Objectives: Antihypertensive therapy is effective to control blood pressure (BP) and to prevent cardiovascular events, but the further treatment strategies for patients who cannot achieve goal BP with low-dose monotherapy is still under dispute. Our study investigates the effects of high-dose amlodipine and valsartan and their low-dose combination on blood pressure variability (BPV) and pulse wave velocity (PWV) to provide references for clinical medication.

Materials and Methods: This study was a prospective, randomized, parallel, case-controlled trial performed in a medical center. A total of 134 outpatients newly diagnosed with essential hypertension or receiving low-dose monotherapy were enrolled and 119 completed the trial. They were randomized into amlodipine 10 mg group (n = 40), valsartan 160 mg group (n = 38) and amlodipine 5 mg + valsartan 80 mg (n = 41) in a 1:1:1 allocation ratio for a 10-week treatment. Demographic data and laboratory indicators were collected at the randomization and 10 weeks after the treatment. The 24-hour ambulatory BP and brachial-ankle PWV were also monitored.

Results: All therapies reduced systolic and diastolic BP (P < 0.05). The 24-hour systolic BPV was significantly decreased in amlodipine and combination groups (3.55 +/- 2.57, 4.11 +/- 2.20 versus 2.23 +/- 2.54 mm Hg, P < 0.05). The effects on diastolic BPV differed between different treatments. PWV was lowered by 3 antihypertensive schemes; the degree of which from strongest to weakest were valsartan, combination and amlodipine (228.87 +/- 60.41 versus 152.49 +/- 49.25 versus 99.35 +/- 35.57 cm/second, P < 0.01).

Conclusions: All further strategies can effectively control BP. The combination treatment reduces both BPV and PWV noticeably, whereas double-dose amlodipine achieves the greatest BPV decrease and valsartan is best in controlling PWV.

Statement of problem. Indirect composite resins (ICR) are promising alternatives as veneering materials for zirconia frameworks. The effects of core-to-dentin thickness ratio (C/Dtr) on the mechanical property of bilayered veneer ICR/yttria-tetragonal zirconia polycrystalline (Y-TZP) core disks have not been previously studied.

Purpose. The purpose of this in vitro study was to assess the effects of C/Dtr on the biaxial flexural strength, reliability, and fracture mode of bilayered veneer ICR/ Y-TZP core disks.

Material and methods. A total of 180 bilayered 0.6-mm-thick composite resin disks in core material and C/Dtr of 2:1, 1:1, and 1:2 were tested with either core material placed up or placed down for piston-on-3-ball biaxial flexural strength. The mean biaxial flexural strength, Weibull modulus, and fracture mode were measured to evaluate the variation trend of the biaxial flexural strength, reliability, and fracture mode of the bilayered disks with various C/Dtr. One-way analysis of variance (ANOVA) and chi-square tests were used to evaluate the variation tendency of fracture mode with the C/Dtr or material placed down during testing (alpha=.05). Light microscopy was used to identify the fracture mode.

Results. The mean biaxial flexural strength and reliability improved with the increase in C/Dtr when specimens were tested with the core material either up and down, and depended on the materials that were placed down during testing. The rates of delamination, Hertzian cone cracks, subcritical radial cracks, and number of fracture fragments partially depended on the C/Dtr and the materials that were placed down during testing.

Conclusion. The biaxial flexural strength, reliability, and fracture mode in bilayered structures of Y-TZP core and veneer ICR depend on both the C/Dtr and the material that was placed down during testing.

