Halogen cation-promoted and solvent-regulated electrophilic cyclization for the regioselective synthesis of 3-haloquinolines and 3-halospirocyclohexadienones.

A novel approach for the production of halogen cations through the reaction of halogens with silver ions is described in this paper. On this basis, the regioselective synthesis of 3-haloquinolines and 3-halospirocyclohexadienones is realized through solvent regulation. The gram-scale reaction and the compatibility of complex substrates demonstrate the synthetic potential of this protocol, which will be an appealing strategy in organic synthesis.

Optimal fibular tunnel direction for anterior talofibular ligament reconstruction: 45 degrees outperforms 30 and 60 degrees.

PURPOSE: There is currently no consensus on the optimal drilling direction of the fibular bone tunnel for anterior talofibular ligament (ATFL) reconstruction, and few studies have investigated the potential injury to the peroneus longus and brevis tendons and the possibility of fibular fractures during the drilling process. The aim of this study was to assess the potential risk of drilling the tunnel from different directions and determine the most appropriate tunnel direction. The hypothesis was that drilling the tunnel in the 45-degree direction would be the safest and most suitable for the fibular tunnel. METHODS: Forty-eight fibular tunnels were drilled on fresh ankle specimens using a K-wire guide and a 5.0 mm hollow drill. Three tunnel orientations were created, parallel to the sagittal plane of the long axis of the fibula and angled 30°, 45°, and 60° to the coronal plane. The length of the fibular tunnel and the distances from the outlet of the K-wire to the peroneus longus and brevis tendons were measured. The occurrence of a fibula fracture was also observed. RESULTS: The lengths of the bone tunnels in the three groups were 32.9 ± 6.1 mm (30°), 27.2 ± 4.4 mm (45°) and 23.6 ± 4.0 mm (60°). The length of the tunnel drilled at 30° was the longest when compared with that of the tunnels drilled at 45° and 60° (all p values < 0.05). The distances from the outlet of the K-wire to the peroneus longus tendon were 3.0 ± 3.8 mm (30°), 3.8 ± 3.2 mm (45°) and 5.3 ± 1.8 mm (60°), and the distances to the peroneus brevis tendon were 4.2 ± 4.0 mm (30°), 6.1 ± 3.8 mm (45°), 7.9 ± 3.5 mm (60°). In terms of protecting the peroneus longus and brevis tendons, drilling in the 60° direction was better than drilling in the 30° and 45° directions (all p values < 0.05). The risk of injury to the peroneal longus and brevis tendons was 62.5% (30°), 31.3% (45°), and 0% (60°). Although no fibular fractures were observed in any of the three directions, drilling the bone tunnel in the 60° direction disrupted the lateral cortex of the fibula. CONCLUSION: This study shows that drilling the tunnel in the 45° direction is less likely to cause injury to the peroneus longus and brevis tendons, while ensuring that the tunnel has a sufficient length and avoiding fracturing the distal fibula. Drilling a fibular bone tunnel in a 45° direction is safer and recommended for ATFL reconstruction.

Breast cancer stem cells, heterogeneity, targeting therapies and therapeutic implications.

Both hereditary and sporadic breast cancer are suggested to develop from a stem cell subcomponent retaining most key stem cell properties but with dysregulation of self-renewal pathways, which drives tumorigenic differentiation and cellular heterogeneity. Cancer stem cells (CSCs), characterized by their self-renewal and differentiation potential, have been reported to contribute to chemo-/radio-resistance and tumor initiation and to be the main reason for the failure of current therapies in breast cancer and other CSC-bearing cancers. Thus, CSC-targeted therapies, such as those inducing CSC apoptosis and differentiation, inhibiting CSC self-renewal and division, and targeting the CSC niche to combat CSC activity, are needed and may become an important component of multimodal treatment. To date, the understanding of breast cancer has been extended by advances in CSC biology, providing more accurate prognostic and predictive information upon diagnosis. Recent improvements have enhanced the prospect of targeting breast cancer stem cells (BCSCs), which has shown promise for increasing the breast cancer remission rate. However, targeted therapy for breast cancer remains challenging due to tumor heterogeneity. One major challenge is determining the CSC properties that can be exploited as therapeutic targets. Another challenge is identifying suitable BCSC biomarkers to assess the efficacy of novel BCSC-targeted therapies. This review focuses mainly on the characteristics of BCSCs and the roles of BCSCs in the formation, maintenance and recurrence of breast cancer; self-renewal signaling pathways in BCSCs; the BCSC microenvironment; potential therapeutic targets related to BCSCs; and current therapies and clinical trials targeting BCSCs.

