Combined gene therapy via VEGF and mini-dystrophin synergistically improves pathologies in temporalis muscle of dystrophin/utrophin double knockout mice.

Duchenne muscular dystrophy (DMD) is a severe X-linked inherited muscular disorder characterized by the loss of dystrophin. We have previously shown that monogene therapy using the mini-dystrophin gene improves muscle function in DMD. However, chronic inflammation plays an important role in progressive muscle degeneration in DMD as well. Vascular endothelial growth factor (VEGF) has been used to enhance muscle vasculature, reduce local inflammation and improve DMD muscle function. Temporalis muscles are the key skeletal muscles for mastication and loss of their function negatively affects DMD patient quality of life by reducing nutritional intake, but little is known about the pathology and treatment of the temporalis muscle in DMD. In this work, we tested the hypothesis that the combined delivery of the human mini-dystrophin and human VEGF genes to the temporalis muscles using separate recombinant adeno-associated viral (rAAV) vectors will synergistically improve muscle function and pathology in adult male dystrophin/utrophin double-knockout (mdx/utrn+/-) mice. The experimental mice were divided into four groups including: dystrophin + VEGF combined, dystrophin only, VEGF only and PBS control. After 2 months, gene expression and histological analysis of the temporalis muscles showed a synergistic improvement in temporalis muscle pathology and function coincident with increased restoration of dystrophin-associated protein complexes and nNOS in the dystrophin + VEGF combined group. We also observed significantly reduced inflammatory cell infiltration, central nucleation, and fibrosis in the dystrophin + VEGF combined group. We have demonstrated the efficacy of combined rAAV-mediated dystrophin and VEGF treatment of temporalis muscles in a DMD mouse model.

The Content and Principle of the Rare Ginsenosides Produced from Gynostemma pentaphyllum after Heat Treatment.

Ginsenoside Rg3, Rk1, and Rg5, rare ginsenosides from Panax ginseng, have many pharmacological effects, which have attracted extensive attention. They can be obtained through the heat treatment of Gynostemma pentaphyllum. In this study, scanning electron microscopy (SEM) and thermal gravity-differential thermal gravity (TG-DTG) were employed to investigate this process and the content change in ginsenosides was analyzed using liquid chromatography-mass spectrometry (LC-MS). SEM and TG-DTG were used to compare the changes in the ginsenosides before and after treatment. In SEM, the presence of hydrogen bond rearrangement was indicated by the observed deformation of vascular bundles and ducts. The before-and-after changes in the peak patterns and peaks values in TG-DTG indicated that the content of different kinds of compounds produced changes, which all revealed that the formation of new saponins before and after the heat treatment was due to the breakage or rearrangement of chemical bonds. Additionally, the deformation of vascular bundles and vessels indicated the presence of hydrogen bond rearrangement. The glycosidic bond at the 20 positions could be cleaved by ginsenoside Rb3 to form ginsenoside Rd, which, in turn, gave rise to ginsenoside Rg3(S) and Rg3(R). They were further dehydrated to form ginsenoside Rk1 and Rg5. This transformation process occurs in a weak acidic environment provided by G. pentaphyllum itself, without the involvement of endogenous enzymes. In addition, the LC-MS analysis results showed that the content of ginsenoside Rb3 decreased from 2.25 mg/g to 1.80 mg/g, while the contents of ginsenoside Rk1 and Rg5 increased from 0.08 and 0.01 mg/g to 3.36 and 3.35 mg/g, respectively. Ginsenoside Rg3(S) and Rg3(R) were almost not detected in G. pentaphyllum, and the contents of them increased to 0.035 and 0.23 mg/g after heat treatment. Therefore, the rare ginsenosides Rg3(S), Rg3(R), Rk1, and Rg5 can be obtained from G. pentaphyllum via heat treatment.

Endoscopic-assisted surgery versus microsurgery for pineal region tumors: a single-center retrospective study.