The stability of the mercury ion mediated dU-Hg-II-dU pair depends on substituents introduced at the 5-position of the pyrimidine moiety. To this end, a series of oligonucleotides were synthesized with dU modification in central position. Common and new phosphoramidites were utilized. Hybridization experiments provided 12-mer duplexes with non-canonical "dU-dU" pairs. In most cases Hg2+ stabilizes duplexes by metal ion mediated base pair formation identified by higher duplex melting. Among the three types of dU derivatives incorporated in duplex DNA those with small aliphatic side chains have only a minor impact on the stability of the mercury-mediated base pair, while those with a triple bond in the side chain show hysteresis during duplex heating and cooling cycle implying triple bond interaction with mercury ions. Formation of metal ion mediated base pairs is blocked by space occupying aromatic side chains by side chain-helix stacking interactions. These interactions are too strong to permit mercury ion mediated base pair formation and drive the uridine N(3) acceptor atoms in an unfavorable pairing position.

Pulmonary cryptococcosis with pulmonary cavitation is rare, especially in immunocompetent cryptococcosis patients. We describe here a case of rapidly progressive pulmonary with cavitation in an immunocompetent woman. A 29-year-old woman had a routine chest X-ray as part of a routine examination. The chest X-ray showed pulmonary nodules. She was diagnosed as having bacterial pneumonia even though she had no symptoms and was treated with ampicillin orally. A chest X-ray was repeated 12 days later as follow-up which showed an increase in the nodules. She continued to be asymptomatic and had a normal lung examination. Her complete blood count revealed a normal white blood cell count and her anti-human immunodeficiency virus test was normal, as were her immunoglobulin levels and CD4 counts. She had a computed tomography (CT) scan of the lungs that showed two pulmonary nodules, one with cavitation. She then underwent a CT guided needle biopsy of the cavitary lesion which revealed pulmonary cryptococcosis. A serum latex cryptococcal antigen test revealed a titer of 1:32. She was treated with fluconazole 400 mg IV daily for 7 days, followed by oral fluconazole 200 mg daily for a year. The cavitary lesion gradually disappeared and the nodules decreased in size. A follow-up CT 1 year later was normal. Although rarer cryptococcosis of the lungs with pulmonary cavitation can occur in otherwise healthy patients, requiring long term treatment to improve.

Tumor necrosis factor superfamily-15 (TNFSF15; VEGI; TL1A) is a negative modulator of angiogenesis for blood vessel homeostasis and is produced by endothelial cells in a mature vasculature. It is known to be downregulated by vascular endothelial growth factor (VEGF), a major regulator of neovascularization but the mechanism of this interaction is unclear. Here we report that VEGF is able to stimulate the production of two microRNAs, miR-20a and miR-31, which directly target the 3'-UTR of TNFSF15. Additionally, we show that two VEGF-stimulated cell growth signals, Erk and Akt, are responsible for promoting the expression of miR-20a and miR-31. Treatment of human umbilical vein endothelial cells (HUVECs) with Akt inhibitor LY294002 results in diminished miR20a and miR-31 production, while Erk inhibitor U0126 prevented VEGFstimulated expression of miR-20a but not that of miR-31. Furthermore, inactivation of either Erk or Akt signals restores TNFSF15 gene expression. In an angiogenesis assay, elevated miR-20a or miR-31 levels in HUVECs leads to enhancement of capillary-like tubule formation in vitro, whereas lowered miR-20a and miR-31 levels results in an inhibition. These findings are consistent with the view that miR-20a and miR-31 mediate VEGF-induced downregulation of TNFSF15. Targeting these microRNA molecules may therefore provide an effective approach to inhibit angiogenesis.

Here, the authors present a thermo-responsive shape memory polymer (SMP) foam that can be programmed to control the preosteoblast behavior by changing porous architecture during cell cultivation. The preosteoblast cells are seeded on the SMP foams with temporarily compressed pore structure. Results show that cells preferentially align along the pore length direction. After the pore recovery at 37 degrees C, cells remain attached and viable but change their topography in a tangential direction along the pore edge. This work indicates the shape-memory actuated porous structure in SMP foam can control the cell behavior. This may provide an effective method for studying cell responses to dynamic environment and facilitate the healthy and optimal development of tissue engineering.

