Fourth People's Hospital of Changzhou

BACKGROUND: Epidemiological studies have repeatedly investigated the association between anxiety and hypertension. However, the results have been inconsistent. This study aimed to summarize the current evidence from cross-sectional and prospective studies that evaluated this association. METHODS: Seven common databases were searched for articles published up to November 2014. Cross-sectional and prospective studies that reported an association between the two conditions in adults were included. Data on prevalence, incidence, unadjusted or adjusted odds ratios or hazard ratios, and 95% confidence intervals (CIs) were extracted or calculated by the authors. The pooled odds ratio was calculated separately for cross-sectional and prospective studies using random-effects models. The Q test and I2 statistic was used to assess heterogeneity. A funnel plot and modified Egger linear regression test were used to estimate publication bias. RESULTS: The search yielded 13 cross-sectional studies (n=151,389), and the final pooled odds ratio was 1.18 (95% CI 1.02-1.37; P Q<0.001; I (2)=84.9%). Eight prospective studies with a total sample size of 80,146 and 2,394 hypertension case subjects, and the pooled adjusted hazard ratio was 1.55 (95% CI 1.24-1.94; P Q<0.001; I (2)=84.6%). The meta-regression showed that location, diagnostic criteria for anxiety, age, sex, sample size, year of publication, quality, and years of follow-up (for prospective study) were not sources of heterogeneity. CONCLUSION: Our results suggest that there is an association between anxiety and increased risk of hypertension. These results support early detection and management of anxiety in hypertensive patients.

AIM: This study aimed to determine whether circular RNA (circRNA) molecules in peripheral blood mononuclear cells (PBMCs) could be used as novel non-invasive biomarkers for major depressive disorder (MDD). MATERIALS & METHODS: Differentially expressed circRNAs were screened using an Arraystar Human CircRNA Array (which includes 13,617 human circRNAs) and qRT-PCR. Thirty MDD patients were randomly selected to retest the circRNA levels after 4-week and 8-week antidepressant regimens. RESULTS: Four differentially expressed circRNAs were identified between MDD patients and controls, and only down-regulated hsa_circRNA_103636 was significantly altered after the 8-week treatment in MDD patients. CONCLUSION: These results suggest that altered expression of hsa_circRNA_103636 in PBMCs is a potential novel biomarker for the diagnosis and treatment of MDD.

BACKGROUND: Diabetic retinopathy (DR) is a retinopathy resulting from diabetes mellitus (DM) which was classified into non-proliferative DR (NPDR) and proliferative DR (PDR). Without an early screening and effective diagnosis, patients with PDR will develop serious complications. Therefore, we sought to identify special serum microRNAs (miRNAs) that can serve as a novel non-invasive screening signature of PDR and test its specificity and sensitivity in the early diagnosis of PDR. METHODS: In total, we obtained serum samples from 90 PDR cases, 90 matched NPDR patients and 20 controls. An initial screening of miRNA expression was performed through TaqMan Low Density Array (TLDA). The candidate miRNAs were validated by individual reverse transcription quantitative real-time PCR (RT-qPCR) arranged in an initial and a two-stage validation sets. Moreover, additional double-blind testing was performed in 20 patients clinically suspected of having DR to evaluate the diagnostic value and accuracy of the serum miRNA profiling system in predicting PDR. RESULTS: Three miRNAs were significantly increased in patients with PDR compared with NPDR after the multiple stages. The areas under the receiver operating characteristic (ROC) curves of the validated three-serum miRNAs signature were 0.830, 0.803 and 0.873 in the initial and two validation sets, respectively. Combination of miR-21, miR-181c, and miR-1179 possessed a moderate ability to discrimination between PDR and NPDR with an area under ROC value of 0.89. The accuracy rate of the three-miRNA profile as PDR signature was 82.6%. CONCLUSIONS: These data provide evidence that serum miRNAs have the potential to be sensitive, cost-effective biomarkers for the early detection of PDR. These biomarkers could serve as a dynamic monitoring factor for detecting the progression of PDR from NPDR.

