BACKGROUND: One of the most important treatment modalities for non-small cell lung cancer (NSCLC) is immune checkpoint inhibitor. Nevertheless, a small percentage of patients do not respond well to these therapies, highlighting the significance of identifying important CD8+ T cell subsets for immunotherapy and creating trustworthy biomarkers. The purpose of this study is to assess the potential utility of TIM3+CD8+ T cells as new biomarkers by examining their expressions in various areas of the NSCLC tumor microenvironment. METHODS: Based on biopsy techniques, tumor tissue samples were obtained from patients with NSCLC and categorized into tumor central and non-central regions. Using flow cytometry, the infiltration of TIM3+CD8+ T cells and the surface expression of programmed cell death 1 (PD-1) on these cells were examined, and their correlations with the effectiveness of immunotherapy were assessed. RESULTS: The non-central region of tumor tissues had considerably larger infiltration of TIM3+CD8+ T lymphocytes compared to the non-central region (P<0.0001). This pattern was found in both subgroups with tumor diameters ≥3 cm or <3 cm (P<0.01). In comparison to TIM3-CD8+ T cells, TIM3+CD8+ T cells showed higher levels of PD-1 (P<0.001), with more PD-1+TIM3+CD8+ T cells invading the non-central region (P<0.01). Clinical responders to immunotherapy had considerably lower infiltration levels of TIM3+CD8+ T cells in the tumor non-central region compared to non-responders, with lower levels correlated with better clinical outcomes (P<0.01), while no correlation was identified in the tumor central region (P>0.05). According to reciever operating characteristic (ROC) curve analysis, TIM3+CD8+ T cells in the tumor non-central region had an area under the curve (AUC) of 0.9375 for predicting the effectiveness of immunotherapy, which was considerably higher than that of TIM3+CD8+ T cells in the tumor central region and programmed cell death ligand 1 (PD-L1) [tumor proportion score (TPS)]. CONCLUSIONS In the tumor microenvironment of NSCLC, TIM3+CD8+ T cells show regional distribution patterns. The expression of this cell population in the non-central region of the tumor microenvironment may be a biomarker for predicting the effectiveness of immunotherapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Lung Neoplasms/metabolism* ; Hepatitis A Virus Cellular Receptor 2/immunology* ; Tumor Microenvironment/immunology* ; CD8-Positive T-Lymphocytes/metabolism* ; Male ; Female ; Middle Aged ; Aged ; Adult ; Programmed Cell Death 1 Receptor/metabolism* ; Immunotherapy ; Clinical Relevance

Environmental monitoring technologies competition can effectively improve the comprehensive quality and technical skills of technical personnel by means of professional theory exams and on-site practical assessment. In view of the undertaking work of the Second National Competition of Professional and Technical Personnel in Ecology and Environment Monitoring (special competition for radiation monitoring), this paper summarized the experience and gains in the aspects of preliminary preparation, field implementation, achievement generation, etc., analyzed the problems in national radiation environmental monitoring through the achievements of the special competition for radiation monitoring, and put forward recommendations for the next step, in order to provide reference for undertaking similar major events in the future and provide ideas and directions for national radiation environmental monitoring.

