[摘 要] 近年来，以T淋巴细胞为主的免疫细胞疗法在血液系统肿瘤和部分实体瘤中取得了一定的进展。然而，其对大部分实体瘤治疗的有效性和安全性仍面临着诸多挑战，如肿瘤抗原异质性和免疫逃逸、免疫细胞浸润能力差、免疫抑制微环境、代谢微环境阻碍和T细胞耗竭等，这些问题限制了免疫细胞对实体瘤治疗的疗效进一步的提升。通过寻找新抗原、设计多靶点CAR、过表达趋化因子受体及细胞因子、敲除抑制性信号分子、增强T细胞代谢能力、联合免疫检查点抑制剂，以及表观遗传修饰等手段能够有效改善免疫细胞在实体瘤治疗中的效果。本文系统性地对TIL、TCR-T细胞和CAR-T细胞为代表的免疫细胞对实体瘤治疗的研究现状、面临的挑战和解决策略进行评述。

Objective:To dynamically investigate the iodine nutritional status of residents in water source high iodine areas in Hebei Province, so as to provide basis for taking targeted prevention and control measures and accurate intervention strategies.Methods:According to the "National Monitoring Program for Water Source High Iodine Areas (2018 Edition)", water source high iodine monitoring was carried out in 5 cities and 35 counties (cities, districts, hereinafter referred to as counties) of Hebei Province. According to the survey results of drinking water iodine of residents of Hebei Province in 2017, the administrative villages with a median water iodine above 100 μg/L were sorted according to the water iodine value. The systematic sampling method was adopted. Five administrative villages were selected in each county, if there were less than 5 administrative villages, all of them were selected (if the median water iodine was > 300 μg/L, at least one village shall be selected). The iodine content in drinking water of residents among the monitoring sites, salt iodine, urinary iodine and thyroid volume of children aged 8 - 10, as well as salt iodine and urinary iodine of pregnant women were tested. Water iodine was detected by the "Method Suitable for the Detection of Water Iodine in Iodine Deficient and High Iodine Areas" recommended by the National Iodine Deficiency Reference Laboratory of the Chinese Center for Disease Control and Prevention. Salt iodine was detected by semi quantitative method. Urinary iodine was detected by "Arsenic Cerium Catalytic Spectrophotometry Method" (WS/T 107-2006). Children's thyroid volume was detected by B-ultrasound.Results:A total of 239 water samples were collected in 167 villages, 35 counties, the median water iodine was 163.95 μg/L, ranging from 5.53 - 930.82 μg/L. A total of 6 772 edible salt samples were monitored, including 3 495 non-iodine salt samples and the rate of non-iodine salt was 51.61% (3 495/6 772). A total of 6 101 urine samples of children were tested, the median urinary iodine was 328.00 μg/L. A total of 6 103 children aged 8 - 10 were carried out B-ultrasound detection of thyroid volume in 35 counties. The goiter rate of children was 5.01% (306/6 103), and the rate of nodules was 0.56% (34/6 103). A total of 713 urine samples of pregnant women were tested, and the median urinary iodine was 221.70 μg/L.Conclusions:The iodine nutrition of children in water source high iodine areas of Hebei Province is at an excess level, and the iodine nutrition of pregnant women is at an appropriate level. In addition to stopping the supply of iodized salt, we should further expand the coverage of water improvement and iodine reduction projects in high iodine areas, and strengthen the monitoring of iodine nutrition status of key populations.

Objective:To master the iodine nutritional level of children aged 8-10 and pregnant women in non-iodine excess areas in Hebei Province, and provide scientific basis and targeted prevention and treatment strategies for prevention and treatment of iodine deficiency disorders.Methods:Iodine nutrition analysis was conducted in 162 counties (cities and districts, hereinafter referred to as counties) of Hebei Province in 2018. Each monitoring county was divided into 5 sampling areas according to east, west, south, north and middle locations. One township/street was randomly selected in each area, 1 primary school was selected in each township/street, and 40 non-boarding students aged 8-10 were selected from each primary school. In each monitoring county, 20 pregnant women were selected from each of the 5 townships/streets. Both children and pregnant women were collected samples for salt and urinary iodine (with a random urine sample) detection. The iodine content of salt was tested using the "General Test Method for Salt Industry-Determination of Iodine" (GB/T 13025.7-2012), and Sichuan salt and other fortified edible salt used the arbitration method. The urinary iodine content was tested using the "Arsenic-Cerium Catalytic Spectrophotometric Determination of Iodine in Urine" (WS/T 107-2006).Results:A total of 31 883 samples of edible salt were collected from children's homes in 162 counties, among which 28 539 were iodized salt, 26 456 were qualified iodized salt, the iodized salt coverage rate was 88.36% (after population standardization), and the qualified iodized salt consumption rate was 81.03% (after population standardization). A total of 31 883 urine samples were collected from children, with the median urinary iodine of 193.13 μg/L. There was one county with a median urinary iodine < 100 μg/L, and the median urinary iodine in 150 counties was 100-299 μg/L. A total of 15 572 salt samples of pregnant women were collected, among which the iodized salt samples were 14 260, the qualified iodized salt samples were 13 363, the iodized salt coverage rate was 90.10% (after population standardization), and the qualified iodized salt consumption rate was 83.54% (after population standardization). A total of 15 569 pregnant women were collected urine samples, the median urinary iodine was 164.86 μg/L, and the number of counties with a median urinary iodine < 150 μg/L was 67.Conclusions:Iodine nutrition of children and pregnant women is appropriate at the provincial level, but children and pregnant women in some counties are at risk of iodine deficiency. In the future, the prevention and treatment of iodine deficiency disorders should focus on the iodine nutrition monitoring of the special needs.

