Objective To investigate the relationships of serum levels of G protein-coupled es-trogen receptor-1(GPER1)and interleukin-38(IL-38)with pregnancy outcomes in patients with gestational diabetes mellitus(GDM).Methods A total of 120 patients with GDM(GDM group)and 103 pregnant women with normal glucose tolerance(control group)were enrolled between Janu-ary 2022 and June 2024.Serum GPER1,IL-38,and glycometabolic and lipometric indicators were measured at 24 to 28 weeks of gestation.Pearson correlation analysis was used to assess the correla-tions of GPER1 and IL-38 with glucolipid indicators.Pregnancy outcomes of GDM patients were re-corded.Factors influencing adverse pregnancy outcomes in GDM patients and the predictive value of GPER1 and IL-38 for adverse pregnancy outcomes were analyzed.Results The serum levels of GPER1 and IL-38 in the GDM group were significantly lower than those in the control group(P＜0.05).Moreover,GPER1 and IL-38 were negatively correlated with glucolipid indicators(P＜0.05).High HOMA-IR and excessive gestational weight gain were identified as risk factors for ad-verse pregnancy outcomes in GDM patients,while high GPER1 and high IL-38 were protective factors(P＜0.05).The areas under the receiver operating characteristic(ROC)curves for predicting ad-verse pregnancy outcomes in GDM patients were 0.780 for GPER1 and 0.789 for IL-38,respectively.The area under the ROC curve for the combined prediction of GPER1 and IL-38 was 0.887.The predictive value of the combined GPER1 and IL-38 was higher than that of GPER1 or IL-38 alone(P＜0.05).Conclusion Reduced serum levels of GPER1 and IL-38 in GDM patients are associated with glycometabolic and lipometric disorders,insulin resistance,and adverse pregnancy outcomes.GPER1 combined with IL-38 exhibits high value in predicting pregnancy outcomes in GDM patients.

Hepatocellular carcinoma (HCC) is one of the fastest growing cancers in the world, ranking fourth among the causes of cancer-induced death in the world. At present, the field of HCC treatment is developing rapidly, and immunotherapy has been recognized as a promising treatment method, in which T cells play a key role in HCC immunotherapy. However, in the case of virus infection or in tumor microenvironment (TME), T cells will be continuously stimulated by antigens and then fall into the state of T cell exhaustion (Tex). This state will not only reduce the immunity of patients but also lead to poor efficacy of immunotherapy. Therefore, to deeply analyze the mechanism of Tex and to explore effective strategies to reverse Tex is the key point in the immunotherapy for HCC. This review aims to summarize the mechanism of Tex in HCC patients, and the current situation and shortcomings of drug research and development to reverse Tex at this stage, in order to provide theoretical basis for the optimization of immunotherapy regimen for HCC patients.
Humans ; Carcinoma, Hepatocellular/therapy* ; Liver Neoplasms/therapy* ; Immunotherapy/methods* ; T-Lymphocytes/immunology* ; Tumor Microenvironment/immunology* ; Animals ; T-Cell Exhaustion

Objective:To investigate the main influencing factors of mild cognitive impairment(MCI)in the elderly and explore the interaction between high fluoride exposure and related co-factors on MCI.Methods:A cross-sectional study was conducted from May to December 2024 in four towns in the rural areas of Tianjin(two historically high-fluoride towns and two non-high-fluoride towns). A total of 125 elderly people aged 60 years and above were randomly selected from each township.MCI was diagnosed using the Mini-Mental State Examination(MMSE)and Montreal Cognitive Assessment-Basic(MoCA-B)according to the diagnostic criteria for MCI.Binary logistic regression was used to analyze the influencing factors of MCI, and conditional logistic regression was employed to assess multiplicative and additive interaction effects.Results:A total of 481 participants were included, with 354 in the normal group and 127 in the MCI group, and the incidence of MCI was 26.40%.Univariate analysis showed that MCI was associated with age, annual household income per capita, high fluoride exposure, life stress, depression, and abnormal urinalysis( χ2=4.241, 4.017, 4.552, 7.143, 4.151, 5.113, all P<0.05). Multivariate logistic regression revealed that after adjusting for other confounders, high fluoride exposure( OR=1.816, 95% CI: 1.177-2.802), age ≥70 years( OR=1.584, 95% CI: 1.034-2.428), depression( OR=2.106, 95% CI: 1.042-4.254), and abnormal urinalysis( OR=1.595, 95% CI: 1.041-2.444)increased the risk of MCI.Compared with severe life stress, moderate stress( OR=0.254, 95% CI: 0.082-0.790)reduced the risk of MCI.No multiplicative or additive interaction was found between high fluoride exposure and depression, life stress, or abnormal urinalysis. Conclusions:High fluoride exposure, age ≥70 years, depression, abnormal urinalysis, and severe life stress may increase the risk of MCI in the elderly, but there is no interaction among them.

