This study aimed at comparing bortezomib, thalidomide, and lenalidomide in patients with multiple myeloma (MM) for safety and efficacy using meta-analysis. This meta-analysis identified 17 randomized controlled trials (RCTs) including 6742 patients. These RCTs were separated according to the different agent-based regimens and to autologous stem-cell transplantation (ASCT). Complete response (CR), progression-free survival (PFS), overall survival (OS), and adverse events (AE) were combined. The total weighted risk ratio (RR) of CR was 3.29 [95% confidence interval (95% CI): 2.22-4.88] (P < 0.0001) for the novel agent-based regimens. These novel agent-based regimens showed greater benefit in terms of PFS of all subgroups irrespective of whether the patient received ASCT or not. The hazard ratio (HR) for PFS was 0.64 [95% CI: 0.60-0.69] (P < 0.00001). Improvements of OS could be found only in the bortezomib- and thalidomide-based regimens without ASCT. The pooled HRs were 0.74 [95% CI: 0.65-0.86] (P < 0.0001) and 0.80 [95% CI: 0.70-0.90] (P = 0.0004), respectively. Several AEs were shown more frequently in the novel agent-based regimens compared with controls such as hematologic events (neutropenia, anemia, and thrombocytopenia), gastrointestinal infection, peripheral neuropathy, thrombosis, and embolism events. In conclusion, in spite of the AEs, novel agent-based regimens are safe and effective for the treatment of MM.

Lung cancer is among the most common malignancies with a poor 5-year survival rate reaching only 16%. Thus, new effective treatment modalities and drugs are urgently needed for the treatment of this malignancy. In this study, we conducted the first investigation of the effects of Biochanin A on lung cancer and revealed the mechanisms underlying its potential anticancer effects. Biochanin A decreased cell viability in a time-dependent and dose-dependent manner and suppressed colony formation in A549 and 95D cells. In addition, Biochanin A induced S phase arrest and apoptosis and decreased mitochondrial membrane potential (ΔΨm) in A549 and 95D cells in a dose-dependent manner. Our results of subcutaneous xenograft models showed that the growth of Biochanin A group was significantly inhibited compared with that of control groups. Finally, P21, Caspase-3, and Bcl-2 were activated in Biochanin A-treated cells and Biochanin A-treated xenografts which also demonstrated that Biochanin A induced cell cycle arrest and apoptosis in lung cancer cells by regulating expression of cell cycle-related proteins and apoptosis-related proteins. In conclusion, this study suggests that Biochanin A inhibits the proliferation of lung cancer cells and induces cell cycle arrest and apoptosis mainly by regulating cell cycle-related protein expression and activating the Bcl-2 and Caspase-3 pathways, thus suggesting that Biochanin A may be a promising drug to treat lung cancer.

Ulva prolifera is the major causative species in the green tide, a serious marine ecological disaster, which bloomed in the Yellow Sea and the Bohai Sea of China. However, it is also a popular edible seaweed and its extracts exerts anti-inflammatory and antioxidant effects. The present study investigated the effects of ethanol extract of U. prolifera (EUP) on insulin sensitivity, inflammatory response, and oxidative stress in high-fat-diet- (HFD-) treated mice. HFD-treated mice obtained drinking water containing 2% or 5% EUP. The results showed that EUP supplementation significantly prevented HFD-induced weight gain of liver and fat. EUP supplementation also improved glucose tolerance and insulin resistance in HFD-treated mice. Moreover, EUP supplementation prevented the increased expression of genes involved in triglyceride synthesis and proinflammatory genes and the decreased expression of genes involved in fatty acid oxidation in liver of HFD-treated mice. Furthermore, EUP supplementation decreased reactive oxygen species content, while increasing glutathione content and glutathione peroxidase activity in HFD-treated mice. In conclusion, our results showed that EUP improved insulin resistance and had antilipid accumulation and anti-inflammatory and antioxidative effects on HFD-treated mice. We suggested that U. prolifera extracts may be regarded as potential candidate for the prevention of nonalcoholic fatty liver disease.

