MicroRNA-143-3p ameliorates collagen-induced arthritis by polarizing naive CD4+ T cells into Treg cells.

BACKGROUND: Rheumatoid arthritis (RA) is a persistent and systemic autoimmunity disease. The abnormal differentiation of Treg cells is important in pathogenesis. Despite previous studies showed that microRNAs (miRNAs, miR) are pivotal modulators of Treg cells, the effect of miRNAs on Treg cell differentiation and function is not clear. Our study wants to reveal the relationship of miR-143-3p with the differentiative ability and biofunction of Treg cells during the development of RA. METHODS: The Expressing level of miR-143-3p and cell factor generation in peripheral blood (PB) of RA sufferers were identified by ELISA or RT-qPCR. The roles of miR-143-3p in Treg cell differentiation were studied via ShRNA/lentivirus transfection. Male DBA/1 J mice were separated into control, model, control mimics, and miR-143-3p mimics groups to analyze the anti-arthritis efficacy, the differentiative ability of Treg cells, and the expression level of miR-143-3p. RESULTS: Our team discovered that the Expressing level of miR-143-3p was related to RA disease activities in a negative manner, and remarkably related to antiinflammation cell factor IL-10. In vitro, the expression of miR-143-3p in the CD4+ T cells upregulated the percentage of CD4+ CD25+ Fxop3+ cells (Tregs) and forkhead box protein 3 (Foxp3) mRNA expression. Evidently, miR-143-3p mimic intervention considerably upregulated the content of Treg cells in vivo, validly avoided CIA progression, and remarkably suppressed the inflammatory events of joints in mice. CONCLUSION: Our findings indicated that miR-143-3p could ameliorate CIA through polarizing naive CD4+ T cells into Treg cells, which may be a novel strategy to treat autoimmune diseases such as RA.

Panax notoginseng saponins (PNS) attenuate Th17 cell differentiation in CIA mice via inhibition of nuclear PKM2-mediated STAT3 phosphorylation.

CONTEXT: Rheumatoid arthritis (RA) is an autoimmune disease with aberrant Th17 cell differentiation. Panax notoginseng (Burk.) F. H. Chen (Araliaceae) saponins (PNS) have an anti-inflammatory effect and can suppress Th17 cell differentiation. OBJECTIVE: To investigate mechanisms of PNS on Th17 cell differentiation in RA, and the role of pyruvate kinase M2 (PKM2). MATERIALS AND METHODS: Naive CD4+T cells were treated with IL-6, IL-23 and TGF-ß to induce Th17 cell differentiation. Apart from the Control group, other cells were treated with PNS (5, 10, 20 µg/mL). After the treatment, Th17 cell differentiation, PKM2 expression, and STAT3 phosphorylation were measured via flow cytometry, western blots, or immunofluorescence. PKM2-specific allosteric activator (Tepp-46, 50, 100, 150 µM) and inhibitor (SAICAR, 2, 4, 8 µM) were used to verify the mechanisms. A CIA mouse model was established and divided into control, model, and PNS (100 mg/kg) groups to assess an anti-arthritis effect, Th17 cell differentiation, and PKM2/STAT3 expression. RESULTS: PKM2 expression, dimerization, and nuclear accumulation were upregulated upon Th17 cell differentiation. PNS inhibited the Th17 cells, RORγt expression, IL-17A levels, PKM2 dimerization, and nuclear accumulation and Y705-STAT3 phosphorylation in Th17 cells. Using Tepp-46 (100 µM) and SAICAR (4 µM), we demonstrated that PNS (10 µg/mL) inhibited STAT3 phosphorylation and Th17 cell differentiation by suppressing nuclear PKM2 accumulation. In CIA mice, PNS attenuated CIA symptoms, reduced the number of splenic Th17 cells and nuclear PKM2/STAT3 signaling. DISCUSSION AND CONCLUSIONS: PNS inhibited Th17 cell differentiation through the inhibition of nuclear PKM2-mediated STAT3 phosphorylation. PNS may be useful for treating RA.

Triptolide inhibits Th17 differentiation via controlling PKM2-mediated glycolysis in rheumatoid arthritis.

