[Feasibility study of expectant management of different degrees of vaginal fluid in pregnant women with premature rupture of membranes in the second trimester].

Objective: To investigate the feasibility of expectant management of different degrees of vaginal fluid in pregnant women with premature rupture of membranes in the second trimester. Methods: A retrospective cohort study was conducted to collect 103 pregnant women who were diagnosed with premature rupture of membranes in the second trimester of pregnancy and insisted on continuing the pregnancy in Shanxi Bethune Hospital from July 2012 to July 2022. According to the degree of vaginal fluid, pregnant women were divided into rupture group (with typical vaginal fluid, 48 cases) and leakage group (without typical vaginal fluid, 55 cases). The rupture latency (the time from rupture of membranes to termination of pregnancy), gestational weeks of termination, indications and methods of termination of pregnancy, maternal infection related indicators and perinatal outcomes were compared between the two groups. Univariate regression model was used to analyze the correlation between different degrees of vaginal fluid in pregnant women with premature rupture of membranes and maternal and neonatal outcomes. Results: (1) Obstetric indicators: there was no significant difference in the gestational age of rupture of membranes between the two groups (P>0.05). However, the proportion of rupture latency >28 days in the leakage group was significantly higher than that in the rupture group [42% (23/55) vs 13% (6/48); χ2=33.673, P<0.001], and the incidence of pregnancy termination ≥28 weeks was significantly higher [47% (26/55) vs 19% (9/48); χ2=9.295, P=0.002]. (2) Indications and methods of termination: the incidence of progressive reduction of amniotic fluid as the indication for termination in the leakage group was significantly lower than that in the rupture group [22% (12/55) vs 42% (20/48); χ2=4.715, P=0.030], and the incidence of full-term termination in the leakage group was significantly higher than that in the rupture group [31% (17/55) vs 12% (6/48); χ2=5.008, P=0.025], while there were no significant differences in the indications of termination of pregnancy, including amniotic cavity infection, uterine contraction failure and fetal distress between the two groups (all P>0.05). The incidence of induced labor or spontaneous contraction in the leakage group was significantly lower than that in the rupture group [53% (29/55) vs 81% (39/48); χ2=9.295, P=0.002], while the cesarean section rate and vaginal delivery rate were similar between the two groups (both P>0.05). (3) Infection related indicators: the incidence of amniotic cavity infection in the leakage group was significantly higher than that in the rupture group [31% (17/55) vs 13% (6/48); χ2=4.003, P=0.045]. However, there were no significant differences in the elevation of inflammatory indicators, the positive rate of cervical secretion bacterial culture and the incidence of tissue chorioamnionitis between the two groups (all P>0.05). (4) Perinatal outcomes: the live birth rate in the leakage group was significantly higher than that in the rupture group [51% (28/55) vs 27% (13/48); χ2=5.119, P=0.024]. The proportion of live births with 1-minute Apgar score >7 in the leakage group was significantly higher than that in the rupture group [38% (21/55) vs 17% (8/48); χ2=4.850, P=0.028]. However, there were no significant differences in the birth weight of live births and the incidence of neonatal complications between the two groups (all P>0.05). (5) Univariate regression analysis showed that compared with the rupture group, the leakage group had a higher risk of pregnancy termination at ≥28 gestational weeks (RR=2.521, 95%CI: 1.314-4.838; P=0.002), amniotic infection (RR=2.473, 95%CI: 1.061-5.764; P=0.025), perinatal survival (RR=1.880, 95%CI: 1.104-3.199; P=0.014). Conclusion: Compared with pregnant women with typical vaginal fluid in the second trimester of premature rupture of membranes, expectant treatment for pregnant women with atypical vaginal fluid is more feasible, which could effectively prolong the gestational weeks and improve the perinatal live birth rate.

[Application of Padua prediction score and serum albumin level in evaluating venous thromboembolism in rheumatic inpatients].

