Objective: Src homology phosphotyrosin phosphatase 2 (SHP2) has been implicated in the progression of several cancer types. However, its function in endometrial cancer (EC) remains unclear. Here, we report that the ten-eleven translocation 3 (TET3)-mediated DNA demethylation modification is responsible for the oncogenic role of SHP2 in EC and explore the detailed mechanism. Methods: The transcriptomic differences between EC tissues and control tissues were analyzed using bioinformatics tools, followed by protein-protein interaction network establishment. EC cells were treated with shRNA targeting SHP2 alone or in combination with isoprocurcumenol, an epidermal growth factor receptor (EGFR) signaling activator.The cell biological behavior was examined using cell counting kit-8, colony formation, flow cytometry, scratch assay, and transwell assays, and the median inhibition concentration values to medroxyprogesterone acetate/gefitinib were calculated. The binding of TET3 to the SHP2 promoter was verified. EC cells with TET3 knockdown and combined with SHP2 overexpression were selected to construct tumor xenografts in mice. Results: TET3 and SHP2 were overexpressed in EC cells. TET3 bound to the SHP2 promoter, thereby increasing the DNA hydroxymethylation modification and activating SHP2 to induce the EGFR/extracellular signal-regulated kinase (ERK) pathway. Knockdown of TET3 or SHP2 inhibited EC cell malignant aggressiveness and impaired the EGFR/ERK pathway. Silencing of TET3 inhibited the tumorigenic capacity of EC cells, and ectopic expression of SHP2 or isoprocurcumenol reversed the inhibitory effect of TET3 knockdown on the biological activity of EC cells. Conclusion TET3 promoted the DNA demethylation modification in the SHP2 promoter and activated SHP2, thus activating the EGFR/ERK pathway and leading to EC progression.

Objective:To explore the optimal regimen of standardized mite allergen immunotherapy for airway allergic diseases in children, and to observe the clinical efficacy, safety and compliance.Method:Use a retrospective real-world study, clinical data from 156 children aged 5-16 years who received subcutaneous immunotherapy (SCIT) with double mite allergen preparation in the pediatrics department of the Third Affiliated Hospital of Sun Yat sen University from June 2019 to September 2020 were selected for allergic rhinitis (AR) and/or allergic asthma (bronchial asthma, BA), including gender, age, total VAS(visual analogue scale) score and CSMS(combined symptom and medication scores) score at different time points (before treatment, 4-6 months, 1 year, and 2 years after initiation of desensitization), peripheral blood eosinophil counts (EOS), serum total IgE (tIgE), specific IgE (tIgE), and serum IgE (tIgE), specific IgE (sIgE), tIgG4, and incidence of local and systemic adverse reactions. All patients had a consistent regimen during the initial treatment phase (dose-escalation phase), which was performed as directed. Among them, 81 cases (observation group) continued to continue subcutaneous injection of 1 ml of vial No. 3 every 4-6 weeks during the dose maintenance phase, while 75 cases (control group) followed the old traditional regimen during the maintenance phase (i.e., change to a new vial to halve the amount of vial No. 3 by 0.5 ml, and then 0.75 ml after 1-2 weeks, and 1 ml in a further interval of 1-2 weeks). The clinical efficacy, safety and adherence to the treatment were compared between the two groups.Results:A total of 81 cases of 156 children were included in the observation group, of which 58 children with AR, 15 children with BA, and 8 children with AR combined with BA; 75 cases were included in the conventional control group, of which 52 children with AR, 16 children with BA, and 7 children with AR combined with BA. In terms of safety, the difference in the incidence of local and systemic adverse reactions between the two groups was not statistically significant ( χ2=1.541 for local adverse reactions in the control group, χ2=0.718 for the observation group; χ2=0.483 for systemic adverse reactions in the control group, χ2=0.179 for the observation group, P value >0.05 for all of these), and there were no grade Ⅱ or higher systemic adverse reactions in any of them. In the control group, there were 15 cases of dropout at 2 years of follow-up, with a dropout rate of 20.0%; in the observation group, there were 7 cases of dropout at 2 years of follow-up, with a dropout rate of 8.6%, and there was a statistically