Objective To detect the expression of scleroderma-related autoantibodies, such as anti-Scl-70, anli-centromere antibody ( ACA)and anti-RNA polymerase Ⅲ ( ARA) , and their relationship with clinical features in Chinese systemic sclerosis (SSc) patients. Methods One hundred and thirty-five Chinese SSc patients from the clinical database of the Scleroderma Trials and Research Group proposed by European League Against Rheumatism's Scheroderma Trial and Research Group( EUSTAR) were consecutively enrolled. The expression of ARA, anti-Scl-70 and ACA were detected through linear immunoblotting, double immunodiffusion and indirect irnmunofluorescence, respectively. The relevance between the existing of autoantibodies and clinical manifestations was analyzed statistically. Results Among the 135 Chinese SSc patients, the prevalence of anti-Scl-70, ACA, ARA were 49. 6% , 13.3 % and 8.9% respectively. Patients with anti-Scl-70 antibody had significantly shorter disease course [(71 ±59) month vs (90 ± 103) month, P = 0.041] , higher proportion of interstitial lung disease ( P = 0. 031) but lower of pulmonary arterial hypertension (P =0.042). Modified Rodnan's skin score (P=0.008) and prevalence of facial and cervical cutaneous sclerosis (P = 0. 002) , distal (to elbow/knee ) cutaneous sclerosis ( P = 0. 004 ) and digital pitting scarring/disappear of digital pad were all significantly higher in anti-Scl-70 positive group. Patients with AC A had longer disease course ( P = 0. 036) , lower IgM level ( P = 0. 045) and were less prevalent of interstitial lung disease ( P =0. 045). Patients with ARA had higher serum creatinine and urea nitrogen level ( P ＜ 0.001) although otherwise features had unremarkable differences. Conclusion Scleroderma-related autoantibodies have relevance with different clinical manifestation and detection of these autoantibodies may be helpful to the diagnosis of SSc, organ involvement evaluation and predicting outcomes. The clinical relevances of autoantibodies in Chinese SSc patients may differ from other areas or races.

Objective To examine the impact of case management on hospitalizations of the chronically and severely mentally ill patients in Zhongshan. Methods Patients with severe and chronic mental illness,aged ≥ 15 years and living in pilot area were divided into two groups naturally since the program of case management launched, 65 cases in the group of case management and 112 patients in the group of standard management. Hospitalizations of the two groups before and after case management were compared. Results Data were analysised with MIXED procedure. Length of stay in days per admission (LOS) of both groups decreased with time in years (F=11.02, P=0.001), and the decline in LOS of case management group was greater than that of standard management group (F=9.02, P=0.003). The average admissions of case management group was more than that of standard management group (F=4.98,P=0.03). There was no significant differences in average hospitalization incidents before and after case management in both groups(case management group 5.13%vs. 5.38%, standard management group 7.14%vs. 8.92%, P>0.05). Conclusions Case management was effective in reducing hospitalizations for a group of Chinese with chronic and severe mental illness, and may contribute to the balance on mental health resources between community and hospital.

Background Iodine deficiency is a major factor affecting thyroid auto-regulation,the quantity of iodine may greatly influence the synthesis of thyroid hormones (THs).It has long been believed that TH enters the cell through passive diffusion.Recent studies have suggested that several transporters could facilitate transportation of TH.The monocarboxylate transporter 8 (MCT8) was identified as a very active and specific TH transporter.The purpose of this study was to investigate whether iodine insufficient affected the expression of MCT8 in the thyroid gland.Methods Sixty BALB/c mice were randomly divided into two groups:control group was fed with standard feed (iodine concentration of 300 μg/kg); while low-iodine (LI) group received iodine-insufficient feed (iodine concentration of 20-40 μg/kg).After 3 months,10 mice of each group were sacrificed.The remaining 20 mice of each group were kept till 6 months.From the LI group,we randomly selected 15 mice and injected triiodothyronine (T3,100 μg/kg body weight per day) intraperitoneally for 24,48 or 72 hours (5 mice for each time-point).Then,all the mice were sacrificed.Mouse serum thyroxine (T4),T3,and thyroid-stimulating hormone (TSH) levels were determined by chemiluminescence immunoassay (CIA).The protein content or messenger RNA (mRNA) level of thyroid MCT8 was measured by Western blotting analysis or real time RT-PCR respectively.MCT8 subcellular location in thyroid tissues was probed with immunohistochemistry (IHC) assay.Results We found that mouse serum T3 and T4 levels decreased and TSH level increased by the end of the third month.Consistent with these findings,there was significant goiter and hypothyroidism in the LI group.Meanwhile,the MCT8 mRNA increased to 1.36-fold of the level in the control group at the 3rd month.At 6th month,the serum T4 level in LI mice remained at a lower level,and MCT8 mRNA expression continued rising to nearly 1.60-fold compared with the control group.The protein content was also about 3 times higher than that in the control group.IHC results also revealed MCT8 was of higher expression and localized in the cytoplasm of thyroid follicular cells.After providing exogenous T3 to iodine deficient mice,the serum T3 and T4 gradually increased,whereas MCT8 mRNA and protein both started to decrease and returned to the same level as the control group.Conclusion There is a compensatory increase in thyroid MCT8 expression to enhance its capability to transport TH from thyroid to the blood circulation in iodine deficient mice.

