This study investigated the effects and underlying mechanisms of the luteolin-naringenin combination(LN)on liver injury induced by acetaminophen(APAP).Forty-eight Kunming mice were randomly allocated into six groups:a normal control group,an APAP-induced liver injury model group,a positive drug treatment group,and three LN treatment groups with low,medium,and high doses.After the final drug administration,the mice were fasted for 12 hours prior to eu-thanasia for sample collection.Serum transaminase activity,oxidative stress indices,and hematoxy-lin-eosin(HE)staining were assessed to evaluate the effects of LN on APAP-induced hepatic inju-ry.Additionally,Western blot analysis was conducted to examine the expression levels of sphingo-sine kinase 1(SPHK1)and endoplasmic reticulum stress(ERS)-related proteins,thereby elucida-ting the potential mechanisms by which LN mitigates APAP-induced liver injury.The results dem-onstrated that varying concentrations of LN effectively ameliorated serum aminotransferase activi-ty and oxidative stress levels induced by APAP in a dose-dependent manner.Histopathological ex-amination via HE staining revealed significant improvement in APAP-induced liver tissue injury following treatment with different concentrations of LN.Furthermore,Western blot analysis indi-cated that the protein expressions of SPHK1,CHOP,p-IRE1α,ATF6,p-PERK,p-eIF2α,and ATF4 were markedly reduced after administration of various concentrations of LN.The results demonstrate that LN exhibits a significant protective effect against APAP-induced liver injury by inhibiting the SPHK1-mediated aberrant expression of ERS-related molecules.This study high-lights the importance of targeting SPHK1 in the treatment of APAP liver injury and provides a no-vel therapeutic approach through the multi-target and multi-pathway combination of monomers.

Objective:To analyze the effects of shift work on the renal function of oil workers and investigate whether there is a measured response relationship between shift work and renal dysfunction.Methods:In this study, oil workers who participated in physical examinations at the North China Oilfield Downhole Hospital were selected as the study subjects, and the physical examinations as well as questionnaires of the study subjects in 2017 and 2018 were collected as the baseline data, which included blood biochemical indexes, socio-demographic characteristics, history of life behaviors, occupational exposures, and occupational histories. Three follow-up surveys were subsequently conducted in April 2019, April 2020, and January 2021. The presence of renal dysfunction in the study population was determined based on the glomerular filtration rate tested at the medical examination hospital. The exposure of the study subjects to shift work was assessed using the weighted shift index (WSI), the relationship between different levels of shift work and renal dysfunction was analyzed using Cox regression, and the measure of WSI and renal dysfunction was explored by restricted cubic spline (RCS). response relationship.Results:A total of 2292 study participants were included in this study, and the prevalence density of renal dysfunction was 87.44 k/year, of which the prevalence of renal dysfunction in females (30.31%), those with per capita monthly income <2, 000 yuan (27.00%), those who consume alcohol (27.10%), those who are hypertensive (23.05%), those who are exposed to high temperatures (27.37%), those who are exposed to organic solvents (30.42%), and those who are engaged in shift work (25.87%) were to be found had a higher prevalence of renal dysfunction ( P<0.05). After correcting for age, sex, and other risk factors, there was a nonlinear association between intensity of shift work and renal dysfunction, with a hazard ratio ( HR) of 1.29 (95% CI: 0.98-1.59) for the development of renal dysfunction in petroleum workers for shift work performed at higher intensities, and moderate intensity of exposure to shift work reduced the risk of renal dysfunction in petroleum workers ( HR=0.54 with a 95% CI: 0.39-0.75, P<0.001) . Conclusion:Prolonged shift work increases the risk of renal dysfunction in oil workers, and the occurrence of renal dysfunction in oil workers is influenced by multiple factors.

