Discovery of a new cryptic Achalinus Peters, 1869 (Serpentes, Xenodermidae) species from Hunan Province, China.

A new species, Achalinusshenisp. nov., from central Hunan Province is described, based on the results of molecular systematics and morphological characters according to five specimens. Our molecular phylogeny inferred from the mitochondrial CO1 gene fragment revealed that this new species is most closely related to A.yunkaiensis, but a considerable amount of genetic divergence exists between them (p-distance ranging from 5.8% to 6.4%) and much distinct genetic divergence exists compared with other known Achalinus species (p-distance ranging from 10.4% to 15.8%), supporting its validity. Morphologically, it can be distinguished from its congeners by: (1) dorsal scales strongly keeled, 23 rows throughout the body, the outmost row smooth and significantly enlarged; (2) tail relatively short, TaL/TL 0.183 ~ 0.224; (3) the suture between internasals subequal to the suture between prefrontals; (4) loreal one, subrectangular, LorH/LorL 0.53 ~ 0.57; (5) ventrals 161-170, anal entire, subcaudals 55-61, not paired; (6) the length of supraocular equal to or longer than the length of upper anterior temporal; and (7) vertebral line inconspicuous and subcaudal streak absent. Currently, 27 species of Achalinus are known in the world, amongst which 20 species are distributed in China. Moreover, a key to species of the genus Achalinus is provided in this study.

Biological sex influences sleep phenotype in mice experiencing spontaneous opioid withdrawal.

Aversive symptoms, including insomnia experienced during opioid withdrawal, are a major drive to relapse; however, withdrawal-associated sleep symptomatology has been little explored in preclinical models. We describe here a model of opioid withdrawal in mice that resembles the sleep phenotype characteristic of withdrawal in humans. Male and female C57BL/6 mice were instrumented with telemeters to record electroencephalogram, electromyogram, activity and subcutaneous temperature. All mice received two treatments separated by a 16-day washout period: (1) saline (volume: 10 ml kg-1 ); or (2) ascending doses of morphine (5, 10, 20, 40 and 80 mg kg-1 ; volume: 10 ml kg-1 ) for 5 days at Zeitgeber time 1 and Zeitgeber time 13. Recordings for the first 71 hr after treatment discontinuation (withdrawal days 1-3) and for 24 hr on withdrawal days 5 and 7 were scored for sleep/wake state, and sleep architecture and electroencephalogram spectral data were analysed. Morphine was acutely wake- and activity-promoting, and non-rapid eye movement and rapid eye movement sleep were increased during the dark phase on withdrawal day 2 in both sexes. While non-rapid eye movement delta power (0.5-4.0 Hz), a measure of sleep intensity, was reduced during the light phase on withdrawal day 1 and the dark phase on withdrawal day 2 in both sexes, female mice also exhibited changes in the duration and the number of bouts of sleep/wake states. These observations of fragmented sleep on withdrawal days 1-3 suggest poorer sleep consolidation and a more pronounced withdrawal-associated sleep phenotype in female than in male mice. These data may indicate a greater sensitivity to morphine, a more distinct aversive sleep phenotype and/or a faster escalation to dependence in female mice.

Evaluation of the efficacy of the hypocretin/orexin receptor agonists TAK-925 and ARN-776 in narcoleptic orexin/tTA; TetO-DTA mice.

The sleep disorder narcolepsy, a hypocretin deficiency disorder thought to be due to degeneration of hypothalamic hypocretin/orexin neurons, is currently treated symptomatically. We evaluated the efficacy of two small molecule hypocretin/orexin receptor-2 (HCRTR2) agonists in narcoleptic male orexin/tTA; TetO-DTA mice. TAK-925 (1-10 mg/kg, s.c.) and ARN-776 (1-10 mg/kg, i.p.) were injected 15 min before dark onset in a repeated measures design. EEG, EMG, subcutaneous temperature (Tsc ) and activity were recorded by telemetry; recordings for the first 6 h of the dark period were scored for sleep/wake and cataplexy. At all doses tested, TAK-925 and ARN-776 caused continuous wakefulness and eliminated sleep for the first hour. Both TAK-925 and ARN-776 caused dose-related delays in NREM sleep onset. All doses of TAK-925 and all but the lowest dose of ARN-776 eliminated cataplexy during the first hour after treatment; the anti-cataplectic effect of TAK-925 persisted into the second hour for the highest dose. TAK-925 and ARN-776 also reduced the cumulative amount of cataplexy during the 6 h post-dosing period. The acute increase in wakefulness produced by both HCRTR2 agonists was characterised by increased spectral power in the gamma EEG band. Although neither compound provoked a NREM sleep rebound, both compounds affected NREM EEG during the second hour post-dosing. TAK-925 and ARN-776 also increased gross motor activity, running wheel activity, and Tsc , suggesting that the wake-promoting and sleep-suppressing activities of these compounds could be a consequence of hyperactivity. Nonetheless, the anti-cataplectic activity of TAK-925 and ARN-776 is encouraging for the development of HCRTR2 agonists.