Perioperative dexmedetomidine reduces delirium in elderly patients after non-cardiac surgery: a systematic review and meta-analysis of randomized-controlled trials.

BACKGROUND: Delirium is a frequent postoperative complication in elderly patients after non-cardiac surgery. We performed this updated meta-analysis to ascertain more precisely the efficacy of dexmedetomidine (DEX) on the incidence of postoperative delirium (POD) in elderly patients after non-cardiac surgery. METHODS: We searched PubMed, EMBASE, the Cochrane Library, Web of Science, and the Cumulative Index of Nursing and Allied Health Literature (CINAHL) from inception until February 24, 2019. In this meta-analysis, we included randomized-controlled trials comparing the effect of DEX vs normal saline (NS) or other anesthetic drugs on POD incidence in elderly (either ≥ 60 or ≥ 65 yr old) patients undergoing non-cardiac surgery. We performed subgroup analyses of the DEX dosing strategy (starting time, dose, and duration of administration, with or without loading dose) and the strategy of various control drugs. A random-effects model was used for all analyses. RESULTS: We included 11 studies involving 2,890 patients in our meta-analysis. The pooled results of these studies revealed that DEX significantly reduced the incidence of POD (relative risk [RR], 0.47; 95% confidence interval [CI], 0.38 to 0.58; P < 0.001) compared with the control group. Meanwhile, the incidences of hypotension (RR, 1.20; 95% CI, 1.04 to 1.39; P = 0.01) and bradycardia (RR, 1.33; 95% CI, 1.08 to 1.63; P = 0.007) were increased in the DEX group. Subgroup analyses revealed a decrease in POD incidence when DEX was administered intraoperatively (RR, 0.43; 95% CI, 0.33 to 0.57; P < 0.001) and postoperatively (RR, 0.38; 95% CI, 0.27 to 0.54; P < 0.001) with a loading dose (RR, 0.49; 95% CI, 0.36 to 0.69; P < 0.001) compared with NS (RR, 0.49; 95% CI, 0.37 to 0.64; P < 0.001) and other anesthetic drugs (RR, 0.40; 95% CI, 0.26 to 0.60; P < 0.001). There were significant differences in the time to extubation (standardized mean difference, -0.60; 95% CI, -1.17 to -0.03; P = 0.04) and the length of hospital stay (mean difference, -0.50 days; 95% CI, -0.97 to -0.03; P = 0.04). The amount of data for the duration of mechanical ventilation and length of intensive care unit stay were insufficient to perform a meta-analysis. CONCLUSION: Perioperative dexmedetomidine reduces the incidence of POD in elderly patients after non-cardiac surgery, but this comes at the cost of an increased incidence of hypotension and bradycardia.

Time-course Study on Left Ventricular Function in a Rabbit Model of Ischemia-reperfusion Injury With Morphine Preconditioning.

AIMS: To analyze the left ventricular longitudinal function in a rabbit model of myocardial ischemia reperfusion with morphine preconditioning through strain rate imaging and to evaluate the effect of morphine preconditioning. METHODS: A myocardial ischemia-reperfusion model was induced by occlusion and recanalization of the coronary artery in 40 male New Zealand white rabbits, which were divided into a sham group, morphine group, and vehicle control group. Routine echocardiography data were recorded 1 day before and within 28 days after the operation. Dynamic images were also collected and analyzed off-line using Doppler tissue imaging software. RESULTS: On the first day after the operation, the global and regional systolic functions of the left ventricle in the morphine and vehicle control groups were lower than those in the sham group. After ischemia reperfusion, some of the values of the above-mentioned parameters decreased over time, which was more obvious in the vehicle control group at each examined time point. CONCLUSIONS: The current study revealed that detection of changes in regional myocardial function after myocardial ischemia reperfusion by strain rate imaging is objective and accurate. In addition, our results indicated that morphine preconditioning significantly attenuates myocardial ischemia-reperfusion injury in rabbits.

The impact of general anesthesia on the outcomes of preterm infants with gestational age less than 32 weeks delivered via cesarean section.

