This article summarizes the overview, occurrence, adverse effects, assessment tools, influencing factors and interventions of kinesiophobia in breast cancer survivors, with a view to providing basis for preventing and reducing the occurrence of kinesiophobia in breast cancer survivors, improving the rehabilitation effect and the quality of life.

Objective:To investigate the impact of exogenous lactate on the replication of dengue virus type 2 (DENV-2) in Raw264.7 cells, mouse bone marrow-derived macrophages (BMDMs) and THP-1 cells and explore its association with cell activation.Methods:BMDMs from BALB/c mouse bone marrow were prepared and evaluated by flow cytometry to detect the proportion of F4/80 + CD11b + cells. Glucose transporter type 1 (GLUT1), hexokinase 2 (HK2), and monocarboxylate transporters 4 (MCT4) expression at mRNA level in BMDMs at different time points after DENV-2 infection were measured by qRT-PCR. The content of lactate in the culture supernatants was quantified via colorimetric assay. CCK-8 assay was used to evaluate the impacts of different concentrations of lactate on the viability of Raw264.7 cells, BMDMs, and THP-1 cells. qRT-PCR was used to detect the expression of DENV-2 E gene, TGF-β, CD86, retinoic acid-inducible gene Ⅰ (RIG-Ⅰ), IFN-β, interferon-stimulated gene 15 (ISG15), and ISG56 at mRNA level in cells infected with DENV-2 at different MOIs in the presence of different concentrations of lactate. Meanwhile, flow cytometry was used to analyze the expression of CD86 and CD206. Results:The percentage of BMDMs was (87.53±1.66)%. GLUT1 expression at mRNA level exhibited a decrease in BMDMs at 24 h after DENV-2 (MOI=3) infection following a transient increase at 12 h ( P<0.05), while HK2 expression at mRNA level was higher that than in blank control and inactivated DENV-2 infection groups at 12, 24, and 36 h ( P<0.01). Besides, there was an increase in both MCT4 mRNA level and the content of lactate in culture supernatants at 24 h after DENV-2 (MOI=1.5) infection ( P<0.05). The viability of the three types of cells remained above 80% when the concentration of lactate was 31.25 mmol/L. Lactate at the concentration of 35 mmol/L increased the expression of the DENV E gene at mRNA level in DENV-2-infected BMDMs at MOI=1 or MOI=2 ( P<0.05). Besides, it promoted the expression of DENV E gene at mRNA level in Raw264.7 and THP-1 cells ( P<0.001) as well as the expression of CD163, TGF-β, RIG-Ⅰ, IFN-β, ISG15 and ISG56 at mRNA level in BMDMs at MOI=1.5, but inhibited the expression of CD86 at mRNA level in BMDMs ( P<0.05). It also up-regulated CD206 protein expression ( P<0.01) and down-regulated CD86 protein expression ( P>0.05) in BMDMs. Conclusions:Exogenous lactate enhances DENV-2 replication in both human- and murine-derived macrophages and that might correlate with M2 macrophage polarization.