Background and Objectives: Induced pluripotent stem cells (iPSCs) are usually generated by reprogramming differentiated cells through the introduction of specific transcription factors, but this is a difficult and inefficient process.Valproic acid (VPA) is a histone deacetylase inhibitor that significantly improves the efficiency of iPSC generation.But its role and mechanism are still unclear. Methods: and Results: We transduced Bactrian camel fetal fibroblasts (BCFFs) with retroviruses carrying defined factors (OCT4, SOX2, KLF4, c-MYC and EGFP; OSKMG) in the presence of VPA. Cells were collected (Day 7) and analyzed using RNA-seq technology. Afterwards, different groups of cells and transcriptomics results were detected by PCR and qRT-PCR technology. The results showed that VPA promoted the expression of the endogenous gene c-Myc and inhibited cell proliferation; at the same time, it promoted the expression of VEGF and other genes related to angiogenesis. Conclusions When VPA is added to the culture medium, only the cells that have begun to reprogram can break the G2/M repression through the expression of the endogenous gene c-Myc, and use the nutrients and space in the culture dish to proliferate normally, which can achieve the purpose of directly improving the efficiency of reprogramming.Another new discovery for Bactrian camels, VPA significantly increased the expression of VEGFC and other genes, promoting the transformation of fibroblasts to endothelial cells (different from the mesenchymal-to-epithelial transition process of other species) to accelerate the early induction of Bactrian camels iPSc process. Overall, this study proved the new mechanism of VPA in enhancing the induction of pluripotency from the transcriptome level.

Background and Objectives: Induced pluripotent stem cells (iPSCs) are usually generated by reprogramming differentiated cells through the introduction of specific transcription factors, but this is a difficult and inefficient process.Valproic acid (VPA) is a histone deacetylase inhibitor that significantly improves the efficiency of iPSC generation.But its role and mechanism are still unclear. Methods: and Results: We transduced Bactrian camel fetal fibroblasts (BCFFs) with retroviruses carrying defined factors (OCT4, SOX2, KLF4, c-MYC and EGFP; OSKMG) in the presence of VPA. Cells were collected (Day 7) and analyzed using RNA-seq technology. Afterwards, different groups of cells and transcriptomics results were detected by PCR and qRT-PCR technology. The results showed that VPA promoted the expression of the endogenous gene c-Myc and inhibited cell proliferation; at the same time, it promoted the expression of VEGF and other genes related to angiogenesis. Conclusions When VPA is added to the culture medium, only the cells that have begun to reprogram can break the G2/M repression through the expression of the endogenous gene c-Myc, and use the nutrients and space in the culture dish to proliferate normally, which can achieve the purpose of directly improving the efficiency of reprogramming.Another new discovery for Bactrian camels, VPA significantly increased the expression of VEGFC and other genes, promoting the transformation of fibroblasts to endothelial cells (different from the mesenchymal-to-epithelial transition process of other species) to accelerate the early induction of Bactrian camels iPSc process. Overall, this study proved the new mechanism of VPA in enhancing the induction of pluripotency from the transcriptome level.

