Objective To explore the potential causal relationship between 91 inflammatory factors and the risk of lung cancer (LC). Methods By extracting related data of inflammatory factors and LC and its subtypes from public databases of Genome-wide Association Studies (GWAS), bidirectional, repeated, multivariable Mendelian randomization (MR) and subgroup MR methods were used for analysis. The inverse variance weighted method was mainly used for causal inference, and a series of sensitivity analyses were applied to verify the strength of the results. Results Higher levels of CD5, interleukin-18 (IL-18), and oncostatin-M (OSM) were causally associated with a lower risk of LC, while nerve growth factor-β (NGF-β) and S100 calcium-binding protein A12 (S100A12) were associated with an increased risk of LC. Subgroup MR analysis results showed that IL-18 had a causal relationship with a reduced risk of lung adenocarcinoma, while NGF-β and S100A12 had a causal relationship with an increased risk of lung adenocarcinoma; CD5 and OSM had a causal relationship with a reduced risk of lung squamous cell carcinoma; NGF-β had a causal relationship with an increased risk of small cell lung cancer. Conclusion Five inflammatory factors, including CD5, IL-18, OSM, NGF-β, and S100A12 have a causal correlation with the risk of LC, providing potential targets for early screening of LC patients and development of therapeutic drugs.

OBJECTIVE: To explore the serological and molecular genetic characteristics of a family with subtype B(A)06. METHODS: A neonatal hyperbilirubinemia patient who was treated at Henan Children's Hospital on June 15, 2023 due to "yellowing of the skin and gradual aggravation", and was found to have inconsistent ABO forward and reverse typing through blood type testing, was selected as the research subject. Six milliliters of peripheral blood were collected from the newborn and her family members (grandfather, grandmother, father, mother and aunt) respectively. ABO blood group identification was performed by the blood group serological method. Human genomic DNA was extracted using the nucleic acid extraction or purification reagent BT-01. ABO gene exons 2 to 7 were amplified by PCR. The PCR-specific products that were successfully amplified were sequenced by Sanger method. Taking ABO*A1.01 as the reference sequence, the ABO gene sequences of the newborn and her family members were analyzed to determine the ABO genotype. The procedures followed in this study were approved by the Ethics Committee of Henan Children's Hospital (Ethics No.: 2022-K-L036). RESULTS: The serological results of ABO blood group showed that the newborn, her grandfather, father and aunt were all incompatible with the forward and reverse typing. The blood group phenotype of the newborn was AwB or B(A), the blood group phenotype of the grandfather was A2B or B(A), the blood group phenotype of the father and aunt were A2B, and the blood group phenotype of the grandmother and mother were both O. The screening test results of hemolytic disease of the newborn showed that the free test detected IgG anti-A1 antibody, while the elution test, direct antiglobulin test and antibody screening results were all negative. The Sanger sequencing results showed that the newborn had variations of c.261delG, c.297A>G, c.526C>G, c.657C>T, c.703G>A, c.796C>A and c.930G>A. Her grandfather had variations of c.297A>G, C.526C>G, c.657C>T, c.703G>A, c.796C>A, c.803G>C and c.930G>A. Her grandmother had variations of c.106G>T, c.188G>A, c.189C>T, c.220C>T, c.261delG, c.297A>G, c.646T>A, c.681G>A, c.771C>T and c.829G>A. Her father and aunt had variations of c.106G>T, c.188G>A, c.189C>T, c.220C>T, c.261delG, c.297A>G, c.526C>G, c.646T>A, c.657C>T, c.681G>A, c.703G>A, c.771C>T, c.796C>A, c.829G>A and c.930G>A. Her mother had variations of c.106G>T, c.188G>A, c.189C>T, c.220C>T, c.261delG, c.297A>G, c.646T>A, c.681G>A, c.771C>T, and c.829G>A.The genotype of the newborn was ABO*BA.06/ABO*O.01.01, her grandfather was ABO*BA.06/ABO*B.01, her grandmother was ABO*O.01.02/ABO*O.01.02, her father and aunt were ABO*BA.06/ABO*O.01.02, and her mother was ABO*O.01.01/ABO*O.01.02. The ABO*BA.06 allele of the newborn, grandfather, father and aunt was caused by the c.803C>G variation in exon 7 based on the ABO*B.01 allele. The ABO*BA.06 allele can be stably inherited in this family. CONCLUSION The blood type of neonatal patients with B(A)06 subtype can be accurately determined by gene sequencing technology. If the forward typing is ≤ 3+ agglutination intensity in newborn ABO blood group identification, the reason should be carefully analyzed, and the molecular biology technology and family gene sequencing results should be used to jointly determine if necessary.
Humans ; ABO Blood-Group System/genetics* ; Female ; Pedigree ; Male ; Infant, Newborn ; Asian People/genetics* ; Genotype ; China ; Blood Grouping and Crossmatching ; Hyperbilirubinemia, Neonatal/blood* ; East Asian People