OBJECTIVE: To investigate the status of venous thromboembolism (VTE) in rheumatic inpatients, and to explore the efficiency of Padua prediction score (PPS) in the patient population. In addition, to analyze the relationship between serum albumin and VTE in rheumatic inpatients. METHODS: Data of inpatients with rheumatology were retrospectively collected and analyzed at Sichuan Provincial People's Hospital from September 2018 to September 2019. Occurrence of VTE was compared between high (PPS≥4) and low (PPS < 4) risk groups. PPS were analyzed in the VTE and non-VTE patients. Multivariate Logistic regression model was used to analyze the risk factors in PPS and the relationship between serum albumin and VTE. RESULTS: A total of 1 547 patients were included in this study, and 27 (1.7%) had symptomatic VTE. Among the symptomatic VTE cases, 19 (1.2%) had deep vein thrombosis (DVT) only, 6 (0.4%) had pulmonary thromboembolism (PTE) only, and 2 (0.1%) were diagnosed with DVT and PTE. PPS in the VTE and non-VTE groups were 3.33±1.78 and 1.80±0.97 respectively (P < 0.05).The number of patients with PPS≥4 in the VTE group and non-VTE group was 37.0% and 4.3% respectively (P < 0.01). The average serum albumin level in the VTE group was lower than that in non-VTE group [(29.79±6.36) g/L vs. (35.17±6.31) g/L, P < 0.001]. Seventy-six cases was divided into high-risk group of VTE, while 1 471 cases were in the low-risk group, and the incidence of VTE was 13.2% and 1.2% respectively (P < 0.001). Logistic regression analysis showed that ongoing hormonal treatment, age≥70 years, trauma and/or surgery ≤30 d, reduced mobility and previous VTE were risk factors of VTE in the rheumatology patients, OR values were 7.11, 7.07, 3.40, 2.40 and 2.00, respectively. Lower serum albumin level was the risk factor of VTE in the rheumatology patients [OR=0.88 (95%CI: 0.82-0.94)]. CONCLUSION: The incidence of VTE was relatively higher in the hospitalized patients in Department of Rheumatology and Immunology. Glucocorticoid therapy was the highest risk factor of VTE and lower serum albumin level also was the risk factor. Although the PPS can reflect the risk of VTE in rheumatic inpatients to some extent, its effectiveness is limited. PPS can be optimized for quantitative VTE risk assessment of rheumatic inpatients in the future.

[Clinical observation of microsurgical removal of the hemilateral tuberculum sellae meningiomas through contralateral eyebrow arch approach].

The current study aimed to investigate the clinical feasibility of microscopic resection of hemilateral tuberculum sellae meningiomas (TSM) via the contralateral eye brow arch approach. The clinical data of 34 patients with TSM who underwent microsurgery from January 2016 to June 2021 in the Neurosurgery Department of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine and the First Affiliated Hospital of Henan University were collected and reviewed. The postoperative visual acuity improvement rate was 88.5% (23/26), and the total tumor resection rate was 88.2% (30/34); the postoperative visual acuity improvement in patients with total tumor resection was better than that of patients with partial resection [90.9% (20/22) vs 3/4]. Meanwhile, the postoperative visual acuity improvement in patients with the superior optic nerve and laterl-superior optic nerve was better than that of patients with the lateral optic nerve type (12/14, 8/8 vs 3/4). Supraorbital skin numbness occurred in 3 cases after operation, and the symptoms disappeared during follow-up; 2 cases had mild disturbance of hormone level, and urine output of 2 cases increased after operation, which returned to normal level after symptomatic treatment; 1 case had subcutaneous effusion which was absorbed after treatment. There were no complications such as olfactory disturbance and intracranial infection. During follow-up for 3-60 (33±6) months, recurrence occurred in 2 cases and reoperation was performed. For the hemilateral TSM, according to the preoperative evaluation of the origin of the TSM and the side with visual impairment, the contralateral eyebrow approach is selected to fully expose the tumor base below the optic nerve. It is beneficial to fully resect the tumor under direct vision, and the symptoms of postoperative visual impairment are significantly improved, indicating that the current surgical method can be used in the clinical setting.

Psoriasis and progression of Parkinson's disease: a Mendelian randomization study.

BACKGROUND: Epidemiological studies have suggested psoriasis was associated with an increased risk of Parkinson's disease (PD). However, whether psoriasis has an effect on PD progression is not explored yet. OBJECTIVES: To evaluate the causal role of psoriasis in PD progression. METHODS: We conducted a two-sample Mendelian randomization analysis using summary statistics from genome-wide association study of psoriasis (N = 33 394), age at onset (N = 28 568) and progression (N = 4093) of PD. RESULTS: One standard deviation increase in genetically determined psoriasis risk was significantly associated with faster progression to dementia (OR = 1.07, 95% CI: 0.1.03-1.1, P = 4.71E-04). Meanwhile, higher psoriasis risk was nominally associated with faster progression of PD measured by time to Hoehn and Yahr stage 3 (OR = 1.05, 95% CI: 1.02-1.08, P = 1.53E-03) and depression (OR = 1.06, 95% CI: 1.02-1.11, P = 1.77E-03) of PD. The results were robust under all sensitivity analyses. CONCLUSIONS: These results suggested psoriasis accelerated overall progression of PD, and increased risk of dementia and depression of PD. A deeper understanding of neuroinflammation and immune response is likely to elucidate the potential pathogenesis of PD progression and identify novel therapeutic targets.