CONTEXT: Rheumatoid arthritis (RA) is an autoimmune disease with the aberrant differentiation of T helper 17 (Th17) cells. Pyruvate kinase M2 (PKM2), a key enzyme of glycolysis, was associated with Th17 cell differentiation. AIM: To investigate the potential therapeutic effects of triptolide (TP) in collagen-induced arthritis (CIA) and Th17 cell differentiation, and elucidated the underlying mechanisms. METHODS: PKM2 expression and IL-17A production in peripheral blood of RA patients were detected by RT-qPCR or ELISA. Flow cytometry and ELISA were employed to assess the effect of Th17 cell differentiation by TP. PKM2 expression and other glycolysis-related factors were detected using RT-qPCR and Western Blot. PKM2 specific inhibitor Compound 3 K was used to verify the mechanisms. Male DBA/1J mice were divided into control, model, and TP (60 µg/kg) groups to assess the anti-arthritis effect, Th17 cell differentiation and PKM2 expression. RESULTS: PKM2 expression positively correlated with IL-17A production in RA patients. PKM2 expression was increased upon Th17 cell differentiation. Down-regulating PKM2 expression could strongly reduce Th17 cell differentiation. Molecular docking analysis predicted that TP targeted PKM2. TP treatment significantly reduced Th17 cell differentiation, PKM2 expression, pyruvate, and lactate production. In addition, compared with down-regulating PKM2 alone (Compound 3 K treatment), co-treatment with TP and Compound 3 K further significantly decreased PKM2-mediated glycolysis and Th17 cell differentiation. In CIA mice, TP repressed the PKM2-mediated glycolysis and attenuated joint inflammation. CONCLUSION: TP inhibited Th17 cell differentiation through the inhibition of PKM2-mediated glycolysis. We highlight a novel strategy for the use of TP in RA treatment.

miR-338-3p inhibits autophagy in a rat model of allergic rhinitis after PM2.5 exposure through AKT/mTOR signaling by targeting UBE2Q1.

Exposure to fine particulate matter (PM2.5) increases the incidence of allergic rhinitis (AR). microRNA (miRNA) can regulate cell proliferation, invasion and apoptosis. However, the mechanism of miR-338-3p in mediating PM2.5-induced autophagy in AR animal models remains unknown. To explore the mechanism of miR-338-3p in PM2.5-induced autophagy in AR, the human nasal epithelium cells and AR model exposed to PM2.5 were deployed. The results showed that miR-338-3p was down-regulated in both nasal mucosa of PM2.5-exacerbated AR rat models and PM2.5-treated RPMI-2650 cells. Forced expression of miR-338-3p could inhibit autophagy in vitro. miR-338-3p specifically bound to UBE2Q1 3'-untranslated region (3' UTR) and negatively regulated its expression. Overexpression of UBE2Q1 attenuated the inhibitory effects of miR-338-3p on PM2.5-induced autophagy of RPMI-2650 cells through AKT/mTOR pathway. Moreover, our in vivo study found that after administration of agomiR-338-3p in AR rats model, the expression of autophagy-related proteins decreased and nasal symptoms alleviated. In conclusion, this study revealed that miR-338-3p acts as an autophagy suppressor in PM2.5-exacerbated AR by directly targeting UBE2Q1 and affecting AKT/mTOR pathway.

MicroRNA-26b-5p alleviates murine collagen-induced arthritis by modulating Th17 cell plasticity.

Rheumatoid arthritis (RA) is a chronic autoimmune disease, and the abnormal differentiation of IL-17-producing T helper (Th17) cells is an important factor in the pathogenesis. Previous studies have shown that microRNAs (miRNAs, miR) act as key regulators of Th17 cells. However, the effects of miRNAs on Th17 cell differentiation and plasticity in RA are not clear. In this study, not only low miR-26b-5p expression and high IL-17A level were observed in the peripheral blood of RA patients, but also the negative correlation between miR-26b-5p and IL-17A was explored. The changes in collagen-induced arthritis (CIA) mice were consistent with those in RA patients. The results of in vitro experiments showed that miR-26b-5p mainly inhibited the initial differentiation of Th17 cells but did not impact the differentiation of induced-Treg into Th17-like cells. Meanwhile, miR-26b-5p mimics treatment alleviated inflammatory responses and reduced Th17 proportion in CIA mice. These results indicated that miR-26b-5p could alleviate the development of mice CIA by inhibiting the excessive Th17 cells, and that miR-26b-5p could modulate the plasticity of Th17 cell differentiation in RA, mainly block the initial differentiation. This may provide a novel strategy for the clinical treatment of RA.