significant difference in the dropout rates of the patients in the two groups ( χ2=4.147, P<0.05). Comparison of serological indexes and efficacy (compared with baseline at 3 different time points after treatment, i.e., 4-6 months, 1 year and 2 years after treatment), CSMS scores of the observation group and the conventional control group at 4-6 months, 1 year and 2 years after treatment were significantly decreased compared with the baseline status ( t-values of the conventional group were 13.783, 20.086 and 20.384, respectively, all P-values <0.001, and t-values of the observation group were 15.480, 27.087, 28.938, all P-values <0.001), and VAS scores also decreased significantly from baseline status in both groups at 4-6 months, 1 year, and 2 years of treatment ( t-values of 14.008, 17.963, and 27.512 in the conventional control group, respectively, with all P-values <0.001, and t-values of 9.436, 13.184, and 22.377 in the observation group, respectively; all P-values <0.001). Intergroup comparisons showed no statistically significant differences in CSMS at baseline status, 4-6 months, 1 year and 2 years ( t-values 0.621, 0.473, 1.825, and 0.342, respectively, and P-values 0.536, 0.637, 0.070, and 0.733, respectively), and VAS was no statistically significant difference in comparison between groups at different time points ( t-values of 1.663, 0.095, 0.305, 0.951, P-values of 0.099, 0.925, 0.761, 0.343, respectively); suggesting that the treatment regimens of the observation group and the conventional control group were clinically effective, and that the two regimens were comparable in terms of efficacy. The peripheral blood eosinophil counts of the observation group and the conventional control group decreased significantly from the baseline status at 4-6 months, 1 year and 2 years of treatment ( t-values of the conventional group were 3.453, 5.469, 6.273, P-values <0.05, and the t-values of the observation group were 2.900, 4.575, 5.988, P-values <0.05, respectively). 4-6 months, 1 year and 2 years compared with the baseline status tIgE showed a trend of increasing and then decreasing ( t-value in the conventional group was -5.328, -4.254, -0.690, P-value was 0.000, 0.000, 0.492, respectively, and t-value in the observation group was -6.087, -5.087, -0.324, P-value was 0.000, 0.000, 0.745, respectively). However, the results of intergroup comparisons showed no statistically significant differences in serological indices and efficacy between the two groups in terms of peripheral blood eosinophil counts at baseline status, 4-6 months, 1 year and 2 years ( t-values of 0.723, 1.553, 0.766, and 0.234, respectively; P-values of 0.471, 0.122, 0.445, and 0.815, respectively), tIgE ( t-values of 0.170, -0.166, -0.449, 0.839, P-values 0.865, 0.868, 0.654, 0.403, respectively), tIgG4 ( t-values 1.507, 1.467, -0.337, 0.804, P-values 0.134, 0.145, 0.737, 0.422, respectively). Conclusion:Both immunotherapy regimens for airway allergic diseases with double mite allergen subcutaneous immunotherapy have significant clinical efficacy, low incidence of adverse reactions, and the observation group has better patient compliance than the control group.

Objective:To explore the optimal regimen of standardized mite allergen immunotherapy for airway allergic diseases in children, and to observe the clinical efficacy, safety and compliance.Method:Use a retrospective real-world study, clinical data from 156 children aged 5-16 years who received subcutaneous immunotherapy (SCIT) with double mite allergen preparation in the pediatrics department of the Third Affiliated Hospital of Sun Yat sen University from June 2019 to September 2020 were selected for allergic rhinitis (AR) and/or allergic asthma (bronchial asthma, BA), including gender, age, total VAS(visual analogue scale) score and CSMS(combined symptom and medication scores) score at different time points (before treatment, 4-6 months, 1 year, and 2 years after initiation of desensitization), peripheral blood eosinophil counts (EOS), serum total IgE (tIgE), specific IgE (tIgE), and serum IgE (tIgE), specific IgE (sIgE), tIgG4, and incidence of local and systemic adverse reactions. All patients had a consistent regimen during the initial treatment phase (dose-escalation phase), which was performed as directed. Among them, 81 cases (observation group) continued to continue subcutaneous injection of 1 ml of vial No. 3 every 4-6 weeks during the dose maintenance phase, while 75 cases (control group) followed the old