POLE2 knockdown suppresses lymphoma progression via downregulating Wnt/ß-catenin signaling pathway.

Lymphoma is the most common malignant tumor arising from immune system. Recently, DNA polymerase epsilon subunit 2 (POLE2) was identified to be a tumor promotor in a variety of malignant tumors. However, the biological role of POLE2 in lymphoma is still largely unclear. In our present study, the expression patterns of POLE2 in lymphoma tissues were identified by immunohistochemistry (IHC) staining of human tissue microarray. Cell viability was determined by CCK-8 assay. Cell apoptosis and cycle distribution were evaluated by Annexin V and PI staining, respectively. Cell migration was analyzed by transwell assay. Tumor growth in vivo was observed by a xenograft model of mice. The potential signaling was explored by human phospho-kinase array and immunoblotting. POLE2 was significantly upregulated in human lymphoma tissues and cells. POLE2 knockdown attenuated the proliferation, migration capabilities of lymphoma cells, as well as induced cell apoptosis and cycle arrest. Moreover, POLE2 depletion impaired the tumor growth in mice. Furthermore, POLE2 knockdown apparently inhibited the activation of ß-Catenin and downregulated the expression of Wnt/ß-Catenin signaling-related proteins. POLE2 knockdown suppressed the proliferation and migration of lymphoma cells by inhibiting Wnt/ß-Catenin signaling pathway. POLE2 may serve as a novel therapeutic target for lymphoma.

Amuc_1100 pretreatment alleviates acute pancreatitis in a mouse model through regulating gut microbiota and inhibiting inflammatory infiltration.

Amuc_1100 is a membrane protein from Akkermansia muciniphila, which has been found to play a role in host immunological homeostasis in the gastrointestinal tract by activating TLR2 and TLR4. In this study we investigated the effects and underlying mechanisms of Amuc_1100 on acute pancreatitis (AP) induced in mice by intraperitoneal injection of caerulein and lipopolysaccharide (LPS). The mice were treated with the protein Amuc_1100 (3 µg, i.g.) for 20 days before caerulein injection. Cecal contents of the mice were collected for 16S rRNA sequencing. We found that pretreatment with Amuc_1100 significantly alleviated AP-associated pancreatic injury, reduced serum amylase and lipase. Amuc_1100 pretreatment significantly inhibited the expression of proinflammatory cytokines (TNF-α, IL-1ß, IFN-γ and IL-6) in spleen and pancreas through inhibiting NF-κB signaling pathway. Moreover, Amuc_1100 pretreatment significantly decreased the inflammatory infiltration, accompanied by the reduction of Ly6C+ macrophages and neutrophils in the spleen of AP mice. Gut microbiome analysis showed that the abundance of Bacteroidetes, Proteobacteria, Desulfobacterota and Campilobacterota was decreased, while the proportion of Firmicutes and Actinobacteriota was increased in AP mice pretreated with Amuc_1100. We further demonstrated that Amuc_1100 pretreatment restored the enrichment of tryptophan metabolism, which was mediated by intestinal flora. These results provide new evidence that Amuc_1100 lessens the severity of AP through its anti-inflammatory properties with a reduction of macrophages and neutrophil infiltration, as well as its regulation of the composition of intestinal flora and tryptophan metabolism.

T6SS and T4SS Redundantly Secrete Effectors to Govern the Virulence and Bacterial Competition in Pectobacterium PccS1.

Previous studies revealed that the type VI secretion system (T6SS) has an essential role in bacterial competition and virulence in many gram-negative bacteria. However, the role of T6SS in virulence in Pectobacterium atrosepticum remains controversial. We examined a closely related strain, PccS1, and discovered that its T6SS comprises a single-copy cluster of 17 core genes with a higher identity to homologs from P. atrosepticum. Through extensive phenotypic and functional analyses of over 220 derivatives of PccS1, we found that three of the five VgrGs could be classified into group I VgrGs. These VgrGs interacted with corresponding DUF4123 domain proteins, which were secreted outside of the membrane and were dependent on either the T6SS or type IV secretion system (T4SS). This interaction directly governed virulence and competition. Meanwhile, supernatant proteomic analyses with strains defective in the T6SS and/or T4SS confirmed that effectors, such as FhaB, were secreted redundantly to control the virulence and suppress host callose deposition in the course of infection. Notably, this redundant secretion mechanism between the T6SS and T4SS is believed to be the first of its kind in bacteria.

