Objective To explore the potential categories of self-efficacy in patients with rheumatoid arthritis(RA),analyze their influencing factors,and provide references for the development of personalized care measures.Methods Patients with RA who visited the rheumatology and immunology outpatient department of a tertiary hospital in Changzhou from March 2022 to March 2023 were selected.A general information questionnaire,the Chinese version of the Rheumatoid Arthritis Self-Efficacy Scale(C-RASE),and Compliance Questionnaire Rheumatology(CQR)were used to investigate RA patients.Latent class analysis was used to classify self-efficacy,and logistic regression analysis was conducted to explore the influencing factors of self-efficacy.Results A total of 219 subjects were included in the survey.The score of C-RASE was(100.68±12.64).The self-efficacy of RA patients was divided into a high efficacy-low support group(105.18±10.18),a moderate efficacy-diverse needs group(93.21±4.16),and a low efficacy-high fatigue group(84.07±13.96).Logistic regression analysis showed that disease duration(OR=1.062,P=0.024),education(OR=5.405,P=0.036;OR=12.347,P=0.021),and erythrocyte sedimentation rate(OR=1.019,P=0.020;OR=1.019,P=0.027)were factors affecting patients'self-efficacy.The treatment compliance scores of the 3 latent class categories(F=10.902,P＜0.001)and the rate of good treatment compliance(x2=16.053,P＜0.001)were statistically significant.Conclusion RA patients exhibit significant heterogeneity in their self-efficacy levels,and there are variations in treatment adherence among patients in different self-efficacy categories.Nurses should prioritize the attention towards the population groups with moderate efficacy-diverse needs,as well as the groups with low efficacy-high fatigue,implementing cognitive behavioral interventions to assist them in setting clear goals and providing specific plans and guidance to improve their health outcomes.

[Objective]To summarize Professor WANG Xiaoming's academic experience in the treatment of children with tic disorder with the method of harmonizing the liver and spleen.[Methods]The essence of Professor WANG's method of treating children with tic disorder was analyzed from four aspects:theoretical source,theoretical basis,specific application and case study.[Results]The pathogenesis of children's tic disorder is mainly"liver effulgence and spleen deficiency",which is manifested as liver Yang hyperactivity,liver wind internal movement,spleen and stomach disharmony,even spleen and stomach weakness and muscle dystrophy.Therefore,in the treatment of this disease,the general idea is to harmonize the liver and spleen.Professor WANG stresses that the using this method to treat tic disorders,needs to flexibly sooth the liver,soften the liver,strengthen the spleen,relax the tendons,eliminate accumulation and stagnation,and other methods to adjust the liver and spleen,often choose Tianma Gouteng Drink,Erchen Decoction,Chaihu Shugan Powder,Sini Powder and other prescriptions for treatment.In the medical case of the article,Professor WANG distinguished the syndrome of liver effulgence and spleen deficiency,and treated it to harmonize the liver and spleen,the prescription was Tiaohe Zhidong Decoction,and the effect was remarkable.[Conclusion]Professor WANG's clinical treatment of children with tic disorder takes the coordination of liver and spleen as the starting point.According to the different clinical manifestations and syndrome groups of children,flexible prescription has a remarkable effect on relieving the tic symptoms of children,which is worth learning and promoting.