Pineal region tumors are extremely deep-seated and surgically challenging. The exposure and visualization obtained by microscopic surgery are relatively limiting. The application of high-definition endoscopes has recently provided neurosurgeons with a much more magnified and clearer view of the anatomy in the pineal region. The present study was performed to compare endoscopic-assisted surgery (ES) with microsurgery (MS) for pineal region tumors. We retrospectively analyzed patients admitted to our hospital for treatment of pineal region tumors from January 2016 to June 2019. All patients consented to undergo tumor resection with ES or MS. We compared the extent of resection, postoperative rate of hydrocephalus, complications, and outcomes between the two groups to estimate the safety and efficacy of ES. In total, 41 patients with pineal region tumors were divided into 2 groups: the ES group (n = 20) and MS group (n = 21). The rate of gross total resection was significantly higher in the ES than MS group (90.0% vs. 57.1%, p = 0.04). The rate of postoperative hydrocephalus was significantly lower in the ES than MS group (11.8% vs. 52.9%, p = 0.03). No significant differences were found in complications or the Karnofsky Performance Score between the two groups. ES can be used to safely and effectively achieve complete resection of pineal region tumors. In patients with obstructive hydrocephalus, ES provides a new way to directly open the aqueduct for cerebrospinal fluid recovery following tumor resection.

GNAI1 and GNAI3 Reduce Colitis-Associated Tumorigenesis in Mice by Blocking IL6 Signaling and Down-regulating Expression of GNAI2.

BACKGROUND & AIMS: Interleukin 6 (IL6) and tumor necrosis factor contribute to the development of colitis-associated cancer (CAC). We investigated these signaling pathways and the involvement of G protein subunit alpha i1 (GNAI1), GNAI2, and GNAI3 in the development of CAC in mice and humans. METHODS: B6;129 wild-type (control) or mice with disruption of Gnai1, Gnai2, and/or Gnai3 or conditional disruption of Gnai2 in CD11c+ or epithelial cells were given dextran sulfate sodium (DSS) to induce colitis followed by azoxymethane (AOM) to induce carcinogenesis; some mice were given an antibody against IL6. Feces were collected from mice, and the compositions of microbiomes were analyzed by polymerase chain reactions. Dendritic cells (DCs) and myeloid-derived suppressor cells (MDSCs) isolated from spleen and colon tissues were analyzed by flow cytometry. We performed immunoprecipitation and immunoblot analyses of colon tumor tissues, MDSCs, and mouse embryonic fibroblasts to study the expression levels of GNAI1, GNAI2, and GNAI3 and the interactions of GNAI1 and GNAI3 with proteins in the IL6 signaling pathway. We analyzed the expression of Gnai2 messenger RNA by CD11c+ cells in the colonic lamina propria by PrimeFlow, expression of IL6 in DCs by flow cytometry, and secretion of cytokines in sera and colon tissues by enzyme-linked immunosorbent assay. We obtained colon tumor and matched nontumor tissues from 83 patients with colorectal cancer having surgery in China and 35 patients with CAC in the United States. Mouse and human colon tissues were analyzed by histology, immunoblot, immunohistochemistry, and/or RNA-sequencing analyses. RESULTS: GNAI1 and GNAI3 (GNAI1;3) double-knockout (DKO) mice developed more severe colitis after administration of DSS and significantly more colonic tumors than control mice after administration of AOM plus DSS. Development of increased tumors in DKO mice was not associated with changes in fecal microbiomes but was associated with activation of nuclear factor (NF) κB and signal transducer and activator of transcription (STAT) 3; increased levels of GNAI2, nitric oxide synthase 2, and IL6; increased numbers of CD4+ DCs and MDSCs; and decreased numbers of CD8+ DCs. IL6 was mainly produced by CD4+/CD11b+, but not CD8+, DCs in DKO mice. Injection of DKO mice with a blocking antibody against IL6 reduced the expansion of MDSCs and the number of tumors that developed after CAC induction. Incubation of MDSCs or mouse embryonic fibroblasts with IL6 induced activation of either NF-κB by a JAK2-TRAF6-TAK1-CHUK/IKKB signaling pathway or STAT3 by JAK2. This activation resulted in expression of GNAI2, IL6 signal transducer (IL6ST, also called GP130) and nitric oxide synthase 2, and expansion of MDSCs; the expression levels of these proteins and expansion of MDSCs were further increased by the absence of GNAI1;3 in cells and mice. Conditional disruption of Gnai2 in CD11c+ cells of DKO mice prevented activation of NF-κB and STAT3 and changes in numbers of DCs and MDSCs. Colon tumor tissues from patients with CAC had reduced levels of GNAI1 and GNAI3 and increased levels of GNAI2 compared with normal tissues. Further analysis of a public human colorectal tumor DNA microarray database (GSE39582) showed that low Gani1 and Gnai3 messenger RNA expression and high Gnai2 messenger RNA expression were significantly associated with decreased relapse-free survival. CONCLUSIONS: GNAI1;3 suppresses DSS-plus-AOM-induced colon tumor development in mice, whereas expression of GNAI2 in CD11c+ cells and IL6 in CD4+/CD11b+ DCs appears to promote these effects. Strategies to induce GNAI1;3, or block GNAI2 and IL6, might be developed for the prevention or therapy of CAC in patients.

