ObjectiveTo investigate the effects of the combination of components from Tripterygii Radix et Rhizoma and Chuanxiong Rhizoma on rheumatoid arthritis fibroblast-like synoviocytes （RA-FLSs） and the underlying mechanism. MethodsRA-FLSs were grouped as follows： blank control， positive control （methotrexate）， Tripterygii Radix et Rhizoma components， Chuanxiong Rhizoma components， and components from Tripterygii Radix et Rhizoma+Chuanxiong Rhizoma. The cell-counting kit-8 （CCK-8） assay was employed to the cell proliferation， invasion， and apoptosis. The levels of tumor necrosis factor （TNF）-α， interleukin （IL）-6， reactive oxygen species （ROS）， and malondiadehyde （MDA） in cells were measured. Western blot was employed to determine the protein levels of nuclear factor erythroid 2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， nuclear factor-kappa B （NF-κB） p65， phosphorylated inhibitory subunit of NF-κBα （p-IκBα）， cysteinyl aspartate-specific protease-3 （Caspase-3）， and B-cell lymphoma 2 （Bcl-2）. Real-time PCR was employed to determine the mRNA levels of Nrf2， HO-1， and NF-κB p65. ResultsThe cells in the groups of positive control， Tripterygii Radix et Rhizoma components， Chuanxiong Rhizoma components， and components from Tripterygii Radix et Rhizoma+Chuanxiong Rhizoma were treated with 2.50 mg·L^-1 methotrexate， 0.20 mg·L^-1 triptolide + 0.20 mg·L^-1 celastrol， 5.00 mg·L^-1 ferulic acid + 20.00 mg·L^-1 ligustrazine， 0.20 mg·L^-1 triptolide + 0.20 mg·L^-1 celastrol + 5.00 mg·L^-1 ferulic acid + 20.00 mg·L^-1 ligustrazine， respectively. Compared with the blank control group， drug administration reduced the proliferation and invasion and increased the apoptosis of cells （P<0.01）， lowered the levels of TNF-α， IL-6， ROS， and MDA （P<0.01）， up-regulated the mRNA and protein levels of Caspase-3， Nrf2， and HO-1 （P<0.01）， and down-regulated the mRNA and protein levels of Bcl-2， NF-κB p65， and p-IκBα （P<0.01）. Compared with the Tripterygii Radix et Rhizoma components group， the combination of components from Tripterygii Radix et Rhizoma+Chuanxiong Rhizoma inhibited the proliferation and invasion （P<0.05） and promoted the apoptosis of RA-FLSs， up-regulated the mRNA levels of Nrf2 and HO-1 and protein levels of Nrf2 and Caspase-3 （P<0.05）， and down-regulated the protein levels of NF-κB p65 and p-IκBα （P<0.05）. ConclusionThe combination of components from Chuanxiong Rhizoma and Tripterygii Radix et Rhizoma can inhibit the proliferation and invasion and promote the apoptosis of RA-FLSs and alleviate oxidative stress and inflammation by inhibiting the NF-κB signaling pathway， activating the Nrf2/HO-1 pathway， and regulating the expression of Bcl-2/Caspase-3.

