[The analysis to data from Chinese Rheumatism Data Center external quality assurance program for autoantibodies in 2021].

To evaluate the data obtained from the external quality assurance program initiated by Chinese Rheumatism Data Center (CRDC-QAP) for autoantibodies detection in 2021, so as to assess the consensus and differences in cross-laboratory testing to autoantibodies in China. This is a retrospective study. After collecting data from the first half year (from May 15th to July 10th) and the second half year (from August 15th to November 19th) of CRDC-QAP program for autoantibody detection in 2021, it firstly analyzed the qualitative consensus of the cross-laboratory results. Secondly, it compared the positivity grade of numeric results according to the Sample to cut-off ratio (S/CO ratio) calculation. Finally, the mean and coefficient variation (CV) of numeric results from three major manufacturers were calculated. A total of 303 and 332 clinical labs voluntarily participated in the first half year and the second half year of CRDC-QAP program for autoantibody detection in 2021, respectively. Except for anti-ß2 glycoprotein type I (aß2-GPI) IgM, the cross-laboratory consensus of qualitative results for the other autoantibodies is greater than 96%. As for anti-cyclic citrullinated peptide antibody (anti-CCP) and anti mitochondrial antibody-M2 (AMA-M2), the numeric results from more than 90% laboratories showed the same positivity grade. More than 50% of laboratories used chemiluminescence immunoassay (CLIA) for quantitative evaluation of autoantibody. The CV of numeric results from different manufacturers showed certain differences(P<0.01) with the range from 0 to 238%. Although high consensus can be observed in term of qualitative result for autoantibody detection in cross-laboratory, there are still certain differences in numeric results in term of positivity grade and manufacturer-based CV.

[Effect of fragmented sleep on postoperative cognitive function and central neuroinflammation].

Objective: To investigate the effect of sleep fragmentation on perioperative neurocognitive disorders (PND) and central neuroinflammation by simulating sleep patterns of postoperative patients with sleep fragmentation in aged mice. Methods: Thirty-two elderly ICR mice were randomly divided into four groups (n=8): normal group (C), surgery group (S), fragmented sleep group (F), and surgery+fragmented sleep group (D). Fragmented sleep was conducted after internal fixation of tibia fractures, cognitive function was evaluated by novel object recognition (NOR) and fear conditioning (FC) test, and changes in expression of inflammatory cytokines in hippocampus were detected by ELISA. Results: NOR test: the recognition index (RI) of mice in group C, group S, group F and group D was 0.69±0.07, 0.48±0.07, 0.54±0.10 and 0.50±0.12, respectively. The RI of mice in group S, group F and group D was significantly lower than that in group C (t=4.885, 3.521 and 4.433, all P<0.01). There was no significant difference in RI between group S and group D (t=0.967 1, P>0.05). Contextual FC test: the freezing time of mice in group C, group S, group F and group D was(21.34±6.48), (13.83±4.26), (11.50±6.25) and (6.17±4.77) s, respectively. The freezing time of mice in group S, group F and group D was significantly lower than that in group C (t=2.722, 3.566, 5.496, P<0.05 or P<0.01). The freezing time of mice in group D was significantly lower than that in group S (t=2.774, P<0.05). Cue FC test: the freezing time of mice in group C, group S, group F and group D was (74.36±17.09), (43.91±9.71), (46.34±13.43) and (24.90±14.21) s, respectively. The freezing time of mice in group S, group F and group D was significantly lower than that in group C (t=4.393, 4.043 and 7.136, all P<0.01). The freezing time of mice in group D was significantly lower than that in group S (t=2.743, P<0.05). The levels of TNF-α, IL-6 and IL-1ß in hippocampus of mice in group S, F and D were significantly higher than those in group C, while the levels of TNF-α and IL-6 in hippocampus of mice in group D were significantly higher than those in group S, with statistically significant differences (P<0.05 or P<0.01). Conclusion: Postoperative fragmented sleep aggravates postoperative cognitive impairment and increases the hippocampal neuroinflammation in aged mice.

[Modified memory sub-test of Syndrom Kurz test in middle-aged and elderly Chinese].