Activation of voltage-dependent K+ channels strongly limits hypoxia-induced elevation of [Ca2+ ]i in rat carotid body glomus cells.

KEY POINTS: We studied the role of the large-conductance Ca2+ -activated K+ channel (BK) and voltage-dependent K+ channels (Kv) on [Ca2+ ]i responses to a wide range of hypoxia at different resting cell membrane potential (Em ). BK/Kv were mostly closed at rest in normoxia. BK/Kv became basally active when cells were depolarized by elevated [KCl]o (>12 mm). Regardless of whether BK/Kv were closed or basally open, hypoxia-induced elevation of [Ca2+ ]i was enhanced 2- to 3-fold by inhibitors of BK/Kv. Hypoxia-induced elevation of [Ca2+ ]i was enhanced ∼2-fold by an inhibitor of Kv2, a major Kv in rat glomus cells. Hypoxia did not inhibit BK in inside-out patches. Our study supports a scheme in which activation of BK/Kv strongly limits the magnitude of hypoxia-induced [Ca2+ ]i rise, with Kv having a much greater effect than BK. ABSTRACT: Large-conductance KCa (BK) and other voltage-dependent K+ channels (Kv) are highly expressed in carotid body (CB) glomus cells, but their role in hypoxia-induced excitation is still not well defined and remains controversial. We addressed this issue by studying the effects of inhibitors of BK (IBTX) and BK/Kv (TEA/4-AP) on [Ca2+ ]i responses to a wide range of hypoxia at different levels of resting cell membrane potential (Em ). IBTX and TEA/4-AP did not affect the basal [Ca2+ ]i in isolated glomus cells bathed in 5 mm KClo , but elicited transient increases in [Ca2+ ]i in cells that were moderately depolarized (11-20 mV) by elevation of [KCl]o (12-20 mm). Thus, BK and Kv were mostly closed at rest and activated by depolarization. Four different levels of hypoxia (mild, moderate, severe, anoxia) were used to produce a wide range of [Ca2+ ]i elevation (0-700 nm). IBTX did not affect the rise in [Ca2+ ]i , but TEA/4-AP strongly (∼3-fold) enhanced [Ca2+ ]i rise by moderate and severe levels of hypoxia. Guangxitoxin, a Kv2 blocker, inhibited the whole-cell current by ∼50%, and enhanced 2-fold the [Ca2+ ]i rise elicited by moderate and severe levels of hypoxia. Anoxia did not directly affect BK, but activated BK via depolarization. Our findings do not support the view that hypoxia inhibits BK/Kv to initiate or maintain the hypoxic response. Rather, our results show that BK/Kv are activated as glomus cells depolarize in response to hypoxia, which then limits the rise in [Ca2+ ]i . Inhibition of Kv may provide a mechanism to enhance the chemosensory activity of the CB and ventilation.

TASK-1 (K2P3) and TASK-3 (K2P9) in Rabbit Carotid Body Glomus Cells.

Glomus cells isolated from rabbit and rat/mouse carotid bodies have been used for many years to study the role of ion channels in hypoxia sensing. Studies show that hypoxia inhibits the inactivating K+ channels (Kv4) in rabbits, but inhibits TASK in rats/mice to elicit the hypoxic response. Because the role of TASK in rabbit glomus cells is not known, we isolated glomus cells from rabbits and studied the expression of TASK mRNA in the whole carotid body (CB), changes in [Ca2+]i and TASK activity. RT-PCR showed that rabbit CB expressed mRNA for TASK-3 and several Kv (Kv2.1, Kv3.1 and Kv3.3). In rabbit glomus cells in which 20 mM KClo elevated [Ca2+], anoxia also elicited a strong rise in [Ca2+]. In cell-attached patches with 140 mM KCl in the pipette, basal openings of ion channels with single-channel conductance levels of 16-pS, 34-pS, and 42-pS were present. TREK-like channels were also observed. In inside-out patches with high [Ca2+]i, BK was activated. The 42-pS channel opened spontaneously and briefly. The 16-pS and 34-pS channels showed properties similar to those of TASK-1 and TASK-3, respectively. TASK activity in cell-attached patches was lower than that in rat glomus cells under identical recording conditions. Hypoxia (~0.5%O2) reduced TASK activity by ~52% and depolarized the cells by ~30 mV. Our results show that the O2-sensitive TASK contributes to the hypoxic response in rabbit glomus cells.

