Potential SLA Hp-4.0 haplotype-restricted CTL epitopes identified from the membrane protein of PRRSV induce cell immune responses.

Swine leukocyte antigen (SLA) class I molecule-restricted T-cell epitopes, which induce cytotoxic T lymphocyte (CTL) responses, play a critical role in the clearance of porcine reproductive and respiratory syndrome virus (PRRSV) and the development of efficient protective vaccines. The SLA-1*04:01:01, SLA-2*04:01, and SLA-3*04:01 alleles, assigned the Hp-4.0 haplotype, are highly prevalent and usually present in all pig breeds. However, the SLA Hp-4.0 haplotype-restricted CTL epitopes in the structural membrane (M) protein of PRRSV are still unknown. In this study, we predicted 27 possible 9-mer epitope peptides in M protein with high binding scores for SLA-1*04:01:01 using CTL epitope prediction tools. In total, 45 SLA class I complexes, comprising the predicted peptide, extracellular region of the SLA-I molecules, and ß2-microglobulin, were constructed in vitro to detect the specific binding of these peptides to SLA-1*04:01:01 (27 complexes), SLA-2*04:01 (9 complexes), and SLA-3*04:01 (9 complexes), respectively. Our results showed that the M27 (T91WKFITSRC), M39 (N130HAFVVRRP), and M49 (G158RKAVKQGV) peptides bind specifically to SLA-1*04:01:01, SLA-2*04:01, and SLA-3*04:01, respectively. Subsequently, using peripheral blood mononuclear cells (PBMCs) isolated from the homozygous Hp-4.0 and Hp-26.0 haplotype piglets vaccinated with commercial PRRSV HuN4-F112 strain, we determined the capacities of these 27 potential peptides to stimulate their proliferation with a Cell Counting Kit-8 and their secretion and expression of interferon gamma (IFN-γ) with an ELISpot assay and real-time qPCR, respectively. The immunological activities of M27, M39, and M49 were therefore confirmed when they efficiently induced PBMC proliferation and IFN-γ secretion in PBMCs from piglets with the prevalent SLA Hp-4.0 haplotype. The amino acid sequence alignment revealed that M27, M39, and M49 are highly conserved among 248 genotype II PRRSV strains collected between 1998 and 2019. These findings contribute to the understanding of the mechanisms of cell-mediated immune responses to PRRSV. Our study also provides a novel strategy for identifying and confirming potential SLA haplotype-restricted CTL epitopes that could be used to develop novel peptide-based vaccines against swine diseases.

Develop a radiomics-based machine learning model to predict the stone-free rate post-percutaneous nephrolithotomy.

Radiomics and machine learning have been extensively utilized in the realm of urinary stones, particularly in forecasting stone treatment outcomes. The objective of this study was to integrate clinical variables and radiomic features to develop a machine learning model for predicting the stone-free rate (SFR) following percutaneous nephrolithotomy (PCNL). A total of 212 eligible patients who underwent PCNL surgery at the Second Affiliated Hospital of Nanchang University were included in a retrospective analysis. Preoperative clinical variables and non-contrast-enhanced CT images of all patients were collected, and radiomic features were extracted after delineating the stone ROI. Univariate analysis was conducted to identify clinical variables strongly correlated with the stone-free rate after PCNL, and the least absolute shrinkage and selection operator algorithm (lasso regression) was utilized to screen radiomic features. Four supervised machine learning algorithms, including Logistic Regression, Random Forest (RF), Extreme Gradient Boosting (XGBoost), and Gradient Boosting Decision Tree (GBDT), were employed. The clinical variables with strong correlation and screened radiomic features were integrated into the four machine learning algorithms to construct a prediction model, and the receiver operating curve was plotted. The area under the receiver operating curve (AUC), the accuracy rate, the specificity, etc., were used to evaluate the predictive performance of the four models. After analyzing postoperative statistics, the stone-free rate following the procedure was found to be 70.3% (n = 149). Among the various clinical variables examined, factors, such as stone number, stone diameter, stone CT value, stone location, and history of stone surgery, were identified as statistically significant in relation to the stone-free rate after PCNL. A total of 121 radiomic features were extracted, and through lasso regression, 7 features most closely associated with the stone-free rate post-PCNL were identified. The predictive accuracy of different models (Logistic Regression, RF, XGBoost, and GBDT) for determining the stone-free rate after PCNL was evaluated, yielding accuracies of 78.1%, 76.6%, 75.0%, and 73.4%, respectively. The corresponding area under the curve AUC (95%CI) were 0.85 (0.83-0.89), 0.81 (0.76-0.85), 0.82 (0.78-0.85), and 0.77 (0.73-0.81), positioning these models among the top performers in logistic regression prediction. In terms of predictive importance scores, the key factors identified by the logistic regression model were number of stone, zone percentage, stone diameter, and surface area. Similarly, the RF model highlighted number of stone, stone CT value, stone diameter, and surface area as the top predictors. Among the four machine learning models, the logistic regression model demonstrated the highest accuracy and discrimination ability in predicting the stone-free rate following PCNL. In comparison to XGBoost and GBDT, RF also exhibited superior accuracy and a certain level of discrimination ability. However, based on the performance of all four models, logistic regression is more likely to aid in clinical decision-making by assisting clinicians in diagnosing PCNL in patients. This enables us to effectively predict the presence of residual stones post-surgery and ultimately select patients who are suitable candidates for PCNL.

