OBJECTIVE To provide a scientific basis for the quality evaluation and clinical application of Qingwen hufei granules. METHODS Fourteen batches of Qingwen hufei granules were used as samples to establish high-performance liquid chromatography （HPLC） fingerprints using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine （2012 Edition）. The chromatographic peaks were identified and the similarity was evaluated. Cluster analysis （CA）， principal component analysis （PCA）， and orthogonal partial least squares-discriminant analysis （OPLS-DA） were used to conduct chemical pattern recognition analysis on the 14 batches of samples. Meanwhile， the contents of neochlorogenic acid （NGA）， chlorogenic acid （CHA）， cryptochlorogenic acid （CGA）， forsythoside A （FTA）， 3，5-O-dicaffeoylquinic acid （3，5-O- DA）， 4，5-O-dicaffeoylquinic acid （4，5-O-DA）， and angoroside C （AGC） in the samples were determined by HPLC. RESULTS The methodological investigation results of both the fingerprint and the content determination complied with the relevant requirements. Fourteen common peaks were indicated in the HPLC fingerprints of the 14 batches of samples， and 7 of them were identified [NGA （peak 2）， CHA （peak 3）， CGA （peak 5）， FTA （peak 11）， 3，5-O-DA （peak 12）， 4，5-O-DA （peak 13）， and AGC （peak 14）]； the similarity of each sample was greater than 0.94. The results of CA and PCA showed that the samples could be classified into 3 categories； the results of OPLS-DA indicated that peak 4 （unknown）， peak 11 （FTA）， peak 8 （unknown）， peak 9 （unknown）， and peak 1 （unknown） were the differential components. The content ranges of NGA， CHA， CGA， 3，5-O-DA， FTA， 4，5-O-DA and AGC in the 14 batches of samples were 0.210 4-0.458 7， 0.269 1-0.506 3， 0.228 1-0.461 1， 0.443 9-1.044 6， 0.066 7-0.155 7， 0.062 8-0.143 8， and 0.057 4-0.105 7 mg/g， respectively. CONCLUSIONS The HPLC fingerprint and multi-component content determination methods established in this study are efficient and reliable， and can be used for the quality evaluation of Qingwen hufei granules.

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 verify the validity of the atopic dermatitis control tool (ADCT) in assessing disease control in patients with atopic dermatitis (AD) .Methods:Based on a cross - sectional study, demographic data, comorbidities and information on disease assessment - related scales such as the ADCT, the pruritus numerical rating scale (NRS), the patient-oriented eczema measure (POEM), and the dermatological life quality index (DLQI) were collected from patients with AD at Tianjin Medical University General Hospital from June 2021 to March 2023. The reliability and validity of the ADCT were assessed using these data. The discrimination power of the ADCT total score was evaluated by comparing the differences in the mean ADCT total scores among adjacent POEM/DLQI subgroups based on POEM/DLQI response classifications (POEM: clear or almost absent, mild, moderate, severe, very severe; DLQI: no effect, mild effect, moderate effect, serious effect, very serious effect). According to the ADCT scores, the AD patients were divided into an uncontrolled AD group (ADCT scores ≥ 7 points) and a controlled AD group (ADCT scores < 7 points). Differences between the above two groups were analyzed in terms of ADCT item scores, mean pruritus NRS scores, POEM total scores, DLQI total scores, and DLQI dimension scores to evaluate the validity of the ADCT in assessing AD disease control.Results:A total of 338 patients with AD were included, comprising 170 (50.30%) males and 168 (49.70%) females, and they were aged 17 to 89 (41.36 ± 17.63) years. Reliability analysis showed that the Cronbach′s α coefficient and split-half reliability coefficient of the ADCT were 0.886 and 0.878 respectively (both > 0.70), and the test- retest reliability coefficient was 0.977 (> 0.70, P < 0.001). Content validity analysis showed that the Pearson correlation coefficients between the ADCT item scores and the ADCT total score ranged from 0.753 to 0.852 (all P < 0.001) ; confirmatory factor analysis revealed that the Chi-square to degree of freedom ratio ( χ2/df) was 2.896 (< 5), the Tucker-Lewis index was 0.976 (> 0.9), the comparative fit index was 0.991 (> 0.9), the standardized root mean square residual was 0.026 (< 0.08), and the root-mean-square error of approximation was 0.075 (< 0.08) ; convergent validity analysis showed that the standardized factor loadings of all observed variables ranged from 0.689 to 0.905 (all > 0.500), combined reliability coefficient was 0.896 (> 0.700), and the average extracted variance value was 0.591 (> 0.500) ; criterion validity analysis showed that the correlation coefficients of the ADCT total score with other patient - reported outcome measures (the mean pruritus NRS scores, peak pruritus NRS scores, POEM total scores, and DLQI total scores) and DLQI dimension scores ranged from 0.649 to 0.730 and from 0.303 to 0.647, respectively (all P < 0.001). Analysis of the discrimination power of the ADCT total score showed significant differences in the mean ADCT total scores among adjacent POEM/DLQI subgroups (all P ≤ 0.001). The uncontrolled AD group (287 cases) showed significantly increased ADCT item scores, mean pruritus NRS score, POEM total score, DLQI total score, and DLQI dimension scores compared with the controlled AD group (51 cases, all P<0.001) . Conclusion:The ADCT exhibited good reliability, validity and discriminability based on the cross-sectional study, and can efficiently and reliably assess disease control in AD patients.

