[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 To analyze the epidemiological characteristics and related occupational diagnosis situations of occupational heat illness (OHI) diagnosed by Guangdong Province Hospital for Occupational Disease Prevention and Treatment (GDHOD) from 2011 to 2022. Methods A total of 203 patients who applied for OHI diagnosed in GDHOD from 2011 to 2022 were recruited as research subjects using the retrospective analysis method. Clinical data of OHI diagnosed cases was collected from "Occupational Diseases and Hazards Monitoring Information System" under "China Disease Prevention and Control Information System", and data of cases that diagnosed as non-OHI were collected from the occupational disease diagnosis file of GDHOD for retrospective analysis. Resultsi) The number of OHI diagnosed patients was 174 among 203 cases, with a rate of 85.7%. ii) The heat stroke accounted for 72.4% with a mortality rate of 7.5%, male patients accounted for 86.2% among the 174 OHI diagnosed cases. The median age of onset was 47 years, and patients aged 45-60 years accounting for 56.3%. The median working period of onset of illness was 80 days, with 20.1%, 40.8%, 53.4% and 70.1% of cases occurring within 1, 30, 90 and 365 days of working, respectively. The patients were concentrated in the Pearl River Delta region, accounting for 93.1%. The peak incidence of OHI occurred from May to September, accounted for 96.6%, with the highest incidence occurred in July. About 67.3% of cases occurred on days when the maximum temperature was ≥35.0 ℃. Cases occurred between 12:00 and 18:00 accounting for 74.1%, and cases occurred within 8 hours of work accounting for 75.2%. OHI of patients occurred during operations in non-heat-source workshops accounted for 43.7% of cases, while outdoor operations accounted for 39.7%. OHI patients in manufacturing and small private enterprises accounted for 55.2% and 62.6%, and the main occupations were workshop operators, loaders/unloaders, and sanitation workers, comprising 63.2% of cases. iii) Among the 29 cases diagnosed as non-OHI, accounting for 86.2% patients with high-temperature work history who did not meet clinical diagnostic criteria, most of them were diagnosed as OHI precursor. Conclusion OHI patients in Guangdong Province predominantly occur in summer and autumn, with heat stroke being the primary condition. Middle-aged males, workers in non-heat-source workshops and outdoor settings have higher risk of OHI. OHI cases are concentrated in specific region and enterprise. The OHI prevention should be enhanced on high-risk workers, who work in the Pearl River Delta region, manufacturing, and small private enterprises.

Objective:To investigate the correlation of preoperative platelet distribution width (PDW) with clinical features and prognosis of patients with medullary thyroid carcinoma (MTC) .Methods:The clinical data of 160 MTC patients admitted to Zhejiang Cancer Hospital in Department of Head and Neck Surgery from Jun. 2007 to Sep. 2021 were retrospectively collected. There were 74 males and 86 females, aging 8-77 years (mean 48.73±13.76). The median was used to determine the cut-off value of PDW and divided into low PDW group and high PDW group. The correlation between preoperative PDW and clinicopathological features of MTC patients was analyzed by Chi-square test and Spearman correlation test. The relationship of preoperative PDW with overall survival (OS) and disease free survival (DFS) of patients were analyzed by Kaplan-meier and Log-rank test. Univariate and multivariate Cox regression analyses were used to analyze the risk factors for DFS in MTC patients.Results:The preoperative PDW level was closely correlated with the tumor size ( χ2=4.46, P=0.035), TNM stage ( χ2=5.02, P=0.025), bilateral lesions ( χ2=4.94, P=0.026) ,multiple lesions ( χ2=5.19, P=0.023), capsular invasion ( χ2=5.75, P=0.017), extrandular invasion ( χ2=4.27, P=0.039), and vascular tumor thrombus ( χ2=4.48, P=0.034) in MTC patients ( P<0.05). Spearman correlation test showed that preoperative PDW level was negatively correlated with clinical stage ( r=-0.166, P=0.036), lymph node metastasis ( r=-0.187, P=0.018), multiple lesions ( r=-0.176, P=0.026) and vascular tumor thrombus ( r=-0.220, P=0.005) in MTC patients ( P<0.05). Survival analysis showed that reduced PDW predicted worse DFS for MTC ( χ2=9.989, P=0.002). Multivariate Cox regression analysis showed that low PDW ( OR=0.847, 95% CI:0.724-0.992, P=0.040) and lymph node metastasis ( OR=4.913, 95% CI:2.415-9.995, P<0.001) were independent risk factors for DFS in MTC patients. Conclusion:Preoperative decreased PDW is a high risk factor for poor prognosis of MTC and can be used as an indicator to predict recurrence in MTC patients.