To analyze the clinical and genetic features of oculopharyngodistal myopathy (OPDM) patients and compare the phenotypic differences among various causative genes.

AIM:This study explores whether curcumin(Cur)promotes mitophagy to attenuate nonalcoholic steatohepatitis(NASH)in mice,as well as the possible molecular mechanisms involved.METHODS:A high-fat and high-cholesterol diet was used to replicate the NASH mouse model.Thirty-two male C57BL/6J mice were randomly divided into normal control(NC)group,high-fat and high-cholesterol model(M)group,M+low-dose Cur(Cur-L)group,and M+high-dose Cur(Cur-H)group,with 8 mice in each group.The weight of 8 mice in each group was recorded weekly.After feeding for 18 weeks,the serum and liver of mice were collected.Serum levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein(LDL-C),alanine aminotransferase(ALT),aspartate aminotransferase(AST),and tumor necrosis factors-α(TNF-α)were measured.Liver index was calculated,and steatosis,inflammation,and fibrosis of the liver were observed by HE and Masson staining.Western blot analysis was performed to detect the protein expression of mi-tophagy-related protein,TNF-α and α-SMA in the liver.(2)HepG2 cells were treated with oleic acid and cholesterol to replicate the hepatocyte injury model,which was divided into NC group,Cur group,M group,and M+Cur group.Small interfering RNA for PTEN-induced kinase 1(PINK1)knockdown was used to explore the relationship between PINK1-me-diated mitophagy and NASH.Compound C(CC)was used to inhibit AMP-activated protein kinase(AMPK)to explore the effect of the AMPK/silent information regulator 1(Sirt1)pathway on mitophagy.The lipid droplets of HepG2 cells were ob-served by oil red O staining,and the levels of TC,TG,LDL-C,ALT,and AST in cell suspension were detected.RE-SULTS:(1)Compared with M group,treatment with Cur significantly reduced the body weight,liver coefficient,and se-rum levels of TC,TG,LDL-C,ALT,AST,and TNF-α in NASH mice,while the steatosis and fibrosis in the liver were improved(P<0.05).(2)Different concentrations of Cur could increase or decrease the expression of mitophagy-related proteins in HepG2 cells in a concentration gradient.Compared with the M group,Cur reduced lipid droplets and de-creased TC,TG,LDL-C,ALT,and AST levels(P<0.05).(3)Compared with the NC group,the expression levels of mi-tophagy-related proteins in the liver of mice in the M group decreased,and the expression levels of TNF-α and α-SMA pro-teins increased.Different concentrations of Cur intervention promoted the increase of mitophagy-related proteins and the decrease of TNF-α and α-SMA proteins(P<0.05).(4)After Cur intervention,the expression levels of mitophagy-related proteins increased and the expression levels of in TNF-α and α-SMA levels decreased in HepG2 cells induced by oleic acid and cholesterol(P<0.05).(5)Compared with M group,oleic-acidand cholesterol-induced mitophagy function in HepG2 cells was decreased after PINK1 knockdown(P<0.05).After CC inhibited AMPK,Cur increased the expression of p-AMPK(P<0.01),Sirt1(P<0.01),peroxisome proliferator-activated receptor γ coactivator-1α(P>0.05),PINK1(P<0.01)and parkin(P<0.01)proteins to some extent.CONCLUSION:Treatment with Cur attenuates liver injury in NASH mice and reduces lipid accumulation in HepG2 cells induced by oleic acid and cholesterol,and the mechanism may be related to promotion of mitophagy,which may involve the AMPK/Sirt1 signaling pathway.

