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Cyclin-dependent kinase 12 (CDK12) is a transcription-associated kinase that participates in various cellular processes. However, its regulatory role in the progression of diffuse large B-cell lymphoma (DLBCL), which is the most prevalent subtype of non-Hodgkin lymphoma (NHL), is still elusive and controversial.The expression of CDK12 was detected by immunohistochemistry (IHC), RT-qPCR was performed to detect miR-28-5p expression of OCI-LY3 and SU-DHL-4 cells. MTT and soft agarose colony formation assays were used to detect cell proliferation. The cell apoptosis was determined by flow cytometry. The protein expressions changes of MYC, EZH2 and the biomarkers of BCR signaling were also detected. A subcutaneous transplantation tumor model of OCI-LY3 cells in nude mice was established to evaluate anticarcinogenic activities of CDK12 knockdown. Elevated expression of CDK12 was observed while miR-28-5p was downregulated in DLBCL tissues. CDK12 knockdown or miR-28-5p overexpression could inhibit proliferation and promote apoptosis of DLBCL cells. miR-28-5p inhibition could reverse the effect of CDK12 knockdown on proliferation and apoptosis of DLBCL cells. In addition, CDK12 knockdown could inhibit DLBCL tumor growth in the mice model. CDK12 activated MYC to repress miR-28-5p/EZH2 and amplified tonic BCR signaling to promote the development of DLBCL, which might provide potential therapeutic targets for future therapeutic intervention in DLBCL.

Although long non-coding RNA (lncRNA) HCP plays essential roles in human cancers, its function and mechanism in multiple myeloma (MM) have not crystallized. HCP5 level in MM was assessed through qRT-PCR. A series of functional investigations were conducted to evaluate the influences of HCP5 on proliferation and apoptosis. Bioinformatics analysis and RIP/RNA pull-down assays were carried out to determine the relationships among HCP5, miR-128-3p, and PLAGL2. Relative protein level was determined through Western blot. A xenograft tumor model was applied for validating the roles of HCP5/miR-128-3p/PLAGL2 axis in vivo. HCP5 was significantly increased in MM. HCP5 knockdown effectively thwarted the proliferative rate and cell cycle of MM cell lines and suppressed tumor growth. HCP5 regulated PLAGL2 expression by sponging miR-128-3p. PLAGL2 overexpression effectively rescued cells from influences by sh-HCP5 on cell proliferative and apoptotic rates. Additionally, HCP5 knockdown significantly inhibited Wnt/β-catenin/cyclin D1 signaling, and these effects were eliminated by PLAGL2 overexpression. Our study revealed that HCP5/miR-128-3p/PLAGL2 is closely correlated to MM development by modulating Wnt/β-catenin/cyclin D1 signaling. HCP5 promoted cell proliferation and tumor formation of MM cells by activating the Wnt/β‐catenin/CCND1 signaling pathway by sponging miR-128-3p to increase PLAGL2 expression

An amendment to this paper has been published and can be accessed via the original article.

In order to design a complex laser resonator with multi-parameters, the method of particle swarm optimization (PSO) algorithm is employed. The parameters influencing the resonator stability and mode size distribution are taken into consideration, and the stability criteria index and the mode size distribution are used as target values. The absolute values of the differences between practical and the target values are set as the fitness function for the PSO. By minimizing the fitness function, a laser resonator with the optimized cavity parameters can be found. The analyses for the design example demonstrate the feasibility and validity of the PSO method in the computer aided design of multi- parameters laser resonator. Applying PSO algorithm in the intelligent design of solid state laser resonators can realize the transition from manual trial-and-error to computer intelligent design of the laser resonators.