OBJECTIVE： To establish the method for the content determination of astragaloside Ⅳ， emodin and chrysophanol in Jianpi yishen pills （JYP） and to investigate the effects of JYP on calcium， phosphorus metabolism and inflammatory factors in chronic renal failure （CRF） model rats. METHODS： HPLC method was adopted. The determination of astragaloside Ⅳ， emodin and chrysophanol was perform on Agilent Zorbax SB-C18， Agilent TC C18 column， respectively； mobile phase consisted of acetonitrile-water （36 ∶ 64， V/V） and methanol-0.1％ phosphoric acid solution （75 ∶ 25， V/V）； the detectors were evaporative light-scattering detector and diode-array detector （detection wavelength of 254 nm）； the column temperatures were set at 30 ℃and 25 ℃ at the flow rate of 1.0 mL/min； the sample sizes were 20 and 10 μL. SD rats were randomly divided into normal group， model group， Niaoduqing group （1.80 g/kg） and JYP low-dose， medium-dose and high-dose groups （1.71， 3.43， 6.85 g/kg）， with 10 rats in each group. Except for normal group， CRF model of other groups were established by 5/6 nephrectomy in other groups. Four months after modeling， normal group and model group were given constant volume of water intragastrically； admi- nistration groups were given relevant medicine intragastrically， once a day， for consecutive 12 weeks. The levels of serum creatinine （Scr）， urea nitrogen （BUN）， parathyroid hormone （PTH） and inflammatory factors （IL-6， TNF-α） were measured by ELISA. Methyl thymol blue colorimetric method and phosphomolybdic acid method were used to detect the contents of blood calcium and phosphorus. Correlation of inflammatory factors with related calcium and phosphorus metabolism indexes （blood calcium， blood phosphorus， PTH） were investigated with Pearson assay. RESULTS： The linear range of astragaloside Ⅳ， emodin and chrysophanol were 54.537-381.759， 2.960-20.720， 6.318-44.223 μg/mL， respectively. The limits of quantitation were 0.010， 0.288， 0.216 μg/mL； the limits of detection were 0.003， 0.096， 0.072 μg/mL. RSDs of precision， reproducibility and stability tests were all lower than 3.0％. The recoveries were 97.18％-102.33％（RSD＜3％，n＝9）. After modeling （before medication）， serum contents of Scr and BUN in model group and administration group were increased significantly， compared with normal group （P＜0.01）. After medication， above indexes of administration group were decreased significantly， compared with model group and the same group before medication （P＜0.01）. Compared with normal group， the content of blood calcium were decreased significantly， while the contents of IL-6 and TNF-α were increased significantly （P＜0.01）. Compared with model group， the content of blood calcium were increased significantly in JYP medium-dose and high-dose groups， while serum content of PTH in Niaoduqing group， serum contents of PTH and IL-6 in JYP medium-dose and high-dose groups as well as serum content of TNF-α in administration group were decreased significantly （P＜0.05 or P＜0.01）. JYP had no significant effect on blood phosphorus in rats， and there was no correlation of inflammatory factors with related calcium and phosphorus metabolism indexes （P＞0.05）. CONCLUSIONS： The established content determination method is simple， specific and sensitive， and can be used for content determination of astragaloside Ⅳ， emodin and chrysophanol in JYP. JYP can improve renal function of CRF model rats， relieve calcium metabolism disorder and inhibit the expression of inflammatory factors.

Objective To analyze the Oncomelania hupensis snail distribution and the changes of snail situation in Chang-zhou City from 2013 to 2016,so as to provide the evidence for formulating the schistosomiasis prevention and control interven-tions. Methods The data of snail monitoring in Changzhou City from 2013 to 2016 were collected and statistically analyzed. Re-sults The total area with snails was 40.17 hm2 and the newly discovered area was 30.63 hm2 in Changzhou City from 2013 to 2016. In the four years,3454 snails were dissected,and no schistosome infected snails were found. There were totally 51 spots with snails,and the areas with snails of different types of marshland,inland and mountain were 12.13(30.19％),25.54 hm2 (63.57％)and 2.51 hm2(6.24％),respectively. In the newly discovered snail environment,the areas of types of marshland and inland were 8.00 hm2(26.12％)and 22.63 hm2(73.88％),respectively. The main causes for snail existence were external input and adjacent diffusion. In the past four years,the total snail control area with molluscicides was 71.74 hm2,the consolidated snail control area with molluscicides was 155.15 hm2,and the total environmental modification areas in the current snail spots and historic snail spots were 15.90 hm2 and 11.30 hm2 respectively. Conclusion The diffusion of snails in inland rivers is the key of the newly discovered snail areas in Changzhou City in recent years,and the snail monitoring and control measures should be strengthened in the future.