Increase in cytosolic Ca2+ produced by hypoxia and other depolarizing stimuli activates a non-selective cation channel in chemoreceptor cells of rat carotid body.

The current model of O2 sensing by carotid body chemoreceptor (glomus) cells is that hypoxia inhibits the outward K(+) current and causes cell depolarization, Ca(2+) influx via voltage-dependent Ca(2+) channels and a rise in intracellular [Ca(2+)] ([Ca(2+)]i). Here we show that hypoxia (<5% O2), in addition to inhibiting the two-pore domain K(+) channels TASK-1/3 (TASK), indirectly activates an ∼20 pS channel in isolated glomus cells. The 20 pS channel was permeable to K(+), Na(+) and Cs(+) but not to Cl(-) or Ca(2+). The 20 pS channel was not sensitive to voltage. Inhibition of TASK by external acid, depolarization of glomus cells with high external KCl (20 mm) or opening of the Ca(2+) channel with FPL64176 activated the 20 pS channel when 1 mm Ca(2+) was present in the external solution. Ca(2+) (10 µm) applied to the cytosolic side of inside-out patches activated the 20 pS channel. The threshold [Ca(2+)]i for activation of the 20 pS channel in cell-attached patches was ∼200 nm. The reversal potential of the 20 pS channel was estimated to be -28 mV. Our results reveal a sequential mechanism in which hypoxia (<5% O2) first inhibits the K(+) conductance and then activates a Na(+)-permeable, non-selective cation channel via depolarization-induced rise in [Ca(2+)]i. Our results suggest that inhibition of K(+) efflux and stimulation of Na(+) influx both contribute to the depolarization of glomus cells during moderate to severe hypoxia.

Cystic adventitial disease of the popliteal artery: report of two cases.

Cystic adventitial disease (CAD) of the popliteal artery is a rare vascular disorder in which a mucin-containing cyst develops in the adventitial layer of the artery. We report two such cases, each of which was treated differently. The first case was of a 49-year-old man, treated by excision of the involved arterial segment and interposition of an autologous saphenous vein graft. The second case was of a 36-year-old man, treated by local excision of the affected arterial segment and interposition with prosthetic bypass grafting. Both patients presented with rapidly progressing intermittent claudication of the lower extremities, but without remarkable evidence of atherosclerotic disease. Physical examination revealed diminished or absent popliteal, posterior tibial and dorsalis pedis pulses in the lower extremities. Color Doppler ultrasound of the popliteal artery revealed hypoechoic cystic lesions surrounding the vessel, and popliteal arterial stenosis, in both patients. Surgery resulted in immediate improvement of the arterial pulse distal to the lesion. Both patients recovered uneventfully. Thus, resection of the involved artery segment and interposition bypass grafting, using either patient or prosthetic veins, offers favorable results for CAD of the popliteal artery.

Construction of Fe0.64Ni0.36@graphite nanoparticles via corrosion-like transformation from NiFe2O4 and surface graphitization in flexible carbon nanofibers to achieve strong wideband microwave absorption.

Recently, microwave absorption (MA) materials have attracted intensive research attention for their ability to counteract the effects of ever-growing electromagnetic pollution. However, conventional microwave absorbers suffer from complex fabrication processes, poor stability and different optimal thicknesses for minimum reflection loss (RLmin) and widest effective absorption bandwidth (EAB). To address these issues, we have used electrospinning followed by high-temperature annealing in argon to develop a flexible microwave absorber with strong wideband absorption. The MA properties of the carbon nanofibers (CNFs) can be tuned by adjusting annealing temperature, and are dependent on the composition and microstructure of the CNFs. The absorber membrane obtained at 800 °C consists of Fe0.64Ni0.36@graphite core-shell nanoparticles (NPs) embedded in CNFs, formed via a corrosion-like transformation from NiFe2O4 to Fe0.64Ni0.36 followed by surface graphitization. This nanostructure greatly enhances magnetic-dielectric synergistic loss to achieve superior MA properties, with an RLmin of -57.7 dB and an EAB of 6.48 GHz (11.20-17.68 GHz) both acquired at a thickness of 2.1 mm. This work provides useful insights into structure-property relationship of the CNFs, sheds light on the formation mechanism of Fe0.64Ni0.36@graphite NPs, and offers a simple synthesis route to fabricate light-weight and flexible microwave absorbers.