Synthesis, Characterization, and Antifungal Activity of Novel Benzo[4,5]imidazo[1,2-d][1,2,4]triazine Derivatives.

A series of novel fused heterocyclic compounds bearing benzo[4,5]imidazo[1,2-d][1,2,4]triazine 4a-4w were designed and conveniently synthesized via the intermediates 2-(halogenated alkyl)-1H-benzo[d]imidazoles 2a, 2b, and 2-((1-(substituted phenyl)hydrazinyl)alkyl)-1H-benzo[d]imidazoles 3a-3g. The structures of all target compounds were characterized by FT-IR, ¹H NMR, 13C NMR, and EI-MS, of which, the structure of compound 4n was further determined by the single crystal X-ray diffraction. The crystal structure of 4n was crystallized in the triclinic crystal system, space group P 1 ¯ with a = 9.033 (6) Å, b = 10.136 (7) Å, c = 10.396 (7) Å, α = 118.323 (7)°, ß = 91.750 (8)°, γ = 104.198 (7)°, Z = 2, V = 800.2 (9) ų; total R indices: R1 = 0.0475, wR2 = 0.1284. The antifungal activity of title compounds 4a-4w in vitro against the phytopathogenic fungi Botrytis cinerea (B. cinerea), Rhizoctonia solani (R. solani) and Colletotrichum capsici (C. capsici) were evaluated, the bioassay results demonstrated that most of the title compounds exhibited obvious fungicidal activities at 50 µg/mL. This work indicated that benzo[4,5]imidazo[1,2-d][1,2,4]triazine derivatives could be considered as a new leading structure in searching for novel agricultural fungicides.

Overactivation of corticotropin-releasing factor receptor type 1 and aquaporin-4 by hypoxia induces cerebral edema.

Cerebral edema is a potentially life-threatening illness, but knowledge of its underlying mechanisms is limited. Here we report that hypobaric hypoxia induces rat cerebral edema and neuronal apoptosis and increases the expression of corticotrophin releasing factor (CRF), CRF receptor type 1 (CRFR1), aquaporin-4 (AQP4), and endothelin-1 (ET-1) in the cortex. These effects, except for the increased expression of CRF itself, could all be blocked by pretreatment with an antagonist of the CRF receptor CRFR1. We also show that, in cultured primary astrocytes: (i) both CRFR1 and AQP4 are expressed; (ii) exogenous CRF, acting through CRFR1, triggers signaling of cAMP/PKA, intracellular Ca(2+), and PKCε; and (iii) the up-regulated cAMP/PKA signaling contributes to the phosphorylation and expression of AQP4 to enhance water influx into astrocytes and produces an up-regulation of ET-1 expression. Finally, using CHO cells transfected with CRFR1(+) and AQP4(+), we show that transfected CRFR1(+) contributes to edema via transfected AQP4(+). In conclusion, hypoxia triggers cortical release of CRF, which acts on CRFR1 to trigger signaling of cAMP/PKA in cortical astrocytes, leading to activation of AQP4 and cerebral edema.

Optimization of ultrasonic assisted extraction of antioxidants from black soybean (Glycine max var) sprouts using response surface methodology.