Characterizing the critical role of metabolism in osteosarcoma based on establishing novel molecular subtypes.

OBJECTIVE: Osteosarcoma is the third most frequently diagnosed cancer among adolescents. Immunotherapy is an effective curative treatment for metastatic osteosarcoma patients. This study aimed to further reveal the significance of metabolism in tumor progression, and to categorize molecular subtypes for guiding personalized therapy. MATERIALS AND METHODS: Univariate Cox regression analysis was performed to screen metabolism-related genes associated with osteosarcoma prognosis. A molecular subtyping system was developed by unsupervised consensus clustering. Survival analysis and functional analysis were used to evaluate the performance of subtyping and characterize the TME of subtypes. Stepwise Akaike information criterion (stepAIC) was employed to optimize the prognostic model. RESULTS: C1 and C2 subtypes showed distinct prognosis, with more favorable survival in C2 subtype. C2 subtype presented a higher immune infiltration and active anti-tumor response. Notably, C2 subtype was predicted to have better immune response to immune checkpoint blockade. In addition, a 5-gene prognostic signature with robust ability to classify patients into high-risk and low-risk groups was developed. CONCLUSIONS: The study revealed the critical role of metabolism in tumorigenesis by comparing the features between the two subtypes. Oncogenic pathways including epithelial mesenchymal transition (EMT), glycolysis and hypoxia may be closely involved in the correlation with metabolism. Importantly, we developed a novel subtyping system and a 5-gene signature with high potential to be applied in clinical practice.

Hyperhidrosis in Parkinson's disease: a 3-year prospective cohort study.

BACKGROUND: Although hyperhidrosis is a common symptom in patients with Parkinson's disease (PD), no study has yet examined it longitudinally. OBJECTIVES: We conducted a 3-year prospective cohort study to investigate the development, evolution and correlates of hyperhidrosis in patients with PD. METHODS: A total of 224 patients with early-stage PD were enrolled at baseline and followed up annually for three consecutive years. Hyperhidrosis was assessed using hyperhidrosis question (item 30) of the Non-Motor Symptoms Scale (NMSS). The generalized estimating equations model was applied to investigate the correlates of both presence and severity of hyperhidrosis. RESULTS: The frequency of hyperhidrosis in PD had an overall increasing tendency from 24.1% at baseline to 34.4% after 3 years, although hyperhidrosis was not always persistent in all patients over the 3-year study period. The presence of hyperhidrosis was found to be associated with dyskinesia (OR 2.27 [1.02-5.04], P = 0.045), the sexual function domain subscore of the NMSS (OR 1.04 [1.01-1.07], P = 0.016), the Hamilton Anxiety Rating Scale (HARS) score (OR 1.08 [1.03-1.13], P = 0.001) and the Unified Parkinson's Disease Rating Scale part III score (OR 1.02 [1.00-1.04], P = 0.036). Only the HARS score was associated with the severity of hyperhidrosis (B 0.08 [0.03-0.12], P = 0.001). CONCLUSIONS: Hyperhidrosis is common in PD, and its frequency increases along with disease duration. Hyperhidrosis in PD is associated not only with motor severity and motor complication such as dyskinesia, but also with non-motor symptoms such as sexual dysfunction and anxiety.

[Transcranial sonographic characteristics of Parkinson's disease with symptoms of restless legs syndrome].