Rules of acupoint selection in treatment of inflammatory bowel disease with acupuncture-moxibustion based on complex network analysis. / åŸºäºŽå¤æ‚ç½‘ç»œåˆ†æžé’ˆç¸æ²»ç–—ç‚Žæ€§è‚ ç— çš„é€‰ç©´è§„å¾‹.

OBJECTIVES: To analyze the rules of acupoint selection and compatibility of acupuncture and moxibustion in treatment of inflammatory bowel disease (IBD) based on complex network technology and provide the reliable evidences for acupoint selection in treatment of this disease with acupuncture and moxibustion. METHODS: The clinical studies on acupuncture-moxibustion treatment of IBD were searched from the databases including CNKI, Wanfang, VIP, PubMed and Embase. The studies were screened and the acupoint prescriptions were extracted to set up the database of acupuncture-moxibustion treatment for IBD. Using Microsoft Excel 2021 software, the use times of acupoint, the use frequency (%) of acupoint, meridian tropism and the use of special point were imported. With SPSS Modeler 18.0 software adopted, the association rules were analyzed on the acupoint prescriptions. The acupoint co-occurrence network diagram, k-core network diagram, and community analysis diagram were drawn by Gephi 0.9.5 software. RESULTS: A total of 156 studies were included, composed of 175 acupoint prescriptions, 75 acupoints, with 1 378 use times in total and around 8 acupoints in one prescription. Regarding the top use frequency, Tianshu (ST25), Zusanli (ST36), Guanyuan (CV4), Zhongwan (CV12) and Pishu (BL20) were listed. The top meridians involved were the foot-yangming stomach meridian, the foot-taiyang bladder meridian and the Conception Vessel. The front-mu point had been used with the highest frequency among the special points. ST36 and ST25 were a pair of points with the highest frequency in treatment. The k-core hierarchical analysis was adopted to optimize acupoint prescriptions, and 22 core acupoints were obtained, i.e. ST25, ST36, CV4, CV12, BL20, Dachangshu (BL25), Shangjuxu (ST37), Shenshu (BL23), Qihai (CV6), Sanyinjiao (SP6), Mingmen (GV4), Xingjian (LR2), Yinlingquan (SP9), Neiting (ST44), Taichong (LR3), Xiajuxu (ST39), Shuifen (CV9), Shenque (CV8), Ganshu (BL18), Weishu (BL21), Hegu (LI4) and Quchi(LI11), which were classified into three core acupoint groups by community analysis. CONCLUSIONS: Through complex network analysis, it is found that the local acupoints on the chest and abdomen are generally selected in treatment with acupuncture-moxibustion for IBD, the combination of the nearby and distal points is considered simulta-neously, and the acupoint prescription is modified according to syndrome/pattern differentiation；and among special points, the front-mu point is widely used in treatment. All of these rules provide the ideas for the acupoint selection of acupuncture-moxibustion in treatment of IBD.

Research hotspots for pediatric fractures from 2017 to 2022: A bibliometric and visual analysis via Citespace.

Objective: This review provides guidance and ideas for researchers through a comprehensive and comparative analysis of the present state, trends, and hotspots in the pediatric fracture literature over the past 6 years. Methods: We used Citespace 6.1.R6 software to explore the country/region distribution, institutions, journals, keyword analysis, and co-cited references of the literature from Web of Science core database. Results: There are 6472 pieces of pediatric fracture-related literature, including 2962 from 2017 to 2019 and 3510 from 2020 to 2022. The country with the most papers is the United States, and US institutions and journals also have a pivotal position in this field. Research hotspots for pediatric fractures in 2017-2019: The topic with the most attention is bone mineral density leading to related bone diseases. Treatment for pediatric fractures, including supracondylar humeral fractures, Monteggia fractures, forearm fractures, knee fractures, and ankle fractures in children, is another topic of greater interest. Brain injuries and dental injuries in children due to abuse and trauma are also concerning issues. Research hotspots for pediatric fractures in 2020-2022: comparison with 2017-2019 revealed a relative decrease regarding ankle-related epiphyseal injuries, but there is a higher focus on the epidemiology of fractures in children, risk factors, and reasons for childhood trauma. We have confirmed through literature co-citations that the literature of high interest is also in these aspects. Conclusion: Researchers and clinicians can quickly learn about topics of interest through authoritative journals and highly cited literature and rapidly master the current status and frontiers of the field through study, providing ideas for future work.

