Background Recent advances in understanding the toxic effects of inorganic arsenic have revealed that arsenic exposure impacts multiple endocrine organs, thereby altering their functions. However, the mechanisms underlying arsenic-induced thyroid injury remain unclear. Objective To investigate the mechanisms by which sodium arsenite (NaAsO₂) affects the proliferation and apoptosis of normal thyroid cells (Nthy-ori3-1) through the estrogen receptor (ER)-phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Methods Nthy-ori3-1 cells were cultured in vitro and divided into the following groups: a control group (complete medium without drugs, 0 μmol·L⁻¹), and NaAsO₂-treated groups at 1, 2, and 4 μmol·L⁻¹. Additionally, 1 μmol·L⁻¹ of the ER inhibitor ICI182780 was used to intervene in the NaAsO₂ exposure groups, resulting in the following combinations: 1 μmol·L⁻¹ NaAsO₂ + ICI182780, 2 μmol·L⁻¹ NaAsO₂ + ICI182780, and 4 μmol·L⁻¹ NaAsO₂ + ICI182780. The median lethal concentration of NaAsO₂ was determined using cell viability assay. Cell viability was assessed at 24, 36, and 48 h using Cell Counting Kit-8 (CCK-8) assay. Colony formation ability was evaluated via plate cloning assay. Apoptosis was detected using Hoechst 33342 staining. Protein and mRNA expression levels of ERα, ERβ, c-MYC, Bax, Bcl-2, PI3K, p-PI3K, AKT, and p-AKT were measured using Western blot (WB) and real-time quantitative PCR (qRT-PCR), respectively. Results The median lethal concentration of NaAsO₂ was determined to be 4.034 μmol·L⁻¹. CCK-8 assay at 24, 36, and 48 h revealed that, compared with the control group, the 1, 2, and 4 μmol·L⁻¹ NaAsO₂ groups significantly inhibited Nthy-ori3-1 cell proliferation (P < 0.001). The plate cloning assays demonstrated a concentration-dependent reduction in colony formation ability (P < 0.001). Following the ICI182780 intervention, the cell viability and colony formation ability in the 1, 2, and 4 μmol·L⁻¹ NaAsO₂ groups were significantly restored compared with the corresponding NaAsO₂-only groups (P < 0.001, P < 0.01). The Hoechst 33342 staining indicated that compared with the control group, the nuclear staining intensity and apoptosis levels in the 1, 2, and 4 μmol·L⁻¹ NaAsO₂ groups increased in a concentration-dependent manner (P < 0.001). However, the ICI182780 intervention reduced the apoptosis levels in the NaAsO₂-treated groups compared with their NaAsO₂-only counterparts (P < 0.001). The WB analysis showed that, compared with the control group, the protein expression of ERα, ERβ, c-MYC, Bcl-2, p-PI3K, and p-AKT in the 1, 2, and 4 μmol·L⁻¹ NaAsO₂ groups decreased manner (P < 0.001, P < 0.01), while the Bax expression increased in a concentration-dependent (P < 0.001); the PI3K and AKT protein levels showed no significant differences (P > 0.05). In the ICI182780-treated NaAsO₂ groups, the ERα, ERβ, c-MYC, Bcl-2, p-PI3K, and p-AKT protein expression increased (P < 0.001, P < 0.01), the Bax expression decreased (P < 0.001), and the PI3K and AKT levels remained unchanged (P > 0.05) compared with the corresponding NaAsO₂-only groups. The mRNA expression patterns of ERα, ERβ, c-MYC, Bcl-2, and Bax were consistent with the WB results. Conclusion NaAsO₂ inhibits proliferation and promotes apoptosis in Nthy-ori3-1 cells in a dose-dependent manner. The underlying mechanism likely involves NaAsO₂-mediated suppression of the ER-PI3K/AKT signaling pathway, which subsequently regulates downstream proliferation- and apoptosis-related genes.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective:To analyze the effect of long-term care insurance on the incidence of falls in old people with disability, and the modification effect of different living arrangements.Methods:Based on the discharge diagnosis records of the hospitalization in urban residents who applied for long-term care insurance in Chengdu from July 2014 to June 2021, those who received long-term care insurance were selected as the intervention group and those who received no long-term care insurance were selected as the control group, the changes in the incidence of falls before and after the long-term care were analyzed using difference-in-differences method, and the modification effects of different living arrangements were explored using stratified analysis.Results:Long-term care insurance significantly reduced the risk for monthly incidence of falls in older adults [average treatment effects on treated (ATT) = -1.21% (95% CI: -1.82%--0.60%)], and the effect increased over time (ATT=-1.26%, 95% CI: -1.93%--0.59%). Long-term care insurance had a significant effect on reducing the incidence of falls in old people living with spouses/family members (ATT=-0.92%, 95% CI: -1.47%--0.37%) and in nursing facilities/hospitals (ATT=-2.10%, 95% CI: -3.81%--0.40%), but it had no significant effect in those living alone. Conclusions:Long-term care insurance can effectively reduce the incidence of falls in old people with disability, showing a positive effect. Living with family members or in nursing facilities/hospitals has a modification effect of the implementation of long-term care insurance policy. It is necessary to pay attention to key populations in the future and expand the coverage of long-term care insurance.

