Objective: To investigate the status of antibiotic exposure in third grade primary school students in Shenzhen,so as to provide evidence for the scientific management of antibiotic use and reduction of population health risks. Methods: From 1 September to 30 October 2021, 200 third grade students from 8 primary schools in Luohu District of Shenzhen were selected by cluster random sampling as research subjects. The body composition was measured, urine samples were collected, and the contents of 35 antibiotics in the samples were detected by mass spectrometry. Relevant dietary habit information of the subjects was collected via questionnaires. The Chi square test was used to compare the detection rate of antibiotics among different genders and weight grades. The Logistic regression model was adopted to evaluate the correlation between the target antibiotic detection rate and dietary habits. Results: At least one type of antibiotic was detected in 198 of the subjects with an overall detection rate of 99.0% . Among the 35 target antibiotics, 23 were detected with detection rates ranging from 0.5%-69.5%. Quinolones had the highest detection rate of 86.5% , followed by macrolides and sulfonamides with detection rates of 77.5% and 76.5%, respectively. The detection rate of antibiotics was 98.3% in boys and 100.0% in girls with no statistically significant difference ( χ 2=1.35, P >0.05). The detection rates of quinolones, macrolides, and sulfonamides varied significantly among children with different BMI categories ( χ 2=38.18, 12.45, 9.76 , all P <0.05). The multivariate Logistic regression model analysis showed that the macrolide detection rate was affected by genders( OR =0.42) and the sulfonamide detection rate was significantly correlated with the frequency of dairy product consumption and being overweight( OR =2.01)(both P <0.05). Enrofloxacin was associated with the weekly consumption frequency of livestock meat such as pork, beef and mutton, as well as the weekly consumption frequency of poultry meat such as chicken, duck and goose ( OR = 2.81,2.17,both P <0.05). Trimethoprim was associated with the weekly frequency of drinking pure milk ( OR =5.49, P < 0.05 ). Conclusions Third grade primary school students in Shenzhen are generally exposed to low dose antibiotics. Macrolides, quinolones, and sulfonamides may be associated with the risk of obesity in primary school students.

ObjectiveTo explore the possible mechanisms of Modified Shoutai Pill （寿胎丸加味方， MSP） in treating polycystic ovary syndrome （PCOS） with hyperandrogenism， insulin resistance， and miscarriage， focusing on inflammatory response and endometrial receptivity. MethodsThirty female SPF-grade SD rats with regular estrous cycles and in proestrus， and 15 male SPF-grade SD rats were housed together in a 2∶1 ratio at 18：00. At 8：00 next morning， rats showing abundant sperm and vaginal plugs were considered pregnant on the day 0.5. The 30 pregnant rats were randomly divided into three groups， normal group， model group， and MSP group， with 10 rats in each group. From day 0.5 to day 13.5 of pregnancy， the MSP group was given 26.6 g/（kg·d） of the MSP via gavage twice a day for 14 consecutive days. The normal group and the model group received 4 ml of normal saline daily. From day 7.5 to day 13.5 of pregnancy， the rats in the model group and MSP group were intraperitoneally injected with dihydrotestosterone （DHT） and insulin （INS） for 7 consecutive days to establish a PCOS model with hyperandrogenism， insulin resistance， and miscarriage. On day 13.5 of pregnancy， an oral glucose tolerance test （OGTT） was performed to measure blood glucose levels at 0， 30， 60， 90， and 120 minutes. On day 14.5， serum level of progesterone （P₄）， estradiol （E₂）， fasting insulin （FINS）， interleukin-6 （IL-6）， and tumor necrosis factor-alpha （TNF-α） were measured by ELISA. The insulin resistance index （HOMA-IR） was calculated. Embryo implantation， miscarriage rate， and average number of live fetuses were observed. Uterine tissue pathology was examined by HE staining， and mRNA expression of Il-6， Tnf-α， leukemia inhibitory factor （Lif）， homeobox gene 10 （Hoxa10）， prolactin family 8 subfamily A member 2 （Prl8a2）， and insulin-like growth factor-binding protein 1 （Igfbp1） in the uterine tissue was detected by qRT-PCR. ResultsCompared with the normal group， the model group had significantly higher blood glucose level at 0， 30， 60， 90， and 120 minutes， increased miscarriage rate， elevated HOMA-IR， decreased average number of live fetuses， lower level of P₄ and E₂， higher level of IL-6， TNF-α， and FINS， and higher mRNA expression of Il-6 and Tnf-α in the uterine tissue. The mRNA expression of Lif， Hoxa10， and Prl8a2 was reduced （P＜0.05 or P＜0.01）. The uterus had a dark red color， visible areas of bleeding， fewer embryos with developmental abnormalities， and increased placental necrosis. Pathological examination revealed thrombus in the decidual layer， unclear decidual cell morphology， loose arrangement， scattered distribution， edema degeneration in the cytoplasm， and nuclear shrinkage or disappearance， with extensive infiltration of inflammatory cells. In contrast， compared with the model group， the MSP group showed significantly lower blood glucose level at 0， 30， 60， 90， and 120 min， reduced miscarriage rate， lower HOMA-IR， increased number of live fetuses， higher level of P₄ and E₂， and lower level of IL-6， TNF-α， and FINS. The mRNA expression of Il-6 and Tnf-α in the uterine tissue was lower， while the expression of Lif， Hoxa10， and Prl8a2 mRNA was higher （P＜0.05 or P＜0.01）. There was significant improvement in uterine and embryo conditions， as well as in uterine tissue pathology. ConclusionThe MSP can reduce the miscarriage rate in a PCOS model with hyperandrogenism， insulin resistance， and miscarriage. Its mechanism may involve inhibiting inflammation， improving endometrial receptivity， and restoring the defects in endometrial decidualization.