IncRNA LUCAT1 acts as a Potential Biomarker and Demonstrates Malignant Biological Behaviors in Gastric Cancer.

BACKGROUND: Gastric cancer (GC) remains the fourth-leading malignancy worldwide and has a high mortality rate. Accumulating evidence reveals that long noncoding RNAs (lncRNAs) play essential roles in tumorigenesis and metastasis and can be used as potential biomarkers for diagnosis and prognosis. METHODS: We downloaded gene expression profiles from the National Center of Biotechnology Information Gene Expression Omnibus (GEO), screened lncRNAs differentially expressed in gastric cancer tissues and adjacent tissues, and then constructed a lncRNA-miRNA-mRNA network. Seventy patients with gastric cancer were divided into two groups according to different clinical characteristics. The expression of lncRNA LUCAT1 in gastric cancer was detected by reverse transcription polymerase chain reaction (RT-PCR). The AGS and SGC-7901 cell lines were used in CCK8 assay, apoptosis, cell cycle test, transwell assay, and wound healing assay. RESULTS: The expression level of LUCAT1 was associated with tumor diameter (p < 0.001), tissue differentiation grade (p = 0.026), and LNM status (p = 0.020) in GC. The results showed that the lncRNA LUCAT1 could promote the proliferation, invasion, and migration of GC cells, inhibit the apoptosis of GC cells, and affect the process of cell cycles. CONCLUSIONS: The lncRNA LUCAT1 may be used as a potential biomarker for early signs of LNM in GC and may play a crucial role in the development of GC.

[Effect of Qingluo Tongbi Compound on Osteoclast Differentiation-related mIRNA Expressions in Adjuvant Induced Arthritis Rats].

Objective To observe the effect of Qingluo Tongbi Compound (QTC) on osteoclast dif- ferentiation-related miRNA expressions in adjuvant induced arthritis (AIA) rats, and to study its mecha- nism for treating rheumatoid arthritis (RA). Methods The synovial fibroblasts and monocytes of peripher- al blood from AIA rats were co-cultured to induce osteoclast-like cells. Differently expressed miRNAs in the late stage osteoclasts differentiation were detected by miRCURY™ Array. Real-time quantitative PCR (RT- PCR) was applied to verify the reliability of miRNA array. QTC drug-containing sera and blank sera were prepared and added to the co-cultured system. The osteoclasts were randomly divided into three groups, the blank group, the blank serum group, and the QTC group. RT-PCR was applied to detect the effect of QTC on related differentially expressed miRNAs. Bioinformatics software was applied to analyze related differentially expressed miRNAs. Results miRNA array results showed that as compared with the monocytes group, there were 211 miRNAs differentially expressed in osteoclast-like cell differentiation, including 88 up-regulated miRNAs and 123 down-regulated miRNAs. Results of RT-PCR were consistent with results of the array. RT-PCR showed that the expression level of miR-140-5p was obviously up-regulated after the intervention of QTC. Results of bioinformatics analyses showed that the target gene of miR-140-5p was sig- nificantly enriched in signaling pathways such as the regulation of actin cytoskeleton, Ras signaling path- ways, cAMP signaling pathways, and Rap1 signaling pathways. Conclusions There were various dysregulated expressions of miRNAs in the anaphase of osteoclast-like cells differentiation. QTC participated the regulation of osteoclast differentiation by effecting the expression of miR-140-5p.

[Metabolomics analysis of Tripterygium wilfordii formulation based on theory of detoxicity compatibility].