Finite element analysis of Kirschner wire fixation for lateral condyle fracture in children in the sagittal plane.

Objective: This study aims to find the optimal arrangement of the Kirschner wire (K-wire) in the sagittal plane for fixation of a pediatric lateral condylar humeral fracture (Milch type II) by using finite element analysis (FEA). Methods: A model of lateral condyle fracture in a 6-year-old boy was developed, and an XYZ coordinate system was established based on this model. The YZ plane was defined as the sagittal plane to investigate the impact of the angle formed by the first and second K-wires on stability. Two configurations were studied for each angle: parallel and divergent. Evaluation indicators included the maximum displacement of the fracture fragment and the maximum von Mises stress in the pins and bone. Results: The model with a -60° angle showed the best performance in both evaluation indicators. The parallel and divergent pin configurations had different performances in each group. The displacement results for negative angles were similar, and this result was better than those for positive angles. Conclusion: We successfully created a model of pediatric lateral condyle humerus fracture (Milch type II) and performed K-wire fixation with varying sagittal plane configurations, combined with FEA. Our findings demonstrate that the angle of -60° between the two pins in the sagittal plane provided the highest level of stability, with divergent configurations proving superior to parallel pinning at this angle.

Cartilaginous predictors of residual acetabular dysplasia (RAD) in developmental dysplasia of the hip following closed or open reduction: A systematic review and meta-analysis.

Object: This study was designed to analyze the cartilaginous predictors of residual acetabular dysplasia (RAD) after early treatment of developmental dysplasia of the hip and their diagnostic accuracy. Study design: Databases such as PubMed, Embase, Cochrane, and Web of science were searched to screen the literature. The quality of the literature was assessed by the QUADAS-2 tool. Qualitative and quantitative synthesis of literature were performed based on extracted data. For quantitative synthesis studies, the sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curve with corresponding confidence intervals were calculated. Results: For the cartilaginous acetabular index (CAI) group, the combined values of sensitivity, specificity, and DOR were 0.80 (95% CI = 0.54-0.93), 0.73 (95% CI = 0.57-0.84), and 10.62 (95% CI = 3.96-28.53), respectively. The corresponding values in the cartilaginous center-edge angle (CCE) group were 0.71 (95% CI = 0.57-0.82), 0.78 (95% CI = 0.66-0.87), and 8.64 (95% CI = 3.08-24.25), respectively. The area under the curve (AUC) of SROC was 0.82 (95% CI = 0.78-0.85) and 0.80 (95% CI = 0.76-0.83) for the CAI and CCE groups. The CAI group had higher sensitivity, DOR, and AUC than the CCE group. Conclusion: Both of these two groups have good diagnostic accuracy, and CAI/L-AI has a little edge over CCE/L-CEA. However, there is still more research needed to determine whether they can be used as independent indications for secondary orthopedic surgery.Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier: [CRD42022338332].

Olfactory Three-Needle Electroacupuncture Improved Synaptic Plasticity and Gut Microbiota of SAMP8 Mice by Stimulating Olfactory Nerve.