Objective To explore the association between different levels of fluoride exposure and dyslipidemia in elderly people, and to analyze the influencing factors and their interactions. Methods A total of 1 143 elderly people over 60 years old were randomly selected from historical high water fluorosis areas and control areas in Tianjin. Logistic regression model and classification tree model were used to analyze the influencing factors of dyslipidemia, and to analyze the interaction between high fluoride exposure and relevant influencing factors on dyslipidemia. Results The prevalence of elevated low density lipoprotein cholesterol (LDL-C) was 5.69% (65/1 143). There was a significant difference in the prevalence of high LDL-C in different fluoride-exposed areas (2 = 0.092，P = 0.762). Multivariate logistic analysis showed that high fluoride exposure (OR=2.306，95%CI：1.185-4.491) and abdominal obesity (OR=2.274，95%CI：1.299-3.978) were risk factors for high LDL-C, while type B personality (OR=0.529，95%CI：0.308-0.908) was a protective factor for high LDL-C. The results of classification tree model showed that abdominal obesity contributed the most to the prevalence of high LDL-C in the elderly, followed by high fluoride exposure and hyperglycemia. There was a significant multiplicative interaction between high fluoride exposure and abdominal obesity on dyslipidemia (OR=5.191,95%CI：1.609-16.745，P=0.006). Conclusion High fluoride exposure may increase the risk of high LDL-C, and there is a multiplicative interaction between high fluoride exposure and abdominal obesity on dyslipidemia.

Objective: To understand the dose response relationship between urinary fluoride and dental fluorosis among children from drinking water borne endemic fluorosis areas in Tianjin, so as to provide a scientific basis for assessing fluoride exposure risk among children from endemic areas and establishing reference values for urinary fluoride. Methods: From January to December 2024, 83 endemic villages were selected in Tianjin. A total of 2 382 children aged 8-12 years from these villages underwent dental fluorosis examination, along with water fluoride and urinary fluoride testing. Additionally, data from areas where the drinking water fluorosis control target was achieved for more than 12 years (10 villages, 50 people per village) were included as controls. A restricted cubic spline model was used to analyze the relationship between urinary fluoride levels and dental fluorosis prevalence, and benchmark dose (BMD) and benchmark dose lower bound (BMDL), as well as reference dose (RfD), were calculated using the benchmark dose method. Results: The prevalence rates of dental fluorosis among children in drinking water borne endemic fluorosis areas and areas of normal fluoride content in water in Tianjin were 10.58%, 7.60%, with a geometric mean urinary fluoride level of 0.72 and 0.60 mg/L,respectively. There were statistically significant differences in both dental fluorosis prevalence and geometric mean urinary fluoride levels between the drinking water borne endemic fluorosis areas group and the areas of normal fluoride content in water ( χ 2/Z = 4.05 , -7.31, both P <0.05). Across different periods of water source improvement, there were statistically significant differences in overall population, male, and female dental fluorosis prevalence rates and geometric mean urinary fluoride levels ( χ 2/H =44.95, 23.96, 21.05; 168.39, 63.93, 107.50, all P <0.01). Significant differences were also observed across age groups among children from drinking water borne endemic fluorosis areas in terms of dental fluorosis prevalence and geometric mean urinary fluoride levels ( χ 2/H =32.14, 79.73, both P <0.01). The results of the restricted cubic spline model showed that the risk of dental fluorosis in different sex, age and overall children in the drinking water borne endemic fluorosis areas increased significantly with rising urinary fluoride concentration(all P-general trend <0.05). The BMD value for the drinking water borne endemic fluorosis areas was 1.72 mg/L, the BMDL was 1.31 mg/L, and the RfD was 1.31 mg/L. Conclusions The prevalence of dental fluorosis among children in the drinking water borne endemic fluorosis areas in Tianjin has been effectively controlled, but it is still higher than that in the areas of normal fluoride content in water. Moreover, urinary fluoride levels and dental fluorosis prevalence among children from drinking water borne endemic fluorosis areas show a clear dose response relationship.