The occurrence of heart failure (HF) is closely correlated with the disturbance of mitochondrial energy metabolism, and trimetazidine (TMZ) has been regarded as an effective agent in treating HF. Intracellular potassium ion (K+) homeostasis, which is modulated by K+ channels and transporters, is crucial for maintaining normal myocardial function and can be disrupted by HF. This study is aimed at exploring the protective effect of TMZ on K+ homeostasis within myocardial tissue in mice with HF. We observed the pathological changes of myocardial tissue under microscopes and further measured the content of adenosine triphosphate (ATP), the activity of Na+-K+ ATPase, and the expression of ATP1α1 at the mRNA and protein levels. Moreover, we also analyzed the changes in K+ flux across the myocardial tissue in mice. As a result, we found that there was a large amount of myocardial fiber lysis and fracture in HF myocardial tissue. Meanwhile, the potassium flux of mice with HF was reduced, and the expression of ATP1α1, the activity of Na+-K+ ATPase, and the supply and delivery of ATP were also decreased. In contrast, TMZ can effectively treat HF by restoring K+ homeostasis in the local microenvironment of myocardial tissues.

Triple-negative breast cancer (TNBC) is a very aggressive malignant type of tumor that currently lacks effective targeted therapies. In hematological malignancies, chimeric antigen receptor T (CAR-T) cells have shown very significant antitumor ability; however, in solid tumors, the efficacy is poor. In order to apply CAR-T cells in the treatment of TNBC, in this study, constitutively activated IL-7 receptor (C7R) that has been reported is used to enhance the antitumor function of constructed CAR-T cells by ourselves. Using in vitro coincubation experiments with target cells and in vivo antitumor experiments in mice, we found that the coexpressed C7R can significantly improve the activation, cell proliferation, and cytotoxicity of CAR-T cells. In addition, the in vivo experiments suggested that the enhanced CAR-T cells displayed significant antitumor activity in a TNBC subcutaneous xenograft model, in which in vivo, the survival time of CAR-T cells was prolonged. Together, these results indicated that CAR-T cells that coexpress C7R may be a novel therapeutic strategy for TNBC.

To evaluate the effects of human bone marrow mesenchymal stem cells (hBMSCs) and osteoblasts (hFOB1.19) on PC3 prostate cancer cells.

This study aims at exploring the clinical efficacy and sonographic changes of photodynamic therapy (PDT) using Hematoporphyrin Monomethyl Ether (HMME) for the treatment of port-wine stains (PWS). Forty-five patients with PWS were recruited between March 2017 and June 2018 from the Department of Dermatology of The Third Affiliated Hospital of Soochow University. Five cases were of the pink type, thirty-nine cases were of the purple-red type, and one case was of the thickened type. All patients received three treatment sessions of PDT. After covering normal skin outside the treated area, patients received an intravenous injection of 5 mg/kg HMME within 20 minutes. The affected areas were exposed to a 532 nm LED light and were kept vertically at a distance of 10 cm. The irradiation energy density was set between 80 and 110 J/cm2 in 15-minute sessions. Intermittent power density adjustment was performed at a rate of 5 mW/cm2, and the treatment was withheld when the endpoint reaction appeared. Three follow-ups were performed before and after treatment, respectively, and the efficacy, thickness, and density of skin before and after treatment were evaluated with high-frequency ultrasound. The overall efficacy rate was 97.78% in forty-five cases after treatment for three sessions. Efficacy was related to age (P = 0.029) and lesion severity (P < 0.001). There were significant differences in the efficacy between the groups of <18 years old, 18-29 years old, and >29 years old (P = 0.029). A marked decrease in the numbers of distorted enlarged blood vessels per unit of the lesion was observed under high-frequency ultrasound. There were significant differences in skin thickness and skin density before and after treatment (F = 14.528, 5.428, P < 0.001). The swelling was reported to varying degrees in the treated areas in 23 patients with cheek lesion and in 6 frontal lesions. Hyperpigmentation after inflammation was observed in four patients that faded spontaneously after two months. In conclusion, photodynamic therapy for the treatment of PWS using HMME is effective and safe with few adverse reactions. Moreover, monitoring the changes in skin thickness and density of lesion tissue using high-frequency ultrasound can objectively evaluate the clinical efficacy of HMME photodynamic therapy and provide the basis for the formulation of individualized photodynamic therapy.

