Analysis of related factors for RA flares after SARS-CoV-2 infection: a retrospective study from patient survey.

SARS-CoV-2 and its variants are widely prevalent worldwide. With frequent secondary and breakthrough infections, immune dysfunction in RA patients, and long-term use of immune preparations, SARS-CoV-2 infection poses a significant challenge to patients and rheumatologists. Whether SARS-CoV-2 infection causes RA flares and what factors aggravate RA flares are poorly studied. A questionnaire survey was conducted on RA patients infected with SARS-CoV-2 after December 7, 2022, in China through a multicenter and inter-network platform regarding general personal condition, primary disease, comorbidity, SARS-CoV-2 vaccination, viral infection, and impact on the primary disease. A total of 306 RA patients were included in this study, and the patient data were analyzed, in which the general condition of RA patients, medication use before SARS-CoV-2 infection and post-infection typing and manifestations, and medication adjustment did not affect the Flare of RA patients after SARS-CoV-2 infection. The control of disease before SARS-CoV-2 infection (OR = 2.10), RA involving pulmonary lesions (OR = 2.28), and the recovery time of COVID-19 (OR = 2.50) were risk factors for RA flare. RA involving pulmonary lesions, control status of disease before infection, and recovery time of COVID-19 disease are risk factors for RA flare after SARS-CoV-2 infection.

Suppression of SAMSN1 contributes to neuroprotection in neonatal rats suffering from hypoxic-ischemic encephalopathy injury.

This article aims to detect the effect of SAM domain, SH3 domain, and nuclear localization signal 1 (SAMSN1) in neonatal rats with neurological dysfunction induced by hypoxia and ischemia (HI). The HI model was created using 7-day postnatal rats. Zea-longa score was utilized to validate the neurological injury after HI. Then, the differentially expressed genes (DEGs) were detected by gene sequencing and bioinformatics analysis methods. The oxygen and glucose deprivation (OGD) models were established in the SY5Y cells and fetal human cortical neurons. In addition, SAMSN1-small interfering RNA, methyl thiazolyl tetrazolium assay, and cell growth curve were employed to evaluate the cell viability variation. Obviously, Zea-longa scores increased in rats with HI insult. Subsequently, SAMSN1 was screened out, and it was found that SAMSN1 was strikingly upregulated in SY5Y cells and fetal neurons post-OGD. Interestingly, we found that SAMSN1 silencing could markedly enhance cell viability and cell growth after OGD. These data suggested that downregulation of SAMSN1 may exert a neuroprotective effect on damaged neurons after HI by improving cell viability and cell survival, which provides a potential theoretical basis for clinical trials in the future to treat neonatal hypoxic-ischemic encephalopathy.

Therapeutic effect of umbilical cord blood cells on spinal cord injury.

Spinal cord injury (SCI) is a nervous system disease characterized by sensory and motor dysfunction, axonal apoptosis, decreased vascular density, and inflammation. At present, surgical treatment, drug treatment, and cell therapy can be used. Surgical treatment can improve motor and independent function scores, and drug treatment can promote the recovery of neurons in the spinal cord, but only improve symptoms. Complete recovery of SCI has not yet been achieved. However, the differentiation of stem cells brings hope for the treatment of SCI. Umbilical cord blood cells (UCBs) are ethically readily available and can repair neuronal damage. However, it is still unclear how they can improve symptoms and repair nerve severity. In this paper, the role of UCBs in the treatment of SCI is described in detail from different aspects such as behavior, morphology, and molecular expression changes, so as to provide new ideas and theoretical directions for future research.

Shape-Reconfigurable Ferrofluids.

Ferrofluids (FFs) can adapt their shape to a magnetic field. However, they cannot maintain their shape when the magnetic field is removed. Here, with a magneto-responsive and reconfigurable interfacial self-assembly (MRRIS) process, we show that FFs can be structured by a magnetic field and maintain their shape, like solids, after removing the magnetic field. The competing self-assembly of magnetic and nonmagnetic nanoparticles at the liquid interface endow FFs with both reconfigurability and structural stability. By manipulating the external magnetic field, we show that it is possible to "write" and "erase" the shape of the FFs remotely and repeatedly. To gain an in-depth understanding of the effect of MRRIS on the structure of FFs, we systematically study the shape variation of these liquids under both the static and dynamic magnetic fields. Our study provides a simple yet novel way of manipulating FFs and opens opportunities for the fabrication of all-liquid devices.