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.

Objective To explore the status of nursing work engagement, nursing work environment and emotional intelligence and their relationship among nurses who work in hematopoietic stem cell transplantation (HSCT) units. Methods A total of 225 HSCT nurses were selected as study subjects by convenience sampling method. Utrecht Work Engagement Scale, Nursing Work Environment Scale and Emotional Intelligence Scale were used to assess the work engagement, work environment and emotional intelligence among these nurses. AMOS 23.0 software was used to construct the structural equation model. Results The median and 25th and 75th percentiles of the score of work engagement of the research subjects were 59.0 (54.0, 64.0) points. The average scores of the nursing work environment and emotional intelligence were (117.8±21.5) and (58.8±10.7) points, respectively. The score of work engagement was positively correlated with the scores of the nursing work environment and emotional intelligence (rank correlation coefficients were 0.550 and 0.431, respectively, both P<0.01). The total score of the nursing work environment was positively correlated with the total score of emotional intelligence (correlation coefficient was 0.271, P<0.01). The nursing work environment influenced the work engagement status of HSCT nurses through the mediating effect of emotional intelligence, with an indirect effect of 0.115 (95% confidence interval: 0.201-0.365), accounting for 20.4% of the total effect. Conclusion Emotional intelligence is a mediating variable between the nursing work environment and work engagement of HSCT nurses.

Objective: To analyze the temporal variation patterns of sickness absenteeism among primary and secondary school students in Shanghai, so as to explore models suitable for predicting peaks and intensity of absenteeism rates. Methods: The seasonal and trend decomposition using loess (STL) method was used to analyze the seasonal and long term trend changes in sickness absenteeism among primary and secondary school students from September 1 in 2010 to June 30 in 2018, in Shanghai. A hierarchical clustering method based on Dynamic Time Warping (DTW) was employed to classify absenteeism symptoms with similar temporal patterns. Based on historical data, the study constructed and evaluated different time series algorithms and machine learning models to optimize the accuracy of predicting the trend of sickness absenteeism. Results: During the research period, the average new absenteeism rate due to illness was 16.86 per 10 000 person day for every academic year, and the trend of sickness absenteeism exhibited both seasonality and a long term upward trend, reaching its highest point in the 2017 academic year (22.47 per 10 000 person day). The symptoms of absenteeism were divided into three categories: high incidence in winter and spring (respiratory symptoms, fever and general discomfort, etc.), high incidence in summer (eye symptoms, nosebleeds, etc.) and those without obvious seasonality (skin symptoms, accidental injuries, etc.).The constructed time series models effectively predicted the trend of absenteeism due to illness, although the accuracy of predicting peak intensity was relatively low. Among them, the multi layer perceptron (MLP) model performed the best, with an root mean squared error (RMSE) of 8.96 and an mean absolute error (MAE) of 4.37, reducing 36.51% and 39.02% compared to the baseline model. Conclusion Time series models and machine learning algorithms could effectively predict the trend of sickness absenteeism, and corresponding prevention and control measures can be taken for absenteeism caused by different symptoms during peak periods.

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.