Umbilical Cord Blood and UC-MSCs Combined with Low-Dose Immunosuppressant in the Treatment of Elderly Patients with Pure Red Cell Aplastic: A Case Series.

INTRODUCTION: At present, cyclosporine (CsA) is the first-line treatment for Pure Red Cell Aplasia (PRCA), but CsA administration can be associated with a number of side effects due to its high toxicity. Therefore, it is urgent to explore a safe and effective treatment for elderly patients who cannot be treated with conventional doses of CsA, especially those with multiple complications. Allogeneic Stem Cell Transplantation (ASCT) for PRCA is a promising treatment, but reports of using umbilical cord blood (UCB) are very rare. CASE PRESENTATION: In this report, UCB and umbilical cord mesenchymal stem cells (UC-MSCs) combined with low-dose CsA (1-3mg/kg/d) were used to treat 3 elderly patients who were diagnosed with PRCA combined with multiple complications in heart, lung, and renal. The treatments were successful without complications, and 12 months after stem cell infusion, the blood tests of the patients came normal. Moreover, the function of the liver, heart, and kidney continued to be stable. CONCLUSION: This report provides an effective regimen of using UCB and UC-MSCs combined with low-dose CsA (1-3 mg/kg/d) to treat PRCA, especially for elderly patients with multiple complications who cannot use the conventional dosage.

Transcriptional mechanism of E2F1/TFAP2C/NRF1 in regulating KANK2 gene in nephrotic syndrome.

The mortality rate linked with nephrotic syndrome (NS) is quite high. The renal tubular injury influences the response of NS patients to steroid treatment. KN motif and ankyrin repeat domains 2 (KANK2) regulates actin polymerization, which is required for renal tubular cells to maintain their function. In this study, we found that the levels of KANK2 in patients with NS were considerably lower than those in healthy controls, especially in NS patients with acute kidney injury (AKI). To get a deeper understanding of the KANK2 transcriptional control mechanism, the core promoter region of the KANK2 gene was identified. KANK2 was further found to be positively regulated by E2F Transcription Factor 1 (E2F1), Transcription Factor AP-2 Gamma (TFAP2C), and Nuclear Respiratory Factor 1 (NRF1), both at mRNA and protein levels. Knocking down E2F1, TFAP2C, or NRF1 deformed the cytoskeleton of renal tubular cells and reduced F-actin content. EMSA and ChIP assays confirmed that all three transcription factors could bind to the upstream promoter transcription site of KANK2 to transactivate KANK2 in renal tubular epithelial cells. Our study suggests that E2F1, TFAP2C, and NRF1 play essential roles in regulating the KANK2 transcription, therefore shedding fresh light on the development of putative therapeutic options for the treatment of NS patients.

Fibrotic Matrix Induces Mesenchymal Transformation of Epithelial Cells in Oral Submucous Fibrosis.

Oral submucous fibrosis (OSF) is a potentially malignant disorder of the oral mucosa; however, whether and how the fibrotic matrix of OSF is involved in the malignant transformation of epithelial cells remains unknown. Herein, oral mucosa tissue from patients with OSF, OSF rat models, and their controls were used to observe the extracellular matrix changes and epithelial-mesenchymal transformation (EMT) in fibrotic lesions. Compared with controls, oral mucous tissues from patients with OSF showed an increased number of myofibroblasts, a decreased number of blood vessels, and increased type I and type III collagen levels. In addition, the oral mucous tissues from humans and OSF rats showed increased stiffness, accompanied by increased EMT activities of epithelial cells. The EMT activities of stiff construct-cultured epithelial cells were increased significantly by exogenous piezo-type mechanosensitive ion channel component 1 (Piezo1) activation, and decreased by yes-associated protein (YAP) inhibition. During ex vivo implantation, oral mucosal epithelial cells of the stiff group showed increased EMT activities and increased levels of Piezo1 and YAP compared with those in the sham and soft groups. These results indicate that increased stiffness of the fibrotic matrix in OSF led to increased proliferation and EMT of mucosal epithelial cells, in which the Piezo1-YAP signal transduction is important.