SFANet: A Spectrum-Aware Feature Augmentation Network for Visible-Infrared Person Reidentification.

Visible-Infrared person reidentification (VI-ReID) is a challenging matching problem due to large modality variations between visible and infrared images. Existing approaches usually bridge the modality gap with only feature-level constraints, ignoring pixel-level variations. Some methods employ a generative adversarial network (GAN) to generate style-consistent images, but it destroys the structure information and incurs a considerable level of noise. In this article, we explicitly consider these challenges and formulate a novel spectrum-aware feature augmentation network named SFANet for cross-modality matching problem. Specifically, we put forward to employ grayscale-spectrum images to fully replace RGB images for feature learning. Learning with the grayscale-spectrum images, our model can apparently reduce modality discrepancy and detect inner structure relations across the different modalities, making it robust to color variations. At feature level, we improve the conventional two-stream network by balancing the number of specific and sharable convolutional blocks, which preserve the spatial structure information of features. Additionally, a bidirectional tri-constrained top-push ranking loss (BTTR) is embedded in the proposed network to improve the discriminability, which efficiently further boosts the matching accuracy. Meanwhile, we further introduce an effective dual-linear with batch normalization identification (ID) embedding method to model the identity-specific information and assist BTTR loss in magnitude stabilizing. On SYSU-MM01 and RegDB datasets, we conducted extensively experiments to demonstrate that our proposed framework contributes indispensably and achieves a very competitive VI-ReID performance.

A new Asian lazy toad of the genus Scutiger Theobald, 1868 (Anura, Megophryidae) from southern Tibet, China.

In this study, a new species named Scutigerluozhaensissp. nov. is described from Luozha, southern Tibet, China. Genetic analysis based on two mitochondrial genes 16S rRNA and COI and the nuclear gene RAG1 revealed that the new species belongs to an independent phylogenetic clade close to S.gongshanensis and S.nyingchiensis and shares no RAG1 haplotype with other species. Morphological comparisons based on examined specimens and literatures indicated that it can be diagnosed from congeners by the following combination of characters: (1) body moderate, male body length 47.0-67.2 mm (n = 13), female body length 49.8-66.2 mm (n = 8); (2) maxillary teeth and budding absent; (3) numerous tiny dense nuptial spines present on dorsal surface of fingers I, II and inner surface of finger III of males in breeding condition with similar size; (4) spine patches on belly of males in breeding condition absent; (5) spines on inner surface of forearm and upper arm of males in breeding condition absent; (6) small patches of black spines present near armpit of males in breeding condition absent; (7) adult males without vocal sac; (8) some large warts and tubercles on dorsum gathered into short skin ridges with several spines present on top; (9) space between upper eyelids wider than upper eyelids; (10) spots or irregular cross bands on limbs absent; (11) webbing between toes rudimentary; (12) coloration of dorsal body olive brown to bronze.

A new species of Achalinus Peters, 1869 (Squamata, Xenodermidae) from Hunan Province, China.

A new species, Achalinushunanensissp. nov., is described from middle and western Hunan Province based on the results of molecular systematics and morphological characters. It diverges from known congeners by a significant genetic divergence (p-distance 3.2%-16.9% based on CO1 mitochondrial gene), and it can be distinguished from all known congeners by the following morphological characters: (1) all dorsal scales strongly keeled, 23 rows throughout the body, the outmost one strongly keeled and enlarged; (2) tail relatively short, TaL/TL 0.221 ~ 0.225; (3) maxillary teeth 23; (4) the suture between internasals 2 × as long as that between prefrontals; (5) loreal one, subrectangular, LorH/LorL 0.62 ~ 0.70; (6) supralabials 6, the 4th and 5th touch the eye; (7) the two anterior temporals in contact with eye; (8) ventrals 163-165, subcaudals 69-72, not paired. This raises the number of known species of Achalinus to 24.