Objective To investigate the role of Toll-like receptor 4(TLR4)in hepatocyte regeneration after acet-aminophen(APAP)-induced injury in human normal liver cell(L02)and its possible mechanism.Methods L02 cells were cultured in vitro,and cell viability was detected by CCK-8 assay.The optimal concentration and duration of APAP and the concentration of TLR4 inhibitor(TAK-242)were determined.The protein expression levels of nu-clear factor-κB(NF-κB),microtubule-associated protein light chain 3(LC3),p62,receptor interacting protein kinase 1(RIP1),receptor interacting protein kinase 3(RIP3),signal transducer and activator of transcription 3(STAT3),phosphorylation of STAT3(p-STAT3),proliferating cell nuclear antigen(PCNA)and Cyclin D1 were detected by Western blot.The mRNA expression levels of TLR4,NF-κB,tumor necrosis factor-α(TNF-α),inter-leukin-6(IL-6),interleukin-1 β(IL-1 β),PCNA,Cyclin D1 and Ki67 were detected by qRT-PCR.Results Ac-cording to the results of CCK-8,L02 cells were treated with 5 mmol/L APAP for 24,36,48 h to simulate liver in-jury and regeneration model in vitro,and TAK-242 100 nmol/L was pretreated 2 ht before APAP to inhibit TLR4.Compared with the control group,the protein levels of NF-κB,RIP1,p-STAT3,PCNA,Cyclin D1 and the mRNA levels of TNF-α,IL-1 β and PCNA increased in the APAP 24 h group;the protein levels of NF-κB,RIP1,RIP3,p-STAT3,PCNA,Cyclin D1 and the mRNA levels of TLR4,NF-κB,TNF-α,IL-1 β,PCNA and Cyclin D1 in-creased in the APAP 36 h group;the protein levels of NF-κB,RIP1,p-STAT3,PCNA,Cyclin D1 and the mRNA levels of TLR4,NF-κB,TNF-α,IL-1β,IL-6,PCNA,Cyclin D1 and Ki67 increased in the APAP 48 h group.The protein levels of NF-κB,RIP1,RIP3,p-STAT3,PCNA,Cyclin D1 and the mRNA levels of TLR4,NF-κB,TNF-α,IL-1β,IL-6,PCNA,Cyclin D1,Ki67 significantly decreased in APAP+TAK-242 24 h and 48 h group than the APAP group at the same time point;the protein levels of NF-κB,PCNA and the mRNA levels of TLR4,NF-κB,TNF-α,IL-1β,IL-6,PCNA and Ki67 in APAP+TAK-242 36 h group were also significantly lower than those in APAP 36 h group.Compared with the control group,autophagy was activated in the APAP group,while autophagy was inhibited in the APAP+TAK-242 group.Conclusion TLR4 may affect the TLR4/NF-κB pathway,up-regulate the levels of inflammatory factors and autophagy,and promote hepatocyte regeneration after APAP-in-duced liver injury in L02 cells.

Objective:To investigate the clinical value of targeted sequencing panel in the detection of genetic variation in neonates in neonatal intensive care unit (NICU).Methods:All neonates (≤28 d of age) admitted in the NICU (case group) and 200 full-term healthy neonates born with no obvious phenotypic abnormalities of Huzhou Maternity and Child Health Care Hospital were enrolled in this prospective study from November 2022 to January 2023. Based on a list of preventable and treatable rare diseases as well as newly screened diseases in China, a targeted sequencing panel suitable for Chinese newborns was designed to target the pathogenic genes and mutation sites associated with 601 genes and 542 diseases. Dried blood spot specimens were prepared and analyzed by the targeted sequencing panel. Pathogenic sites detected by the panel sequencing were verified using Sanger sequencing. The genetic testing results were analyzed according to the clinical features of the neonates. According to the number of primary clinical diagnosis index (including premature infants, neonatal hyperbilirubinemia, hemorrhagic diseases, neonatal infections, ventricular septal defect/patent ductus arteriosus, and others), these patients were divided into four groups with 1, 2, 3, and ≥4 diagnosis index, respectively. Chi-square test and linear correlation Chi-square test were used for statistical analysis. Results:There were 173 patients in the case group and 30.6% (53/173) of them carried pathogenic variants, including 52 positive for pathogenic genes and one with chromosome copy number variant. The positive rate of pathogenic genes was significantly higher in the case group than in the control group [30.1% (52/173) vs. 15.0% (30/200), χ 2=12.26, P<0.001]. Fourteen pathogenic genes were detected in the case group, including FLG, UGT1A1, G6PD, MYH7, AR, ABCC2, ACADS, CYP21A2, GJB2, MEFV, PAH, PKHD1, SCN4A, and HBA. In the case group, the detection rate of pathogenic variants in jaundiced neonates was higher than that in non-jaundiced neonates [35.2% (44/125) vs. 18.8% (9/48), χ 2=4.42, P=0.036]. However, there were no statistically significant differences in the detection rates of pathogenic variants between male and female infants, infants born to mothers of advanced maternal age or not, infants born to mothers with or without gestational diabetes mellitus, premature and term infants, or infants with or without hemorrhagic disorders, neonatal infections, or ventricular septal defects/patent ductus arteriosus in the case group (all P>0.05). The detection rate of pathogenic variants showed a linear increase in infants with 1, 2, 3, and ≥4 diagnosis index [21.1% (8/38), 25.4% (15/59), 38.2% (13/34), and 40.5% (17/42); linear correlation χ 2=4.84, P=0.028]. In the case group, seven genes with a high detection rate of genetic variation (including positive pathogenic genes and carriers) were UGT1A1 [had the highest detection rate, 24.9% (43/173)], GJB2, FLG, DUOX2, ABCA4, G6PD, and MUT. Seven loci with higher mutation frequency were c.211G>A(p.Gly71Arg), c.1091C>T(p.Pro364Leu), c.-41_-40dupTA, and c.686C>A(p.Pro229Gln) in the UGT1A1 gene, c.109G>A(p.Val37Ile) in the GJB2 gene, and c.12064A>T(p.Lys4022Ter) and c.3321del(p.Gly1109GlufsTer13) in the FLG gene. Conclusion:This panel sequencing can provide effective genetic testing for neonates in NICU, especially in children with complex clinical diagnosis.

