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.

The ambiguity of etiology makes temporomandibular joint osteoarthritis (TMJOA) "difficult-to-treat". Emerging evidence underscores the therapeutic promise of exosomes in osteoarthritis management. Nonetheless, challenges such as low yields and insignificant efficacy of current exosome therapies necessitate significant advances. Addressing lower strontium (Sr) levels in arthritic synovial microenvironment, we studied the effect of Sr element on exosomes and miRNA selectively loading in synovial mesenchymal stem cells (SMSCs). Here, we developed an optimized system that boosts the yield of SMSC-derived exosomes (SMSC-EXOs) and improves their miRNA profiles with an elevated proportion of beneficial miRNAs, while reducing harmful ones by pretreating SMSCs with Sr. Compared to untreated SMSC-EXOs, Sr-pretreated SMSC-derived exosomes (Sr-SMSC-EXOs) demonstrated superior therapeutic efficacy by mitigating chondrocyte ferroptosis and reducing osteoclast-mediated joint pain in TMJOA. Our results illustrate Alix's crucial role in Sr-triggered miRNA loading, identifying miR-143-3p as a key anti-TMJOA exosomal component. Interestingly, this system is specifically oriented towards synovium-derived stem cells. The insight into trace element-driven, site-specific miRNA selectively loading in SMSC-EXOs proposes a promising therapeutic enhancement strategy for TMJOA.
MicroRNAs/metabolism* ; Mesenchymal Stem Cells/drug effects* ; Osteoarthritis/drug therapy* ; Exosomes/drug effects* ; Strontium/pharmacology* ; Synovial Membrane/cytology* ; Humans ; Animals ; Temporomandibular Joint Disorders/therapy* ; Temporomandibular Joint

OBJECTIVE: To observe change in serum growth differentiation factor 11 (GDF11) and killer cell lectin-like receptor B1 (KLRB1), to construct a nomogram model for 28-day death in patients with septic shock, and to explore its predictive value. METHODS: A prospective observational study was conducted. The patients with septic shock admitted to the emergency intensive care unit (ICU) of Cangzhou Central Hospital from September 2023 to March 2025 were selected as the septic shock group, the patients with sepsis admitted to the emergency general ward during the same period were selected as the sepsis group, and healthy individuals undergoing physical examination during the same period were selected as the control group. On the day of hospital admission or physical examination for the research subjects, the levels of serum GDF11 and KLRB1 were detected by enzyme-linked immunosorbent assay (ELISA). The patients with septic shock were divided into survival and death groups based on their 28-day survival status. The patients' gender, age, past medical history, infection site, severity of illness, mechanical ventilation, blood purification, infection indicators, biochemical indicators, coagulation function indicators, and blood lactic acid (Lac) were collected. The clinical data of the patients with septic shock between the two groups with different prognoses were compared. Multivariate Logistic regression analysis was used to screen the risk factors for 28-day death in patients with septic shock, and bivariate Pearson correlation analysis was conducted. A nomogram model was constructed based on the risk factors for 28-day death in patients with septic shock. The discrimination and calibration of the nomogram model were evaluated using the receiver operator characteristic curve (ROC curve), Hosmer-Lemeshow goodness-of-fit test, and calibration curve. The clinical utility of the model was evaluated using clinical decision curve analysis (DCA). RESULTS: A total of 168 patients in the emergency ICU were enrolled in the septic shock group, 40 patients in the emergency general ward were enrolled in the sepsis group, and 40 healthy individuals were enrolled in the control group. Compared with the healthy control group, the serum GDF11 levels in the sepsis and septic shock groups were significantly increased (μg/L: 13.09±3.51, 19.28±5.36 vs. 4.17±0.92, both P < 0.05), and the serum KLRB1 levels were significantly decreased (ng/L: 57.36±11.28, 45.52±9.07 vs. 84.19±17.16, both P < 0.05), with more significant changes in the septic shock group (both P < 0.05). Among the 168 patients with septic shock, 96 survived and 72 died within 28 days. Compared with the survival group, the serum GDF11 level in the death group was significantly increased (μg/L: 24.24±4.81 vs. 15.56±4.62, P < 0.05), and the serum KLRB1 level was significantly decreased (ng/L: 28.53±8.69 vs. 58.26±9.45, P < 0.05). There were also statistically significant differences in sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation II (APACHEII) score, procalcitonin (PCT), activated partial thromboplastin time (APTT), D-dimer, and Lac between the two groups. Multivariate Logistic regression analysis showed that SOFA score [odds ratio (OR) = 1.96, 95% confidence interval (95%CI) was 1.38-3.65), Lac (OR = 1.38, 95%CI was 1.09-2.01), GDF11 (OR = 1.54, 95%CI was 1.21-2.33) and KLRB1 (OR = 0.64, 95%CI was 0.41-0.78) were independent risk factors for 28-day death in patients with septic shock (all P < 0.05). Bivariate Pearson correlation analysis showed that SOFA score was significantly positively correlated with Lac and GDF11 (r value was 0.37 and 0.58, respectively, both P < 0.05), and significantly negatively correlated with KLRB1 (r = -0.72, P < 0.05). A nomogram model was constructed based on the risk factors for 28-day death in patients with septic shock. ROC curve analysis showed that the area under the ROC curve (AUC) of the nomogram model for predicting 28-day death in patients with septic shock was 0.963 (95%CI was 0.929-0.990), indicating that the model had good discrimination and predictive ability. The Hosmer-Lemeshow goodness-of-fit test (χ ² = 9.578, P = 0.295) and calibration curve indicated that the predicted values of the model were in good agreement with the actual values. DCA indicated that the model provided a high net benefit for clinical decision-making. CONCLUSIONS The serum GDF11 level was significantly increased and the KLRB1 level was significantly decreased in patients with septic shock. The nomogram model based on GDF11 and KLRB1 could more accurately evaluate the 28-day death of patients with septic shock.
Humans ; Shock, Septic/blood* ; Nomograms ; Prospective Studies ; Prognosis ; Male ; Female ; Middle Aged ; Aged ; Intensive Care Units

