[摘 要] 目的：观察白细胞介素-37（IL-37）在乳腺癌患者的表达变化对CD8+ T细胞活性的影响。方法：纳入2020年7月至2022年9月在新乡医学院第一附属医院就诊的46例乳腺癌患者、24例乳腺良性肿瘤患者、20例对照者。采集外周血，分离血浆和外周血单个核细胞（PBMC），收集接受手术治疗的乳腺癌患者肿瘤组织和癌旁组织，分离组织中肿瘤浸润淋巴细胞（TIL），纯化CD8+ T细胞。ELISA法检测IL-37、可溶型单免疫球蛋白IL-1受体相关蛋白（SIGIRR）表达，实时定量PCR法检测组织中IL-37 mRNA，流式细胞术检测CD8+ T细胞中IL-18受体α链（IL-18Rα）和SIGIRR表达。外源性IL-37刺激纯化的CD8+ T细胞，与乳腺癌细胞系MCF-7共培养，通过测定乳酸脱氢酶水平计算靶细胞死亡比例，ELISA法检测上清中穿孔素、颗粒酶B、干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）水平。结果：乳腺癌患者血浆IL-37水平高于乳腺良性肿瘤患者[（554.17 ± 96.63）pg/mL vs （499.52 ± 78.66）pg/mL，P = 0.020]和对照者[（483.97 ± 47.23）pg/mL，P = 0.003]。乳腺癌患者肿瘤组织中IL-37 mRNA相对表达量高于癌旁组织[（1.88 ± 0.21） vs （1.00 ± 0.53）pg/mL，P < 0.001]。外周血IL-18Rα+ CD8+细胞比例、SIGIRR+ CD8+细胞比例、血浆可溶型SIGIRR水平在乳腺癌患者、乳腺良性肿瘤患者、对照者之间的差异无统计学意义（均P > 0.05）。CD8+ TIL表达IL-18Rα和SIGIRR的比例在肿瘤组织和癌旁组织之间的差异无统计学意义（P > 0.05）。重组人IL-37刺激后，CD8+ T细胞诱导靶细胞死亡比例、上清中IFN-γ和TNF-α水平在直接接触和间接接触共培养系统中均低于无刺激（均P < 0.05）。在直接接触共培养系统中，IL-37刺激后上清中穿孔素和颗粒酶B水平均低于无刺激（均P < 0.001），但在间接接触共培养系统中，上清中穿孔素和颗粒酶B水平在无刺激和IL-37刺激之间的差异无统计学意义（均P > 0.05）。结论：乳腺癌患者中IL-37水平升高可能参与诱导外周血和肿瘤微环境中CD8+ T细胞功能衰竭。

Objective The objective of this study was to investigate the expression of interleukin-38(IL-38)in patients with breast cancer and its regulatory function to CD8+T cell activity.Methods 44 patients with breast cancer,25 patients with benign breast tumor,and 20 controls,who were treated in the First Affiliated Hospital of Xinxiang Medical University from July 2020 and Sep-tember 2022.Mononuclear cells from plasma and peripheral blood of all subjects were isolated,tumor-infiltrating lymphocytes from tumor tissues of breast cancer patients were isolated,and CD8+T cells were purified.IL-38 protein level in the plasma was measured by enzyme-linked immunosorbent assay(ELISA).The relative level of IL-38 mRNA in the tissue was semi-quantified by real-time quantitative PCR.Recombinant human IL-38 was used to stimulate CD8+T cells from peripheral blood and tumor tissue from patients with breast cancer.A co-culture system was established between CD8+T cells and breast cancer MCF-7 cell line.The percentage of target cell death was calculated by measuring lactate dehydrogenase level in the supernatants.The levels of perforin,granzyme B,inter-feron-γ and tumor necrosis factor-α(TNF-α)in the supernatants were measured by ELISA.The immune checkpoint molecules ex-pression in CD8+T cells were detected by flow cytometry.Results The levels of plasma IL-38 were significantly higher in patients with breast cancer(74.23±19.88 pg/mL)compared with in patients with benign breast tumor(62.87±16.27 pg/mL,P=0.018)and controls(61.77±12.75 pg/mL,P=0.013).The relative expression of IL-38 mRNA in tumor tissues was significantly higher than in para-tumor tissues(1.57±0.22 vs.1.00±0.18,P<0.001).The proportion of target cell death induced by peripheral and tumor-in-filtrating CD8+T cells,and the levels of perforin and granzyme B secretion in direct contact co-culture group were higher than those in indirect contact co-culture group(P<0.05).There were no significant differences of either interferon-γ or TNF-α levels between di-rect contact and indirect contact co-culture group(P>0.05).In the direct contact co-culture group,the levels of target cell death pro-portion,perforin,granzyme B,interferon-γ and TNF-α l in the IL-38 stimulation group were lower than those in the non-stimulation group(P<0.05).In the indirect contact co-culture group,the target of cell death proportion,interferon-γ and TNF-α the IL-38 stimulation group were also lower than those in the non-stimulation group(P<0.05).However,there were no statistical differences of either perforin or granzyme B levels between the IL-38 stimulation group and non-stimulation group within the indirect contact co-culture group(P>0.05).There were also no differences in the levels of immune checkpoint molecules in CD8+T cells between the non-stimulation group and the IL-38 stimulation group(P>0.05).Conclusion Highly expressed IL-38 in patients with breast cancer may be involved in inducing CD8+T cell functional failure.