[Clinical evaluation of Compound Chamomile and Lidocaine Hydrochloride Gel for postoperative hypospadias in children].

OBJECTIVE: To evaluate the clinical efficacy of Compound Chamomile and Lidocaine Hydrochloride Gel for postoperative hypospadias in children. METHODS: From January to December 2020, we treated 116 children with distal hypospadias in the Department of Urology, Department of Pediatrics and the Seventh Medical Center of the PLA General Hospital, 58 by primary Snodgrass urethroplasty only (the control group) and the other 58 with Compound Chamomile and Lidocaine Hydrochloride Gel smeared on the penis postoperatively in addition (the trial group). We compared the operation time and postoperative pain score, edema regression and incidence of infection between the two groups, followed by statistical analysis using T test and Chi-square test. RESULTS: All the operations were successfully completed by the same surgeon under general anesthesia. There were no statistically significant differences between the trial and control groups in age (ï¼»2.5 ± 0.8ï¼½ vs ï¼»2.4 ± 0.6ï¼½ yr, P > 0.05) or operation time (ï¼»95.6 ± 14.5ï¼½ vs ï¼»97.1 ± 15.2ï¼½ min, P > 0.05). No incision infection occurred in any of the cases. The pain scores at dressing removal were remarkably lower in the trial than in the control group at 2 hours (1.4 ± 1.0 vs 2.6 ± 1.3, P < 0.05), 24 hours (2.2 ± 1.3 vs 3.9 ± 1.6, P < 0.05), 48 hours (1.2 ± 0.7 vs 1.6 ± 0.9, P < 0.05) and 72 hours after surgery (2.5 ± 0.8 vs 3.7 ± 1.8, P < 0.05). Significantly more cases of edema regression were achieved in the trial than in the control group at 2 weeks postoperatively (35 vs 19, P < 0.05). CONCLUSIONS: Compound Chamomile and Lidocaine Hydrochloride Gel can effectively relieve pain, reduce edema and accelerate edema regression after surgery in children with hypospadias, and therefore deserves wide clinical application.、.

Incidental finding of an asymptomatic pulmonary valve papillary fibroelastoma: A case report.

Primary cardiac tumors are rare, but papillary fibroelastoma (PFE) is reportedly the most common form, which usually occurs on the left-side valves of the heart. However, PFE involving the tricuspid and pulmonary valves has also been documented. Although PFE is benign and seldom associated with valvular dysfunction, the associated embolic complications may lead to serious consequences. Most patients with PFE lack specific clinical symptoms and the diagnosis is incidental. Surgical resection is the mainstay treatment for PFE in order to prevent the occurrence of embolic complications. In this report, we present a case of a rare asymptomatic PFE of the pulmonary valve, which was incidentally noted during a routine examination with transthoracic echocardiography (TEE). There was neither valvular dysfunction nor hemodynamic change. The PFE was surgically removed, and the diagnosis was further confirmed with histopathology.

Platelet to Lymphocyte Ratio Predicts Contrast-Induced Nephropathy in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

We investigated the relationship between platelet to lymphocyte ratio (PLR) and contrast-induced nephropathy (CIN) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). We enrolled 5719 patients in 3 tertiary hospitals from January 2005 to December 2010. The PLR was calculated as the ratio of platelet to lymphocyte counts on admission. Serum creatinine level was measured before and within 72 hours after contrast medium administration. To evaluate the relation between PLR and CIN, the 5719 patients were divided into a CIN group and a non-CIN group. Contrast-induced nephropathy occurred in 252 (4.4%) patients. Patients in the CIN group had significantly higher PLR than those in the non-CIN group (173.8 [62.3] and 116.2 [51.7], respectively; P < .001). In logistic regression analysis, PLR was an independent predictor of CIN (odds ratio: 1.432, 95% confidence interval: 1.205-1.816, P = .031), along with age, diabetes mellitus, creatinine, estimated glomerular filtration rate, and neutrophil to lymphocyte ratio. In conclusion, a higher PLR was an independent risk factor for the development of CIN in patients with STEMI undergoing pPCI.

Two new phases in the ternary RE-Ga-S systems with the unique interlinkage of GaS4 building units: synthesis, structure, and properties.