Comparison of the effect between traditional conservation and nasointestinal tube placement in adhesive small bowel obstruction: A matched case-control study.

Adhesive small bowel obstruction (ASBO) causes a major burden in emergency medicine. Owing to in situ decompression, nasointestinal tube (NIT) placement has been increasingly used in clinical practice compared with traditional conservation (TC); however, the indications remain controversial. This study was designed to explore the indications for each treatment in ASBOs and then suggest the optimal strategy. After propensity score matching, 128 pairs were included (the NIT and TC groups). The occurrence of severe adverse events (SAEs), peri-treatment clinical parameters, and radiological features were compared between the successful and failed treatment groups. According to different stages of the entire treatment, the independent risk factors for adverse effects for ASBO were analysed in phase I and phase II. In phase I, normal red blood cells (RBC) levels (p = 0.011) and a balanced sodium ion level (p = 0.016) positively affected the outcomes of TC treatment. In phase II, for the TC group, the successful treatment rate reached 79.5% for patients with ASBOs whose normal RBC levels (p = 0.006) or decreasing white blood cells (WBC) levels (p = 0.014) after treatment. For the NIT group, the treatment success rate was 68.1% for patients whose electrolyte imbalance could be reversed or whose neutrophil count/lymphocyte ratio (NLR) levels was lower than 4.3 (p = 0.018). TC treatment is highly recommended for patients with normal RBC counts and sodium levels pretreatment. After dynamic monitoring of the treatment process, for both the TC and NIT groups, once ASBOs had elevated inflammatory biomarkers or irreversible electrolyte disturbances, surgical interference was preferred.

A Machine Learning Method for a Blood Diagnostic Model of Pancreatic Cancer Based on microRNA Signatures.

This study aimed to construct a blood diagnostic model for pancreatic cancer (PC) using miRNA signatures by a combination of machine learning and biological experimental verification. Gene expression profiles of patients with PC and transcriptome normalization data were obtained from the Gene Expression Omnibus (GEO) database. Using random forest algorithm, lasso regression algorithm, and multivariate cox regression analyses, the classifier of differentially expressed miRNAs was identified based on algorithms and functional properties. Next, the ROC curve analysis was used to evaluate the predictive performance of the diagnostic model. Finally, we analyzed the expression of two specific miRNAs in Capan-1, PANC-1, and MIA PaCa-2 pancreatic cells using qRT-PCR. Integrated microarray analysis revealed that 33 common miRNAs exhibited significant differences in expression profiles between tumor and normal groups (P value < 0.05 and |logFC| > 0.3). Pathway analysis showed that differentially expressed miRNAs were related to P00059 p53 pathway, hsa04062 chemokine signaling pathway, and cancer-related pathways including PC. In ENCORI database, the hsa-miR-4486 and hsa-miR-6075 were identified by random forest algorithm and lasso regression algorithm and introduced as major miRNA markers in PC diagnosis. Further, the receiver operating characteristic curve analysis achieved the area under curve score > 80%, showing good sensitivity and specificity of the two-miRNA signature model in PC diagnosis. Additionally, hsa-miR-4486 and hsa-miR-6075 genes expressions in three pancreatic cells were all up-regulated by qRT-PCR. In summary, these findings suggest that the two miRNAs, hsa-miR-4486 and hsa-miR-6075, could serve as valuable prognostic markers for PC.

Molecular Face-Rotating Polyhedra: Chiral Cages Inspired by Mathematics.