Cardiopulmonary exercise testing (CPET) has been used for prognosis in idiopathic pulmonary arterial hypertension (IPAH). We explored whether sex differences had an impact on prognostic assessments of CPET in IPAH. Data were retrieved from 21 male and 36 female incident IPAH patients who underwent both right heart catheterization and CPET from 2010 to 2016 at Shanghai Pulmonary Hospital. Cox proportional hazards analysis was used to assess the prognostic value of CPET. The mean duration of follow-up was 22±15 months. Nine men and 15 women had an event. The differences in clinical parameters in the whole population were not the same as the inter-subgroup differences. Event-free women had significantly higher cardiac output, lower pulmonary vascular resistance and percentage of predicted FVC compared with event men (all P

Pulmonary hypertension (PH), as a complication of bronchiectasis, is associated with increased mortality. However, hemodynamic characteristics and the efficacy of pulmonary arterial hypertension (PAH) therapies in patients with bronchiectasis and PH remain unknown. Patients with bilateral bronchiectasis and concurrent PH were included in the study. Patient characteristics at baseline and during follow-up, as well as survival, were analyzed. This observational study was conducted in 36 patients with a mean age of 51.5 years (range, 17‒74 years). The 6 min walking distance was 300.8 ± 3.3 m. The mean pulmonary arterial pressure (PAP) was 41.5 ± 1.7 mmHg, cardiac output was 5.2 ± 1.4 L/min, and pulmonary vascular resistance was 561.5 ± 281.5 dyn∙s∙cm(-5). The mean PAP was > 35 mmHg in 75% of the cases. Mean PAP was inversely correlated with arterial oxygen saturation values (r =-0.45, P = 0.02). In 24 patients who received oral PAH therapy, systolic PAP was reduced from 82.4 ± 27.0 mmHg to 65.5 ± 20.9 mmHg (P = 0.025) on echocardiography after a median of 6 months of follow-up. The overall probability of survival was 97.1% at 1 year, 83.4% at 3 years, and 64.5% at 5 years. Given the results, we conclude that PH with severe hemodynamic impairment can occur in patients with bilateral bronchiectasis, and PAH therapy might improve hemodynamics in such patients. Prospective clinical trials focusing on this patient population are warranted.

There is no cure for pulmonary hypertension due to left heart disease (PH-LHD), but the rationale for using sildenafil to treat pulmonary arterial hypertension with heart failure with reduced ejection fraction (HFrEF) has been supported by short-term studies. We performed a meta-analysis to evaluate the effectiveness of sildenafil for PH-LHD with HFrEF. A systematic literature search of PubMed, EMBASE and the Cochrane Central Register of Controlled Trials was conducted from inception through October 2014 for randomized trials and for observational studies with control groups, evaluating the effectiveness of sildenafil to treat PH-LHD with HFrEF. Sildenafil therapy decreased pulmonary arterial systolic pressure both at the acute phase and at the 6-month follow-up (weighted mean difference (WMD): -6.03 mm Hg, P=0.02; WMD: -11.47 mm Hg, P0.00001, respectively). Sildenafil was found to reduce mean pulmonary artery pressure (WMD: -3 mm Hg, P=0.0004) and pulmonary vascular resistance (WMD: -60.0 dynes cm(-5), P=0.01) at the 3-month follow-up. Oxygen consumption at peak significantly increased to 3.66 ml min(-1) kg(-1) (P0.00001), 3.36 ml min(-1) kg(-1) (P0.00001) and 2.60 ml min(-1) kg(-1) (P=0.03) at 3, 6 and 12 months, respectively. There were significant reductions in ventilation to CO2 production slope of -2.00, -4.68 and -7.12 at 3, 6 and 12 months, respectively (P0.00001). Sildenafil was superior to placebo regarding left ventricular ejection fraction at the 6-month follow-up (WMD: 4.35, P0.00001), and it significantly improved quality of life. Sildenafil therapy could effectively improve pulmonary hemodynamics and cardiopulmonary exercise testing measurements of PH-LHD with HFrEF, regardless of acute or chronic treatment.

