Objective To explore the characteristics of response to joint attention(RJA)under diverse guiding behaviors for pre-schoolers with moderate to severe autism spectrum disorder(ASD). Methods From March to May,2023,21 children with moderate to severe ASD and 16 children with developmental de-lays matched the physiological ages were selected from Jiaxing Sunlight Rehabilitation Kindergarten,and 16 typ-ical developmental children matched the physiological ages were selected from the kindergartens nearby.They accepted a behavioral experiment on RJA.The number of RJA,frequence of RJA and the coefficient of variation of guiding behaviors needed to RJA were compared among the three groups. Results About half of the ASD group responded after guiding of head-turning,and the others required higher levels of guiding.The frequence of RJA after guiding of head-turning was less in the ASD group than in the typical devel-opment group(χ2>6.170,P<0.05),and the coefficient of variation of guiding behaviors was more(d=4.039,P<0.001). Conclusion Preschoolers with moderate to severe ASD are able to respond to joint attention,and this ability is poorer than typically developing children.The guiding behavior of the evaluator should be considered in assessing and intervening RJA in preschoolers with ASD.

Multiple primary lung cancer(MPLC)refers to patients with two or more primary lesions of lung cancer.It can be divided into synchronous MPLC(sMPLC)and metachronous MPLC(mMPLC)based on the timing of occurrence.In recent years,the detection rate of MPLC has gradually increased.However,considerable controversy exists in distinguishing MPLC from intrapulmonary metastasis(IM),especially when the histopathological types are identical.Given the significant differences in treatment strategies and prognosis in clinical practice currently,accurate diagnosis of MPLC is cru-cial for personalized precision therapy.Molecular genetics and sequencing technologies offer effective strategies for assessing the clonal origin of tumors.There have been reports of coexisting mutations in the epidermal growth factor receptor(EGFR)and anaplastic lymphoma kinase(ALK)fusion genes in non-small cell lung cancer,but case of EGFR mutation following an ALK mutation has not been mentioned.This article accurately diagnoses and retrospectively analyzes the clinical data of a case of ALK mutant adenocarcinoma in a male patient who developed an EGFR mutation with multiple metastases four years after surgery,and reviews the relevant literature.This paper aims to deepen the understanding of mMPLC and provide clinical refer-ences for the diagnosis and treatment of such patients.

Objective:To investigate the correlation between serum uric acid levels and thyroid hormones in hospitalized elderly gout patients.Methods:A total of 646 hospitalized gout patients, including 616 males and 30 females, aged(68.8±5.1)years, who were hospitalized at the Department of Gout, Chu Hsien-I Memorial Hospital from April 2014 to December 2019, were retrospectively analyzed.Clinical information was collected and relevant biochemical tests were conducted.Serum uric acid (SUA)levels were divided into quartiles and their associations with thyroid hormone levels were analyzed.Results:With the increase of SUA, body mass index, the prevalence of obesity, the prevalence of dyslipidemia, and the prevalence of fatty liver, the number of involved joints, cholesterol, low-density lipoprotein cholesterol, triacylglycerol, and homeostasis model assessment trended upward significantly( P<0.05); FUA showed a downward trend( F=9.42, P>0.05). The prevalence of subclinical hypothyroidism in older patients was 11.3%(73 cases). With the increase of SUA, the prevalence of subclinical hypothyroidism and free triiodothyronine levels showed an upward trend, whereas free thyroxine levels showed a downward trend( P<0.01). Conclusions:In elderly gout patients, the prevalence of subclinical hypothyroidism increases with SUA levels.Hyperuricemia and multiple metabolic disorders are independent risk factors for subclinical hypothyroidism in these patients.