OBJECTIVE: To investigate the effects and mechanisms of olfactory three-needle (OTN) electroacupuncture (EA) stimulation of the olfactory system on cognitive dysfunction, synaptic plasticity, and the gut microbiota in senescence-accelerated mouse prone 8 (SAMP8) mice. METHODS: Thirty-six SAMP8 mice were randomly divided into the SAMP8 (P8), SAMP8+OTN (P8-OT), and SAMP8+nerve transection+OTN (P8-N-OT) groups according to a random number table (n=12 per group), and 12 accelerated senescence-resistant (SAMR1) mice were used as the control (R1) group. EA was performed at the Yintang (GV 29) and bilateral Yingxiang (LI 20) acupoints of SAMP8 mice for 4 weeks. The Morris water maze test, transmission electron microscopy, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining, Nissl staining, Golgi staining, Western blot, and 16S rRNA sequencing were performed, respectively. RESULTS: Compared with the P8 group, OTN improved the cognitive behavior of SAMP8 mice, inhibited neuronal apoptosis, increased neuronal activity, and attenuated hippocampal synaptic dysfunction (P<0.05 or P<0.01). Moreover, the expression levels of synaptic plasticity-related proteins N-methyl-D-aspartate receptor 1 (NMDAR1), NMDAR2B, synaptophysin (SYN), and postsynaptic density protein-95 (PSD95) in hippocampus were increased by OTN treatment (P<0.05 or P<0.01). Furthermore, OTN greatly enhanced the brain-derived neurotrophic factor (BDNF)/cAMP-response element binding (CREB) signaling and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling compared with the P8 group (P<0.05 or P<0.01). However, the neuroprotective effect of OTN was attenuated by olfactory nerve truncation. Compared with the P8 group, OTN had a very limited effect on the fecal microbial structure and composition of SAMP8 mice, while specifically increased the genera Oscillospira and Sutterella (P<0.05). Interestingly, the P8-N-OT group showed an abnormal fecal microbiota with higher microbial α-diversity, Firmicutes/Bacteroidetes ratio and pathogenic bacteria (P<0.05 or P<0.01). CONCLUSIONS: OTN improved cognitive deficits and hippocampal synaptic plasticity by stimulating the olfactory nerve and activating the BDNF/CREB and PI3K/AKT/mTOR signaling pathways. Although the gut microbiota was not the main therapeutic target of OTN for Alzheimer's disease, the olfactory nerve was essential to maintain the homeostasis of gut microbiota.

Voltage- and receptor-mediated activation of a non-selective cation channel in rat carotid body glomus cells.

A recent study showed that hypoxia activates a Ca2+-sensitive, Na+-permeable non-selective cation channel (NSC) in carotid body glomus cells. We studied the effects of mitochondrial inhibitors that increase Ca2+ influx via Ca2+ channel (Cav), and receptor agonists that release Ca2+ from endoplasmic reticulum (ER) on NSC. Mitochondrial inhibitors (NaCN, FCCP, H2S, NO) elevated [Ca2+]i and activated NSC. Angiotensin II and acetylcholine that elevate [Ca2+]i via the Gq-IP3 pathway activated NSC. However, endothelin-1 (Gq) and 5-HT (Gq) showed little or no effect on [Ca2+]i and did not activate NSC. Adenosine (Gs) caused a weak rise in [Ca2+]i but did not activate NSC. Dopamine (Gs) and γ-aminobytyric acid (Gi) were ineffective in raising [Ca2+]i and failed to activate NSC. Store-operated Ca2+ entry (SOCE) produced by depletion of Ca2+ stores with cyclopiazonic acid activated NSC. Our results show that Ca2+ entry via Cav, ER Ca2+ release and SOCE can activate NSC. Thus, NSC contributes to both voltage- and receptor-mediated excitation of glomus cells.

Role of cystathionine-γ-lyase in hypoxia-induced changes in TASK activity, intracellular [Ca2+] and ventilation in mice.

Cystathionine-γ-lyase (CSE) is a multifunctional enzyme, and hydrogen sulfide (H2S) is one of its products. CSE and H2S have recently been proposed to be critical signaling molecules in hypoxia-induced excitation of carotid body (CB) glomus cells and the chemosensory response. Because the role of H2S in arterial chemoreception is still debated, we further examined the role of CSE by studying the effects of hypoxia on TASK K+ channel activity, cell depolarization, [Ca2+]i and ventilation using CSE+/+ and CSE-/- mice. As predicted, hypoxia reduced TASK activity and depolarized glomus cells isolated from CSE+/+ mice. These effects of hypoxia were not significantly altered in glomus cells from CSE-/- mice. Basal [Ca2+]i and hypoxia-induced elevation of [Ca2+] were also not significantly different in glomus cells from CSE+/+ and CSE-/- mice. In whole-body plethysmography, hypoxia (10%O2) increased minute ventilation in both CSE+/+ and CSE-/- mice equally well, and no significant differences were found in either males or females when adjusted by body weight. Together, these results show that deletion of the CSE gene has no effects on hypoxia-induced changes in TASK, cell depolarization, [Ca2+]i and ventilation, and therefore do not support the idea that CSE/H2S signaling is important for CB chemoreceptor activity in mice.

