Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal microbiota. Methods Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs(OH-PAHs)in 36-month-old children.Subsequently,37 children were categorized into low-and high-exposure groups based on the sum of the ten OH-PAHs.Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples.Furthermore,fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq. Results The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group(variable importance for projection>1,P<0.05).Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene,fluorine,and phenanthrene(r=0.336-0.531).The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states,including amino acid,lipid,and nucleotide metabolism.Additionally,these distinct metabolites were significantly associated with specific intestinal flora abundances(r=0.34-0.55),which were mainly involved in neurodevelopment. Conclusion Higher PAH exposure in young children affected metabolic homeostasis,particularly that of certain gut microbiota-derived metabolites.Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.

Objective To observe the clinical efficacy of adjuvant PD-1 inhibitor in the treatment of patients with hepatocellular carcinoma after microwave ablation and the changes of lymphocyte subsets before and after treatment.Methods A total of 56 patients with hepatocellular carcinoma who underwent microwave ablation in our hospital were randomly divided into two groups according to different treatments,with 28 cases in each group.Patients in the group A received adjuvant treatment with PD-1 inhibitors after microwave ablation,while patients in the group B received microwave ablation alone.The local efficacy of microwave ablation,the survival of patients after adjuvant treatment of PD-1 inhibitor and the occurrence of related adverse reactions were observed.Peripheral venous blood was collected to detect the number of T lymphocyte subsets before microwave ablation in the two groups,after microwave ablation in the group B,and after six cycles of immunotherapy in the group A.Results There was no significant difference in the complete ablation rate of cases between group A and group B(89.3% vs.85.7%,P=0.69),and there was no significant difference in the complete ablation rate of lesions between group A and group B(91.7% vs.85.3%,P=0.40).The median progression-free survival(mPFS)of the group A was not yet reached,the mPFS of group B was 12.6 months,and there was a statistically significant difference in the mPFS between the two groups(P=0.03).The median overall survival(mOS)of the two group were not yet reached.The proportion of CD4+T lymphocytes after treatment in the group A significantly increased compared with that in the group B[(37.05±2.22)% vs.(29.23±2.88)%,P=0.03],while the proportion of CD8+T lymphocytes[(21.08±2.23)% vs.(27.18±1.75)%,P=0.04)]and the proportion of Treg cells[(4.26±0.31)% vs.(5.22±0.34)%,P=0.04]significantly decreased.There was no serious adverse reactions in all patients after microwave ablation,and 28 patients in the group A had no adverse reactions above grade 3 after PD-1 inhibitor treatment.Conclusion Adjuvant PD-1 inhibitor therapy after microwave ablation can prolong the progression-free survival of patients,enhance the function of T lymphocytes,and weaken the role of immunosuppressive cells,which may be an effective strategy to delay the recurrence of liver cancer after microwave ablation.

This study aimed to investigate the effect and mechanism of Zuogui Jiangtang Qinggan Formula(ZGJTQG) on the glucolipid metabolism of type 2 diabetes mellitus(T2DM) complicated with non-alcoholic fatty liver disease(NAFLD). NAFLD was induced by a high-fat diet(HFD) in MKR mice(T2DM mice), and a model of T2DM combined with NAFLD was established. Forty mice were randomly divided into a model group, a metformin group(0.067 g·kg~(-1)), and high-and low-dose ZGJTQG groups(29.64 and 14.82 g·kg~(-1)), with 10 mice in each group. Ten FVB mice of the same age were assigned to the normal group. Serum and liver tissue specimens were collected from mice except for those in the normal and model groups after four weeks of drug administration by gavage, and fasting blood glucose(FBG) and fasting insulin(FINS) levels were measured. The levels of total cholesterol(TC), triglyceride(TG), and low-density lipoprotein(LDL) were detected by the single reagent GPO-PAP method. Very low-density lipoprotein(VLDL) was detected by enzyme-linked immunosorbent assay(ELISA). Alanine aminotransferase(ALT) and aspartate ami-notransferase(AST) were determined by the Reitman-Frankel assay. The pathological changes in the liver were observed by hematoxylin-eosin(HE) staining and oil red O staining. Real-time fluorescence-based quantitative polymerase chain reaction(real-time PCR) and Western blot were adopted to detect the mRNA and protein expression of forkhead transcription factor O1(FoxO1), microsomal triglyceride transfer protein(MTP), and apolipoprotein B(APOB) in the liver. The results showed that high-dose ZGJTQG could signi-ficantly reduce the FBG and FINS levels(P<0.05, P<0.01), improve glucose tolerance and insulin resistance(P<0.05, P<0.01), alleviate the liver damage caused by HFD which was reflected in improving liver steatosis, and reduce the serum levels of TC, TG, LDL, VLDL, ALT, and AST(P<0.05, P<0.01) in T2DM mice combined with NAFLD. The findings also revealed that the mRNA and protein expression of FoxO1, MTP, and APOB in the liver was significantly down-regulated after the intervention of high-dose ZGJTQG(P<0.05, P<0.01). The above study showed that ZGJTQG could effectively improve glucolipid metabolism in T2DM combined with NAFLD, and the mechanism was closely related to the regulation of the FoxO1/MTP/APOB signaling pathway.
Mice ; Animals ; Non-alcoholic Fatty Liver Disease/metabolism* ; Diabetes Mellitus, Type 2/metabolism* ; Liver ; Lipoproteins, LDL/metabolism* ; Signal Transduction ; Diet, High-Fat/adverse effects* ; RNA, Messenger/metabolism*