Objective: To evaluate the transcranial sonographic characteristics in patients with Parkinson's disease (PD) with symptoms of restless legs syndrome (RLS). Methods: Patients with diagnosis of definite PD from the Second Affiliated Hospital of Soochow University and 3 other participating hospitals between September 2018 and December 2019 were consecutively enrolled. Concurrent RLS symptoms were determined using Non-motor Symptoms Questionnaire. Transcranial sonography (TCS) and clinical assessments were performed during the same time and the related variables were compared between the two groups using t-test, non-parametric test, Chi-square test and Spearman correlation analysis, respectively. Results: Among 349 patients with PD, the prevalence of RLS symptoms was 22.6%. Compared to patients without RLS symptoms, those with RLS had longer disease duration (43.0 (24.0, 91.0) months vs 37.0 (20.0, 60.0) months, P<0.05) and higher Hoehn-Yahr stage (2.5 (2.0, 3.0) vs 2.0 (1.5, 2.5), P<0.01).TCS revealed that patients with RLS symptoms were more likely to have abnormality in the raphe nucleus (21.50% vs 7.78%, χ²=15.9, P<0.001) and increased third ventricle width ((6.22±1.97) mm vs (5.16±1.90) mm, P<0.001). No significant differences were found regarding parameters of substantia nigra. Conclusions: Concurrent RLS symptoms are common in PD patients. Abnormal echogenicity of raphe nucleus and increased third ventricle width could be characteristics of TCS in PD patients with RLS symptoms.

Pro-inflammatory and pro-fibrotic role of long non-coding RNA RMRP in pediatric asthma through targeting microRNA-206/CCL2 axis.

Asthma is an inflammatory pulmonary illness that plagues infants and young children. We carried out this investigation to examine the role of long noncoding RNA (lncRNA) RNA component of mitochondrial RNA processing endoribonuclease (RMRP) in an asthmatic mouse model induced by ovalbumin (OVA) and human airway smooth muscle cells (ASMCs). Eight-week-old mice were sensitized with OVA to simulate pediatric asthma. The expression patterns of RMRP, microRNA-206 (miR-206) and C-C motif ligand 2 (CCL2) in pulmonary tissues were evaluated by qPCR. In addition, the concentrations of interleukin (IL)-4, IL-5 and IL-13 cytokines in bronchoalveolar lavage fluid were detected by ELISA. The expression of RMRP and CCL2 was elevated, while miR-206 was reduced in OVA-induced mice. Our findings indicated that administration of RMRP overexpression in ASMCs increased the levels of biomarkers in asthma. RMRP functioned as a sponge for miR-206 to upregulate CCL2 expression. Blockade of the TGF-ß/Smad2 signaling pathway in ASMCs overexpressing RMRP suppressed the inflammatory cytokines and cell viability, while enhancing apoptosis. The RMRP/miR-206/CCL2 regulatory axis is implicated in the occurrence of pediatric asthma.

PARP inhibitors as maintenance therapy in newly diagnosed advanced ovarian cancer: a meta-analysis.

BACKGROUND: Up to 70% of patients with advanced ovarian cancer have a relapse after primary therapy. New agents and approaches are urgently needed to avoid or slow down this recurrence. OBJECTIVES: To investigate the efficacy of PARP inhibitors (PARPis) as maintenance treatment in patients with newly diagnosed advanced ovarian cancer. SEARCH STRATEGY: PubMed, MEDLINE, EMBASE, Cochrane Library and Web of Science databases. SELECTION CRITERIA: All randomised clinical trials (RCTs) that compared PARPis with placebo as first-line maintenance therapy in ovarian cancer. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data. Pooled hazard ratio (HR) and risk ratio (RR) with 95% confidence interval (CI) were calculated. MAIN RESULTS: PARPis were associated with significant improvement of progression-free survival (PFS) in advanced epithelial ovarian cancer (AeOC) (HR = 0.53, 95% CI 0.40-0.71; P < 0.0001). The benefit was not only in women with BRCA mutations (HR = 0.35, 95% CI 0.29-0.42; P < 0.00001) and homologous recombination deficiency (HRD) (HR = 0.43, 95% CI 0.32-0.60; P < 0.00001), but also in those with nonmutated BRCA (HR = 0.72, 95% CI 0.63-0.82; P < 0.00001) and even non-HRD (HR = 0.83, 95% CI 0.70-0.99; P = 0.04). CONCLUSIONS: PARP inhibitors are effective as maintenance therapy among patients with newly diagnosed advanced ovarian cancer after platinum-based chemotherapy, regardless of BRCA mutation or HRD status. TWEETABLE ABSTRACT: PARPis provide a significant PFS benefit as first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer.

[Clinical characteristics and related factors of rheumatoid arthritis complicated with tuberculosis infection].