Objectives To explore the clinical significance of autoantibodiesin individuals who accept a routine physical examination.Methods From April to June 2012, the serum of 932 individualsincluding 649 males and 283 females, from department of routine physical examination center of Peking Union Medical College Hospitalwerecollected , it uesd IIF for ANA, line immunoassay ( LIA) for specific ANAs antibodies and ELISA for the other antibodies , includinganti-CCP antibodies , AMA-M2, ACL antibodies and anti-anti-β2GPⅠantibodies.Chi-square test was used for data measurement of positive rate of autoantibodies in men and women;Fisher′s exact test was used when the data not meet the conditions of Chi-square test.Individualswith high-risk of autoimmune disease according to the results ofautoantibodies ( Titersof autoantibodies≥2-fold cut-off and accompanied with other autoimmune diseases related laboratory abnormalities) were recalled to visit doctor.Results Of the 932 cases, the overall positive rate of ANA was 11.27%.The positive rate of ANA was19.79%inwomen, which was significantly higher than thatin men (7.09%)(χ2 =32.6, P<0.01); the overall positive rate of ANAswas 8.69%, and the positive rate of ANA was13.43%inwomen, whichwas significantly higher than that in men ( 6.63%) (χ2 =11.49, P <0.01);the overall positive rates of AMA-M2, anti-CCP antibodies , anti ACL antibodies and anti β2GPⅠantibodies were 3.22%, 0.54%, 2.90%and 0.21% respectively , which were 2.83%, 0.71%, 3.18%and 0.71 % in women , and 3.39%, 0.46%, 2.77% and 0.00% in men respectively , there was no statistically significant of positive rate between female and male 58 patients accounting for 6.22% in high-risk of autoimmune disease were recalled , of which 15 cases, accounting for 1.61% were diagnosed or highly suspected of autoimmune diseases (AID) of the 15 patients, 11 patients accounting for 1.18% were diagnosed AID, including 6 CTD, 3 pSS, 1 RA and 1 pSS/PBC;4 patients were highly suspected as AID , including 3 suspected CTD and 1 suspected pSS.The titers concentration of the positive antibodies in patients with confirmed or suspected AID ≥ 3 times cut-off.Conclusions The positive rate of autoantibodies in individuals of physical examination is high , but there is clinical significance when the titers concentration of positive autoantibodies ≥ 3 times of the cut-off.Positive-autoantibodies patients with high-risk of autoimmune disease need professional clinician to provide follow-up, consulting and health education for early discovery, timely diagnosis, and proper treatment of AID.

Objective:To study the role of a novel brain-derived peptide hypoxic-ischemic brain damage associated peptide (HIBDAP) in regulating pyroptosis of oxygen-glucose deprived (OGD) microglia.Methods:The sequence of HIBDAP was coupled with the sequence of cell-penetrating peptide transactivator of transcription (TAT) to form TAT-HIBDAP. Fluorescein isothiocyanate (FITC) labeled TAT-HIBDAP was added to microglia cells and observed under fluorescence microscope. Microglia cells were treated with different concentrations of TAT-HIBDAP (1, 5, 10, 20 μmol/L) and then OGD process. Cell pyroptosis was analyzed using lactate dehydrogenase (LDH) assay. The concentration of TAT-HIBDAP with the most prominent inhibiting effects was determined and selected for subsequent experiments. The pyroptosis morphology of the control group, the OGD group and the HIBDAP group (5 μmol/L TAT-HIBDAP+OGD) was observed using transmission electron microscope. The mRNA and protein expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes were examined using real-time quantitative PCR and Western Blot analysis.Results:Fluorescence microscope showed FITC-labeled TAT-HIBDAP could successfully enter microglia cells. Compared with the OGD group, low concentrations of TAT-HIBDAP (1, 5, 10 μmol/L) could significantly reduce microglia pyroptosis and the concentration of 5 μmol/L showed the most prominent effects. Compared with the control group, OGD group showed typical pyroptosis morphology and HIBDAP group showed significantly improved morphology. The mRNA and protein expression of NLRP3 inflammasomes in the OGD group were significantly higher than the control group and also the HIBDAP group.Conclusions:The novel brain-derived peptide HIBDAP may reduce the expression of NLRP3 inflammasomes and inhibit the pyroptosis of OGD microglia.

? Frailty is a multidimensional syndrome, reflecting the decline of the body's physiological reserve. The patients are often accompanied by a variety of diseases. The postoperative complications and mortality were significantly increased on frail patients due to improper anesthesia and perioperative management. Enhanced recovery after surgery optimizes perioperative treatment and achieves rapid recovery compared with traditional measures. However, perioperative management of patients with frailty is still in the exploratory stage. Common assessment methods for weakness are the debilitating phenotype and the debilitating index. This article focuses on the perioperative related problems of debilitated patients (low nutritional status, poor mental condition, complicated condition and many complications, multi-disciplinary collaboration, prone to fall and fall), and provide the basis for the frailty management of elderly medical workers.