Recent research has demonstrated that static magnetic fields (SMF) can generate an analgesic effect in different conditions. The present study explored effects of SMF on pain levels and expressions of P2X3 receptors in trigeminal ganglion (TG) in mice after experimental tooth movement (tooth movement induced by springs between teeth). Experiments were performed in male mice (body mass: 25-30g) and divided into SMF+force group, force group, and no force group. Exposure time was over 22h per day. Mouse Grimace Scale was used for evaluating orofacial pain levels during experimental tooth movement at 4h and 1, 3, 7, and 14 days. Meanwhile, expression levels of P2X3 receptors in the TG were evaluated by immunohistochemistry and western blotting at same time points. We finally found that during experimental tooth movement, pain levels of mice peaked at 3 days, and then decreased. While pain levels of mice were reduced in the SMF environment at 4h, 1 and 3 days, there was a significant difference at 1 and 3 days. Meanwhile, under the action of SMF, expression levels of P2X3 receptors in TG were significantly lower at 4h, 3 and 7 days. These results suggest that SMF can reduce pain levels in mice, and down-regulate P2X3 receptors in TG. Bioelectromagnetics. 38:22-30, 2017. (c) 2016 Wiley Periodicals, Inc.

ObjectiveThis study examined the pattern of adjunctive antidepressant use in schizophrenia patients and its demographic and clinical correlates in a nationwide survey in China.

MethodsFourteen thousand and thirteen patients in 45 Chinese psychiatric hospitals or centers were interviewed (4,486 in 2002, 5,288 in 2006, and 4,239 in 2012). Patients' sociodemographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. Chi-square test, independent-samples t test, Mann-Whitney U test, and multiple logistic regression analysis were used in data analyses.

ResultsAntidepressant use was found in 5.2% of the study population with 4.6% in 2002, 4.3% in 2006, and 6.9% in 2012, respectively. A significant increase in use from 2006 to 2012 was found (p<.001). Multiple logistic regression analyses in the whole population revealed that patients receiving adjunctive antidepressants were more likely to be outpatients in tertiary referral centers (level-III hospitals) and who had an earlier age of onset, less severe global illness, but more depressive symptoms. They were less likely to receive first-generation antipsychotics but more likely to receive benzodiazepines (R-2=0.255, p<.001).

ConclusionsDespite an increasing trend, the frequency of antidepressant use in schizophrenia in China was considerably lower than in Western countries. The benefits and risks associated with concomitant use of antidepressants in schizophrenia need to be studied further.

Several imaging modalities have been widely applied for the detection of cancer and its pathological activity in combination with probes capable of improving the contrast between healthy and cancerous tissues. Biocompatible polymeric nanoassemblies have been developed for precise detection of malignant tumors by enhancing the selectivity and sensitivity of the imaging. Exploiting the compartmentalized structure of the nanoassemblies advantageously allows delivering both imaging and therapeutic agents for cancer multifunctional imaging and theranostics, i.e., the combination of therapy and diagnosis tool on a single platform. Thus, nanoassemblies have high potential not only for cancer molecular imaging but also for tracing nanoparticles in biological systems, studying their biological pathways, gathering pathological information, monitoring therapeutic effects, and guiding pinpoint therapies. In this review, polymeric nanoassemblies for optical imaging, magnetic resonance imaging, multifunctional imaging, and image-guided therapy, emphasizing their role in cancer diagnosis and theranostics are highlighted.