Cardiovascular Effects of High-Frequency Magnetic Seizure Therapy Compared With Electroconvulsive Therapy.

BACKGROUND: Magnetic seizure therapy (MST) is a novel convulsive therapy that has been shown to have antidepressant efficacy comparable to electroconvulsive therapy (ECT) with fewer cognitive side effects. However, the cardiovascular (CVS) effects of high frequency MST in comparison to ECT have not been investigated. MATERIALS AND METHODS: Forty-five patients with depression received 6 treatment sessions of 100 Hz MST versus 6 bifrontal ECT treatments in a nonrandomized comparative clinical design. Data on CVS function including heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and rate pressure product (RPP) were collected at baseline (T0), after the induction of anesthesia but before the electrical stimulation (T1), during convulsion (T2), 2 minutes after cessation of motor seizure (T3), 5 minutes after cessation of motor seizure (T4), and 10 minutes after cessation of motor seizure (T5). Comparisons were made with baseline data and between MST and ECT groups. RESULTS: There were statistically significant elevations in the maximum HR, SBP, DBP, and RPP in patients receiving ECT compared with MST both in the initial and sixth treatments (all P < 0.05). Particularly, at T2, the ECT group had significantly higher HR, SBP, DBP, and RPP than those in MST group both in initial and sixth treatment (all P < 0.001). At the sixth treatment, the ECT group had significantly higher SBP, DBP, and RPP during the treatment than in the MST group (all P < 0.001). LIMITATIONS: The anesthetic choices for this study may limit the generalizability of our findings. The sample size was relatively small. CONCLUSIONS: Compared with ECT, high-frequency MST has fewer CVS side effects and may be a safer option for depression patients with CVS disorders.

Whether it is safe to start anticoagulation after intracranial hemorrhage within 2 weeks: A systematic review and meta-analysis.

Whether restarting anticoagulation (RA) treatment after intracranial hemorrhage (ICH) is still controversial. We performed a systematic review and meta-analysis to summarize the relationship between anticoagulation after ICH with the recurrence of hemorrhagic events, ischemic events, and long-term mortality. Medline, Embase, and the Cochrane Central Register of Controlled Trials, from inception to November 2020. We searched the published medical literature to ensure cohort studies involving ICH associated with anticoagulation in adults. Primary outcomes were long-term mortality, hemorrhagic events, and ischemic events (myocardial infarction, pulmonary embolism, ischemic stroke, or systemic embolization). We concluded seven retrospective cohorts, including 1876 intracranial hemorrhage patients with indications of anticoagulation. The ratio of the anticoagulant restart was 35.3% (664n). RA was associated with a significantly lower incidence of recurrent ischemic events (pooled odds ratio [OR] 0.29, 95% confidence interval [CI] 0.19% to 0.45%, p = 0.97) and death events (pooled OR 0.56, 95% CI 0.40%-0.79%, p = 0.27). There is no evidence that early recovery of anticoagulation (within 2 weeks or 1 month) is associated with the occurrence of hemorrhagic events (within 2 weeks: pooled OR 0.80, 95% CI 0.3-2.12, p = 0.52 vs. within 1 month: pooled OR 1.14, 95% CI 0.77-1.68, p = 0.82). Based on these, recovery of anticoagulation after ICH is beneficial for long-term mortality and recurrence of ischemic events. The meta-analysis showed a resumption of oral anticoagulation within 2 weeks or 1 month in patients who had a cerebral hemorrhage was beneficial and did not increase the risk of hemorrhagic events and reduced the occurrence of ischemic and fatal endpoint events.

The differentially expressed proteins related to clinical viral encephalitis revealed by proteomics.

To screen out the prospective biomarkers of viral encephalitis (VE), analyze the biological process and signaling pathways involved by differentially expressed proteins (DEPs). A total of 11 cerebrospinal fluid (CSF) samples with VE and 5 with non-nervous system infection were used to perform label-free proteomic techniques. Then, the bioinformatic analysis of DEPs was applied by Interproscan software. Moreover, 73 CSF samples in the VE group and 53 in the control group were used to verify the changes of some DEPs by enzyme-linked immunosorbent assay (ELISA). Thirty-nine DEPs were identified, including 18 upregulated DEPs and 21 downregulated DEPs. DEPs were mainly enriched in cell adhesion molecules by Kyoto Encyclopedia of Genes and Genomes analysis pathway analysis. The DEPs related to axon tissue were obviously downregulated and the most significant downregulated proteins were neurexin 3, neurofascin, and neuroligin 2 (NLGN2). Moreover, the protein expression of NLGN2 in the VE group was significantly higher than that in the control group by ELISA. The correlation analysis of NLGN2 in the VE group revealed that there was a weak positive correlation with CSF protein and a weak negative correlation with CSF chloride. The clinical VE may be closely related to NLGN2 and the cell adhesion molecule pathway.

