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 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.

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 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 assess the capability of seven reference medical laboratories to detect BCR::ABL1 p210 transcription levels and to compare the results among those laboratories.Methods:The interlaboratory comparison was carried out in two stages. The samples were prepared by the reference laboratory. The quantitative values of BCR::ABL1 p210 of the comparison samples covered 0.001%-0.01%, 0.01%-0.1%, 0.1%-1%, 1%-10% and>10% in each stage. Real-time quantitative PCR (RT-PCR) and dPCR (digital PCR) were used to examine the samples. The conversion factor (CF) was calculated and validated for each laboratory.Results:In the RT-PCR comparison, one laboratory was failed to detect BCR::ABL1 p210 in fourteen samples at the first stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.133-0.338) and 95% limits of agreement within ±5 folds (upper limit 0.147-0.785, lower limit -0.770--0.109), and the corresponding CF values were calculated and validated. In the dPCR comparison, one laboratory did not report results at the second stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.026-0.267) and 95% limits of agreement within±5 folds (upper limit 0.084-0.991, lower limit -0.669--0.135), and the corresponding CF values were calculated and validated. The samples with BCR::ABL1 p210 quantitative values of 0.01%-0.1%, 0.1%-1%, 1%-10% and >10% could be detected by both RT-PCR and qPCR. When the quantitative value of BCR::ABL1 p210 was 0.001%-0.01%, the detection rate of dPCR was higher than that of RT-PCR (85.56% vs. 68.00%).Conclusions:A good consistency is present among various laboratories. The quantitative value of BCR::ABL1 p210 is comparable among laboratories as shown by the CF value conversion. For quantitative detection of BCR::ABL1 p210 deep molecular reaction, dPCR has a higher positive detection rate and more advantages than RT-PCR. To ensure the accuracy and reproducibility of the BCR::ABL1 p210 test, it is imperative for every laboratory to enhance their daily quality control practices.

Hepatitis E virus(HEV)is one of the most common pathogens in acute viral hepatitis.There are at least eight distinct genotypes of HEV.Only humans can contract HEV genotypes 1 and 2,but zoonotic viruses like genotypes 3 and 4 are mostly spread by eating undercooked or in-fected pork in some affluent nations.As a result,boars,both domestic and wild,are typically regar-ded as primary hosts of HEV.Nevertheless,during the past few years,a growing body of research has demonstrated that a number of other wild ruminant animals,such as wild deer and goats,are also susceptible to HEV infection.Determining their participation in the epidemiological cycle of hepatitis E thus requires an understanding of the risk variables that influence the transmission be-tween wild ruminants and humans.With an emphasis on published serological and molecular re-search,this review offers a broad summary of the body of knowledge currently available on the epi-demiology of HEV in wild ruminants.It addresses potential risk factors that could impact the spread of HEV among animals as well as their potential to serve as a source of infectious zoonotic illnesses.It presents an overview of the most recent developments in the epidemiology of HEV in wild ruminants and offers a framework for HEV prevention and management based on science.

To identify the intestinal roundworms of Eclectus roratus and Psittacula alexandri from the Guangdong region by morphological analysis and molecular biology techniques,and to amplify the mitochondrial genome of parrot roundworms using PCR,as well as to carry out phylogenetic analyses based on the sequences of their mitochondrial genes.The results showed that the parrot roundworms identified in this identification belongs to Ascaridia.nymphii and its mitochondrial genome consists of 12 protein coding genes,22 tRNA genes,2 ribosomal RNA genes and two non-coding regions.Phylogenetic analyses showed that A.nymphii identified in this study is located in the same evolutionary branch as the previously reported Ascaridia sp.,is closely related and con-stitutes a separate clade of avian ascarids with pigeon roundworms and chicken roundworms.This study provides important data for the classification,molecular epidemiology and population genetic evolution of parrot roundworms.