Objective: To determine the causal association between long-term Nitrogen dioxide (NO₂) exposure and the risk of cardiovascular hospitalization. Methods: Based on a sub-cohort of a community-based prospective cohort study, a total of 36 271 participants were recruited from 35 communities randomly selected in Guangzhou in 2015. The annual average exposure of NO₂, demographic characteristics, lifestyle factors, and information on the causes of hospitalization was collected. We applied marginal structural Cox models to investigate the effect of NO₂ on cardiovascular hospitalization. Demographic and behavioral factors also stratified results. Results: The mean age of participants in the present study was (50.9±17.8) years, and the cardiovascular admission rate was 8.7%, with 203 822 person-years of follow-up. The annual mean NO₂ concentration was 48.7 μg/m³ during 2015-2020. For each 10 μg/m³ increase in NO₂ concentrations, the HRs (95%CIs) of total cardiovascular hospitalization, cardiovascular hospitalization, and cerebrovascular hospitalization were 1.33 (1.16-1.52), 1.36 (1.16-1.60) and 1.25 (1.00-1.55), respectively. Participants who were never married/married, with secondary education, high exercise frequency, or non-smokers/current smokers may be more susceptible than their counterparts. Conclusion: Long-term exposure to NO₂ significantly increased hospitalization risk for cardiovascular disease.
Humans ; Adult ; Middle Aged ; Aged ; Nitrogen Dioxide ; Prospective Studies ; Cardiovascular Diseases/epidemiology* ; Causality ; Hospitalization

Objective To understand the prevalence and influencing factors of hypertension among the elderly aged 60 years and above in Mianyang City,Sichuan Province,so as to provide clues for targeted prevention and control of hypertension. Methods A total of 115 775 permanent residents aged 60 and above screened out from Mianyang demonstration sites from October 2017 to April 2019 were investigated by questionnaire and physical examination,and the data of personal basic information,lifestyle,body height,body weight,waist circumference,and blood pressure were collected.SPSS 22.0 was used for descriptive analysis,single factor analysis,and Logistic regression analysis. Results The prevalence rate of hypertension in the elderly aged 60 years and above in Mianyang was 50.60%.Specifically,the prevalence rates of hypertension in men and women were 50.27% and 50.85%,respectively.The prevalence rate of hypertension increased with the increase in age([Formula: see text]=370.199,P<0001).Multivariate Logistic regression analysis showed that the independent risk factors of hypertension included age of 70-79 years(OR=1.327,95%CI=1.292-1.363,P<0.001),the age of 80 years and above(OR=1.455,95%CI=1.386-1.527,P<0.001),widowhood(OR=1.343,95%CI=1.296-1.392,P<0.001),divorce(OR=1.255,95%CI=1.033-1.525,P=0.022),overweight(OR=1.431,95%CI=1.391-1.473,P<0.001),obesity(OR=2.171,95%CI=2.076-2.270,P<0.001),waist-to-height ratio>0.5(OR=1.317,95%CI=1.281-1.354,P<0.001),history of diabetes(OR=1.865,95%CI=1.791-1.941,P<0.001),history of smoking(OR=1.107,95%CI=1.068-1.148,P<0.001),and history of drinking(OR=1.950,95%CI=1.894-2.009,P<0.001).Living in urban-rural fringe areas(OR=0.628,95%CI=0.594-0.664,P<0.001),education background of junior high school and above(OR=0.942,95%CI=0.912-0.974,P<0.001),and low body weight(OR=0.785,95%CI=0.742-0.830,P<0.001) were protective factors for hypertension. Conclusions More than 50% of the elderly aged 60 years and above in Mianyang suffer from hypertension.The elderly with advanced age,widowhood,divorce,overweight,obesity,waist-to-height ratio>0.5,diabetes history,smoking history,and drinking history are the high-risk groups of hypertension.
Aged ; Male ; Humans ; Female ; Overweight ; Hypertension/etiology* ; Waist Circumference ; Obesity ; Risk Factors ; Prevalence ; Body Weight ; China/epidemiology* ; Body Mass Index

