Objective: To explore the longitudinal associations between dietary macronutrients and lung function in schoolaged children, so as to provide the nutritional research evidence for promoting children s lung health. Methods: In November 2021, two primary schools located in Chengdu, Sichuan Province were selected from the Southwest China Childhood Nutrition and Growth (SCCNG) cohort by a stratified cluster random sampling method, enrolling a total of 1 112 school aged children aged 8 to 13 years. At baseline, the dietary and sociodemographic characteristics of the children were assessed. One year later, the forced vital capacity (FVC) of the children was measured and converted into Z scores (FVC- Z ), while the vital capacity index (VCI) was also calculated. Generalized linear regression analysis was employed to examine the associations between dietary macronutrients and lung function, considering interactions with gender and age, followed by stratified analysis. Results: After adjusting for confounding factors, the analysis results of the generalized linear regression model showed that the carbohydrate energy ratio was negatively correlated with FVC- Z ( β =-0.02) and VCI ( β =-0.16), while the fat energy ratio showed a positive correlation with FVC- Z ( β =0.03) and VCI ( β =0.23) ( P <0.05). The protein energy ratio was positively correlated with FVC- Z ( β =0.09) and VCI ( β =0.60) specifically in girls ( P <0.05). Additionally, there was an interaction effect of age on the associations between macronutrients and lung function ( P <0.01); in children aged 8-9 and 10-11, the carbohydrate energy supply ratio was negatively correlated with FVC- Z ( β =-0.04, -0.03) and VCI ( β =-0.29, -0.21), and fat energy supply ratio was positively correlated with FVC- Z ( β =0.07, 0.05) and VCI ( β =0.46, 0.32) ( P <0.05). Conclusions There are age and sex differences in the association of dietary macronutrients with lung function, with a low carbohydrate, high fat diet promoting lung function in children. Additionally, protein intake appears to have a positive influence on the lung function of girls. The early school age period may represent a critical window for dietary interventions aimed at promoting lung health.

Flagella are the main motility structure of Clostridioides difficile that affects the adhesion, colonization, and virulence of C. difficile in the human gastrointestinal tract. The FliL protein is a single transmembrane protein bound to the flagellar matrix. This study aimed to investigate the effect of the FliL encoding gene flagellar basal body-associated FliL family protein (fliL) on the phenotype of C. difficile. The fliL gene deletion mutant (ΔfliL) and its corresponding complementary strains (: : fliL) were constructed using allele-coupled exchange (ACE) and the standard molecular clone method. The differences in physiological properties such as growth profile, antibiotic sensitivity, pH resistance, motility, and spore production ability between the mutant and wild-type strains (CD630) were investigated. The ΔfliL mutant and the : : fliL complementary strain were successfully constructed. After comparing the phenotypes of strains CD630, ΔfliL, and : : fliL, the results showed that the growth rate and maximum biomass of ΔfliL mutant decreased than that of CD630. The ΔfliL mutant showed increased sensitivity to amoxicillin, ampicillin, and norfloxacin. Its sensitivity to kanamycin and tetracycline antibiotics decreased, and the antibiotic sensitivity partially returned to the level of CD630 strain in the : : fliL strain. Moreover, the motility was significantly reduced in the ΔfliL mutant. Interestingly, the motility of the : : fliL strain significantly increased even when compared to that of the CD630 strain. Furthermore, the pH tolerance of the ΔfliL mutant significantly increased or decreased at pH 5 or 9, respectively. Finally, the sporulation ability of ΔfliL mutant reduced considerably compared to the CD630 strain and recovered in the : : fliL strain. We conclude that the deletion of the fliL gene significantly reduced the swimming motility of C. difficile, suggesting that the fliL gene is essential for the motility of C. difficile. The fliL gene deletion significantly reduced spore production, cell growth rate, tolerance to different antibiotics, acidity, and alkalinity environments of C. difficile. These physiological characteristics are closely related to the survival advantage in the host intestine, which is correlated with its pathogenicity. Thus, we suggested that the function of the fliL gene is closely related to its motility, colonization, environmental tolerance, and spore production ability, which consequently affects the pathogenicity of C. difficile.
Humans ; Clostridioides/metabolism* ; Clostridioides difficile/metabolism* ; Bacterial Proteins/metabolism* ; Virulence ; Anti-Bacterial Agents/metabolism*

