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To investigate the pharmacodynamic material basis, mechanism of actions and targeted diseases of Salicornia europaea L. (SE) based on the network pharmacology method, and to verify the antidepressant-like effect of the SE extract by pharmacological experiments.Retrieval tools including Chinese medicine (CM), PubMed, PharmMapper, MAS 3.0 and Cytoscape were used to search the components of SE, predict its targets and related therapeutic diseases, and construct the "Component-Target-Pathway" network of SE for central nervous system (CNS) diseases. Further, protein-protein interaction (PPI) network, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) function annotation of depression-related targets were analyzed to predict the antidepressant mechanism of SE. Chronic unpredictable mild stress (CUMS) model was used to construct a mouse model with depression-like symptoms. And the animals were randomly divided into 6 groups (n=10) including the normal group (nonstressed mice administered with distilled water), the CUMS group (CUMS mice administered with distilled water), the venlafaxine group (CUMS mice administered with venlafaxine 9.38 mg/kg), SE high-, medium-, and low-dose groups (CUMS mice administered with SE 1.8, 1.35 and 0.9 g/kg, respectively). Then some relevant indicators were determined for experimental verification by the forced swim test (FST), the tail suspension test (TST) and open-field test (OFT). Dopamine (DA) concentration in hippocampus and cerebral cortex, IL-2 and corticosterone (CORT) levels in blood, and nuclear factor E2 related factor 2 (Nrf2), kelch-like epichlorohydrin related protein 1 (Keap1), NAD(P) H dehydrogenase [quinone] 1 (NQO1) and heme oxygenase-1 (HO-1) levels in mice were measured by enzyme linked immunosorbent assay (ELISA) and Western blot respectively to explore the possible mechanisms.The "target-disease" network diagram predicted by network pharmacology, showed that the potential target of SE involves a variety of CNS diseases, among which depression accounts for the majority. The experimental results showed that SE (1.8, 1.35 g/kg) significantly decreased the immobility period, compared with the CUMS group in FST and TST in mice after 3-week treatment, while SE exhibited no significant effect on exploratory behavior in OFT in mice. Compared with CUMS group, the SE group (0.9 g/kg) showed significant differences (P0.05) in DA levels in the hippocampus and cerebral cortex. In addition, compared with CUMS control group, SE (1.8 g/kg) group showed a significant effect on decreasing the activities of CORT (P0.05), and serum IL-2 level with no statistical significance. Finally, Western blot results showed that compared with the model group, Nrf2, Keap1, NQO1 and HO-1 protein expressions in SE group (1.8 g/kg) were up-regulated (all P0.01).The SE extract may have an antidepressant effect, which appeared to regulate Nrf2-ARE pathway and increased levels of DA and CORT in the hippocampus and cortex.

Reduced drug uptake and elevated drug efflux are two major mechanisms in cancer multidrug resistance (MDR). In the present study, a new multistage O

Although the development of safe and efficient cancer therapeutic agents is essential, this process remains challenging. In this study, a mitochondria-targeted degradable nanoplatform (PDA–MnO2-IR780) for synergistic photothermal, photodynamic, and sonodynamic tumor treatment was investigated. PDA–MnO2-IR780 exhibits superior photothermal properties owing to the integration of polydopamine, MnO2, and IR780. IR780, a photosensitizer and sonosensitizer, was used for photodynamic therapy and sonodynamic therapy. When PDA–MnO2-IR780 was delivered to the tumor site, MnO2 was decomposed by hydrogen peroxide, producing Mn2+ and oxygen. Meanwhile, alleviating tumor hypoxia promoted the production of reactive oxygen species during photodynamic therapy and sonodynamic therapy. Moreover, large amounts of reactive oxygen species could reduce the expression of heat shock proteins and increase the heat sensitivity of tumor cells, thereby improving the photothermal treatment effect. In turn, hyperthermia caused by photothermal therapy accelerated the production of reactive oxygen species in photodynamic therapy. IR780 selectively accumulation in mitochondria also promoted tumor apoptosis. In this system, the mutual promotion of photothermal therapy and photodynamic therapy/sonodynamic therapy had an enhanced therapeutic effect. Moreover, the responsive degradable characteristic of PDA–MnO2-IR780 in the tumor microenvironment ensured excellent biological safety. These results reveal a great potential of PDA–MnO2-IR780 for safe and highly-efficiency synergistic therapy for cancer.