ConspectusMolecular polyhedral cages, notable for their enclosed inner cavities, can possess varying degrees of symmetry, spanning from regular Platonic polyhedra to lower symmetry forms that may display chirality. Crafting chiral molecular cages typically involves using building blocks containing stereogenic elements or arranging achiral components in a manner that lacks mirror and inversion symmetries. Achieving precise control over their chirality poses both significance and challenges.In this Account, we present an overview of our research endeavors in the realm of chiral molecular polyhedral cages, drawing inspiration from Buckminster Fuller's "Face-Rotating Polyhedra (FRP)". Mathematically, FRP introduce a unique form of chirality distinguished by a rotating pattern around the center of each face, setting it apart from regular polyhedra.Molecular FRP can be constructed using two types of facial building blocks. The first includes rigid, planar molecules such as truxene and triazatruxene, which exhibit either clockwise or counterclockwise rotations in two dimensions. The second category involves propeller-like molecules, e.g., tetraphenylethylene, 1,2,3,4,5-penta(4-phenylaldehyde)pyrrole, and tridurylborane, displaying dynamic stereochemistry.The synthesis of FRP may potentially yield a diverse array of stereoisomers. Achieving high stereoselectivity becomes feasible through the selection of building blocks with specific substitution patterns and rigidity. Prominent noncovalent repulsive forces within the resulting cages often play a pivotal role in the dynamic covalent assembly process, ultimately leading to the formation of thermodynamically stable FRP products.The capacity to generate a multitude of stereoisomers, combined with the integration of chiral vertices, has facilitated investigations into phenomena such as chiral self-sorting and the "sergeant and soldiers" chiral amplification effect in FRP. Even the inclusion of one chiral vertex significantly impacts the stereochemical configuration of the entire cage. While many facial building blocks establish a stable rotational pattern in FRP, other units, such as tridurylborane, can dynamically transition between P and M configurations within the cage structures. The kinetic characteristics of such stereolabile FRP can be elucidated through physicochemical investigations.Our research extends beyond the FRP concept to encompass mathematical analysis of these structures. Graph theory, particularly the coloring problem, sheds light on the intricate facial patterns exhibited by various FRP stereoisomers and serves as an efficient tool to facilitate the discovery of novel FRP structures. This approach offers a fresh paradigm for designing and analyzing chiral molecular polyhedral cages, showcasing in our work the synergy between mathematics and molecular design.

Efficacy of Qingpeng ointment (a Tibetan medicine) for acute gouty arthritis: a multi-center, randomized, double-blind, placebo-controlled trial.

BACKGROUND: This study aims to assess the efficacy and safety of Qingpeng ointment (QPO), a Tibetan medicine for alleviating symptoms in individuals with acute gouty arthritis (AGA). METHODS: This study was a randomized, double-blind, placebo-controlled trial that involved individuals with AGA whose joint pain, as measured on a visual analog scale (VAS) from 0 to 10, was equal to or greater than 3. The participants were randomly assigned to either the QPO or the placebo group and received their respective treatments twice daily for seven consecutive days. In case of intolerable pain, the participants were allowed to use diclofenac sodium sustained-release tablets as a rescue medicine. The primary outcomes measured were joint pain and swelling, while the secondary outcomes included joint mobility, redness, serum uric acid levels, C-reactive protein levels, and the amount of remaining rescue medicine. Any adverse events that occurred during the trial were also recorded. RESULTS: A total of 203 cases were divided into two groups, with balanced baselines: 102 in the QPO group and 101 in the placebo group. For joint pain, differences between the groups were notable in the VAS scores [1.75 (0, 3.00) versus 2.00 (1.00, 3.50); P = 0.038], changes in VAS [5.00 (3.00, 6.00) versus 4.00 (2.00, 6.00); P = 0.036], and disappearance rate [26.47% compared to 15.84%; P = 0.046] after treatment. Concerning joint swelling, significant between-group differences were observed in the VAS scores [1.00 (0, 2.30) versus 2.00 (0.70, 3.00); P = 0.032] and disappearance rate [33.33% compared to 21.78%; P = 0.046] at treatment completion. The QPO group exhibited a statistically significant mobility improvement compared to the placebo group (P = 0.004). No significant differences were found in other secondary outcomes. Five patients, four from the QPO group and one from the other, encountered mild adverse events, primarily skin irritation. All of these cases were resolved after dosage reduction or discontinuation of the medication. CONCLUSIONS: Compared to the placebo, QPO exhibits positive effects on AGA by alleviating pain, reducing swelling, and enhancing joint mobility, without causing significant adverse effects. TRIAL REGISTRATION: ISRCTN34355813. Registered on 25/01/2021.