Penpulimab, an Fc-Engineered IgG1 Anti-PD-1 Antibody, With Improved Efficacy and Low Incidence of Immune-Related Adverse Events.

Background: IgG4 anbibodies are deficient in stability and may contribute to tumor-associated escape from immune surveillance. We developed an IgG1 backbone anti-programmed cell death protein-1 (PD-1) antibody, penpulimab, which is designed to remove crystallizable fragment (Fc) gamma receptor (FcγR) binding that mediates antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP) and proinflammatory cytokine release. Methods: Aggregation of different anti-PD-1 antibodies was tested by size exclusion chromatography, and melting temperature midpoint (Tm) and aggregation temperature onset (Tagg) were also determined. The affinity constants of penpulimab for PD-1 and human FcγRs were measured by surface plasmon resonance and biolayer interferometry. ADCC and ADCP were determined in cellular assays and antibody-dependent cytokine release (ADCR) from human macrophages was detected by ELISA. Binding kinetics of penpulimab to human PD-1 was determined by Biacore, and epitope/paratope mapping of PD-1/penpulimab was investigated using x-ray crystallography. Additionally, patients from six ongoing trials were included for analysis of immune-related adverse events (irAEs). Results: Penpulimab demonstrated better stability and a lower level of host-cell protein residue compared with IgG4 backbone anti-PD-1 antibodies. As expected, penpulimab exhibited no apparent binding to FcγRIa, FcγRIIa_H131, FcγRIIIa_V158 and FcγRIIIa_F158, elicited no apparent ADCC and ADCP activities, and induced no remarkable IL-6 and IL-8 release by activated macrophages in vitro. Penpulimab was shown in the co-crystal study to bind to human PD-1 N-glycosylation site at N58 and had a slower off-rate from PD-1 versus nivolumab or pembrolizumab. Four hundred sixty-five patients were analyzed for irAEs. Fifteen (3.2%) patients had grade 3 or above irAEs. No death from irAEs was reported. Conclusions: IgG1 backbone anti-PD1 antibody penpulimab has a good stability and reduced host cell protein residue, as well as potent binding to the antigen. Fc engineering has eliminated Fc-mediated effector functions of penpulimab including ADCC, ADCP and reduced ADCR, which may contribute to its more favorable safety profile. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: AK105-101: NCT03352531, AK105-201: NCT03722147, AK105-301: NCT03866980, AK105-202:NCT03866967, AK105-203: NCT04172571, AK105-204: NCT04172506.

The development of sleep/wake disruption and cataplexy as hypocretin/orexin neurons degenerate in male vs. female Orexin/tTA; TetO-DTA Mice.

Narcolepsy Type 1 (NT1), a sleep disorder with similar prevalence in both sexes, is thought to be due to loss of the hypocretin/orexin (Hcrt) neurons. Several transgenic strains have been created to model this disorder and are increasingly being used for preclinical drug development and basic science studies, yet most studies have solely used male mice. We compared the development of narcoleptic symptomatology in male vs. female orexin-tTA; TetO-DTA mice, a model in which Hcrt neuron degeneration can be initiated by removal of doxycycline (DOX) from the diet. EEG, EMG, subcutaneous temperature, gross motor activity, and video recordings were conducted for 24-h at baseline and 1, 2, 4, and 6 weeks after DOX removal. Female DTA mice exhibited cataplexy, the pathognomonic symptom of NT1, by Week 1 in the DOX(-) condition but cataplexy was not consistently present in males until Week 2. By Week 2, both sexes showed an impaired ability to sustain long wake bouts during the active period, the murine equivalent of excessive daytime sleepiness in NT1. Subcutaneous temperature appeared to be regulated at lower levels in both sexes as the Hcrt neurons degenerated. During degeneration, both sexes also exhibited the "Delta State", characterized by sudden cessation of activity, high delta activity in the EEG, maintenance of muscle tone and posture, and the absence of phasic EMG activity. Since the phenotypes of the two sexes were indistinguishable by Week 6, we conclude that both sexes can be safely combined in future studies to reduce cost and animal use.