The construction of high-efficiency tumor theranostic platform will be of great interest in the treatment of cancer patients; however, significant challenges are associated with developing such a platform. In this study, we developed high-efficiency nanotheranostic agent based on ferroferric oxide, manganese dioxide, hyaluronic acid and doxorubicin (FMDH-D NPs) for dual targeting and imaging guided synergetic photothermal-enhanced chemodynamic/chemotherapy for cancer, which improved the specific uptake of drugs at tumor site by the dual action of CD44 ligand hyaluronic acid and magnetic nanoparticles guided by magnetic force. Under the acidic microenvironment of cancer cells, FMDH-D could be decomposed into Mn

Objective: To investigate the effect of Fuhe decoction on the behavior and levels of monoamine neurotransmitters in different brain regions in a depression rat model induced by chronic unpredictable mild stimulation (CUMS) combined with social isolation. Methods: Fifty male SD rats were randomly divided into a blank group, model group, fluoxetine group, Chaiqinwendan decoction group, and Fuhe decoction group. Chronic unpredictable mild stimulation combined with a social isolation method was used to replicate the depression rat model. After 42 days of administration, a tail suspension test and high-performance liquid electrochemical detection (HPLC-ECD) were used to detect the behavioral changes and changes in the content of monoamine neurotransmitters norepinephrine (NE), dopamine (DA), 5-hydroxytrytamine (5-HT), and metabolites in different brain regions of rats in each group before and after treatment. Results: Compared with the model group, the epinephrine (E) content in the Fuhe decoction group was highly significantly increased (P

Stroke is a major cause of death and disability in China, and no therapies have proven effective to prevent it. Popular belief holds that the lunar cycle affects human physiology, behavior, and health. The aim of our study is to determine whether the lunar cycle impacts the incidence of stroke subtypes [intracerebral hemorrhage (ICH), transient ischemic attack (TIA) and ischemic stroke (IS)]. We retrospectively extracted the discharge registry data of all patients with first-ever acute stroke hospitalized in the affiliated hospital of Beijing University of Traditional Chinese Medicine during 2002-2015. The onset times of stroke were assigned to four primary lunar phases based on NASA definitions. Chi-square tests and multiple logistic regression analyses were used to estimate the association between the lunar cycle and stroke incidence with adjustment for age, sex and season. A total of 5,965 patients with stroke (4,909 admissions for ischemic stroke IS, 754 admissions for ICH, and 302 admissions for TIA) were evaluated in our study. Subgroup analysis indicated that the admission rates of different sexes for IS tended to have opposite variation during the four moon phases. More female patients were admitted during the new moon than in the first and third quarters, while fewer male patients were admitted during the new moon than in the first and third quarters (χ2 = 15.589, P = .001). Multiple logistic regression analyses revealed that men were more likely to be admitted for IS in the first quarter than during the new moon (odds ratio [OR] = 1.252, 95% confidence interval [CI] = 1.076-1.456) (P = .004), and a corresponding trend was also identified for the third quarter (OR = 1.235, 95% CI = 1.062-1.437) (P = .006). No significant gender differences were shown in ICH or TIA. No sex difference is obvious during the full moon. Moon phases seem to affect both genders, but in very different ways. It seems that the new moon is a protective factor for male ischemic stroke patients and a risk factor for female ones. Woman tends to be more vulnerable than ever at the new moon, so deserves more attention and care. The mechanisms underlying this observation are worth studying further.

