恶性黑色素瘤的发病率和病死率在逐年增长，引发广泛关注。目前恶性黑色素瘤的治疗方式主要为手术、化疗和靶 向治疗，总体疗效极差。然而，PD-1抗体治疗恶性黑色素瘤的成功，使广大研究者把希望聚焦于生物免疫治疗。肿瘤浸润淋巴细 胞（tumor infiltrating lymphocyte，TIL）是从肿瘤组织分离出的淋巴细胞，经体外扩增后得到的能够杀伤肿瘤细胞的细胞群，具有 高杀瘤活性和高靶向性特点。临床试验研究发现，TIL对恶性黑色素瘤治疗效果显著且稳定，但其临床疗效尚未完全阐明。本文 对TIL免疫治疗的发展及其在恶性黑色素瘤治疗中的研究新进展作一综述，以期为恶性黑色素瘤的治疗提供新的策略。

Objective To investigate the feasibility and stability of medical gas suction feeding device for copying the model of respiratory failure in dogs. Methods The self-designed medical gas suction feeding device was used to establish the model of respiratory failure in dogs. After regulating the proportion of oxygen (O2), carbon dioxide (CO2) and nitrogen (N2), the fraction of inspiration O2 (FiO2) was decreased, while the forced inspiratory carbon dioxide (FiCO2) was increased. At the same time, the breathing out pathway was open to make the arterial oxygen partial pressure p (O2) and arterial blood carbon dioxide partial pressure p (CO2) reached and stabilized in a stable condition. The arterial blood samples between default state and 1 hour, 2 hour after modeling were collected to detect the blood gas index. Results One hour after the establishment of model, the p (O2) was≤60 mmHg (1 mmHg=0.133 kPa), and p (CO2) was≥50 mmHg (1 mmHg=0.133 kPa), which suggested that the dog model of respiratory failure was established successfully. Compared with the basic state, data of pH, oxygen content, oxygen saturation (SaO2) and residual alkali (BE) were decreased at 1 hour and 2 hour after modeling (P < 0.05). The p (O2), oxygen content, SaO2 were decreased in 2 hour after modeling compared with those of 1h after modeling (P<0.05). There were no significant differences in pH, p (CO2), TCO2, HCO3-and BE between 1 hour and 2 hour after modeling (P > 0.05). Conclusion Under the regulation of the medical gas suction feeding device, the respiratory failure state of large experimental animals is successfully established.

Objective To explore the association of COX-2 Gly587Arg polymorphism with the risk of primary liver cancer.Methods Two hundred and seventy patients with primary liver cancer and 540 health people were selected as our subjects.DNA were extracted from peripheral blood lymphocytes,and genotypes were measured by polymerase chain reaction-restriction fragment length polymorphism method.Odds ratios(OR) and 95％ confidence intervals(CI) were estimated by logistic regression.Results Two kinds of genotype (587Gly/ Gly and Gly/Arg) were found in all participants.No one carried 587Arg/Arg genotype.Among primary liver cancer patients,91.5％ (247/270,) 8.5％ (23/270) of individuals carried 587Gly/Arg and Gly/Arg genotype,which was significantly higher than that of controls (96.5％ (521/540,) 3.5％ (19/540)).Multivariate Logistic regression analysis showed that individual carried 587Gly/Arg genotype had an increased risk of developing primary liver cancer (OR =2.56,95％ CI =1.37-4.79,P =0.003) compared with 587Gly/Gly carriers.Conclusion COX-2 Gly587Arg polymorphism is a risk factor for primary liver cancer in Han.

Objective To establish a rapid, simple, sensitive, and specific multiplex real-time PCR method for quantitative detection of Campylobacter jejuni, Salmonella and Shigella in tree shrews.Methods Specific primers and probes were designed, according to the HipO gene of Campylobacter jejuni, inV gene of Salmonella and ipaH gene of Shigella.The primers were confirmed by single pathogen quantitative PCR, and the sensitivity and specificity of the multiplex PCR were analyzed.Finall, the samples of experimental tree shrews were detected by this multiplex PCR method.Results The PCR element of TaqMan-MGB real-time PCR assay was able to quantitatively amplify the Campylobacter jejuni, Salmonella or Shigella.Appropriate standard amplification curves of Campylobacter jejuni, Salmonella and Shigella in the multiplex quantitative PCR were obtained.The sensitivity of this method was 1×103 ng/μL.There was no false positive detection from other bacterial strains.Conclusions This multiplex quantitative real-time PCR method has good application and development prospects in the detection of microorganisms in tree shrews.