Objective:To summarize the clinical characteristics, treatment, and prognosis of children with anti-GT1a antibody-positive Guillain-Barré syndrome (GBS).Methods:A case series study was conducted, including 25 children diagnosed with serum anti-GT1a antibody-positive GBS at Guangzhou Women and Children′s Medical Center from March 2019 to December 2024. Clinical data, treatment protocols, and follow-up outcomes were analyzed. Mann Whitney U test was used to compare the changes in Hughes functional grading scale (HFGS). Results:A total of 25 children included 12 boys and 13 girls, and the age at first onset was (71±8) months. There were 16 children (64%) had preceding infections, and of which 13 children had predominantly respiratory tract infections. At disease peak, neurological manifestations included limb weakness (21 cases (84%)), bulbar palsy (13 cases (52%)), drowsiness (7 cases (28%)), limb pain (9 cases (36%)), ataxia (6 cases (24%)), respiratory muscle paralysis (5 cases (20%)), ophthalmoplegia (5 cases (20%)), and unilateral facial nerve palsy (4 cases (16%)). Cerebrospinal fluid analysis in 23 children revealed albuminocytological dissociation in 18 children. All 25 children underwent whole-spine magnetic resonance imaging (MRI), demonstrated spinal nerve root enhancement in 18 children, with leptomeningeal enhancement combined with spinal nerve root enhancement in 1 child. Electromyography in 16 children showed 15 children abnormality, of which demyelinating lesions in 8 children, mixed demyelinating-axonal changes in 4 children, and pure axonal involvement in 3 children. Intravenous immunoglobulin (IVIG) was administered to 21 cases (84%), of which 3 children required mechanical ventilation and blood purification (plasma exchange in 2 children and immunoadsorption in 1 child) due to disease progression. Four children (16%) received intravenous methylprednisolone (IVMP) instead of IVIG, with 1 child requiring ventilatory support due to respiratory muscle paralysis, and the tracheal tube was removed after continued sequential IVMP treatment. The hospitalization duration of 25 children was (23±3) d. At discharge, HFGS was 1.6 (0.6, 2.7) score. At a follow-up of 12 (4, 18) months, HFGS was 0.1 (0.0, 0.5) score, and higher than that at discharge ( Z=4.38, P<0.05). Two children relapsed but achieved remission after IVIG retreatment with no recurrence during 1-year follow-up. Conclusions:Anti-GT1a antibody-positive GBS in children predominantly presents with limb weakness and bulbar palsy, occasionally complicated by respiratory failure in the acute phase. Demyelinating neuropathy and spinal nerve root enhancement on MRI are characteristic. IVIG therapy yields favorable outcomes, with low residual disability. Relapses are rare but manageable with re-treatment.