Objective:To investigate the clinicopathological characteristics and prognostic factors of biliary neuroendocrine neoplasms (NENs).Methods:The retrospective cohort study was conducted. The clinicopathological data of 36 patients who underwent surgical treatment for biliary NENs at The First Hospital of Jilin University from January 2013 to December 2023 were collected. There were 22 males and 14 females, aged (59±9)years. Observation indicators: (1) clinicopatholo-gical characteristics of patients; (2) follow-up; (3) prognostic factors analysis of patients. Compari-son of measurement data with normal distribution among multiple groups was conducted using the ANOVA. Comparison of measurement data with skewed distribution among multiple groups was conducted using the Kruskal-Wallis H test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. The Kaplan-Meier method was used to calculate survival rate and plot survival curve, and Log-rank test was used for survival analysis. The Cox risk regression model was used for univariate and multivariate analyses. Results:(1) Clinicopatholo-gical characteristics of patients. None of the 36 patients with biliary NENs had carcinoid syndrome. There were 11 cases with tumor located at gallbladder, 14 cases with tumor located at bile duct, and 11 cases with tumor located at ampulla of Vater. There were significant differences in weight loss and TNM stage among biliary NENs patients with different tumor location ( χ2=9.14, 6.54, P<0.05). Of the 36 patients, there were 12 cases with neuroendocrine tumors, 16 cases with neuroendocrine carcinomas, and 8 cases with mixed neuroendocrine-non-neuroendocrine neoplasms. (2) Follow-up. All 36 patients were followed up for 39(range, 10-93)months. Of the 36 patients, 19 patients experienced tumor recurrence and 16 patients experienced tumor metastasis. There were 18 patients died. The median overall survival time of 36 patients was 30 months, with the 1-, 2-, 3-year overall survival rates of 63.9%, 51.0%, and 35.7%, respectively. The 1-, 2-, 3-year recurrence-free survival rates were 47.5%, 34.1% and 21.3%, respectively. The 1-, 2-, 3-year overall survival rates of 19 patients with tumor recurrence were 55.6%, 55.6% and 27.8%, respectively. The 1-, 2-, 3-year overall survival rates of 17 patients without tumor recurrence were 71.3%, 50.4% and 42.0%, respectively. There was no significant difference in overall survival between patients with and without tumor recurrence ( χ2=0.24, P>0.05). (3) Prognostic factors analysis of patients. Results of multivariate analysis showed that pathological type as neuroendocrine carcinomas and mixed neuroendocrine-non-neuroendocrine neoplasms, non-R 0 margin were independent risk factors influencing overall survival time of patients ( hazard ratio=5.50, 5.33, 14.04, 95% confidence interval as 1.32-23.01, 1.17-24.35, 2.67-73.79, P<0.05). Conclusions:Biliary NENs lack specific clinical manifestations. Poorly differentiated neuroendocrine carcinomas are the most common pathological type. Pathological type as neuroendocrine carcinomas and mixed neuroendocrine-non-neuroendocrine neoplasms, non-R 0 margin are independent risk factors influencing prognosis of patients.