Objective:To investigate the effects of miR-497 on cytobiology behaviors of papillary thyroid carcinoma (PTC) by targetingly regulating the expression of Yes-associated protein 1 (YAP1) .Methods:Human TPC-1 cells were divided into control group, miR-497 group, si-YAP1 group and miR-497+si-YAP1 group. The liposome transfection was conducted by LipofectamineTM3000. The targeted relationship between miR-497 and YAP1 was validated by Luciferase Reporter Assay. The cell proliferation activity in each group was detected by MTT method. The apoptosis rates were analyzed by flow cytometry. The number of invasion cells was detected by Transwell. The cell migration rates were detected by scratch assay. The expression of Cyclin D1, matrix metalloproteinase 2 (MMP-2) , MMP-9, matrix metalloproteinase inhibitor-1 (TIMP-1) and activated caspase 3 (cleaved Caspase-3) was detected by Western blot. SPSS 22.0 was used to analyze data, and normally distributed measurement data were expressed as ( ± s) . One-way ANOVA was analyzed for the difference between multiple groups, and SNK-q were analyzed for the difference between two groups. Results:Compared with the control group, the expression of YAP1 mRNA and protein was decreased in miR-497 group and si-YAP1 group ( q=14.682, 14.597; 23.743, 23.571; P<0.05) , cell proliferation activity, number of invasion cells and migration rate were decreased ( q=4.724, 4.568, 3.841; 4.216, 3.952, 3.274; P<0.05) , apoptosis rate was increased ( q=3.783; 4.336; P<0.05) , expression of CyclinD1, MMP-2, MMP-9 and cleared Caspase-3 proteins was decreased ( q=5.823, 5.981, 6.036, 6.485; 5.934, 6.110, 6.573, 6.614; P<0.05) , and expression of TIMP-1 protein was increased ( q=6.071; 6.148; P<0.05) . Compared with si-YAP1 group, miR-497 level was increased in miR-497+si-YAP1 group ( q=14.726, P<0.05) , the expression of YAP1 mRNA and protein was decreased ( q=3.089, 3.126; P<0.05) , cell proliferation activity, number of invasion cells and migration rate were decreased ( q=2.654, 2.537, 2.246; P<0.05) , apoptosis rate was increased ( q=2.875, P<0.05) , expression of CyclinD1, MMP-2, MMP-9 and cleared Caspase-3 proteins was decreased ( q=4.371, 4.365, 4.383, 4.368; P<0.05) , and expression of TIMP-1 protein was increased ( q=4.275, P<0.05) . Conclusion:MiR-497 can negatively targetingly regulate the expression of YAP1, inhibit proliferation, invasion and migration of TPC-1 cells.

Objective: This paper discussed possible mechanisms of mobile phone addiction on mental health of vocational college students, and to explore the role of selfcontrol and selfesteem in this association. Methods: Totally 898 vocational college students from Liaocheng, Kunming and Wuhan were selected by random cluster sampling. Subjects were investigated with the Mobile Phone Addiction Index, DepressionAnxietyStress Scale (short version), SelfControl Scale, and SelfEsteem Scale. Results: About 27.6% of the participants selfreported mobile phone addiction. Mobile phone addiction score (45.80±10.41)was positively correlated with mental health(36.18±9.13)(P<0.01). A significant negative correlation was found between mobile addiction tendency with selfcontrol and selfesteem (both P<0.01). Male students scored higher on depression, anxiety and stress than female students(t=3.57, P<0.01). Selfcontrol played a partial intermediary role in the association between mobile phone addiction and mental health(β=-0.36, P<0.01). The influence of mobile phone addiction tendency on depression and stress were moderated by selfesteem. Conclusion Mobile phone addiction has a direct and indirect effect on mental health through selfcontrol. With increasing level of selfesteem, effect of mobile phone addiction on mental health tends to become weaker.