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

OBJECTIVE: Several epidemiological observational studies have related particulate matter (PM) exposure to Inflammatory bowel disease (IBD), but many confounding factors make it difficult to draw causal links from observational studies. The objective of this study was to explore the causal association between PM _2.5 exposure, its absorbance, and IBD. METHODS: We assessed the association of PM _2.5 and PM _2.5 absorbance with the two primary forms of IBD (Crohn's disease [CD] and ulcerative colitis [UC]) using Mendelian randomization (MR) to explore the causal relationship. We conducted two-sample MR analyses with aggregated data from the UK Biobank genome-wide association study. Single-nucleotide polymorphisms linked with PM _2.5 concentrations or their absorbance were used as instrumental variables (IVs). We used inverse variance weighting (IVW) as the primary analytical approach and four other standard methods as supplementary analyses for quality control. RESULTS: The results of MR demonstrated that PM _2.5 had an adverse influence on UC risk (odds ratio [ OR] = 1.010; 95% confidence interval [ CI] = 1.001-1.019, P = 0.020). Meanwhile, the results of IVW showed that PM _2.5 absorbance was also causally associated with UC ( OR = 1.012; 95% CI = 1.004-1.019, P = 0.002). We observed no causal relationship between PM _2.5, PM _2.5 absorbance, and CD. The results of sensitivity analysis indicated the absence of heterogeneity or pleiotropy, ensuring the reliability of MR results. CONCLUSION Based on two-sample MR analyses, there are potential positive causal relationships between PM _2.5, PM _2.5 absorbance, and UC.
Humans ; Mendelian Randomization Analysis ; Particulate Matter/analysis* ; Polymorphism, Single Nucleotide ; Inflammatory Bowel Diseases/genetics* ; Air Pollutants/analysis* ; Crohn Disease/genetics* ; Colitis, Ulcerative/genetics* ; Genome-Wide Association Study ; Risk Factors ; Environmental Exposure

OBJECTIVE: Lipid oxidation is involved in the pathogenesis of atherosclerosis and may be contribute to the development of Ischemic stroke (IS). However, the lipid profiles associated with IS have been poorly studied. We conducted a pilot study to identify potential IS-related lipid molecules and pathways using lipidomic profiling. METHODS: Serum lipidomic profiling was performed using LC-MS in 20 patients with IS and 20 age- and sex-matched healthy controls. Univariate and multivariate analyses were simultaneously performed to identify the differential lipids. Multiple testing was controlled for using a false discovery rate (FDR) approach. Enrichment analysis was performed using MetaboAnalyst software. RESULTS: Based on the 294 lipids assayed, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models were used to distinguish patients with IS from healthy controls. Fifty-six differential lipids were identified with an FDR-adjusted P less than 0.05 and variable influences in projection (VIP) greater than 1.0. These lipids were significantly enriched in glycerophospholipid metabolism (FDR-adjusted P = 0.009, impact score = 0.216). CONCLUSIONS Serum lipid profiles differed significantly between patients with IS and healthy controls. Thus, glycerophospholipid metabolism may be involved in the development of IS. These results provide initial evidence that lipid molecules and their related metabolites may serve as new biomarkers and potential therapeutic targets for IS.
Humans ; Pilot Projects ; Lipidomics ; Male ; Female ; Biomarkers/blood* ; Middle Aged ; Ischemic Stroke/blood* ; Aged ; China ; Lipids/blood* ; Adult ; Case-Control Studies ; East Asian People