The high absorption rate of transplanted fat has limited the application of autogenous fat grafts in the clinical setting. Therefore, this study aimed to evaluate the effects of platelet-rich plasma (PRP) and adipose-derived stem cells (ASCs) on fat regeneration by investigating the impact of PRP and conditioned medium on the biological characteristics of ASCs. Fat grafts were prepared with ASCs at densities of 10(7)/ml, 10(6)/ml, 10(5)/ml, 10(4)/ml and 0/ml with and without PRP and injected subcutaneously into nude mice. Liquid overflow method, haematoxylin and eosin staining, and immunohistochemical analyses were used to examine the fat grafts. The residual fat volume of the 10(5)/ml ASC+PRP group was significantly higher than that of other treatment conditions after 90days. Furthermore, histological examination revealed that in 10(5)/ml ASCs-treated grafts normal adipocyte area and capillary formation were increased dramatically compared with other treatment conditions. It is concluded that fat grafts consisting of PRP and 10(5)/ml ASCs constitute an ideal transplant strategy, which may result in decreased absorption and accelerated fat regeneration. This simple and reliable method could provide a valuable and needed tool in plastic and reconstructive surgery. Copyright (c) 2014 John Wiley & Sons, Ltd.

The purpose of the current study was to compare and investigate the effect of fixed and individual valgus correction angle (VCA) on postoperative alignment restoration. It is hypothesized that individual VCA would be more accurate than fixed VCA in postoperative limb alignment restoration.

Four hundred and fifty-two patients with 546 consecutive uncomplicated primary total knee arthroplasties performed by a single surgeon, with 302 knees that had individual VCA (group A) and 244 knees that had fixed 5A degrees VCA (group B), were enroled in this study. Preoperative and postoperative full-length standing hip-to-ankle radiographs were used to assess limb alignment. Postoperative hip-knee-ankle angle (theta), femoral component angle (alpha) and tibial component angle (beta) were measured and compared between the two groups.

Mean postoperative theta angle and alpha angle were 178.9A degrees (SD 1.3A degrees) and 89.1A degrees (SD 1.1A degrees) in the group A, whereas they were 177.8A degrees (SD 1.9A degrees) and 87.9A degrees (SD 1.5A degrees) in the group B. There were significant differences in both parameters between the two groups (p = 0.021 and 0.016, respectively). Mean postoperative beta was 89.8A degrees (SD 1.2A degrees) in the group A and 89.7A degrees (SD 1.3A degrees) in the group B, and no significant difference was detected. There were 114 (37.7 %), 221 (73.2 %) and 265 (87.7 %) knees that had restoration of mechanical axis to +/- 1A degrees, +/- 2A degrees, +/- 3A degrees of neutral, respectively, and 37 (12.3 %) outliers (>+/- 3A degrees) in the group A, whereas there were 48 (19.7 %), 122 (50.0 %) and 170 (69.7 %) knees that had restoration of mechanical axis to +/- 1A degrees, +/- 2A degrees, +/- 3A degrees of neutral, respectively, and 74 (30.3 %) outliers in the group B. Group A had a higher percentage of restoration of limb alignment and fewer outliers than those in the group B, and this difference was statistically significant (p < 0.001).

The results from the present study demonstrated that individual VCA for distal femoral resection could enhance the accuracy of postoperative limb alignment restoration compared with fixed VCA. For clinical relevance, individual VCA should be recommended for routine use in all patients in order to achieve the expected postoperative neutral limb alignment and reduce the risk of postoperative malalignment due to the planning error of a fixed VCA.

Prospective comparative study, Level II.

Purpose The aim of this study was to combine intra-articular and peri-articular with wound infiltration analgesia (multi-site infiltration analgesia, MIA) for patients undergoing total knee arthroplasty (TKA) and compare its pain management and early rehabilitation effect with the commonly used nerve block including adductor cannel block (FNB) and femoral nerve block (ACB).

Method We conducted a prospective randomized controlled trial and 77 patients were included for analysis. The patients were randomized over three groups. The first group (26 patients) received multi-site infiltration analgesia (MIA group), the second group (27 patients) received femoral nerve block (FNB group), and the third group (24 patients) received adductor cannel block (ACB group).