Synergy of nanodiamond-doxorubicin conjugates and PD-L1 blockade effectively turns tumor-associated macrophages against tumor cells.

BACKGROUND: Tumor-associated macrophages (TAMs) are the most abundant stromal cells in the tumor microenvironment. Turning the TAMs against their host tumor cells is an intriguing therapeutic strategy particularly attractive for patients with immunologically "cold" tumors. This concept was mechanistically demonstrated on in vitro human and murine lung cancer cells and their corresponding TAM models through combinatorial use of nanodiamond-doxorubicin conjugates (Nano-DOX) and a PD-L1 blocking agent BMS-1. Nano-DOX are an agent previously proved to be able to stimulate tumor cells' immunogenicity and thereby reactivate the TAMs into the anti-tumor M1 phenotype. RESULTS: Nano-DOX were first shown to stimulate the tumor cells and the TAMs to release the cytokine HMGB1 which, regardless of its source, acted through the RAGE/NF-κB pathway to induce PD-L1 in the tumor cells and PD-L1/PD-1 in the TAMs. Interestingly, Nano-DOX also induced NF-κB-dependent RAGE expression in the tumor cells and thus reinforced HMGB1's action thereon. Then, BMS-1 was shown to enhance Nano-DOX-stimulated M1-type activation of TAMs both by blocking Nano-DOX-induced PD-L1 in the TAMs and by blocking tumor cell PD-L1 ligation with TAM PD-1. The TAMs with enhanced M1-type repolarization both killed the tumor cells and suppressed their growth. BMS-1 could also potentiate Nano-DOX's action to suppress tumor cell growth via blocking of Nano-DOX-induced PD-L1 therein. Finally, Nano-DOX and BMS-1 achieved synergistic therapeutic efficacy against in vivo tumor grafts in a TAM-dependent manner. CONCLUSIONS: PD-L1/PD-1 upregulation mediated by autocrine and paracrine activation of the HMGB1/RAGE/NF-κB signaling is a key response of lung cancer cells and their TAMs to stress, which can be induced by Nano-DOX. Blockade of Nano-DOX-induced PD-L1, both in the cancer cells and the TAMs, achieves enhanced activation of TAM-mediated anti-tumor response.

Interleukin 10 Plays an Important Role in Neonatal Rats with Hypoxic-Ischemia Associated with B-Cell Lymphoma 2 and Endoplasmic Reticulum Protein 29.

Interleukin 10 (IL-10) is a synthetic inhibitor of human cytokines with immunomodulatory and anti-inflammatory effects. This study was designed to investigate the expression variation of IL-10 in the multiple sites including cortex, hippocampus, and lung tissues of neonatal hypoxic-ischemic (HI) rats and explore the crucial role of IL-10 in alleviating HI brain damage. In this study, neonatal Sprague-Dawley rats were subjected to the right common carotid artery ligation, followed by 2 h of hypoxia. The expression of IL-10 in the cortex, hippocampus, and lung tissues was measured with immunohistochemistry, real-time quantitative polymerase chain reaction (RT-qPCR), and western blot (WB). Immunofluorescence double staining was performed to observe the localization of IL-10 in neurons and astrocytes. Moreover, not-targeting and targeting IL-10 siRNA lentivirus vectors were injected into the rats of the negative control (NC) and IL-10 group, respectively, and the mRNA levels of B-cell lymphoma 2 (Bcl-2) and endoplasmic reticulum protein 29 (ERp29) were detected by RT-qPCR following IL-10 silence. The results demonstrated that the IL-10 expression was markedly increased after HI and IL-10 were colocalized with neurons and astrocytes which were badly injured by HI insult. In addition, Bcl-2 and ERp29 were remarkably decreased following IL-10 mRNA interference compared with the NC group. Our findings revealed that IL-10 exerted its antiapoptotic and neuroprotective effects by regulating the expression of Bcl-2 and ERp29, indicating that IL-10 may be a promising molecule target for HIE treatment.