Objective: Findings on the effect of the lunar cycle on mental illness are conflicting. We investigated the association between the lunar cycle and a number of psychiatric presentations of schizophrenia and determined which subtypes were susceptible to lunar phases.Methods: We evaluated 13,067 patients admitted to Zhumadian Psychiatric Hospital between January 1, 2012, and December 31, 2017 (73 lunar cycles). Patients were retrospectively assigned to lunar phase based on their admission date: new moon +/- 1 day, first quarter +/- 1 day, full moon +/- 1 day, and third quarter +/- 1 day. The International Statistical Classification of Diseases, 10th revision (ICD-10), was used for diagnosis. We used a Chi-squared goodness of fit test to evaluate the distribution of admissions across the lunar phase and R*C Chi-squared tests to compare age, sex, birth season, and clinical subtype distributions by phase. We used multiple logistic regression to further identify the relationship between clinical subtype and lunar phase.Results: Psychiatric admissions for schizophrenia varied significantly across the lunar cycle (χ2 = 36.400, p .05).Conclusions: Psychiatric admissions for schizophrenia show lunar periodicities. People with schizophrenia tend to be stable in the new moon, but their condition is easily aggravated during the first quarter and full moon. Patients with paranoid schizophrenia are more susceptible to deterioration at the full moon, so merit more attention and care from communities, families, and hospitals.

BACKGROUND The incidence of metabolic syndrome (MetS) is increasing, and n-3 polyunsaturated fatty acids (PUFAs) in salmon (Oncorhynchus) phospholipids can effectively reduce the risk of MetS. RESULTS Under the intervention of 4% salmon phospholipid, the levels of fasting blood glucose (FBG), insulin, monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were significantly reduced in the plasma of MetS mice, whereas adiponectin was significantly increased. By screening, we found that the 18 differential metabolites, consisting of seven triglycerides (TGs), six diglycerides (DGs), one phosphatidylethanolamine (PE), three sphingomyelins (SMs) and one eicosanoid, could be the key differential metabolites, and two metabolic pathways were significantly affected: glycerolipid metabolism and glycerophospholipid metabolism. CONCLUSION 4% salmon phospholipids could affect MetS by inhibiting insulin resistance, reducing inflammatory factors and promoting the synthesis of PE, yet the mechanism required further study. Our results could help in the treatment of MetS. © 2021 Society of Chemical Industry.

Pulmonary hypertension (PH) is a cardiopulmonary disease characterized by a progressive increase in pulmonary vascular resistance. One of the initial pathogenic factors of PH is pulmonary arterial remodeling under various stimuli. Current marketed drugs against PH mainly relieve symptoms without significant improvement in overall prognosis. Discovering and developing new therapeutic drugs that interfere with vascular remodeling is in urgent need. Puerarin is an isoflavone compound extracted from the root of Kudzu vine, which is widely used in the treatment of cardiovascular diseases. In the present study, we evaluated the efficacy of puerarin in the treatment of experimental PH. PH was induced in rats by a single injection of MCT (50 mg/kg, sc), and in mice by exposure to hypoxia (10% O

Neuropathic pain is one of the most common and notorious neurological diseases. The changes in cerebral structures after nerve injury and the corresponding contributions to neuropathic pain are not well understood. Here we found that the majority of glutamatergic neurons in the area 2 of midcingulate cortex (MCC Cg2Glu) were inhibited by painful stimulation in male mice. Optogenetic manipulation revealed that these neurons were tonically involved in the inhibitory modulation of multimodal nociception. We further identified the projections to GABAergic neurons in the zona incerta (ZIGABA) mediated the pain inhibitory role. However, MCC Cg2Glubecame hypoactive after nerve injury. Although a brief activation of the MCC Cg2Gluto ZIGABAcircuit was able to relieve the aversiveness associated with spontaneous ongoing pain, consecutive activation of the circuit was required to alleviate neuropathic allodynia. In contrast, glutamatergic neurons in the area 1 of MCC played opposite roles in pain modulation. They became hyperactive after nerve injury and only consecutive inhibition of their activity relieved allodynia. These results demonstrate that MCC Cg2Gluconstitute a component of intrinsic pain inhibitory circuitry and their hypoactivity underlies neuropathic pain. We propose that selective and persistent activation of the MCC Cg2Gluto ZIGABAcircuit may serve as a potential therapeutic strategy for this disease.SIGNIFICANCE STATEMENTGlutamatergic neurons in the area 2 of midcingulate cortex (MCC Cg2Glu) are tonically involved in the intrinsic pain inhibition via projecting to GABAergic neurons in the zona incerta. They are hypoactive after nerve injury. Selective activation of the circuit compensates the reduction of its analgesic strength and relieves neuropathic pain. Therefore, MCC Cg2Gluand the related analgesic circuit may serve as therapeutic targets for neuropathic pain. In contrast, MCC Cg1Gluhave an opposite role in pain modulation and become hyperactive after nerve injury. The present study provides novel evidence for the concept that neuropathic pain is associated with the dysfunction of endogenous pain modulatory system and new perspective on the treatment of neuropathic pain.