Dual-drug loaded pH-responsive hydrogels were prepared as a delivery system carrying, as exemplars, both anti-cancer and anti-bacterial agents for pH controlled drug release. The hydrogels were composed of poly(l-lactide)-co-polyethyleneglycol-co-poly(l-lactide) dimethacrylates (with various molecular weights of l-lactide oligomers) as a macromolecular crosslinker and copolymerized with acrylic acid and N-isopropylacrylamide. The biodegradability, biocompatibility and mechanical properties of the hydrogels were characterized with the hydrogels being nontoxic to cells, while showing a reversible >80% reduction in volume at pH 1.2 compared to pH 7.4. Drug release profiles showed differential release of tetracycline over doxorubicin at pH 1.2, with both drugs being released equally at pH 7.4. Biodegradability was tunable by altering the crosslinking density and pH, with the total degradation of the best gels observed within 2 weeks at pH 7.4.

The Systemic Inflammation Response Index (SIRI), based on peripheral lymphocyte, neutrophil, and monocyte counts, was recently investigated as a prognostic marker for several tumors. However, use of the SIRI has not been reported for nasopharyngeal carcinoma (NPC). We evaluated the prognostic value of the SIRI in primary and validation cohorts. We also established an effective prognostic nomogram for NPC based on clinicopathological parameters and the SIRI. The predictive accuracy and discriminative ability of the nomogram were determined using the concordance index (C-index) and a calibration curve and were compared with tumor-node-metastasis classifications. Our Kaplan-Meier survival analysis results showed that the SIRI was associated with the overall survival of patients with NPC in the primary and validation cohorts. The SIRI was identified to be an independent prognostic factor for NPC. In addition, we developed and validated a new prognostic nomogram that integrated clinicopathological factors and the SIRI. This nomogram can efficiently predict the prognosis of patients with NPC. The SIRI is a novel, simple and inexpensive prognostic predictor for patients with NPC. The SIRI has important value for predicting the prognosis of patients with NPC and developing individualized treatment plans.

Oxidative stress has been reported to serve an important role in the development and progression of diabetic nephropathy (DN). Epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells promotes renal fibrosis in DN, while the mechanism of reactive oxygen species (ROS)-mediated EMT is not fully understood. The aim of the present study was to investigate the effect of high glucose-induced ROS on the activation of the transforming growth factor (TGF)-1/phosphoinositide 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway in a normal rat kidney tubular epithelial cell line (NRK-52E) and rats with type 1 diabetes. In vitro, high glucose-stimulated ROS production resulted in increased TGF-1 expression as well as an increase in the Akt and mTOR phosphorylation ratio, resulting in EMT. When cells were pre-treated with ROS inhibitors, changes in TGF-1, Akt and mTOR were significantly ameliorated. In vivo, diabetic rats experienced a significant decline in renal function and severe renal fibrosis compared with control rats at 8 weeks following streptozocin injection. Levels of malondialdehyde and TGF-1/PI3K/Akt/mTOR pathway activation were increased in the renal cortex of rats with diabetes compared with the control rats. Furthermore, renal fibrosis was further aggravated in DN compared with the control rats. The results of the present study suggest that ROS serves an important role in mediating high glucose-induced EMT and inhibits activation of the TGF-1/PI3K/Akt/mTOR pathway.