Objective:To analyze the effects of shift work on the renal function of oil workers and investigate whether there is a measured response relationship between shift work and renal dysfunction.Methods:In this study, oil workers who participated in physical examinations at the North China Oilfield Downhole Hospital were selected as the study subjects, and the physical examinations as well as questionnaires of the study subjects in 2017 and 2018 were collected as the baseline data, which included blood biochemical indexes, socio-demographic characteristics, history of life behaviors, occupational exposures, and occupational histories. Three follow-up surveys were subsequently conducted in April 2019, April 2020, and January 2021. The presence of renal dysfunction in the study population was determined based on the glomerular filtration rate tested at the medical examination hospital. The exposure of the study subjects to shift work was assessed using the weighted shift index (WSI), the relationship between different levels of shift work and renal dysfunction was analyzed using Cox regression, and the measure of WSI and renal dysfunction was explored by restricted cubic spline (RCS). response relationship.Results:A total of 2292 study participants were included in this study, and the prevalence density of renal dysfunction was 87.44 k/year, of which the prevalence of renal dysfunction in females (30.31%), those with per capita monthly income <2, 000 yuan (27.00%), those who consume alcohol (27.10%), those who are hypertensive (23.05%), those who are exposed to high temperatures (27.37%), those who are exposed to organic solvents (30.42%), and those who are engaged in shift work (25.87%) were to be found had a higher prevalence of renal dysfunction ( P<0.05). After correcting for age, sex, and other risk factors, there was a nonlinear association between intensity of shift work and renal dysfunction, with a hazard ratio ( HR) of 1.29 (95% CI: 0.98-1.59) for the development of renal dysfunction in petroleum workers for shift work performed at higher intensities, and moderate intensity of exposure to shift work reduced the risk of renal dysfunction in petroleum workers ( HR=0.54 with a 95% CI: 0.39-0.75, P<0.001) . Conclusion:Prolonged shift work increases the risk of renal dysfunction in oil workers, and the occurrence of renal dysfunction in oil workers is influenced by multiple factors.

This study investigated the effects and underlying mechanisms of the luteolin-naringenin combination(LN)on liver injury induced by acetaminophen(APAP).Forty-eight Kunming mice were randomly allocated into six groups:a normal control group,an APAP-induced liver injury model group,a positive drug treatment group,and three LN treatment groups with low,medium,and high doses.After the final drug administration,the mice were fasted for 12 hours prior to eu-thanasia for sample collection.Serum transaminase activity,oxidative stress indices,and hematoxy-lin-eosin(HE)staining were assessed to evaluate the effects of LN on APAP-induced hepatic inju-ry.Additionally,Western blot analysis was conducted to examine the expression levels of sphingo-sine kinase 1(SPHK1)and endoplasmic reticulum stress(ERS)-related proteins,thereby elucida-ting the potential mechanisms by which LN mitigates APAP-induced liver injury.The results dem-onstrated that varying concentrations of LN effectively ameliorated serum aminotransferase activi-ty and oxidative stress levels induced by APAP in a dose-dependent manner.Histopathological ex-amination via HE staining revealed significant improvement in APAP-induced liver tissue injury following treatment with different concentrations of LN.Furthermore,Western blot analysis indi-cated that the protein expressions of SPHK1,CHOP,p-IRE1α,ATF6,p-PERK,p-eIF2α,and ATF4 were markedly reduced after administration of various concentrations of LN.The results demonstrate that LN exhibits a significant protective effect against APAP-induced liver injury by inhibiting the SPHK1-mediated aberrant expression of ERS-related molecules.This study high-lights the importance of targeting SPHK1 in the treatment of APAP liver injury and provides a no-vel therapeutic approach through the multi-target and multi-pathway combination of monomers.

Objective To analyze the detection of helicobacter pylori(Hp)in different parts of gastric antrum,and to provide clinical guidance for finding the best biopsy site for Hp.Methods Patients who underwent 13C urea breath test and electronic gastroscopy from January 2020 to December 2022 were retrospectively analyzed and divided into 13C urea breath test positive group[delta over baseline(DOB)≥4]and 13C urea breath test negative group(DOB<4)according to DOB value.Gastroscopy reports and pathological data of patients were collected.According to different biopsy sites in gastric antrum,patients were divided into conventional biopsy site group,elevated erosive site group and flat erosive site group,and the detection rate of Hp in different biopsy sites was compared.13C urea breath test positive group was divided into group A(435)according to DOB value,and the gastric antral biopsy and pathology of each group were classified and analyzed.Combined with endoscopic reports and pathological data,patients were divided into atrophic gastritis group and non-atrophic gastritis group.Results In the 13C urea breath test positive group,the detection rate of Hp in the elevated erosive site group(96.4%)was higher than that in the conventional biopsy site group(92.7%)and the flat erosive site group(93.9%),and the difference was statistically significant(P = 0.036).In DOB group A,the detection rate of Hp was the highest at the site of elevated erosive and the lowest at the site of conventional biopsy,and the detection rate of Hp at the three biopsy sites was compared,the difference was statistically significant(P = 0.016);There was no significant difference in the detection rate of Hp at three biopsy sites between group B and group C(P = 0.622;P = 0.721);the non-atrophic gastritis group,the detection rate of Hp at the elevated erosive site(96.5%)was higher than that at the conventional biopsy site(91.2%)and the flat erosive site(92.0%),and the difference was statistically significant(P = 0.043).There was no significant difference in the detection rate of Hp at three biopsy sites in the atrophic gastritis group(P = 0.614).13C urea breath test negative group:There was no significant difference in Hp detection rate among the three biopsy sites(P = 0.255).Conclusion For patients with positive 13C urea breath test but low DOB value,the positive rate of Hp in the elevated erosive site is higher.For non-atrophic gastritis patients,the detection rate of Hp was higher in the elevated erosive sites than in the conventional biopsy sites.But for patients with atrophic gastritis,there was little difference in the detection rate of Hp in different parts of antrum.For patients with negative 13C urea breath test,there was no significant difference in Hp detection rate among the three biopsy sites.In future clinical work,for similar patients,precise biopsy can be performed to improve the detection rate of Hp.