Background Psychotic major depression (PMD) is a subtype of depression with a poor prognosis. Previous studies have failed to find many differences between patients with PMD and those with non-psychotic major depression (NMD) or schizophrenia (SZ). We compared sociodemographic factors (including season of conception) and clinical characteristics between patients with PMD, NMD, and schizophrenia. Our aim was to provide data to help inform clinical diagnoses and future etiology research. Methods This study used data of all patients admitted to Shandong Mental Health Center from June 1, 2016 to December 31, 2017. We analyzed cases who had experienced an episode of PMD (International Classification of Diseases, Tenth Revision codes F32.3, F33.3), NMD (F32.0–2/9, F33.0–2/9), and SZ (F20–20.9). Data on sex, main discharge diagnosis, date of birth, ethnicity, family history of psychiatric diseases, marital status, age at first onset, education, allergy history, and presence of trigger events were collected. Odds ratios (OR) were calculated using logistic regression analyses. Missing values were filled using the k-nearest neighbor method. Results PMD patients were more likely to have a family history of psychiatric diseases in their first-, second-, and third-degree relatives ([OR] 1.701, 95% confidence interval [CI] 1.019–2.804) and to have obtained a higher level of education (OR 1.451, 95% CI 1.168–1.808) compared with depression patients without psychotic features. Compared to PMD patients, schizophrenia patients had lower education (OR 0.604, 95% CI 0.492–0.741), were more often divorced (OR 3.087, 95% CI 1.168–10.096), had a younger age of onset (OR 0.934, 95% CI 0.914–0.954), less likely to have a history of allergies (OR 0.604, 95% CI 0.492–0.741), and less likely to have experienced a trigger event 1 year before first onset (OR 0.420, 95% CI 0.267–0.661). Season of conception, ethnicity, and sex did not differ significantly between PMD and NMD or schizophrenia and PMD. Conclusions PMD patients have more similarities with NMD patients than SZ patients in terms of demographic and clinical characteristics. The differences found between PMD and SZ, and PMD and NMD correlated with specificity of the diseases. Furthermore, allergy history should be considered in future epidemiological studies of psychotic disorders.

The GERT network model based on the knowledge transfer process of high-tech industrial innovation cluster is constructed, and the knowledge transfer measurement coefficient is put forward, and the influence parameters are introduced to analyze the influence of parameters on the knowledge transfer measurement coefficient Furthermore, combined with examples and using numerical simulation, this paper explores the changing characteristics of knowledge transfer performance of high-tech industrial innovation clusters. The results show that enhancing R&D incentives and enterprises' absorptive capacity can improve the knowledge transfer performance in the process of knowledge transfer in high-tech industrial innovation clusters. The coefficient of knowledge transfer measure has a threshold value, and when it reaches the threshold value, the incentive and absorption ability is the best. The research conclusions can provide decision-making reference for improving the knowledge transfer performance of high-tech industrial innovation clusters.