Network pharmacology identifies the inhibitory effect of Yiqiyangyinquyu prescription on salivary gland inflammation in Sjögren's syndrome.

This study aimed to explore the mode of action of Yiqiyangyinquyu prescription (YP) against Sjögren's syndrome (SS) by combining network pharmacology with molecular docking techniques. YP's active components and target proteins were identified using the BATMAN-traditional Chinese medicine database. Concurrently, targets associated with SS were extracted from databases, including Genecards, Online Mendelian Inheritance in Man, and Therapeutic Target Database. The standard targets were then imported into the STRING database to construct a protein-protein interaction network. We then conducted gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses, which were succeeded by molecular docking studies to validate core active components and key targets. Finally, in vitro experiments and molecular dynamics simulation were conducted to substantiate the therapeutic efficacy of YP in treating SS. A total of 206 intersection targets and 46 active compounds were identified. Gene ontology analysis unveiled that YP targets were primarily enriched in cellular responses to chemical stress, inflammation, and cell proliferation. Key enriched signaling pathways encompassed the interleukin 17, hypoxia-inducible factor-1, tumor necrosis factor (TNF-α), and advanced glycation end products-receptor for AGEs (AGE-RAGE) signaling pathways. Molecular docking results demonstrated high-affinity between neotanshinone C, tanshiquinone B, miltionone I, TNF-α, interleukin 1 beta (IL-1ß), and interleukin 6 (IL-6). Noteworthy, TNF-α, considered the most important gene in YP against SS, binds to YP most stably, which was further validated by molecular dynamics simulation. In vitro experiments confirmed YP's capacity to reduce TNF-α, IL-1ß, and IL-6 expression, effectively alleviating SS-related inflammation. YP demonstrated a significant anti-inflammatory effect by suppressing inflammatory cytokines (TNF-α, IL-6, and IL-1ß), providing experimental evidence for its clinical application in treating SS.

Genome-wide DNA methylation sequencing reveals epigenetic features and potential biomarkers of Sjögren syndrome.

AIM: Sjögren syndrome (SS) is a slowly progressive, inflammatory, autoimmune disease. The aim of this study was to construct the DNA methylation profiles of whole blood of SS patients and healthy controls (HC), and to explore the role of differentially methylated genes in the pathogenesis of the disease. METHODS: Whole-genome bisulfite sequencing was performed on three SS patients and four HC. The biological function of genes associated with differentially methylated regions (DMRs) was investigated using Gene Ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis, using network-based key driver analysis (KDA) to find KDA genes. In clinical samples of SS patients and controls, the expression levels of KDA genes were validated by quantitative real-time polymerase chain reaction and immunohistochemical analysis. Moreover, the diagnostic value of KDA genes for SS was confirmed using receiver operating characteristic curves. RESULTS: We identified 322 DMRs, annotated as 162 associated genes. Six genes were selected via the number of networks of KDA genes. Differential expression of genes such as human leukocyte antigen (HLA) class I, ADAR, and OAS2 was observed in patients' peripheral blood mononuclear cells and the minor salivary glands, which can be used as potential diagnostic biomarkers for SS. CONCLUSION: Clinical sample validation suggested that HLA class I, ADAR, and OAS2 might play a role in the development of SS. Our study shows epigenetic regulatory mechanisms and potential disease markers associated with SS, which in turn will enable us to identify new therapeutic targets.

[Effect of acupuncture on HIF-1α/NLRP3 inflammatory signaling pathway in the rats with cerebral ischemia-reperfusion injury].