An increased level of reactive oxygen species is a key factor in neuronal apoptosis and epileptic seizures. Irisin reportedly attenuates the apoptosis and injury induced by oxidative stress. Therefore, we evaluated the effects of exogenous irisin in a kainic acid (KA)-induced chronic spontaneous epilepsy rat model. The results indicated that exogenous irisin significantly attenuated the KA-induced neuronal injury, learning and memory defects, and seizures. Irisin treatment also increased the levels of brain-derived neurotrophic factor (BDNF) and uncoupling protein 2 (UCP2), which were initially reduced following KA administration. Furthermore, the specific inhibitor of UCP2 (genipin) was administered to evaluate the possible protective mechanism of irisin. The reduced apoptosis, neurodegeneration, and spontaneous seizures in rats treated with irisin were significantly reversed by genipin administration. Our findings indicated that neuronal injury in KA-induced chronic epilepsy might be related to reduced levels of BDNF and UCP2. Moreover, our results confirmed the inhibition of neuronal injury and epileptic seizures by exogenous irisin. The protective effects of irisin may be mediated through the BDNF-mediated UCP2 level. Our results thus highlight irisin as a valuable therapeutic strategy against neuronal injury and epileptic seizures.
Rats ; Animals ; Kainic Acid/toxicity* ; Brain-Derived Neurotrophic Factor/metabolism* ; Fibronectins/metabolism* ; Hippocampus/metabolism* ; Rats, Sprague-Dawley ; Epilepsy/metabolism* ; Seizures/prevention & control*

OBJECTIVE：To study the current situation of pharmacovigilance work in large ，medium and small-scale pharmaceutical manufacturers in Jiangsu Province ，and to provide reference for the pharmacovigilance development of drug manufacturers with different scales. METHODS ：The situation of pharmacovigilance work in 108 manufacturers in Jiangsu province was investigated through a questionnaire survey and related websites. The pharmacovigilance work （organization，personnel and training，document，computer system ），drug safety monitoring （case report ，regular safety update report ，post-marketing safety research） and drug risk management （signal management ， risk management plan ， risk control measures ， drug safety communication）of different manufacturers were investigated to put forward the suggestions. RESULTS & CONCLUSIONS ：There was no significant difference in the organizational structure （independently established specialized agencies ）among manufacturers of different scales （P＝0.60）. Most of the manufacturers had less than 50％ of the proportion in the independent establishment of specialized institutions for pharmacovigilance. There was significant difference in personnel and training （situation and number of full-time staff in charge ，medical and clinical pharmacy personnel number ），document（formulating training management system ， entrusted management and key monitoring procedures ），computer system （P＜0.05）. There was no difference in the main collection ways of case reports among manufacturers of different scales ；however，the number of independent reports in 2019（P＜ 0.01），the proportion of quality control process for regular safety update reports （P＝0.01），and the proportion of carrying out post-marketing safety research in recent five years （P＜0.01）in large-scale manufacturers were all significantly higher than small- and medium-scale manufacturers. The proportions of large-scale manufacturers （70.00％） and medium-scale manufacturers （84.38％），which considered “lack of technical guidelines ”as an important factor affecting signal management ，were higher than that of small-scale manufacturers （53.57％）（P＝0.01）；the proportions of large-scale manufacturers （60.00％）and medium-scale manufacturers（50.00％），which had carried out risk management plans in the past five years ，were higher than that of small-scale manufacturers（30.36％）（P＝0.04）；the proportion of large-scale manufacturers （50.00％），which adopted the measures in recent 5 year，was higher than medium-scale manufacturers （37.50％）and small-scale manufacturers （25.00％）；the proportions of large-scale manufacturers （70.00％ ） and medium-scale manufacturers （59.38％ ）， which carried out communication for pharmacists，were higher than small-scale manufacturers （32.14％）（P＜0.01）. Large-scale manufacturers outperformed small- and medium-scale manufacturers in terms of pharmacovigilance system ，drug safety monitoring and drug risk management. Large-scale manufacturers had a certain degree of lack of initiative on performing risk management plans ，medium-scale manufacturers on full-time staffs in charge ，and small-scale manufacturers on pharmacovigilance system. So ，it is recommended that large-scale manufacturers take effective control of variety risk as the goal and actively risk management ；medium-scale manufacturers should continuously enhance the awareness of responsibility and improve the investment of resources on pharmacovigilance work ； small-scale manufacturers should pay more attention to improving the pharmacovigilance system and the compliance of specific work.