ObjectiveTo investigate the association of the polymorphisms of the acetyl-CoA acetyltransferase 1 （ACAT1） gene and the melatonin receptor 1B （MTNR1B） gene with the susceptibility to nonalcoholic fatty liver disease （NAFLD）. MethodsA total of 164 healthy controls and 228 NAFLD patients were enrolled in this study. PCR and sequencing methods were used to determine the genotypes of the polymorphisms of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus， and fasting venous blood samples were collected for biochemical analysis. The t-test was used for comparison of normally distributed continuous data between groups， and the non-parametric Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups； the chi-square test was used for comparison of categorical data between groups. ResultsThere were no significant differences between the NAFLD group and the healthy control group in the genotype distribution of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus （all P>0.05）. The carriers of AA genotype at the rs1044925 locus of the ACAT1 gene had a significantly higher level of low-density lipoprotein than the carriers of C allele （Z=-2.08， P=0.04）， and the carriers of G allele at the rs10830963 locus of the MTNR1B gene had a significantly higher level of fasting blood glucose than the carriers of CC genotype （Z=-3.01， P<0.01）. ConclusionThe polymorphisms of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus were not associated with the susceptibility to NAFLD. The rs1044925 locus of the ACAT1 gene and the rs10830963 locus of the MTNR1B gene are associated with the levels of low-density lipoprotein and fasting blood glucose， respectively.

Objective: To explore the effects of group sports game intervention on social ability and quality of life of children with austism spectrum disorders (ASD),so as to provide reference for rehabilitation intervention of social and quality of life of children with ASD. Methods: From September 2021 to January 2022, 72 children with ASD aged 4-6 in the children s rehabilitation department of Xiangyang Central Hospital were selected to participate in the study, and were randomly divided into experimental group ( n =36) and control group ( n =36). The control group received routine rehabilitation training (including individual sports game training), and the experimental group replaced individual sports game training with group sports game training on the basis of routine rehabilitation.The course content mainly included three parts: warm up before class, group sports games and relaxation after class. The course combined social skills with sports games, and was carried out in a group form (divided into 12 groups with 3 people in each group), and was trained five times a week for 60 minutes, for a total of 12 weeks. The scores of Childhood Autism Rating Scale (CARS), Autism Treatment Evaluation Checklist (ATEC), Social Responsiveness Scale (SRS) and Pediatric Quality of Life Inventory Version 4.0 Generic Core Scales (PedsQL 4.0) were observed before and after treatment. t-test and χ 2 test were used for statistical analysis. Results: There was no significant difference in SRS scores between the experimental group and the control group before intervention ( t =-0.63, P >0.05). After the intervention, the total response rate in the experimental group was 83.33 %, higher than 41.67% in the control group χ 2=13.33, P <0.05),and the SRS scores decreased in the experimental group and control group ( t =17.75,8.71, P <0.05). The SRS scale score of the experimental group Social perception (17.67±4.12) , social cognition (30.33±4.99) , social communication (50.33±9.39) , social motivation (24.25±6.78) scores and total scores ( 152.67± 25.82) were lower than those of the control group(22.17±5.34，36.00±4.13，62.58±11.07，34.42±7.13，186.33±29.03)( t = -4.88，-2.03，-2.13，-3.58，-3.01， P ＜0.05).After the intervention, the scores of social function (53.33±18.01) and total score (283.83±51.83) on PedsQL 4.0 scale in experimental group were higher than those in control group(23.33±15.13，218.00±39.01) ( t =4.42，3.52， P ＜0.05). After the intervention, Autism Treatment Evaluation Scale (ATEC) scores of experimental groups(44.33±14.72) was lower than that in control group ( 59.33±16.95)( t =-2.32, P ＜0.05). Conclusion The intervention of group sports game has a significant effect on improving social ability and life quality of children with ASD.