Response surface methodology (RSM) using a central composite design (CCD) was employed to optimize the conditions for extraction of antioxidants from black soybean (Glycine max var) sprouts. Three influencing factors: liquid-solid ratio, period of ultrasonic assisted extraction and extraction temperature were investigated in the ultrasonic aqueous extraction. Then Response Surface Methodology (RSM) was applied to optimize the extraction process focused on DPPH radical-scavenging capacity of the antioxidants with respect to the above influencing factors. The best combination of each significant factor was determined by RSM design and optimum pretreatment conditions for maximum radical-scavenging capacity were established to be liquid-solid ratio of 29.19:1, extraction time of 32.13 min, and extraction temperature of 30 °C. Under these conditions, 67.60% of DPPH radical-scavenging capacity was observed experimentally, similar to the theoretical prediction of 66.36%.

Expression of hypoxia-inducing factor-1α and matrix metalloproteinase-9 in the recipient parasylvian cortical arteries with different hemodynamic sources in adult moyamoya disease.

Objective: In our latest research, we have demonstrated that the recipient parasylvian cortical arteries (PSCAs) with hemodynamic sources from the middle cerebral artery (M-PSCAs) has a higher risk of postoperative cerebral hyperperfusion (CHP) syndrome than those from non-M-PSCAs in adult moyamoya disease (MMD) patient. However, whether there are differences between M-PSCAs and non-M-PSCAs in vascular specimens characteristics has not been studied. In this study, we further investigate the vascular specimen of recipient PSCAs by histological and immunohistochemical methods. Methods: 50 vascular specimens of recipient PSCAs were obtained from 50 adult MMD patients during the combined bypass surgeries in our departments of Zhongnan hospital. 4 recipient PSCAs samples were also obtained in the same way from the middle cerebral artery occlusion patients. The samples were received the pathological sectioning, hematoxylin and eosin staining, and immunohistochemistry, then the vascular wall thickness, matrix metalloproteinase-9 (MMP-9) and hypoxia-inducing factor-1α (HIF-1α) were analyzed. Results: M-PSCAs adult MMD patients had a thinner intima than non-M-PSCAs in the recipient PSCAs specimens. In recipient non-M-PSCAs vascular specimens, the immunoreactivity indicating HIF-1α and matrix metalloproteinase-9 (MMP-9) was significantly higher than M-PSCAs groups. The logistic regression analyses showed that the M-PSCAs was an independent risk factor of postoperative cerebral hyperperfusion (CHP) syndrome (OR 6.235, 95% CI1.018-38.170, P = 0.048) in MMD. Conclusion: Our results indicate that M-PSCAs adult MMD patients had thinner intima than non-MCAs adult MMD patients in the PSCAs. More importantly, HIF-1α and MMP-9 were overexpressed in non-M-PSCAs vascular specimens.

A flow self-regulating superficial temporal artery-middle cerebral artery bypass based on side-to-side anastomosis for adult patients with moyamoya disease.

OBJECTIVE: Side-to-side (S-S) superficial temporal artery-middle cerebral artery (STA-MCA) bypass was reportedly used to treat a special moyamoya disease (MMD) patient with collaterals arising from the donor STA. However, the S-S technique is not routinely performed to date, and its benefits are still unknown for adult MMD. The purpose of this study was to investigate the possibility of routine use of the S-S technique for adult MMD. METHODS: The authors retrospectively analyzed the clinical data of 50 adult patients (65 hemispheres, including 30 in the end-to-side [E-S] group and 35 in the S-S group) with MMD who underwent STA-MCA bypass. The patient demographic characteristics, clinical courses, technical details, intraoperative blood flow data, postoperative and preoperative relative cerebral blood flow (rCBF) values, modified Rankin Scale (mRS) scores, and short-term revascularization results were compared between the 2 groups. RESULTS: There were no significant differences observed in terms of the baseline characteristics, bypass patency rates, postoperative/preoperative rCBF values, incidence of cerebral hyperperfusion syndrome (CHS), mRS scores, and short-term revascularization results between the 2 groups (all p > 0.05). Intraoperative blood flow analysis showed that the increase of STA flow in the E-S group was significantly higher than that of proximal STA flow in the S-S group (p = 0.008). Although the increases of proximal and distal recipient flow in the E-S group seemed greater than those in the S-S group, the results were not statistically significant (p = 0.086 for proximal flow and p = 0.076 for distal flow). CHS symptoms in the S-S group were milder and with much shorter duration. The follow-up angiographic data of the representative case demonstrated that both frontal and parietal STA branches and the occipital artery participated in postoperative collateralization. CONCLUSIONS: S-S anastomosis can achieve comparable clinical effects to standard E-S construction. S-S anastomosis used in adult MMD demonstrated mild CHS symptoms with short duration and had the potential to arouse all scalp arteries as donor sources for revascularization through the intact distal STA branch via flow self-regulation.