Objective:To analyze the types and distribution of pathogenic variants for neonatal genetic diseases in Huzhou, Zhejiang Province.Methods:One thousand neonates (48 ~ 42 h after birth) born to Huzhou region were selected as the study subjects. Dry blood spot samples were collected from the newborns, and targeted capture high-throughput sequencing was carried out for pathogenic genes underlying 542 inherited diseases. Candidate variants were verified by Sanger sequencing.Results:Among the 1 000 newborns, the male to female ratio was 1.02 : 1.00. No pathogenic variants were detected in 253 cases, whilst 747 cases were found to carry at least one pathogenic variant, which yielded a carrier rate of 74.7%. The most frequently involved pathogenic gene was FLG, followed by GJB2, UGT1A1, USH2A and DUOX2. The variants were classified as homozygous, compound heterozygous, and hemizygous variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), 213 neonates were verified to have carried pathogenic and/or likely pathogenic variants, with a positive rate of 21.3%. The most commonly involved genes had included UGT1A1, FLG, GJB2, MEFV and G6PD. Conclusion:Newborn screening based on high-throughput sequencing technology can expand the scope of screening and improve the positive predictive value. Genetic counseling based on the results can improve the patients′ medical care and reduce neonatal mortality and childhood morbidity, while provide assistance to family members′ health management and reproductive decisions.

The number of investigator initiated research (IIR) is increasing. But the recognition and management of IIR in China is still in its infancy, and there is a lack of specific and operable guidance for the implementation process. Based on our practical experiences, previous literature reports, and current policy regulations, the authors took prospective IIR as an example to summarize the implementation process of IIR into 14 steps, which are as the following: study initiation, ethical review, study registration, study filing, case report form design, database establishment, standard operating procedure making, investigator training, informed consent, data collection, data entry, data verification, data locking and data archiving.