OBJECTIVES: Shelter hospital was an alternative way to provide large-scale medical isolation and treatment for people with mild coronavirus disease 2019 (COVID-19). Due to various reasons, patients admitted to the large shelter hospital was reported high level of psychological distress, so did the healthcare workers. This study aims to introduce a comprehensive and multifaceted psychosocial crisis intervention model. METHODS: The psychosocial crisis intervention model was provided to 200 patients and 240 healthcare workers in Wuhan Wuchang shelter hospital. Patient volunteers and organized peer support, client-centered culturally sensitive supportive care, timely delivery of scientific information about COVID-19 and its complications, mental health knowledge acquisition of non-psychiatric healthcare workers, group activities, counseling and education, virtualization of psychological intervention, consultation and liaison were exhibited respectively in the model. Pre-service survey was done in 38 patients and 49 healthcare workers using the Generalized Anxiety Disorder 7-item (GAD-7) scale, the Patient Health Questionnaire 2-item (PHQ-2) scale, and the Primary Care PTSD screen for the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (PC-PTSD-5). Forty-eight healthcare workers gave feedback after the intervention. RESULTS: The psychosocial crisis intervention model was successfully implemented by 10 mental health professionals and was well-accepted by both patients and healthcare workers in the shelter hospital. In pre-service survey, 15.8% of 38 patients were with anxiety, 55.3% were with stress, and 15.8% were with depression; 16.3% of 49 healthcare workers were with anxiety, 26.5% were with stress, and 22.4% were with depression. In post-service survey, 62.5% of 48 healthcare workers thought it was very practical, 37.5% thought more practical; 37.5% of them thought it was very helpful to relief anxiety and insomnia, and 27.1% thought much helpful; 37.5% of them thought it was very helpful to recognize patients with anxiety and insomnia, and 29.2% thought much helpful; 35.4% of them thought it was very helpful to deal with patients' anxiety and insomnia, and 37.5% thought much helpful. CONCLUSIONS Psychological crisis intervention is feasible, acceptable, and associated with positive outcomes. Future tastings of this model in larger population and different settings are warranted.
Humans ; COVID-19 ; Sleep Initiation and Maintenance Disorders ; Crisis Intervention ; Psychosocial Intervention ; SARS-CoV-2 ; Mental Health ; Depression/epidemiology* ; Health Personnel/psychology* ; Anxiety/etiology*

OBJECTIVE: To summarize and analyze the diagnostic ideas of new occupational lung tumors in Guangdong Province.METHODS: According to the Law of the People′s Republic of China on the Prevention and Control of Occupational Disease and the GBZ 94-2002 Diagnostic Criteria of Occupational Cancer, the key diagnostic points of 6 new occupational lung tumors diagnosed in Guangdong Province from 2010 to 2011 were analyzed. RESULTS: There were 9 cases of 6 new kinds of new occupational tumors were diagnosed in Guangdong Province in 2010-2011. The cases included 3 occupational lung cancer of coke oven workers, 2 occupational lung cancer caused by asbestos, 1 occupational mesothelioma caused by asbestos, 1 occupational lung cancer caused by arsenate, 1 occupational lung cancer caused by chromate salt, and 1 occupational lung cancer caused by asphalt. During the process, the diagnosis was based on the principles of the comprehensive analysis and the attribution diagnosis, combined with occupational history, occupational disease hazard exposure history, clinical data and auxiliary examination results. If the patients were diagnosed with a primary tumor, the patients′ exposure history to occupational carcinogens should be tracked, traced and confirmed, and the diagnosis should be confirmed by referring to the list of occupational carcinogens and literature reports of the International Labor Organization, and not limited to only the personnel in a particular industry. CONCLUSION: During the diagnostic process of occupational tumors, attention should be paid to confirm the exposure history of occupational carcinogen. The key is to determine the exposure of corresponding occupational carcinogen, the route and the time of exposure and the incubation period.

