Heat defense is crucial for survival and fitness. Transmission of thermosensory signals into hypothalamic thermoregulation centers represents a key layer of regulation in heat defense. Yet, how these signals are transmitted into the hypothalamus remains poorly understood. Here, we reveal that lateral parabrachial nucleus (LPB) glutamatergic prodynorphin and cholecystokinin neuron populations are progressively recruited to defend elevated body temperature. These two nonoverlapping neuron types form circuits with downstream preoptic hypothalamic neurons to inhibit the thermogenesis of brown adipose tissues (BATs) and activate tail vasodilation, respectively. Both circuits are activated by warmth and can limit fever development. The prodynorphin circuit is further required for regulating energy expenditure and body weight homeostasis. Thus, these findings establish that the genetic and functional specificity of heat defense neurons occurs as early as in the LPB and uncover categorical neuron types for encoding two heat defense variables, inhibition of BAT thermogenesis and activation of vasodilation.

This study first multicenter assessment of HLH in China shows some different features in Chinese children with HLH compared with those in western countries, including older age, vulnerability to EBV infection, and a high proportion of patients with single monoallelic genetic mutations.

Low-dose propranolol is effective and safe for Chinese children with IH, and larger-scale studies are merited. Mechanisms underlying IH pathogenesis, and possible involvement of the renin-angiotensin-aldosterone system, deserve study.

ObjectiveTo observe the safety and short-term efficacy of apatinib in the treatment of recurrent, metastatic cervical cancer in patients who have already received more than two kinds of comprehensive treatment.MethodsForty-eight patients with recurrent or metastatic cervical cancer after radiotherapy or surgery who received apatinib between June 2016 and June 2017 were involved in this study. These patients experienced progression after first-line or second-line chemotherapy. There were 38 patients with cervical squamous cell carcinoma, 8 with adenocarcinoma, and 2 with adenosquamous carcinoma. Progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (AEs) were reviewed and evaluated.ResultsAll patients had complete follow-up records, and the median follow-up time was 14.5 months (5.5–20.5 months). Among the 48 patients, 14.58% achieved a partial response and 52.08% achieved stable disease. The overall response rate and disease control rate were 14.58% and 66.67%, respectively. The median time that the 48 patients received oral apatinib was 8.2 months. The median PFS was 4.6 months (95% confidence interval [CI]=3.31–5.26) and OS was 13.9 months (95% CI=8.37–17.96). The main apatinib-related adverse reactions were leukopenia (37.5%), neutropenia (41.67%), hemorrhage (37.5%), hypertension (33.33%), proteinuria (12.5%), fatigue (37.5%), and hand-foot syndrome (27.08%). Most of them were grade 1–2, and no drug-related death occurred.ConclusionsApatinib can improve the disease control rate of recurrent and metastatic cervical cancer when chemotherapy has failed, and the treatment is well tolerated. This represents that apatinib may be a new treatment option for metastatic cervical cancer patients.

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Background Lung injury due to zinc chloride smoke inhalation is very common in military personnel and leads to a high incidence of pulmonary complications and mortality. The aim of this study was to uncover the underlying mechanisms of lung injury due to zinc chloride smoke inhalation using a rat model. Methods: Histopathology analysis of rat lungs after zinc chloride smoke inhalation was performed by using haematoxylin and eosin (H&E) and Mallory staining. A lung injury rat model of zinc chloride smoke inhalation (smoke inhalation for 1, 2, 7 and 14 days) was developed. First, isobaric tags for relative and absolute quantization (iTRAQ) and weighted gene co-expression network analysis (WGCNA) were used to identify important differentially expressed proteins. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to study the biological functions of differentially expressed proteins. Then, analysis of lung injury repair-related differentially expressed proteins in the early (day 1 and day 2) and middle-late stages (day 7 and day 14) of lung injury after smoke inhalation was performed, followed by the protein-protein interaction (PPI) analysis of these differentially expressed proteins. Finally, the injury repair-related proteins PARK7 and FABP5 were validated by immunohistochemistry and western blot analysis. Results Morphological changes were observed in the lung tissues after zinc chloride smoke inhalation. A total of 27 common differentially expressed proteins were obtained on days 1, 2, 7 and 14 after smoke inhalation. WGCNA showed that the turquoise module (which involved 909 proteins) was most associated with smoke inhalation time. Myl3, Ckm, Adrm1 and Igfbp7 were identified in the early stages of lung injury repair. Gapdh, Acly, Tnni2, Acta1, Actn3, Pygm, Eno3 and Tpi1 (hub proteins in the PPI network) were identified in the middle-late stages of lung injury repair. Eno3 and Tpi1 were both involved in the glycolysis/gluconeogenesis signalling pathway. The expression of PARK7 and FABP5 was validated and was consistent with the proteomics analysis. Conclusion The identified hub proteins and their related signalling pathways may play crucial roles in lung injury repair due to zinc chloride smoke inhalation.

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