Study of active ingredients in black soybean sprouts and their safety in cosmetic use.

Active ingredients in different lengths of black soybean sprouts were extracted with water. Concentrations of the main proteins and polysaccharides were determined by the Forint phenol assay and phenol-sulfuric acid assay, respectively. Anti-oxidizing capacities of the extracts were measured in vitro using the DPPH scavenging test and whitening capacity was measured in vitro using the tyrosinase inhibition test. The effects of the bean sprout extracts on human skin fibroblasts damnified by H2O2 were studied using an MTT colorimetric assay. The safety of the extracts was determined using the red blood cell (RBC) test, chick chorioallantoic membrane (CAM) assay and human patch test. Results show that DPPH radical scavenging rates at different shoot lengths were all greater than 95%, while the tyrosinase inhibition capacity of the extracts reached 98%. Hemolysis rate in all extracts were lower than 10%, below the 20% regulatory limit for the RBC test. No signs of allergic reactions were observed in the human patch tests. The optimum extract was obtained from bean sprouts grown to 0.5 cm. Extracts of black bean sprouts are safe and can be used as additives in anti-aging and whitening cosmetic products.

How to choose the surgical side when cerebral blood flow and cerebrovascular response are contradictory in bilateral moyamoya disease?: A case report.

INTRODUCTION: Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by progressive occlusion of the internal carotid artery and the secondary formation of collateral vessels. Bypass surgery is an effective treatment for MMD. Comprehensive evaluation of cerebral blood flow (CBF) and cerebrovascular response (CVR) is the common hemodynamic indication to surgery, the changes of which are usually identical. THE PATIENTS MAIN CONCERNS AND IMPORTANT EXAMINATIONS: We reported a rare case of MMD in a 34-year-old pregnant woman with transient ischemic attacks (TIAs) for 1 month, manifesting as frequent weakness in right limbs for several minutes without obvious cause. The diagnostic digital subtraction angiography (DSA) examination revealed Suzuki Grade I in left side and Grade IV in right side under modified Suzuki scoring. No-hyperventilation test single-photon emission computed tomography (no-HVT SPECT) showed more decreased CBF in the right side of the brain, but HVT SPECT demonstrated a more impaired CVR on the left side. Comprehensively, which side should be operated on is confusing when the changes of CVR and CBF are inconsistent. THE MAIN DIAGNOSIS, THERAPEUTICS INTERVENTIONS, AND OUTCOMES: The patient was diagnosed with bilateral MMD and underwent combined bypass surgery on the left side of the brain. The symptoms of admission were completely relieved after surgery and there were no further cerebrovascular events during the follow-up period of 4 months. CONCLUSION: CVR is a primary surgical indication of MMD, especially when the impairment of CVR and CBF are not consistent in the ipsilateral hemisphere. Meanwhile, HVT is the vital vasoactive challenges test for measuring CVR in MMD.

Lysosomal-associated transmembrane protein 5 deficiency exacerbates cerebral ischemia/reperfusion injury.

Lysosomal-associated transmembrane protein 5 (LAPTM5) has been demonstrated to be involved in regulating immunity, inflammation, cell death, and autophagy in the pathophysiological processes of many diseases. However, the function of LAPTM5 in cerebral ischemia-reperfusion (I/R) injury has not yet been reported. In this study, we found that LAPTM5 expression was dramatically decreased during cerebral I/R injury both in vivo and in vitro. LAPTM5 knockout (KO) mice were compared with a control, and they showed a larger infarct size and more serious neurological dysfunction after transient middle cerebral artery occlusion (tMCAO) treatment. In addition, inflammatory response and apoptosis were exacerbated in these processes. Furthermore, gain- and loss-of-function investigations in an in vitro model revealed that neuronal inflammation and apoptosis were aggravated by LAPTM5 knockdown but mitigated by its overexpression. Mechanistically, combined RNA sequencing and experimental verification showed that the apoptosis signal-regulating kinase 1 (ASK1)-c-Jun N-terminal kinase (JNK)/p38 pathway was mainly involved in the detrimental effects of LAPTM5 deficiency following I/R injury. Specifically, LAPTM5 directly interacts with ASK1, leading to decreased ASK1 N-terminal dimerization and the subsequent reduced activation of downstream JNK/p38 signaling. In conclusion, LAPTM5 was demonstrated to be a novel modulator in the pathophysiology of brain I/R injury, and targeting LAPTM5 may be feasible as a stroke treatment.