Objective:To develop the Core Occupational Stress Scale (COSS) for key occupational populations, and to assess the reliability and validity of COSS in China.Methods:According to the literature review, in-depth interview and expert evaluation, the item pool of COSS was established. A total of 20 981 employees (3 703 employees from 2018 and 17 178 employees from 2019) of manufacturing, medical, and traffic polices, etc. from Beijing, Tianjin, Shanghai, Chongqing, Jiangsu, Shandong, Zhejiang, Hunan, Guangdong and Hubei were investigated using convenient sampling of those participating in general or occupational health examination of the day. Item differential test and exploratory factor analysis (EFA) were used to screen items from the item pool; confirmatory factor analysis (CFA) was used to test structure validity; criterion and convergent validity were tested by Pearson correlation. Cronbach′s α coefficient was used to test the reliability of the scale. Results:The EFA suggested a four-factor structure for a 17-item version of COSS, which were social support, organization and reward, demand and effort, and control. It explained 62.06% of the total variance and factor loadings ranged from 0.447 to 0.918. The CFA confirmed the hypothesized four-factor model (GFI=0.904, CFI=0.912, RMSEA=0.079). The COSS scores were positively correlated with burnout, depressive symptoms, and effort-reward imbalance scores with rranging from 0.357 to 0.567 ( P<0.05). The total COSS and each dimension of Cronbach′s α coefficients were 0.772-0.896. Conclusions:The COSS has good reliability and validity and can be used as an occupation stress assessment for occupational populations in China.

Objective:To analyze the mediating effect of psychological capital (PsyCap) between occupational stress and suicidal ideation.Methods:In September 2017, stratified-cluster sampling method was adopted to select employees of an electronic manufacturing service industry as respondents for a questionnaire survey in Jiangsu province. The demographic characteristics of employees were collected. A total of 2 465 employees were investigated, and 2 216 valid questionnaires were collected. The level of occupational stress and PsyCap was assessed by the Effort-Reward Imbalance Scale(ERI)and PsyCap Questionnaire.Results:The age of 2 216 employees was (28.70±5.26) years old, including 1 230 males (55.5%). The scores of occupational stress on effort, reward and over-commitment were (3.08±0.63), (3.73±0.60) and (2.51±0.68), respectively. The average ERI index (ratio of effort to return) was (0.88±0.39). The total score of PsyCap was (86.62±15.23). The detection rate of suicidal ideation within two weeks was 13.9% (309/2 216). The average score of effort and over-commitment and the ERI index were positively correlated with the number of suicidal ideation detected within two weeks, with correlation coefficients about 0.081, 0.141 and 0.164, respectively. The average score of reward and total score of PsyCap were negatively correlated with the number of suicidal ideation detected within two weeks, with correlation coefficients about -0.206 and -0.228, respectively. The mediating effect results showed that PsyCap had mediating effect on the effort, reward, over-commitment and suicidal ideation of occupational stress respectively, with mediating effect values of -0.087 (95% CI: -0.018,-0.019), -0.299 (95% CI: -0.428,-0.200) and 0.096 (95% CI: 0.0394, -0.170). The mediating effect percentages were 9.43%, 17.92%, and 9.54%, respectively. Conclusion:PsyCap has a mediating effect between effort, reward, over-commitment of occupational stress and suicidal ideation.

Objective:To develop the Core Occupational Stress Scale (COSS) for key occupational populations, and to assess the reliability and validity of COSS in China.Methods:According to the literature review, in-depth interview and expert evaluation, the item pool of COSS was established. A total of 20 981 employees (3 703 employees from 2018 and 17 178 employees from 2019) of manufacturing, medical, and traffic polices, etc. from Beijing, Tianjin, Shanghai, Chongqing, Jiangsu, Shandong, Zhejiang, Hunan, Guangdong and Hubei were investigated using convenient sampling of those participating in general or occupational health examination of the day. Item differential test and exploratory factor analysis (EFA) were used to screen items from the item pool; confirmatory factor analysis (CFA) was used to test structure validity; criterion and convergent validity were tested by Pearson correlation. Cronbach′s α coefficient was used to test the reliability of the scale. Results:The EFA suggested a four-factor structure for a 17-item version of COSS, which were social support, organization and reward, demand and effort, and control. It explained 62.06% of the total variance and factor loadings ranged from 0.447 to 0.918. The CFA confirmed the hypothesized four-factor model (GFI=0.904, CFI=0.912, RMSEA=0.079). The COSS scores were positively correlated with burnout, depressive symptoms, and effort-reward imbalance scores with rranging from 0.357 to 0.567 ( P<0.05). The total COSS and each dimension of Cronbach′s α coefficients were 0.772-0.896. Conclusions:The COSS has good reliability and validity and can be used as an occupation stress assessment for occupational populations in China.