Achieving Uniform Li Plating/Stripping at Ultrahigh Currents and Capacities by Optimizing 3D Nucleation Sites and Li2 Se-Enriched SEI.

Lithium (Li) has garnered considerable attention as an alternative anodes of next-generation high-performance batteries owing to its prominent theoretical specific capacity. However, the commercialization of Li metal anodes (LMAs) is significantly compromised by non-uniform Li deposition and inferior electrolyte-anode interfaces, particularly at high currents and capacities. Herein, a hierarchical three-dimentional structure with CoSe2 -nanoparticle-anchored nitrogen-doped carbon nanoflake arrays is developed on a carbon fiber cloth (CoSe2 -NC@CFC) to regulate the Li nucleation/plating process and stabilize the electrolyte-anode interface. Owing to the enhanced lithiophilicity endowed by CoSe2 -NC, in situ-formed Li2 Se and Co nanoparticles during initial Li nucleation, and large void space, CoSe2 -NC@CFC can induce homogeneous Li nucleation/plating, optimize the solid electrolyte interface, and mitigate volume change. Consequently, the CoSe2 -NC@CFC can accommodate Li with a high areal capacity of up to 40 mAh cm-2 . Moreover, the Li/CoSe2 -NC@CFC anodes possess outstanding cycling stability and lifespan in symmetric cells, particularly under ultrahigh currents and capacities (1600 h at 10 mA cm-2 /10 mAh cm-2 and 5 mA cm-2 /20 mAh cm-2 ). The Li/CoSe2 -NC@CFC//LiFePO4 full cell delivers impressive long-term performance and favorable flexibility. The developed CoSe2 -NC@CFC provides insights into the development of advanced Li hosts for flexible and stable LMAs.

MOF-Derived Bifunctional Co0.85Se Nanoparticles Embedded in N-Doped Carbon Nanosheet Arrays as Efficient Sulfur Hosts for Lithium-Sulfur Batteries.

Lithium-sulfur batteries possess the merits of low cost and high theoretical energy density but suffer from the shuttle effect of lithium polysulfides and slow redox kinetics of sulfur. Herein, novel Co0.85Se nanoparticles embedded in nitrogen-doped carbon nanosheet arrays (Co0.85Se/NC) were constructed on carbon cloth as the self-supported host for a sulfur cathode using a facile fabrication strategy. The interconnected porous carbon-based structure of the Co0.85Se/NC could facilitate the rapid electron and ion transfer kinetics. The embedded Co0.85Se nanoparticles can effectively capture and catalyze lithium polysulfides, thus accelerating the redox kinetics and stabilizing sulfur cathodes. Therefore, the Co0.85Se/NC-S cathode could maintain a stable cycle performance for 400 cycles at 1C and deliver a high discharge specific capacity of 1361, 1001, and 810 mAh g-1 at current densities of 0.1, 1, and 3C, respectively. This work provides an efficient design strategy for high-performance lithium-sulfur batteries with high energy densities.

Susceptibility of porcine pulmonary microvascular endothelial cells to porcine reproductive and respiratory syndrome virus.

Microvascular endothelial cells possess versatile functions and their roles in a variety of viral infections have been documented. Porcine reproductive and respiratory syndrome virus (PRRSV) infection induces severe lung inflammatory lesions in piglets, which is manifested as pulmonary endothelial dysfunction. However, the underlying mechanism of PRRSV affecting porcine pulmonary microvascular endothelial cells (PMECs) remains unknown. This study aimed to evaluate the susceptibility of PMECs to PRRSV. Primary PMECs were isolated and purified from piglet lungs, and the expression of three PRRSV receptors was characterized using immunofluorescence. Overt cytopathic effects of the PRRSV strain HN in PMECs were observed at day five post-infection, and PRRSV antigens in PMECs were determined at both RNA and protein levels using immunofluorescence and quantitative RT-PCR assays. The viral antigen significantly increased at 96 hr post-infection, and infectious virus was recovered from the supernatant of the infected PMECs. The results show that PMECs can be infected with the PRRSV strain HN, and that their receptor expression pattern is different from that of alveolar macrophages. The results of this study shed light on the potential roles of PMECs in PRRSV infection and provide a comprehensive understanding of the pathogenesis underlying its severe manifestation.