Background: s/Aims: Transmembrane 6 superfamily member 2 (TM6SF2) E167K variant is closely associated with the occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the role and mechanism of TM6SF2 E167K variant during MASLD progression are not yet fully understood. Methods: The Tm6sf2167K knock-in (KI) mice were subjected to high-fat diet (HFD). Hepatic lipid levels of Tm6sf2167K KI mice were detected by lipidomics analysis. Thin-layer chromatography (TLC) was used to measure the newly synthesized triglyceride (TG) and phosphatidylcholine (PC). Results: The TM6SF2 E167K variant significantly aggravated hepatic steatosis and injury in HFD-induced mice. Decreased polyunsaturated PC level and increased polyunsaturated TG level were found in liver tissue of HFDinduced Tm6sf2167K KI mice. Mechanistic studies demonstrated that the TM6SF2 E167K variant increased the interaction between TM6SF2 and PNPLA3, and impaired PNPLA3-mediated transfer of polyunsaturated fatty acids (PUFAs) from TG to PC. The TM6SF2 E167K variant increased the level of fatty acid-induced malondialdehyde and reactive oxygen species, and decreased fatty acid-downregulated cell membrane fluidity. Additionally, the TM6SF2 E167K variant decreased the level of hepatic PC containing C18:3, and dietary supplementation of PC containing C18:3 significantly attenuated the TM6SF2 E167K-induced hepatic steatosis and injury in HFD-fed mice. Conclusions The TM6SF2 E167K variant could promote its interaction with PNPLA3 and inhibit PNPLA3-mediated transfer of PUFAs from TG to PC, resulting in the hepatic steatosis and injury during MASLD progression. PC containing C18:3 could act as a potential therapeutic supplement for MASLD patients carrying the TM6SF2 E167K variant.

Objective To investigate the relationship between Fat Mass- and obesity-associated gene (FTO) polymorphisms and the susceptibility of non-alcohol-related fatty liver disease (NAFLD) in a Han population from Qingdao region of China. Methods A total of 119 NAFLD patients were recruited from Qingdao Municipal Hospital and Chengyang District People's Hospital and 187 control individuals who received annual physical examination were also included. Their clinicopathological information and study questionnaire were collected. Their fasting venous blood was extracted for biochemical analyses and FTO polymorphism genotyping using the polymerase chain reaction combined with DNA sequencing. The data were statistically assessed. Results The data showed statistically significant differences in age, BMI, ALT, GGT, TG and Bil between NAFLD patients and normal controls (all P < 0.05). FTO polymorphism genotyping data showed three genotypes of FTO rs1421085 (TT, CT, and CC), rs8050136 (TT, CT, and CC) and rs9939609 (TT, AT, AA). However, there was no statistical difference in both allele frequency and genotype of FTO rs1421085, rs9939609, and rs8050136 between NAFLD and controls (all P > 0.05) and there was also no statistical difference in clinical parameters among these genotype carriers (all P > 0.05). Conclusion NAFLD patients showed significantly statistical differences in age, BMI, ALT, GGT, TG, and BIL vs. those of normal controls. However, this study did not find any association of FTO rs1421085, rs9939609, and rs8050136 polymorphisms with NAFLD susceptibility in this Qingdao region of Han Chinese population.

Objective:To analyze the characteristics and prognosis of hearing loss in children with bacterial meningitis.Methods:This was a single-center retrospective cohort study. Patients diagnosed with bacterial meningitis who were hospitalized in Beijing Children′s Hospital between 2010 and 2016 and older than 28 days and younger than 18 years at symptom onset were included in this study ( n=573). All clinical information including hearing assessment results during hospitalization were reviewed. All patients with hearing loss were followed up to repeat their hearing test and assess their hearing condition with parents′ evaluation of aural and (or) oral performance of children (PEACH). Patients were grouped according to their hearing assessment results, and Logistic regression analysis was used to analyze the risk factors for hearing loss in patients with bacterial meningitis. Results:Five hundred and seventy-three patients were enrolled in this study, including 347 males and 226 females. The onset age ranged from 29 days to 15.8 years. Two hundred and forty-six patients had identified causative pathogens, among whom 92 cases (37.4%) were pneumococcal meningitis cases. Hearing loss was found in 160 cases (27.9%) during hospitalization, involving 240 ears. Permanent hearing loss was found in 20 cases (16.9%), involving 32 ears. In the patients with permanent hearing loss, 87.5% (28/32) of ears were identified as severe or profound hearing loss during hospitalization. Logistic regression analysis showed that dystonia, the protein concentration level in cerebrospinal fluid>1 g/L, glucose concentration level lower than 1 mmol/L and subdural effusion were independent risk factors for hearing loss ( OR=2.426 (1.450-4.059), 1.865 (1.186-2.932), 1.544 (1.002-2.381) and 1.904 (1.291-2.809)). Conclusions:Hearing loss is a common sequela of bacterial meningitis in children. Most patients have transient hearing loss, but patients with severe or profound hearing impairment have a higher risk of developing permanent hearing loss.