OBJECTIVE: To observe the effects of Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture therapy on the expression of hypoxia-inducible factor 1α (HIF-1α) and Nod-like receptor protein 3 (NLRP3) in cerebral ischemia-reperfusion rats, and to explore the mechanism of acupuncture against cerebral ischemia-reperfusion injury. METHODS: Seventy-two male SD rats were randomly divided into a sham-operation group, a model group, an acupuncture group and a non-point acupuncture group, with 18 rats in each one. Using modified Longa thread embolization method, the rat model of acute focal cerebral ischemia was prepared; and after 2 h ischemia, the reperfusion was performed to prepared the model of cerebral ischemia-reperfusion. Immediately after reperfusion, Xingnao Kaiqiao acupuncture method was applied to bilateral "Neiguan" (PC 6) and "Shuigou" (GV 26) in the acupuncture group, while in the non-point acupuncture group, acupuncture was delivered at non-points and all of the needles were retained for 30 min in these two groups. The samples were collected 24 h after reperfusion in the rats of each group. Zea-Longa neurological deficit score was used to evaluate the degree of cerebral neurological impairment, TTC staining was adopted to observe the volume percentage of cerebral infarction, HE staining was provided to observe the morphological changes of brain, and Western blot was applied for detecting the expression of HIF-1α and NLRP3 proteins in the cerebral cortex on the right side. RESULTS: Compared with the sham-operation group, neurological deficit score and volume percentage of cerebral infarction were increased in the model group (P<0.01), and HIF-1α and NLRP3 protein expression was elevated (P<0.01). Compared with the model group, neurological deficit score and volume percentage of cerebral infarction were decreased (P<0.01), and HIF-1α and NLRP3 protein expression was lower (P<0.01) in the acupuncture group. There was no significant difference in above indexes in the non-point acupuncture group compared with the model group (P>0.05). Compared with the sham-operation group, the brain tissue of the rats in the model group and the non-point acupuncture group was loose and edema, and the nuclei were shriveled. The brain tissue morphology in the acupuncture group was similar to that of the sham-operation group. CONCLUSION: Acupuncture can alleviate cerebral ischemia-reperfusion injury, and its mechanism may be related to the regulation of HIF-1α/NLRP3 signaling pathway to attenuate inflammatory response.

Quantum Simulation of the Shortcut to the Adiabatic Passage Using Nuclear Magnetic Resonance.

Quantum adiabatic shortcut technology provides a technique to accelerate the quantum adiabatic process and has been widely used in various fields of quantum information processing. In this work, we proposed a two-level quantum shortcut adiabatic passage model. Then, exploiting the nuclear magnetic resonance, we experimentally simulated the dynamics of quantum shortcut adiabatic passage using the water molecules.

Clinical characteristics and management of coexistent cardiomyopathy in patients with bicuspid aortic valve.

BACKGROUND: Bicuspid aortic valve (BAV) is the most common congenital heart disease. However, the prevalence, clinical characteristics, and current management of BAV associated with inherited cardiomyopathy, including hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and left ventricular noncompaction (LVNC) have not been well described. METHODS: Consecutive patients diagnosed with BAV at a large tertiary cardiovascular referral center between 2009 and 2018 were retrospectively assessed for HCM, DCM, and LVNC based on clinical and echocardiographic criteria. Patients with coexistent conditions were investigated further. RESULTS: Of 3533 patients with BAV screened, 57 (1.6%) had concomitant cardiomyopathy. BAV was combined with HCM in 30 of these patients, with DCM in 19, and with LVNC in eight. Forty-six patients (80.7%) were male, and the mean age at first diagnosis was 47 years for BAV with HCM, 49 years for BAV with DCM, and 35 years for BAV with LVNC. Heart failure and aortic valve dysfunction were common in these patients, and the prevalence of coexisting aortopathy was 43.3%, 26.3% and 25.0%, respectively, for BAV with HCM, DCM and LVNC. During the index hospitalization, 24 of the 57 patients (42.1%) underwent surgery, 16 (28%) underwent aortic valve and/or aortic surgery, and 16 of the 30 patients with HCM had a Morrow procedure. There were no deaths or other major adverse cardiovascular events. CONCLUSIONS: The prevalence of inherited cardiomyopathy was higher in our patients with BAV than in the general population. Aortopathy and heart failure were common, with almost half of patients requiring surgery at diagnosis.

Simple and Versatile Nitrooxylation: Noncyclic Hypervalent Iodine Nitrooxylating Reagent.

Organic nitrates are broadly applied as pharmaceuticals (acting as efficient nitric oxide donor), energetic materials, building blocks in organic synthesis, etc. However, practical and direct methods to access organic nitrates efficiently are still rare, mainly due to the lack of powerful nitrooxylating reagents. Herein, we report bench-stable and highly reactive noncyclic hypervalent iodine nitrooxylating reagents, oxybis(aryl-λ3 -iodanediyl) dinitrates (OAIDNs, 2), which are prepared just by using aryliodine diacetate and HNO3 . The reagents are used to achieve a mild and operationally simple protocol to access diverse organic nitrates. By employing of 2, zinc-catalyzed regioselective nitrooxylation of cyclopropyl silyl ethers is realized efficiently to access the corresponding ß-nitrooxy ketones with high functional-group tolerance. Moreover, a series of direct and catalyst-free nitrooxylations of enolizable C-H bonds are carried out smoothly to afford the desired organic nitrates within minutes by just mixing the substrates with 2 in dichloromethane.