Objective:To investigate therapeutic effect of reinfusion of tumor-infiltrating lymphocyte(TIL)with clustered regularly interspaced short palindromic repeats/CRISPR-associated 9(CRISPR/CAS9)knockout programmed death-1(PD-1)on colon cancer in mice.Methods:Subcutaneous injection of CT26 was used to establish mouse colon cancer model.TIL was extracted from tumor tissue of three model mice,and peripheral blood lymphocytes were extracted.PD-1 gene was knocked out of TIL.Reinfusion experiments were divided into control group(Control),lymphocyte group(Lym),tumor-bearing mouse TIL group(TIL),lentivirus empty empty group(pVSV-G-PX458-NC)and PX458-PD-1-sgRNA1 group(PD-1-sgRNA1),with 10 mice in each group.Tumor tissue quality and tumor inhibition rate were detected in each group.TUNEL was used to detect cell apoptosis in tumor tissues of mice.ELISA was used to detect contents of TNF-α and IFN-γ in tumor tissues of mice.Immunohistochemistry was used to detect expressions of CD4+T and CD8+T cells in tumor tissue.Immunofluorescence was used to detect expressions of proliferating cell nuclear antigen-67(Ki-67)and vascular endothelial growth factor(VEGF).Western blot was used to detect expressions of PD-1 and its ligand PD-L1 in tumor tissues.Results:PD-1-sgRNA1 could significantly inhibit growth of mouse tumor cells in vivo,inhibit expressions of Ki-67 and VEGF in tumor tissues,as well as expressions of PD-1 and PD-L1,elevate apoptosis rate,contents of TNF-α and IFN-γ in tumor tissues,and expressions of CD4+T and CD8+T cells(all P<0.05).Conclusion:Reinfusion of TIL with CRISPR/CAS9 knockout PD-1 can significantly inhibit expressions of Ki-67 and VEGF in colon cancer mice,enhance infiltration of CD4+T and CD8+T cells,induce tumor cell apoptosis and inhibit tumor growth.

Objective: To analyze the second hand smoke exposure and related factors of nonsmoking junior middle school students in Beijing, so as to provide a data support for formulating tobacco control measures. Methods: The multistage cluster random sampling method was used to select junior middle school students in Beijing. The valid data of 4 494, 4 915 and 3 792 nonsmoking middle school students were obtained from three waves of youth tobacco epidemic surveillance in 2013 (September to October), 2019 (August to November) and 2021 (September to December) wave, respectively. The information was collected by the national youth tobacco epidemic surveillance questionnaire. The complex sampling data analysis module of SPSS 21.0 was used to descriptive analysis and multivariate Logistic regression. Results: The proportions of secondhand smoke exposure of nonsmoking junior middle school students in the four types of places in the past 7 days in 2013, 2019 and 2021 in Beijing were 76.4%, 71.4% and 65.7%, respectively, with statistically significant differences (χ2=126.10, P<0.01). The proportions of that found someone smoking in the campus in the three waves of survey were 34.7%, 27.9% and 21.1% (χ2=209.78), the proportion of that found teachers smoking daily were 2.7%, 1.8% and 1.3% (χ2=22.14) (P<0.01), respectively. Multivariate Logistic regression analysis showed both parents smoking (OR=8.47, 95%CI=4.36-16.48), father smoking (OR=3.51, 95%CI=2.75-4.49), and friends smoking (OR=1.88, 95%CI=1.39-2.55) were the influencing factors of secondhand smoke exposure in four types of places of nonsmoking junior middle school students in 2013. Both parents smoking (OR=2.37, 95%CI=1.33-4.22), father smoking (OR=2.80, 95%CI=2.33-3.37), friends smoking (OR=2.24, 95%CI=1.71-2.92), and teaching the tobacco hazards in class (OR=0.77, 95%CI=0.64-0.93) were the influencing factors of secondhand smoke exposure in four types of places for nonsmoking middle school students in 2019. Both parents smoking (OR=3.93, 95%CI=2.29-6.75), fathers smoking (OR=3.30, 95%CI=2.72-3.99), and teaching the tobacco hazards in the class (OR=0.81, 95%CI=0.68-0.97) were the influential factor of secondhand smoke exposure in four types of places of nonsmoking junior middle school students in 2021 (P<0.05). Conclusions The secondhand smoke exposure of nonsmoking middle school students in Beijing has improved, but still is a high level. It is necessary to take corresponding measures to effectively protect nonsmoking junior middle school students from the harm of secondhand smoke.