Objective To explore function-structure covariant patterns in Alzheimer's disease(AD)and mild cognitive impairment(MCI),and to investigate their associations with cognitive function and activities of daily living.Methods three-way parallel group independent component analysis(three-way pGICA),was used to identify the covariant patterns of resting-state functional MRI temporal data,gray matter density maps,and fractional anisotropy(FA)maps,and the differences between different groups were compared.Furthermore,the associations of covariant patterns with the Montreal Cognitive Assessment-Basic(MoCA_B)Scale scores and Activities of Daily Living Scale scores were analyzed.Results The function-structure covariant patterns in AD and MCI were characterized by the enhanced negative functional connectivity between the left posterior salience network and the right default mode network,the decreased gray matter density in the bilateral dorsolateral prefrontal cortex,and the reduced FA values in the left superior corona radiata(correlations:P<0.001,FDR corrected).Compared with HC group,AD group showed significant abnormalities in all identified covariant patterns(P<0.01,FDR corrected),but MCI group only exhibited a significant decrease in gray matter density in the bilateral dorsolateral prefrontal cortex(P<0.05,FDR corrected).Additionally,AD group had significantly lower FA value in the left superior corona radiata than MCI group(P<0.05,FDR corrected).The loadings reflecting the degree of covariation were significantly correlated with the Activities of Daily Living Scale scores(P<0.05,FDR corrected)but not with MoCA_B Scale scores.Conclusion The function-structure covariant patterns in AD and MCI are consistent with the declines in activities of daily living.The multimodal fusion analysis(three-way pGICA)provides a novel approach to understand the brain damage mechanisms underlying the covariant evolution of MCI and AD.

Objective:To establish normal reference value ranges for dynamic balance function parameters in healthy Chinese adults aged 20-69 years. Methods:A total of 100 healthy subjects were selected and evenly divided into five age groups: 20-29, 30-39, 40-49, 50-59, and 60-69 years, with equal gender distribution in each group. Balance function was assessed using the EquiTest system （NeuroCom）, with following tests performed Sensory Organization Test （SOT）, Motor Control Test （MCT）, Adaptation Test （ADT）, and Limits of Stability （LOS） test. All parameters were statistically analyzed and expressed as ±S. Results:The normal reference ranges for SOT, MCT, ADT, and LOS parameters were established for each age group. Multiple balance function parameters demonstrated a gradual decline with advancing age, with more pronounced deterioration observed after the age of 60. Specific findings included decreased vestibular ratio and reduced visual preference in SOT, as well as prolonged reaction time, impaired directional control, and reduced maximum excursion in the backward direction during LOS testing. Conclusion:This study is the first to establish age-specific reference ranges for dynamic balance function parameters in a healthy Chinese population aged 20-69 years, providing localized and objective criteria for the assessment of balance function and supporting clinical diagnosis of balance-related disorders in China.
Humans ; Middle Aged ; Adult ; Postural Balance/physiology* ; Reference Values ; Aged ; Male ; Female ; Young Adult ; Healthy Volunteers

Objective To investigate alterations in interhemispheric functional connectivity(FC)in the cerebral cortices connected via the corpus callosum in patients with Alzheimer's disease(AD),and to explore their relationships with cognitive function and activities of daily living.Methods Resting-state functional magnetic resonance imaging data were collected from 28 patients with Alzheimer's dementia(d-AD),47 patients with mild cognitive impairment(MCI),and 37 healthy controls(HC).Using a trancallosal tract template,32 pairs of homologous cortical brain regions directly connected to 32 subregions of the corpus callosum were selected as regions of interest for interhemispheric FC analysis.Further correlation analyses were performed between FC values in patient groups and their scores on the Montreal Cognitive Assessment-Basic(MoCA-B)Scale and the Activities of Daily Living(ADL)Scale.Results Compared with HC group,both MCI and d-AD groups exhibited hyperconnectivity(significantly increased FC)in interhemispheric non-homologous brain regions.Specifically,hyperconnectivity in the MCI group was scattered across the frontal,parietal,temporal,and occipital lobes,while in the d-AD group,it was concentrated within the precentral and postcentral gyri.Notably,hyperconnectivity involving the prefrontal and occipital lobes in the MCI group showed significant declines in the d-AD group.The interhemispheric homologous FC in the d-AD group reduced more significantly than the MCI group.Additionally,in the d-AD group,2 interhemispheric FC within the prefrontal lobe(between the bilateral orbital parts of the inferior frontal gyrus,and between the left medial frontal gyrus and the right middle frontal gyrus)were correlated with MoCA-B scores,and 2 FC(between the bilateral middle occipital gyri,and between the left inferior parietal lobule and the right middle frontal gyrus)were correlated with ADL scores.Conclusion MCI and d-AD exhibit distinct patterns of interhemispheric FC alterations,and the interhemispheric FC changes in AD patients are non-progressive.The close relationships between interhemispheric homologous/non-homologous FC and MoCA-B/ADL scores in d-AD patients provide an objective basis and reference for clinical neuromodulation.