OBJECTIVE: To investigate the clinical characteristics and high risk factors of Rheumatoid arthritis (RA) complicated with tuberculosis infection. METHODS: Patients with rheumatoid arthritis diagnosed in the hospital of Sichuan Provincial People's Hospital from January 2007 to January 2017 was retrospectively collected, who were enrolled in the study group. A control group was randomly selected from the RA patients hospitalized in the same period without co-infection at a ratio of 1 :2. The general data, clinical data, laboratory test data, treatment plan, etc. of the two groups were collected in detail for single factor statistical analysis. Then multivariate Logistic regression was used to analyze the independent risk factors of RA complicated with tuberculosis infection with statistical significance in univariate analysis. RESULTS: The clinical manifestations of fever (83.3%) were most common, followed by cough (69%) and body mass loss (45.2%). In the infected group, pulmonary tuberculosis accounted for 73.3%. In the infected group the chest CT showed two or more cases, accounting for 59%. There were 9 cases (33.3%) occurring in the typical tuberculosis occurrence site. Compared with the control group, the erythrocyte sedimentation rate (ESR), C-reaction protein (CRP) levels, and the daily average dose of glucocorticoid in 1 year in the infected group were higher than those in the control group. And those differences were statistically significant(P < 0.05). There were no significant differences in gender, age, disease duration, disease activity score, white blood cell (WBC), platelet (PLT), hemoglobin (Hb), immunoglobulin G (IgG), complement (C), Anti cyclic citrullinated peptide antibody (anti-CCP), CD4+T cell count, and immunosuppressant use (P > 0.05). Multivariate Logistic regression analysis showed that CRP levels(OR=1.016, 95%CI:1.002-1.031) and the daily average dose of glucocorticoid in 1 year(OR=1.229, 95%CI:1.066-1.418)were the independent risk factors of RA complica-ted with tuberculosis infection. CONCLUSION: RA patients with tuberculosis infection are mainly phthisis. The clinical manifestations of RA combined with tuberculosis infection are lack of specificity, and the chest imaging features of pulmonary tuberculosis are diverse, which are easy to be misdiagnosed. CRP levels and the daily average dose level of glucocorticoid in 1 year were risk factors for RA and tuberculosis infection.

The medial compartment and patellofemoral joint degenerate more severely in early stage knee osteoarthritis: a cross-sectional study.

OBJECTIVE: The purpose of this study was to compare the differences of degenerative characteristics of medial, lateral regions, femoral, patellar, and tibia parts of the knee joint in the early stage of knee osteoarthritis (OA). PATIENTS AND METHODS: A total of 66 patients with early-stage knee OA and 22 healthy volunteers who have no knee-related clinical symptoms were enrolled in this cross-sectional study. T2 mapping and 3D dual-echo images were acquired with a 3.0T MR scanner. The degenerative changes of the articular cartilage were quantified by a T2 mapping and cartilage thicknesses analysis. Any structural changes were conducted using the Whole Organ Magnetic Resonance Imaging Score (WORMS). RESULTS: In patients with knee OA, the thicknesses of medial cartilages were significantly thinner than lateral ones (2.13 mm vs. 2.34 mm, p<0.0001), but with higher T2 values (40.38 ms vs. 38.4 ms, p<0.0001) and WORMS scores (12.12 vs. 0.47, p=0.004). No significant differences were observed between medial and lateral cartilage in the healthy volunteers. The T2 values of the femoral (p<0.001) and patellar (p=0.012) cartilages of OA patients were higher than that of the healthy controls. Within OA group, the T2 values of femoral (p<0.0001) and patellar (p<0.0001) cartilages were higher than tibial ones. Moreover, the WORMS scores of femoral (p=0.001) and patellar (p<0.0001) cartilages were higher than that of the tibial ones. CONCLUSIONS: This study demonstrates that the medial compartment and patellofemoral knee joint degenerate more severely in patients with early-stage knee OA.

Skp2/p27 axis regulates chondrocyte proliferation under high glucose induced endoplasmic reticulum stress.