Hole Storage Interfacial Regulation of Sb2Se3 Photocathode with Significantly Enhanced Photoelectrochemical Performance.

Although interfacial engineering materials for antimony selenide (Sb2Se3) photocathodes have been intensively studied, most of the previous research has focused on the development of photogenerated electron transfer promoters. In this work, Sb2Se3 photocathodes are innovatively modified by using ferrihydrite (Fh), which has been widely used as a hole storage layer in photoanodes. After modifying Fh, the photocurrent density of the Sb2Se3 photocathode was increased from -0.27 to -1.6 mA cm-2 at 0 VRHE with the onset potential positive shift about 150 mV, and an impressive injection efficiency of 83.84% was achieved. The major contribution of Fh to the photoelectrochemical (PEC) performance enhancement was demonstrated by various characterization studies. The results show that the enhancement performance of PEC is largely attributed to the capture of back-migrating holes by Fh, the reduction of interfacial charge transfer resistance, and the significant increase in electrochemical active surface area (ECSA). This work presents new insights into the application of hole storage layers in Sb2Se3-based photocathodes.

Synthesis of Highly Luminescent Chiral Nanographene.

Chiral nanographenes with both high fluorescence quantum yields (ΦF ) and large dissymmetry factors (glum ) are essential to the development of circularly polarized luminescence (CPL) materials. However, most studies have been focused on the improvement of glum , whereas how to design highly emissive chiral nanographenes is still unclear. In this work, we propose a new design strategy to achieve chiral nanographenes with high ΦF by helical π-extension of strongly luminescent chromophores while maintaining the frontier molecular orbital (FMO) distribution pattern. Chiral nanographene with perylene as the core and two dibenzo[6]helicene fragments as the wings has been synthesized, which exhibits a record high ΦF of 93 % among the reported chiral nanographenes and excellent CPL brightness (BCPL ) of 32 M-1 cm-1 .

Surveillance and control of infectious disease in primary and middle schools in Hebei Province from 2019 to 2021 / 中国学校卫生

Objective@#To understand the infectious disease prevention and control among primary and secondary schools in Hebei Province from 2019 to 2021 and to provide a scientific basis for promoting epidemic prevention and control in schools.@*Methods@#Relevant indicators of infectious disease prevention and control in primary and secondary schools were collected and screened from the on site supervision and inspection data uploaded from various places, and analyzed with SPSS 22.0 software.@*Results@#The qualified rates of infectious disease prevention and control in primary and secondary schools in Hebei Province from 2019 to 2021 were 77.11%, 89.74% and 96.24%, respectively, the difference was statistically significant( χ 2=455.45, P <0.01). The qualified rates of infectious disease prevention and control in primary schools, middle schools and high schools from 2019 to 2021 increased by year, the difference was statistically significant( χ 2=319.49, 118.74, 25.73, P <0.05). The qualified rates of six infectious disease prevention and control indicators such as morning inspection record, special person responsible for epidemic report, registration record of absence due to illness increased by year, the difference was statistically significant( χ 2=140.34, 9.10, 113.55 , 163.71 , 286.74, 329.18, P <0.05).@*Conclusion@#Steady improvement in school infectious disease prevention and control has been observed, while qualification rate in primary school and rural area still need to be improved, with missing or late report. Government support and talent policy, hardware and sofeware construction, as management level should be strengthened.

Effect of acupuncture on HIF-1α/NLRP3 inflammatory signaling pathway in the rats with cerebral ischemia-reperfusion injury / 中国针灸