[Objective] To perform genetic analysis on samples with weak agglutination and mixed agglutination of ABO blood group antigens in neonates, and to investigate the molecular biological characteristics of ABO subtypes in neonates. [Methods] Serological identification of ABO blood group was performed by tube method and microcolumn gel method. The ABO exons 2-7 were amplified by PCR, and the amplified products were sequenced by Sanger sequencing method to determine the genotype. [Results] Among the ABO blood group serological results of 14 neonates, 8 cases showed weakened A antigen, and 6 cases showed weakened B antigen. Seven samples were identified with ABO subtype alleles, with genotypes as A102/B101+c.538C>T, Aw26/B102, A205/O02, A205/B101(2 cases), Aw26/O02, B(A)06/O01, B101/O01(3 cases), A102/O01(2 cases), A102/B101 and B101/O02. Additionally, three other family members were also found to carry B(A)06 allele in a pedigree investigation. [Conclusion] For samples showing weakened antigens in ABO blood type identification of neonates, it is necessary to consider the possibility of ABO subtype in addition to age factors, and genetic testing can be used to prevent missed detection of ABO subtypes in neonates.

Objective To isolate pathogenic bacteria from the skin of a nude mouse exhibiting squamous skin scurfs, and perform bacterial identification, traceability analysis, and pathogenicity studies to provide a new approach for the diagnosis of pathogens in nude mice with squamous skin scurfs. MethodsSkin swab samples were collected from a nude mouse exhibiting squamous skin scurfs for nucleic acid testing, bacterial isolation and culture, biochemical identification, 16S rDNA gene amplification and sequencing, and whole genome sequencing to construct a phylogenetic tree. Fifteen BALB/c nude mice were randomized into a saline-treated control group, a high-concentration group treated with 1.8×10⁸ CFU/mL of the isolated bacterial suspension, and a low-concentration group treated with 1.8×10⁷ CFU/mL of the isolated bacterial suspension. Pathogenicity was assessed by animal infection experiments and observation of histopathological changes in skin tissue using HE staining. Results The nucleic acid test for Corynebacterium bovis was negative, excluding infection by this organism. The pathogen isolated on mannitol salt agar and blood agar, combined with Gram staining, suggested a Gram-positive Staphylococcus species. The isolated strain was identified by 16S rDNA sequencing and a fully automated microbial identification system as Staphylococcus xylosus. Phylogenetic tree analysis based on whole genome sequencing showed that the strain was most closely related to an isolate from leafy vegetables in South Korea (GenBank GCA_00207825.1). In the high-concentration group, squamous skin scurfs appeared on the head, neck, and back of nude mice on the 17th day post-infection, while in the low concentration group, similar symptoms appeared on the 20th day post-infection and gradually spread to other areas. The scaling symptoms were transient, lasting for 7 days in the high-concentration group and 3 days in the low-concentration group, after which the skin returned to normal. The infection rate was 33.33% in both the high- and low-concentration groups. No significant pathological changes were observed in the skin tissues of infected mice compared to the control group, indicating marked individual differences in the pathogenicity of the strain in nude mice. Conclusion A strain of Staphylococcus xylosus was isolated from the skin of a nude mouse exhibiting squamous skin scurfs. The strain is an opportunistic pathogen that causes transient squamous skin scurfs without significant histopathological changes, and there are individual differences in the sensitivity of nude mice to this strain. These findings can provide valuable data for pathogen identification in immunodeficient or gene knockout mice.