Objective:To explore differences in the radiation-induced intestinal injury in mice exposed to ultra-high dose rate (FLASH) and conventional-dose-rate (CONV) pulsed X-ray irradiation in order to provide evidence for the application of ultra-high dose rate pulsed X-rays in gastrointestinal radiotherapy.Methods:Using the random number table method, 32 C57BL/6J mice were randomly divided into four groups: a sham irradiation group (SHAM), two conventional dose rate groups (CONV0.067 and CONV0.1), and an ultra-high dose rate group (F215), with each group containing eight mice. All groups, except SHAM, received a single 12 Gy abdominal X-ray irradiation at dose rates of 0.067, 0.1, and 215 Gy/s, respectively. At 3 d post-irradiation, histopathological (hematoxylin-eosin staining, HE staining), immunohistochemical, and Western blot analysis were performed to assess the histopathological markers and oxidative stress indicators of intestinal tissues, as well as relevant proteins involved in signaling pathways.Results:At 3 d post-irradiation, mice in all irradiation groups suffered from varying degrees of intestinal tissue degeneration and necrosis, epithelial cell shedding, villus shortening, and crypt loss ( t = 5.75, 8.79, 5.71, P < 0.05). Regarding oxidative stress, at 3 d post-irradiation, mice in the CONV0.067 and CONV0.1 groups showed significantly lower levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), glutathione (GSH), and total antioxidant capacity (T-AOC) compared to those in the F215 group ( t = 7.06-10.64, P < 0.01). In contrast, their malondialdehyde (MDA) levels were significantly elevated ( t = 11.06, 8.31, P < 0.01), with no statistical significance observed between them and mice in the F215 group ( P > 0.05). Immunohistochemical and Western blot analyses indicated that at 3 d post-irradiation, mice in the three irradiation groups exhibited an upward trend in the Nrf2 and HO-1 protein levels and a downward trend in the Keap1 protein level compared to those in the SHAM group. Notably, statistical significance was observed between the F215 group and the two conventional dose rate groups ( t = 4.89-20.95, P < 0.05). These result were consistent with the prior changes in antioxidant markers. Conclusions:Ultra-high-dose-rate X-ray irradiation reduces acute RIII by alleviating oxidative stress and modulating the expression of the Keap1-Nrf2-HO-1 signaling pathway.

Objective:To investigate the situation of mild cognitive impairment (MCI) in elderly people in fluorosis areas, and analyze its potential influencing factors.Methods:From April to October 2020, a cluster random sampling method was used to select local elderly people aged 60 and older in areas of drinking-water-borne endemic fluorosis in Tianjin, and their general information was collected through face-to-face surveys. Terminal drinking water samples were collected from survey subjects. Water fluoride concentration was measured using ion-selective electrode method. Cognitive function was evaluated using the Mini-Mental State Examination (MMSE), and survey subjects were categorized into MCI group and control group based on MMSE scores. Logistic regression and Chi-squared automatic interaction detection classification tree models were constructed to analyze the influencing factors of MCI.Results:A total of 677 subjects were included, including 160 cases in the MCI group and 517 cases in the control group, with a MCI detection rate of 23.63%. The detection rates of MCI in the high fluoride exposure group and non high fluoride exposure group were 30.82% (94/305) and 17.74% (66/372), respectively, with a statistically significant difference between the groups (χ 2 = 15.88, P < 0.001). The results of univariate analysis showed that MCI was associated with high fluoride exposure, age, per capita annual household income, sleep duration, personality, and interpersonal relationships (χ 2 = 15.88, 16.17, 12.32, 8.91, 14.03, 9.81, P < 0.05). The results of multiple logistic regression analysis showed that moderate interpersonal relationships ( OR = 2.13, 95% CI: 1.08, 4.20) and high fluoride exposure ( OR = 1.91, 95% CI: 1.03, 3.54) were both risk factors for MCI ( P < 0.05). The classification tree model analysis result showed that high fluoride exposure was the primary factor affecting MCI in elderly people in fluorosis areas, followed by per capita annual household income, personality, and age. Conclusions:The detection rate of MCI in the high fluoride exposure group of elderly people in fluorosis areas is higher than that in the non high fluoride exposure group. High fluoride exposure, interpersonal relationships, per capita annual household income, personality, and age are all influencing factors of MCI in elderly people in fluorosis areas.