Objective To investigate the clinical features and prognostic characteristics of head and neck cancer in patients with esophagus cancer and triple primary carcinoma(TPC).Methods A total of 30 patients with head and neck cancer with esophagus cancer TPC were collected in Zhejiang Cancer Hospital from January 2007 to December 2016.The distribution of cancer kinds and the incidence of synchronous and metachronous cancer were described.The clinical characteristics and prognosis were also compared in synchronous and metachronous cancer.The influence of number of hospitalization and different treatments on the survival time were analyzed.Results The TPC of "laryngeal pharynx + esophagus + lung" and "laryngeal pharynx + esophagus + oropharynx" had the highest incidence,that was 20.0％ in 30 patients (6/30).The second type was "laryngeal pharynx + esophagus + larynx".Fifteen cases were synchronous cancer and other 15 cases were metachronous cancer.The rate of surgery was 73.3％ (11/15),and the number of hospitalization who more or equal than 5 was 73.3％ (11/15) in the synchronous cancer.While the rate of surgery was 33.3％ (5/15),and the number of hospitalization who more or equal than 5 was 33.3％ (5/15) in the metachronous cancer.There were significant differences between synchronous and metachronous cancer (x2 =4.661,4.661,all P ＜ 0.05).The 1-year,3-year and 5-year survival rates were 39.9％,19.9％ and 0.0％ in patients with synchronous cancer.The mean survival time was (18.4 ± 6.2)months.In contrast,the survival rates were 78.7％,77.8％ and 59.1％ in metachronous cancer.The mean survival time was (122.2 ± 17.2) months.There were significant differences between the two groups (survival rate:x2 =10.934,P =0.001;mean survival time:t =3.201,P =0.003).The survival rate of the number of hospitalization more than or equal to 5 times had significant difference compared with those less than 5 times (x2 =10.574,P =0.001).There was no statistically significant difference in the improvement of OS between single operation,chemotherapy and target treatment (P ＞ 0.05).Conclusion Head and neck cancer in patients with esophagus cancer TPC can still has a high survival rate through active combined modality therapies,especially in metachronous carcinoma.

Objective: To explore the effects of miR-149-3p on the proliferation, apoptosis, invasion and migration of cervical cancer HeLa cells and the possible mechanisms. Methods: HeLa cells were randomly divided into five groups, including untransfected (HeLa) group, mimic-scramble group (the negative control of miR-149 mimic), miR-149 mimic group, FOXP3 over-expression (pc-FOXP3) group, and co-transfection (mimic+pc-FOXP3) group. The targeted relationship of miR-149-3p and FOXP3 was verified by luciferase assay. The expressions of miR-149-3p and FOXP3 mRNA were tested by quantitative real-time reverse transcription PCR (qRT-PCR). The protein levels of FOXP3 were measured by Western blotting. The proliferation was detected by CCK-8; the apoptosis was tested by flow cytometry, the cell invasion was measured by transwell invasion assay and cell migration was detected by scratch assay. Results: The luciferase assay showed that miR-149-3p could target combine with FOXP3. Compared with untransfected group, the expression of miR-149-3p was increased while mRNA level of FOXP3 was decreased in miR-149 mimic group (all P<0.01). Moreover, the protein level of FOXP3 in miR-149 mimic group was lower than that in untransfected group (P<0.01), while the protein level of FOXP3 in pcFOXP3 group was higher than that in untransfected group (P<0.01); Compared with pc-FOXP3 group, the protein levels of FOXP3 in mimic+pc-FOXP3 group were reduced (P<0.01). The proliferation in miR-149 mimic group was lower than that in untransfected group (P<0.01), while the proliferation in pc-FOXP3 was higher than that in untransfected group (P<0.01); compared with pc-FOXP3 group, the proliferation in mimic+pc-FOXP3 group was decreased (P<0.01). The apoptosis rate of HeLa cells in miR-149 mimic group was higher than that in untransfected group (P<0.01), while the apoptosis rate in pc-FOXP3 was lower than that in untransfected group (P< 0.01); compared with pc-FOXP3 group, the apoptosis in mimic+pc-FOXP3 group was elevated (P<0.01). The number of invasive cells per field and wound healing rate in miR-149 mimic group was lower than those in untransfeccted group (P<0.01) while the invasive cells and wound healing rate in pc-FOXP3 group was higher than those in untransfeceted group (P<0.01); compared with pc-FOXP3 group, the number of invasive cells per field and wound healing rate in mimic+pc-FOXP3 group was reduced (P<0.01). Conclusion: miR-149-3p inhibits proliferation, invasion and migration and promotes apoptosis of cervical cancer HeLa cells via targeting FOXP3.