Chemotherapy induced peripheral neuropathy (CIPN) is a serious adverse effect of chemotherapeutics with limited pathogenetic mechanism been known. Whether microcirculatory disturbance is involved in CIPN has not been reported. Considering that tissue factor (TF) is an endogenous coagulation factor, we hypothesize CIPN may be induced by the high expression of TF in macrophages and sciatic nerve, which induces the molecular signal related to ischemia and hypoxia. Oxaliplatin (L-OHP) was used to establish CIPN model. Von Frey Hairs was used to measure nociception. The murine macrophage cell line Raw 264.7 was used for cell experiments. Gelatin zymography and western blotting were used to measure the activity or expression of protein. TF expression and MMP-9/2 activity in sciatic nerve and blood are significantly increased by L-OHP. L-OHP increased the release of HSP70 from macrophage and enhanced the expression of p-p38 and HIF-1α in vivo and in vitro. Hirudin significantly suppressed the overexpression of p38, HIF-1α and activation of MMP-9/2 induced by L-OHP and attenuated CIPN in mice. This study suggests that a novel HSP70-TLR-4-p38-TF-HIF-1a axis may play a pivotal role in the pathological process of CIPN. It is also shown that the use of anticoagulant Hirudin can inhibit the above mechanisms and improve CIPN.

An S. maltophilia strain named WJ66 was isolated from a patient; WJ66 showed resistance to more antibiotics than the other S. maltophilia strains. This bacteraemia is resistant to sulphonamides, or fluoroquinolones, while the representative strain of S. maltophilia, K279a, is sensitive to both. To explore drug resistance determinants of this strain, the draft genome sequence of WJ66 was determined and compared to other S. maltophilia sequences. Genome sequencing and genome-wide evolutionary analysis revealed that WJ66 was highly homologous with the strain K279a, but strain WJ66 contained additional antibiotic resistance genes. Further analysis confirmed that strain WJ66 contained an amino acid substitution (Q83L) in fluoroquinolone target GyrA and carried a class 1 integron, with an aadA2 gene in the resistance gene cassette. Homology analysis from the pathogen-host interaction database showed that strain WJ66 lacks raxST and raxA, which is consistent with K279a. Comparative genomic analyses revealed that subtle nucleotide differences contribute to various significant phenotypes in close genetic relationship strains.

We conducted a meta-analysis to investigate the controversial association of CD147 expression with HCC prognosis and clinicopathological characteristics. Eight studies from PubMed (1966-2016), EMBASE (1980-2016), Cochrane Library (1996-2016), Web of Science (1945-2016), China National Knowledge Infrastructure (1982-2016), and Wanfang databases (1988-2016) were considered. The associations between CD147 expression and clinicopathological parameters and overall survival (OS) or DFS/RFS were reassessed using the meta-analysis for odds ratio (OR) or hazard ratio (HR) and 95% confidence interval (CI). CD147 expression was associated with DFS/RFS (HR = 3.26; 95% CI: 1.82-5.83; P < 0.0001) but not with OS (HR = 1.35; 95% CI: 0.56-3.29; P = 0.51). We also delved deeper into the association between median survival time and CD147 expression owing to significant heterogeneity and found significant differences between high and low CD147 expression groups with respect to median survival time. CD147 expression was closely associated with the TNM stage (OR = 0.18; 95% CI: 0.04-0.85; P = 0.03) and venous invasion (OR = 6.29; 95% CI: 1.70-23.20; P = 0.006). In contrast, there was no association between CD147 expression and tumor stage, cirrhosis, differentiation, lymph node metastasis, HBsAg, and serum AFP levels. Thus, CD147 expression is potentially closely related to HCC survival and associated clinicopathological parameters, paving the way for further research.