Background: Recent advancements in China's perinatal and neonatal intensive care have significantly reduced neonatal mortality, yet preterm births before 32 weeks remain the primary cause of neonatal fatalities and contribute to long-term disabilities. The prognosis of very preterm infants (VPIs) is significantly affected by factors including the intrauterine environment, delivery method and neonatal intensive care. Cesarean section which often used for preterm births has implications that are not fully understood, particularly concerning the type of anesthesia used. This study examines the impact of general anesthesia (GA) during cesarean delivery on VPI outcomes, aiming to identify strategies for mitigating GA-associated risks. Methods: This cohort study analyzed 1,029 VPIs born via cesarean section under 32 weeks' gestation at our single-center from 1 January 2018, to 31 December 2022. Detailed medical records, encompassing perioperative information, maternal data and neonatal outcomes were meticulously examined. The primary aim of this investigation was to compare maternal characteristics and neonatal outcomes between VPIs delivered under GA and neuraxial anesthesia (NA). A significance level of p < 0.05 was established. Results: Of the 1,029 VPIs analyzed, 87.95% (n = 905) were delivered via NA and 12.05% (n = 124) via GA. Mothers with hypertensive pregnancy diseases and emergency operations were more inclined to choose GA. VPIs delivered under GA showed a lower Apgar score at one and 5 minutes (p < 0.01), increased need for tracheal intubation resuscitation (32.2% vs. 12.2%, p < 0.01) and a greater incidence of severe neurological injury (SNI) (14.5% vs. 5%, p < 0.01). Multivariable analysis revealed GA was significantly associated with lower Apgar scores at one (OR 6.321, 95% CI 3.729-10.714; p < 0.01) and 5 minutes (OR 4.535, 95% CI 2.975-6.913; p < 0.01), higher risk of tracheal intubation resuscitation (OR = 3.133, 95% CI = 1.939-5.061; p < 0.01) and SNI (OR = 3.019, 95% CI = 1.615-5.643; p < 0.01). Furthermore, for VPIs delivered under GA, a prolonged interval from skin incision to fetus delivery was associated with a lower 5-min Apgar score (p < 0.01). Conclusion: This study revealed the significant impact of GA on adverse outcomes among VPIs. In cases when GA is required, proactive measures should be instituted for the care of VPIs such as expediting the interval from skin incision to fetal delivery.

Manganese Enhances the Osteogenic Effect of Silicon-Hydroxyapatite Nanowires by Targeting T Lymphocyte Polarization.

Biomaterials encounter considerable challenges in extensive bone defect regeneration. The amelioration of outcomes may be attainable through the orchestrated modulation of both innate and adaptive immunity. Silicon-hydroxyapatite, for instance, which solely focuses on regulating innate immunity, is inadequate for long-term bone regeneration. Herein, extra manganese (Mn)-doping is utilized for enhancing the osteogenic ability by mediating adaptive immunity. Intriguingly, Mn-doping engenders heightened recruitment of CD4+ T cells to the bone defect site, concurrently manifesting escalated T helper (Th) 2 polarization and an abatement in Th1 cell polarization. This consequential immune milieu yields a collaborative elevation of interleukin 4, secreted by Th2 cells, coupled with attenuated interferon gamma, secreted by Th1 cells. This orchestrated interplay distinctly fosters the osteogenesis of bone marrow stromal cells and effectuates consequential regeneration of the mandibular bone defect. The modulatory mechanism of Th1/Th2 balance lies primarily in the indispensable role of manganese superoxide dismutase (MnSOD) and the phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK). In conclusion, this study highlights the transformative potential of Mn-doping in amplifying the osteogenic efficacy of silicon-hydroxyapatite nanowires by regulating T cell-mediated adaptive immunity via the MnSOD/AMPK pathway, thereby creating an anti-inflammatory milieu favorable for bone regeneration.

Construction of an interferon regulatory factors-related risk model for predicting prognosis, immune microenvironment and immunotherapy in clear cell renal cell carcinoma.