Background The current oil production determines oil workers’ occupational noise exposure. Without effective protection, noise will affect various aspects of worker’s body functions, including acting on the adrenal cortex system and resulting in renal function damage. Objective To evaluate the associations of noise exposure and its cumulative exposure level with renal function impairment of oil workers. Methods Oil workers from a collective medical examination in a hospital were selected as the study subjects. In accordance with the national standard Measurement of Physical Agents in the Workplace Part 8: Noise (GBZ/T 189.8—2007), noise exposure was measured three times at the oil workers' work site, and their average value was calculated to obtain the cumulative noise exposure (CNE). A questionnaire survey was conducted to collect general information such as socio-demographic characteristics, family history, lifestyles, and occupational history. All blood biochemical indicators were measured in the fasting state. Renal function impairment was judged based on the glomerular filtration rate. The relationship between CNE and renal function was analyzed using receiver operating characteristic curve (ROC) for workers with noise exposure. Results A total of 2 917 subjects were included in the study and their prevalence of renal function impairment was 14.2%. The univariate analysis results suggested statistically significant differences in the prevalence of renal function impairment among the oil workers grouped by having hypertension or not, gender, age, marital status, marital status, smoking, and alcohol consumption (P＜0.05); the prevalence of renal impairment was significantly higher in those with abnormal values of uric acid, total cholesterol, triglycerides, high-density lipoprotein, and fasting glucose than in those with normal values (P＜0.05); the oil workers with noise exposure [n=1565, 53.7%, equivalent sound level ≥80 dB(A)] showed a higher prevalence of renal function impairment than those without (P＜0.05). The results of multiple logistic regression analysis showed that being female (OR=2.811, 95%CI: 1.960-4.030), age at 31 years and above (OR_31-40=3.502, 95%CI: 1.402-8.751; OR_41-50=4.255, 95%CI: 1.759-10.291; OR_≥51=7.179, 95%CI: 2.864-17.996), showing abnormal uric acid (OR=5.932, 95%CI: 4.486-7.843), having hypertension (OR=1.593, 95%CI: 1.230-2.063), alcohol consumption (OR=2.648, 95%CI: 1.346-5.212), and smoking (OR=1.816, 95%CI: 1.133-2.911) had higher risks of developing renal function impairment; besides, those exposed to noise had 1.351 times (95%CI: 1.073-1.702) higher risks of developing renal function impairment than non-exposed individuals. Noise-exposed oil workers in the renal impairment group had higher noise exposure intensity and CNE compared to the noise-exposed oil workers in the normal renal function group (P＜0.05), and the workers had an increased risk of renal function impairment when the CNE was >95.85 dB(A)·year versus CNE ≤ 95.85 dB(A)·year (OR=2.583, 95%CI: 1.956-3.411). Conclusion Exposure to noise, higher noise exposure intensity, and higher level of CNE may be associated with developing renal function impairment in oil workers. Oil workers with CNE above 95.85 dB(A)·year are at an increased risk of renal impairment.