Objective:To analyze the clinical features,treatment and prognosis of drug induced hypersensitivity syndrome related hemophagocytic lymphohistiocytosis (DIHS-HLH).Methods:This was a retrospective case study. Clinical characteristics, laboratory results, treatment and prognosis of 9 patients diagnosed with DIHS-HLH in Beijing Children′s hospital between January 2020 and December 2022 were summarized. Kaplan-Meier survival analysis was used to calculate the overall survival rate.Results:Among all 9 cases, there were 6 males and 3 females, with the age ranged from 0.8 to 3.1 years. All patients had fever, rash, hepatomegaly and multiple lymph node enlargement. Other manifestations included splenomegaly (4 cases), pulmonary imaging abnormalities (6 cases), central nervous system symptoms (3 cases), and watery diarrhea (3 cases). Most patients showed high levels of soluble-CD25 (8 cases), hepatic dysfunction (7 cases) and hyperferritinemia (7 cases). Other laboratory abnormalities included hemophagocytosis in bone marrow (5 cases), hypofibrinogenemia (3 cases) and hypertriglyceridemia (2 cases). Ascending levels of interleukin (IL) 5, IL-8 and interferon-γ (IFN-γ) were detected in more than 6 patients. All patients received high dose intravenous immunoglobulin, corticosteroid and ruxolitinib, among which 4 patients were also treated with high dose methylprednisolone, 2 patients with etoposide and 2 patients with cyclosporin A. After following up for 0.2-38.6 months, 7 patients survived, and the 1-year overall survival rate was (78±14)%. Two patients who had no response to high dose immunoglobulin, methylprednisolone 2 mg/(kg·d) and ruxolitinib died. Watery diarrhea, increased levels of IL-5 and IL-8 and decreased IgM were more frequently in patients who did not survive.Conclusions:For children with fever, rash and a suspicious medication history, when complicated with hepatomegaly, impaired liver function and high levels of IL-5 and IL-8, DIHS-HLH should be considered. Once diagnosed with DIHS-HLH, suspicious drugs should be stopped immediately, and high dose intravenous immunoglobulin, corticosteroid and ruxolitinib could be used to control disease.

Objective:To analyze the efficacy and safety of the L-DEP regimen (asparaginase, liposome doxorubicin, etoposide and methylprednisolone) as a salvage therapy for the refractory primary hemophagocytic lymphohistocytosis triggered by Epstein-Barr virus infection (EBV-pHLH) in children.Methods:In this retrospective case study, clinical and laboratory data before and after L-DEP regimen of 4 children diagnosed with EBV-pHLH in Beijing Children′s hospital between January 2016 and June 2022 were collected, and the efficacy and safety of L-DEP regimen for the treatment of EBV-pHLH were analyzed.Results:Among 4 patients, there were 3 females and 1 male with the age ranged from 0.8 to 7.0 years. Two of them showed compound heterozygous mutations of PRF1, one with a heterozygous mutation of UNC13D, one homozygous mutation of ITK. Before the L-DEP therapy, all of them had anemia and a soaring level of soluble CD25, 3 patients had neutropenia and thrombopenia, 3 patients had a high level of ferritin, 3 patients had hypofibrinogenemia and 1 patient had hypertriglyceridemia. After receiving 1 or 2 cycles of L-DEP treatment, three achieved remission, including complete remission (1 case) and partial remission (2 cases), and the other one had no remission. The levels of blood cell counts, soluble CD25, triglyceride, fibrinogen and albumin were recovered gradually in 3 patients who got remission. All four patients underwent hematopoietic stem cell transplantation (HSCT) after L-DEP regimen, and three survived. All patients had no severe chemotherapy related complications. The main side effects were bone marrow suppression, infection and pancreatitis, which recovered after appropriate treatments, apart from one who died from severe infection after urgent HSCT.Conclusion:L-DEP regimen could be served as an effective and safe salvage treatment for refractory pediatric EBV-pHLH, and also provide an opportunity for patients to receive HSCT.