OBJECTIVE We have previously shown that inhibition of phosphodiesterase-4(PDE4)protects against neuronal damage in models of Parkinson's dis-ease(PD).However,the mechanisms have not yet been completely revealed.Here we aimed to elucidate the pharmacological effects and mechanisms of action of rof-lupram(ROF),an novel PDE4 inhibitor,in experimen-tal models of PD.METHODS The survival rate,apopto-sis rate and toxicity level of SH-SY5Y cells were deter-mined by MTT,flow cytometry and lactate dehydroge-nase detection kit.At the same time,LYT staining was used to detect the changes of lysosome fluorescence intensity:Western blotting was used to detect the changes of lysosome associated proteins,Sirtuin1 and α-Syn;NAD/NADH assay kit was used to determine the change of NAD content.To explore whether SIRT1 inhibitor(EX527)and lysosomal inhibitor could block the effect of ROF.In addition,ROT was used to stimulate C57BL/6J mice to construct a mouse model of PD to verify the effect and mechanism of ROF.The changes of motor function were evaluated by behavioral experiments(pole climb-ing,bar rotating and balance beam experiments).Super-oxide dismutase kit and Western blotting were used to detect the changes of SOD activity and expression of related proteins in substantia nigra.RESULTS We showed that pretreatment with ROF significantly attenu-ated cell apoptosis in ROT-treated SH-SY5Y cells.Fur-thermore,ROF significantly enhanced the lysosomal function,as evidenced by the increased levels of mature cathepsin D(CTSD)and lysosomal-associated mem-brane protein 1(LAMP1)through increasing NAD+/NADH and the expression of sirtuin 1(SIRT1).Pretreatment with an SIRT1 inhibitor selisistat(SELI,10 μ mol·L-1)attenuated the neuroprotection of ROF,and ROF-increased expression levels of LAMP1 and mature CTSD.Moreover,inhibition of CTSD by pepstatin A(20 μmol·L-1)attenuated the protective effects of ROF.In vivo study was conducted in mice exposed to ROT(10 mg·kg-1·d-1,ig)for six weeks;then,ROT-treated mice received ROF(0.5,1 and 2 mg·kg-1·d-1,ig)for four weeks.ROF significantly ameliorated motor deficits,which was accompanied by increased expression levels of tyro-sine hydroxylase,SIRT1,mature CTSD,and LAMP1 in the substantia nigra pars compacta.CONCLUSION Taken together,these results demonstrate that ROF exerts a neuroprotective action in PD models.The mech-anisms underlying ROF neuroprotective effects appear to be associated with NAD+/SIRT1-dependent activation of lysosomal function.

The negative effects of low temperature can readily induce a variety of diseases. We sought to understand the reasons why cold stress induces disease by studying the mechanisms of fine-tuning in macrophages following cold exposure. We found that cold stress triggers increased macrophage activation accompanied by metabolic reprogramming of aerobic glycolysis. The discovery, by genome-wide RNA sequencing, of defective mitochondria in mice macrophages following cold exposure indicated that mitochondrial defects may contribute to this process. In addition, changes in metabolism drive the differentiation of macrophages by affecting histone modifications. Finally, we showed that histone acetylation and lactylation are modulators of macrophage differentiation following cold exposure. Collectively, metabolism-related epigenetic modifications are essential for the differentiation of macrophages in cold-stressed mice, and the regulation of metabolism may be crucial for alleviating the harm induced by cold stress.
Acetylation ; Animals ; Cold-Shock Response ; Epigenesis, Genetic ; Macrophages/metabolism* ; Mice ; Mitochondria/metabolism*

Overlap myoclonic epilepsy with ragged-red fibers (MERRF)-Leigh syndrome is a rare mitochondrial encephalomyopathy. A case of MERRF-Leigh syndrome associated with mitochondrial DNA 8344A>G (m.8344A>G) mutation was reported in this article. The patient has suffered from the disease since 15-year old with myoclonus, exercise intolerance, ataxia, limb weakness, dysphasia, dyspnea, blurred vision and hearing loss. Magnetic resonance imaging revealed lesions on right thalamus, bilateral medulla and lumbar spinal cord and atrophy of cervical spinal cord. Electromyography showed predominantly axonal damage of both sensory nerve and motor nerve. Histochemical analyses revealed ragged red fibers, ragged blue fibers, succinate dehydrogenase-stronghly reactive vessels and decreased cytochrome oxidase activity. Gene tests demonstrated a high level of m.8344A>G mutation and m. 14484T>C mutation. MERRF-Leigh overlap syndrome with m.8344A>G mutation was rare. Bulbar paralysis following myoclonus is the main clinical symptom.

The 30th International Symposium on Amyotrophic Lateral Sclerosis-Motor Neuron Disease was held in Perth, Australia from December 4 to 6, 2019. This article mainly introduces the clinical research of this meeting, including epidemiology, non-motor symptoms, auxiliary examinations and biomarkers, etc., while the basic research includes genomics and genetics, protein metabolism abnormalities, neuroimmunity and inflammation, synapse pathology and preclinical treatment strategies,