Objective: To investigate the prevalence of dyslipidemia among adults in Moyu County, Hotan Prefecture, Xinjiang Uygur Autonomous Region, so as to provide insights into the management of dyslipidemia. Methods: The physical examination data of permanent residents at ages of 18 years and older were collected from Moyu County from 2018 to 2019, including demographic features, height, body weight, blood pressure and blood biochemical parameter measurements. The epidemiological characteristics of dyslipidemia were analyzed among residents. Results: Totally 166 142 adults were investigated, with a mean age of (41.08±15.72) years. There were 77 744 men (46.76%), 34 728 obese adults (20.90%), 5 776 adults with diabetes (3.48%) and 26 294 adults with hypertension (15.83%). The levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were (1.38±0.98), (4.13±1.19), (1.31±0.41) and (2.25±0.77) mmol/L, respectively. The prevalence of dyslipidemia was 29.72%, and the detection rates of high TG, high TC, low-HDL-C and high LDL-C were 9.73%, 4.59%, 19.65% and 1.99%, respectively. The prevalence of dyslipidemia was higher in men than in women (33.97% vs. 25.98%; χ2=1 264.729, P<0.001), and the prevalence increased with age (χ2=539.382, P<0.001) and body mass index (χ2=3 601.833, P<0.001). The prevalence of dyslipidemia was 35.48% among patients with hypertension (χ2=497.251, P<0.001) and 46.07% among patients with diabetes (χ2=766.142, P<0.001). There were 9 059 adults with two and more abnormal blood lipid indexes (18.35%), and the detection rates of two and more abnormal blood lipid indexes were 26.50%, 24.14% and 33.15% among patients with obesity, hypertension and diabetes, respectively. Conclusions The prevalence of dyslipidemia among adults in Moyu County is lower than the national level, and low-HDL cholesterolemia is the most common type of dyslipidemia. The prevalence of dyslipidemia is high among patients with obesity, hypertension and diabetes mellitus, in whom abnormality of multiple blood lipid indexes is measured.

Background: Brucella infection induces brucellosis, a zoonotic disease. The intracellular circulation process and virulence of Brucella mainly depend on its type IV secretion system (T4SS) expressing secretory effectors. Secreted protein BspJ is a nucleomodulin of Brucella that invades the host cell nucleus. BspJ mediates host energy synthesis and apoptosis through interaction with proteins. However, the mechanism of BspJ as it affects the intracellular survival of Brucella remains to be clarified. Objectives: To verify the functions of nucleomodulin BspJ in Brucella's intracellular infection cycles. Methods: Constructed Brucella abortus BspJ gene deletion strain (B. abortus ΔBspJ) and complement strain (B. abortus pBspJ) and studied their roles in the proliferation of Brucella both in vivo and in vitro. Results: BspJ gene deletion reduced the survival and intracellular proliferation of Brucellaat the replicating Brucella-containing vacuoles (rBCV) stage. Compared with the parent strain, the colonization ability of the bacteria in mice was significantly reduced, causing less inflammatory infiltration and pathological damage. We also found that the knockout of BspJ altered the secretion of cytokines (interleukin [IL]-6, IL-1β, IL-10, tumor necrosis factor-α, interferon-γ) in host cells and in mice to affect the intracellular survival of Brucella. Conclusions BspJ is extremely important for the circulatory proliferation of Brucella in the host, and it may be involved in a previously unknown mechanism of Brucella's intracellular survival.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations are often associated with non-EGFR genetic alterations, which may be a reason for the poor efficacy of EGFR tyrosine kinase inhibitors (TKIs). Here we conducted this study to explore whether EGFR-TKIs combined with chemotherapy would benefit advanced lung adenocarcinoma patients with both sensitive EGFR mutation and concomitant non-EGFR genetic alterations. METHODS: Cases of advanced lung adenocarcinoma with EGFR mutation combined with concomitant non-EGFR genetic alterations were retrospectively collected. And the patients were required to receive first-line EGFR-TKIs and chemotherapy combination or EGFR-TKIs monotherapy. Demographic, clinical and pathological data were collected, and the electronic imaging data were retrieved to evaluate the efficacy and time of disease progression. Survival data were obtained through face-to-face or telephone follow-up. The differences between the two groups in objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were investigated. RESULTS 107 patients were included, including 63 cases in the combination group and 44 cases in the monotherapy group. The ORR were 78% and 50% (P=0.003), and DCR were 97% and 77% (P=0.002), respectively. At a median follow-up of 13.7 mon, a PFS event occurred in 38.1% and 81.8% of patients in the two groups, with median PFS of 18.8 mon and 5.3 mon, respectively (P<0.000,1). Median OS was unreached in the combination group, and 27.8 mon in the monotherapy group (P=0.31). According to the Cox multivariate regression analysis, combination therapy was an independent prognostic factor of PFS CONCLUSIONS: In patients with EGFR-mutant advanced lung adenocarcinoma with concomitant non-EGFR genetic alterations, combination of TKIs and chemotherapy was significantly superior to EGFR-TKIs monotherapy, which should be the preferred treatment option.
Adenocarcinoma of Lung/genetics* ; ErbB Receptors/genetics* ; Humans ; Lung Neoplasms/pathology* ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Retrospective Studies