MicroRNAs (miRNA, miR) have been implicated as promising blood-based biomarkers for schizophrenia patients. This study aimed to clinically validate miRNA as potential schizophrenia biomarkers. Plasma levels of 10 miRNAs were analyzed using qPCR in a cohort of 61 schizophrenia patients and 62 normal controls, as well as 25 patients particularly selected for a six-week antipsychotic treatment course. Positive And Negative Syndrome Scale (PANSS), Global Assessment Scale (GAS) and Clinical Global Impression (CGI) were administered to assess the clinical symptoms. The results demonstrated that a panel of miRNAs consisting of miR-30e, miR-181b, miR-34a, miR-346 and miR-7 had significantly increased expression levels with significant combined diagnostic value (AUC:0.713; sensitivity:35.5%; specificity:90.2%). In response to pharmacological treatment, expression levels of miR-132, miR-181b, miR-432 and miR-30e were significantly decreased. In addition, the improvement of clinical symptomatology was significantly correlated with the changes of miR-132, miR-181b, miR-212 and miR-30e expression levels. Furthermore, the decreases of plasma levels of miR-132 and miR-432 were significantly greater in high-effect subgroup than those in low-effect subgroup after six-week treatment course. We conclude that miR-30e, miR-181b, miR-34a, miR-346 and miR-7 combined as a panel are potentially useful non-invasive biomarkers for schizophrenia diagnosis. Markers miR-132, miR-181b, miR-30e and miR-432 are potential indicators for symptomatology improvements, treatment responses and prognosis for schizophrenia patients.

Abstract Purpose To compare the long‐term clinical efficacy provided by intra‐articular injections of either Pure Platelet‐rich Plasma (P‐PRP) or sham saline to treat knee osteoarthritis (KOA). Methods This prospective, parallel‐group, double‐blind, multi‐center, sham‐controlled randomized clinical trial recruited participants with KOA from orthopedic departments at nine public hospitals (five tertiary medical centers, four secondary medical units) starting January 1, 2014, with follow‐up completed on February 28, 2021. Participants were randomly allocated to interventions in a 1:1 ratio. Data were analyzed from March 1, 2021, to July 15, 2021. Three sessions (1 every week) of P‐PRP or sham saline injected by physicians. The primary outcome was the Western Ontario and McMaster Universities Arthritis Index (WOMAC) at 3, 6, 12, 24, 60 months of follow‐up. Secondary outcomes included the International Knee Documentation Committee (IKDC) subjective score, visual analogue scale (VAS) score, intra‐articular biochemical marker concentrations, cartilage volume, and adverse events. Laboratory of each hospital analyzed the content and quality of P‐PRP. Results 610 participants (59% women) with KOA who received three sessions of P‐PRP ( n = 308, mean age 53.91 years) or sham saline ( n = 302, mean age 54.51 years) injections completed the trial. The mean platelet concentration in PRP is 4.3­fold (95% confidence interval 3.6–4.5) greater than that of whole blood. Both groups showed significant improvements in IKDC, WOMAC, and VAS scores at 1 month of follow‐up. However, only the P‐PRP group showed a sustained improvement in clinical outcome measurements at month 24 ( P &lt; 0.001). There were statistically significant differences between the P‐PRP and sham saline groups in all clinical outcome measurements at each follow‐up time point ( P &lt; 0.001). The benefit of P‐PRP was clinically better in terms of WOMAC‐pain, WOMAC‐physical function and WOMAC‐total at 6, 12, 24, and 60 months of follow‐up. No clinically significant differences between treatments were documented in terms of WOMAC‐stiffness at any follow‐up. A clinically significant difference favoring P‐PRP group against saline in terms of IKDC and VAS scores was documented at 6, 12, 24 and 60 months of follow‐up. At 6 months after injection, TNF‐α and IL‐1β levels in synovial fluid were lower in the P‐PRP group ( P &lt; 0.001). Tibiofemoral cartilage volume decreased by a mean value of 1171 mm 3 in the P‐PRP group and 2311 mm 3 in the saline group over 60 months and the difference between the group was statistically significant (intergroup difference, 1140 mm 3 , 95% CI − 79 to 1320 mm 3 ; P &lt; 0.001). Conclusions In this randomized clinical trial of patients with KOA, P‐PRP was superior to sham saline in treating KOA. P‐PRP was effective for achieving at least 24 months of symptom relief and slowing the progress of KOA, with both P‐PRP and saline being comparable in safety profiles.