OBJECTIVE@#To observe the effects of Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture therapy on the expression of hypoxia-inducible factor 1α (HIF-1α) and Nod-like receptor protein 3 (NLRP3) in cerebral ischemia-reperfusion rats, and to explore the mechanism of acupuncture against cerebral ischemia-reperfusion injury.@*METHODS@#Seventy-two male SD rats were randomly divided into a sham-operation group, a model group, an acupuncture group and a non-point acupuncture group, with 18 rats in each one. Using modified Longa thread embolization method, the rat model of acute focal cerebral ischemia was prepared; and after 2 h ischemia, the reperfusion was performed to prepared the model of cerebral ischemia-reperfusion. Immediately after reperfusion, Xingnao Kaiqiao acupuncture method was applied to bilateral "Neiguan" (PC 6) and "Shuigou" (GV 26) in the acupuncture group, while in the non-point acupuncture group, acupuncture was delivered at non-points and all of the needles were retained for 30 min in these two groups. The samples were collected 24 h after reperfusion in the rats of each group. Zea-Longa neurological deficit score was used to evaluate the degree of cerebral neurological impairment, TTC staining was adopted to observe the volume percentage of cerebral infarction, HE staining was provided to observe the morphological changes of brain, and Western blot was applied for detecting the expression of HIF-1α and NLRP3 proteins in the cerebral cortex on the right side.@*RESULTS@#Compared with the sham-operation group, neurological deficit score and volume percentage of cerebral infarction were increased in the model group (P<0.01), and HIF-1α and NLRP3 protein expression was elevated (P<0.01). Compared with the model group, neurological deficit score and volume percentage of cerebral infarction were decreased (P<0.01), and HIF-1α and NLRP3 protein expression was lower (P<0.01) in the acupuncture group. There was no significant difference in above indexes in the non-point acupuncture group compared with the model group (P>0.05). Compared with the sham-operation group, the brain tissue of the rats in the model group and the non-point acupuncture group was loose and edema, and the nuclei were shriveled. The brain tissue morphology in the acupuncture group was similar to that of the sham-operation group.@*CONCLUSION@#Acupuncture can alleviate cerebral ischemia-reperfusion injury, and its mechanism may be related to the regulation of HIF-1α/NLRP3 signaling pathway to attenuate inflammatory response.

[Acupuncture regulates autophagic flux to antagonize cerebral ischemic injury in rats].

OBJECTIVE: To observe the effect of acupuncture on the cerebral infarct volume and expressions of Beclin1, microtubule-associated protein 1 light chain 3 (LC3) and p62 proteins related to cell autophagy in rats with cerebral ischemia (CI), so as to explore its mechanisms underlying improvement of CI injury. METHODS: Male SD rats were randomized into 3 groups: sham operation, model and acupuncture which were further divided into 4 subgroups according to different ischemia time-points: 3, 6, 12 and 24 h (n=7 in each subgroup). The CI model was established by occlusion of the middle cerebral artery (MCAO) with surgical suture-embolus. For rats of the acupuncture group, acupuncture was applied to "Shuigou" (GV26) and bilateral "Neiguan" (PC6), and twirled for 1-3 min every time, 10 times altogether, and kept for 30 min. The neurological deficit score accoding to Longa's method was used for assessing the neurological function. The CI volume was measured after 2, 3, 5-triphenyltetrazolium chloride staining. The expression levels of autophagy-related proteins Beclin1，LC3 and p62 in the brain tissue were detected using Western blot. RESULTS: Compared with those of the sham operation group，the neurological deficit scores at 2, 3, 6， 12 and 24 h after CI, and the infarct volumes, the expression levels of Beclin1 and the ratios of LC3-Ⅱ/LC3-Ⅰ at 3, 6, 12 and 24 h were considerably increased (P<0.01, P<0.05), and the expression levels of p62 at 3, 6, 12 and 24 h were significantly decreased (P<0.01) in the model group. Relevant to the model group, acupuncture stimulation of GV26 and PC6 induced an obvious decrease in the neurological deficit scores at 6, 12 and 24 h, CI volumes at 3, 6, 12 and 24 h, and the expression levels of Beclin1 and the ratios of LC3-Ⅱ/LC3-Ⅰ both at 6 and 12 h (P<0.01, P<0.05), and an evident increase in the expression levels of p62 at 6, 12 and 24 h after CI (P<0.05, P<0.01). CONCLUSION: Acupuncture stimulation of GV26 and PC6 can reduce the CI volume and improve neurological function in CI rats， which may be related to its efficacy in down-regulating the expression of Beclin1 and the ratio of LC3-Ⅱ/LC3-Ⅰ, and up-regulating the expression of p62 in the ischemic brain tissue， thereby improving autophagy flux.

Cobalt-Catalyzed Effective Access to Quinoxalines with Insights in Annulation of Terminal Alkynes and o-Phenylenediamines.