The Jugular Process: A Key Anatomical Landmark for Approaches to the Jugular Foramen.

OBJECTIVE: To describe the morphology and anatomical relationship of the jugular process (JP) and to elucidate its utility as a surgical landmark in the lateraland posterior lateral approaches to the jugular foramen. MATERIALS AND METHODS: Eight dry adult skulls and 10 silicon-injected cadaver heads were used for this study. The distances to selected structures and the thickness of the JP at 3 selected sites were measured. We also included the data of 20 thin-sliced 3-dimensional computed tomography scans. The radiology data of these patients were transferred to a workstation for 3-dimensional reconstruction. RESULTS: The JP, an irregular trapezoid structure, is an important surgical landmark when approaching the jugular foramen. Laterally the JP is rough with 1 or 2 prominences to which the rectus capitis lateralis is attached. The JP is relatively flat medially. The condylar part of the occipital bone could be conceived as a "3-story building." The JP, hypoglossal canal, and lateral and posterior condylar emissary veins are located on the middle floor. The stylomastoid foramen is found constantly in the triangle formed by the styloid process, JP, and the base of the mastoid process. CONCLUSIONS: The JP is an important surgical landmark in the identification of jugular foramen, especially in the lateral and posterior approaches. A better understanding of its morphology and its relationship with the surrounding structures is a prerequisite for accurate surgical planning and intraoperative orientation.

Rectus Capitis Lateralis Muscle: A Cadaveric Study of a Key Surgical Landmark in the Posterior and Lateral Approaches to the Jugular Foramen.

OBJECTIVE: The rectus capitis lateralis (RCL) is a small cervical muscle that arises from the transverse process of C1 and is intimately related to the jugular process and jugular foramen. We describe its morphology, neurovascular relationships, and its utility as one of the key surgical landmarks in approaches to the jugular foramen. METHODS: Eight cadaveric heads were used to perform far-lateral and transmastoid approaches to the jugular foramen. The neurovascular relationships of the RCL were studied. RESULTS: The RCL originates from the transverse process of C1 and inserts onto the jugular process. It can be found in the muscular interval between the posterior belly of the digastric muscle and the superior oblique muscle with the occipital artery coursing between it and the posterior belly of the digastric muscle. It lies directly posterior to the internal jugular vein and cranial nerves (CNs) IX-XI as they exit the jugular foramen. The vertebral artery courses medially to the RCL as it exits foramen transversarium of C1. As the facial nerve exits the stylomastoid foramen, it is anterolateral to the RCL before turning to enter the parotid gland. The CN XII is seen between the RCL and the occipital condyle from a posterior view. CONCLUSIONS: The RCL usually is preserved unless jugular process needs to be removed to expose the jugular foramen. The RCL is an important surgical landmark for the early identification of the vertebral artery, internal jugular vein, facial nerve, and CNs IX-XII in approaches to the jugular foramen.

Application of Dextroscope in a Rare Type of Angiomatous Meningioma Characterized With Coral-Like Vessels.

A 43-year-old female diagnosed with meningioma was admitted to our department. Preoperative imaging revealed a spherical lesion located in the sphenoid ridge with obvious enhancement and inhomogeneous density into 3 layers on magnetic resonance (MR) images, coral-like vessel images inside the tumor was obtained after the raw computed tomography angiography data were imported into the Dextroscope virtual-reality system. Due to her progressive headache and visual deterioration, surgery was performed after comprehensive study in the Dextroscope system, details about the correlation among skull base, lesion, branches of internal carotid artery, and vessels inside the tumor were well demonstrated in this system. It is diagnosed as a rare type of angiomatous meningioma, based on the abnormal manifestation on images, which even make it important to make further evaluation before making any surgical plan. Surgical resection has been the optimal treatment for most meningiomas and is meticulously performed accordingly. The patient is doing fine with no evidence of tumor recurrence on recent MR scans.

Clinical Characteristics and Prognostic Factors of Treatment in Pediatric Posterior Cranial Fossa Ependymoma.