AIM:To evaluate corrective effect and stability of corneal morphology in patients with moderate to high myopia after 2a treatment of femtosecond laser assisted laser in situ keratomileusis(FS-LASIK)Xtra.METHODS:Retrospective case-control study. A total of 30 cases(58 eyes)Patients with moderate to high myopia combined with astigmatism who planned to undergo refractive surgery in our hospital from August 2019 to August 2020 were included, and different types of surgery were performed respectively based on the relevant index of keratoconus screening in the preoperative corneal topography. They were divided into FS-LASIK group and Xtra group, with 15 cases(29 eyes)in each group. Uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), spherical equivalent(SE)and the corneal curvature of the anterior and posterior surfaces of different diameters(3, 5 and 7 mm)measured by Sirius three-dimensional corneal topography were observed preoperatively and 3 mo, 1 and 2 a postoperatively.RESULTS: The UCVA of the two groups of patients at different time points after surgery was significantly increased compared with preoperatively(both P<0.01), and there was no difference in UCVA and SE between the two groups(P>0.05). After 2 a postoperatively, residual astigmatism was -0.25-0 D in 25 eyes(86%)of the FS-LASIK Xtra group and 24 eyes(83%)of the FS-LASIK group. The actual corrected SE and expected corrected SE of both groups were positively correlated(both P<0.05). There were differences in corneal curvature on the surface of different diameter areas(3, 5, and 7 mm)between the two groups at 3 mo, 1, and 2 a postoperatively compared with preoperatively. After 1 and 2 a postoperatively, the corneal posterior surface curvature of the FS-LASIK Xtra group with corneal diameter of 3 and 5 mm was higher than that of the FS-LASIK group(P<0.05).CONCLUSIONS:FS-LASIK Xtra has good safety, efficacy and predictability in correcting patients with moderate to high myopia.

Objective:To explore the relationship between macrophage infiltration in the coronary plaque and downstream myocardial perfusion in mice.Methods:The experimental group consisted of 20 ApoE knockout mice models of the coronary plaque established by feeding with cholesterol-rich diets, and the control group consisted of 20 sex- and age-matched C57BL/6 mice with the same genetic background as ApoE mice.Adenosine stress myocardial contrast echocardiography was performed on all experimental animals to obtain the values of A, β and A×β of the left ventricular myocardium in anteroseptal and posterior walls both in the resting status and during adenosine stress. Concentrations of serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were determined using mouse enzyme-linked immunosorbent assay kits according to the manufacturer′s instructions. The degree of macrophage infiltration in the coronary plaque was evaluated by pathological immunohistochemistry staining and the correlations with the above indicators were analyzed.Results:There were no statistically significant differences in heart rate and left ventricular structural parameters between two groups (all P>0.05). The experimental group had a lower left ventricular ejection fraction( P=0.021), and higher weight and serum levels of triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, IL-6, and TNF-α than the control group (all P<0.05). The values of A, β and A × β of the left ventricular myocardium in anteroseptal and posterior walls in the experimental group were significantly lower than those in the control group during adenosine stress (all P<0.05). In the experimental group, the value of the macrophage infiltration found in the plaque of the left main coronary artery correlated positively with the level of serum TNF-α ( r=0.63, P=0.003) and negatively correlated with the values of A×β of the left ventricular myocardium in anteroseptal and posterior walls during adenosine stress ( r=-0.74, P<0.001; r=-0.72, P<0.001; respectively). Conclusions:Myocardial perfusion in ApoE knockout mice models of the coronary atherosclerosis was related with degree of macrophage infiltration in the coronary plaque, and macrophages may play a role by releasing inflammatory mediator TNF-α.

Objective: To investigate the effect of Guangdong Shenqu (GSQ) on intestinal flora structure in mice with food stagnation through 16S rDNA sequencing. Methods: Mice were randomly assigned to control, model, GSQ low-dose (GSQL), GSQ medium-dose (GSQM), GSQ high-dose (GSQH), and lacidophilin tablets (LAB) groups, with each group containing 10 mice. A food stagnation and internal heat mouse model was established through intragastric administration of a mixture of beeswax and olive oil (1:15). The control group was administered normal saline, and the model group was administered beeswax and olive oil to maintain a state. The GSQL (2 g/kg), GSQM (4 g/kg), GSQH (8 g/kg), and LAB groups (0.625 g/kg) were administered corresponding drugs for 5 d. After administration, 16S rDNA sequencing was performed to assess gut microbiota in mouse fecal samples. Results: The model group exhibited significant intestinal flora changes. Following GSQ administration, the abundance and diversity index of the intestinal flora increased significantly, the number of bacterial species was regulated, and α and β diversity were improved. GSQ administration increased the abundance of probiotics, including Clostridia, Lachnospirales, and Lactobacillus, whereas the abundance of conditional pathogenic bacteria, such as Allobaculum, Erysipelotrichaceae, and Bacteroides decreased. Functional prediction analysis indicated that the pathogenesis of food stagnation and GSQ intervention were primarily associated with carbohydrate, lipid, and amino acid metabolism, among other metabolic pathways. Conclusion The digestive mechanism of GSQ may be attributed to its role in restoring diversity and abundance within the intestinal flora, thereby improving the composition and structure of the intestinal flora in mice and subsequently influencing the regulation of metabolic pathways.