Objective:To learn about the iodine nutrition status of pregnant women in Tianjin and analyze the influencing factors of moderate to severe iodine deficiency in pregnant women.Methods:From January 2022 to December 2024, a stratified random sampling method was adopted. Each year, five sampling areas were divided into the east, west, south, north and central directions in 16 districts of Tianjin. Ten pregnant women from one township/street in each area were selected for questionnaire surveys. Household salt samples and random urine samples were collected to measure salt iodine and urinary iodine levels. Multivariate logistic regression was used to analyze the influencing factors of moderate to severe iodine deficiency in pregnant women, and a restricted cubic spline model was used to analyze the dose-response relationship between the risk of moderate to severe iodine deficiency in pregnant women and salt iodine level.Results:A total of 2 532 pregnant women in Tianjin were surveyed, with an age of (30.70 ± 4.44) years. Among them, 53.20% (1 347/2 532) had received health education, and 52.45% (1 328/2 532) actively supplemented iodine. A total of 2 532 household salt samples of pregnant women were tested, with a median salt iodine level of 23.66 mg/kg. The coverage rate of iodized salt was 74.45% (1 885/2 532), the qualified rate of iodized salt was 87.59% (1 651/1 885), and the consumption rate of qualified iodized salt was 65.21% (1 651/2 532). A total of 2 532 urine samples of pregnant women were tested, with a median urinary iodine level of 151.68 μg/L. Among them, 652, 1 348 and 532 urine samples were collected from pregnant women in the early, middle, and late stages of pregnancy, respectively, with median urinary iodine levels of 150.80, 153.00 and 143.68 μg/L, respectively. Multivariate logistic regression analysis showed that consuming iodized salt was a protective factor for the moderate to severe iodine deficiency in pregnant women ( OR = 0.70, 95% CI: 0.58 - 0.86, P < 0.001). Restricted cubic spline analysis showed that there was a linear dose-response relationship between the risk of moderate to severe iodine deficiency in pregnant women and salt iodine level ( Poverall < 0.001, Pnonlinear = 0.065). Further stratified analysis revealed that there was a linear dose-response relationship between the risk of moderate to severe iodine deficiency in pregnant women who had received iodine supplementation and salt iodine level ( Poverall = 0.018, Pnonlinear = 0.554), while there was a nonlinear dose-response relationship between the risk of moderate to severe iodine deficiency in pregnant women who had not received iodine supplementation and salt iodine level ( Poverall < 0.001, Pnonlinear = 0.029). Conclusions:From 2022 to 2024, the overall iodine level of pregnant women in Tianjin is appropriate, but some pregnant women are at risk of iodine deficiency. Consuming iodized salt is a protective factor against the moderate to severe iodine deficiency in pregnant women. It is still necessary to further implement comprehensive prevention and control measures mainly based on iodized salt.

Objective:To investigate the prevalence of dental fluorosis in children in Tianjin and study its influencing factors.Methods:From January to December 2023, 5 affected villages were selected from each of the drinking water-borne endemic fluorosis (drinking water-borne fluorosis for short) areas of 10 agricultural areas in Tianjin, and 50 children aged 8 - 12 years (gender and age balanced) were selected from each affected village for questionnaire survey and dental fluorosis examination. At the same time, water samples from affected villages and children's one random urine sample were collected to test for fluoride levels in water and urine. Multivariate logistic regression was used to analyze the influencing factors of dental fluorosis prevalence in children, and a restricted cubic spline model was used to analyze the dose-response relationship between the years of water improvement and dental fluorosis prevalence.Results:A total of 50 water samples were collected, with water fluoride levels ranging from 0.05 to 0.85 mg/L. All affected villages had completed the water improvement and the water fluoride levels were qualified. A total of 2 439 urine samples were collected from children, with urinary fluoride levels ranging from 0.05 to 12.56 mg/L and a geometric mean of 0.82 mg/L. A total of 2 439 children were examined for dental fluorosis, with a detection rate of 22.67% (553/2 439). The results of multivariate logistic regression analysis showed that age ( OR = 1.26, 95% CI: 1.15 - 1.37, P < 0.001), father's education level of junior high school or below ( OR = 1.57, 95% CI: 1.04 - 2.38, P = 0.033), and high urinary fluoride (0.74 - 1.58 mg/L: OR = 1.59, 95% CI: 1.19 - 2.13, P = 0.002; 1.59 - 12.56 mg/L: OR = 2.00, 95% CI: 1.48 - 2.70, P < 0.001) were risk factors for dental fluorosis prevalence in children. The total annual household income with 40 000 to 80 000 yuan ( OR = 0.76, 95% CI: 0.58 - 0.99, P = 0.041), father's occupation was self-employed and other occupation ( OR = 0.69, 95% CI: 0.51 - 0.92, P = 0.013), the years of water improvement in affected villages ≥10 years ( OR = 0.39, 95% CI: 0.30 - 0.50, P < 0.001), and the material of the drinking water container at home was stainless steel products ( OR = 0.58, 95% CI: 0.40 - 0.85, P = 0.005), ceramic or glass products ( OR = 0.66, 95% CI: 0.48 - 0.90, P = 0.010) were protective factors for dental fluorosis prevalence in children. By constructing a restricted cubic spline model, it was found that there was a linear dose-response relationship between the prevalence of dental fluorosis in children and the years of water improvement in affected villages ( Poverall < 0.001, Pnonlinear = 0.059). The longer the years of water improvement, the lower the risk of dental fluorosis prevalence. Conclusions:The detection rate of dental fluorosis in children in Tianjin is relatively high. The fluoride reduction and water improvement measures implemented in drinking water-borne fluorosis areas can effectively reduce the risk of dental fluorosis prevalence. Factors such as age, urinary fluoride, economic conditions, and lifestyle also have important impacts on the prevalence of dental fluorosis.