Objective To investigate whether Toll-like receptor 4 (TLR4) inhibition affects liver regeneration during acetaminophen (APAP)-induced liver injury in mice, as well as the mechanism of TLR4 involved in liver regeneration. Methods A total of 78 male CD-1 mice were divided into nine groups using a random number table, i.e., three control groups (normal control group, solvent control group, inhibitor control group) with 6 mice in each group and six experimental groups (APAP 24-hour group, TAK-242+APAP 24-hour group, APAP 48-hour group, TAK-242+APAP 48-hour group, APAP 72-hour group, TAK-242+APAP 72-hour group) with 10 mice in each group. The mice in the experimental groups were given a single dose of intraperitoneally injected APAP (300 mg/kg), and TAK-242 was intraperitoneally injected at a dose of 3 mg/kg at 3 hours before APAP administration. Serum and liver tissue samples were collected at different time points. The biochemical method was used to measure the serum level of alanine aminotransferase (ALT); HE staining was used to observe liver pathological changes; RT-PCR, Western blot, and immunohistochemistry were used to measure the expression levels of Cyclin D1, PCNA, Ki-67, STAT3, and p-STAT3. The t -test was used for comparison of normally distributed continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t -test was used for further comparison between two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups and further comparison between two groups. Results Compared with the normal control group, the APAP 24-hour and 48-hour groups had a significantly higher serum level of ALT (both P < 0.05), and the TAK-242+APAP 24-hour and 48-hour groups had a significantly higher serum level of ALT than the APAP group at the same time point (both P < 0.05). HE staining showed typical central lobular necrosis in the liver of APAP-treated mice, and the TAK-242+APAP 24-hour and 48-hour groups had a significantly larger necrotic area than the APAP group at the same time point (both P < 0.05). RT-PCR, Western blot, and immunohistochemistry showed that the TAK-242+APAP 24-hour, 48-hour, and 72-hour groups had significantly lower mRNA and protein expression levels of Cyclin D1 than the APAP group at the same time point (all P < 0.05); the TAK-242+APAP 24-hour, 48-hour, and 72-hour groups had a significantly lower mRNA expression level of PCNA than the APAP group at the same time point (all P < 0.05), and the TAK-242+APAP 24-hour and 48-hour groups had a significantly lower protein expression level of PCNA than the APAP group at the same time point (all P < 0.05); the TAK-242+APAP 24-hour and 72-hour groups had a significantly lower mRNA expression level of Ki-67 than the APAP group at the same time point (all P < 0.05), and the TAK-242+APAP 24-hour, 48-hour, and 72-hour groups had a significantly lower protein expression level of Ki-67 than the APAP group at the same time point (all P < 0.05). In addition, the TAK-242+APAP 24-hour and 48-hour groups had a significantly lower phosphorylation level of STAT3 than the APAP group at the same time point (both P < 0.05). Conclusion TLR4 may promote liver regeneration by increasing the phosphorylation level of STAT3 during APAP-induced liver injury in mice.

Objective : To used Toll⁃like receptor 4( TLR4) inhibitor ( TAK⁃242) investigate the role of TLR4 in the early stage of acetaminophen (APAP) Ⅳinduced acute liver injury in mice. Methods : Fifty⁃eight male institute of cancer research( ICR) mice were randomly divided into control group ( normal control group , solvent control group , inhibitor control group) and experimental group (APAP 4 ⁃ hour group , APAP + TAK⁃242 4 ⁃ hour group , APAP 12 ⁃ hour group , APAP + TAK⁃242 12 ⁃ hour group) . Mice in the experimental group were given a single dose of APAP (300 mg/kg) and TAK⁃242 (3 mg/kg) were given intraperitoneal injection 3 ⁃ hour before APAP injection. The serum alanine aminotransferase (ALT) level and liver index of mice in each group were compared ; HE staining showed pathological changes of liver tissue;the level of high mobility group box⁃1 (HMGB1) was determined by immunohistochemistry;the levels of TLR4 , HMGB1 and nuclear factor kappa B(NF⁃κB) protein were detected by Western blot;the levels of monocyte chemoattractant protein⁃1( MCP⁃1) , interleukin( IL) Ⅳ1β , tumor necrosis factor⁃α ( TNF⁃α ) and IL⁃6 genes were determined by real⁃time fluorescence quantitative PCR ( RT⁃qPCR) . The content of IL⁃6 in liver tissue was determined by enzyme linked immunosorbent assay (ELISA) . Results : HE staining showed liver tissue of mice obvious swelling and congestion of in APAP group at 4 ⁃hour and typical lobular central necrosis in APAP group at 12 ⁃ hour;the degree of liver necrosis in APAP + TAK⁃242 groups at 4 ⁃ hour and 12⁃ hour was less than that in APAP group at the same time point. Compared with the normal control group , serum ALT level , liver index , TLR4 , HMGB1 , NF⁃κB protein content , MCP⁃1 , IL⁃1β , TNF⁃α , IL⁃6 gene levels and IL⁃6 content in liver tissue of APAP 4 ⁃ hour group increased ; serum ALT level , liver index , HMGB1 protein content and IL⁃6 content in liver tissue increased in APAP 12 ⁃ hour group. Compared with APAP 4 ⁃ hour group , serum ALT level , liver index , TLR4 , HMGB1 , NF⁃κB protein content , MCP⁃1 , IL⁃1β , TNF⁃α , IL⁃6 gene level and IL⁃6 content in liver tissue decreased in APAP + TAK⁃242 4 ⁃ hour group. Compared with APAP 12 ⁃hour group , the levels of TLR4 , HMGB1 protein and MCP⁃1 , IL⁃1β , TNF⁃α genes in APAP + TAK⁃242 12 ⁃ hour group decreased. Conclusion nhibition of TLR4 may inhibit TLR4/HMGB1 pathway to reduce the inflammatory response in the early stage of acetaminophen⁃induced acute liver injury in mice.