Objective: To investigate the applicability of the modified memory sub-test of syndrom kurz test (SKT-M) in middle-aged and elderly Chinese. Methods: Between March 1, 2017, and October 31, 2017, at HwaMei Hospital, 132 patients receiving elective great saphenous vein high ligation and stripping operation and 96 their accompanying dependents, 55-75 years old, were randomly divided into the SKT-M group (n=121) and auditory verbal learning test -huashan version (AVLT-H) group (n=107) using random numeral method. The two groups underwent two corresponding neuropsychological tests respectively on the day before surgery and the second day after surgery. Results: There was no significant difference in the baseline characteristics and all the neuropsychological indices at the two time points between patients and dependents (P>0.05). As a consequence, the data of the patients and dependents were integrated to compare the applicability of SKT-M and AVLT-H. The "low-score" ratio of SKT-M immediate recall (2.4%) was lower than that of AVLT-H test (12.1%) (χ(2)=8.138, P<0.01). Besides, the "low-score" ratio of SKT-M delayed recall (5.7%) was also lower than that of AVLT-H test (20.5%) (χ(2)=11.167, P<0.01). The influence factors of SKT-M were less than that of AVLT-H test. However, the learning effect of SKT-M immediate recall was more significant, for its first testing sore (23.1±5.4) was significantly higher than the second one (21.9±5.1) (t=-3.971, P<0.001). Conclusion: The SKT-M has better applicability to 55-75 years old Chinese than AVLT-H test, but its learning effect should be noted.

[EMA/CO regimen for chemotherapy 24 patients with ultra high-risk gestational trophoblastic neoplasia].

Objective: To evaluate etoposide, methotrexate and dactinomycin (EMA) /cyclophosphamide and vincristine (CO) regimen for treatment of ultra high-risk gestational trophoblastic neoplasia (GTN) . Methods: A total of twenty-four ultra high-risk patients who had International Federation of Gynecology and Obstetrics (FIGO) prognostic scores greater or equal to 12 with liver, brain, or extensive metastases did poorly when treated with primary chemotherapy admitted in Women's Hospital, School of Medicine, Zhejiang University from January 2001 to December 2015. All of the patients were treated by EMA/CO regimen and followed up to death or December 2017. The clinical data of patients were analyzed retrospectively and the efficacy and toxicity of EMA/CO were evaluated. Results: All of the cases with ultra high-risk GTN had FIGO prognostic scores ≥12 (ranged 12-18, median 13.0) . Twenty patients (83%, 20/24) received EMA/CO regimen as primary treatment and 4 patients (17%, 4/24) had a history of failed chemotherapy. Seven patients (29%, 7/24) had metastasis of liver or brain and 17 patients (71%, 20/24) had no metastasis of liver and brain. Twenty-four patients received totally 167 courses of EMA/CO regimen (average 7.0 courses) . Sixteen patients achieved complete remission and 8 patients showed drug-resistant. The complete remission rate was 67% (16/24) and the resistance rate was 33% (8/24) . Of the 16 patients who got complete remission, 6 cases were treated with EMA/CO regimen alone, and 10 cases were treated by chemotherapy combined with surgery. For the 8 patients who showed drug-resistant to EMA/CO, 5 cases of them received EMA/etoposide and cisplatin (EP) regimen and 3 cases got remission, 1 case received methotrexate, dactinomycin and cyclophosphamide (MAC) regimen and got remission, 2 cases gave up treatment because of economic factors. The side effects of EMA/CO mainly included Ⅲ-Ⅳ degree neutropenia, anemia and alopecia. The incidence of Ⅲ-Ⅳ degree neutropenia during the treatment of EMA/CO was 21.6% (36/167) , the incidence of anemia was 96.4% (161/167) , and the incidence of alopecia was 60.5% (101/167) . In these 24 ultra high-risk GTN patients, 4 patients died during follow-up. In the 20 patients who got complete remission, no recurrence or secondary tumor by chemotherapy were occurred. Conclusion: EMA/CO is an effective regimen with manageable toxicity for patients with ultra high-risk GTN.

[Curative effects and influenced factors of primary chemotherapy with single-agent methotrexate on low-risk gestational trophoblastic neoplasia].

Objective: To evaluate the efficacy of primary chemotherapy with single-agent methotrexate (MTX) for low-risk gestational trophoblastic neoplasia and to analysis the influenced factors. Methods: We retrospectively reviewed 259 cases with low-risk gestational trophoblastic neoplasia whose primary chemotherapies were MTX 0.4 mg·kg(-1) (maximum 25 mg) daily for 5 days every other week. Patients' data between January 2001 and June 2015 was collected and the relationships of different factors to outcomes of chemotherapy were also evaluated. Results: 183 of the 259 patients (70.66%, 183/259) achieved complete primary remission and all patients achieved complete remission after salvage chemotherapy. Univariate analysis showed that FIGO score, serum level of HCG before treatment and interval months from previous pregnancy were significantly associated with outcome of chemotherapy (P=0.001, 0.018, 0.014 respectively). Logistic regression analysis showed that the FIGO score (OR=4.094) and antecedent pregnancy (OR=0.268) were two independent factors predictive for the outcome of chemotherapy. Conclusions: Primary chemotherapy with single-agent MTX may still be one of the options for patients with low risk GTN. The FIGO score and antecedent pregnancy are two independent risk factors of outcome of single-agent MTX chemotherapy.