Objective:To master the situation of iodine deficiency disorders and iodine nutrition status of the population in Hebei Province, and to evaluate the effect of salt iodization intervention.Methods:According to "National Surveillance Program on iodine deficiency disorders", in 2018, iodine deficiency disorders surveillance was carried out in 162 counties (cities, districts). Each monitoring county (city, district) was divided into 5 sampling areas according to its locations of east, west, south, north and middle. One township/street was selected in each area, 1 primary school was selected in each township/street, and 40 non-boarding students aged 8 - 10 were selected from each primary school. In each monitoring county, 20 pregnant women were selected from each of the 5 townships/streets. Both children and pregnant women were collected urine and salt samples for detection of iodine levels. The thyroid volume of students was detected by B-ultrasound.Results:A total of 31 883 urine samples were collected from children aged 8 - 10 years in 162 counties (cities, districts), with the median urinary iodine of 193.13 μg/L. There was one county (cities, districts) with a median urinary iodine below 100 μg/L, and the median urinary iodine in 150 counties (cities, districts) was 100 - 299 μg/L. A total of 8 941 children aged 8 - 10 years were tested thyroid by B-ultrasound. A total of 232 cases of goiter were detected, and the rate of goiter was 2.59% (232/ 8 941). A total of 15 569 urine samples of pregnant women were tested, the median urinary iodine was 164.86 μg/L, and the number of counties (cities, districts) with a median urinary iodine below 150 μg/L was 67. A total of 47 455 salt samples were tested across the province, including 31 883 salt samples from children's homes and 15 572 salt samples from pregnant women's homes. The iodized salt coverage rate was 88.79%, and the consumption rate of qualified iodized salt was 81.69%.Conclusions:The iodized salt coverage rate and the consumption rate of qualified iodized salt in Hebei Province are all below 90%. The iodine nutrition of children aged 8 - 10 years is at an appropriate level. The thyroid enlargement rate of children is below the national standard, and the iodine nutrition of pregnant women is generally at an appropriate level. But pregnant women in 67 counties (cities, districts) have a risk of iodine deficiency.

Objective:To master the iodine content of drinking water in all counties (cities, districts) and clarify the distribution characteristics of water iodine and the distribution range of water-borne high iodine areas in Hebei Province.Methods:In all counties (cities, districts) of Hebei Province, water samples in townships (towns, street office, hereinafter referred township) were collected according to different water supply methods to detect iodine content in 2017; in townships with a median of water iodine ≥10 μg/L, the administrative village (neighborhood committee, hereinafter referred village) was used as a unit to collect water sample to detect iodine content.Results:A total of 2 199 townships in 168 counties (cities, districts) were surveyed for water iodine. The median range of water iodine of the townships was 0.0 - 1 113.7 μg/L. The median of water iodine in 1 579 townships was < 10 μg/L, accounting for 71.81% of the total; the number of townships with water iodine of 10 μg/L or more was 620. The village water iodine survey was carried out in the townships with water iodine of 10 μg/L or more, the number of villages monitored was 17 930. The number of villages with a median of water iodine of less than 10 μg/L was 2 312 (12.89%), and there were 6 104 villages with water iodine of 100 μg/L or more, accounting for 34.04%. The number of villages with median of water iodine ≥300 μg/L was 1 577 (8.80%). The water-borne high iodine areas in Hebei Province were distributed in 39 counties (cities, districts) of five cities, namely, Cangzhou, Handan, Xingtai, Hengshui and Langfang. They were mainly distributed in sheet shape or spot shape.Conclusion:The water-borne high iodine areas in Hebei Province are widely distributed, in the form of sheet or spot.

Seventy-three patients with type 2 diabetes mellitus were divided into atheroselerosis(AS) group and non-AS group according to the intima-media thickness(IMT)of the carotid artery.The plasma visfatin level in AS group was higher than that in non-As group[(44.95±10.14 vs 34.52±9.08)μg/L,P<0.05],and both of them were higher than that of the control [(24.46±7.18)μg/L,both P<0.05 ].The visfatin level Was positively correlated with IMT,waist-to-hip ratio,visceral fat thickness,fasting insulin,and HOMA insulin resistance index.Age,duration of diabetes,HbA_(1C),and visfatin level were the major risk factors for IMT of the carotid artery.

Objective To investigate the correlation between colony-stimulating activities of serum from patients with severe aplastic anemia (SAA) and their responses to immunosuppressive therapy (IST).Methods The effects in vitro of a total 50 test serum samples from SAA patients before and after IST, and from normal subjects on healthy human marrow colony growth of BFU-E and CFU-GM were examined to reflect their burst promoting activities (BPAs) and granulocyte/macrophage colony-stimulating activities (GM-CSAs). Serum erythropoietin (Epo) level was also measured with ELISA method before and after IST in SAA patients.Results The results showed that the BPAs of sera from SAA patients before IST were higher significantly than that of normal controls (P<0.001), after IST, the BPAs of sera from SAA patients had no obvious changes. Serum GM-CSAs from 13 of 22 SAA patients were normal, and the other 9 patients were extremely lower compared with normal subjects; after IST, their serum GM-CSAs also had no obvious changes. Serum Epo concentrations in SAA patients both at diagnosis and after IST were higher significantly than normal (P<0.001); however, serum concentrations declined in responded patients (P>0.05), while further increased in nonresponded patients (P>0.05).Conclusion Serum GM-CSA of SAA patients was a predictive factor for responsiveness to IST, and a normal value was associated with a good response.