OBJECTIVE: Diabetes mellitus is closely related to osteoarthritis (OA) and may be an independent risk factor for the development of OA. As one of the main characteristics of diabetes, endoplasmic reticulum (ER) stress resulting from glucose metabolism disorder is one of the main causes of cartilage degeneration. The aim of our study is to illuminate the effect of high glucose to chondrocytes (CHs) and the role of Skp2 in high-glucose induced ER stress in CHs. PATIENTS AND METHODS: We compared the ER stress status between healthy and diabetic OA cartilage using Western blot and quantitative reverse-transcription polymerase chain reaction (RT-PCR) methods. Different concentration of glucose was used to culture CHs for both 24 h and 72 h. Furthermore, Tunicamycin (TM) and 4-Phenylbutyric acid (4-PBA) were used to mediate ER stress of CHs, and human recombinant Skp2 protein was used to promote Skp2 expression. CH viability was determined by CCK8 assay, and cell proliferation was determined by flow cytometry. Western and RT-PCR were performed to measure related gene expression. RESULTS: ER stress makers GADD34, GRP78, and MANF were upregulated in diabetic OA cartilage. The long-term high glucose increased GADD34, GRP78, and MANF expression, but decreased collagen II and proliferation of CHs, and Skp2 expression was negative related to the ER stress level. Additionally, Skp2 overexpression partly reversed ER stress-induced collagen II and proliferation suppression by the suppression of p27 expression. CONCLUSIONS: High glucose raises the ER stress in CHs and overexpression of Skp2 promotes CH proliferation under high glucose treatment.

Over-expression of DJ-1 attenuates effects of curcumin on colorectal cancer cell proliferation and apoptosis.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Over-expression of DJ-1 attenuates effects of curcumin on colorectal cancer cell proliferation and apoptosis, by H. Shang, T. Wang, F. Shang, M. Li, Y. Luo, K.-M. Huang, published in Eur Rev Med Pharmacol Sci 2019; 23 (7): 3080-3087-DOI: 10.26355/eurrev_201904_17591-PMID: 31002157" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17591.

Glutamine protects myocardial ischemia-reperfusion injury in rats through the PI3K/Akt signaling pathway.

OBJECTIVE: To study the protective mechanism of glutamine (Gln) on myocardial ischemia-reperfusion (IR) injury in rats through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. MATERIALS AND METHODS: A total of 30 healthy SD rats weighing 200-300 g were used in this experiment. They were randomly divided into 3 groups: sham group (n=10), myocardial IR injury group (IR group, n=10), IR+Gln group (n=10). The protein expression levels of phosphorylated Akt (p-Akt), total Akt (t-Akt), phosphorylated mammalian target of rapamycin (p-mTOR), mTOR, proliferating cell nuclear antigen (PCNA), P21, and Tubulin were determined by Western blotting (WB). Quantitative Polymerase Chain Reaction (qPCR) was applied to detect the messenger ribonucleic acid (mRNA) levels of Akt and mTOR. 3-(4,5)-dimethylthiazol(-z-y1)-3,5-diphenyl tetrazolium bromide (MTT) test was utilized to examine the proliferation ability of cardiomyocytes in vitro. Besides, the contents of the inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) were measured via enzyme-linked immunosorbent assay (ELISA). Cell apoptosis in each group was examined through Hoechst staining. RESULTS: Compared with those in the sham group, ratios of p-AKT/AKT, p-mTOR/mTOR, and the level of PCNA extremely significantly decreased, but the level of P21 notably increased in IR group (p<0.01). In comparison with those in the IR group, ratios of p-AKT/AKT, p-mTOR/mTOR, and the level of PCNA were remarkably raised, while the level of P21 was remarkably reduced in IR+Gln group (p<0.05). QRT-PCR results manifested that there were no significant differences in the mRNA levels of Akt and mTOR among the three groups [no significant difference (NS)]. Moreover, the cell proliferation ability in IR group was remarkably lower than that in the sham group (p<0.01), while it was enhanced in the IR+Gln group compared with that in the IR group (p<0.05). Additionally, IR group had significantly elevated expression levels of TNF-α and IL-6 compared with the sham group (p<0.01), whereas the IR+Gln group had notably decreased expression levels of TNF-α and IL-6 compared with IR group (p<0.05). In comparison with that in the sham group, the apoptosis in IR group was significantly raised (p<0.01), and compared with that in the IR group, the apoptosis in the IR+Gln group prominently decreased (p<0.05). The contents of the inflammatory cytokines, TNF-α, and IL-6 presented the same trends among the three groups. CONCLUSIONS: Gln activates the PI3K/Akt signaling pathway by increasing the levels of p-AKT and p-mTOR. Gln can increase the PCNA level and reduce the P21 level, so as to enhance the proliferation ability of cardiomyocytes. Besides, Gln reduces the levels of inflammatory cytokines, TNF-α, and IL-6, and inhibits cell apoptosis. Finally, Gln can protect cells from myocardial IR injury by activating the PI3K/Akt signaling pathway.