Helicobacter Pylori and Autoimmune Diseases: Involving Multiple Systems.

The modern Gastroenterology have witnessed an essential stride since Helicobacter pylori was first found in the stomach and then its pathogenic effect was discovered. According to the researches conducted during the nearly 40 years, it has been found that this bacterium is associated with a natural history of many upper gastrointestinal diseases. Epidemiological data show an increased incidence of autoimmune disorders with or after infection with specific microorganisms. The researches have revealed that H. pylori is a potential trigger of gastric autoimmunity, and it may be associated with other autoimmune diseases, both innate and acquired. This paper reviews the current support or opposition about H. pylori as the role of potential triggers of autoimmune diseases, including inflammatory bowel disease, autoimmune thyroiditis, type 1 diabetes mellitus, autoimmune liver diseases, rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, as well as Sjogren's syndrome, chronic urticaria and psoriasis, and tried to explain the possible mechanisms.

Endoscope-Assisted Microsurgery in Pediatric Cases With Pineal Region Tumors: A Study of 18 Cases Series.

Background: An endoscope-assisted technique was recently introduced to microsurgery (MS) and may compensate for the disadvantages of MS for deep-seated lesions. This study was performed to identify the effectiveness and safety of endoscopic-assisted microsurgery (EAM) and share our experience of EAM for pediatric cases with pineal region tumors. Method: We retrospectively analyzed the clinical data of consecutive pediatric cases with pineal region tumors treated by EAM or MS from January 2016 to June 2020. These data included the patient population, clinical manifestations, preoperative examination findings, surgical approach, pathological results, and clinical outcomes. The clinical outcomes were analyzed in the EAM group and MS group with a focus on the gross total resection (GTR) rate, postoperative hydrocephalus remission rate, and Karnofsky performance score (KPS). Studies on the surgical management of children with pineal region tumors in the last decade were reviewed. Result: Eighteen children successfully underwent tumor resection via MS (n = 8) or EAM (n = 10). The children's mean age was 11.4 ± 4.7 years, and the male to female ratio was 7:2. Seventeen patients (94.4%) complicated preoperative hydrocephalus, and 16 (88.9%) presented headache with nausea and/or vomiting. The pathological examination revealed germ cell tumors in 11 (61.1%) patients, neuroepithelial tumors in 4 (22.2%) patients, and a pineoblastoma, arachnoid cyst, and atypical teratoid rhabdoid tumor in 1 (5.6%) patient each. GTR was more commonly achieved in the EAM than MS group (80.0 vs. 50.0%, respectively), and the postoperative hydrocephalus remission rate was higher in the EAM than MS group (87.5 vs. 50.0%, respectively). At a mean follow-up time of 23.6 ± 11.5 weeks, the mean improvement of the KPS 6 months postoperatively was greater in the EAM than MS group (24.0 ± 9.7 vs. 17.5 ± 7.1 points, respectively). Conclusion: EAM combines endoscopic and microsurgical techniques and can be safely and effectively performed to achieve GTR of pineal region tumors in pediatric patients. In children with pineal region tumors who have obstructive hydrocephalus, EAM could improves hydrocephalus remission rates by checking and clearing the midbrain aqueduct under visualization.

Combined Endovascular and Surgical Treatment for Brain Arteriovenous Malformations in Biplanar Hybrid Operating Room.