Background The presence of formaldehyde, ammonia, benzene, toluene, and xylene in indoor air of public places has been confirmed to cause health damage. The employees of barber and beauty shops are exposed to relatively enclosed space for a long time, and could surfer more serious health risks from indoor air chemical pollutants. Objective To analyze the concentrations of common indoor air chemical pollutants in barber shops and beauty salons in Liaocheng City, and explore potential health risks of the pollutants for employees. Methods Using a stratified randomized sampling method, 8 to 10 barber shops and 5 to 10 beauty salons were selected in the main urban area of Liaocheng City to conduct monitoring of the sanitary conditions of public places in winter and summer every year from 2016 to 2021; the indoor air concentrations of formaldehyde, ammonia, benzene, toluene, and xylene in the selected sites were measured, and a questionnaire survey was conducted to collect exposure characteristics of indoor pollutants. The concentration distributions of the five chemical pollutants were obtained from the monitoring data for 6 consecutive years, and the health risk assessment model recommended by the U.S. Environmental Protection Agency was used to perform health risk assessment of inhalation exposure. Results In 2016–2021, the median indoor air concentrations of formaldehyde, ammonia, benzene, toluene, and xylene in the two types of sites were lower than the limits of Hygienic Indicators and Limits for Public Places (GB 37488-2019), but the concentrations of some monitoring sites were higher than the limits. The disqualification rates of the five pollutants in the barber shops were 16.8%, 2.7%, 2.4%, 6.4%, and 12.0%, respectively. The disqualification rate of formaldehyde was the highest in all pollutants (22.0%), while the disqualification rates of ammonia, toluene, and xylene were 1.3%, 2.0%, and 2.0% in beauty salons respectively. Both formaldehyde and benzene were found to have carcinogenic risks (CR) in the two types of public places. Both median values of CR were greater than 1.0×10⁻⁶, and both maximum values were greater than 1.0×10⁻⁴. Formaldehyde had the highest non-carcinogenic risk in the indoor air of barber shops and beauty salons. The median non-carcinogenic hazard quotients (HQ) of formaldehyde were both greater than 1, and the maximum values were 16.72 and 12.19 times of the standard value; ammonia and toluene had the lowest non-carcinogenic risks, and their maximum values of HQ were less than 1; the median HQs of benzene and xylene were far less than 1, but their maximum risk values of barber shop were greater than 1. Conclusion For the sake of worker's health, formaldehyde and benzene should be the indoor air pollutant control priority for barber shops and beauty salons in Liaocheng; formaldehyde poses the most serious health hazard to practitioners and should be given high attention and necessary measures to reduce the hazard; benzene poses certain carcinogenic risks, with some of its highest values exceeding 10⁻⁴, which is higher than the recommended safety threshold.