Objective: To investigate the clinicopathological features and HER2 expression of metaplastic squamous cell carcinoma (MSCC) of the breast. Methods: A total of 47 MSCC cases diagnosed in the Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China from January 2010 to December 2021 were reviewed. The clinical information (including the follow-up data of HER2 positive patients) and pathological features were collected and analyzed. Results: All of the patients were female. Among the 47 cases, 25 were pure squamous cell carcinoma (PSCC) and 22 were mixed metaplastic carcinoma with squamous cell component (MMSC). The median age of the patients was 54 years (range, 29-84 years). The maximum diameter of the mass ranged from 0.8 to 10.0 cm, with a mean value of 3.3 cm, 85.7% (24/28) of the cases were smaller than 5 cm, and only 4 cases were larger than or equal to 5 cm. 89.5% of the MMSC presented with a solid mass. Cystic changes were more commonly found in the PSCC group (50%, P<0.05) than the MMSC group. 36.7% (11/30) of the patients had lymph node metastasis at the time of diagnosis. The squamous cell carcinoma component in all cases showed diffuse or patchy expression of p63, p40 and CK5/6. 55.3% (26/47) of the cases showed triple-negative phenotype. Among the 7 HER2-positive patients, 6 were MMSC group, which had a significantly higher rate of HER2-positivity than that in the PSCC group (1 case). In 1 MMSC case, immunohistochemistry showed HER2 2+in the invasive ductal carcinoma component and HER2 negativity (0) in the squamous cell carcinoma component, but HER2 FISH was negative in invasive ductal carcinoma and positive in squamous cell carcinoma component. Six HER2-positive MSCC patients received anti-HER2-targeted therapy, including two patients who received neoadjuvant chemotherapy combined with anti-HER2-targeted therapy before surgery. One patient achieved pathological complete remission, while the other achieved partial remission (the residual tumors were squamous cell carcinoma components). After 9-26 months of follow-up, four patients had no disease progression, two patients developed pulmonary metastases, and one patient showed local recurrence. Conclusions: MSCC is a group of heterogeneous diseases. PSCC and MMSC may be two different entities. Most of the MSCC are triple-negative and HER2 positivity is more commonly seen in MMSC with invasive ductal carcinoma component. Some HER2-positive MSCC patients can achieve complete remission or long-term progression-free survival after receiving anti-HER2 targeted therapy, but the squamous cell carcinoma component may be less sensitive to targeted therapy than the invasive ductal carcinoma component.
Carcinoma, Ductal ; Carcinoma, Squamous Cell/pathology* ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Receptor, ErbB-2/metabolism*

OBJECTIVETo analyze the clinical features and diagnostic points of occupational acute dimethylformamide (DMF) poisoning and to explore the mechanism of occupational acute DMF poisoning.

METHODSA comprehensive analysis was performed on the clinical data of 16 cases of occupational acute DMF poisoning, including symptoms, signs, and laboratory testing results.

RESULTSThe main clinical features of occupational acute DMF poisoning were digestive system impairments, especially abdominalgia. Hemorrhagic gastroenteritis was not found by gastroscopy. There was no significant correlation between the degree of abdominalgia and alanine aminotransferase level (r(s) = 0.109, P>0.05).

CONCLUSIONAbdominalgia is recommended to be one of the reference indices for the diagnosis and degrading of occupational acute DMF poisoning, The mechanism of DMF poisoning remains unclear but it is considered to be related to methyl isocyanate, the intermediate product of DMF metabolism.

Abdominal Pain ; chemically induced ; Alanine Transaminase ; metabolism ; Dimethylformamide ; poisoning ; Humans ; Occupational Exposure ; Solvents ; poisoning

OBJECTIVETo investigate the inhibitory effects of CaMKIIN on acute myeloid leukemia cell line HL-60 to explore a novel therapeutic target of leukemia.