Objective To investigate the predictive factors for central lymph node metastasis (CLNM) in papillary thyroid microcarcinoma(PTMC).Methods A retrospective study including 2511 cases of PTMC admitted from Jan.2013 to Jan.2016 were enrolled in our study.Chi-square test was used in univariate analysis.Logistic regression analysis was applied for multivariate analysis.The relation between age,sex,tumor size,multifocality,thyroidal extension,nodular goiter and central lymph node metastasis is analyzed.Results Univariate analysis showed that age,sex,tumor size,multifocality,thyroidal extension and nodular goiter had statistical significance.Age less than 45(P＜0.001,x2=17.442);Male gender(P＜0.001,x2=17.029);Tumor size less than 5 mm (P＜0.001,x2=70.164.);Extrathyroid extension factor (P＜0.001,x2=63.197);Nodular hyperplasia factor (P=0.017,x2=5.611).Multivariate analysis showed there was a significant relationship between multifocality and the central lymph node positivity.The odds ratio (OR) was 1.587 in patients with tumor foci ≥2(P＜0.001).While OR increased sharply near to 3 in patients withtumor foci ≥3(OR=2.730).Tumor size(OR=1.926);Extrathyroid extension(OR=1.606).Conclusions Multifocalty,tumor size and thyroidal extension are the main predicative factors for central lymph node metastasis in PTMC.Among them,tumor foci ≥ 3 is an important predictor.Besides the conventional factors such as tumor size,thyroidal extension etc,multifocalty should also be taken into consideration.

Peripheral blood circulating tumor DNA(ctDNA) is a kind of DNA that is released into the blood circulation system after the tumor cell somatic cell DNA is exfoliated or when the cell apoptosis is released.ctDNA is a characteristic tumor biomarker, known as " liquid biopsy" . It can reflect the invasion and metastasis of the tumor, and can monitor the effect and prognosis of the tumor.The current research is mainly focused on relatively mature breast cancer, lung cancer and other diseases.In this study, the development of ctDNA inspection technology and its current research status at home and abroad are reviewed.

Objective The survival and prognosis factors of thoracic esophageal squamous cell carcinoma patients after radical resection was investigated.Methods 1923 patients of thoracic esophageal squamous cell carcinoma after radical resection were included in our study from January 1th 2000 to January 1th 2010 in Zhejiang Cancer Hospital,1 670 male and 253 female.the age in the majority with 40 to 59 years old(1 076/1 923,56.0％).Eighteen prognosis factors were collected.A multivariate analysis of these selected variables was performed using Cox proportional model and prognosis index.We used life table for accumulated survival rate.Results The accumulated survival rate for all patients were 82％,48％ and 35％ in 1 year,3 years and 5 years,respectively.Median survival time was 35.42 months.The significant prognosis factors included body mass index,length of tumor,depth of invasion,differentiation degree,lymph node metastatic degree and region,complication of surgery.Conclusion The prognosis of thoracic esophageal squamous cell carcinoma was affected by multi-factors and prognosis index can predict survival condition.