The accumulation of uremic toxins such as urea nitrogen, blood creatinine, and uric acid of patients with renal failure in vivo would lead to aggravated kidney damage. In this study, coated aldehyde oxy-starch (CAO) was used as an adsorbent to investigate its in vitro adsorption performance on renal failure indexes for urea, indoxyl sulfate (INS), monomethylamine (MMA), dimethylamine (DMA), uric acid (UA), and creatinine (Cr). The effects of variables such as pH, temperature, concentration, dosage, and time on the adsorption capacity of CAO were systematically investigated, employing analytical techniques of high-performance liquid chromatography (HPLC) and gas chromatography (GC). The results revealed that CAO exhibited a strong adsorption capacity for urea, INS, and MMA, alongside a moderate adsorption capacity for DMA, UA, and Cr. The adsorption kinetics and thermodynamic studies indicated that the adsorption of urea and UA by CAO were fitted in pseudo-first-order kinetics, and the adsorption isotherm aligned with the Freundlich adsorption model. The enthalpy change ΔH of urea in adsorption was in the range of 40 to 60 kJ·mol^-1, which demonstrated the presence of strong adsorption force due to the interactions of coordinating groups. The ΔH of UA was greater than 80 kJ·mol^-1, indicating the generation of chemical bonds during the adsorption. Both of them, Gibbs free energy ΔG was less than 0, within the range of -20 to 0 kJ·mol^-1, suggested that the adsorption of urea and UA by CAO occurred spontaneously as physical adsorption process. The adsorption entropy ΔS of urea and UA was > 0, which indicated an increase in entropy throughout the adsorption. The infrared spectroscopygram showed the formation of a chemical bond, specifically the imine bond, following the adsorption of urea by CAO, thereby indicating a chemical reaction during the adsorption. This study elucidates the adsorption mechanism of CAO on various indexes of renal failure, providing a scientific basis for its clinical usage.

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia in the elderly. This study aimed to evaluate urban-rural disparities in its prevalence and management in elderly Chinese. METHODS: Consecutive participants aged ≥ 65 years attending outpatient clinics were enrolled for AF screening using handheld single-lead electrocardiogram (ECG) from April 2017 to December 2022. Each ECG rhythm strip was reviewed from the research team. AF or uninterpretable single-lead ECGs were referred for 12-lead ECG. Primary study outcome comparison was between rural and urban areas for the prevalence of AF. The Student's t-test was used to compare mean values of clinical characteristics between rural and urban participants, while the Pearson's chi-square test was used to compare between-group proportions. Multivariate stepwise logistic regression analysis was performed to estimate the association between AF and various patient characteristics. RESULTS: The 29,166 study participants included 13,253 men (45.4%) and had a mean age of 72.2 years. The 7073 rural participants differed significantly (P ≤ 0.02) from the 22,093 urban participants in several major characteristics, such as older age, greater body mass index, and so on. The overall prevalence of AF was 4.6% (n = 1347). AF was more prevalent in 7073 rural participants than 22,093 urban participants (5.6% vs. 4.3%, P < 0.01), before and after adjustment for age, body mass index, blood pressure, pulse rate, cigarette smoking, alcohol consumption and prior medical history. Multivariate logistic regression analysis identified overweight/obesity (OR = 1.35, 95% CI: 1.17-1.54) in urban areas and cigarette smoking (OR = 1.62, 95% CI: 1.20-2.17) and alcohol consumption (OR = 1.42, 95% CI: 1.04-1.93) in rural areas as specific risk factors for prevalent AF. In patients with known AF in urban areas (n = 781) and rural areas (n = 338), 60.6% and 45.9%, respectively, received AF treatment (P < 0.01), and only 22.4% and 17.2%, respectively, received anticoagulation therapy (P = 0.05). CONCLUSIONS In China, there are urban-rural disparities in AF in the elderly, with a higher prevalence and worse management in rural areas than urban areas. Our study findings provide insight for health policymakers to consider urban-rural disparity in the prevention and treatment of AF.