Connexin 43 (Cx43) has been identified to be important for cerebral ischemia/reperfusion (I/R) injury as well as protection from it. This study was aimed at investigating the relationship between phosphorylated Cx43 (p-Cx43), transforming growth factor-β1 (TGF-β1 (TGF.

Rheumatoid arthritis is a systemic autoimmune disease characterized by chronic inflammation of multiple joints, with disruption of joint cartilage. The proliferation of synovial fibroblasts in response to multiple inflammation factors is central to the pathogenesis of rheumatoid arthritis. Our previous studies showed that 4-HNE may induce synovial intrinsic inflammations by activating NF-κB pathways and lead to cell apoptosis. However, the molecular mechanisms of how synovial NF-κB activation is modulated are not fully understood. Here, the present findings demonstrated that 4-HNE may induce synovial intrinsic inflammations by mTORC1 inactivation. While ectopic activation of mTORC1 pathway by the overexpression of Pim-2 may disrupt the initiation of inflammatory reactions and maintain synovial homeostasis, our findings will help to uncover novel signaling pathways between inflammations and oxidative stress in rheumatoid arthritis development and imply that Pim-2/mTORC1 pathway may be critical for the initiation of inflammatory reactions in human rheumatoid arthritis synovial cells.

To evaluate the efficacy and safety of Qingpeng ointment for the treatment of subacute and chronic eczema.

Threatened abortion (TA) is a common complication with high incidence in the first trimester of pregnancy, which will end in miscarriage if not treated properly. The Chinese herbs Cuscutae Semen (Tusizi in Chinese) and Herba Taxilli (Sangjisheng in Chinese) first recorded in the ancient classic medical book Shennong Bencao Jing are effective and widely used as an herb pair for the treatment of TA, while the active ingredients and the functional mechanism of Tusizi-Sangjisheng herb pair treating TA are still unknown. In order to exploit the relationship between those two herbs and TA, systems pharmacology analysis was carried out in this study. A total of 75 ingredients of Tusizi-Sangjisheng were collected from Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP). 12 bioactive compounds were screened, and 153 directly related targets were predicted by systematic models. Besides, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to systematically explore the potential mechanisms of Tusizi-Sangjisheng treating TA. Meanwhile, Compound-Target (C-T), Target-Disease (T-D), and Target-Pathway (T-P) networks were constructed to further quest the underlying functional mechanisms of Tusizi-Sangjisheng. As a result, 31 targets and 3 key pathways were found to be directly related to TA that includes mitogen-activated protein kinases (MAPKs), phosphatidylinositol-3-kinase/protein kinase B (PI3K-Akt), and transforming growth factor-β (TGF-β) signaling pathways. The results in this study may provide some valuable clues about the molecular mechanisms of the efficient Chinese herb pair Tusizi-Sangjisheng in the treatment of TA.

Immune checkpoint inhibitors (ICIs) have been increasingly used in the treatment of various types of tumors with favorable results. But these treatments also led to a variety of immune-related adverse events (irAEs). Neurological irAEs such as Guillain-Barré Syndrome are rare and may have serious consequences once they occur. A systematic literature search was performed in PubMed and Embase for all case reports of GBS associated with ICIs published in English reporting on human beings from 1990 up to date. A total of 30 case reports (total patients = 33) were used for final analysis. The included cases were from 11 countries, covering 10 tumor types, with melanoma accounting for the largest number. The mean age was 62.2 ± 11.1 years old, and males were dominant (male: 26 and female: 7). The median time of initial symptoms was 8.2 weeks after the 1st dose of ICIs. The most common manifestations of GBS associated with ICIs were weakness, hyporeflexia or areflexia, and paresthesia in order. The GBS subtypes suggested by electrophysiological results were acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), and Miller Fisher syndrome (MFS). The protein level of CSF in patients with GBS related to ICIs was 180.68 ± 152.51 mg/dl. Immediate termination of ICIs followed by intravenous immunoglobulin was the preferred treatment option. 72.7% of patients recovered or had residual mild dysfunction after treatment. Elderly male patients with melanoma were most likely to develop ICI-related GBS. The specific neurological symptoms, CSF analysis, and electrophysiological examination were important means of diagnosis.