Background: Interferon regulatory factors (IRFs) played complex and essential roles in progression, prognosis, and immune microenvironment in clear cell renal cell carcinoma (ccRCC). The purpose of this study was to construct a novel IRFs-related risk model to predict prognosis, tumor microenvironment (TME) and immunotherapy response in ccRCC. Methods: Multi-omics analysis of IRFs in ccRCC was performed based on bulk RNA sequencing and single cell RNA sequencing data. According to the expression profiles of IRFs, the ccRCC samples were clustered by non-negative matrix factorization (NMF) algorithm. Then, least absolute shrinkage and selection operator (LASSO) and Cox regression analyses were applied to construct a risk model to predict prognosis, immune cells infiltration, immunotherapy response and targeted drug sensitivity in ccRCC. Furthermore, a nomogram comprising the risk model and clinical characteristics was established. Results: Two molecular subtypes with different prognosis, clinical characteristics and infiltration levels of immune cells were identified in ccRCC. The IRFs-related risk model was developed as an independent prognostic indicator in the TCGA-KIRC cohort and validated in the E-MTAB-1980 cohort. The overall survival of patients in the low-risk group was better than that in the high-risk group. The risk model was superior to clinical characteristics and the ClearCode34 model in predicting the prognosis. In addition, a nomogram was developed to improve the clinical utility of the risk model. Moreover, the high-risk group had higher infiltration levels of CD8+ T cell, macrophages, T follicular helper cells and T helper (Th1) cells and activity score of type I IFN response but lower infiltration levels of mast cells and activity score of type II IFN response. Cancer immunity cycle showed that the immune activity score of most steps was remarkably higher in the high-risk group. TIDE scores indicated that patients in the low-risk group were more likely responsive to immunotherapy. Patients in different risk groups showed diverse drug sensitivity to axitinib, sorafenib, gefitinib, erlotinib, dasatinib and rapamycin. Conclusions: In brief, a robust and effective risk model was developed to predict prognosis, TME characteristics and responses to immunotherapy and targeted drugs in ccRCC, which might provide new insights into personalized and precise therapeutic strategies.

A Web-Based Prediction Tool to Improve Identification of Patients With Undersized Hamstring Tendon Autograft in Anterior Cruciate Ligament Reconstruction.

BACKGROUND: An undersized hamstring tendon (HT) autograft is significantly associated with a higher graft failure rate in anterior cruciate ligament reconstruction (ACLR) surgery. The ability to accurately predict inadequate HT graft diameter is critical, as it could assist surgeons in making better graft choices and surgical plans. PURPOSE: To develop a web-based prediction tool to better assess the size of HT autograft and to help clinicians accurately identify patients with potentially undersized HT grafts in order to make appropriate clinical decisions. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: A total of 588 patients who received primary arthroscopic single-bundle ACLR surgery with gracilis tendon (GT) and semitendinosus tendon (ST) autograft were retrospectively reviewed. According to the size of 4-strand HT graft, patients were divided into diameter ≥8 mm and <8 mm groups. The least absolute shrinkage and selection operator method and logistic regression were used to identify the independent factors associated with HT graft diameter and establish the models. The prediction performance of the model was evaluated by concordance index and calibration combined with external validation. The diagnostic performance of the prediction model was assessed by sensitivity, specificity, predictive values, and likelihood ratios. Decision curve analysis was used to evaluate the clinical utility of the model. RESULTS: Among the numerous indicators, sex, weight, height, thigh length, and ST-GT diameter (measured on plane 1 of a magnetic resonance imaging scan) were identified to be highly correlated predictors that could provide satisfactory prediction performance in determining the HT graft diameter. Based on these predictors, a prediction model named the HTD model was developed with satisfactory discrimination (concordance index, 0.932) and calibration (mean absolute error, 0.039). When the probability calculated by the HTD model was >65%, the sensitivity and specificity of predicting 4-strand HT graft diameter ≥8 mm were 86.7% and 90.2%, respectively. CONCLUSION: As a useful supplementary prediction tool, the HTD model could accurately predict the diameter of HT autograft during preoperative planning.

Itaconate Attenuates Neuroinflammation and Exerts Dopamine Neuroprotection in Parkinson's Disease through Inhibiting NLRP3 Inflammasome.