Tripterygium wilfordii Hook. f. induced-hepatotoxicity was the main limitation for its usage in clinic. Qingluo Tongbi formulation showed obvious attenuation for hepatotoxicity in clinic and fundamental research in vivo. To explore the potential mechanism of the attenuation, we conducted a study on the plasma metabolomic profiles of T. wilfordii and Qingluo Tongbi formulation in rats by a sensitive gas chromatography-mass spectrometry (GC-MS/MS) method. In plasma samples, a total of 72 compounds were analyzed by EI source MS, and were successfully identified by matching NIST database. The semi-quantification results were then calculated by OPLS-DA model with SIMCA-P 13.0 software. The three groups were clearly distinguished in OPLS-DA score plot. In addition, the observation values of Qingluo Tongbi formulation showed the obvious trend towards the control levels, suggesting the detoxicity effect of the formulation. Variation metabolites were further analyzed by VIP and One Way ANOVAs, and the results showed a significant increase in compounds of glycogenic amino acids, such as alanine, proline, serine and glutamine after the administration of T. wilfordii, indicated that the tissue proteins were decomposed and amino acids were leakage into blood. Qingluo Tongbi formulation could reverse the amino acids into normal level. On the contrary, the levels of glucose, lactic acid and hydroxy butyrate decrease, and the formulation can relieve the disorder in the levels of lactic acid, suggesting the regulation of the energy metabolism. Additionally, the level of branched chain amino acid was decreased, suggested the toxicity was induced, but the formulation cannot increase it into the normal levels. Nevertheless, all the above results suggested that the classical Qingluo Tongbi formulation displayed the liver protection effect by adjusting the amino acid levels and regulating the energy metabolism. Qingluo Tongbi formulation was developed based on traditional Chinese medicine theory "detoxicity compatibility", and contained Panax notoginseng (Burk.) F. H. Chen to nourish blood and absorb clots. Modern pharmacology suggested that its liver protection effect was correlated with the promotion of protein synthesis. Another important herb is Rehmannia glutinosa Libosch., which can regulate the energy metabolism. Both were consistent with the metabolomic results in this study, which explained the potential mechanism of "detoxicity compatibility" theory. Therefore, the currently developed metabolomic approach and the obtained results would be highly useful for the comprehensive toxicity studies for other herbal medicines and various complex deoxicity formulations.

[Effects of Wine-processing on Rhei Radix et Rhizoma on Upper-energizer Disease and Effects on Activities of Energy Metabolism Enzymes in Liver].

OBJECTIVE: To compare the effects of crude and wine-processed Rhei Radix et Rhizoma on upper-energizer disease and hepatic energy metabolism in mice. METHODS: The streptococcal pneumonia rats model and acetic acid burning mouth ulcers rats model were established and randomly divided into three groups: model group, crude Rhei Radix et Rhizoma group and wine-processed Rhei Radix et Rhizoma group. The pathologic changes were observed after the rats had been administrated with water extracts of crude and wine-processed Rhei Radix et Rhizoma respectively. The normal ICR mice were randomly divided into three groups: control group, crude Rhei Radix et Rhizoma group and wine-processed Rhei Radix et Rhizoma group. The influence of water extracts of crude and wine-processed Rhei Radix et Rhizoma on the activities of Na+, K-ATPase, Ca2+ -ATPase and succinic dehydrogenase(SDH) in the mice were compared. RESULTS: Compared with the crude one,the wine-processed Rhei Radix et Rhizoma significantly decreased the inflammation scores (P <0. 05), and promoted the tissue repair of acetic acid burning mouth ulcers rats model. The wine-processed one could also obviously reduce and normalize the level of leucocyte and neutrophilic granulocyte, lower the TNF-α level (P <0. 05), and relieve inflammatory exudation of the lung tissue. The inhibitory effects of wine-processed Rhei Radix et Rhizoma on the activities of SDH, Ca2+-ATPase and Na+, K + -ATPase were weaker than those of the crude one (P > 0. 05). CONCLUSION: After having been processed with wine, the efficacy of Rhei Radix et Rhizoma on upper-energizer disease is enhanced, and the inhibition on the activity of energy metabolism enzyme in liver tends to be weakened.

Celastrol: The new dawn in the treatment of vascular remodeling diseases.

Evidence is mounting that abnormal vascular remodeling leads to many cardiovascular diseases (CVDs). This suggests that vascular remodeling can be a crucial target for the prevention and treatment of CVDs. Recently, celastrol, an active ingredient of the broadly used Chinese herb Tripterygium wilfordii Hook F, has attracted extensive interest for its proven potential to improve vascular remodeling. Substantial evidence has shown that celastrol improves vascular remodeling by ameliorating inflammation, hyperproliferation, and migration of vascular smooth muscle cells, vascular calcification, endothelial dysfunction, extracellular matrix remodeling, and angiogenesis. Moreover, numerous reports have proven the positive effects of celastrol and its therapeutic promise in treating vascular remodeling diseases such as hypertension, atherosclerosis, and pulmonary artery hypertension. The present review summarizes and discusses the molecular mechanism of celastrol regulating vascular remodeling and provides preclinical proof for future clinical applications of celastrol.