Aiming to reveal the role of ADCS-Exos in secretion of inflammatory factors, Th17 and regulatory T (Treg) cell differentiation from naïve CD4+ T cells in hypertrophic scaring formation and maturation is explored. ELISA, qRT-PCR, and immunoblotting are performed to assay the local inflammatory factors IL-6, IL-10, IL-17A, and TNF-α, and transcriptional factors of RORϒt and Foxp3, in scaring tissue from patients and mice wound models treated with or without ADCS-Exos. Immunohistochemistry staining and immunoblotting are conducted to assay the extracellular matrix (ECM) deposition in vitro and in vivo. The results show that IL-6, IL-10, IL-17A, TNF-α, RORϒt, and Foxp3 are increased on mRNA and protein levels in hypertrophic scaring compared with atrophic scaring and normal skin. Naïve CD4+ T cells treated with ADCS-Exos in vitro can produce significantly less IL-6, IL-17A, TNF-α, and RORϒt and more IL-10 and Foxp3 on mRNA and protein levels. In addition, mice in ADSC-Exos-treated group demonstrate less collagen deposition; decreased IL-17A, TNF-α, and RORϒt; and increased IL-10 and Foxp3 production.

To explore the antiprostate cancer effects of Celastrol on prostate cancer cells' proliferation, apoptosis, and cell cycle distribution, as well as the correlation to the regulation of hERG.

To compare the effect of sutureless versus standard suture (double-layer suture) during renorrhaphy in laparoscopic or robotic-assisted partial nephrectomy on perioperative and renal function outcomes.

The dysregulated long noncoding RNAs (lncRNAs) have been described to be crucial regulators in the progression of ovarian carcinoma. The infiltration status of immune cells is also related to the clinical outcomes in ovarian carcinoma. The present research is aimed at constructing an immune-associated lncRNA signature with potential prognostic value for ovarian carcinoma patients.

Currently, it still remains a difficult problem to treat apical insufficiency of young permanent teeth resulted from pulp necrosis or periapical periodontitis. Previous studies have demonstrated that the treatment of revascularization using stem cells from apical papilla (SCAPs) results in increased root length and thickness of traumatized immature teeth and necrotic pulp. In this study, we investigated the role of 1,25-dihydroxyvitamin D3 in regulating the adhesion, spreading, proliferation, and osteogenic differentiation of SCAP, laying the foundation for subsequent clinical drug development. The immature tooth samples were collected in clinical treatment. SCAPs with stable passage ability were isolated and cultured. The multidifferentiation potential was determined by directed induction culture, while the stem cell characteristics were identified by flow cytometry. There were three groups: group A-SCAPs general culture group; group B-SCAPs osteogenesis induction culture group; and group C-SCAPs osteogenesis induction culture+1,25-dihydroxyvitamin D3 group, and the groups were compared statistically. The proliferation of SCAPs in each groups was detected through CCK-8 assay. RT-qPCR was used to detect the transcription levels of Runx2, ALP, Col I, and OCN of SCAPs in each groups. Results exhibited that the isolated SCAPs had multidifferentiation potential and stem cell characteristics. After 24 h culturing, cells in group C spread better than those in groups A and B. The proliferation activity of SCAPs factored by CCK-8 ranked as group C > group B > group A, while the transcription levels of Runx2, ALP, Col I, and OCN leveled as group C > group B > group A. These results suggested that 1,25-dihydroxyvitamin D3 can significantly promote the adhesion, spreading, and proliferation of SACPs and improve the osteogenic differentiation of SCAPs by means of regulating upward the transcription level of osteogenic differentiation marker.