Background: Early-stage osteoarthritis (OA) is characterized by articular subchondral bone resorption and emerging evidence suggests that mechanical overloading is likely involved. Here, we identified whether and why mechanical overloading could trigger subchondral bone resorption in early-stage OA. Methods: A new mechanical overloading monitoring system for real-time pressure measurement in situ in vivo and a numerically controlled loading device for tissue pressurized culture in vitro were developed. Micro-CT was used to analyze the alterations of microarchitecture in subchondral bone and TRAP staining was harnessed to measure osteoclast differentiation of macrophages. Real-time qPCR, Western blot, ELISA, and immunostaining were conducted to clarify the expression, location, and interaction of relative proteins. Findings: Temporomandibular joint disc displacement yielded about 5 times higher pressure on the articular surface than that of the controls, causing subchondral bone resorption in 3-7 days after disc displacement. RANTES was increased in synovial fluid in early-stage OA in human and expressed in condylar cartilage of rat OA model at 1 week after disc displacement. Mechanistically, RANTES could promote osteoclast recruitment and formation through binding to its receptors CCRs and activating Akt2 pathway. Either Blockade of CCRs or Knockdown of Akt2 rescued RANTES-mediated osteoclast differentiation in vitro . Knockdown of Akt2 prevented the early subchondral bone resorption in OA in vivo. Interpretation: This study unravels a novel mechanism that disc displacement-induced mechanical overloading activates the RANTES-CCRs-Akt2 axis, which plays a critical initial role for the early condylar bone resorption in OA. Funding Information: This work was supported by grants from the National Natural Science Foundation of China (82170979, 81970920, 81772873). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The approval of synovial fluid experimentations was obtained from the Biomedical Institutional Review Board of the Peking University School and Hospital of Stomatology (PKUSSIRB-201947100), and written informed consents were attained from all participants. The approval of animal studies was obtained from the Peking University Animal Ethics Committee (LA2019310).

Background: Emerging evidence shows that lncRNA WFDC21P could promote STAT3 phosphorylation and microRNA 4293 SNP is associated with the risk of carcinomas, but the oncogenic functions of WFDC21P and miR-4293 in lung carcinoma are unclear.Methods: mRNA sequencing of lung carcinoma and control para-carcinoma tissues was performed to screen the potential targets. WFDC21P and miR-4293 levels were evaluated in lung carcinoma cells and tissues by qRT-PCR. The function of WFDC21P and miR-4293 on proliferation, apoptosis and metastasis were assessed by MTT, FACS, western blot, transwell assays, colony formation assays and xenografts experiment. RNA immunoprecipitation assays were implemented to verify the relationship between WFDC21P and mRNA-decapping enzyme 2 (DCP2). Furthermore, gain/loss of miR-4293 functions were used to determine its targeting relationship of DCP2. Results: WFDC21P expression is markedly enhanced in lung carcinoma tissue and cells. Moreover, WFDC21P promotes tumor cell proliferation and metastasis but suppresses apoptosis. Mechanistic investigations identified DCP2 can directly bind to WFDC21P and down-regulates its expression. DCP2 as a direct target of miR-4293 and its expression is suppressed by miR-4293. Consequently, miR-4293 can further promote WFDC21P expression by regulating DCP2. With positive correlation to WFDC21P expression, miR-4293 also plays oncogenic role in lung carcinoma. Furthermore, knockdown of WFDC21P results in functional attenuation of miR-4293 on tumor promotion. In vivo xenograft growth is also promoted by both WFDC21P and miR-4293. Conclusion: Our results establish oncogenic roles for both WFDC21P and miR-4293, and demonstrate that interactions between miRNAs and lncRNAs through DCP2 are important in lung carcinoma pathogenesis.

Global myocardial work (MW) analysis by pressure-strain loops (PSL) allows the non-invasive assessment of left ventricular (LV) function. We aimed to investigate the relationship between LV global MW and the degree of coronary artery stenosis in suspected coronary artery disease (CAD) patients with normal LV ejection fraction and regional wall motion. A total of 164 suspected CAD patients were divided into four groups according to coronary artery angiography. The results showed that global work efficiency (GWE) as the most significant predictor in all MW parameters had the optimal cut-off value of 94.5% for detecting moderate stenosis, and the sensitivity and specificity was 89.7% and 85.8%, respectively. A cut-off value of 94.0% for GWE was the most significant predictor of severe stenosis, and the sensitivity and specificity was 81.4% and 76.1%, respectively. In conclusion, LV global MW is a sensitive tool in detecting the degree of coronary artery stenosis and a potential valuable method to provide early diagnosis for CAD patients.