[Effect of moxibustion on the expressions of hypoxia inducible factor-1α and vascular endothelial growth factor in ankle synovial tissue of rats with adjuvant arthritis].

OBJECTIVE: To observe the effect of moxibustion on the expressions of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in ankle synovial tissue of rats with adjuvant arthritis(AA), so as to explore the mechanism of moxibustion in inhibiting synovial angiogenesis and improving joint symptoms of rheumatoid arthritis. METHODS: Sixty healthy male SD rats were randomly divided into normal group, model group, moxibustion group and medication group, with 15 rats in each group. AA rat model was established by subcutaneous injection of Freund's complete adjuvant into the right hind paw. Rats in the moxibustion group were treated with "Zusanli" (ST36), "Guanyuan" (CV4) and "Ashi" point moxibustion, 20 min each time, once a day, for consecutive 3 weeks. Rats in the medication group were given methotrexate (0.35 mg/kg) intragastric administration, twice a week, for consecutive 3 weeks. Foot plantar volume of rats was measured by toe volume mea-suring instrument. HE staining was used to observe the histopathology of ankle synovium. The protein expressions of HIF-1α and VEGF in ankle synovial tissue were detected by immunohistochemistry and Western blot. RESULTS: Compared with the normal group, the foot plantar volume and the protein expressions of HIF-1α and VEGF in synovial tissue of ankle joint were significantly increased (P<0.01) in the model group, the synovial tissue showed obvious hyperplasia and a large number of neovasculogenesis. Following the interventions, the foot plantar volume and the protein expressions of HIF-1α and VEGF in synovial tissue of ankle joint were significantly decreased (P<0.05, P<0.01) in both moxibustion and medication groups in contrast to the model group, and there was no obvious proliferation of synovial tissue, and only a few neovascularization was observed. Compared with the medication group, the foot plantar volume was decreased (P<0.05) in the moxibustion group. CONCLUSION: Moxibustion can improve joint swelling and inhibit synovial angiogenesis in AA rats, and its mechanism may be related to down-regulating of HIF-1α and VEGF protein expressions.

Tomentosin suppressed M1 polarization via increasing MERTK activation mediated by regulation of GAS6.

ETHNOPHARMACOLOGICAL RELEVANCE: Xanthium sibiricum Patrin ex Widder (X. sibiricum) are widely used traditional herbal medicines for arthritis treatment in China. Rheumatoid arthritis (RA) is characterized by progressive destructions of joints, which is accompanied by chronic, progressive inflammatory disorder. According to our previous research, tomentosin was isolated from X. sibiricum and revealed anti-inflammatory activity. However, the potential therapeutic effect of tomentosin on RA and the anti-inflammatory mechanism of tomentosin remain to be clarified. The present study lays theoretical support for X. sibiricum in RA treatment, also provides reference for further development of X. sibiricum in clinic. AIM OF THE STUDY: To investigate the effect of tomentosin in collagen-induced arthritis (CIA) mice and reveal its underlying mechanism. MATERIALS AND METHODS: In vivo, tomentosin (10, 20 and 40 mg/kg) was given to CIA mice for seven consecutive days, to evaluate its therapeutic effect and anti-inflammatory activity. In vitro, THP-1-derived macrophages were used to verify the effect of tomentosin on inflammation. Then, molecular docking and experiments in vitro was conducted to predict and explore the mechanism of tomentosin inhibiting inflammation. RESULTS: Tomentosin attenuated the severity of arthritis in CIA mice, which was evidenced by the swelling of the hind paws, arthritis scores, and pathological changes. Particularly, tomentosin effectively reduced the ratio of M1 macrophage and TNF-α levels in vitro and vivo. Then, molecular docking and experiments in vitro was carried out, indicating that tomentosin inhibited M1 polarization and TNF-α levels accompanied by the increase of MERTK and up-regulated GAS6 levels. Moreover, it has been proved that GAS6 was necessary for MERTK activation and tomentosin could up-regulate GAS6 levels effectively in transwell system. Further mechanistic studies revealed that tomentosin suppressed M1 polarization via increasing MERTK activation mediated by regulation of GAS6 in transwell system. CONCLUSION: Tomentosin relieved the severity of CIA mice by inhibiting M1 polarization. Furthermore, tomentosin suppressed M1 polarization via increasing MERTK activation mediated by regulation of GAS6.