OBJECTIVE: Combined surgical and endovascular treatment for vascular disorders has become prevalent in recent years. However, reports on one-session hybrid surgery for arteriovenous malformations (AVMs) are relatively rare. The safety and efficiency of combined treatment for brain AVMs were analyzed in biplanar hybrid operating room (OR) at one stage. METHODS: We retrospectively analyzed 20 patients with AVMs undergoing combined surgical and endovascular treatment from October 2015 to June 2018. The data for resection rate, microcatheter adhesion, surgical position and postoperative outcomes were analyzed. Total resection or near-total resection was achieved in all cases. RESULTS: A total of 13 patients were under combined endovascular and surgical procedures, and 7 experienced surgery with intraoperative digital subtraction angiography. Sitting position was applied in 3 of them; 2 niduses in cerebellum, and 1 in parietal lobe. Compared with admission modified Rankin Scale (mRS) in all patients, postoperative 12-month mRS showed a significant decline. Besides, 3 patients experienced microcatheter adhesion after endovascular embolization, thereafter underwent surgical adhesion removal while nidus resection was done. CONCLUSION: Combined endovascular and surgical modality in a hybrid OR at one stage provides a safe strategy for the treatment of AVMs. The biplanar hybrid neurointerventional suite is endowed with unconstrained operating angle which enables combined endovascular and surgical treatment in sitting position. It also reduces the risk of microcatheter adhesion, which enables interventional radiologists to perform aggressively.

Effect of Tang-Shen-Ning decoction on podocyte epithelial-esenchymal transformation via inhibiting Wnt/ß-catenin pathway in diabetic mice.

BACKGROUND: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). Podocyte epithelial-esenchymal transformation (EMT) induced by the activated Wnt/ß-catenin pathway plays a key role in DN. Tang-Shen-Ning (TSN), a Chinese herbal formula, has been shown to decrease proteinuria and protect the renal function in DN. However, the effect of TSN on the Wnt/ß-catenin pathway and podocyte EMT is unclear. METHODS: TSN was orally administrated in KK-Ay mice for 4 weeks, at a daily dose of 20 g/kg body weight in our in vivo study. Rat serum containing TSN was added in podocyte cultured in high glucose for 24 h. The levels of 24 h urine protein, serum creatinine and blood urea nitrogen were detected by ELISA. Nephrin, Synaptopodin, P-cadherin, desmin, FSP-1, and collagen I protein and mRNA expressions were detected by western blot, immunohistochemistry, immunofluorescence, and RT-PCR. Snail, ß-catenin, and TCF/LEF were detected by Western blot, RT-PCR and luciferase. RESULTS: TSN significantly decreased 24-h urine protein, serum creatinine, and blood urea nitrogen in DN mice. Further, TSN also significantly increased the expression of nephrin, synaptopodin, and P-cadherin, while the expression of desmin, fibroblast-specific protein 1 (FSP-1), and collagen I of podocytes was significantly decreased. Moreover, TSN significantly inhibited the activation of the Wnt/ß-catenin pathway in podocytes cultured under high glucose (HG). Notably, the effect of TSN on podocyte EMT was reversed by activation of the Wnt/ß-catenin pathway. CONCLUSIONS: TSN could protect podocytes from injury in DN, partly via inhibiting the activation of the Wnt/ß-catenin pathway and ameliorating podocyte EMT.

Clinical Characteristics and Outcomes of 421 Patients With Coronavirus Disease 2019 Treated in a Mobile Cabin Hospital.