Objective:To analyze the mediating effect of psychological capital (PsyCap) between occupational stress and suicidal ideation.Methods:In September 2017, stratified-cluster sampling method was adopted to select employees of an electronic manufacturing service industry as respondents for a questionnaire survey in Jiangsu province. The demographic characteristics of employees were collected. A total of 2 465 employees were investigated, and 2 216 valid questionnaires were collected. The level of occupational stress and PsyCap was assessed by the Effort-Reward Imbalance Scale(ERI)and PsyCap Questionnaire.Results:The age of 2 216 employees was (28.70±5.26) years old, including 1 230 males (55.5%). The scores of occupational stress on effort, reward and over-commitment were (3.08±0.63), (3.73±0.60) and (2.51±0.68), respectively. The average ERI index (ratio of effort to return) was (0.88±0.39). The total score of PsyCap was (86.62±15.23). The detection rate of suicidal ideation within two weeks was 13.9% (309/2 216). The average score of effort and over-commitment and the ERI index were positively correlated with the number of suicidal ideation detected within two weeks, with correlation coefficients about 0.081, 0.141 and 0.164, respectively. The average score of reward and total score of PsyCap were negatively correlated with the number of suicidal ideation detected within two weeks, with correlation coefficients about -0.206 and -0.228, respectively. The mediating effect results showed that PsyCap had mediating effect on the effort, reward, over-commitment and suicidal ideation of occupational stress respectively, with mediating effect values of -0.087 (95% CI: -0.018,-0.019), -0.299 (95% CI: -0.428,-0.200) and 0.096 (95% CI: 0.0394, -0.170). The mediating effect percentages were 9.43%, 17.92%, and 9.54%, respectively. Conclusion:PsyCap has a mediating effect between effort, reward, over-commitment of occupational stress and suicidal ideation.

Objective To detect the levels of neutrophil extracellular traps (NETs) in patients with antiphospholipid syndrome (APS) and to preliminarily explore its formation mechanism.Methods Plasma samples from 27 APS patients and 30 healthy controls were collected.The circulating free DNA (cf-DNA) in plasma was detected by the PicoGreen nucleic acid quantitative assay kit,and the concentration of citrulline histone 3 (CitH3) was analyzed by enzyme-linked immuno sorbent assay (ELISA).The association of cf-DNA/NETs with thrombotic events in APS patients was further analyzed.The neutrophils in healthy controls were separated by density gradient centrifugation and stimulated with anti-β2GPl/β2GPI complex (100 μg/mL) for 4 h,and the cf-DNA/NETs in the culture supernatant was determined.TLR-4 inhibitor-TAK242 (5 μmol/L) was further used to observe whether the stimulation of the anti-β2GPI/β2GPI complex on cells could be intervened.The differences between groups were analyzed by analysis of variance (ANOVA) or rank sum test,Sidak or Dunnett's test were used to compare the mean of multiple samples and the correlation between variables was analyzed by Spearman's correlation test.Results The concentration of cf-DNA/NETs and CitH3 were significantly increased in plasma of APS patients compared with that in healthy controls [175.7(70.6,205.7) ng/ml vs 29.8(7.6,115.7) ng/ml,Z=-3.654,P＜0.05;19.5(7.8,26.4) ng/ml vs 3.3(0.84,10.3) ng/ml,Z=-3.932,P＜0.05],and there was a significant positive correlation between the cf-DNA/NETs and CitH3 (r=0.447,P=0.019).In the APS group,there was no significant difference in cf-DNA/NETs between patients with arterial thrombosis and those with venous thrombosis [177.1(67.8,297.2) ng/ml vs 184.7(82.4,233.9) ng/ml,Z=-0.301,P=0.786],whereas cf-DNA/NETs in the patients who experienced a new thrombotic event in 1 month was significantly higher than those with a history of thrombosis [192.1(83.6,328.8) ng/ml vs 90.0(42.8,184.7) ng/ml,Z=-2.006,P=0.046].In vitro,anti-β2GPI/β2GPI complex (100 μg/ml) stimulated the release of cf-DNA/NETs from neutrophils,which was significantly increased compared with the control group (t=10.39,P＜0.05),while TAK242 significantly inhibited the stimulating effects of anti-β2GPI/β2GPI complex on cells (t=4.22,P＜0.05).Conclusion The level of cf-DNA/NETs in peripheral blood of APS patients is significantly increased,which may play an important role in APS thrombosis.Anti-β2GPI/β2GPI complex induces the formation of cf-DNA/NETs through TLR4 and participates in the pathological process of APS.