-risk EC. CEUS parameters (enhanced intensity, AUC, and " focal" perfusion mode) are related to high-risk EC. The combination of CEUS and transvaginal ultrasound helps to pre-evaluate the pathological prognostic factors of endometrial malignant lesions before surgery, providing a basis for clinical follow-up treatment.

Objective:To explore the effects of semaglutide on glucolipid metabolism and bone metabolism in patients with type 2 diabetes mellitus (T2DM).Methods:A total of 96 T2DM patients treated in the Second People′s Hospital of Hefei from May 2022 to May 2023 were divided into the study group (48 cases) and the control group (48 cases) by treatment methods. The patients in the study group were treated with semaglutide, and the patients in the control group were treated with metformin, respectively, they were treated for 12 weeks. The levels of glucolipid metabolism, body mass index (BMI), bone metabolism, serum levels of adipocytokine 13 (apelin-13), feeding inhibitory factor 1 (nesfatin-1) and chemerin were compared between the two groups before and after treatment, and the incidence of adverse reactions was recorded.Results:After treatment, the improvement of glucolipid metabolism index in the study group were better than those in the control group ( P<0.05). After treatment, the BMI in the study group was lower than that in the control group: (24.26 ± 1.08) kg/m 2 vs. (25.40 ± 1.36) kg/m 2, there was statistical difference ( P<0.05). After treatment, the levels of total type Ⅰ collagen amino terminal lengthening peptide (TPINP) and bone gla protein (BGP) in the study group were higher than those in the control group and β C-terminal telopeptide of type Ⅰcollagen (β-CTX) was lower than that in the control group: (48.50 ± 9.27) μg/L vs. (44.85 ± 8.20) μg/L, (20.73 ± 6.34) μg/L vs. (18.05 ± 6.20) μg/L, (0.30 ± 0.10) μg/L vs.(0.36 ± 0.08) μg/L, there were statistical differences ( P< 0.05). After treatment, the levels of serum apelin-13 in the study group was higher than that in the control group, while the levels of nesfatin-1 and chemerin were lower than those in the control group: (1 500.43 ± 153.36) ng/L vs. (1 350.24 ± 142.30) ng/L, (3.06 ± 0.65) μg/L vs. (3.75 ± 0.78) μg/L, (9.85 ± 2.46) μg/L vs. (11.37 ± 2.34) μg/L, there were statistical differences ( P<0.05). The incidence of adverse reactions between the two groups had no statistical difference ( P>0.05). Conclusions:Semaglutide can significantly improve glucolipid metabolism, bone metabolism, decrease BMI, nesfatin-1 and chemerin levels, and increase apelin-13 level in T2DM patients.

The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer.Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis(YTE-17),attributing these effects to the regu-lation of multiple signaling pathways.However,knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited.In this study,we conducted isobaric tags for relative and absolute quantification(iTRAQ)analysis on intestinal epithelial cells(IECs)exposed YTE-17,both in vitro and in vivo,revealing a significant inhibition of the Wnt family member 5a(Wnt5a)/c-Jun N-terminal kinase(JNK)signaling pathway.Subsequently,we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment(TME),specifically focusing on macrophage-mediated T helper 17(Th17)cell induction in a colitis-associated cancer(CAC)model with Wnt5a deletion.Additionally,we performed the single-cell RNA sequencing(scRNA-seq)on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition,lineage,and functional status of immune mesenchymal cells during different stages of colorectal cancer(CRC)progression.Remarkably,our findings demon-strate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17,leading to the restoration of regulatory T(Treg)/Th17 cell balance in azoxymethane(AOM)/dextran sodium sulfate(DSS)model.Furthermore,we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages.Notably,our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical β-catenin oncogenic pathway in vivo.Specifically,we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with β-catenin activity within the TME,involving macrophages and T cells.In summary,our study undergoes the po-tential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment,thereby mitigating the risk of malignancies.