traditional regimen during the maintenance phase (i.e., change to a new vial to halve the amount of vial No. 3 by 0.5 ml, and then 0.75 ml after 1-2 weeks, and 1 ml in a further interval of 1-2 weeks). The clinical efficacy, safety and adherence to the treatment were compared between the two groups.Results:A total of 81 cases of 156 children were included in the observation group, of which 58 children with AR, 15 children with BA, and 8 children with AR combined with BA; 75 cases were included in the conventional control group, of which 52 children with AR, 16 children with BA, and 7 children with AR combined with BA. In terms of safety, the difference in the incidence of local and systemic adverse reactions between the two groups was not statistically significant ( χ2=1.541 for local adverse reactions in the control group, χ2=0.718 for the observation group; χ2=0.483 for systemic adverse reactions in the control group, χ2=0.179 for the observation group, P value >0.05 for all of these), and there were no grade Ⅱ or higher systemic adverse reactions in any of them. In the control group, there were 15 cases of dropout at 2 years of follow-up, with a dropout rate of 20.0%; in the observation group, there were 7 cases of dropout at 2 years of follow-up, with a dropout rate of 8.6%, and there was a statistically significant difference in the dropout rates of the patients in the two groups ( χ2=4.147, P<0.05). Comparison of serological indexes and efficacy (compared with baseline at 3 different time points after treatment, i.e., 4-6 months, 1 year and 2 years after treatment), CSMS scores of the observation group and the conventional control group at 4-6 months, 1 year and 2 years after treatment were significantly decreased compared with the baseline status ( t-values of the conventional group were 13.783, 20.086 and 20.384, respectively, all P-values <0.001, and t-values of the observation group were 15.480, 27.087, 28.938, all P-values <0.001), and VAS scores also decreased significantly from baseline status in both groups at 4-6 months, 1 year, and 2 years of treatment ( t-values of 14.008, 17.963, and 27.512 in the conventional control group, respectively, with all P-values <0.001, and t-values of 9.436, 13.184, and 22.377 in the observation group, respectively; all P-values <0.001). Intergroup comparisons showed no statistically significant differences in CSMS at baseline status, 4-6 months, 1 year and 2 years ( t-values 0.621, 0.473, 1.825, and 0.342, respectively, and P-values 0.536, 0.637, 0.070, and 0.733, respectively), and VAS was no statistically significant difference in comparison between groups at different time points ( t-values of 1.663, 0.095, 0.305, 0.951, P-values of 0.099, 0.925, 0.761, 0.343, respectively); suggesting that the treatment regimens of the observation group and the conventional control group were clinically effective, and that the two regimens were comparable in terms of efficacy. The peripheral blood eosinophil counts of the observation group and the conventional control group decreased significantly from the baseline status at 4-6 months, 1 year and 2 years of treatment ( t-values of the conventional group were 3.453, 5.469, 6.273, P-values <0.05, and the t-values of the observation group were 2.900, 4.575, 5.988, P-values <0.05, respectively). 4-6 months, 1 year and 2 years compared with the baseline status tIgE showed a trend of increasing and then decreasing ( t-value in the conventional group was -5.328, -4.254, -0.690, P-value was 0.000, 0.000, 0.492, respectively, and t-value in the observation group was -6.087, -5.087, -0.324, P-value was 0.000, 0.000, 0.745, respectively). However, the results of intergroup comparisons showed no statistically significant differences in serological indices and efficacy between the two groups in terms of peripheral blood eosinophil counts at baseline status, 4-6 months, 1 year and 2 years ( t-values of 0.723, 1.553, 0.766, and 0.234, respectively; P-values of 0.471, 0.122, 0.445, and 0.815, respectively), tIgE ( t-values of 0.170, -0.166, -0.449, 0.839, P-values 0.865, 0.868, 0.654, 0.403, respectively), tIgG4 ( t-values 1.507, 1.467, -0.337, 0.804, P-values 0.134, 0.145, 0.737, 0.422, respectively). Conclusion:Both immunotherapy regimens for airway allergic diseases with double mite allergen subcutaneous immunotherapy have significant clinical efficacy, low incidence of adverse reactions, and the observation group has better patient compliance than the control group.