Objective : To explore the effect of Wilms′ tumor 1-associated protein(WTAP) on tissue collagen deposition in pulmonary fibrosis caused by bleomycin. Methods : 60 mice were randomly divided into four groups: control group(Control group), Bleomycin-induced pulmonary fibrosis group(BLM group), pulmonary fibrosis lentivirus empty vector control group(BLM+LV-NC group), pulmonary fibrosis WTAP lentivirus group virus group(BLM+LV-WTAP group). Experimental pulmonary fibrosis mouse model was established by subcutaneous injection of bleomycin(35 mg/kg) into the abdomen, twice a week for a total of 8 times. After modeling, Western Blot was used to detect the protein expression of fibrosis-related markers α-smooth muscle actin(α-SMA), type I collagen(Collagen Ⅰ), fibronectin(Fibronectin), and WTAP protein. Masson staining and Sirius Red staining were used to detect collagen deposition. RT-qPCR was used to detect WTAP mRNA expression, WTAP lentivirus infection effect, and Collagen Ⅰ mRNA expression. Results: Compared with the Control group, the expression of pulmonary fibrosis markers α-SMA(P<0.001), Collagen Ⅰ(P<0.001), and Fibronectin(P<0.01) protein in the BLM group all increased. Masson staining(P<0.001) and Sirius Red staining(P<0.001) confirmed that significant collagen deposition occurred in the lung tissue of the BLM group. In addition, the expression of WTAP protein in the lung tissue of the BLM group increased(P<0.01). Compared with the Control group, the expression of WTAP mRNA in the BLM group increased(P<0.001). Compared with the BLM+LV-NC group, the expression of WTAP mRNA in the tissues of the BLM+LV-WTAP group decreased(P<0.001), proving that virus infection is effective. After infection with WTAP lentivirus, collagen fiber deposition decreased(P<0.001), Collagen Ⅰ mRNA(P<0.001) level decreased, and protein(P<0.001) expression decreased in the BLM+LV-WTAP group. Conclusion Knocking down of WTAP can reduce collagen deposition in bleomycin-induced pulmonary fibrosis tissue in mice and improve experimental pulmonary fibrosis.

Objective: To investigate the effect of sirtuin 2(SIRT2) on the proliferation and migration of cardiac fibroblasts(CFs)in C57BL/6 mice under angiotensin II(Ang Ⅱ) stimulation. Methods : The hearts were taken from 1 to 2 days C57BL/6 milk mice. After cutting and digesting, CFs were extracted by different adhesion centrifugation. After CFs attachment, the cells were cultured under control medium and Ang Ⅱ(100 nmol/L) medium and treated using OE-SIRT2 plasmid to overexpression the SIRT2 gene. RT-qPCR was used to detect mRNA expression of SIRT2 proliferating cell nuclear antigen(PCNA), periostin(POSTN)and type Ⅰ collagen procollagen A1(Col1A1), Western blot assay was used to measure the protein expression levels of SIRT2, PCNA, POSTN and Col1A1, CCK-8 assay and EdU assay were used to evaluate CFs proliferation rate, Transwell experiment was used to assess CFs migration activity. Results: Compared with control group, Ang Ⅱ stimulation led to down-regulation of SIRT2 expression in CFs, increased collagen expression, and promoted CFs proliferation and migration. The expression of SIRT2 was up regulated in CFs treated with OE-SIRT2 plasmid under Ang Ⅱ stimulation, Col1A1, POSTN and PCNA expression was down regulated, and CFs proliferation and migration ability decreased. Conclusion Overexpression of SIRT2 can inhibit the proliferation and migration of CFs under Ang Ⅱ stimulation, indicating that SIRT2 may be a key regulatory point in the onset and progression of cardiac fibrosis.

Non-neoplastic lesions were added in the 5th edition WHO classification of adrenal cortical tumor based on the recent update, including adrenal rests, adrenal cysts, congenital adrenal hyperplasia and adrenocortical nodular disease. A range of tumor concepts were updated or refined based on tumor cell origin, histopathology, oncology and molecular biology. The most significant nomenclature change in the field of adrenal cortical pathology involves the refined classification of adrenal cortical nodular disease, which now includes sporadic nodular adrenocortical disease, bilateral micronodular adrenal cortical disease, and bilateral macronodular adrenal cortical disease. The 5th edition WHO classification endorses the nomenclature of the HISTALDO classification to help the classification of aldosterone producing adrenal cortical lesions, which uses CYP11B2 immunohistochemistry to identify functional sites of aldosterone production. The 5th edition WHO classification does not change the Weiss and Lin-Weiss-Bisceglia histopathologic criteria for diagnosing adrenal cortical carcinomas, and underscores the diagnostic and prognostic impact of angioinvasion in these tumors. Reticulin algorithm and Helsinki scoring system were added to assist the differential diagnosis of adrenal cortical neoplasms in adults. Pediatric adrenal cortical neoplasms are assessed using the Wieneke system. The 5th edition WHO classification places an emphasis on an accurate assessment of tumor proliferation rate using both the mitotic count (mitoses per 10 mm 2) and Ki-67 labeling index which play an essential role in the dynamic risk stratification of affected patients. This review highlights advances in knowledge of histological features, ancillary studies, and associated genetic findings that increase the understanding of the adrenal cortex pathologies in the 5th edition WHO classification.