OBJECTIVE: The purpose of this study was to explore the clinical features and risk factors of outcomes in pediatric posterior cranial fossa ependymoma. We aim to provide evidence-based recommendations for the improvement of prognoses. PATIENTS AND METHODS: The clinical data, treatment modalities, approaches performed, recurrence rates and times, as well as the outcomes of 94 cases were analyzed retrospectively. The characters of neuroimaging were further studied. RESULTS: In data from the most recent follow-up, 27 cases had tumor recurrence. The time for tumor recurrence was 13.7 ± 7.7 months. The estimated overall survival and progression-free survival, based on Kaplan-Meier analysis, was 42.2 ± 2.9 months and 38.7 ± 3.4 months, respectively. Univariate analysis showed that being free of recurrence is closely related to the high tumor sphericity (p = 0.018), homogeneity of tumor texture (p = 0.001), and gross total resection (GTR; p < 0.001). Mortality is linked to low sphericity (p = 0.017) and brain stem edema (p = 0.005). Cerebellar mutism is correlated with posterosuperior compression of the 4th ventricle roof by the tumor. The incidence rate of cerebellar ataxia, cerebellar mutism, and cerebellar dysarthria is related to the rostral extension of the tumor within the 4th ventricle. The recurrence rate is higher in subtotal resection (STR) than in GTR, and the difference is significant (p < 0.001). Although there is no significant difference between the recurrence rates in the three types, an earlier recurrence is prone with tumors located in the paramidline-lateral compared to the midline (p = 0.021) and paramidline-medial areas (p = 0.042). CONCLUSIONS: Based on our data, GTR is indicated as the most optimal choice. Recurrence is linked to lower tumor sphericity, inhomogeneous tumor texture, and STR/partial resection. Tumor located on the lateral side might be prone for an early recurrence.

Clinical Features and Prognostic Risk Factors of Choroid Plexus Tumors in Children.

BACKGROUND: Decision-making concerning the treatment of choroid plexus tumor (CPT) in pediatric patients remains a topic of considerable debate. The aim of this work was to describe clinical features and prognostic risk factors of CPT in the pediatric population and to provide theoretical opinions regarding clinical decisions for CPT. METHODS: The data of 96 patients with CPT and younger than 14 years were retrospectively analyzed. Clinical characteristics such as pathological type of CPTs, rate and severity of hydrocephalus, treatment and outcome, and recurrence were investigated. For categorical variables, the Pearson's Chi-square test was performed. The Mann-Whitney U-test was used for comparisons between nonnormally distributed parameters. Log-rank test was used for progression-free survival (PFS). RESULTS: The study included 70 choroid plexus papilloma (CPP) cases, 17 atypical choroid plexus papilloma (aCPP) cases, and 9 choroid plexus carcinoma (CPC) cases. Compared with patients with CPP or aCPP, patients with CPC had a shorter disease course (median: CPP, 4 months; aCPP, 2 months; CPC, 1 month; H: 23.5, P < 0.001), higher rate of acute hydrocephalus (CPP, 27.1%; aCPP, 52.9%; CPC, 77.8%; χ2 = 10.9, P < 0.05), and lower incidence of cure rate (CPP, 85.7%; aCPP, 70.5%; CPC, 33.3%; χ2 = 13.5, P < 0.05). The severity of hydrocephalus with tumor in the lateral or third ventricle was significantly higher than that with tumors in the fourth ventricle (severe hydrocephalus: lateral ventricle, 51.7%; third ventricle, 47.0%; fourth ventricle, 11.1%; χ2 = 26.0, P < 0.001). Patients with gross total surgical resection had no better PFS than those with partial resection because of the use of adjuvant therapy in the latter (χ2 = 4.0, P > 0.05). Patients with CPC experienced shorter time for recurrence than those with CPP or aCPP (χ2 = 40.1, P < 0.0001). CONCLUSIONS: Our results indicated that CPP in the fourth ventricle could trigger serious clinical symptoms at an early stage, requiring early intervention. Adjuvant treatment might be necessary for patients with partially resected CPP, aCPP, and CPC to achieve a favorable outcome.

Correlations between serum hepatitis B surface antigen and hepatitis B core antibody titers and liver fibrosis in treatment-naïve CHB patients.