Results MIA showed better pain control at rest during the first 12 hours (p < 0.05 respectively) and less opioid consumption after operation than the other two groups (p < 0.05, respectively), but ACB and FNB revealed similar outcomes (p > 0.05). At the same time, there are no significant differences in pain score with activity, vital signs, and occurrence of complication (p > 0.05, respectively) among the three groups. When evaluated the early rehabilitation, MIA and ACB had similar outcomes on post-operative muscle strength (p > 0.05), but they showed better quadriceps strength when compared FNB (p < 0.05). Although the knee ROM of the patients with FNB showed better results (p < 0.05), their ambulation ability was inferior to those in MIA group (p < 0.05 and ACB group (p < 0.05) early after the operation, besides, MIA patients were superior to ACB patients (p < 0.05). Furthermore, MIA spent less time on operation and post-operative hospital stays when compared with FNB and ACB (p < 0.05, respectively), while the ACB and FNB were without significant difference (p < 0.05, respectively).

Conclusion ACB was not inferior to FNB on pain control, but it was better on early mobilization. However, MIA that combine intra-articular and peri-articular with wound infiltration analgesia after TKA was more effective on pain control at rest, with better efficacy on early rehabilitation and easier to perform when compared with these commonly used nerve block. We recommended our MIA for pain relief and fast rehabilitation after TKA.

We aimed to report surgical outcomes in female urethral diverticula and to investigate the risk factors for diverticula recurrence.

A total of 66 patients underwent urethral diverticulectomies from January 2009 to October 2015 at out institution. Patient and diverticula characteristics were collected. Mean follow-up was 28.8 months (range 4-85 months). Recurrence was defined as requiring a repeat diverticulectomy.

Mean age was 44.9 years. Mean duration of symptoms was 28.1 months. Seven cases had previous urethral surgeries. Mean diverticula size was 2.8 cm. Main clinical symptoms included dribbling (n = 41), vaginal mass (n = 41), dysuria (n = 33), frequency/urgency (n = 29), infection (n = 24), stress urinary incontinence (SUI) (n = 20) and dyspareunia (n = 8). 10 cases had proximal diverticula, 10 cases had multiple diverticula, and 35 cases had horseshoe/circumferential diverticula. Postoperatively, the recurrence rate was 19.7 %. Preoperative SUI disappeared in 14 cases, and de novo SUI was developed in six cases. One case developed urethral stricture, and no cases reported urinary fistula. Among 60 cases with pathological results, neoplastic change was seen in one case (1.7 %). Besides, atypical hyperplasia (n = 2) and metaplasia (n = 3) were observed. Univariate analysis suggested that age, duration, follow-up, diverticula size and diverticula shape were not associated with surgical outcomes. Patients with multiple diverticula (p = 0.032), proximal diverticula (p = 0.042) and those with previous urethral procedures (p = 0.004) were at risk of recurrent diverticula confirmed by multivariate logistic regression analysis.

The surgical outcomes of urethral diverticulectomies were acceptable. Multiple diverticula, proximal diverticula and previous urethral surgery were three independent risk factors for recurrent diverticula.

Parkinson's disease (PD) with akinetic rigidity (PDAR) is more likely to develop cognitive deficits compared to PD with tremor-dominant symptoms (PDTD). The default mode network (DMN) is highly relevant for cognitive processes, so this study tested the functional connectivity (FC) of DMN in cognitively unimpaired PDAR patients. Resting-state fMRI data were collected in 21 cognitively unimpaired early stage drug-naive patients with PDAR and 21 healthy controls (HC). PD patients were matched closely to HCs for demographic and cognitive variables. FC of DMN was evaluated by seed-based correlation approach. Compared to HCs, despite comparable cognitive performance and no statistically discernible GM volume differences, a disruption in the DMN of PDAR subjects was detected. A decreased FC of DMN was found, specifically prominent in the posterior DMN. We also found a significantly increased FC of the anterior DMN. Three parts of left medial prefrontal regions (anterior, ventral, and dorsal) had significantly increased FC with the cerebellum. In addition, increased FC values of the anterior and ventral parts were negatively correlated with cognitive scores. An evident decline of FC of posterior DMN and enhanced compensatory FC of anterior DMN suggested an early functional disruption of DMN in PDAR prior to clinical evidence of cognitive impairment. It could be hypothesized that the dysfunction of DMN connectivity may have a role in the development of cognitive decline in PD. However, further longitudinal studies are warranted to understand the underlying neural mechanisms and their relevance to clinical and cognitive outcomes in PDAR subtype.