A novel methodology for the annulation of terminal alkynes and o-phenylenediamines by using a combination of a cobalt catalyst and oxygen as a terminal oxidant is reported. This method shows wide substrate scope and good functional group tolerance and provides a wide range of quinoxalines in good to high yields. The method is demonstrated by its gram-scale and broad potential applications. Furthermore, this protocol serves as a powerful tool for the late-stage functionalization of various complex bioactive molecules and drugs to provide a new class of molecules containing two distinct bioactive molecules directly linked. Detailed mechanistic studies reveal that the current reaction goes through a novel mechanism different from the previously reported glyoxal mechanism.

[Effect of Xingnao Kaiqiao acupuncture on safety of rt-PA intravenous thrombolysis in patients with cerebral infarction: a randomized controlled trial].

OBJECTIVE: To assess the effect of Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture on the efficacy and safety of intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in patients with cerebral infarction. METHODS: A total number of 142 patients of cerebral infarction undergoing rt-PA intravenous thrombolysis were randomized into an acupuncture-medication group (71 cases) and a western medication group (71 cases, 1 case dropped off). In the western medication group, rt-PA intravenous thrombolysis was given. In the acupuncture-medication group, besides the intervention as the control group, Xingnao Kaiqiao acupuncture was provided at Shuigou (GV 26), Neiguan (PC 6), Sanyinjiao (SP 6), Jiquan (HT 1), etc. once daily. One treatment session contained 6 treatments and 1 session was required. Before and after treatment, the score of the National Institute of Health stroke scale (NIHSS), the levels of the relevant indexes of symptomatic intracerebral hemorrhage (sICH) (platelet [PLT], D-dimer and fibrinogen), the incidences of sICH and adverse effect were compared between groups. The efficacy was assessed in two groups. RESULTS: After treatment, NIHSS scores and the levels of D-dimer were reduced compared with those before treatment in both groups (P<0.05), and those in the acupuncture-medication group were lower than the western medication group (P<0.05). The level of fibrinogen in the acupuncture-medication group was increased in comparison with that before treatment (P<0.05), and also higher than the western medication group (P<0.05). The incidence of sICH was 0% (0/71) in the acupuncture-medication group, lower than 8.6% (6/70) in the western medication group (P<0.05). The effective rate was 97.2% (69/71) in the acupuncture-medication group, higher than 87.1% (61/70) in the western medication group (P<0.05). The incidence of adverse effect was 2.8% (2/71) in the acupuncture-medication group, lower than 12.9% (9/70) in the western medication group (P<0.05). CONCLUSION: Xingnao Kaiqiao acupuncture may improve the efficacy of rt-PA intravenous thrombolysis in the patients with cerebral infraction and decrease the incidences of sICH and adverse effect. The mechanism may be related to the regulation of fibrinogen and D-dimer levels.

A novel missense mutation in obscurin gene in a Chinese consanguineous family with left ventricular noncompaction.

BACKGROUND: Left ventricular noncompaction (LVNC) is an increasingly recognised cardiomyopathy of which a significant percentage are genetic in origin. The purpose of the present study was to identify potential pathogenic mutation leading to disease in a Chinese LVNC family. METHODS: A 3-generation family affected by LVNC was recruited. Clinical assessments were performed on available family members, with clinical examination, ECG, echocardiography and cardiac MRI. The proband (I-2), the proband's daughter (II-1, affected) and mother (III-1, unaffected) were selected for WGS. Sanger sequencing were performed in all of the 4 surviving family members. RESULTS: Combined whole genome sequencing with linkage analysis identified a novel missense mutation in the giant protein obscurin (OBSCN NM_001098623, c.C19063T), as the only plausible disease-causing variant that segregates with disease among the four surviving individuals, with interrogation of the entire genome excluding other potential causes. This c.C19063T missense mutation resulted in p.R6355W in the encoded OBSCN protein. It affected a highly conserved residue in the C terminus of the obscurin-B-like isoform between the PH and STKc domains, which was predicted to affect the function of the protein by different bioinformatics tools. CONCLUSIONS: Here we present clinical and genetic evidence implicating the novel R6355W missense mutation in obscurin as the cause of familial LVNC. This expands the spectrum of obscurin's roles in cardiomyopathies. It furthermore highlights that rare obscurin missense variants, currently often ignored or left uninterpreted, should be considered to be relevant for cardiomyopathies and can be identified by the approach presented here. This study also provided new insights into the molecular basis of OBSCN mutation positive LVNC.