Objective:To investigate the awareness of prevention and treatment knowledge of drinking water-borne endemic fluorosis among children in Tianjin, explore its influencing factors, analyze the needs of children's health education methods, and provide a basis for carrying out health education in school.Methods:From January to December in 2024, a stratified sampling method was employed to select two endemic villages from each of the 10 areas with drinking water-borne endemic fluorosis in Tianjin as survey sites. In each village, no fewer than 50 children aged 8 - 12 (gender and age balanced) were recruited to conduct a questionnaire survey. Multivariate logistic regression analysis was used to analyze the influencing factors of children's awareness of prevention and treatment knowledge.Results:A total of 1 678 valid questionnaires were collected. The overall awareness rate of prevention and control knowledge of drinking water-borne endemic fluorosis among children in Tianjin was 67.62% (11 346/16 780). Children had the highest awareness of the hazards of drinking water-borne endemic fluorosis (83.61%, 1 403/1 678), while their awareness of the clinical manifestations of dental fluorosis was the lowest (44.87%, 753/1 678). Multivariate logistic regression analysis showed that children in higher grades [grades 5 to 6, OR (95% CI) = 1.66 (1.36, 2.03), P < 0.001], with a larger number of permanent residents in the family [≥6 people, OR (95% CI) = 1.58 (1.13, 2.23), P = 0.008], whose mothers had a college education or above [ OR (95% CI) = 1.45 (1.08, 1.95), P = 0.014], and who had received health education [ OR (95% CI) = 1.46 (1.19, 1.78), P < 0.001] had a higher awareness rate of the prevention and control knowledge of drinking water-borne endemic fluorosis. There were statistically significant differences in the demand rates for access to prevention and control knowledge via school teachers, promotional videos, and online/WeChat official accounts among children of different grades ( P < 0.05). Conclusions:The awareness rate of prevention and treatment knowledge of drinking water-borne endemic fluorosis among children in Tianjin is relatively low. Special attention should be paid to children with a small number of permanent residents in the family, mothers with low educational levels, and who have not received health education. At the same time, detailed health publicity services should be carried out for children of different grades.

Renal transplantation is one of the main treatment methods for end-stage renal disease,and tacrolimus(TAC)is an immunosuppressant widely used in renal transplantation,to achieve anti-transplant rejection by inhibiting T cell activation and proliferation.However,in addition to the significant efficacy.TAC has a series of adverse reactions in the application of renal transplantation,including nephrotoxic-related diseases,cardiovascular diseases,neurological diseases,etc.Therefore,it is important to take corresponding management measures to improve the effectiveness of TAC.On the basis of previous studies on adverse reactions,this article aims to provide reference and guidance for further clinical practice of rational drug use after renal transplantation.