Parkinson's disease (PD) is a common age-associated neurodegenerative motor disorder, which is mainly caused by dopaminergic neuron loss in the substantia nigra. This study aimed to evaluate the function and the underlying molecular mechanism of itaconate in PD. PD models were established in vivo and in vitro using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium (MPP+), respectively. Pole and rotarod tests were applied to evaluate the motor coordination of mice. The expression of tyrosine hydroxylase (TH) in MPTP-induced mice and the MPP+ revulsive PD cell model were detected using Western blotting and immunofluorescence. The inflammatory factors level was detected by quantitative real-time polymerase chain reaction. The content of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS) in substantia nigra, striatum, and SH-SY5Y cells were analyzed. Moreover, the apoptosis of MPP+ revulsive SH-SY5Y cells was determined using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) staining and flow cytometry. The expression of apoptosis- and Nod-like receptor family protein 3 (NLRP3) inflammasome-associated proteins was measured using Western blotting and immunofluorescence. Itaconate attenuated motor deficits of MPTP-induced PD mice. Itaconate inhibited dopamine neuronal damage, inflammatory response, oxidative stress, and neuronal apoptosis in MPTP-caused PD mice and the MPP+ revulsive PD cell model. Additionally, itaconate notably repressed the activation of NLRP3 inflammasome. This research demonstrated that itaconate could attenuate neuroinflammation and exert dopamine neuroprotection in PD through inhibiting NLRP3 inflammasome.

Analysis of Visual Risk Factors of Anterior Cruciate Ligament Injury of Knee Joint.

This study aimed to explore whether the defect of visual function is a risk factor of knee anterior cruciate ligament (ACL) sports injury and to provide a theoretical basis for the primary prevention of ACL sports injury. This cross-sectional study included 392 participants divided into two groups: the sports injury group (287 with sports injury of knee) and the control group (105 healthy volunteers). Participants in the sports injury group were further divided into the ACL-Intact group (133) and the ACL-Deficient group (154). Participants in the sports injury group received a questionnaire about the conditions of their injury (including injury action, site condition, weather, contact) and a visual examination by synoptophore (including binocular vision, subjective and objective oblique angle, visual fusion range, stereoacuity). Participants in the control group only received the visual examination. In the end, we found that low visual fusion range (p = 0.003) and injury action, especially quick turn (p = 0.001), sudden stop (p < 0.001) and jump (p = 0.001), are the major risk factors for ACL injury in the analysis of the integrated data. In addition, athletes with low vision fusion range have increased risk of ACL sports injury when they make a sudden stop on wooden floor, plastic floor or cement floor on cloudy days (OR = 13.208). Visual factors, especially low fusion range, significantly increase the risk of ACL sports injury.

Morphine preconditioning, cardioprotection and left ventricular remodelling in rabbits.

OBJECTIVE: The objective of this study was to investigate, in a rabbit model, the cardioprotective effect of morphine preconditioning against cardiac remodelling. METHODS AND RESULTS: In male New Zealand rabbits myocardial I/R injury was established by ligating the left descending coronary artery followed by perfusion. The rabbits were randomly divided into: (i) a normal saline sham group (S), (ii) a morphine sham group (MS), (iii) a normal saline group (NS); (iv) a morphine preconditioning group (MPC). After I/R injury, cardiac function was evaluated by echocardiography and biologic markers at day 1, day 3, day 7, day 14, day 21 and day 28. At day 1 after I/R injury, in comparison to the NS group, morphine preconditioning: (i) significantly improved haemodynamic parameters; (ii) reduced myocardial infarct size; (iii) lowered troponin I level. At day 28 after I/R injury, the concentration of B-type natriuretic peptide was significantly lower in the MPC group compared to the NS group. The MPC group had heavier left ventricles than the MS group while the NS group had heavier right ventricles than the other groups, respectively. Furthermore, the MPC group showed improved haemodynamic parameters. Echocardiography showed a higher left ventricular ejection fraction and fractional shorting in the MPC group compared to the NS group at each observation point. CONCLUSION: After I/R injury and morphine preconditioning by a single dose, we have observed a prolonged cardioprotective effect and an improved cardiac function. Morphine preconditioning may reduce post-infarction remodelling.

Protective effect of propofol preconditioning on ischemia-reperfusion injury in human hepatocyte.