OBJECTIVE: To detect the mutation site in a pedigree affected with autosomal dominant polycystic kidney disease (ADPKD) and verify its impact on the protein function. METHODS: Peripheral blood samples were collected from the proband and his pedigree members for the extraction of genomic DNA. Mutational analysis was performed on the proband through whole-exome sequencing. Suspected variant was verified by Sanger sequencing. A series of molecular methods including PCR amplification, restriction enzyme digestion, ligation and transformation were also used to construct wild-type and mutant eukaryotic expression vectors of the PKD2 gene, which were transfected into HEK293T and HeLa cells for the observation of protein expression and cell localization. RESULTS: The proband was found to harbor a c.2051dupA (p. Tyr684Ter) frame shift mutation of the PKD2 gene, which caused repeat of the 2051st nucleotide of its cDNA sequence and a truncated protein. Immunofluorescence experiment showed that the localization of the mutant protein within the cell was altered compared with the wild-type, which may be due to deletion of the C-terminus of the PKD2 gene. CONCLUSION The c.2051dupA (p. Tyr684Ter) mutation of the PKD2 gene probably underlay the pathogenesis of ADPKD in this pedigree.
DNA Mutational Analysis ; Female ; Frameshift Mutation ; HEK293 Cells ; HeLa Cells ; Humans ; Male ; Pedigree ; Polycystic Kidney, Autosomal Dominant/physiopathology* ; Protein Kinases/genetics* ; Protein Transport/genetics* ; Whole Exome Sequencing

OBJECTIVE: To analyze the pathogenic variant of preaxial polydactyly in a Chinese Han pedigree and identify the cause of polydactyly. METHODS: The peripheral blood DNA of the proband and her parents was extracted. The polydactyly-related genes were detected by trio whole exome sequencing, and the suspected pathogenic gene was screened out. Sanger sequencing was applied to other members of the pedigree. RESULTS: The results of gene sequencing showed that the LMBR1 gene had a heterozygous variant of c.423+4909(IVS5)C>T in 6 patients of the pedigree. The same variant was not detected in family members with normal phenotype. Based on the ACMG guidelines, c.423+4909(IVS5)C>T of the LMBR1 gene was predicted to be pathogenic (PM1+PM2+PP1-S(PS)+PP4+PP5). CONCLUSION The heterozygous C>T variant at position 4909 of intron 5 of the LMBR1 gene probably underlies the disease in this pedigree.
China ; Female ; Humans ; Mutation ; Pedigree ; Polydactyly/genetics* ; Thumb ; Whole Exome Sequencing