Objective: To explore the utilization and effects of informatization in perfecting the community health service mode. Method:Through purposive sampling, 12 community health service centers in Beijing, Shang-hai, Chengdu, and Zhengzhou were selected for site investigation. The heads of the health administrative department and community health service centers were interviewed, with a focus on the construction and utilization of the local community health informatization and a discussion of the role of informatization in perfecting the community health service mode. Results:The information systems can be divided into core systems, core auxiliary systems, and periph-eral support systems. Informatization provides strong support to perfecting the community health service mode in opti-mizing the service process, improving work efficiency, strengthening institutional cooperation, promoting quality regu-lation, optimizing performance appraisal, and strengthening doctor-patient interaction. Conclusion: Informatization plays a key role in perfecting the community health service mode. Recommendations were proposed to strengthen community health informatization construction and utilization:optimizing service processes, promoting the efficient co-ordination of safe health services, optimizing performance appraisals, and strengthening doctor-patient interaction.

Objective:To analyze the concerning guarantee mechanisms during the transformation of the com-munity health service mode. Method:Purposive sampling was adopted. Twelve community health service centers in Beijing, Shanghai, Zhengzhou, and Chengdu, where the transformation of the community health service mode was pi-loted earlier and representative, were selected as the field survey sites. The qualitative method was used to collect da-ta accompanied by the quantitative method. Results: The guarantee mechanisms related to the transformation of the community health service mode could be concluded into four main types:collaboration mechanism, health profession-al training mechanism, incentive mechanism, and policy guarantee mechanism. All of the four mechanisms contribu-ted to the improvement of general teamwork, dual referral systems, and the development of contract and appointment services. Conclusion:During the transformation of the community health service mode, priority strategies include top-down design, health professional training mechanisms, and performance-based incentive mechanism, all of which should be implemented in the future.

Objective:To analyze the structure modes of general practice teams in community health care cen-ters in order to provide empirical evidence for the transformation of the community health service mode. Method:Pur-posive sampling was adopted. Twelve community health service centers in Beijing, Shanghai, Zhengzhou and Cheng-du, where the transformation of the community health service mode was piloted earlier and representative, were se-lected as the field survey sites. The qualitative method was used to collect the data accompanied by the quantitative method. Results:The structure models of general practice teams could be divided into four types:1) general practi-tioner+nurse+nurse assistant+pharmacist, 2) physician (general practitioner, herbalist physician) +nurse+com-munity volunteers, 3 ) physician ( general practitioner/herbalist physician ) +nurse +assistant +community volun-teers, and 4) general practitioner+nurse+assisting team (professionals of public health and maternal care, etc) +supportive team ( pharmacists, health technician, etc) . Conclusion:The paper verified the common sense conclusion that general practitioners should play an essential role in general practice teamwork. The four general practice team models analyzed above positively contributed to the improvement of efficiency and quality, the relationship between health professionals and patients, the promotion of community participation, and the combination between preventive care and clinical care.

Objective:To analyze the progress of the contracting service model in community health centers in the typical areas in China, and provide empirical evidence for the hierarchical system targeted to make first contact and orderly dual transfer. Methods: Purposive sampling was adopted. Twelve community health centers in Beijing, Shanghai , Zhengzhou and Chengdu areas where the general practitioner model was conducted earlier and set to be the representative one, were selected as the field survey sites. A thematic framework analysis was used to describe the key factors around the contacting service model. Results:This model was developed around the following key factors:using the general practice team as the main service provider, taking the patients with chronic diseases as the main contracting groups and extending to their family members with the number of contracted ranging around 1500~2000 , freely providing both essential public health and medical services, fully using the family physician room as the con-tracting service platform and highlighting the actively serving concept, building the financial and non-financial incen-tives, health insurance benefits and green transfer mechanisms in order to efficiently guarantee the contracting service development. Conclusions: Based on the information platform, the contracting service model in the sample sites played a great role in the appointment and referral services development as well as the self-health management among residents, improving the relationship between physicians and patients, and promoting the formation of orderly health service pursuing pattern.