Purpose Circular RNAs (circRNA) represent a novel class of widespread and diverse endogenous RNAs that regulate gene expression in mammals. microRNA-7 (miR-7) is a well-demonstrated suppressor of hepatocellular carcinoma (HCC). Recent studies have showed that one such circRNA, ciRS-7 (also termed as Cdr1as) was the inhibitor and sponge of miR-7 in the embryonic zebrafish midbrain and islet cells. However, the relationships among ciRS-7, miR-7 and clinical features of HCC remain to be clarified.

Methods Expression levels of ciRS-7, miR-7 and three miR-7-targeted mRNAs in 108 pairs of HCC and their matched non-tumor tissues were examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The protein production of these three miR-7-targeted mRNAs was further verified by Western blot. The relationship between ciRS-7 level and clinicopathological features as well as the recurrence of HCC patients was analyzed. The univariate and multivariate logistic regression analyses were used to detect the risk factors of hepatic microvascular invasion (MVI). The correlation among ciRS-7, miR-7 and miR-7-targeted mRNAs was evaluated using Spearman's correlation test.

Results There was no significant difference of ciRS-7 expression levels between the HCC tissues and the matched non-tumor tissues (0.67 +/- 1.49 vs. 0.44 +/- 0.45, p = 0.13), and the ciRS-7 levels in more than half of HCC tissues (65 out of 108, 60.2 %) were down-regulated when compared with their matched non-tumor tissues. However, the expression of ciRS-7 was significantly correlated with the following three clinicopathological characteristics of HCC patients: age <40 years (p = 0.02), serum AFP >= 400 ng/mu l (p < 0.01) and hepatic MVI (p = 0.03). Meanwhile, up-regulated ciRS-7 expression was not only an independent risk factor of hepatic MVI but also had a capable predictive ability for MVI (AUC = 0.68, p = 0.001) at the cut-off value of 0.135. Furthermore, the expression of ciRS-7 in HCC tissues with concurrent MVI was inversely correlated with that of miR-7 (r = -0.39, p = 0.007) and positively related with that of two miR-7-targeted genes [PIK3CD (r = 0.55, p < 0.001) and p70S6K (r = 0.34, p = 0.021)]. In addition, the median recurrent time of patients from higher ciRS-7 level group was shorter than that of lower ciRS-7 group (18 vs. 25 months), but no significant difference was observed (p = 0.38).

Conclusions The expression levels of ciRS-7 were comparable between HCC and matched non-tumor tissues. However, the highly ciRS-7 expression in HCC tissues was significantly correlated with hepatic MVI, AFP level and younger age and thus partly related with the deterioration of HCC. Especially, ciRS-7 was one of the independent factors of hepatic MVI. These data suggested that ciRS-7 may be a promising biomarker of hepatic MVI and a novel therapy target for restraining MVI.

In recent years, submucosal tunneling endoscopic resection (STER) has emerged as a novel therapeutic endoscopic technique for upper gastrointestinal submucosal tumors (SMTs). The aim of this study was to evaluate the safety and efficacy of STER for upper gastrointestinal SMTs.

A systematic search of both English and Chinese databases was performed until November 15, 2015. Complete resection and en bloc resection rates were considered the primary outcome measures. Prevalence of complications was considered the secondary outcome measure. A random-effects model was used to generate conservative estimates of the prevalence of the main outcome variables. All data analyses were performed using Meta-Analyst software (version beta 3.13).