Outcomes of individualized goal-directed therapy based on cerebral oxygen balance in high-risk patients undergoing cardiac surgery: A randomized controlled trial.

STUDY OBJECTIVE: To investigate whether optimizing individualized goal-directed therapy (GDT) based on cerebral oxygen balance in high-risk surgical patients would reduce postoperative morbidity. DESIGN: This was a prospective, randomized, controlled study. SETTING: The study was performed in the First Affiliated Hospital of Anhui Medical University, Hefei, China, from April 2017 to July 2018. PATIENTS: 146 high-risk adult patients undergoing valve replacements or coronary artery bypass surgery with cardiopulmonary bypass (CPB) were enrolled. INTERVENTION: Patients were randomized to an individualized GDT group or usual care group. Individualized GDT was targeted to achieve the following goals: A less than 20% decline in the regional cerebral oxygen saturation (rScO2) level from baseline; a less than 20% decline in the mean arterial pressure (MAP) from baseline, as well as a bispectral index (BIS) of 45-60 before and after CPB and 40-45 during CPB. MEASUREMENTS: The primary outcome was a composite endpoint of 30-day mortality and major postoperative complications. MAIN RESULTS: 128 completed the trial and were included in the modified intention-to-treat analysis. Early morbidity was similar between the GDT (25 [39%] of 65 patients) and usual care groups (33 [53%] of 63 patients) (relative risk 0.73, 95% CI 0.50-1.08; P = 0.15). Secondary analysis showed that 75 (59%) of 128 patients achieved individual targets (irrespective of intervention) and sustained less morbidity (relative risk 3.41, 95% CI 2.19-5.31; P < 0.001). CONCLUSIONS: In high-risk patients undergoing cardiac surgery, individualized GDT therapy did not yield better outcomes, however, the achievement of preoperative individual targets may be associated with less morbidity. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03103633. Registered on 1 April 2017.

Neuroprotection of Cyperus esculentus L. orientin against cerebral ischemia/reperfusion induced brain injury.

Orientin is a flavonoid monomer. In recent years, its importance as a source of pharmacological active substance is growing rapidly due to its properties such as anti-myocardial ischemia, anti-apoptosis, anti-radiation, anti-tumor, and anti-aging. However, the neuroprotective effects of Orientin on stroke injury have not been comprehensively evaluated. The aim of the present study was thus to investigate the neuroprotective capacity and the potential mechanisms of Cyperus esculentus L. orientin (CLO) from Cyperus esculentus L. leaves against ischemia/reperfusion (I/R) injury using standard orientin as control. For in vitro studies, we treated HT22 cells with CoCl2 as an in vitro ischemic injury model. HT22 cells in the control group were treated with CoCl2. For in vivo studies, we used rat models of middle cerebral artery occlusion, and animals that received sham surgery were used as controls. We found that CLO protected CoCl2-induced HT22 cells against ischemia/reperfusion injury by lowering lipid peroxidation and reactive oxygen species formation as well as decreasing protein oxidation. However, CLO did not reduce the release of lactate dehydrogenase nor increase the activity of superoxide dismutase. Results showed that CLO could decrease neurological deficit score, attenuate brain water content, and reduce cerebral infarct volume, leading to neuroprotection during cerebral ischemia-reperfusion injury. Our studies indicate that CLO flavonoids can be taken as a natural antioxidant and bacteriostastic substance in food and pharmaceutical industry. The molecular mechanisms of CLO could be at least partially attributed to the antioxidant properties and subsequently inhibiting activation of casepase-3. All experimental procedures and protocols were approved on May 16, 2016 by the Experimental Animal Ethics Committee of Xinjiang Medical University of China (approval No. IACUC20160516-57).

Using Prognosis-Related Gene Expression Signature and Connectivity Map for Personalized Drug Repositioning in Multiple Myeloma.