Objective To investigate the expression levels of secreted frizzled-related protein 5 (sFRP5), heat shock protein 60 (HSP60) and solute carrier family 16 member 11 (SLC16A11) in serum of patients with gestational diabetes mellitus (GDM) and their relationships with insulin resistance. Methods A total of 120 GDM patients in the hospital from January 2022 to December 2023 were selected as study group, and another 120 healthy pregnant women in the same period were selected as control group. The expression levels of serum sFRP5, HSP60 and SLC16A11 were detected; the levels of insulin resistance-related indicators[fasting blood glucose (FBG), fasting insulin (FINS), and homeostasis model assessment of insulin resistance (HOMA-IR)]were measured and calculated; the Pearson's correlation method was used to analyze the correlations of serum sFRP5, HSP60 and SLC16A11 with insulin resistance; the Logistic regression andysis and receiver operating characteristic (ROC) curve analysis were used to assess the relationships of serum sFRP5, HSP60 and SLC16A11 with GDM. Results The serum sFRP5 expression in the study group was significantly lower than that in the control group, while the serum HSP60, SLC16A11, FBG, FINS and HOMA-IR levels were significantly higher than those in the control group (P < 0.05). Pearson's correlation analysis showed that serum sFRP5 was negatively correlated with HSP60, SLC16A11, FBG, FINS and HOMA-IR (P < 0.05); serum HSP60 was positively correlated with SLC16A11, FBG, FINS and HOMA-IR (P < 0.05); serum SLC16A11 was positively correlated with FBG, FINS and HOMA-IR (P < 0.05). Multivariate Logistic regression analysis revealed that HSP60, SLC16A11, FBG, FINS and HOMA-IR were risk factors for GDM in pregnant patients, while sFRP5 was a protective factor (P < 0.05). The area under the curve (AUC) for the combined diagnosis of GDM in pregnant patients by serum sFRP5, HSP60 and SLC16A11 was 0.924, indicating that the combined diagnostic value of three indicators was superior to that of each individual indicator (all P < 0.05). Conclusion GDM patients exhibit decreased serum sFRP5 level and increased HSP60 and SLC16A11 levels; three indicators are factors influencing the occurrence of GDM in pregnant patients, and are associated with insulin resistance; the combination of three indicators exhibits high diagnostic efficacy for GDM.

Background Arsenic can enter the hypothalamus to induce estrogen effect and interfere with the function of the neuroendocrine system. The thyroid endocrine system (hypothalamic-pituitary-thyroid axis) is one of the main endocrine systems, and the mechanism of arsenic-induced thyroid endocrine toxicity is still unclear. Objective To investigate the effects of different arsenic exposure levels on estradiol (E2), hypothalamic thyrotropin-releasing hormone (TRH), and their receptor (ERα, ERβ, and TRHR) mRNAs in rats and the possible hypothalamic toxic pathway and mechanism. Methods Seventy Wister rats were randomly divided a control group (sterile water); low-, medium-, and high-dose arsenic exposure groups [0.8, 4.0, and 20.0 mg·kg⁻¹ sodium arsenite (NaAsO₂)]; estrogen receptor inhibitor (ICI182780) intervention + low-, medium-, and high-dose arsenic exposure groups; with 10 animals in each group, half male and half female. Rats in the arsenic exposure groups were exposed to NaAsO₂ by drinking water for 19 weeks, and rats in the intervention groups were injected with 0.5 mg·kg⁻¹ ICI182780 via tail vein at week 9, 3 times a week. The levels of E2 and TRH in serum of rats were detected by ELISA. The expression levels of estrogen receptor α (ERα), estrogen receptor β (ERβ), and TRH receptor (TRHR) mRNAs in hypothalamus of rats were detected by real-time PCR (RT-PCR). Results (1) E2 and its receptor mRNA: Compared with the control group, the serum E2 level of female rats was increased in the low-dose and the medium-dose arsenic exposure groups (P<0.05), and the serum E2 level of male rats was increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05), and the change of female E2 was greater than that of male rats. Compared with the control group, the relative expression levels of ERα mRNA and ERβ mRNA in female rats were increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05), so were the relative expression levels of ERα mRNA in male rats (P<0.05). (2) TRH and its receptor mRNA: Compared with the control group, the serum TRH level of female rats was increased in the high-dose arsenic group (P<0.05), the relative expression level of TRHR mRNA was increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05). Results (1) and results (2) suggested that females were more likely than males to have abnormal changes in E2, TRH, and related receptor genes after arsenic exposure. (3) Compared with female rats in the medium-high dose arsenic exposure group, the expressions of TRH and TRHR induced by arsenic exposure were inhibited after the intervention of ICI182780 (P<0.05), suggesting that arsenic in the hypothalamus may have toxic effects on TRH and TRHR by inducing estrogen-like effects. Conclusion Arsenic exposure can induce estrogen-like effects in the hypothalamus, interfere with thyroid function, and show dose-dependent and sex differences. E2 and TRH and their receptors may be the toxic pathway of arsenic-related estrogen-like effect.