Two novel ternary rare-earth chalcogenides, Yb6Ga4S15 and Lu5GaS9, have been prepared by solid-state reactions of an elemental mixture at high temperatures. Their structures were determined on the basis of single-crystal X-ray diffraction. Yb6Ga4S15 crystallizes in the monoclinic space group C2/m (no.12) [a = 23.557(2) Å, b = 3.7664(4) Å, c = 12.466(1) Å, ß = 90.915(9)°, V = 1105.9(2) Å3 and Z = 2], whereas Lu5GaS9 crystallizes in the triclinic space group P1[combining macron] (no.2) [a = 7.735(3) Å, b = 10.033(4) Å, c = 10.120(4) Å, α = 106.296(4)°, ß = 100.178(5)°, γ = 101.946(3)°, V = 714.1(5) Å3 and Z = 2]. Both the structures feature complicated three dimensional frameworks with the unique interlinkages of GaS4 as basic building units. Significantly, photo-electrochemical measurements indicated that title compounds were photoresponsive under visible-light illumination. Furthermore, the UV-visible-near IR diffuse reflectance spectra, thermal stabilities, electronic structures, physical properties as well as a structure change trend of the ternary rare-earth/gallium/sulfur compounds have been evaluated.

Role of tripartite motif protein 27 as a gametogenesis-related protein in human germ cells.

BACKGROUND: The distribution and functional integrity of members of the tripartite motif (TRIM) protein family are essential for cell proliferation, development and apoptosis, and TRIM proteins have been linked to various cancers. To explore the diagnostic potential and mechanisms of TRIM27 in human spermatogenesis and oogenesis, we analyzed its localization pattern and putative roles in human testes and ovaries. METHODS: TRIM27 mRNA and protein levels in human testes and ovaries were investigated using RT-PCR and western blotting, respectively. TRIM27 was abundantly transcribed in human testes and ovaries, particularly during the early stages of spermatogenesis, and localized in the nuclei of primary spermatocytes. Immunofluorescence also revealed a diffuse distribution in the cytoplasm of round spermatids, and the protein was abundant in ovary tissue during various stages of oogenesis development. RESULTS: TRIM27 mRNA and protein was abundantly transcribed in male and female human germ cells by RT-PCR and western blotting in the human testes followed by the ovary. Immunohistochemical results revealed TRIM27 protein was abundant in the sex body of primary spermatocytes undergoing meiotic prophase during the first cycle of spermatogenesis. Moreover, Trim27 was diffusely localized in the cytoplasm of spermatids and round spermatids. Furthermore, TRIM27 was localized to both the nucleus and cytoplasm of human ovary cells. CONCLUSIONS: TRIM27 as a gametogenesis-related protein could play multiple roles in the regulation of sex body formation and germ cell proliferation during spermatogenesis and oogenesis. The identification and characterization of TRIM27 enhances our understanding of the molecular mechanisms underpinning its functions, and provides insight into its potential role in the pathogenesis of germ cell differentiation and infertility.

Saikosaponin a functions as anti-epileptic effect in pentylenetetrazol induced rats through inhibiting mTOR signaling pathway.

OBJECTIVE: Saikosaponin a (SSa), which is one major bioactive compound isolated from radix bupleuri, has been demonstrated to exhibit the properties of anticonvulsant and antiepileptic in few reports. This study aims to clarify the molecular mechanism by which SSa protects against pentylenetetrazol (PTZ) induced epileptic seizure. METHODS: PTZ induced rat and hippocampal neuron were established. Treated rats or hippocampal neuron with SSa, and mTOR, P70S6K, IL-1ß and TNF-α were then determined. RESULTS: In PTZ induced rat, SSa significantly reduced seizure severity and duration while markedly elevated seizure latency, and it also down-regulated hippocampal p-mTOR, p-70S6K, L-1ß and TNF-α expression. In hippocampal neurons exposed to PTZ, p-mTOR and p-70S6K expression levels were also decreased by SSa. Pre-incubated hippocampal neurons with leucine, an mTOR agonist, reversed the effects of SSa on decreasing cytokines expression and inhibiting cell apoptosis. The treatment of mTOR inhibitor rapamycin prevented against the increase of cytokines expression and hippocampal neuron apoptosis induced by PTZ. Leucine also canceled the alleviation of seizures and induction of hippocampal caspase-3 activity in PTZ induced rat with the treatment of SSa. CONCLUSION: SSa protects against PTZ induced epileptic seizure and hippocampal neuron apoptosis through inhibiting mTOR signaling pathway.