Objective: Src homology phosphotyrosin phosphatase 2 (SHP2) has been implicated in the progression of several cancer types. However, its function in endometrial cancer (EC) remains unclear. Here, we report that the ten-eleven translocation 3 (TET3)-mediated DNA demethylation modification is responsible for the oncogenic role of SHP2 in EC and explore the detailed mechanism. Methods: The transcriptomic differences between EC tissues and control tissues were analyzed using bioinformatics tools, followed by protein-protein interaction network establishment. EC cells were treated with shRNA targeting SHP2 alone or in combination with isoprocurcumenol, an epidermal growth factor receptor (EGFR) signaling activator.The cell biological behavior was examined using cell counting kit-8, colony formation, flow cytometry, scratch assay, and transwell assays, and the median inhibition concentration values to medroxyprogesterone acetate/gefitinib were calculated. The binding of TET3 to the SHP2 promoter was verified. EC cells with TET3 knockdown and combined with SHP2 overexpression were selected to construct tumor xenografts in mice. Results: TET3 and SHP2 were overexpressed in EC cells. TET3 bound to the SHP2 promoter, thereby increasing the DNA hydroxymethylation modification and activating SHP2 to induce the EGFR/extracellular signal-regulated kinase (ERK) pathway. Knockdown of TET3 or SHP2 inhibited EC cell malignant aggressiveness and impaired the EGFR/ERK pathway. Silencing of TET3 inhibited the tumorigenic capacity of EC cells, and ectopic expression of SHP2 or isoprocurcumenol reversed the inhibitory effect of TET3 knockdown on the biological activity of EC cells. Conclusion TET3 promoted the DNA demethylation modification in the SHP2 promoter and activated SHP2, thus activating the EGFR/ERK pathway and leading to EC progression.

Objective: Src homology phosphotyrosin phosphatase 2 (SHP2) has been implicated in the progression of several cancer types. However, its function in endometrial cancer (EC) remains unclear. Here, we report that the ten-eleven translocation 3 (TET3)-mediated DNA demethylation modification is responsible for the oncogenic role of SHP2 in EC and explore the detailed mechanism. Methods: The transcriptomic differences between EC tissues and control tissues were analyzed using bioinformatics tools, followed by protein-protein interaction network establishment. EC cells were treated with shRNA targeting SHP2 alone or in combination with isoprocurcumenol, an epidermal growth factor receptor (EGFR) signaling activator.The cell biological behavior was examined using cell counting kit-8, colony formation, flow cytometry, scratch assay, and transwell assays, and the median inhibition concentration values to medroxyprogesterone acetate/gefitinib were calculated. The binding of TET3 to the SHP2 promoter was verified. EC cells with TET3 knockdown and combined with SHP2 overexpression were selected to construct tumor xenografts in mice. Results: TET3 and SHP2 were overexpressed in EC cells. TET3 bound to the SHP2 promoter, thereby increasing the DNA hydroxymethylation modification and activating SHP2 to induce the EGFR/extracellular signal-regulated kinase (ERK) pathway. Knockdown of TET3 or SHP2 inhibited EC cell malignant aggressiveness and impaired the EGFR/ERK pathway. Silencing of TET3 inhibited the tumorigenic capacity of EC cells, and ectopic expression of SHP2 or isoprocurcumenol reversed the inhibitory effect of TET3 knockdown on the biological activity of EC cells. Conclusion TET3 promoted the DNA demethylation modification in the SHP2 promoter and activated SHP2, thus activating the EGFR/ERK pathway and leading to EC progression.

Objective: Oxygen-glucose deprivation (OGD) is used to mimic ischemia in vitro to observe whether endoplasmic reticulum (ER) stress is involved in human dental pulp cells (hDPCs) after OGD and to better understand the regulatory mechanism of hDPCs in ischemia. Methods: hDPCs were cultured in glucose-free DMEM and hypoxia (volume fraction 2% O2) to establish an hDPCs OGD model in vitro, which mimics hDPCs ischemia in vitro. hDPCs were divided into a control group (normal culture) and an experimental group (OGD 0 h, 2 h, 4 h and 8 h groups). After pretreatment with OGD for 0, 2, 4 and 8 h, hDPC viability was measured by methylthiazol tetrazolium (MTT) assay. qRT-PCR was used to detect the mRNA expression of ER stress markers [splicing x-box binding protein1 (sXBP1), activating transcription Factor 4 (ATF4) and C/EBP homologous protein (chop)]. Western blot was used to detect the protein expression of ER stress markers [phosphorylated RNA-activated protein kinase-like ER-resident kinase (p-perk) and phosphorylated eukaryotic initiation factor-2α (p-eIF2α)]. Results: Compared with OGD 0 h group, cell viability of hDPCs decreased when exposed to OGD treatment for 2 h, 4 h and 8 h. Compared with the control group, mRNA expressions of ER stress makers (sXBP1, ATF4 and chop) and the protein expressions of ER stress protein markers (p-perk andp-eIF2α) increased in OGD treatment cells after 4 h were higher in OGD cells. The differences were statistically significant (P<0.05). Conclusion The results indicate that ER stress response is involved in hDPCs in OGD treatment.