Background A number of studies have shown that heavy metals in atmospheric PM_2.5 have impacts on human health, while studies on the impact of long-term and low-concentration exposure to lead in PM_2.5 on human health are limited. Objective To investigate the pollution characteristics of lead in ambient PM_2.5 and assess its chronic health risks. Methods Daily PM_2.5 concentration data in Jinan from 2014 to 2019 were collected, and the year-by-year trend of PM_2.5 concentration was analyzed. Licheng District (an industrial area) and Shizhong District (a residential area) were elected to install an ambient PM_2.5 monitoring stationrespectively. The sampling instrument was a 100 L·min⁻¹ high-flow PM_2.5 sampler, with a cumulative sampling time of 20-24 h per day, using a quartz fiber filter membrane for lead detection and a glass fiber filter membrane for PM_2.5 determination. The sampling frequency was 7 consecutive days per month from the 10^th to the 16^th (A total of 493 d were sampled and some were missing; 172 d during the heating period and 321 d during the non-heating period). Two PM_2.5 samples were collected in one monitoring site each day. A total of 986 samples were collected in one monitoring site. The lead content in PM_2.5 samples was detected by inductively coupled plasma mass spectrometry. The concentration of PM_2.5 was measured by weighing method. The annual average concentration and enrichment factor of lead in PM_2.5, the change trend of lead content per unit mass of PM_2.5, and the difference between heating period and non-heating period from 2014 to 2019 were estimated. Technical guide for environment health risk assessment of chemical exposure (WS/T 777-2021) was used to assess the health risks of exposure to lead in PM_2.5. Results The average annual concentration of lead in PM_2.5 ranged from 23.2 ng·m⁻³ to 154.7 ng·m⁻³. The average concentration in heating period from 2015 to 2019 was higher than that in non-heating period, and the differences in 2015, 2017, and 2019 were statistically significant (P < 0.01 or 0.001). The enrichment factors ranged from 200 to 1342 in 2014 to 2019. The average enrichment factors in heating period in 2015, 2017, and 2018 was higher than those in non-heating period, and the difference was statistically significant (P < 0.05 or 0.001). The lead contents per unit mass of PM_2.5 ranged from 493 ng·mg⁻¹ to 1944 ng·mg⁻¹, and the differences between heating period and non-heating period in 2014, 2017, and 2018 were statistically significant (P < 0.05 or 0.001). The average annual concentration and enrichment factor of lead in PM_2.5 showed a downward trend, and thus the lead content per unit mass of PM_2.5 also decreased. From 2014 to 2019, the carcinogenic risk of lead in PM_2.5 in Jinan ranged from 1.69×10⁻⁸ to 2.45×10⁻⁶, showing a significant downward trend year by year, and the 95^th percentile decreased by 3%-46% from the previous year. The carcinogenic risk level of lead was reduced to an acceptable level (<1×10⁻⁶) after 2017. Conclusion From 2015 to 2019, lead concentration and enrichment factor in PM_2.5 increase during heating period compared with non-heating period, but it is not completely consistent of lead content in PM_2.5 per unit mass. From 2014 to 2016, exposure to lead in PM_2.5 may elevate carcinogenic risk to human. After 2017, the carcinogenic risks of exposure to lead in PM_2.5 are at an acceptable level.

Background The incidence of Legionnaires' disease is increasing globally and artificial water environment is becoming a common source of outbreaks. Molecular typing techniques can help prevent and control Legionella. Objective To understand the molecular epidemiological characteristics of Legionella pneumophila in artificial water environment of Shanghai hospitals, and provide a scientific basis for the prevention and control of Legionnaires' disease. Methods Water samples were collected from artificial water environment in 14 hospitals from May to October each year from 2019 to 2020 in Shanghai. A total of 984 water samples were collected from 8 Grade-A tertiary hospitals and 6 non-Grade-A tertiary hospitals, including 312 samples of cooling water, 72 samples of chilled water, and 600 samples of tap water. The water samples were isolated and serotyped for Legionella pneumophila and preserved, and the positive rate of Legionella pneumophila in the samples was used as an indicator of contamination. The preserved strains were resuscitated and 81 surviving strains were obtained for pulsed field gel electrophoresis (PFGE) typing analysis. Results A total of 124 Legionella pneumophila positive water samples were detected, with a positive rate of 12.60%. The positive rate was higher in the Grade-A tertiary hospitals (16.54%, 87/526) than in the non-Grade-A tertiary hospitals (8.08%, 37/458) (χ²=15.91, P<0.001). The positive rate of cooling water (23.40%) was the highest among different types of water samples, and the difference was statistically significant (χ²=61.19, P<0.001). The difference in positive rate of tap water was statistically significant among different hospital departments (χ²=11.37, P<0.05). The positive rate in 2019 (15.06%) was higher than that in 2020 (9.84%) (χ²=6.23, P<0.05). From May to October, August had the highest annual average positive rate (16.46%) and October had the lowest (8.54%), but the difference in positive rates among months was not statistically significant (χ²=5.39, P=0.37). The difference in positive rate among districts was statistically significant (χ²=24.88, P<0.001). A total of 131 strains of Legionella pneumophila were isolated, with serotype 1 (80.15%, 105/131) predominating. Among the 81 surviving strains of Legionella pneumophila subjected to PFGE typing, the band-based similarity coefficients ranged from 41.30% to 100%. Among the 29 PFGE band types (S1-S29) recorded, each band type included 1-10 strains, and S28 was the dominant band type. Four clusters (I-IV) of PFGE band types were identified, accounting for 66.67% (54/81) of all strains and containing 13 band types. Conclusion Legionella pneumophila contamination is present in the artificial water environment of hospitals in Shanghai from 2019 to 2020, and the contamination in tap water deserves attention. The detected serotype of Legionella pneumophila is predominantly type 1, and PFGE typing reveals the presence of genetic polymorphism. Therefore, the monitoring and control of Legionella pneumophila in hospital artificial water environment should be strengthened.