Neuroligin-3 (NLGN3) is necessary and sufficient to promote glioma cell growth. The recruitment of Gi1/3 to the ligand-activated receptor tyrosine kinases (RTKs) is essential for mediating oncogenic signaling.

BACKGROUND The criteria for diagnosing depression are based on behavioral observation and self-reporting of symptoms by the patients or guardians without any biological validation of the disease. This study aimed to identify long non-coding RNAs (lncRNAs) in peripheral blood mononuclear cells (PBMCs) as robust and predictive biomarkers for diagnosis and therapy response in major depressive disorder (MDD). MATERIAL AND METHODS We used human lncRNA 3.0 microarray profiling (which covers 30,586 human lncRNAs), using PBMCs from five MDD patients and five controls. Differentially expressed lncRNAs in the PBMCs of MDD patients were identified, of which 10 candidate lncRNAs were selected for real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis in a larger cohort of 138 MDD patients and 63 healthy controls. Then among the 138 MDD patients who received standard antidepressant treatment, 30 were randomly selected for lncRNAs expression retesting and symptomatology assessments after three-weeks and six-weeks of antidepressant treatment. RESULTS Six lncRNAs (TCONS_00019174, ENST00000566208, NONHSAG045500, ENST00000517573, NONHSAT034045, and NONHSAT142707) were significantly downregulated in MDD patients compared to control patients, and the area under the receiver operator curve (ROC) of these six lncRNAs cases, combined, was 0.719 (95% confidence interval (CI): 0.617-0.821). There was no difference in the expression of these six lncRNAs based on gender (p>0.05) or age (p>0.05). CONCLUSIONS These results suggest that the combined expression of six lncRNAs in PBMCs may serve as a potential biomarker for diagnosis and therapy response of MDD in the clinical setting.

Bone marrow stem cells are able to repair infarcted human myocardium following intracoronary transplantation via the infarct-relative artery. However, traditional reperfusion strategies fail to open the artery in some patients, making effective delivery impossible. Our previous study demonstrated a safe and efficient approach to delivering bone marrow stem cells via a noninfarcted artery in an animal myocardial infarction model. The objective of the present study was to evaluate the safety and feasibility of autologous bone marrow mesenchymal stem cell transplantation via such an approach in patients with acute myocardial infarction (AMI). Sixteen patients with anterior AMI who had successfully undergone percutaneous coronary intervention (PCI) were enrolled in this pilot, randomized study. Three weeks after PCI, cultured bone marrow mesenchymal stem cells were injected into the myocardium via either the infarct-relative artery (left anterior descending branch artery, LAD) or a noninfarct-relative artery (right coronary artery, RCA). The safety and feasibility of the cell infusion were evaluated during the procedure and during 6 months of follow-up. In addition, 2D echocardiography, technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) and 18F-deoxyglucose single photon emission computed tomography were employed to examine cardiac function, myocardial perfusion, and viable cardiomyocytes, respectively, at day 4 after PCI and 6 months after the cell infusion. There were no arrhythmia and any other side-effects, including infections, allergic reactions or adverse clinical events, during, immediately after, or 6 months after cell transplantation. Cardiac function and myocardial perfusion had improved 6 months after PCI/bone marrow stem cells transplantation. Viable cardiomyocytes metabolism was detected in the infarcted areas in both groups after the cell infusion, as demonstrated by 18F-deoxyglucose. Intracoronary infusion of autologous bone marrow mesenchymal stem cells via a noninfarct-relative artery appears safe and feasible in the treatment of patients with AMI.