Despite significant advances in transplantation, acute cellular rejection (AR) remains a major obstacle that is most prevalent in the first months post heart transplantation (HT). Current treatments require high doses of immunosuppressive drugs followed by maintenance therapies that have systemic side effects including early infection. In this study, we attempted to prevent AR with a myocardial-targeted galectin-7-siRNA delivery method using cationic microbubbles (CMBs) combined with ultrasound targeted microbubble destruction (UTMD) to create local immunosuppression in a rat abdominal heterotopic heart transplantation acute rejection model.Galectin-7-siRNA (siGal-7) bound to CMBs were synthesized and effective ultrasound-targeted delivery of siGal-7 into target cells confirmed in vitro. Based on these observations, three transplant rat models were tested：①isograft (ISO); ② Allograft (ALLO) +UTMD; and ③ALLO + PBS. UTMD treatments were administered at 1, 3, 5, 7 days after HT. Galectin 7 expression was reduced by 50% compared to ALLO + PBS (p 0.005), and this was associated with significant reductions in both galectin 7 and Interleukin-2 protein levels (p 0.001). The ALLO + UTMD group had Grade II or less inflammatory infiltration and myocyte damage in 11/12 rats using International Society For Heart and Lung Transplantation grading, compared to 0/12 rats with this grading in the ALLO + PBS group at 10 days post HT (p 0.001).Ultrasound-targeted galectin-7-siRNA knockdown with UTMD can prevent acute cellular rejection in the early period after allograft heart transplantation without the need for systemic immunosuppression.Microbubble, Acute Rejection, Heart Transplantation, Galectin-7, RNA.

Pain sensitization after partial infraorbital nerve transection (p-IONX) in mice not only presents in orofacial region, but also spreads to distant body parts. The roles of toll-like receptor 4 (TLR4) in orofacial pain and the spreading process are still unclear. Here, we found that mice with deficient TLR4 because of Tr4 gene point mutation (C3H/HeJ) or spontaneous deletion (C57BL/10ScNJ) developed tactile allodynia and thermal hyperalgesia in the vibrissal pad in a parallel way to their respective wild types (C3HeB/FeJ or C57BL/6J) after p-IONX. However, allodynia in the hind paw was absent in mice with TLR4 deficiency. Pharmacological antagonism of TLR4 with LPS-RS, administered either intracisternally or intrathecally, abrogated allodynia in the hind paw without affecting the hypersensitivity in the vibrissal pad and hyperalgesia in the hind paw. Although TNF-α expression was upregulated in both the medulla and lumbar cord, the expression of TLR4 downstream molecule MyD88 increased only in the lumbar cord after p-IONX in wild types. By contrast, hind paw hypersensitivity after partial sciatic nerve ligation was significantly attenuated by TLR4 deletion. The hypersensitivity, which did not spread to the vibrissal pad, was accompanied with upregulation of MyD88 in the lumbar cord rather than in the medulla. These results suggest that TLR4 participates in the spread of allodynia component of orofacial pain to distant body sites, but not trigeminal neuropathic pain or the spread of its hyperalgesia component. This study suggests that TLR4 may serve as a potential target for the management of widespread allodynia associated with orofacial pain.

Interstitial lung disease represents a group of diffuse pulmonary diseases that mainly affects pulmonary mesenchyme and alveolar spaces, resulting in loss of alveolar-capillary functions. It is also a common complication or an important factor that influences the prognosis of rheumatoid arthritis, dermatomyositis, systemic sclerosis. Searching for the biomarkers for the early diagnosis of the disease and/or indicative of the activity of the condition has been a subject of active investigations. KL-6, expressed on type II pneumocytes, is seen as the most promising biomarker for the diagnosis of the disease. This review summarizes the recent researches about the use of KL-6 in the diagnosis and treatment of interstitial lung disease. DOI: 10.11855/j.issn.0577-7402.2017.04.15