A total of 28 studies were included in the final meta-analysis. The pooled complete resection and en bloc resection rates were 97.5 % (95 % CI 96.0-98.5 %) and 94.6 % (95 % CI 91.5-96.7 %), respectively. The common complications associated with STER were air leakage symptoms and perforation. The pooled prevalence of air leakage symptoms was 14.8 % (95 % CI 10.5-20.5 %) for subcutaneous emphysema and pneumomediastinum, 6.1 % (95 % CI 4.0-9.0 %) for pneumothorax and 6.8 % (95 % CI 4.7-9.6 %) for pneumoperitoneum. Additionally, the pooled prevalence of perforation was 5.6 % (95 % CI 3.7-8.2 %). Only a few cases of bleeding were reported in two studies.

STER is a highly feasible and safe treatment option for upper gastrointestinal SMTs.

The aims of this study are to characterize the biological disease-modifying antirheumatic drug (bDMARD) usage patterns in real-life and examine the remission rate of rheumatoid arthritis (RA) patients receiving bDMARDs in routine clinical practice in China. Consenting RA patients (18 years) from 15 teaching hospitals and receiving marketed bDMARDs were included. In total, 802 patients (81.3 % women, 49.0 +/- 13.9 years) were included; 89.5 % were receiving a combination of bDMARDs and conventional synthetic DMARDs (csDMARDS), whereas 10.5 % were receiving bDMARD monotherapy. Etanercept (including EnbrelA (R) and local brand Yi Sai PuA (R) and QiangkeA (R)), tocilizumab, adalimumab, and infliximab were used by 66.6 %, 17.0 %, 7.5 %, and 6.6 % patients, respectively. Etanercept was used at a mean weekly dose of 38.2 +/- 15.6 mg for 25.5 +/- 47.0 weeks and tocilizumab at 94.5 +/- 21.9 mg for 4.7 +/- 7.5 weeks. Overall rate of remission was 12.6 %, 5.4 % , and 3.5 % based on DAS28, CDAI, and SDAI scores, respectively. Compared with patients receiving bDMARDs for < 3 months, those receiving bDMARDs for 3 months exhibited significantly lower DAS28 scores (p < 0.0001), and a significantly higher proportion of patients who received bDMARDs for 12 months achieved the treatment goal (remission or low disease activity, 62.5 % vs. 18.3 %, p < 0.0001). Patients receiving combination therapy with csDMARDs exhibited lower DAS28 scores than patients receiving bDMARD monotherapy (4.3 vs. 4.8, p = 0.011). This large-scale real-world study showed that bDMARD usage patterns in routine clinical practice in China were in accordance with international guidelines for RA management despite the short treatment duration. Longer duration of bDMARD usage and combination therapy showed a favored outcome of RA.

Epileptic seizures, the most common symptom accompanying glioma, are closely associated with tumor growth and patient quality of life. However, the association between glioma and glioma-related epilepsy is poorly understood. In fact, findings related to the location of epileptogenicity have been inconsistent in previous studies. We investigated seizure foci in patients with glioma and the corresponding association between glioma-related epilepsy and the tumoral and peritumoral microenvironment. Clinical characteristics, extracellular electrophysiology, immunohistochemistry, and western blots were conducted on 12 patients with glioma; nine patients had histories of preoperative seizures while three did not. Samples from included patients were used to identify seizure foci and mTOR pathway status. Electrophysiological recordings were conducted on 36 samples (tumor, peritumoral, and normal brain tissues) from 12 patients. Interictal-like discharges (ILDs) were observed in seven of nine peritumoral tissues obtained from patients with glioma that had experienced perioperative seizures. No ILDs were observed in any other sample groups. Western blots and immunohistochemistry for mTOR pathway proteins (mTOR and S6k) suggested that the mTOR pathway was activated in peritumoral tissues of patients with seizure history, but inactivated in patients without seizure history. Our results suggest that mTOR pathway expression in peritumoral tissues is associated with tumor-related seizures, thus providing a potential target for therapeutics aimed at simultaneously controlling gliomas and seizures.