Gastric cancer is one of the most common malignancies globally; cancer stem cells (CSCs) are regarded as being at the root of tumor progression, and there is thus a need to identify potential drugs to target CSCs. The long non-coding RNA MALAT1 promotes epithelial-mesenchymal transition and angiogenesis in colorectal cancer, but it is unknown whether it affects the stemness of gastric cancer cells. Here, we found that knockdown (KD) of MALAT1 attenuated the stemness of non-adherent gastric cancer cell spheroids, as evidenced by a decrease in primary and secondary spheroid formation capacity and expression of stemness markers. In contrast, overexpression (OE) of MALAT1 enhanced the stemness of adherent gastric cancer cells. Notably, KD of MALAT1 enhanced radiosensitivity and chemosensitivity of gastric cancer cell spheroids. We report that MALAT1 directly binds to sox2 mRNA (which encodes a critical master pluripotency factor), enhances the mRNA stability and increases its expression; KD of sox2 partially reversed the effect of MALAT1 OE on the stemness of gastric cancer cells. Importantly, expression of MALAT1 and sox2 exhibited a positive correlation in clinical samples. Therefore, our results indicate the existence of a novel MALAT1-sox2 axis which promotes the stemness of gastric cancer cells and may be a potential target for gastric cancer.

Studies of the effects of low glycemic index (LGI) diets on gestational diabetes mellitus (GDM) have reported conflicting findings.The aim of the study was to evaluate the results of randomized controlled trials (RCTs) that investigated the effects of LGI diets with and without added dietary fiber (DF) on maternal and neonatal outcomes in GDM patients.We searched the MEDLINE, EMBASE, EBSCO, Springer, Ovid, and Cochrane Library databases for studies of the effects of LGI diets in GDM patients. We performed a meta-analysis of the effects of the LGI diets with and without added dietary fiber (DF) on GDM outcomes. Risk ratios (RR) and 95% confidence intervals (CIs) were calculated using random- and fixed-effects models.Five RCTs involving 302 participants were included in our meta-analysis. No statistically significant differences in the risks of cesarean section delivery, large for gestational age, and small for gestational age were observed. The risk of macrosomia in the LGI groups was significantly lower (RR = 0.27; 95% CI: 0.10-0.71; P = 0.008) than that in the control groups. Our subgroup analysis of the effects of DF showed that LGI diets with an increased level of DF, relative to the control diet, reduced the risk of macrosomia beyond that of the LGI diets alone (RR: 0.17 vs 0.47, respectively). The subgroup analysis also showed that LGI diets in which the level of DF was approximately equivalent to that in the control diets significantly reduced the risk of insulin usage (RR = 0.69; 95% CI: 0.52-0.92; P = 0.01).The LGI diets reduced the risk of macrosomia in GDM patients, and LGI diets with added DF reduced the risk of macrosomia further. The LGI diets with levels of DF approximately equivalent to that in the control diets reduced the risk of insulin usage in GDM patients.

BACKGROUND: Although Helicobacter pylori (H.pylori) is the dominant gastrointestinal pathogen, the genetic and molecular mechanisms underlying H.pylori-related diseases have not been fully elucidated. Long non-coding RNAs (lncRNAs) have been identified in eukaryotic cells, many of which play important roles in regulating biological processes and pathogenesis. However, the expression changes of lncRNAs in human infected by H.pylori have been rarely reported. This study aimed to identify the dysregulated lncRNAs in human gastric epithelial cells and tissues infected with H.pylori. METHODS: The aberrant expression profiles of lncRNAs and mRNAs in GES-1 cells with or without H.pylori infection were explored by microarray analysis. LncRNA-mRNA co-expression network was constructed based on Pearson correlation analysis. Gene Ontology (GO) and KEGG Pathway analyses of aberrantly expressed mRNAs were performed to identify the related biological functions and pathologic pathways. The expression changes of target lncRNAs were validated by qRT-PCR to confirm the microarray data in both cells and clinical specimens. RESULTS: Three hundred three lncRNAs and 565 mRNAs were identified as aberrantly expressed transcripts (≥2 or ≤0.5-fold change, P < 0.05) in cells with H.pylori infection compared to controls. LncRNA-mRNA co-expression network showed the core lncRNAs/mRNAs which might play important roles in H.pylori-related pathogenesis. GO and KEGG analyses have indicated that the functions of aberrantly expressed mRNAs in H.pylori infection were related closely with inflammation and carcinogenesis. QRT-PCR data confirmed the expression pattern of 8 (n345630, XLOC_004787, n378726, LINC00473, XLOC_005517, LINC00152, XLOC_13370, and n408024) lncRNAs in infected cells. Additionally, four down-regulated (n345630, XLOC_004787, n378726, and LINC00473) lncRNAs were verified in H.pylori-positive gastric samples. CONCLUSION: Our study provided a preliminary exploration of lncRNAs expression profiles in H.pylori-infected cells by microarray. These dysregulated lncRNAs might contribute to the pathological processes during H.pylori infection.