Objective: To understand the public health emergency response capacity in primary and secondary schools, and to explore the problems and challenges in the prevention and control of public health emergency in primary and secondary schools for specific strategies. Methods: By using the stratified group sampling method, a questionnaire survey on general situation, knowledge, attitude and training, as well as public health emergencies response capacity among 2 988 teachers or leaders responsible for school emergency response in primary and secondary schools from Beijing, Chongqing and Yunnan. Results: Participants varied on their positions, titles, educational background and knowledge accuracy. Higher knowledge accuracy was associated with higher educational background ( χ 2=50.73-203.36, P < 0.05 ). The implementation of regular public health emergency related programs was poorly conducted in high schools (50.0%). Urban schools (42.0%) had higher proportion of qualified health care professionals than rural schools (18.2%), and private schools (48.5%) was higher than public schools (24.7%). The primary challenges included the shortage of guidance from professionals and the lack of related testing equipment (84.91%, 74.03%). Conclusion Although the ability of emergency handling of public health emergencies in schools in the three regions is advancing with the times, there are still many deficiencies, some omissions in the mastery of knowledge. It is suggested to inerease pre service and special training of school health work CDC should strengthen technical guidance and work supervision of infectious disease management in schools.

Objective:To search for and summarize the best evidence on non-pharmacological interventions for orthostatic hypotension in patients with Parkinson disease.Methods:Based on the 6S model, the relevant guidelines, clinical decisions, evidence summaries, systematic reviews and expert consensus on non-pharmacological interventions for orthostatic hypotension in Parkinson disease patients were systematically retrieved from domestic and foreign databases. The search time was from the establishment of the database to December 2022. Two researchers independently screened the literature, evaluated the quality of the included literature, and extracted and summarized evidence that met the quality standards.Results:A total of 15 articles were included, including 4 guidelines, 2 clinical decision-making articles, 1 evidence summary article, 3 systematic evaluations and 5 expert consensus articles. A total of 24 pieces of best evidence were summarized from 7 aspects, including purpose, evaluation, capacity intervention, exercise intervention, posture intervention, physical intervention, health education and support.Conclusions:The best evidence on non-pharmacological intervention for orthostatic hypotension in patients with Parkinson disease can provide a reference for the practice of clinical medical staffs. It is suggested to apply the best evidence in combination with the patient's condition, preference and clinical environment, so as to reduce the incidence of orthostatic hypotension in patients with Parkinson disease and to ensure the safety of patients.

Objective: To examine the associations of arsenic and estrogen levels with the risk of papillary thyroid carcinoma, so as to provide insights into prevention of papillary thyroid carcinoma. Methods: Totally 57 patients with papillary thyroid carcinoma admitted to two tertiary hospitals in Urumqi, Xinjiang Uygur Autonomous Region in 2018 were selected as the case group, while 57 subjects with normal thyroid functions during the same period were selected as the control group. Subjects' gender, age, ethnicity, occupation and medical history of thyroid disease were collected using questionnaire surveys. Serum dimethyl arsenic acid (DMA) and monomethyl arsenic acid (MMA) were determined using high-performance liquid chromatography (HPLC) coupled to hydride generation-atomic fluorescence spectrometry (HG-AFS), serum thyroid hormone (TSH) by radioimmunoassay, estradiol (E2) by enzyme-linked immunosorbent assay and estrogen receptor ERα and ERβ by western blotting. The associations of arsenic and estrogen levels with the risk of papillary thyroid carcinoma were evaluated using a multivariable logistic regression model. Results: There were 16 males (28.07%) and 41 females (71.93%) in the case group, with a mean age of (42.63±11.01) years, and there were 21 males (36.84%) and 36 females (63.16%) in the control group, with a mean age of (40.89±11.30) years. There were no significant differences between the case and control groups in terms of age (χ2=0.373, P=0.542), gender (χ2=1.000, P=0.317) or ethnic composition (χ2=0.291, P=0.590). The serum levels of TSH [2.85 (1.61) vs. 2.45 (1.79) μmol/L], E2 [74.93 (120.44) vs. 61.60 (37.35) pmol/L], ERα [1.49 (1.13) vs. 0.70 (0.31)], ERβ [1.59 (0.55) vs. 0.72 (0.36)], DMA [116.02 (100.48) vs. 32.33 (56.06) μg/L] and MMA [56.92 (47.90) vs. 27.90 (24.99) μg/L] were all significantly higher in the case group than in the control group (Z=-2.414, -2.292, -4.923, -5.167, -5.448 and -4.019, all P<0.05). Multivariable logistic regression analysis showed DMA (OR=1.013, 95%CI: 1.003-1.024) and E2 levels (OR=1.020, 95%CI: 1.004-1.036) were associated with the risk of papillary thyroid carcinoma. Conclusion Increased arsenic load and elevated estradiol levels may be associated with the risk of papillary thyroid carcinoma.