Short communication: Camel milk ameliorates inflammatory responses and oxidative stress and downregulates mitogen-activated protein kinase signaling pathways in lipopolysaccharide-induced acute respiratory distress syndrome in rats.

Acute respiratory distress syndrome (ARDS) is a complex syndrome disorder with high mortality rate. Camel milk (CM) contains antiinflammatory and antioxidant properties and protects against numerous diseases. This study aimed to demonstrate the function of CM in lipopolysaccharide (LPS)-induced ARDS in rats. Camel milk reduced the lung wet:dry weight ratio and significantly reduced LPS-induced increases in neutrophil infiltration, interstitial and intra-alveolar edema, thickness of the alveolar wall, and lung injury scores of lung tissues. It also had antiinflammatory and antioxidant effects on LPS-induced ARDS. After LPS stimulation, the levels of proinflammatory cytokines (tumor necrosis factor-α, IL-10, and IL-1ß) in serum and oxidative stress markers (malondialdehyde, myeloperoxidase, and total antioxidant capacity) in lung tissue were notably attenuated by CM. Camel milk also downregulated mitogen-activated protein kinase signaling pathways. Given these results, CM is a potential complementary food for ARDS treatment.

Cyanidin-3-O-Glucoside Ameliorates Lipopolysaccharide-Induced Injury Both In Vivo and In Vitro Suppression of NF-κB and MAPK Pathways.

Cyanidin-3-O-glucoside (C3G), an anthocyanin belonging to the flavonoid family and commonly present in food and vegetables in human diet, has exhibited anti-inflammatory and anti-oxidant effects. This study aimed to investigate the protective ability of C3G against inflammatory and oxidative injuries, as well as to clarify the possible mechanism in lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs) in vitro and acute respiratory distress syndrome mouse model in vivo. HUVECs or male Kunming mice were pretreated with C3G 1 h before LPS stimulation. C3G significantly inhibited the production of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin (IL) -6, and IL-1ß) in cell supernatants and bronchoalveolar lavage fluid (BALF) as determined by enzyme-linked immunosorbent assay. Histopathologic examination with hematoxylin and eosinstaining showed that C3G pretreatment substantially suppressed inflammatory cell infiltration, alveolar wall thickening, and interstitial edemain lung tissues. C3G markedly prevented LPS-induced elevation of malondialdehyde and myeloperoxidase levels in lung tissue homogenates, wet to dry ratio of lung tissues, total cells, and inflammatory cells (neutrophils and macrophages) in BALF. Moreover, C3G reduced superoxide dismutase activity in the lung tissue homogenates. Western blot assay also showed that C3G pretreatment significantly suppressed LPS-induced activation of nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways by blocking the phosphorylation of inhibitor κB-α, NF-κB/P65, extracellular signal-regulated kinase, p38, and c-Jun NH2-terminal kinase in the lung tissues. In summary, C3G may ameliorate LPS-induced injury, which results from inflammation and oxidation, by inhibiting NF-κB and MAPK pathways and playing important anti-inflammatory and anti-oxidative roles.

Effects of quercetin on LPS-induced disseminated intravascular coagulation (DIC) in rabbits.