BACKGROUND Multiple myeloma (MM) is the second most common hematologic cancer with poor prognosis. Novel therapeutic strategies are needed to decrease the high mortality rate. The aim of this study was to identify prospective agents for MM. MATERIAL AND METHODS A microarray dataset was mined, which contains the transcriptome profiles of 588 MM patients. Univariate Cox analysis was performed to analyze the relationships between genes and clinical outcome. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were determined. Protective and risky genes were uploaded to Connectivity Map (CMAP) database to identify the potentially unknown effects of existing drugs. An example was selected to be docked on the known molecules. RESULTS A total of 1445 genes significantly correlated with the event free survival (EFS) of MM patients were identified and included 676 protective and 769 risky indicators. KEGG pathway analysis revealed that these prognosis-associated genes were enriched in the "cell cycle," "DNA replication," and "P53 signaling pathway". The top t3 most significant potential molecules were vorinostat, trifluoperazine, and thioridazine. CDK1 (cyclin-dependent kinase-1) ranked as the core in the class of prognosis-related genes in MM based on protein-protein interaction (PPI) network analysis. With Sybyl-X 2.0, the majority of the top 10 molecules aforementioned displayed high binding forces with CDK1. Among these molecules, trichostatin A had the greatest ability in combining with CDK1. CONCLUSIONS Genes that mainly accumulate in the cell cycle pathway play an essential role in the prognosis of MM, and these prognosis-related genes also have great value in drug development.

Stevioside attenuates isoproterenol-induced mouse myocardial fibrosis through inhibition of the myocardial NF-κB/TGF-ß1/Smad signaling pathway.

Stevioside, a natural glycoside compound, has many beneficial biological activities, but its protective effect on myocardial fibrosis has not been reported yet. This study aimed to investigate the effect of stevioside. The isoproterenol-induced model mice were orally given stevioside 75-300 mg kg-1 for 40 days. The results showed that after the administration of stevioside, the myocardial hydroxyproline, collagen accumulation, and protein expressions of collagen I/III, α-smooth muscle actin, transforming growth factor-ß1 (TGF-ß1), nuclear factor kappa B p65 (NF-κB p65), Smad2/3, and P-Smad2/3 were decreased, while the glutathione peroxidase and superoxide dismutase levels in serum and myocardial tissues and protein expressions of myocardial peroxisome proliferator-activated receptor γ (PPARγ) and Smad7 were increased. After the preincubation of isoproterenol-stimulated cardiac fibroblasts with the PPARγ antagonist GW9662, stevioside-reduced protein expressions were decreased, but stevioside-induced Smad7 was not affected. These findings demonstrated that stevioside could exert a protective effect on mouse myocardial fibrosis, and its mechanisms were associated with the increments of antioxidant ability, PPARγ activation, and Smad7 expression, which caused a synergistic inhibition of the NF-κB/TGF-ß1/Smad signaling pathway.

Cashmere growth control in Liaoning cashmere goat by ovarian carcinoma immunoreactive antigen-like protein 2 and decorin genes.

OBJECTIVE: The study investigated the biological functions and mechanisms for controlling cashmere growth of Liaoning cashmere goat by ovarian carcinoma immunoreactive antigen-like protein 2 (OCIAD2) and decorin (DCN) genes. METHODS: cDNA library of Liaoning cashmere goat was constructed in early stages. OCIAD2 and DCN genes related to cashmere growth were identified by homology analysis comparison. The expression location of OCIAD2 and DCN genes in primary and secondary hair follicles (SF) was performed using in situ hybridization. The expression of OCIAD2 and DCN genes in primary and SF was performed using real-time polymerase chain reaction (PCR). RESULTS: In situ hybridization revealed that OCIAD2 and DCN were expressed in the inner root sheath of Liaoning cashmere goat hair follicles. Real-time quantitative PCR showed that these genes were highly expressed in SF during anagen, while these genes were highly expressed in primary hair follicle in catagen phase. Melatonin (MT) inhibited the expression of OCIAD2 and promoted the expression of DCN. Insulin-like growth factors-1 (IGF-1) inhibited the expression of OCIAD2 and DCN, while fibroblast growth factors 5 (FGF5) promoted the expression of these genes. MT and IGF-1 promoted OCIAD2 synergistically, while MT and FGF5 inhibited the genes simultaneously. MT+IGF-1/MT+FGF5 inhibited DCN gene. RNAi technology showed that OCIAD2 expression was promoted, while that of DCN was inhibited. CONCLUSION: Activation of bone morphogenetic protein (BMP) signaling pathway up-regulated OCIAD2 expression and stimulated SF to control cell proliferation. DCN gene affected hair follicle morphogenesis and periodic changes by promoting transforming growth factor-ß (TGF-ß) and BMP signaling pathways. OCIAD2 and DCN genes have opposite effects on TGF-ß signaling pathway and inhibit each other to affect the hair growth.