Obesity is associated with colitis in women but not necessarily causal relationship.

The relationship between obesity and female risk of microscopic colitis remains to be discussed.

Underlying reasons for the decline in physical activity during COVID-19.

The article not only successfully evaluated regular physical activities can improve mental well-being during self-isolation and social distancing policies related to the coronavirus disease 2019 (COVID-19), but also concluded that the COVID-19 pandemic may lead to augmented levels of angiotensin-converting enzyme-2. By reading the article of Walid Kamal Abdelbasset, we have some questions and put forward some suggestions on the content of the article.

Intracranial tumors mimicking benign paroxysmal positional vertigo: A case series.

Background: A few intracranial lesions may present only with positional vertigo which are very easy to misdiagnose as benign paroxysmal positional vertigo (BPPV); the clinicians should pay more attention to this disease. Objectives: To analyze the clinical characteristics of 6 patients with intracranial tumors who only presented with positional vertigo to avoid misdiagnosing the disease. Material and methods: Six patients with intracranial tumors who only presented with positional vertigo treated in our clinic between May 2015 to May 2019 were reviewed, and the clinical symptoms, features of nystagmus, imaging presentation, and final diagnosis of the patients were evaluated. Results: All patients presented with positional vertigo and positional nystagmus induced by the changes in head position or posture, including one case with downbeating nystagmus in a positional test, two cases with left-beating nystagmus, one case with apogeotropic nystagmus in a roll test, one case with right-beating nystagmus, and one case with left-beating and upbeating nystagmus. Brain MRI showed the regions of the tumors were in the vermis of the cerebellum, the fourth ventricle, the lateral ventricle, and the cerebellar hemisphere.

Regulatory effect of melatonin on cytokine disturbances in the pristane-induced lupus mice.

Systemic lupus erythematosus (SLE) develops in relation to many environmental factors. In our opinion, it is more important to investigate the effect of melatonin on the environmental- related SLE. In the present study, 0.5 ml pristane were used to induce SLE in female BALB/c mice. Melatonin (0.01, 0.1, 1.0 mg/kg) was orally administered immediately after pristane-injection for 24 weeks. IgM anti ssDNA and histone antibodies were detected after 0, 1, 2, 4, 8 weeks pristane injection. The levels of IL-2, IL-6 and IL-13 were detected after 24 weeks. Renal lesions were also observed. The results showed that melatonin antagonized the increasing levels of IgM anti ssDNA and histone autoantibodies. Melatonin could also decrease the IL-6 and IL-13 production and increase the IL-2 production. Besides, melatonin could lessen the renal lesions caused by pristane. These results suggested that melatonin has a beneficial effect on pristane-induced lupus through regulating the cytokines disturbances.

[Effects of Kuntai Capsule and hormone replacement therapy on cognitive function and mental symptoms of early postmenopausal women: a randomized controlled trial].

BACKGROUND: Conjugated equine estrogen (CEE) treatment, a hormone replacement therapy, is restricted for use in perimenopausal and postmenopausal women because of security issues. Consequently, traditional Chinese herbal medicine has become an alternative choice for the patients with contraindications to hormone replacement therapy. OBJECTIVE: To evaluate the efficacy and safety of Kuntai Capsule and CEE in treating cognitive function disorder and mental symptoms of early postmenopausal women. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 57 cases of early postmenopausal women from Outpatient Department of West China Women and Children's Hospital were included. The subjects were randomly divided into two groups: Kuntai group with 28 cases and CEE group with 29 cases. The patients in Kuntai group received 6 g Kuntai capsules three times a day. The patients in CEE group received CEE 0.3 mg and 0.6 mg alternately once a day (average dose of 0.45 mg/d). The patients with intact uterus in CEE group were treated with 2 mg medroxyprogesterone acetate daily. MAIN OUTCOME MEASURES: In one-year treatment course, the recognition function and mental symptoms of each patient were investigated by questionnaires of Mini-Mental State Examination (MMSE), Kupperman, and quality of life (QOL) every three months. Both intention-to-treat (ITT) and per-protocol set (PPS) analyses were done. RESULTS: The MMSE, Kupperman index and QOL scores at each time point were improved as compared with those before treatment (P<0.05), however there were no statistical differences between the two groups (P>0.05). The MMSE scores showed a tendency to escalate while mental symptoms investigated by Kupperman index and QOL scale showed a downtrend. No severe adverse effects occurred in the study phase and no statistical difference in incidence of side effects between the two groups was found except for vaginal bleeding. The incidence rates of vaginal bleeding in CEE and Kuntai groups were 39.3% and 11.1% respectively (P=0.029). CONCLUSION: Both Kuntai Capsule and CEE may contribute to maintain the cognitive function and ameliorate mental symptoms of early postmenopausal women.