OBJECTIVE: This study was performed to determine whether repetitive transcranial magnetic stimulation (rTMS) combined with neuromuscular electrical stimulation (NMES) effectively ameliorates dysphagia and how rTMS protocols (bilateral vs. unilateral) combined with NMES can be optimized. METHODS: Sixty-four patients were randomly divided into four groups using a random distribution table: the sham rTMS plus NMES (Sham-rTMS/NMES), ipsilesional 10-Hz rTMS plus NMES (Ipsi-rTMS/NMES), contralesional 1-Hz rTMS plus NMES (Contra-rTMS/NMES), and bilateral rTMS plus NMES (Bi-rTMS/NMES) groups. Cortical excitability as measured by the amplitude of the motor evoked potential at the mylohyoid muscle cortical representative area, swallowing function as measured by the Standardized Swallowing Assessment, and the degree of dysphagia were evaluated at baseline, after the stimulation course, and at the 1-month follow-up. RESULTS: Bi-rTMS/NMES produced higher cortical excitability and better swallowing function recovery. Compared with NMES alone, unilateral rTMS plus NMES had additional effects on cortical excitability and rehabilitation of dysphagia, but there were no differences between the Contra-rTMS/NMES and Ipsi-rTMS/NMES groups. No adverse events occurred. CONCLUSION: The combination of rTMS with NMES was superior to NMES alone in improving the recovery of post-stroke dysphagia, and the combination of bilateral rTMS with NMES was more effective than unilateral rTMS combined with NMES.

BACKGROUND AND AIMS: The effect of dapagliflozin (DAPA) on the prognosis of patients with acute myocardial infarction (AMI) is unclear. The present study was conducted to evaluate the association between DAPA administration and adverse events in patients with AMI undergoing percutaneous coronary intervention (PCI). METHODS: This single-center retrospective analysis study included a total of 786 patients with AMI from January 2019 to August 2021 who were or were not administered DAPA at discharge. The primary endpoint was the composite of major adverse cardiovascular events (MACE), including overall deaths, heart failure, nonfatal MI, nonfatal stroke, and unplanned repeat revascularization (URR). Differences in the triglyceride glucose (TyG) index and the atherogenic index of plasma (AIP) both during hospitalization and 12 months after discharge (if achievable) were also compared. RESULTS: During a median follow-up of 23 months, 130 patients had MACE (118 in the DAPA-free group and 12 in the DAPA group). Kaplan-Meier survival analyses revealed that the cumulative incidence of MACE (log-rank test, p = 0.009), heart failure (p = 0.003), nonfatal MI (p = 0.005), and URR (p = 0.031) was higher in the DAPA-free group. In addition, the multivariate Cox analysis showed that DAPA was significantly associated with the reduced risk of MACE (hazard ratio = 0.170, 95% confidence interval = 0.078-0.373, p < 0.001). Considering each specific adverse event, the DAPA-free group was associated with heart failure, nonfatal MI, and URR in multivariate Cox regression analyses. Stratification analyses suggested that DAPA has a strong protective effect in patients with AMI of advanced age with concomitant diabetes or those who are not on angiotensin receptor enkephalinase inhibitors. Furthermore, the TyG index and AIP of the patients 12 months after DAPA administration at discharge were significantly lower than those during hospitalization. CONCLUSIONS: DAPA is an independent protective factor against MACE and may provide incremental prognostic information in patients with AMI undergoing PCI.