INTRODUCTION: Quercetin is widely distributed in plants and has been reported to have effects of anti-inflammation and anti-thrombosis. In this study, we evaluated the protective effect of quercetin on LPS-induced experimental DIC in rabbits, and tried to clarify its mechanism against DIC. MATERIALS AND METHODS: LPS-induced DIC model in rabbits was established through continuous infusion of 100 ug · kg(-1) · h(-1) LPS for a period of 6h. Six groups were divided: quercetin-treated groups (0.5, 1.0, and 2.0 mg·kg(-1) · h(-1), respectively), LPS-control group, heparin-control group (100 IU · kg(-1) · h(-1)), and saline-control group. APTT, PT, and plasma FIB level were measured, the plasma levels of ALT, BUN, and TNF-α were detected, and the activity of Protein C and ATIII was recorded. RESULTS: A continuous injection of LPS induced a gradual impairment of hemostatic parameters, a rise in plasma level of TNF-α, and damage in renal and hepatic function. The intravenous administration of quercetin significantly attenuated the increase of APTT, PT, ALT, BUN, and TNF-α, and the decrease of plasma FIB level and activity of Protein C and ATIII. CONCLUSION: Quercetin may have a protective effect against LPS-induced DIC in rabbits through anti-inflammation and anticoagulation.

RGDC functionalized titanium dioxide nanoparticles induce less damage to plasmid DNA but higher cytotoxicity to HeLa cells.

In this paper, nano-TiO(2) was functionalized by different methods, and its genotoxicity and cytotoxicity were studied in detail. The genotoxicity of nano-TiO(2) was evaluated by observing its interactions with pUC19 plasmid DNA at a single molecule level using atomic force microscopy. The results show that with the assistance of UVA radiation, RGDC functionalized nano-TiO(2) induced less damage to plasmid DNA than unmodified ones. The HeLa cell-specific PDT effect was investigated by cytotoxicity assay correspondingly. RGDC-functionalized nano-TiO(2) shows the highest killing effect to HeLa cells with the assistance of UVA radiation. The reasons that cause the contradiction between genotoxicity and cytotoxicity were analyzed, and the molecular mechanisms of the PDT effects were discussed. The results show that the genotoxicity of nano-TiO(2) to plasmid DNA and its cytotoxicity to HeLa cells are related but also different. The RGDC functionalization is an effective method to increase the cytotoxicity of nano-TiO(2).

The development of Chinese specific human cytomegalovirus polyepitope recombinant vaccine.

Human cytomegalovirus (HCMV) infection is a major cause of morbidity in the recipients of organ transplants and in the congenitally infected infants. HCMV vaccine has emerged as an effective approach to prevent HCMV infection particularly for the development of multiple viral antigens vaccination and human leukocyte antigen (HLA)-restricted polyepitope technology. As the Chinese population makes up more than one fifth of the population worldwide, it is important to develop HCMV vaccines more specific for the Chinese population by targeting Chinese-restricted HLA alleles and antigens. In the present study, we designed a novel chimeric polyepitope vaccine based on the replication-deficient adenovirus Ad5F35, which encodes 83 HCMV T cell epitopes from 15 different HCMV antigens, restricted to 14 HLA I and 7 HLA II alleles that cover 92% of the Chinese population. Our results show that the recombinant adenovirus vaccine Ad5F35-CTL·Th can be efficiently transfected and expressed in peripheral blood mononuclear cells (PBMCs) with little cytopathic activity. Ad5F35-CTL·Th can also be endogenously processed and presented by PBMCs. Ad5F35-CTL·Th-stimulated HCMV-specific cytotoxic T lymphocytes (CTLs) showed strong cytolytic activity against HCMV polyepitope-sensitized target cells. The CTL activity was accompanied by high levels of IFN-γ production after Ad5F35-CTL·Th stimulation. The specificity and vigorous response to the recombinant adenovirus vaccine in vitro makes it a potential candidate to be used for transplantation recipients or congenitally infected infants.

A stannum-bismuth composite film electrode for simultaneous determination of zinc(II) and cadmium(II) using differential pulse anodic stripping voltammetry.

The development and use of 'green' electrode materials is extremely attractive for the routine use of disposable metal sensors. Bismuth is an environmentally-friendly element and a bismuth film electrode was proposed as an alternative to mercury film electrodes. Compared with bismuth, stannum is a more 'environmentally friendly' material. The stannum-bismuth composite film electrode prepared by the in situ electrodeposition of stannum and bismuth on the glassy carbon substrate is reported for the first time. Compared with bismuth film and stannum film electrodes, the stannum-bismuth composite film electrode revealed better electroanalytical performance, and can be used as a possible alternative electrode for electrochemical stripping analysis of trace heavy metals.