BACKGROUND: Blood reperfusion after ischemia is the main measure to restore cell function. This study was aimed to explore the effect of propofol on rat and cell models of liver ischemia-reperfusion (I/R) injury, and to investigate its possible mechanism. METHODS: Wistar rats were divided into four groups: control group, sham group, I/R group, and propofol group. Human hepatocyte HL7702 was divided into six groups: control group, I/R group and propofol (5, 10, 20 and 40 µmol/L) groups. After the animal and cell models were established, the alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA) and adenosine triphosphate (ATP) levels in liver tissues and hepatocytes were measured. Cell viability and apoptosis of hepatocytes were respectively determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry. Furthermore, the expressions of apoptosis-related proteins in hepatocytes were determined by Western blot analysis. RESULTS: ALT, AST and MDA levels were all decreased significantly, and the ATP level was increased significantly in propofol group compared with that in I/R group in both liver tissues and hepatocytes. Additionally, cell viability of hepatocytes in propofol group was higher than that in I/R group, while the percentage of apoptotic cells in propofol group was less than that in I/R group. Moreover, the expression of caspase-3 decreased and the expression of Bcl-2 increased significantly after propofol preconditioning. CONCLUSIONS: Our findings suggested that propofol preconditioning might be an effective strategy for protecting the liver from I/R injury, which might provide a scientific basis for clinical application.

Propofol Protects Rats and Human Alveolar Epithelial Cells Against Lipopolysaccharide-Induced Acute Lung Injury via Inhibiting HMGB1 Expression.

High-mobility group box 1 (HMGB1) plays a key role in the development of acute lung injury (ALI). Propofol, a general anesthetic with anti-inflammatory properties, has been suggested to be able to modulate lipopolysaccharide (LPS)-induced ALI. In this study, we investigated the effects of propofol on the expression of HMGB1 in a rat model of LPS-induced ALI. Rats underwent intraperitoneal injection of LPS to mimic sepsis-induced ALI. Propofol bolus (1, 5, or 10 mg/kg) was infused continuously 30 min after LPS administration, followed by infusion at 5 mg/(kg · h) through the left femoral vein cannula. LPS increased wet to dry weight ratio and myeloperoxidase activity in lung tissues and caused the elevation of total protein and cells, neutrophils, macrophages, and neutrophils in bronchoalveolar lavage fluid (BALF). Moreover, HMGB1 and other cytokine levels were increased in BALF and lung tissues and pathological changes of lung tissues were excessively aggravated in rats after LPS administration. Propofol inhibited all the above effects. It also inhibited LPS-induced toll-like receptor (TLR)2/4 protein upexpression and NF-κB activation in lung tissues and human alveolar epithelial cells. Propofol protects rats and human alveolar epithelial cells against HMGB1 expression in a rat model of LPS-induced ALI. These effects may partially result from reductions in TLR2/4 and NF-κB activation.

Brain-derived neurotrophic factor (BDNF) in the rostral anterior cingulate cortex (rACC) contributes to neuropathic spontaneous pain-related aversion via NR2B receptors.

The rostral anterior cingulate cortex (rACC) plays an important role in pain affect. Previous investigations have reported that the rACC mediates the negative affective component of inflammatory pain and contributed to the aversive state of nerve injury-induced neuropathic pain. Brain-derived neurotrophic factor (BDNF), an activity-dependent neuromodulator in the adult brain, is believed to play a role in the development and maintenance of inflammatory and neuropathic pain in the spinal cord. However, whether and how BDNF in the rACC regulates pain-related aversion due to peripheral nerve injury is largely unknown. Behaviorally, using conditioned place preference (CPP) training in rats, which is thought to reveal spontaneous pain-related aversion, we found that CPP was acquired following spinal clonidine in rats with partial sciatic nerve transection. Importantly, BDNF was upregulated within the rACC in of rats with nerve injury and enhanced the CPP acquisition, while a local injection of a BDNF-tropomyosin receptor kinase B (TrkB) antagonist into the rACC completely blocked this process. Finally, we demonstrated that the BDNF/TrkB pathway exerted its function by activating the NR2B receptor, which is widely accepted to be a crucial factor contributing to pain affect. In conclusion, our results demonstrate that the BDNF/TrkB-mediated signaling pathway in the rACC is involved in the development of neuropathic spontaneous pain-related aversion and that this process is dependent upon activation of NR2B receptors. These findings suggest that suppression of the BDNF-related signaling pathway in the rACC may provide a novel strategy to overcome pain-related aversion.

Research on meteorological conditions and their related diseases in Hefei, China.

Synchronous meteorological data from 9688 cases of patients in the Second People's Hospital of HeFei in AnHui province, China, who suffered from hypertension, cerebrovascular disease, cardiopathy, upper respiratory tract infection, and chronic bronchitis, were analyzed. The results show that there are five kinds of weather processes that greatly affect these diseases. This study provides evidence of the importance of enhancing the people's knowledge of preventing disease and improving the medical- weather service.