Objective:To detect the incidence and analyze the clinical significance of regions of homozygosity (ROH) through the single nucleotide polymorphism array (SNP array).Methods:The SNP array detection results of 5 116 pregnant women in the Third Affiliated Hospital of Guangzhou Medical University from January 2016 to December 2020 were retrospectively analyzed. The pregnant women with ROH (5 Mb as the threshold) were followed up to analyze the relationship between ROH and abnormal fetal phenotype. Whole exon sequencing was performed in 4 cases of consanguineous marriage to detect potential recessive causative genes in the ROH region.Results:(1) A total of 39 cases of ROH were detected, with a positive rate of 0.76% (39/5 116). Among them, 25 cases (64%, 25/39) were detected only on single chromosome, and chromosome 11 had the highest detection rate, suggesting the risk of uniparental disomy; fourteen cases (36%,14/39) were detected on multiple chromosomes, most commonly on chromosomes 11, 1, 3, 4 and 8. (2) The number of cases and detection rate of ROH detected by different prenatal diagnosis indicators were as follows: 12 cases (1.78%, 12/676) in pregnant women with abnormal non-invasive prenatal testing result, 12 cases (0.37%, 12/3 284) in pregnant women with ultrasound abnormality, 4 cases (4/4) in pregnant women with consanguineous marriage, 3 cases (0.92%, 3/326) in pregnant women with previous adverse pregnancy, 2 cases (1.15%, 2/174) in pregnant women with high risk of serology in screening, 2 cases (4.00%, 2/50) in pregnant women with abnormal fetal chromosomal karyotype, 2 cases (0.79%, 2/253) in pregnant women with advanced maternal age, 1 case (0.56%, 1/178) in pregnant women with related parental genetic factors and 1 case (0.58%, 1/171) in pregnant women with the other factors. (3) The follow-up results of 39 cases of prenatal ROH showed that there were 16 cases of term birth, 15 cases of termination of pregnancy, 2 cases of preterm births, 1 case of fetal death and 5 cases lost to follow-up.Conclusions:Chromosomal ROH phenomenon is not rare. By analyzing the detection rate of ROH in prenatal diagnosis, combined with the results of fetal phenotype and postpartum follow-up, the clinical characteristics of ROH are discussed, so as to better understand the relationship between ROH and its phenotype.

Objective:To analyze the correlation among social support, positive coping and job burnout among nurses in Department of Infectious Diseases.Methods:From March 2020 to June 2021, convenience sampling was used to select 110 nurses from Department of Infectious Diseases of 8 ClassⅢ hospitals in Hangzhou, Zhejiang Province as the research object. The General Information Questionnaire, Maslach Burnout Inventory, Social Support Rating Scale (SSRS) , and Simple Coping Style Questionnaire (SCSQ) were used to investigate the nurses. Pearson correlation analysis was used analyze the correlation among job burnout, social support and positive coping. A total of 110 questionnaires were distributed, and 102 effective questionnaires were recovered, with an effective recovery rate of 92.73%.Results:Among the 102 nurses in Department of Infectious Diseases, 17.65% (18/102) were in mild burnout, 57.84% (59/102) were in moderate burnout, and 20.59% (21/102) were in severe burnout. The SSRS total score and each dimension score of nurses in Department of Infectious Diseases were positively correlated with the positive coping subscale score of SCSQ ( P<0.05) , and negatively correlated with the emotional exhaustion subscale and depersonalization subscale score of the Maslach Burnout Inventory ( P<0.05) , but it was positively correlated with the personal achievement subscale score ( P<0.05) . Conclusions:The overall job burnout of nurses in Department of Infectious Diseases was moderate to severe level, and social support and positive coping were correlated with job burnout. Nursing managers should develop measures to reduce the job burnout of nurses in Department of Infectious Diseases.