This study was designed to compare diagnostic categories of thyroid fine needle aspiration cytology (FNAC) and incidence of thyroid tumors in the multi-institutional Asian series with a special focus on diagnostic category IV (suspicious for a follicular neoplasm) and follicular thyroid carcinomas (FTCs). Methods: Distribution of FNAC categories, incidence of thyroid tumors in resection specimens and cytologic diagnoses of surgically confirmed follicular adenomas (FAs) and FTCs were collected from 10 institutes from five Asian countries and were compared among countries and between FAs and FTCs. Results: The frequency of category IV diagnoses (3.0%) in preoperative FNAC were significantly lower compared to those in Western countries (10.1%). When comparing diagnostic categories among Asian countries, category IV was more frequent in Japan (4.6%) and India (7.9%) than in Taiwan (1.4%), Korea (1.4%), and China (3.6%). Similarly, incidence of FAs and FTCs in surgical resection specimens was significantly higher in Japan (10.9%) and India (10.1%) than in Taiwan (5.5%), Korea (3.0%), and China (2.5%). FTCs were more commonly diagnosed as category IV in Japan (77.5%) than in Korea (33.3%) and China (35.0%). Nuclear pleomorphism, nuclear crowding, microfollicular pattern, and dyshesive cell pattern were more common in FTCs compared with FAs. Conclusions: Our study highlighted the difference in FNAC diagnostic categories of FTCs among Asian countries, which is likely related to different reporting systems and thyroid cancer incidence. Cytologic features such as nuclear pleomorphism, nuclear crowding, microfollicular pattern, and dyshesive cell pattern were found to be useful in diagnosing FTCs more effectively.

Purpose To elucidate the clinicopathological characteristics of primary malignant giant cell tumor of bone(PMGCTB)with mainly osteosarcoma-like morphology.Meth-ods Clinicopathologic features of 7 cases of PMGCTB were ret-rospectively analyzed.Results Among 7 patients with PMGCTB,there were 4 females and 3 males,aged between 9 and 66 years(mean age 39.5 years,median age 35 years).The distal femur emerged as the most frequent site to be involved(3/6).The main clinical manifestations included pain and swelling at the original site of the tumor.Radiological findings indicated osteolytic lesions,often combined with sclerotic areas;most ca-ses showed cortical bone destruction and soft tissue masses(5/7).Histologically,the majority of tumors exhibited typical mor-phological features of osteosarcoma with a few or without osteo-clast-like multinucleated giant cells.Positive immunoreaction with H3F3A G34W was confirmed in 6 cases and with H3F3A G34V in 1 case.SATB2 and p63 were positive in all cases,p53 was proved to be wild type,the Ki67 proliferation index ranged approximately from 10％to 50％.H3F3A p.G34W mutation was detected in 6 cases and only 1 case harboring H3F3A p.G34V mutation.Conclusion PMGCTB is exceedingly rare and difficult for accurate diagnosis,especially for those with atypical morphological features.A comprehensive analysis involving ra-diological,immunophenotypic,and molecular detection is neces-sary to rule out other high-grade sarcomas.

Objective:To explore the effects of the scaffolding-based flipped classroom approach in the teaching of Infectious Disease Nursing. Methods:We assigned 152 students of nursing and midwifery majors of grade 2018 (experimental group) to be taught using the scaffolding-based flipped classroom approach and 182 students of grade 2017 (control group) to be taught using the traditional lecture method. Teaching effects were evaluated through students' exam performance and a questionnaire survey. Numerical data were analyzed using the χ2 test and t test with the use of SPSS 18.0, and text data were processed using NVivo 11 for thematic analysis. Results:The experimental group and control group showed significant differences in the interim exam score (83.19±7.96 vs. 79.62±3.14, P<0.001) and final exam score (78.47±6.92 vs. 73.16±8.24, P<0.001). The students of grade 2018 had a high level of participation in online learning. The questionnaire results showed that the scaffolding-based flipped classroom was well recognized in terms of students' overall perception, perceived course quality, perceived value of learning, and satisfaction and the open-ended question, with low scores for learner complaints and loyalty. Conclusions:The scaffolding-based flipped classroom is feasible in the teaching of Infectious Disease Nursing, which can improve students' academic performance and overall competence.