Circular RNAs are a class of endogenous noncoding RNAs that play an important role in gene regulation. These RNAs are involved in the development and progression of various cancers, but their roles in gastric cancer have not yet been thoroughly elucidated. This study showed that hsa_circ_0000467 expression was higher in gastric cancer tissues than in corresponding adjacent tissues ( P &lt; 0.050) and that hsa_circ_0000467 expression levels were correlated with gastric cancer histological grade ( P &lt; 0.050). In addition, hsa_circ_0000467 was remarkably upregulated in gastric cancer cell lines ( P &lt; 0.001). Cell function experiments indicated that hsa_circ_0000467 downregulation decreased the proliferation and invasion ability of BGC‐823 and SGC‐7901 cells and the number of cells entering the G2/M phase. A direct binding interaction was detected between hsa_circ_0000467 and miR‐326‐3p by dual‐luciferase reporter assays. In addition, the results showed that inhibition of miR‐326‐3p reversed the decreases in the proliferation and invasion of BGC‐823 and SGC‐7901 cells caused by hsa_circ_0000647 downregulation. Inhibition of miR‐326‐3p also decreased the number of cells entering the G2/M phase and the expression of cyclin D1. In conclusion, hsa_circ_0000467 plays a regulatory role in the development and progression of gastric cancer by regulating miR‐326‐3p, and this circRNA may be a potential diagnostic marker and therapeutic target of gastric cancer.

Objective: To compare the outcomes of transarterial chemoembolization (TACE) combined with sorafenib versus TACE alone for treating patients with unresectable hepatocellular carcinoma (HCC). Methods: This retrospective analysis included all patients receiving either TACE plus sorafenib therapy or TACE alone for unresectable HCC between February 2008 and August 2015 at the First Affiliated Hospital of Soochow University, China. Propensity score matching (PSM) was carried out to reduce bias due to confounding variables. The primary outcome was overall survival (OS), calculated from the date of the first TACE treatment until the date of death of any cause. A multivariate Cox proportional hazards analysis was conducted to examine determinants of OS. Results: A total of 308 patients were included in the study: 61 receiving TACE plus sorafenib treatment and 247 receiving TACE monotherapy. The PSM cohort included 61 subjects receiving TACE plus sorafenib and 122 subjects receiving TACE alone. In the overall analysis that included all patients, the median OS in the combination group was significantly longer than that in the monotherapy group (29.0 7.2 vs. 14.9 1.1 months; P = 0.008). In the PCM cohort, the median OS was also significantly longer in the combination group (29.0 7.2 vs. 14.9 1.5 months; P = 0.018). Subgroup analysis revealed longer OS in patients receiving combination treatment in both the BCLC-B and BCLC-C subgroups (P < 0.05 for both). Multivariate analyses in the PSM cohort revealed that treatment methods (P = 0.003), number of nodules (P = 0.010), tumor size (P = 0.012), vascular invasion (P = 0.005), and number of TACE (P = 0.029) were independent prognostic factors of OS. The most common adverse events were hand-foot skin reaction (75.4%) and diarrhea (47.5%) in the combination group, and fatigue (19.0%) and liver dysfunction (18.2%) in the monotherapy group. There were no treatment-related deaths in either group.