Inhibition of microRNA-875-5p promotes radioiodine uptake in poorly differentiated thyroid carcinoma cells by upregulating sodium-iodide symporter.

BACKGROUND AND AIM: Poorly differentiated thyroid carcinoma (PDTC) is an endocrine malignancy that is challenging to treat due to its limited radioiodine uptake. microRNAs (miRNAs or miRs) have been shown to be useful in treating many types of tumors, including PDTC. This study aims to evaluate the potential effect of miR-875-5p on the radioiodine uptake of PDTC and to clarify the underlying mechanisms. METHODS: Expression of miR-875-5p and sodium-iodide symporter (NIS) in tissues and cell lines was determined using RT-qPCR. The binding relationship between miR-875-5p and NIS was predicted through in silico analysis and verified by dual-luciferase reporter gene assay. A series of miR-875-5p mimic, miR-875-5p inhibitor, shRNA against NIS, and overexpressed NIS plasmids were introduced into PDTC cells. We then evaluated the cell viability, colony formation, apoptosis, and radioiodine uptake of each PDTC sample via CCK-8 assay, clonogenic assay, flow cytometry, and γ counter, respectively. RESULTS: miR-875-5p was found to be highly expressed, but NIS was poorly expressed in DTC tissues and PDTC cell lines. NIS was verified to be a target gene of miR-875-5p. Upregulation of miR-875-5p was found to induce PDTC cell proliferation, and reduce apoptosis and radioiodine uptake in vitro through down-regulation of NIS. In an in vivo orthotopic model, the enhancement of miR-875-5p led to the reduction of NIS expression and radioiodine uptake in the thyroid tumors. CONCLUSIONS: Altogether, the findings of the current study suggest that down-regulated miR-875-5p expression could promote its target gene NIS to increase radioiodine uptake in PDTC, constituting a preventive strategy against PDTC.

Grey matter abnormalities in Parkinson's disease: a voxel-wise meta-analysis.

BACKGROUND AND PURPOSE: The pathophysiology of Parkinson's disease (PD) remains unclear. Voxel-based morphometry (VBM) detects local structural differences in brain tissue such as grey matter volume (GMV) between groups, which is helpful in understanding the pathophysiology of PD. Published VBM studies of GMV changes in PD have shown inconsistent results. Therefore, a voxel-wise meta-analysis of VBM studies was conducted to detect consistent GMV changes in PD. METHODS: The published literature was searched comparing whole-brain GMV between PD patients and healthy controls (HCs) using VBM. Coordinates were extracted for the clusters of significant GMV differences between PD patients and HCs. The meta-analysis was performed by seed-based d mapping software. RESULTS: A total of 63 studies with 2867 PD patients and 1990 HCs were included. Significant GMV reductions in some brain regions were detected in PD patients, which were involved in the basal ganglia, theory of mind, vocal and visual networks. These findings remained largely unchanged in the jackknife sensitivity analysis, and no significant heterogeneity or publication bias was detected. CONCLUSIONS: Parkinson's disease patients have GMV reductions in a number of brain regions involved in specific networks. These findings provide morphological evidence for the pathophysiology of PD.

Cooperativity and Steep Voltage Dependence in a Bacterial Channel.

This paper reports on the discovery of a novel three-membrane channel unit exhibiting very steep voltage dependence and strong cooperative behavior. It was reconstituted into planar phospholipid membranes formed by the monolayer method and studied under voltage-clamp conditions. The behavior of the novel channel-former, isolated from Escherichia coli, is consistent with a linearly organized three-channel unit displaying steep voltage-gating (a minimum of 14 charges in the voltage sensor) that rivals that of channels in mammalian excitable membranes. The channels also display strong cooperativity in that closure of the first channel permits the second to close and closure of the second channel permits closure of the third. All three have virtually the same conductance and selectivity, and yet the first and third close at positive potentials whereas the second closes at negative potentials. Thus, is it likely that the second channel-former is oriented in the membrane in a direction opposite to that of the other two. This novel structure is named "triplin." The extraordinary behavior of triplin indicates that it must have important and as yet undefined physiological roles.