BACKGROUND: Previous studies have revealed that quantitative hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (qAnti-HBc) levels can be used as predictors of treatment response in both interferon-α and nucleoside analogue therapies. Few data have been published regarding the relationship between quantitative HBsAg or Anti-HBc levels and liver fibrosis stages in patients with chronic hepatitis B (CHB). METHODS: We conducted a cross-sectional study of treatment-naïve CHB patients. A total of 624 CHB patients were recruited. We assessed the serum HBsAg and qAnti-HBc levels, HBV DNA levels, HBV genotypes, BCP/PC mutations, histological fibrosis staging by Scheuer classification. RESULTS: In HBeAg (+) patients, the S0-1 subjects had significantly higher serum HBsAg and lower qAnti-HBc levels than the S2-4 subjects (both p < 0.001). A moderate inverse correlation was present between serum HBsAg levels and fibrosis scores (r = -0.381, p < 0.001), and a moderate positive correlation was found between qAnti-HBc levels and fibrosis scores (r = 0.408, p < 0.001). In the HBeAg (-) patients, the S0-1 subjects also had significantly lower qAnti-HBc levels than the S2-4 subjects (p < 0.001); however, no significant difference in the HBsAg levels was observed between the S0-1 and S2-4 subjects (p > 0.05). Serum qAnti-HBc levels showed a moderate positive correlation with fibrosis scores (r = 0.383, p < 0.001), while serum HBsAg levels exhibited a low inverse correlation with fibrosis scores (r = -0.171, p < 0.001). Multiple logistic regression analysis showed that the parameters for predicting significant fibrosis (S ≥ 2) included age, PLT, qAnti-HBc levels, HBV genotype and BCP/PC mutations in HBeAg (+) group, and age, PLT, qAnti-HBc levels in HBeAg (-) group (all p < 0.05). The AUC of qAnti-HBc levels associated with the diagnosis of significant fibrosis abnormalities in HBeAg (+) and HBeAg (-) patients were 0.734 (95%CI 0.689 to 0.778) and 0.707 (95%CI 0.612 to 0.801), respectively. CONCLUSION: Our study found an association between high serum qAnti-HBc levels and significant fibrosis in both HBeAg (+) and HBeAg (-) treatment-naïve CHB patients. However, low serum HBsAg levels were correlated with moderate to severe fibrosis in HBeAg (+) subjects only.

[Minimally invasive therapy for hallux valgus with deformity of little toe varus].

OBJECTIVE: To explore clinical effect of minimally corrective osteotomy for the treatment of hallux valgus with deformity of little toe varus through small incision. METHODS: From January 2013 to June 2016, 168 hallux valgus patients with deformity of little toe varus were treated by minimally corrective osteotomy through small incision. Among them, 7 males and 161 females were aged from 22 to 75 years old with an average of(59.3±3.5) years old. Preoperative clinical manifestation mainly focus on red and swollen of bunion, pain around with metatarsal bones, and diagnosed as hallux valgus with deformity of little toe varus through small incision. Operative time, postoperative complications, pre and post-operative IMA(angle between the first and the second metatarsal bones), HVA (hallux valgus angle), LDA(valgus angle of the fifth metatarsal bones), MPA(valgus angle of little toe), IM4-5 (angle between the forth and the fifth metatarsal bones) and PASA(fixed angle of proximal joint), postoperative AOFAS score were used to evaluate foot function. RESULTS: One hundred and sixty-eight patients were followed up for 6 to 48 months with an average of (28.6±3.2) months. All wounds were healed well without infection, sinus tract and other complications. Operative time ranged from 16 to 28 min with an average of (18.3±2.1) min. IMA, HVA, LDA, MPA and IM A 4-5 were (10.1±2.1)°, (32.6±4.2)°, (6.9±2.3)°, (18.5±5.2)°, (15.1±2.9)°preoperatively, improved to (8.3±2.2)°, (10.9±2.9)°, (2.7±0.4)°, (6.5±1.6)°, (8.9±1.8)° postoperatively, and had significant differences before and after operation. While there was no difference in PASA before (9.1±2.1)°and after operation(8.7±1.9)°. AOFAS score were improved from (31.6±3.9) before operation to(83.7±5.2) after operation, but no significant difference(P>0.05). According to AOFAS score, 147 patients obtained excellent results, 13 good, 6 moderate and 2 poor. CONCLUSIONS: Minimally corrective osteotomy for the treatment of hallux valgus with deformity of little toe varus through small incision could obtain satisfied clinical effect, and has advantages of small incision, no stitches, beautiful appearance, shorter operation time, and rapid recovery. It is worth popularization in clinical practise.