MTA1 promotes cell proliferation via DNA damage repair in epithelial ovarian cancer.

We examined whether metastasis-associated gene 1 (MTA1) promotes cell proliferation via DNA damage repair in ovarian cancer. MTA1 was successfully down-regulated using small interfering RNA in the epithelial ovarian cancer cell lines SKOV-3 and OVCAR-3. Cell growth was evaluated through MTT and colony formation assays. Fluorescence-activated cell sorting analysis was used to evaluate the distribution of cells in the cell cycle, and cytotoxicity assays were performed to study cell sensitivity to cisplatin. A neutral comet assay was used to measure levels of ionizing radiation-induced DNA damage in SKOV-3 cells, and Western blot analyses were carried out to examine the expression of key proteins involved in DNA damage repair pathways. MTA1 knockdown markedly inhibited cell growth and led to S phase cell cycle arrest. In addition, MTA1 depletion conferred sensitivity of ovarian cancer cells to cisplatin. Moreover, MTA1 depletion increased the level of ionizing radiation-induced DNA damage and caused irreparable damage, which was illustrated by a remarkable increase and persistent existence of a comet tail as well as protein expression levels of γH2AX, pRPA, and pChk1, all of which play critical roles in DNA repair. Thus, MTA1 promotes the proliferation of epithelial ovarian cancer cells by enhancing DNA repair.

Potential role of high-mobility group box 1 protein in the pathogenesis of influenza H5N1 virus infection.

During influenza A virus (IAV) (H5N1) infection, the levels of inflammatory cytokines are markedly elevated in the lungs of infected hosts. One of them, high-mobility group box 1 protein (HMGB1) functions in regulation of cellular transcription and activation of proinflammatory responses, but little is known about its role in viral infection. In this study, we attempted to address this question. Using an IAV (H5N1) - mouse model, lung tissues were analyzed for virus titer, expression of HMGB1 and other inflammatory cytokines and histopathological changes. Moreover, the effect of administration of HMGB1-specific antibody to the infected mice on these parameters was investigated. The results showed that the HMGB1 expression was induced on days 3-7 post infection (p.i.) and primarily localized to epithelial cells of alveoli and bronchioles. The HMGB1-specific antibody reduced the levels of inflammatory cytokines and chemokines and the survival rate, but did not influence the virus titer. Summing up, these data suggest that HMGB1 contributes to the pathogenesis of IAV (H5N1) infection in mice by inducing extensive inflammatory responses and severe pneumonia.

[DNA double-strand breaks repair capacity and risk of differentiated thyroid cancer: a case-control study].

Objective: To study the influencing factors of DNA double-strand breaks (DSB) repair capacity and relationship with differentiated thyroid cancer (DTC). Methods: A total of 140 patients with thyroid diseases admitted to the Henan Cancer Hospital from January 2020 to March 2020 were retrospectively analyzed, including 26 males and 114 females, aged from 18 to 78 years old. According to the pathological results, the patients were divided into DTC group (90 cases) and control group or benign thyroid nodules (BTN) group (50 cases). The DSB repair ability of peripheral blood T lymphocytes was measured by flow cytometry. The data of two groups were compared by Wilcoxon rank sum test to evaluate the relationship between DSB repair ability and the risk of DTC. According to the median repair ability of DSB in BTN group, the repair ability of DSB was divided into high and low categories, and the factors influencing the repair ability of DSB were analyzed by Logistic regression method. SPSS 22.0 software was used to analyze the data. Results: The DSB repair capacity was 27.87% in DTC group and 36.75% in BTN group, with significant difference (Z=-3.999,P<0.05). Logistic regression analysis suggested that patients with thyroid cancer had lower DSB repair capacity than patients without cancer (OR=2.245; 95%CI: 1.067-4.725; P=0.033), and patients with a history of radiation exposure had a reduced DSB repair capacity (OR=2.698; 95%CI: 1.271-5.725, P=0.010). Conclusion: The risk of DTC increases in patients with low DSB repair capacity. Radiation exposure is a risk factor for the reduction of DSB repair capacity.