HCRP1 downregulation confers poor prognosis and induces chemoresistance through regulation of EGFR-AKT pathway in human gastric cancer.

The current study aims to investigate the biological roles and clinical significance of HCRP1 in human gastric cancer. The expression pattern of HCRP1 in gastric cancer tissue and adjacent non-cancerous tissue was detected by immunohistochemistry. HCRP1 downregulation was found in 57 of 137 human gastric cancer samples and correlated with advanced TNM stage, positive nodal status, and relapse. Log-rank test showed that HCRP1 downregulation also correlated with poor overall survival and reduced relapse-free survival. In addition, we found that HCRP1 overexpression inhibited proliferation, colony formation, and invasion in HGC-27 cells. On the other hand, HCRP1 depletion by small interfering RNA promoted proliferation, colony formation, and invasion in SGC-7901 cells. We also treated gastric cancer cells with cisplatin. MTT and Annexin V/PI analysis were carried out to examine change of chemoresistance. We found that HCRP1 overexpression sensitized HGC-27 cells to cisplatin while its depletion reduced sensitivity in SGC-7901 cells. Moreover, we found that HCRP1 overexpression negatively regulated cyclin D1, MMP-2, p-EGFR, p-ERK, and p-AKT. HCRP1 depletion showed the opposite effects. In conclusion, our results suggest that HCRP1 downregulation might serve as an indicator for poor prognosis in gastric cancer patients. HCRP1 reduces drug resistance through regulation of EGFR-AKT signaling.

Efficacy and safety of ranibizumab for wet age-related macular degeneration in Chinese patients.

AIM: To evaluate the clinical efficacy and safety of ranibizumab for wet age-related macular degeneration (wAMD) in Chinese patients and to determine the mean number of injections administered over one year of follow-up. METHODS: This single centre, retrospective observational case series study included data from 121 patients with wAMD (121 eyes) who were diagnosed by indirect ophthalmoscopy, fluorescence fundus angiography (FFA), indocyanine green angiography, and optical coherence tomography. Ranibizumab was injected into the vitreous cavities once per month for 3mo and as needed afterwards. Changes in visual acuity and central foveal thickness (CFT) during the follow-up period were compared, and the mean number of injections over the year was calculated. Patients with one or more adverse events related to the drugs and injections were recorded for further adverse events analysis. RESULTS: The study population included 70 males and 51 females aged between 50 and 87y (mean: 71.32±9.41y). The mean number of injections over the first year was 5±1 (range: 3-9). The mean best-corrected visual acuity by Early Treatment Diabetic Retinopathy Study increased from 43.2±19.3 (95%CI: 39.8-46.7) at baseline to 51.7±20.1 (95%CI: 48.1-55.3), and central foveal thickness (CFT) decreased from 526.5±277.0 µm (95%CI: 476.6-576.4) to 258.2±161.6 µm (95%CI: 229.2-287.3) at 12mo. The differences were statistically significant (P<0.001). Visual acuity significantly improved in 34.1% of the patients (38 eyes), stabilized in 66.1% of the patients (80 eyes), and significantly decreased in 2.5% of the patients (3 eyes). CFT at baseline was an independent risk factor of decreased CFT and increased visual acuity. None of the patients had severe adverse events during the follow-up period. CONCLUSION: Ranibizumab can effectively control disease progression and improve visual acuity in patients with wAMD. The disease conditions of most patients stabilized after a one-year treatment with an average of 5 injections.

Modified O-T advancement flap for reconstruction of skin defects.

BACKGROUND: Round or oval defects are common in skin surgery. Functional and cosmetical reconstruction of defects in reparative process is critical for patients. Various flaps have been described, however, these flaps often result in longer scar or tip necrosis. To overcome these shortcomings, we modified O-T advancement flap on the basis of conventional O-T flap and observed the validity and complications during defect closure. MATERIALS AND METHODS: Defect transverse diameter was marked along the direction of minimum tension at the circular center. Extended line was drawn along defect transverse diameter with the same length of circular diameter. The skin was cut apart, and the flap was separated under the skin. Then the flap tips were sutured and fixed with the opposite center. After drainage, the defects were bandaged under compression. RESULTS: This study includes a total number of 48 patients. We examined the location and size of defect and postoperative clinical courses. The follow-up period was from 3 months to 1 year. Overall, 41 of 48 patients achieved the satisfactory postoperative effect. Recurrence and limb dysfunction complication was not observed, except 2 cases of wound scar, 3 cases of wound infect and 2 cases of flap tip necrosis. CONCLUSION: Modified O-T advancement flap is practical and safety. It overcomes the shortcomings of traditional O-T flap. Reconstruction of modified O-T flap is aesthetically acceptable.