OBJECTIVE: To explore the genetic basis for a Chinese patient with amyotrophic lateral sclerosis (ALS). METHODS: Peripheral blood samples were collected from the patient and his parents for the extraction of genomic DNA. Genetic variant was identified by whole exome sequencing. Candidate variant was verified by Sanger sequencing of his parents and healthy controls. RESULTS: The patient was found to harbor a heterozygous c.420C>G (p.Asn140Lys) variant of the SOD1 gene. The same variant was not detected in his parents and 100 healthy controls. The variant has not been included in HGMD, dbSNP and other databases. CONCLUSION The c.420C>G variant of the SOD1 gene may underlie the ALS in this patient. Above finding has enriched the spectrum of SOD1 gene variants.
Amyotrophic Lateral Sclerosis/genetics* ; China ; Heterozygote ; Humans ; Superoxide Dismutase-1/genetics* ; Whole Exome Sequencing

Objective:Establishment of a new model of human primary colon cancer transplantation tumor in normal immune mice and to provide a reliable experimental animal model for studying the pathogenesis of colon cancer under normal immunity.Methods:Human colon cancer cells come from colon cancer patients who underwent surgery in the Affiliated Hospital of Jining Medical College in 2017. The mice in the cell control group were inoculated with phosphate buffered solution (PBS) containing colon cancer cells, the microcarrier control group was inoculated with PBS containing microcarrier 6, and the cell-microcarrier complex group was inoculated with the PBS containing colon cancer cell-microcarrier complex. The cells of each group were inoculated under the skin of the right axilla of mice by subcutaneous injection, and the time, size, tumor formation rate and pathological changes under microscope were recorded. The transplanted tumor tissue was immunohistochemically stained with the EnVisiion two-step method, and the tumor formation rate of the transplanted tumor was judged according to the proportion of positive cells in the visual field. The polymerase chain reaction (PCR) method was used to detect the expression of human-specific Alu sequence in mice tumor tissue.Results:After inoculation with tumor cells, the mice in the cell control group and the microcarrier control group did not die and did not form tumors; the mice in the cell-microcarrier complex group had palpable subcutaneous tumors in the right axillary subcutaneously on the 5th to 7th days after inoculation, and tumor formation rate is 67% (10/15), and the tumor volume can reach about 500 mm 3 2 to 3 weeks after vaccination. The immunohistochemistry results showed that CK20, CDX-2 and carcinoembryonic antigen were all positively expressed. The PCR results showed that the expression of human-specific Alu sequence can be detected in the transplanted tumor tissue of tumor-bearing mice. Conclusion:Human primary colon cancer cells used microcarrier 6 as a carrier to form tumors in normal immunized mice, and successfully established a new model of human colon cancer transplantation tumor in normal immune mice.

Objective:To explore the knowledge-attitude-practice of pelvic floor muscle training in women with postpartum stress urinary incontinence (SUI) .Methods:From January 2018 to January 2019, we conveniently selected 213 patients in the Pelvic Floor Clinic of a Obstetrics and Gynecology Hospital in Beijing 12 weeks after delivery. We used the Pelvic Floor Muscle Function Training Knowledge-Attitude-Practice and Its Needs in Puerperium Women Questionnaire for investigation, and analyzed the influencing factors of knowledge-attitude-behavior of patients' pelvic floor muscle function training.Results:Among 213 SUI patients, the overall standard score of pelvic floor muscle training knowledge-attitude-practice was (75.70±10.23) . Univariate analysis showed that there were statistical differences in the knowledge-attitude-practice of pelvic floor muscle function training among patients with different age, family monthly income per capita, highest education level, occupational status, delivery method, weight gain during pregnancy, and current urinary incontinence ( P<0.2) .Multiple regression analysis showed that family monthly in comeper capita, weight gain during pregnancy, and current urinary incontinence were the influencing factors of pelvic floor muscle function training knowledge-attitude-practice with a statistical difference ( P<0.05) . Conclusions:Postpartum SUI patients have a positive attitude towards pelvic floor muscle function training, but their cognitive level needs to be improved. Medical and nursing staff should strengthen the publicity and education of relevant knowledge, and enhance patients' awareness of the importance of pelvic floor muscle function training.