Objective:To systematically evaluate the efficacy of different kinds of smoking cessation drugs by network Meta-analysis.Methods:Literature was retrieved from PubMed, Web of Science, Embase, Cochrane Library, CBM, CNKI, VIP, Wan fang database, from the establishment of the database to November 2022, and randomized controlled trials (RCT) about bupropion, varenicline, nicotine replacement therapy (NRT) versus placebo in the treatment of smoking patients were collected. After data extraction from included literature which met inclusion criteria, and quality evaluation with Cochrane 5.1 risk bias evaluation tool, network Meta-analysis was performed by Stata15.1 software.Results:A total of 19 RCTs, involving 6106 patients and three interventions measures (bupropion, varenicline, NRT) and one control measure (placebo) were included. The results of network Meta-analysis showed that in terms of short-term abstinence rate, varenicline [ OR=4.21, 95% CI (2.32, 7.63)], bupropion [ OR=2.81, 95% CI(1.05, 7.54)] were better than placebo ( P<0.05). The surface under the cumulative ranking area (SUCRA): varenicline (90.2%)>bupropion (64.8%)>NRT (41.7%)>placebo (3.2%). In terms of the long-term abstinence rate, varenicline [ OR=3.06, 95% CI (1.59, 5.90)], NRT [ OR=3.39, 95% CI (2.20, 5.21)] were better than placebo ( P<0.05). SUCRA: varenicline (83.8%)>NRT (73.9%)>bupropion (37.2%)>placebo (5.2%). Conclusion:The existing evidence shows that compared with bupropion, NRT, varenicline has the best effect on quitting smoking, but more high-quality randomized trial evidence is needed for verification.

In recent years, liver cancer stem cells (LCSC) have been considered one of the main causes of treatment failure and recurrence of hepatocellular carcinoma (HCC). Many studies have shown that LCSC are a small fraction of cells with the abilities of self-renewal, differentiation, and tumorigenesis in HCC tumor, which can initiate the onset of HCC and affect its proliferation, invasion, metastasis, recurrence, and drug resistance. Therapies based on tumor microenvironment (TME) have been developed recently, and a number of studies have found that targeting the relevant elements of TME has a higher therapeutic value than targeting tumor cells themselves. TME is the microenvironment for the growth of LCSC and HCC cells, and it interacts with LCSC and has a synergistic effect, thereby playing a positive role in the development and progression of HCC. This article introduces how various cellular components and non-cellular components in TME interact with LCSC to regulate the development and progression of the HCC. In addition, this article also describes the molecular targets, therapies, and drugs associated with the main components of TME and LCSCs, in order to seek safer and more effective targeted therapies for HCC.

Objective:To analyse the clinical characteristics and antiviral therapy in immunosuppressed hospitalized patients with influenza.Methods:The clinical data of 273 patients with positive influenza A or B virus nucleic acid admitted in Peking University People’s Hospital from November 2015 to March 2022 were retrospectively analyzed. Among them, 123 were immunosuppressed and 150 were non-immunosuppressed. The clinical characteristics and antiviral therapy in immunosuppressed patients with influenza were analyzed. SPSS 22.0 software was used to analyze the data.Results:Chemotherapy for malignancies was the most common cause of immunosuppression (61.8%, 76/123), followed by haemopoietic stem cell transplantation (24.4%, 30/123). The common symptoms were fever (93.5%, 115/123) and cough (41.5%, 51/123). The proportions of co-infections (22.8%, 28/123) and complications (43.9%, 54/123) in immunosuppressed hospitalized patients were higher than those in non-immunosuppressed patients ( χ2=9.365 and 7.496, both P<0.01). Compared with single drug therapy, combination of antiviral drugs did not shorten the fever time, negative conversion time of virus nucleic acid and the length of hospital stay, and reduce the death ( U/ χ2=312.5, 356.0, 749.5 and 0.185, all P>0.05). Compared to patients without corticosteroids use, the use of corticosteroids did not increase mortality in immunosuppressed patients ( χ2=2.508, P=0.113). Conclusions:Classical symptoms may be absent in immunosuppressed patients with influenza, and early detection of influenza virus is still an important means of early diagnosis. Co-infections and complications are more common in immunosuppressed influenza patients. Immunosuppressed influenza patients did not benefit from the combination of antiviral therapy.

The nail and nail bed are indispensibal structures with important function and esthetics role on the tip of fingers. Injury of the nail and nail bed often seriously affect the appearance and function of the fingers. The correct and timely treatment is essential for the restortation of good function according to the typing and degreement of the injuries. This paper reviewed about the function of nail and nail bed, typing of injury, evaluation of therapeutic effect and reconstruction of nail bed injury.