Objective:To investigate the prevalence and influencing factors of mild visual impairment in type 2 diabetic patients aged ≥50 years living in Funing County, Jiangsu Province.Methods:A population-based cross-sectional study was adopted.Cluster sampling was conducted among diabetic patients aged ≥50 years registered in the Chronic Disease Information Center of Funing County Center for Disease Prevention and Control from March 7th to April 20th, 2019.General information of selected patients was collected.Visual and ocular examinations on site were performed by ophthalmologists and technicians.The International Council of Ophthalmology standard for mild visual impairment, 0.3≤best corrected visual acuity<0.8 was adopted.The influencing factors of mild visual impairment were analyzed by logistic regression.This study protocol was approved by the Ethics Committee of Affiliated Hospital of Nantong University (No.2014-071).Results:Among the included 2 067 patients, 1 909 cases completed the investigation, with a response rate of 92.4%.There were 1 146 patients with mild visual impairment in at least one eye, and the prevalence of mild visual impairment was 60.00%.Among the eyes examined, 1 832 eyes were with mild visual impairment, accounting for 47.98%.Cataract (896/1 632), refractive error (515/1 632) and diabetic retinopathy (166/1 632) were the main causes of mild visual impairment in diabetic patients, accounting for 54.90%, 31.61% and 10.19%, respectively.Aging, female gender, low educational attainment, oral hypoglycemic drugs or subcutaneous insulin injection were risk factors for mild visual impairment in both eyes.Higher educational attainment, more sunshine exposure and exercise were protective factors for mild visual impairment in both eyes.Conclusions:The prevalence of mild visual impairment is relatively high in type 2 diabetic patients.Cataract surgery, correction of refractive error may help to improve mild visual impairment.Strengthening blood glucose control, more physical exercise and outdoor activities may slow the progression of mild visual impairment and prevent it from moderate and severe visual impairment.

Objective:To explore the genetic basis for a child with mental retardation.Methods:The child was subjected to chromosomal microarray analysis (CMA) and targeted capture next-generation sequencing for the exons of genes related to genetic and metabolic diseases. Candidate variants were verified by Sanger sequencing of the child and his parents.Results:CMA suggested that the child has a 47, XYY karyotype. Next-generation sequencing revealed that the child has harbored compound heterozygous variants of the AUH gene, including c. 677G>A (p.R226H) and c. 373C>T (p.R125W), which were respectively inherited from his parents. Based on the American college of Medical Genetics and Genomics (ACMG) standards and guidelines, the c. 677G>A (P.r226h) variant was predicted as variant of uncertain significance (PM2+ PP4+ PP3), whilst the c. 373C>T (P.R125W) variant was predicted as likely pathogenic (PM1+ PM2+ PP3+ PP4). Conclusion:The child had XYY syndrome in conjunct with 3-methylglutaenedioic aciduria type I due to biallelic pathogenic variants of the AUH gene.