Background: In December 2019, a novel coronavirus-associated pneumonia, now known as coronavirus disease 2019 (COVID-19), was first detected in Wuhan, China. To prevent the rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and treat patients with mild symptoms, sports stadiums and convention centers were reconstructed into mobile hospitals. Research Question: It is unknown whether a mobile cabin hospital can provide a safe treatment site for patients with mild COVID-19 symptoms. Study Design and Methods: This study retrospectively reviewed the medical records of 421 patients with COVID-19 admitted to a mobile cabin hospital in Wuhan from February 9, 2020, to March 5, 2020. Clinical data comprised patient age, sex, clinical presentation, chest imaging, nucleic acid testing, length of hospitalization, and outcomes. Results: Of the patients who were discharged from the cabin hospital, 362 (86.0%) were categorized as recovered; 14.0% developed severe symptoms and were transferred to a designated hospital. The most common presenting symptoms were fever (60.6%) and cough (52.0%); 5.2% exhibited no obvious symptoms. High fever (> 39.0°C) was more common in severe cases than in recovered cases (18.6% vs 6.6%). The distribution of lung lesions was peripheral in 85.0% of patients, multifocal in 69.4%, and bilateral in 68.2%. The most common pattern was ground-glass opacity (67.7%), followed by patchy shadowing (49.2%). The incidence of patchy shadowing was higher in patients with severe disease (66.1%) than in those who recovered (31.8%, P < .0001). The median length of hospitalization was 17 days (interquartile range, 14-19 days), and the median time taken for positive real-time reverse transcriptase polymerase chain reaction results to become negative in recovered patients was 8 days (interquartile range, 6-10 days). Interpretation: Mobile cabin hospitals provide a safe treatment site for patients with mild COVID-19 symptoms and offer an effective isolation area to prevent the spread of severe acute respiratory syndrome coronavirus 2.

CARD3 Promotes Cerebral Ischemia-Reperfusion Injury Via Activation of TAK1.

Background Although multiple signaling cascades and molecules contributing to the pathophysiological process have been studied, the treatments for stroke against present targets have not acquired significant clinical progress. Although CARD3 (caspase activation and recruitment domain 3) protein is an important factor involved in regulating immunity, inflammation, lipid metabolism, and apoptosis, its role in cerebral stroke is currently unknown. Methods and Results Using a mouse model of ischemia-reperfusion (I-R) injury based on transient blockage of the middle cerebral artery, we have found that CARD3 expression is upregulated in a time-dependent manner during I-R injury. Further animal study revealed that, relative to control mice, CARD3-knockout mice exhibited decreased inflammatory response and neuronal apoptosis, with reduced infarct volume and lower neuropathological scores. In contrast, neuron-specific CARD3-overexpressing transgenic (CARD3-TG) mice exhibited increased I-R induced injury compared with controls. Mechanistically, we also found that the activation of TAK1 (transforming growth factor-ß-activated kinase 1) was enhanced in CARD3-TG mice. Furthermore, the increased inflammation and apoptosis seen in injured CARD3-TG brains were reversed by intravenous administration of the TAK1 inhibitor 5Z-7-oxozeaenol. Conclusions These results indicate that CARD3 promotes I-R injury via activation of TAK1, which not only reveals a novel regulatory axis of I-R induced brain injury but also provides a new potential therapeutic approach for I-R injury.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: An evidence-based clinical practice guideline (updated version).

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.

Prognostic value of long noncoding RNA ROR in patients with cancer in China: A systematic review and meta-analysis.

BACKGROUND: For cancer, it is common that there is usually a dysregulation of the long noncoding RNA regulator of reprogramming (LncRNA ROR). To illustrate the application of LncRNA ROR, which serves as the prognostic marker for the malignant tumors, it is of great importance to conduct a meta-analysis. METHODS: There were 3 databases being applied. The data used were collected before January 5, 2018. These 3 databases include the OVID, PubMed, and Science databse. To further explore the association between the expression and survival of LncRNA ROR, it calculated the 95% confidence intervals (CIs) and hazard ratios (HRs). Meanwhile, the odds ratios (ORs) have been calculated for the evaluation of the correlation between the pathological and expression parameters of LncRNA ROR. RESULTS: There were 8 researches participated by 720 patients. According to the HR, it has been implied that there was a high LncRNA ROR expression related with the weak disease-free survival (DFS) (HR = 3.48, 95% CI, 2.24-5.41) and overall survival (OS) (HR = 2.47, 95% CI, 1.76-3.47) among the cancer patients with none dramatic heterogeneity. There was also a correlation among lymph node metastasis (OR = 5.38, 95% CI, 2.21-13.12), high tumor stage (OR = 3.80, 95% CI, 1.95-7.41), and larger tumor size (OR = 4.43, 95% CI, 1.26-15.51). CONCLUSIONS: Thus, it can be predicted about the lymph node metastasis and high tumor stage, larger tumor size, DFS, and poor OS based on the high LncRNA ROR. This suggests that high LncRNA ROR can be used as a new indicator of poor prognosis in cancer.