Objective:To explore the prognostic factors associated with clear cell adenocarcinoma (CCAC) of the uterine cervix based on data in the Surveillance, Epidemiology and End Results (SEER) database.Methods:Clinical data were collected from 431 patients with confirmed CCAC in the SEER database from 1976 to 2017. Survival analysis was performed using the Kaplan-Meier method with log-rank test for comparison between subgroups. Cox proportional hazards model was used to analyze the influencing factors of overall survival (OS).Results:The median age [ M ( Q1, Q3)] of 431 patients was 54 years old (40 years old, 71 years old); there were 333 cases (77.3%) of whit. The median OS time of 431 patients was 93 months (95% CI: 47-148 months), and the 1-, 2-, and 5-year OS rates were 80.1%, 65.8% and 54.2%, respectively. The median OS time was not reached in patients with American Joint Committee on Cancer (AJCC) stage Ⅰ, 83 months (95% CI: 21-144 months) for stage Ⅱ, 32 months (95% CI: 16-47 months) for stage Ⅲ, and 9 months (95% CI: 5-13 months) for stage Ⅳ ( P < 0.001). Median OS time was not reached in patients with SEER stage of localized lesions, 46 months (95% CI: 8-83 months) for regional lesions stage, and 9 months (95% CI: 5-12 months) for distant metastases stage ( P < 0.001). Of the patients with clear AJCC staging and some with unspecified AJCC staging, 118 received surgical treatment alone and 119 received postoperative radiotherapy, the median OS time of the two groups was 443 months (95% CI: 162-723 months) and 102 months (95% CI: 75-129 months), and the difference in OS between the two groups was statistically significant ( P < 0.001). Among the patients with AJCC stage Ⅰ, the 5-year OS rates in surgery-only group and postoperative radiotherapy group were 82.5% and 78.5%, the stage Ⅱ were 80.0% and 52.3%, and the stage Ⅲ were 27.8% and 63.3%, respectively; the differences in OS between different stages were not statistically significant (all P>0.05). Among the patients with SEER localized lesions stage, the 5-year OS rates in surgery-only group and postoperative radiotherapy group were 88.9% and 73.1%, and the difference was statistically significant ( P = 0.012); the regional lesions stage were 45.5% and 60.0%, and the difference was not statistically significant ( P = 0.568). The results of multivariate Cox regression analysis showed that AJCC staging (stage Ⅰ vs. stage Ⅳ, HR = 0.281, 95% CI: 0.178-0.543, P < 0.001; stage Ⅱ vs. stage Ⅳ, HR = 0.347, 95% CI: 0.113-0.439, P < 0.001; stage Ⅲ vs. stage Ⅳ, HR = 0.399, 95% CI: 0.030-0.145, P < 0.001), SEER staging (localized lesions stage vs. distant metastases stage, HR = 0.104, 95% CI: 0.059-0.182, P < 0.001; regional lesions stage vs. distant metastases stage, HR = 0.301, 95% CI: 0.195-0.463, P < 0.001) and whether or not receive surgery (yes vs. no, HR = 0.359, 95% CI: 0.241-0.535, P < 0.001) were independent influencing factors of OS in CCAC patients. Conclusions:AJCC staging, SEER staging and surgery are independent influence factors for OS in patients with CCAC, and postoperative radiotherapy may not provide more survival benefit.