Objective To understand the status of knowledge,attitude,and practice of schistosomiasis prevention and con-trol and infection status in Armed Police Forces stationed along the Yangtze River,so as to provide the reference for formulating the schistosomiasis prevention and control measures in Armed Police Forces. Methods A questionnaire survey was conducted in the Armed Police Forces along the Yangtze River in Jiangsu Province,and the investigation content included social demo-graphic data,schistosomiasis prevention knowledge,attitude and behavior. All the subjects were examined for Schistosoma ja-ponicum infection. Results Totally 376 soldiers were investigated in 2 sites. The total passing rate of schistosomiasis knowl-edge was 72.87%. The passing rate among different age groups had no significant difference( χ2 =0.26,P > 0.05). The passing rate of soldiers from endemic areas was significantly higher than that of the soldiers from non-endemic areas( χ2 =4.71,P <0.05). The passing rate of officers was significantly higher than that of the soldiers(χ2 = 4.21,P <0.05). The passing rate of sol-diers with the education levels of junior school,high school,college,undergraduate and above increased gradually,with a sig-nificant difference( χ2 =8.16,P < 0.05). The soldiers with positive attitude accounted for 93.88%. Among the water contact be-haviors,training accounted for 17.55% and participating in the task(such as flood fighting and water work)accounted for 86.44%. When launching,the rate of taking protective measures was 52.93%. The rate of taking protective measures in the knowledge passing group was much higher than that in the knowledge failed group( χ2 =10.55,P < 0.05). The stool was harm-lessly treated in the two camps. Among 376 soldiers,the positive rate of blood examinations was 0.53%,but the stool examina-tions were all negative. Conclusions The overall level of knowledge and correct behavior of schistosomiasis prevention in the Armed Police Forces along the Yangtze River still should be improved. The better health education and behavior intervention are crucial to schistosomiasis prevention in the army.

Objective To analyse the effect of progesterone on peripheral blood corticotropin releasing hormone ( CRH ) and delivery time in women with premature rupture of membranes ( PROM ) .Methods 80 patients who were diagnosed with PROM in Department of Obstetrics and Gynecology, China Medical University were collected.Randomly divided into dexamethasone (DEX) group, dexamethasone plus progesterone (DEX+P) group, progesterone ( P) group and control group, three groups were detected on admission, admission 24 h, 48 h on peripheral white blood cell count, C-reaction protein, CRH level and time of delivery, neonatal weight, and analysis of CRH the level of the correlation and delivery time.Results Compared with the other three groups, the level of CRH in peripheral blood of DEX group were higher (P<0.05);CRH (P<0.05) increased faster;shorter delivery time (P<0.05); the level of CRH was negatively correlated with delivery time (r=-0.832, P<0.05).The results were statistically significant.Conclusion Dexamethasone treatment can make the premature rupture of fetal membranes of peripheral blood CRH levels rise, shorten the delivery time, progesterone can inhibit this process.

Objective To evaluate the effects of dexmedetomidine on the oxidative stress responses during global cerebral ischemia-reperfusion (I/R) in rats.Methods Thirty-six male Sprague-Dawley rats,weighing 250-300 g,were randomly divided into 3 groups (n =12 each) using a random number table:sham operation group (group S),global cerebral I/R group (group I/R) and dexmedetomidine group (group D).Global cerebral ischemia was induced by occlusion of bilateral common carotid arteries combined with hypotension (MAP maintained at 35-45 mmHg).In group D,dexmedetomidine was infused at a rate of 3 μg · kg-1 · h-1until 2 h of reperfusion after a loading dose of dexmedetomidine 3 μg/kg was intravenously injected immediately after onset of reperfusion.The neurological deficit score (NDS) was assessed at 24 h of reperfusion,the rats were then sacrificed,and their brains were immediately removed for determination of cell apoptosis and levels of malondialdehyde (MDA),superoxide dismutase (SOD) and catalase (CAT).Apoptotic rate was calculated.Results Compared with group S,NDS,apoptotic rate and MDA level were significantly increased,and SOD and CAT levels were decreased in I/R and D groups.Compared with group I/R,NDS,apoptotic rate and MDA level were significantly decreased,and SOD and CAT levels were increased in group D.Conclusion Dexmedetomidine attenuates global cerebral I/R injury through inhibiting the oxidative stress responses.