A female patient aged 42 years with deep burn on right lower limb was admitted to Affiliated Hospital of Jining Medical University on January 25, 2019. The patient previously had cerebral infarction, hypertension, and hysteria, with long-term use of aspirin and risperidone. After admission, the patient underwent tangential excision twice. On the third day after the second tangential excision and skin grafting, the muscle strength of the right limb gradually decreased, and the patient was treated with emergency craniocerebral magnetic resonance imaging, which suggested acute cerebral infarction. Improvement of cerebral circulation and vasodilatation were given immediately. The limb muscle strength of the patient gradually recovered on the fifth day after the operation, and no sequela was left when the patient was discharged. After the case was discussed, we think that postoperative decreased blood volume and blood concentration resulting from tangential excision bleeding of deep burn and wound exudate as well as inadequate fluid infusion are the main causes of hemodynamic change, the patient had the basis of multiple cerebral artery stenosis, and superposition of multiple factors led to the occurrence of postoperative acute cerebral infarction. Appropriate increase in the fluid infusion volume during and after surgery and transfusion if necessary to increase blood and oxygen supply to the brain can reduce the occurrence of cerebral infarction.

Structure of biliary system is complex as well as various, making troubles for optimal surgical treatment of biliary disease. Remarkable imaging of biliary system helps surgeon evaluating patients and planning surgeries. There are several methods to obtain accurate anatomical information of biliary system, such as X-ray fluoroscopy, MRI and fluorescence-based imaging. Each has its own advantages and disadvantages. Combination of multi-model imaging technologies may improve visual result of anatomical information of biliary tract. More resolvable, legible, and sequential imaging technology of biliary system remains further study. This article reviews various cholangiography methods widely used in the clinical setting.

Objective: To investigate the application value of augmented reality (AR) technology in pancreatoduodenectomy (PD). Methods: The retrospective and descriptive study was conducted. The clinicopathological data of 3 male patients who underwent PD in Tsinghua University Affiliated Beijing Tsinghua Changgung Hospital from June 2018 to February 2019 were collected. The 3 patients were aged from 52 to 63 years, with a median age of 57 years. Digital imaging and communication standard format data of enhanced computed tomography (CT) scan were collected, the three-dimensional (3D) images of abdominal arteries, portal vein, descending duodenum, pancreatic body and tail, pancreatic head, common bile duct, and pancreatic duct were reconstructed. The results were imported into the AR software. Optical tracking based on two-dimensional codes and manual interactive rigid registration were adopted for intraoperative navigation. Observation indicators: (1) surgical and postoperative conditions; (2) postoperative pathological examination; (3) follow-up. Follow-up using outpatient examination or telephone interview was conducted to detect survival of patients and tumor metastasis and recurrence up to June 2019. The measurement data with skewed distribution were expressed as M (range). Count data were expressed as absolute numbers. Results: (1) Surgical and postoperative conditions: all the 3 patients underwent PD with AR technology as intraoperative navigation successfully. The operation time, volume of intraoperative blood loss, and duration of postoperative hospital stay were 6 hours (range, 5-8 hours), 700 mL (range, 300-900 mL), 11 days (range, 9-12 days). There was no perioperative death or complication occured. After surgery, the patients who underwent PD combined with superior mesenteric vein (SMV) resection and reconstruction had patent SMV on the enhanced computed tomography examination. (2) Postoperative pathological examination: results of pathological examination showed 1 case of intraductal papillary mucinous neoplasm (IPMN) of the pancreas with invasive adenocarcinoma (neoplasm invading SMV), 1 case of insulinoma, and 1 case of periampullary neuroendocrine carcinoma, respectively. (3) Follow-up: 3 patients were followed up for 4-12 months, with a median follow-up time of 6 months. During the follow-up, the patient with IPMN of the pancreas and invasive adenocarcinoma had liver metastasis at 3 months after surgery, and received chemotherapy at other hospital. After 4 cycles of chemotherapy, the metastatic nodule shrank, and the patient was still in follow-up up to deadline of follow-up. Other 2 patients had no recurrence or metastasis. Conclusion AR technique assisted PD is safe and feasible, which is helpful to indentify vascular branches and tracks.

The 29th International Symposium on Amyotrophic Lateral Sclerosis (ALS)-Motor Neuron Disease was held in Glasgow from December 7 to 9, 2018. The symposium was divided into 23 topics, with 109 special reports and paper′s exchange and 515 posters exchange. This article briefly introduces some topics of the symposium, involving basic researches, clinical researches and clinical trials. Among these, basic researches include genetics and genomics, axonal degeneration, disease models, and preclinical therapeutic strategies; Clinical researches include epidemiology, clinical progression, cognitive and psychological change, neuropathology, neurophysiology, neuroimaging and biomarkers.