There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

Objective:To analyze the influencing factors of extremely high cost cases under disease diagnosis related grouping (DRG) payment, for references for further improving China′s medical insurance payment system.Methods:The inpatient medical record homepage and medical insurance settlement list data of medical insurance settlement cases in a tertiary hospital in 2022 were Collected; 19 potential influencing factors such as gender, age, and hospitalization status were used as independent variables, and extremely high cost cases as dependent variables. Single factor analysis and directed acyclic graphs were used to screen for independent variables; Logistic regression model was used to analyze the influencing factors of extremely high cost cases.Results:A total of 17 028 hospitalized patients were contained, including 815 cases with extremely high costs. After analysis, the older the age, the greater the positive impact on cases with extremely high costs ( P<0.001); Third/fourth level surgery had a positive impact on these cases ( P<0.05); Emergency/critical hospitalization negative impact on extremely high cost cases ( P<0.001); Coding downgrade, surgical, intensive care unit discharge, and death positive impact cases with extremely high costs ( P<0.001); The higher the proportion of drugs, the greater the positive impact on cases with extremely high costs ( P<0.001); Compared with treatment costs accounting for ≤10%, treatment costs accounting for (10%, 30%] had a positive impact on cases with extremely high costs ( P<0.001), while treatment costs accounting for >30% had a negative impact ( P=0.007); Complications and/or comorbidities negative impact on thses cases ( P<0.001); The higher the weight of the disease group, the greater the negative impact on cases with extremely high costs ( P<0.001). Conclusions:There were many influencing factors for extremely high cost cases, among which factors such as advanced age, emergency/critical hospital admission, third/fourth level surgery, code downgrade, and high drug proportion would increase the number of extremely high cost cases, accompanied by complications and/or comorbidities, and the high weight of disease group reduce the number of extremely high cost cases. Medical institutions should strengthen internal management by standardizing admission management and optimizing the structure of hospitalization expenses; The medical insurance management department should focus on improving the DRG grouping scheme, scientifically setting the weight of disease groups, and jointly promoting the reform of China′s medical insurance payment system.

OBJECTIVE: To report the blood group antigen and antibody specificity identification methods for a patient with high-frequency antibodies, and the process of finding and providing compatible blood for the patient. METHODS: A patient sent from the Blood Transfusion Department of Shanxi Provincial People's Hospital to Blood Transfusion Technology Research Laboratory of Taiyuan Blood Center in November 2022 was selected for the study. Classical serological methods were used to determine the patient's blood type, screen for unexpected antibodies, identify antibodies, and perform crossmatching. High-frequency antibody identification was carried out using red blood cells treated with various enzymes. Blood group genotyping was conducted using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF) and Sanger sequencing. Multiple strategies were employed to address the patient's blood source problem. The study was approved by the Medical Ethics Committee of Taiyuan Blood Center [Ethics No. 2024 Ethics Review No.(2)]. RESULTS: The patient's blood type was B, RhD positive. Initial screening of the patient's serum with multiple screening cells and antibody identification cells in saline medium was negative, but positive in antiglobulin medium. The patient's serum showed varying reaction intensities with red blood cells treated with different enzymes. MALDI-TOF mass spectrometry and Sanger sequencing revealed a homozygous nonsense variant c.376C>T (p.Gln126Ter) in the ABCG2 gene, resulting in the Jr(a-) phenotype. During family donor selection, the patient's son was found to have a heterozygous variant c.376C>T (p.Gln126Ter), and another heterozygous variant c.421C>A (p.Gln141Lys), which predicted a Jr(a+w) phenotype. Crossmatch tests confirmed the compatibility of blood from the patient's son, which was used to address the urgent blood requirement. Later, rare blood from a Jr(a-) donor from the Guangzhou Blood Center was used for the patient's ongoing treatment, saving the patient's life. CONCLUSION Combining classic serological testing with blood group gene typing techniques successfully identified the rare Jr(a-) blood type and high-frequency anti-Jra antibodies. Enzyme-treated red blood cell identification methods confirmed the presence of anti-Jra antibodies. By searching within the family and seeking help from other blood centers, compatible blood was found. This approach may provide insights for resolving similar complex blood matching problems in the future.
Humans ; Blood Grouping and Crossmatching/methods* ; Blood Group Antigens/immunology* ; Blood Transfusion ; Male ; Isoantibodies/blood* ; Female ; Genotype