Objective:To explore the clinical application value of MRI-PDFF on different liver segments for the evaluation of non-alcoholic fatty liver disease (NAFLD).Methods:178 volunteers from March 2019 to February 2020 were included. PDFF values ??of all nine segments of the liver were measured using CSE3.0T MRI scan. The obtained average value was used to represent the average liver fat content. PDFF values of each or combined liver segment were equally compared with the average value to observe the representativeness of fat content. Receiver operating characteristic curve was used to analyze the diagnostic performance of each liver segment, and the Youden index was used to calculate the cutoff value. Paired-sample t-test or non-parametric Kruskal-Wallis test were used to compare measurement data among groups.Results:178 volunteers average liver fat content ranged from 0.89% to 42.61% with MRI-PDFF, and 71.35% (127/178) of the volunteers had PDFF > 5%. There was no significant difference between SIII, SIVb, SV, and SVIII liver segments when compared with the average value ( P > 0.05). PDFF values ??of SI, SII, and SIV a liver segments were all lower than the average value, while the PDFF values ??of SVI and SVII liver segments were all higher than the average value ( P ??< 0.05). MRI-PDFF sensitivity value for diagnosing liver steatosis of nine liver segments was 85.8% ~ 94.5%, and the specificity was higher than 96.0%. Among them, the SV liver segment had the highest sensitivity (94.5%), and the corresponding optimal diagnostic threshold value was 5.13%. Compared with single and combined liver segment, the PDFF value of SII, SV, SVI combined liver segment had the highest diagnostic performance for fatty liver, with the sensitivity and specificity of 96.9%, and 100%, respectively, and the corresponding optimal diagnostic threshold value was 5.17%. Conclusion:Compared with single and other combined liver segments, MRI-PDFF values of SII, SV, and SVI combined liver segments have higher sensitivity and specificity for the diagnosis of NAFLD, and it can be used as the first choice for the determination of liver fat content with MRI.

Objective To investigate whether there was a correlation between serum liver enzyme levels and blood pressure in the Chinese Han population with nonalcoholic fatty liver disease (NAFLD) in Shandong coastal regions in China. Methods A total of 269 NAFLD patients who lived in Shandong coastal regions and attended or underwent physical examination in Qingdao Municipal Hospital from December 2019 to June 2020 were enrolled, among whom 105 had hypertension and 164 did not have hypertension. Morning blood pressure was measured to calculate mean arterial pressure (MAP), and laboratory tests were performed to measure the serum levels of liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), and alkaline phosphatase (ALP)] and fasting blood glucose (FBG). The independent samples t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. A Pearson correlation analysis was used to investigate the correlation of four liver enzymes with the indices including MAP, and a binary logistic regression model was used to analyze the impact of serum liver enzymes on hypertension. Results Compared with the non-hypertension group, the hypertension group had significantly higher body mass index (BMI), MAP, and GGT (all P < 0.05). For all NAFLD patients and the NAFLD patients without hypertension, male patients had significantly higher BMI, MAP, ALT, AST, and GGT than female patients (all P < 0.05), and for the NAFLD patients with hypertension, male patients had a significantly higher level of GGT than female patients ( P < 0.05). There was a significant difference in the distribution of GGT between the hypertension group and the non-hypertension group, and compared with the non-hypertension group, the hypertension group had a significantly higher proportion of patients with GGT exceeding the normal range ( χ 2 =4.781, P =0.029). Serum GGT level was correlated with MAP within the normal range (70-105 mm Hg) ( r =0.178, P =0.011), while there was no significant correlation when MAP exceeded the normal range ( P =0.415). After adjustment for age and sex, the binary logistic regression model showed that AST level was positively associated with hypertension in the population with NAFLD (odds ratio [ OR ]=1.011, 95% confidence interval [ CI ]: 1.000-1.022, P =0.040), and after further adjustment for BMI and FBG, the results showed that AST level was still positively associated with hypertension ( OR =1.011, 95% CI : 1.000-1.022, P =0.044). Conclusion In Chinese Han population with NAFLD in Shandong coastal regions, higher levels of AST may predict an increased risk of hypertension.