CLDN5 affects lncRNAs acting as ceRNA dynamics contributing to regulating blood­brain barrier permeability in tumor brain metastasis.

The blood­brain barrier (BBB) constitutes an efficient organization of tight junctions that limits the delivery of tumor to the brain. The principal tight junction protein in BBB is claudin­5 (CLDN5), but its mechanism of action remains largely unknown. Long non­coding RNAs (lncRNAs) are aberrantly expressed in many cancers, some lncRNAs play key roles in regulating BBB permeability and are involved in tumor brain metastasis. In particular, lncRNAs can function as competing endogenous RNAs (ceRNAs). Herein, we investigated whether ceRNA dysregulation is associated with alterations of the level of CLDN5 in human brain vascular endothelial hCMEC/D3 cells. The Affymetrix Human Transcriptome Array 2.0 and Affymetrix GeneChip miRNA 4.0 Array were used to detect the expression levels of 2,578 miRNAs, 22,829 lncRNAs, and 44,699 mRNAs in pLL3.7­CLDN5­transfected and pLL3.7 control hCMEC/D3 cells. The distinctly expressed miRNAs, lncRNAs, and mRNAs were subjected to construction of miRNA­lncRNA­mRNA interaction network. A total of 41 miRNAs, 954 lncRNAs, and 222 mRNAs were found to be differentially expressed between the CLDN5­overexpressing and control group. 148 lncRNA acting as ceRNAs were identified based on the miRNA­lncRNA­mRNA interaction network. The function of differential mRNA in the network was determined by GO and pathway analysis. The potential roles of the 27 ceRNAs were revealed, the possible biology functions of these regulatory ceRNAs mainly included tight junction, focal adhesion, cell­cell adhesion, cell growth and apoptosis. The identified sets of miRNAs, lncRNAs and mRNAs specific to CLDN5­overexpressing hCMEC/D3 cells were verified by quantitative real­time RT­PCR experiment. Our study predicts the biological functions of a multitude of ceRNAs associated with the alteration of CLDN5 in brain vascular endothelial cells. Our data suggest that these dysregulated ceRNAs, in conjunction with the high CLDN5 levels, could serve as useful targets of prevention of brain metastasis formation. Further studies are warranted to determine the role of these ceRNAs in facilitating the function of CLDN5 in brain­tumor barrier.

A novel metabolism-based phenotypic drug discovery platform in zebrafish uncovers HDACs 1 and 3 as a potential combined anti-seizure drug target.

Despite the development of newer anti-seizure medications over the past 50 years, 30-40% of patients with epilepsy remain refractory to treatment. One explanation for this lack of progress is that the current screening process is largely biased towards transmembrane channels and receptors, and ignores intracellular proteins and enzymes that might serve as efficacious molecular targets. Here, we report the development of a novel drug screening platform that harnesses the power of zebrafish genetics and combines it with in vivo bioenergetics screening assays to uncover therapeutic agents that improve mitochondrial health in diseased animals. By screening commercially available chemical libraries of approved drugs, for which the molecular targets and pathways are well characterized, we were able to reverse-identify the proteins targeted by efficacious compounds and confirm the physiological roles that they play by utilizing other pharmacological ligands. Indeed, using an 870-compound screen in kcna1-morpholino epileptic zebrafish larvae, we uncovered vorinostat (Zolinza™; suberanilohydroxamic acid, SAHA) as a potent anti-seizure agent. We further demonstrated that vorinostat decreased average daily seizures by ∼60% in epileptic Kcna1-null mice using video-EEG recordings. Given that vorinostat is a broad histone deacetylase (HDAC) inhibitor, we then delineated a specific subset of HDACs, namely HDACs 1 and 3, as potential drug targets for future screening. In summary, we have developed a novel phenotypic, metabolism-based experimental therapeutics platform that can be used to identify new molecular targets for future drug discovery in epilepsy.