WITHDRAWN: The changes of apoptotic signaling in cerebral cortex and hippocampus of cadmium-treated rats.

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A pure nongestational ovarian choriocarcinoma in a 10-year-old girl: case report and literature review.

Nongestational ovarian choriocarcinoma (NGCO) is a rare form of malignancy, which is difficult to diagnose. We present a case of a 10-year-old girl diagnosed with pure nongestational ovarian choriocarcinoma. This patient responded well to conservative surgery and cisplatin-based regimen chemotherapy. Approximately 38 authenticated cases of NGCO have been reported in the English published work to date in the world. We report here the clinical features, differential diagnosis, appropriate management and outcome of our case, together with analysis of the reported cases in the published work.

[Periodic and fractal precipitation in ATP-Co(2+)-decoxycholate gel system].

In the simulation experiments in vitro of the formation of gallstone, adenosine-triphosphate(ATP)-Co(2+)-deoxycholic acid(DC) gel system was chosen to study the periodic precipitation progress. The effect of ATP on the Co(2+)-DC gel system was also determined, and the structure of the periodic precipitation formed was characterized by FTIR. The results show that the patterns formed in the systems with ATP are different, ATP affected the rate and structure of precipitation through its variable participation in the metal coordination complexes as judged by the phosphate P=O bands and the deoxycholate COO- symmetric and asymmetric vibration bands as measured by FTIR Theses spectroscopic differences were correlated with color and pattern differences in the precipitates. ATP has a more remarkable function than AMP to the modes of patterns, meanwhile the system patterns transform from fractal to periodic precipitation. There is a complex interaction among ATP, sodium deoxycholic and Co2+ with a transparent crystal produced. The crystal is deoxycholic acid and the periodic precipitation is composed of ATP and DC covalent to Co2+. These results indicate that stone formation and remodeling is a dynamic, nonlinear progress. Much of the precipitate, as judged by local differences in composition, is not in equilibrium with the general gel environment. The authors conclude that the formation of gallstone features complex and nonlinear chemical character, in which nucleotides as living material play a very important role.

Benazepril, an angiotensin-converting enzyme inhibitor, alleviates renal injury in spontaneously hypertensive rats by inhibiting advanced glycation end-product-mediated pathways.

1. Advanced glycation end-products (AGE) and their receptors (RAGE) have been implicated in renal damage in diabetes. The aim of the present study was to investigate the effects of benazepril, an angiotensin-converting enzyme inhibitor (ACEI), on the formation of AGE, the expression RAGE and other associated components in the oxidative stress pathway in spontaneously hypertensive rats (SHR). 2. Groups of SHR were treated with or without 10 mg/kg per day benazepril for 12 weeks. Systolic blood pressure (SBP) and angiotensin (Ang) II levels were evaluated in SHR and control Wistar-Kyoto (WKY) rats. Renal function was investigated by determining levels of proteinuria and glomerulosclerosis. Furthermore, reactive oxygen species (ROS) in the rat renal cortex were analysed using an H(2)O(2)-based hydroxyl radical-detection assay and the renal content of AGE, RAGE, NADPH oxidase p47phox, nuclear factor (NF)-kappaB p65, phosphorylated (p-) NF-kappaB p65, vascular cell adhesion molecule (VCAM)-1 and transforming growth factor (TGF)-beta1 was determined by immunohistochemistry, quantitative real-time polymerase chain reaction and western blot analysis. 3. Treatment with benazepril inhibited the formation of AngII, reduced SBP and alleviated renal lesions in SHR compared with both untreated SHR and control WKY rats. Benazepril treatment significantly suppressed the accumulation of AGE and expression of RAGE in the kidney of SHR. In addition, benazepril treatment reduced the upregulation of NADPH oxidase p47phox, ROS generation and NF-kappaB p65, p-NF-kappaB p65, VCAM-1 and TGF-beta1 expression in the kidney of SHR compared with both untreated SHR and control WKY rats. 4. The results of the present study provide new insights into the regulation by the renin-angiotensin system of AGE-RAGE, oxidative stress and nephropathy, increasing our understanding of the role of the RAS in nephropathy.