[Rule induction algorithm for brain glioma using support vector machine].

A new proposed data mining technique, support vector machine (SVM), is used to predict the degree of malignancy in brain glioma. Based on statistical learning theory, SVM realizes the principle of data dependent structure risk minimization, so it can depress the overfitting with better generalization performance, since the prediction in medical diagnosis often deals with a small sample. SVM based rule induction algorithm is implemented in comparison with other data mining techniques such as artificial neural networks, rule induction algorithm and fuzzy rule extraction algorithm based on fuzzy max-min neural networks (FRE-FMMNN) proposed recently. Computation results by 10 fold cross validation method show that SVM can get higher prediction accuracy than artificial neural networks and FRE-FMMNN, which implies SVM can get higher accuracy and more reliability. On the whole data sets, SVM gets one rule with the classification accuracy of 89.29%, while FRE-FMMNN gets two rules of 84. 64%, in which the rule got by SVM is of quantity relation and contains more information than the two rules by FRE-FMMNN. All the above show SVM is a potential algorithm for the medical diagnosis such as the prediction of the degree of malignancy in brain glioma.

Hydrogen sulfide and hypoxia-induced changes in TASK (K2P3/9) activity and intracellular Ca(2+) concentration in rat carotid body glomus cells.

Acute hypoxia depolarizes carotid body chemoreceptor (glomus) cells and elevates intracellular Ca(2+) concentration ([Ca(2+)]i). Recent studies suggest that hydrogen sulfide (H2S) may serve as an oxygen sensor/signal in the carotid body during acute hypoxia. To further test such a role for H2S, we studied the effects of H2S on the activity of TASK channel and [Ca(2+)]i, which are considered important for mediating the glomus cell response to hypoxia. Like hypoxia, NaHS (a H2S donor) inhibited TASK activity and elevated [Ca(2+)]i. To inhibit the production of H2S, glomus cells were incubated (3h) with inhibitors of cystathionine-ß-synthase and cystathionine-γ-lyase (DL-propargylglycine, aminooxyacetic acid, ß-cyano-L-alanine; 0.3 mM). SF7 fluorescence was used to assess the level of H2S production. The inhibitors blocked L-cysteine- and hypoxia-induced elevation of SF7 fluorescence intensity. In cells treated with the inhibitors, hypoxia produced an inhibition of TASK activity and a rise in [Ca(2+)]i, similar in magnitude to those observed in control cells. L-cysteine produced no effect on TASK activity or [Ca(2+)]i and did not affect hypoxia-induced inhibition of TASK and elevation of [Ca(2+)]i. These findings suggest that under normal conditions, H2S is not a major signal in hypoxia-induced modulation of TASK channels and [Ca(2+)]i in isolated glomus cells.

[Expressions of VEGF and CXCR4 in diffuse large B cell lymphoma and their clinical significances].

This study was aimed to investigate the expression levels of CXCR4 and VEGF in serum of patients with DLBCL and their clinical significances. The peripheral blood of 44 patients with newly diagnosed DLBCL and 20 healthy adults as a control group were chosen for study. And the expression levels of CXCR4 and VEGF in serum were detected by ELISA. The results showed that the expressions of VEGF and CXCR4 in DLBCL patients were higher than those in the control group (P < 0.05). The expression of VEGF was positively correlated with the expression of CXCR4 in DLBCL patients, and the correlation coefficient was 0.743 (P < 0.05). The VEGF expression in DLBCL patients was correlated with LDH, immunotyping, the number of extranodal involvements, Ann Arbor staging and ECOG performance score; while the expression of CXCR4 was correlated with LDH, immunotyping, the number of extranodal involvements and Ann Arbor staging. Univariate analysis showed that LDH, extranodal involvements, immunotyping, Ann Arbor staging, CXCR4 and VEGF were associated with OS. Multivariate analysis showed that the immunotyping and CXCR4 expression independently associated with OS. It is concluded that both expression levels of VEGF and CXCR4 are significant higher than those in the control group. CXCR4 expression positively correlates with VEGF expression and displays a prognostic significance for OS. This study suggests that combined targeting VEGF and CXCR4 may become a novel therapeutic strategy for diffuse large B cell lymphoma.