Chemosensory systems play an important role in insect behavior, and some key associated genes have potential as novel targets for pest control. Cacopsylla chinensis is an oligophagous pest and has become one of the main pests of pear trees, but little is known about the molecular-level means by which it locates its hosts. In this study, we assembled the head transcriptome of C. chinensis using Illumina sequencing, and 63,052 Unigenes were identified. A total of 36 candidate chemosensory genes were identified, including five different families: 12 odorant binding proteins (OBPs), 11 chemosensory proteins (CSPs), 7 odorant receptors (ORs), 4 ionotropic receptors (IRs), and 2 gustatory receptors (GRs). The number of chemosensory gene families is consistent with that found in other Hemipteran species, indicating that our approach successfully obtained the chemosensory genes of C. chinensis. The tissue expression of all genes using quantitative real-time PCR (qRT-PCR) found that some genes displayed male head, female head, or nymph-biased specific/expression. Our results enrich the gene inventory of C. chinensis and provide valuable resources for the analysis of the functions of some key genes. This will help in developing molecular targets for disrupting feeding behavior in C. chinensis.

Background Over the past decades there have been outbreaks of mumps in many countries, even in populations that were vaccinated. Some studies suggest that the incidence of mumps is related to meteorological changes, but the results of these studies vary in different regions. To date there is no reported study on correlations between mumps incidence and meteorological parameters in Beijing, China. Methods A time series analysis incorporating selected weather factors and the number of mumps cases from 1990 to 2012 in Beijing was performed. First, correlations between meteorological variables and the number of mumps cases were assessed. A seasonal autoregressive integrated moving average model with explanatory variables (SARIMAX) was then constructed to predict mumps cases. Results Mean temperature, rainfall, relative humidity, vapor pressure, and wind speed were significantly associated with mumps incidence. After constructing the SARIMAX model, mean temperature at lag 0 (β = 0.016, p

Clinical studies show that chronic pain can spread to adjacent or even distant body regions in some patients. However, little is known about how this happens. In this study, we found that partial infraorbital nerve transection (p-IONX) in MRL/MPJ mice induced not only marked and long-lasting orofacial thermal hyperalgesia but also thermal hyperalgesia from day 3 postoperatively (PO) and tactile allodynia from day 7 PO in bilateral hind paws. Pain sensitization in the hind paw was negatively correlated with facial thermal hyperalgesia at early but not late stage after p-IONX. After a rapid activation of c-Fos, excitability and excitatory synaptic neurotransmission in lumbar dorsal horn neurons were elevated from day 3 and day 7 PO, respectively. In addition, microglial activation after p-IONX transmitted caudally from the Vc in the medulla to lumber dorsal horn in a time-dependent manner. Inhibition of microglial activation by minocycline at early but not late stage after p-IONX postponed and attenuated pain sensitization in the hind paw. These results indicate that neuropathic pain after p-IONX in MRL/MPJ mice spreads from the orofacial region to distant somatic regions and that a rostral-caudal transmission of central sensitization in the spinal cord is involved in the spreading process of pain hypersensitivity.

Stimuli-responsive metal nanoclusters (NCs) are intriguing materials due to their wide applications in photoluminescence (PL) sensors, bioimaging and catalysis. CO2 gas as a green stimulus could arouse the PL variation of certain metal NCs only under high-pressure condition. Metal NCs responding to the normal-pressure CO2 have not been reported yet. In this work, hydroxyl-terminated hyperbranched polyethylenimine (HPEI-OH) was used to mediate the preparation of water-soluble Au NC assemblies (Au NC-As) with crystallization-induced emission (CIE) nature. HPEI-OH played a multifunctional role, such as reducing Au ions, endowing water solubility to Au NC-As, packing thiolated Au NCs closely and enabling CO2-responsiveness to Au NC-As. Controlling the preparation pH at 2.0 or 3.2, red or yellow-emitting Au NC-As with quantum yield of ca. 4.6% or 5.8% were achieved. The as-prepared CIE-type Au NC-As possessed pH-responsive characteristic and strong PL emission was achieved under acidic condition. The CIE nature rendered not only strong PL emission to Au NC-As, but also strong photoelectron emission verified by the X-ray photoelectron spectroscopy. The introduction of Zn2+ ions extended the application range of Au NC-As from acidic condition till to weak basic condition. Under neutral condition, the formed complex of Zn2+/Au NC-As showed reversible PL response to the normal-pressure CO2/N2 cycling through adsorption and desorption process. Finally, the application of the complex in measuring the CO2 concentration of carbonated beverages was presented.