Tbx3 overexpression in human gastric cancer is correlated with advanced tumor stage and nodal status and promotes cancer cell growth and invasion.

The objective of the current study was to investigate the expression pattern of Tbx3 and its clinicopathological significance in patients with gastric cancer. The expression pattern of Tbx3 in gastric cancer tissues and adjacent noncancerous surface epithelia and mucosal glands was detected by immunohistochemistry. Tbx3 was found to be overexpressed in 46 of 98 human gastric cancer samples, and this correlated with advanced clinical stage, tumor stage, and nodal status. In addition, in the SGC-7901 gastric cancer cell line, Tbx3 overexpression by plasmid transfection promoted growth and invasion. Conversely, depleting Tbx3 expression by small-interfering RNA inhibited proliferation and invasion in BGC-823 cell line. Moreover, Tbx3 accelerated cell cycle progression at the G1/S boundary. Tbx3 also regulated epithelial-to-mesenchymal transition (EMT) to promote cell invasion by repressing E-cadherin expression and increasing expression levels N-cadherin, vimentin. These results indicate that in gastric cancer, Tbx3 plays an important role and might be a useful therapy target.

Sufentanil attenuates impairment of the endothelium-dependent vasodilation induced by hypoxia-reoxygenation in the rat coronary artery.

Sufentanil has been used broadly in cardiac surgery, but the mechanisms by which it modulates coronary vascular tone after ischemia-reperfusion injury are largely unknown. Effects of sufentanil on coronary tone and on the relaxation of rat coronary arteries (CAs) in response to endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitroprusside) relaxing agents in the presence of hypoxia-reoxygenation (H/R) was studied in an in vitro organ chamber setup. Sufentanil (10-7-10-4 mol/L) relaxed rat CA rings in endothelium-dependent and endothelium-independent manners. In endothelium-intact rings, preincubation of H/R-treated CAs with sufentanil (10-5 mol/L) significantly increased the acetylcholine response, but did not augment sodium nitroprusside-induced relaxation. Sufentanil-mediated potentiation of acetylcholine-induced relaxation was not affected by a nitric oxide synthase inhibitor or by intermediate- or small-conductance Ca2+-activated K+ channel blockers. However, potentiation was abolished by iberiotoxin (100 nmol/L), a selective inhibitor of large-conductance Ca2+-activated K+ channels, as well as Rp-cAMPS (30 µmol/L), a cyclic AMP-dependent protein kinase (PKA) inhibitor. Sufentanil induced endothelium-dependent and endothelium-independent relaxation and attenuated H/R-induced impairment of endothelium-dependent vasodilation in the rat CAs. The potentiating effect of sufentanil may involve activation of large-conductance Ca2+-activated K+ channels via cAMP-dependent mechanisms.

The roles of serum CXCL16 in circulating Tregs and gastrointestinal stromal tumor cells.

Gastrointestinal stromal tumors (GIST) are the most common sarcomas of the digestive system. Abnormal expression of CXCL16 and its sole receptor, CXCR6, has been demonstrated in many cancers. However, no studies have shown the relationship between CXCL16 or CXCR6 expression and GIST. In this study, we detected CXCL16 and CXCR6 expression in GIST patient samples by using immunohistochemistry analysis and Western blot analysis. Serum CXCL16 level was determined by using enzyme-linked immunosorbent assay. Circulating Tregs were isolated by using flow cytometry. MTT assay, cell cycle assay, and transwell assay were used to test the effects of recombinant CXCL16 on Tregs and GIST cells in vitro. The levels of CXCL16 and CXCR6 protein were higher in cancer tissues than in normal tissues. Serum CXCL16 level and circulating Tregs were higher in GIST patients than that in the healthy volunteers. CXCL16, CXCR6, serum CXCL16, and circulating Tregs were significantly associated with a decreased survival time of patients. Relative to control cells, high concentration recombinant CXCL16 treated Tregs and GIST cells exhibited lower proliferation and mobility rates as assessed by MTT assay and transwell assay, respectively. Taken together, CXCL16 was observed to mediate the inhibitory effects in Tregs and GIST cells, and these involved suppression of the MEK/ERK signaling pathway.