METHODSHuman CaMK II N gene expression vector pcDNA3.1/hCaMKIIN or empty vector pcDNA3.1/myc-His (-) B was transfected into HL-60 cells by Lipofectamine 2000. Human CaMK II N proteins of transfected cells were detected by Western blot. Cell proliferation affected by human CaMKIIN was determined by MTT. Colony-forming assay was performed by soft agar growth system. The cells transfected with CaMKIIN were stained with Hoechst 33342 to detect the apoptotic proportion under fluorescence microscopy. Cell cycle was analyzed by flow cytometry.

RESULTSHuman CaMKIIN was stably transfected into HL-60 cells, and overexpression of human CaMKIIN inhibited the proliferation of HL-60/CaMKIIN cells compared to HL-60/mock cells and HL-60 cells [(0.44 ± 0.03) vs (0.94 ± 0.05) vs (0.94 ± 0.04), P<0.01]. The colony formation of HL-60/CaMKIIN was also markedly smaller[(21.00 ± 3.05)/500] than that of mock-transfected [(111.00±4.58)/500]] and control cells [(119.00±6.09)/500] (P<0.01). After 72 hrs-culture, the apoptotic proportion in cells transfected with CaMK II N was obviously higher than of cells transfected with mock DNA or control [(22.49 ± 2.15)% vs (7.17 ± 0.72)% vs (6.40 ± 0.55)%, P<0.01]. Up to (82.97 ± 2.90)% human CaMKIIN/HL-60 cells were arrested at G0/G1 phase, which was more than mock-transfected [(40.53 ± 2.38)%] and control cells [(41.63 ± 2.27)%] (P<0.05). Human CaMKIIN could down-regulate expression of Bcl-2 in transfected cells.

CONCLUSIONCaMK IIN up-regulation could inhibit proliferation and induce apoptosis of human acute myeloid leukemia cell HL-60.

Apoptosis ; Cell Proliferation ; Genetic Vectors ; HL-60 Cells ; Humans ; Proteins ; genetics ; metabolism ; Transfection ; Up-Regulation

OBJECTIVETo explore the efficacy and safety of endoscopic submucosal enucleation (ESE) for gastric submucosal tumors (SMTs) originated from muscularis propria.

METHODSA total of 116 patients with gastric SMT originated from muscularis propria underwent ESE in Department of Gastroenterology of the Taizhou Hospital between July 2006 and March 2011. The occurrence of intra-operative and post-operative complications and corresponding treatment were recorded. After the treatment of ESE, the patients were followed up endoscopically.

RESULTSThe success rate of operation was 96.6%. The mean time of the procedure was (51.9±16.3) min. Complications included intra-operative bleeding (n=9, 7.8%), perforation (n=20, 17.2%), and post-operative bleeding (n=3, 2.6%). Among them, 5 cases (4.3%) required surgical intervention. None of patient had other complications such as peritoneal abscess or peritonitis. The mean hospitalization time after ESE was 6.1 days. The median follow-up period was 12 months (range, 3-48 months) and there was no residual tumor or recurrence.

CONCLUSIONESE is a safe and feasible treatment for patients with gastric SMT originated from muscularis propria.

Adult ; Female ; Follow-Up Studies ; Gastrectomy ; methods ; Gastroscopy ; methods ; Humans ; Male ; Middle Aged ; Stomach Neoplasms ; surgery ; Treatment Outcome

OBJECTIVETo evaluate the efficacy and safety of endoscopic mucous resection with transparent cap (EMR-Cap) and endoscopic multi-band mucosectomy (MBM) in the treatment of early esophageal cancer and precancerous lesion.

METHODSA retrospective study was performed to review 30 EMR-Cap cases from December 2008 to December 2009 and 32 MBM cases from January 2010 to January 2011 of early esophageal cancer and precancerous lesions. The differences between these two techniques in efficacy, safety, and cost were compared.

RESULTSIn EMR-Cap group, the median resection time was 26(10-56) min and median procedure time was 43(22-81) min, significantly longer than those in MBM group [10(7-18) min and 32(28-45) min, P=0.036 and 0.038, respectively]. There were no significant differences between the two groups in total thickness and depth of resected lesions (P>0.05). In EMR-Cap group, the median cost was significantly higher than that of MBM group [(5466±354) vs. (4014±368) RMB, P=0.008)].

CONCLUSIONSEMR-Cap and MBM are minimally invasive, safe and effective methods in the treatment of early esophageal cancer and precancerous lesions. Compared to the EMR-Cap, MBM is simple with shorter treatment time and lower cost.

Aged ; Endoscopy ; methods ; Esophageal Neoplasms ; surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Mucous Membrane ; surgery ; Precancerous Conditions ; surgery ; Retrospective Studies ; Treatment Outcome