Objective:To learn about the levels of serum iodine and thyroid function indicators in adults with normal thyroid function in Liaoning Province, to establish the medical reference value range of serum iodine, and to explore the relationship between serum iodine and thyroid function indicators.Methods:From February 2017 to December 2018, one subdistrict and one rural township were selected as the survey sites in the coastal area (Gaizhou City of Yingkou) and inland area (Kangping County of Shenyang) of Liaoning Province, respectively. Permanent residents aged 18 and older who have lived there for 5 years or more were selected as the survey subjects. Blood samples were collected to test the levels of serum iodine and thyroid function indicators [thyroid stimulating hormone (TSH), free triiodothyronine (FT 3), free thyroxine (FT 4), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb)]. The percentile method was used to establish the 95% medical reference value range of serum iodine in adults with normal thyroid function, and Pearson correlation analysis was used to analyze the correlation between serum iodine and thyroid function indicators. Results:A total of 1 621 adults with normal thyroid function were examined, the median serum iodine was 62.0 μg/L, and the 95% medical reference value range was preliminarily determined as 37.0-103.0 μg/L. Among them, the medians serum iodine of males and females (826 and 795 cases) were 62.3 and 61.0 μg/L, respectively, and there was no significant difference between genders ( Z=- 1.26, P = 0.210). The medians serum iodine of adults in coastal and inland areas (827 and 794 cases) were 61.7 and 61.9 μg/L, respectively, and there was no significant difference between areas ( Z = - 0.16, P = 0.870). The medians serum iodine of adults aged 18 - 29, 30 - 39, 40 - 49, 50 - 59 and 60 - 80 (385, 392, 378, 253 and 213 cases) were 61.0, 61.0, 63.0, 65.0 and 62.0 μg/L, respectively, and the difference between ages was statistically significant ( H = 14.52, P = 0.006). Pearson correlation analysis showed that serum iodine was weakly correlated with the level of FT 4 ( r = 0.17, P < 0.001), but not with the levels of TSH, TPOAb and TgAb ( P > 0.05). Conclusions:This study has established the medical reference value range of serum iodine in adults with normal thyroid function in Liaoning Province. Serum iodine is not correlated with the levels of TSH, TPOAb and TgAb.

Objective: To investigate the anti-tumor effect of CTL cells on colon cancer xenograft in nude mice after knocking out the immune check point CTLA-4 by CRISPR/Cas9 technology. Methods: A specific small guide RNA (sgRNA) for CTLA-4 was designed to construct sgRNA/Cas9 plasmid, which was then transfected into CTL using a lentiviral vector to obtain CTL cells with CTLA-4 deletion (CTLA-4 KO CTL). The transfection efficiency of the plasmid and the deletion efficiency of CTLA-4 were verified. BALB/c nude mice were randomly divided into two groups to prophylactically inoculate CTLA-4 KO CTL (experimental group) or CTL (control group); 3 days later, the animals of two groups were inoculated with colon cancer cell line LS174-T to observe the tumor formation rate and tumor formation time. After constructing colon cancer xenograft model in nude mice, the animals were randomly divided into two groups, respectively treated with CTLA-4 KO CTL (experimental group) and CTL (control group) cells to observe the tumor growth volume and survival time of mice. The serum levels of TNF-α and IFN-γ in nude mice were detected. Results: sgRNAwas designed and CRSIPR/Cas9 system with lentivirus as vector was successfully constructed. CTL cells were transfected with the established CRSIPR/ Cas9 system, and the highest transfection efficiency was up to (28.80±0.62)%. After transfection, the deletion efficiency of CTLA-4 was detected by Flow cytometry. The CTLA-4 expression of CTLA-4 KO CTL group was significantly lower than that of CTL group [(0.91±0.25)% vs (42.70±2.72)%, P<0.05]. In prophylactic assay, the formation rate of colon cancer xenografts in the experimental group was significantly lower than that in the control group(33.33%vs100%,P<0.05). In treatment assay, the tumor volume in the experimental group was significantly inhibited compared with the control group ([503±23.9] vs [911.2±51.4] mm3, P<0.05), and the survivaltimeoftheexperimentalgroupwassignificantlyprolonged (mediansurvivaltime:78dvs42d,P<0.05); Moreover, the secretion levels of serumTNF-α([268.93±17.04]pg/mlvs[148.26±20.07]pg/ml,P<0.05) and IFN-γ(315.38±18.67 pg/ml vs 202.92±29.32 pg/ml, P<0.05) in the experimental group were significantly higher than those in the control group. Conclusions: The lentiviral vector CRSIPR/Cas9 system is an effective gene editing method; its successful deletion of CTLA-4 in CTL cells can significantly inhibit the tumor formation rate of colon cancer xenografts in nude mice and enhance the anti-tumor effect of CTLon colon cancer xenografts.