Objective:To explore the influencing factors and related countermeasures of malnutrition in patients with chronic liver failure (CLF) .Methods:The convenient sampling method was used to select 80 CLF patients admitted to Hangzhou First People's Hospital from March 2019 to March 2021. The clinical data of CLF patients were collected and patients were divided into the malnutrition group (57 cases) and the non-malnutrition group (23 cases) according to the presence or absence of malnutrition. Logistic regression analysis was used to explore the influencing factors of malnutrition in CLF patients, and to propose corresponding nursing strategies.Results:The incidence of malnutrition in 80 CLF patients was 71.25%. Between malnutrition group and non-malnutritrion group, there were statistical differences in age, smoking, body mass index (BMI) , disease course, etiological composition, Child-Push classification, number of adverse events, triceps skin fold thickness (TSF) , arm muscle circumference (AMC) , gastrocnemius muscle circumference (GC) , prealbumin (PA) and albumin (ALB) ( P<0.05) . Multivariate Logistic regression analysis showed that age, smoking, etiology, Child-Push classification and number of adverse events were the influencing factors of malnutrition in CLF patients ( P<0.05) . Conclusions:There are many influencing factors of malnutrition in CLF patients, and medical staff should warn the relevant factors and give targeted predictive nursing interventions to reduce the risk of malnutrition in patients.

Objective:To explore the influence factors of neurodevelopmental disorders in children with SCN8A-related early-onset epilepsy through analyzing their clinical characteristics and following up their neurodeve-lopmental status. Methods:A retrospective analysis was carried out on 21 children (13 males and 8 females, the age ranged from 4 months to 8 years, average 31.6 months)with SCN8A-related early-onset epilepsy treated in Guangzhou Women and Children′s Medical Center and Kunming Children′s Hospital between January 2017 and February 2021.All patients underwent whole-exome sequencing and Sanger sequencing.The pathogenicity was estimated according to the American College of Medical Genetics and Genomics guidelines.The clinical data of all patients were also collected, including the age of onset of the disease, forms of seizures, seizure frequency, neurological development at onset, electroencephalogram (EEG) and brain magnetic resonance imaging (MRI). Besides, the patients were followed up to acquire the effect of sodium channel blockers after the onset of seizures, the process or improvement of neurodeve-lopment, EEG evaluation and neurodevelopmental outcomes.Patients were grouped based on data analysis results.The Fisher′s exact test was conducted to measure the effect of various factors on the neurodevelopmental process and outcome, and corresponding coe-fficients were calculated. Results:The average onset age of 21 patients was 0-9 months.The follow-up duration was 4 months-8 years.Three cases died.Sixteen cases (76.2%) had early infantile epileptic encephalopathy (EIEE), 5 cases (23.8%) had epilepsy without encephalopathy, and 1 case had benign infantile epilepsy.Fourteen cases (66.7%) belonged to drug resistant epilepsy.Only one child showed normal neurodevelopment.Eleven children showed delayed neurodevelopment, but improvement was observed.Nine children were retrogressed and stagnated in terms of neurodevelopment.Small age at onset ( Fisher=9.517, P=0.020, r=0.571), high seizure frequency ( Fisher=10.512, P=0.003, r=0.572), EEG background ( Fisher=10.512, P=0.003, r=0.572), epileptic discharges ( Fisher=8.288, P=0.008, r=0.542), and EEG changes before and after treatment ( Fisher=10.437, P=0.009, r=0.586) were important factors affecting the neurodevelopmental process.Neurodevelopmental outcome was normal in only 1 case, 1 child belonged to mild mental retardation (MR), 7 children belonged to moderate MR, 3 children belonged to severe MR, and 9 children belonged to profound MR.Statistical analysis indicated that the clinical phenotype ( Fisher=10.059, P=0.004, r=0.739) and drug resistance ( Fisher=13.706, P=0.001, r=0.640) were significantly correlated with neurodevelopmental outcomes.However, the forms of seizures, EEG findings at onset and mutation sites were not related to neurodevelopmental disorders. Conclusions:Most children with SCN8A-related early-onset epilepsy are accompanied with neurodevelopmental retardation of varying degrees.Epileptic encephalopathy and poor response to drug treatment will lead to severe neurodevelopmental disorders.