ObjectiveTo validate the efficacy of Yunpi Huatan Tongqiao prescription （YHTP） in down-regulating glycolysis to modulate microglia phenotype and improve inflammation and cognitive memory deficits in obstructive sleep apnea （OSA） mice. MethodForty-eight male Balb/C mice were randomly divided into a normal group， a model group， a montelukast sodium group （30 mg·kg^-1）， and low， medium， and high dose groups of YHTP （8.28， 16.56， and 33.12 g·kg^-1）， with 8 mice in each group. All groups， except the normal group， received intraperitoneal injections of lipopolysaccharide （LPS） and underwent chronic intermittent hypoxia （CIH） modeling for 4 weeks. Subsequently， the mice were treated with medications for 4 weeks and then sampled. Animal behavioral tests assessed memory impairment due to hypoxia. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to measure mRNA expression levels of M1-associated inflammatory factors interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and markers such as T lymphocyte activation antigen （CD86） and inducible nitric oxide synthase （iNOS）， as well as M2-associated inflammatory factors interleukin-10 （IL-10）， transforming growth factor-β （TGF-β）， and the marker mannose receptor （CD206） in hippocampal tissue. Western blot was employed to detect differences in the expression of M1 and M2 microglia phenotypic markers （CD86， CD206） and glycolysis-related proteins glucose transporter type 1 （GLUT1）， hexokinase 2 （HK2）， phosphofructokinase （PFKM）， pyruvate kinase 2 （PKM2）， and monocarboxylic acid transporter 1 （MCT1）. ResultBehavioral tests showed that compared to the results in the normal group， the Y-maze autonomous alternation rate was significantly reduced in the model group （P<0.01）. The latency time for the target hole in the Barnes' maze during the training period （days 2， 3， 4） and testing period （days 5， 12） was significantly increased （P<0.05， P<0.01）. M1 glial cell markers CD86 and iNOS， as well as inflammatory factors IL-1β and TNF-α mRNA， were significantly elevated （P<0.01）. In contrast， the mRNA expression of M2 glial cell markers IL-10， CD206， and TGF-β was significantly reduced （P<0.01）. The protein expression of glycolytic proteins HK2， PFKM， PKM2， MCT1， and the M1 marker CD86 was significantly increased （P<0.05， P<0.01）， while M2 marker CD206 protein expression was significantly decreased （P<0.01）. Compared to the results in the model group， the Y-maze autonomous alternation rate was significantly increased in the medium and high dose groups of YHTP （P<0.05， P<0.01）. The latency time for the target hole during the training （day 4） and testing periods （days 5， 12） was significantly reduced （P<0.01）. Real-time PCR results indicated that mRNA expression levels of M1-related pro-inflammatory factors in the hippocampal tissue were significantly reduced in the low， medium， and high dose groups of YHTP （P<0.01）， while M2-related inflammatory factors' mRNA expression was significantly increased （P<0.01）. Western blot results showed that in the medium and high dose groups of YHTP， the expression of the M1 marker CD86 in the hippocampus was reduced， whereas the expression of the M2 marker CD206 was significantly increased （P<0.01）， with a significant decrease in the expression of glycolysis-related proteins （P<0.01）. ConclusionYHTP can improve inflammation and cognitive impairment induced by hypoxia in OSA model mice. This is achieved by downregulating glycolysis in brain microglia， inhibiting M1 activation， reducing pro-inflammatory factor release， and promoting M2 activation， thereby exerting a therapeutic effect on inflammation and cognitive impairment caused by OSA.

Literature related to children's adenoid hypertrophy was retrieved to form an expert questionnaire.According to the group standard writing rules of the China Association of Chinese Medicine,the peer consultation,quality evaluation and suitability eval-uation were completed through three rounds of Delphi expert questionnaire surveys and expert discussion meetings,and the Clinical Practice Guidelines for TCM in Children with Adenoidal Hypertrophy was finally formed.The guidelines have been formulated to clarify the scope of application of the guidelines,normative reference documents,terms and definitions,diagnosis,syndrome differentiation,treatment,prevention and care,and to provide an important reference for the clinical practice and diagnosis and treatment norms of tra-ditional Chinese medicine for children with adenoid hypertrophy.