The in-hospital mortality of severe pulmonary hypertension (PH) with right heart failure (RHF) is high despite the use of vasoactive and PH-specific therapies. We conducted a prospective analysis evaluating the safety and outcomes of fasudil hydrochloride (Chuan Wei) therapy in acute RHF. PH patients hospitalized between April 2009 and November 2010 were treated with 30 mg of i.v. fasudil three times daily over 30 min, until they experienced relief of RHF symptoms. Adverse and serious adverse events were recorded. Odds ratios (ORs) and 95% confidence intervals were calculated for both in-hospital mortality and re-hospitalization. Multivariate adjustments were made for age, gender and World Health Organization functional class. There were no significant differences between the fasudil group and the control group in demographics, hemodynamics, and PH-specific and vasoactive therapies. Of the 209 study patients, 3 of the 74 patients (4.1%) in the fasudil arm died, and 19 of the 135 patients (14.1%) in the control arm died (P=0.005). Fasudil decreased both in-hospital mortality (OR=0.258 (0.074-0.903); P=0.034) and 30-day re-hospitalization (OR=0.200 (0.059-0.681); P=0.010). Fasudil was well tolerated; one patient discontinued treatment. Intravenous fasudil may be given safely in patients with PH and acute RHF, and may reduce the rates of both in-hospital mortality and 30-day re-hospitalization.

To investigate the clinical effect of sequential therapeutic intervention Yupei Qisun [compensating for weakness by invigorating Kidney (Shen) and Spleen (Pi) in advance] in Chinese medicine (CM) and hysteroscopic endometrial mechanical stimulation on the treatment of infertile patients with repeated implantation failure (RIF); and to study the differences in patients' endometrial thickness and type on the day of embryo transfer, serum hormone levels on embryo transfer day and clinical pregnancy outcomes.In the clinical study, 168 frozen-thawed embryo transfer (FET) cycles for couples with RIF conforming to the research protocol were randomly divided into three groups: a CM group with 56 cycles (CM combined with FET), a hysteroscopy group with 55 cycles (hysteroscopic endometrial mechanical stimulation), and a control group with 57 cycles (conventional FET). Differences in endometrial thickness on the embryo transfer day, levels of serum estradiol (E2) and progesterone (P) on the embryo transfer day, the E2/P ratio on the embryo transfer day, biochemical and clinical pregnancy rates, implantation rate, abnormal pregnancy rate and other indices were compared among the three groups.Endometrial thickness, E2 and P levels, and the E2/P ratio on embryo transfer day and other factors had no significant differences among groups. The biochemical pregnancy, clinical pregnancy, and implantation rates of the CM and hysteroscopy groups were significantly higher than the control group (P0.05), and there were no significant differences between these two groups. The abnormal pregnancy rate had no significant difference among the three groups.Sequential therapy of Yupei Qisun could significantly improve the clinical outcomes of rif-fet cycles, being equivalent to hysteroscopic endometrial mechanical stimulation, and provided a reliable method to treat such infertile couples.

Two series of polynitro heterocyclic compounds with three conformations are designed based on the obtained dodecahydrodiimidazo [4,5-b:4′,5′-e]pyrazine “565” structure. First, the conformations including boat, chair, and plane, are optimized at B3PW91/6-311+G(d,p) level and some important properties are calculated. Based on the bond order, bond dissociation enthalpies and molecular energy analysis, it is found that the boat conformation owns lower energy and better bond order than the other two, and thus is most stable. Then, a further study on the electrical potential surfaces (EPS) proves that the stability of boat conformation can be contributed to the better balance between the positive and negative EPS. Next, according to molecular energy gap and density of state, the effect of each group on molecule is investigated: electrons on nitro group, compared with those on the framework, are easier to be activated so as to cause decomposition, thus nitro groups will determine the stability of molecule. Finally, the explosive velocity, pressure, and impact sensitivity of designed compounds are calculated. Results show that their explosive performances are significantly better than current energetic materials, and it is extraordinary enough that some compounds among them also maintain very good sensitivity.