[A Predictive Model for Hemoglobin Change before and after Collection of Apheresis Autologous Red Blood Cells in Patients].

OBJECTIVE: To analyze the affecting factors of hemoglobin changes in apheresis red blood cells (RBCs), and to establish a predictive model for the evaluation of apheresis. METHODS: The clinical data of 130 patients undergoing selective surgery for apheresis autologous RBCs from January 2017 to December 2018 were collected. The change of hemoglobin and its affecting factors before and after apheresis were analyzed. The predictive model of the hemoglobin change was established by machine learning algorithm and compared with the theoretical predictive model. RESULTS: The average Hb level in the 300 ml autologous RBC group decreased by 22.61±8.85 g/L, and the average Hb in 400 ml group decreased by 29.08±7.25 g/L. The change of Hb was mainly affected by Hb level before apheresis and peripheral circulation blood volume (P＜0.05). Sex, age, and the interval time between blood collection and operation not significantly influenced Hb change (P＞0.05). The initially established predictive model by the machine learning (MAE 6.27) is superior to the theoretical predictive model (MAE 8.11). CONCLUSION: The predictive model established by the machine learning can provide a reference for more accurate evaluation of apheresis autologous red blood cells.

Long noncoding RNA HOTTIP is associated with male infertility and promotes testicular embryonal carcinoma cell proliferation.

BACKGROUND: It has been proposed that lncRNAs, widely transcribed from genomes, play pivotal regulatory roles in a variety of biological processes, but their function in regulating spermatogenesis in human males is rarely reported. METHODS: QRT-PCR was adopted to detect HOTTIP expression level in testicular tissues from hypospermatogenesis (Hypo) patients or controls. The proliferation levels of NT2 and 293T were measured via CCK-8 and EdU detection. Meanwhile, luciferase reporter gene assay and bioinformatics analysis were carried out to identify a target of HOTTIP. Additionally, the underlying mechanism of HOTTIP's function was investigated using western blotting and RIP analysis. RESULTS: The research results manifested that the expression of HOTTIP in testicular tissues from Hypo patients was prominently reduced in comparison with that in control testicular tissues. Interestingly, it was noted that HOTTIP exhibited a high expression in testicular embryonal carcinoma cell line NT2 compared with that in normal control cell line 293T. It was denoted in cell function evaluation that cell proliferation was impeded by downregulated HOTTIP but evidently stimulated by overexpressed HOTTIP. Moreover, HOTTIP was capable of positively modulating HOXA13 expression via the competitive binding to miR-128-3p. CONCLUSION: Therefore, HOTTIP acting as ceRNAs to promote testicular embryonal carcinoma cell proliferation.

Th17 cell pathogenicity and plasticity in rheumatoid arthritis.

CD4+ Th cells play an important role in the development of rheumatoid arthritis (RA) by regulating adaptive immune response. As major subsets of CD4+ Th cells, Th17 cells can produce a large number of hallmark cytokines such as IL-17A and IL-17F, which participate in host defense and immune homeostasis. However, increasing researches have shown that Th17 cells are unstable and exhibit a certain degree of plasticity, which aggravates their pathogenicity. Furthermore, the plasticity and pathogenicity of Th17 cells are closely related with the disease activity in RA. In this paper, the characteristics including phenotype, differentiation, plasticity, and pathogenicity of Th17 cells in RA will be systematically summarized. This will contribute to clarify the immunologic mechanism of RA and further provide a novel strategy for the clinical treatment of autoimmune diseases.