This retrospective cohort study attempts to investigate pregnancy complications and adverse pregnancy outcomes in women of advanced maternal age (AMA). Data were extracted from electronic medical records system at West China Second University Hospital of Sichuan University from January 2013 to July 2016. The study cohort consisted 8 subgroups of women on 4 different age levels (20–29 years, 30–34 years, 35–39 years and ≥40 years) and 2 different parities (primiparity and multiparity). In the study period, 38811 women gave birth at our hospital, a randomized block was used to include 2800 women of singleton pregnancy >28 gestational weeks, with 350 patients in each subgroup. Maternal complications and fetal outcomes were collected and defined according to relevant guidelines. Confounding factors representing maternal demographic characteristics were identified from previous studies and analysed in multivariate analysis. There was an increasing trend for the risks of adverse pregnancy outcomes with increasing age, especially in AMA groups. Our study showed that AMA, primiparity, maternal overweight or obesity, lower educational level and residence in rural area increased pregnancy complications and adverse fetal outcomes. Increased professional care as well as public concern is warranted.

Summary Introduction The upregulation of Nav1.8 in primary afferents plays a critical role in the development and persistence of neuropathic pain. The mechanisms underlying the upregulation are not fully understood. Aims The present study aims to investigate the regulatory effect of histamine on the expression of Nav1.8 in primary afferent neurons and its involvement in neuropathic pain. Results Histamine at 10−8 M increased the expression of Nav1.8 in cultured DRG neurons. This effect could be blocked by H2 receptor antagonist cimetidine or famotidine, but not by H1 receptor antagonist pyrilamine or dual H3/H4 antagonist thioperamide. Peri-sciatic administration of histamine increased Nav1.8 expression in the sciatic nerve and L4/L5 DRG neurons in a dose-dependent manner, accompanied with remarkable mechanical allodynia and heat hyperalgesia in the ipsilateral hindpaw. Famotidine but not pyrilamine or thioperamide inhibited Nav1.8 upregulation and pain hypersensitivity. In addition, famotidine (40 mg/kg, i.p.) not only suppressed autotomy behavior in the rat neuroma model of neuropathic pain but also attenuated mechanical allodynia and thermal hyperalgesia following partial sciatic nerve ligation. Moreover, famotidine inhibited Nav1.8 upregulation in the neuroma and ligated sciatic nerve. Conclusions Our findings indicate that histamine increases Nav1.8 expression in primary afferent neurons via H2 receptor-mediated pathway and thereby contributes to neuropathic pain. H2 receptor antagonists may potentially be used as analgesics for patients with neuropathic pain.

Based on the V-type diesel engine crankshaft system, the paper combined the finite element method (fem) and multi-body dynamics method together, made a virtual simulation analysis. First, by 3d software and finite element software to establish the multi-body dynamic models of the crankshaft, bearing and piston, then simulated the actual engine working condition, and got the data such as crankshaft acceleration, velocity and displacement by the multi-body dynamics simulation analysis. By calculation, the paper found that by using the combination of finite element and multi-body simulation method, can we effectively simulate the diesel engine crankshaft dynamics characteristics.

In the process of calculating the crankshaft frequency and vibration mode, free mode is always applied for the crankshaft modal analysis. Considering the effect of centrifugal force generated by the rotation to the crankshaft frequency and vibration mode, the frequency and vibration mode of multi-speed cases are calculated, and compared, which fully shows the vibration situation of the crankshaft in the process of actual working situations, the results match actual situation.

Considering the effect of centrifugal force generated by the rotation to the crankshaft frequency and vibration mode, the frequency and vibration mode of multi-speed cases are calculated. The results showed that the impact of the centrifugal force on the crankshaft vibration increases with the increase of rotational speed, especially in the high speed region, this phenomenon is more obvious. From low speed to high speed, the vibration frequency has a large deviation, which shows that in this case, it is necessary to consider the frequency change caused by pre-stress.