Objective To study the smoking status and revalent cause factors among medical college students in Nanchang and provide information for smoking control .Methods A questionnaire survey was conducted among 935 medical students by stratified cluster random sampling method .912 questionnaires were valid .The valid rate was 97 .540% .Results The total smoking rate was 14 .364% (131/192) .The smoking rate of male was higher than female(χ2 =49 .982 ,P<0 .05) .There was a great difference among different grades(χ2 =22 .503 ,P<0 .05) .There were many factors associated with smoking conducts ,in which older ,higher family income ,higher monthly cost of living ,allowing to smoking in the home were risk factors ,but mother′s educational level ,correct knowledge about the hazards of tobacco were protective factors .Conclusion The smoking rate of medical students is not high .The smoking status are influenced by many factors .Intervention should pay more attention to focus group and better prevent medical students from smoking .

Objective To evaluate the effect of BML-111 on NF-κB pathway during acute lung injury induced by hemorrhagic shock and resuscitation in rats.Methods Thirty-two adult male Sprague-Dawley rats,weighing 200-250 g,were randomly divided into 4 groups (n =8 each) using a random number table:sham operation group (group S),hemorrhagic shock and resuscitation group (group HSR),BML-111 group,and BML-111 + BOC-2 (lipoxin A4 receptor antagonist) group (group BOC-2).The animals were anesthetized with intraperitoneal pentobarbital sodium.Hemorrhagic shock was induced by blood letting and maintained for 30 min.The animals were then resuscitated for 30 min by infusion of the shed blood and lactated Ringer's solution.In group BOC-2,BOC-2 (50 μg/kg) was injected intraperitoneally before blood letting.In BML-111 and BOC-2 groups,BML-111 (1 mg/kg) was injected intraperitoneally at the beginning of resuscitation.The rats were sacrificed at 2 h after the end of resuscitation and lungs were removed for determination of pathological changes,myeloperoxidase (MPO) activity,intercellular adhesion molecule-1 (ICAM-1) expression (by immunohistochemistry),tumor necrosis factor-alpha (TNF-α) content (by ELISA),and NF-κB p65 and IκB-α expression (by Western blot).Results Compared with group S,the MPO activity,ICAM-1 expression,and TNF-α content were significantly increased,NF-κB p65 expression was up-regulated,and IκB-α expression was down-regulated in group HSR.Compared with group.HSR,the MPO activity,ICAM-1 expression,and TNF-α content were significantly decreased,NF-κB p65 expression was down-regulated,IκB-α expression was up-regulated,and pathological changes of lung were attenuated in group BML-111.Compared with group BML-111,the MPO activity,ICAM-1 expression,and TNF-α content were significantly increased,NF-κB p65 expression was up-regulated,and lκ:B-α expression was down-regulated,and pathological changes of lung were aggravated in group BOC-2.Conclusion BML-1 11 inhibits activation of NF-κB pathway and inflammatory responses,thus mitigating acute lung injury induced by hemorrhagic shock and resuscitation in rats.

Objective To exPlore the effect of mammalian target of raPamycin ( mTOR ) inhibitor eVerolimus on radiosensitiVity of human non_small cell lung cancer cell line in vitro by using eVerolimus to inhibit mTOR signaling Pathway of A549. Methods Human non_small cell lung cancer cell line A549 was subjected to radiation alone or in combination with eVerolimus treatment. The 50%inhibition concentration ( IC50 ) of eVerolimus in A549 cells was detected by methylthiazol tetrazolium ( MTT) assay in vitro. EVerolimus at the 20%inhibition concentration ( IC20 ) was used to Pretreat A549 cells for 24 h. Cells were then irradiated by X_ray with 2,4,6,8 Gy. The cell surViVal fraction was comPuted by clone formation. Cell surViVal curVe was fitted by multitarget one_hit model, and mean lethal dose ( D0 ), dose quasithreshold ( Dq ), surViVal fraction at 2 Gy ( SF2 ), and sensitization enhancement ratio (SER) were calculated. The exPression ofγ_H2AX was determined by Western blotting and then the relatiVe gray Values were analyzed. Results EVerolimus significantly imProVed the sensitiVity of A549 cells to radiation. The D0 , Dq and SF2 of eVerolimus+irradiation grouP were significantly lower than those of irradiation grouP. The SER was 1. 36. The residual amount of γ_H2AX Protein in the eVerolimus + irradiation grouP was significantly higher than that of the irradiation grouP. Conclusion EVerolimus inhibiting mTOR signaling Pathway can increase the radiosensitiVity of A549 cells.