IMPORTANCE: The outcome of older patients with acute myeloid leukemia (AML) remains unsatisfactory. Recent studies have shown that HLA-mismatched microtransplant could improve outcomes in such patients. OBJECTIVE: To evaluate outcomes in different age groups among older patients with newly diagnosed AML who receive HLA-mismatched microtransplant. DESIGN, SETTING, AND PARTICIPANTS: This multicenter clinical study included 185 patients with de novo AML at 12 centers in China, the United States, and Spain in the Microtransplantation Interest Group. Patients were divided into the following 4 age groups: 60 to 64 years, 65 to 69 years, 70 to 74 years, and 75 to 85 years. The study period was May 1, 2006, to July 31, 2015. EXPOSURES: Induction chemotherapy and postremission therapy with cytarabine hydrochloride with or without anthracycline, followed by highly HLA-mismatched related or fully mismatched unrelated donor cell infusion. No graft-vs-host disease prophylaxis was used. MAIN OUTCOMES AND MEASURES: The primary end point of the study was to evaluate the complete remission rates, leukemia-free survival, and overall survival in different age groups. Additional end points of the study included hematopoietic recovery, graft-vs-host disease, relapse rate, nonrelapse mortality, and other treatment-related toxicities. RESULTS: Among 185 patients, the median age was 67 years (range, 60-85 years), and 75 (40.5%) were female. The denominators in adjusted percentages in overall survival, leukemia-free survival, relapse, and nonrelapse mortality are not the sample proportions of observations. The overall complete remission rate was not significantly different among the 4 age groups (75.4% [52 of 69], 70.2% [33 of 47], 79.1% [34 of 43], and 73.1% [19 of 26). The 1-year overall survival rates were 87.7%, 85.8%, and 77.8% in the first 3 age groups, which were much higher than the rate in the fourth age group (51.7%) (P = .004, P = .008, and P = .04, respectively). The 2-year overall survival rates were 63.7% and 66.8% in the first 2 age groups, which were higher than the rates in the last 2 age groups (34.2% and 14.8%) (P = .02, P = .03, P < .001, and P < .001, respectively). The 1-year cumulative incidences of nonrelapse mortality were 10.2%, 0%, 3.4%, and 26.0% in the 4 age groups and 8.1% in all patients. The median times to neutrophil and platelet recovery were 12 days and 14 days after induction chemotherapy, respectively. Five patients had full or mixed donor engraftment, and 30.8% (8 of 26) of patients demonstrated donor microchimerism. Two patients (1.1%) developed severe acute graft-vs-host disease. CONCLUSIONS AND RELEVANCE: Microtransplant achieved a high complete remission rate in AML patients aged 60 to 85 years and higher 1-year overall survival in those aged 60 to 74 years.

BACKGROUND Dysfunction of long non-coding RNAs (lncRNAs) has been demonstrated to be involved in psychiatric diseases. However, the expression patterns and functions of the regulatory lncRNAs in schizophrenia (SZ) patients have rarely been systematically reported. MATERIAL AND METHODS The lncRNAs in peripheral blood mononuclear cells (PBMCs) were screened and compared between the SZ patients and demographically-matched healthy controls using microarray analysis, and then were validated by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) method. Three verified significantly dysregulated lncRNAs of PBMCs were selected and then measured in SZ patients before and after the antipsychotic treatment. SZ symptomatology improvement was measured by Positive And Negative Syndrome Scale (PANSS) scores. RESULTS One hundred and twenty-five lncRNAs were significantly differentially expressed in SZ patients compared with healthy controls, of which 62 were up-regulated and 63 were down-regulated. Concurrent with the significant decrease of the PANSS scores of patients after the treatment, the PBMC levels of lncRNA NONHSAT089447 and NONHSAT041499 were strikingly decreased (P<0.05). Down-regulation of PBMC expression of NONHSAT041499 was significantly correlated to the improvement of positive and activity symptoms of patients (r=-0.444 and -0.423, respectively, P<0.05, accounting for 16.9% and 15.1%, respectively), and was also significantly associated with better outcomes (odds ratio 2.325 for positive symptom and 12.340 for activity symptom). CONCLUSIONS LncRNA NONHSAT089447 and NONHSAT041499 might be involved in the pathogenesis and development of SZ, and the PBMC level of NONHSAT041499 is significantly associated with the treatment outcomes of SZ.