Objective:To explore the will of the aged to participate in long-term care insurance in Qinhuangdao and its influencing factors under the background of aging of population.Methods:From April to May 2019, we selected 450 elderly people as subjects by stratified cluster random sampling in Qinhuangdao. All elderly people were investigated with the self-designed Long-term Care Insurance Need Questionnaire for the Aged. The individual characteristics, economic state and consciousness were analyzed with the methods of descriptive analysis, chi-square test and Logistic regression analysis.Results:A total of 445 valid questionnaires were collected. There were 60.7% (270/445) of aged with the wills to participate in long-term care insurance and 57.8% (156/270) of them hope the insurance mostly in cash or nursing service. Single factor analysis showed that there were statistical differences in the wills to participate in long-term care insurance among the aged with different ages, education levels, with or without a spouse, living situation, number of children, number of sons, primary caregivers, conscious health status, number of chronic diseases, number of hospitalizations in the past year, main source of income, monthly income, type of medical security, preference for care places (χ 2=50.228, 19.662, 26.504, 36.934, 16.456, 23.963, 44.482, 27.684, 24.783, 29.278, 22.313, 14.836, 10.446, 9.087; P<0.05) . Logistic regression analysis showed that the influencing factors of the will of the aged to participate in long-term care insurance included the ages, spouses and caregivers with statistical differences ( P<0.05) . Conclusions:Elderly people in Qinhuangdao are not willing to participate in long-term care insurance, and the elderly who are low age, have no spouse and have no caregivers are more willing to participate in long-term care insurance.

Objective To analyze the heterogeneities of hepatitis B virus ( HBV ) reverse transcriptase domain (RT) gene mutations related to nucleos (t)ide analogues (NAs) resistance.Methods Blood samples from 2765 chronic hepatitis B patients with virological breakthrough or poor drug response treated in Ningbo No .2 Hospital and Ningbo Fourth Hospital from April 2011 to March 2018 were collected . According to the medication status , it was divided into LAM monotherapy group ( n =603 ) , LdT monotherapy group (n=147), ADV monotherapy group (n=68), ETV monotherapy group (n=10) and the sequential or combined drug resistance of NAs group (n=365).The resistance mutation sites and drug resistance patterns (pathways) of each group were analyzed .The SPSS 19.0 software was used to analyze the data.Results Among 2765 serum samples, the NAs-related HBV-RT resistance mutations were detected in 1193 cases with an overall mutation rate of 43.15％.The mutation rate of LAM monoclonal resistance group was 62.62％ (603/963) with 19 mutation types, the most common single point mutation was rtM204I/V (40.30％, 243/603).The mutation rate of LdT monoclonal resistance group was 45.51％(147/323), and there were 3 mutation types, with the single point mutation rtM204I/V being the most common (59.86％, 88/147).The mutation rate of the ADV monoclonal resistance group was 17.80％(68/382), mainly rtA181T single point mutation (64.71％, 44/68).The mutation rate of the ETV monoclonal resistance group was 4.06％(10/246), and the single point mutation of rtT184A/G/S/I/L/F was the most common one (80.00％, 8/10).The mutation rate of the sequential or combination therapy group was 41.91％ (365/871), among which the mutation rate of the LAM/LdT poor response or the resistance with the sequential ADV group was 63.39％(142/224), and the most single mutation point was rtA181V/T ( 35.21％, 50/142 );the mutation rate of LAM/LdT poor response or drug-resistant with combined ADV group was 42.19％ (54/128), and the most common mutation point was rtA181V/T (46.30％, 25/54);the mutation rate of LAM/LdT with poor response or resistance after sequential ETV 1.0 mg was 44.66％(117/262), and the most common mutation point was rtL180M+M204I/V+S202G/I (31.62％, 37/117);the LAM/LdT poor response or the drug-resistant ETV combined with ADV group had a mutation rate of 7.14％(5/70), all of which were multi-site mutations;the mutation rate of poor response to ADV or resistant with sequential ETV 0.5 mg group was 28.14％(47/167), all of which were multi-site mutations.Secondary ( compensation ) sites such as rtV173L, rtL180M, and rtV214A, and single-point mutations such as rtV207I/L/G, rtS213Tand rtN238T, which were not fully defined , were detected.The resistance patterns ( pathways ) of NAs monotherapy were relatively simple , and the resistance patterns ( pathways ) of NAs experienced patients ( sequential or combined treatment group ) were complex and diverse, and multiple resistance patterns (pathways) existed, along with NAs increasing in species.Non-first-line NAs-related resistance patterns ( pathways ) showed an overall downward trend sand ETV-related drug-resistant mutation showed an overall upward trend .Conclusion The NAs-related HBV resistance mutation sites ( patterns ) are complex and diverse , especially multi-site mutations , refractory drug resistance mutations, multidrug resistance mutations and cross-resistance mutations.Therefore, the optimization of antiviral treatment strategies and drug resistance management concepts need to be continuously updated .