Objective:To analyze changes in energy metabolism and oxylipin metabolism in macrophages after stimulation by Mycobacterium marinum ( M. marinum) using targeted metabolomics, and to provide insights into the mechanisms underlying the immune defense by macrophages against M. marinum infections. Methods:Mouse bone marrow-derived macrophages were obtained from the bilateral femurs of mice, and cultured cells were divided into two groups: the active M. marinum group and the inactivated M. marinum group. Bacterial suspensions were prepared using M. marinum clinical isolates; the active M. marinum group was treated with live M. marinum suspensions for 12 hours, while the inactivated M. marinum group with inactivated M. marinum suspensions for 12 hours. Cell morphology was observed through microscopy, and cell length was measured. Cell lysates collected from both groups were subjected to liquid chromatography-tandem mass spectrometry analysis to detect energy and oxylipin metabolites. A t-test was utilized to compare the lengths of macrophages between the two groups, while principal component analysis and orthogonal partial least squares-discriminant analysis were conducted to identify differential metabolites. Results:Under the microscope, macrophages in the active M. marinum group formed more granuloma-like cell aggregates compared with those in the inactivated M. marinum group; the macrophages were significantly thinner and longer in the inactivated M. marinum group (439.52 ± 91.67 μm) than in the active M. marinum group (289.96 ± 70.11 μm, P < 0.001). Principal component analysis and orthogonal partial least squares-discriminant analysis of energy metabolism and oxylipin metabolism in macrophages demonstrated good separation between the two groups. As for the energy metabolism, a total of 12 differential metabolites were identified, with the amino acid metabolism showing the most significant changes. Specifically, there was a significant increase in the content of L-citrulline, while the content of L-leucine and serine decreased. As for the oxylipin metabolism, 20 differential metabolites were identified, with the arachidonic acid metabolism showing the most significant changes. Conclusions:Macrophages stimulated by live M. marinum exhibited altered amino acid metabolism and arachidonic acid metabolism compared with those stimulated by inactivated M. marinum, characterized by an increase in L-citrulline content, a decrease in L-leucine and serine levels, and alterations in arachidonic acid content.

During the development of therapeutic microRNAs (miRNAs or miRs), it is essential to define their pharmacological actions. Rather, miRNA research and therapy mainly use miRNA mimics synthesized in vitro. After experimental screening of unique recombinant miRNAs produced in vivo, three lead antiproliferative miRNAs against human NSCLC cells, miR-22-3p, miR-9-5p, and miR-218-5p, were revealed to target folate metabolism by bioinformatic analyses. Recombinant miR-22-3p, miR-9-5p, and miR-218-5p were shown to regulate key folate metabolic enzymes to inhibit folate metabolism and subsequently alter amino acid metabolome in NSCLC A549 and H1975 cells. Isotope tracing studies further confirmed the disruption of one-carbon transfer from serine to folate metabolites by all three miRNAs, inhibition of glucose uptake by miR-22-3p, and reduction of serine biosynthesis from glucose by miR-9-5p and -218-5p in NSCLC cells. With greater activities to interrupt NSCLC cell respiration, glycolysis, and colony formation than miR-9-5p and -218-5p, recombinant miR-22-3p was effective to reduce tumor growth in two NSCLC patient-derived xenograft mouse models without causing any toxicity. These results establish a common antifolate mechanism and differential actions on glucose uptake and metabolism for three lead anticancer miRNAs as well as antitumor efficacy for miR-22-3p nanomedicine, which shall provide insight into developing antimetabolite RNA therapies.

Depression is one of the most common mental disorders, which can be accompanied by cognitive symptoms in addition to core symptoms.With the improvement of the awareness of the disease, people pay more attention to the cognitive symptoms of depression. The cognitive impairment of patients not only appears in the onset of the disease, but also persists during the remission of the disease, which has a negative impact on the patients’ social function. Some cognitive assessment tools such as cognitive tests, event-related potential(ERP) and eye movement tracking technology have been used to assess cognitive impairment in patients with depression, which show that there are multidimensional cognitive impairments. Some therapeutic methods such as exercise therapy, repetitive transcranial magnetic stimulation(rTMS) and drug therapy have shown the potential to improve the cognitive function of patients with depression. This article reviews related researches in recent years to explore the cognitive impairment and therapeutic methods of patients with depression.