The overuse of medications for primary headache disorders is a worldwide phenomenon that plays an im-portant role in the chronicity of headache disorders.The high treatment cost and co-morbidity with various diseases pose a heavy burden on individuals and societies.In the third edition of the International Classification of Headache Disorders,medication overuse headache(MOH)is recognized as a separate secondary entity to most primary headache disorders.This article reviews the overview,epidemiology,pathophysiological mechanisms,diagnostic criteria,and treatments of MOH,discusses some unsolved questions,and summarizes the current debate on MOH.

Exosomes are cell-secreted/derived vesicular nanoparticles that mediate a novel form of intercellular communication. Cell secreted mRNA and microRNAs(miRNAs) can undergo functional transfer between cells with exosomes and be delivered to recipient cells as endogenous miRNAs, while regulating multiple target genes or signals. The intercellular communication mediated by exosomes and intestinal microbiome-host cell communication are involved in the pathogenesis and development of inflammatory bowel disease(IBD). This paper review the role of exosomes in the mode of cell communication, and discuss the pathogenesis, progression, therapeutic and diagnostic role of exosomes in IBD, as well as its clinical application prospects, in perspective of intercellular communication.

Perinatal depression is a psychological disorder that occurs during pregnancy and within one year of delivery, which can seriously affect the physical and mental health of pregnant and postpartum women, as well as the cognitive and behavioral abilities of offspring, with potential multigenerational effects. Therefore, it is important to identify its potential modifiable risk factors. Phthalic acid esters (PAEs), as common environmental endocrine disruptors, can affect maternal estrogen through multiple mechanisms and are important potential modifiable risk factors for developing maternal perinatal depression. At present, studies on the correlation between PAEs and perinatal depression are still very limited, and the mechanisms by which PAEs affect perinatal depression have not been clarified. Based on existing epidemiological and toxicological studies at home and abroad, the article briefly introduced the characteristics of multiple pathways, high doses, and long-term exposure to maternal PAEs, focused on reviewing the current status of epidemiological studies, pointed out the possible associations between some specific PAEs exposure and elevated risk of perinatal depression. It also summarized the potential roles of hormone-neurotransmitter pathway, inflammation mediation, gene regulation, and other possible mechanisms in the association between exposure to PAEs and perinatal depression. The article concluded with a look at how future research on the association between exposure to PAEs and perinatal depression can be scientifically validated, with a view to providing more high-quality evidence for the scientific prevention of the onset and progression of maternal depressive symptoms.

Objective: To investigate the mechanism of resveratrol promoting fibronectin type Ⅲ domain-containing 5 (FNDC5) degradation in skeletal muscle of male obese mice． Methods: Six-week-old male C57BL /6 mice were randomly divided into three groups : standard control diet ( SCD) ，high-fat diet ( HFD) and high-fat diet treated with resveratrol (HFD + RES) ．HFD + RES group was intervened with resveratrol via gavage ［400 mg / kg · d) ］ while fed HFD for 20 weeks．The body mass，serum TG，TC，LDL-C and HDL-C levels were detected．The pathological changes in skeletal muscle were detected by HE staining．The expression of FNDC5，SIRT1，SIRT2，LC3， p62，Beclin-1，ATG5，ATG7 was assessed by immunohistochemistry，RT-PCR and Western blot respectively. Results: The body mass ，serum TG ，TC and LDL-C levels increased significantly ，meanwhile HDL-C levels decreased in HFD group．Lipid deposition between skeletal muscle fibers were obvious in HFD group．The immuno- histochemistry results showed that protein expression levels of SIRT1，SIRT2 and LC3 obviously decreased，while the protein levels of FNDC5 and p62 obviously increased．The expression levels of FNDC5 significantly increased， while the gene expression levels of SIRT1，SIRT2，LC3，Atg7 and Beclin-1 obviously decreased．All these responses were attenuated by treatment with RES． Conclusion RES has obvious effects of lipid-lowering and promoting FNDC5 degradation in skeletal muscle tissues，which may be related with SIRT1 and SIRT2-induced autophagy， thus resulting in degradation of FNDC5 .

ObjectiveTo explore the mechanism of Qihuang Yiqi Shexue prescription （QHYQSX） in the treatment of immune thrombocytopenia （ITP） model mice based on the autophagy mediated by the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR）/Unc-51-like kinase 1 （ULK1） signaling pathway. MethodFifty BALB/c mice were randomly divided into normal group， model group， high- and low-dose QHYQSX groups， and prednisone group， with 10 mice in each group. The ITP model was induced by intraperitoneal injection of anti-platelet serum （APS） of guinea pig. On the 8th day of the APS injection， drugs were administered by gavage for 14 days. Peripheral blood platelet （PLT） count and hemoglobin （Hb） concentration were detected. Spleen and thymus were separated， weighed， and the organ index was calculated. Sternum was sampled for bone marrow smear， and bone marrow megakaryocytes were classified under a microscope. Thrombopoietin （TPO）， interleukin-6 （IL-6）， IL-10， tumor necrosis factor-α （TNF-α）， transforming growth factor-β₁ （TGF-β₁）， and interferon-γ （IFN-γ） in the serum were detected by enzyme-linked immunosorbent assay（ELISA）. AMPK， mTOR， ULK1， microtubule-associated protein light chain 3 （LC3）， Beclin1， and p62 mRNA expression levels in the spleen were detected by Real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR）. The protein expression of AMPK， p-AMPK， p-mTOR， p-ULK1， LC3Ⅱ/LC3Ⅰ， Beclin1， and p62 in the spleen was detected by Western blot. ResultCompared with the normal group， the model group showed reduced peripheral blood PLT count， Hb， and TPO levels （P<0.05，P<0.01）， increased spleen and thymus indexes （P<0.01）， decreased number of bone marrow megakaryocytes （P<0.01）， elevated serum levels of IL-6， TNF-α， and IFN-γ （P<0.01）， and reduced IL-10 and TGF-β₁ levels （P<0.01）. Compared with the model group， the groups with drug intervention showed increased PLT counts and TPO levels （P<0.01）， decreased spleen and thymus indexes （P<0.05， P<0.01）， elevated number of bone marrow megakaryocytes （P<0.05， P<0.01）， reduced serum levels of IL-6， TNF-α， and IFN-γ （P<0.05， P<0.01）， and up-regulated IL-10 and TGF-β₁ levels （P<0.05，P<0.01）. Compared with the low-dose QHYQSX group， the high-dose QHYQSX group and the prednisone group showed different degrees of significant differences in improving PLT counts and levels of cellular inflammatory factors （P<0.05， P<0.01）. Real-time PCR and Western blot results showed that compared with the normal group， the model group showed up-regulated mRNA expression of AMPK， LC3， and Beclin1 and protein expression of p-AMPK/AMPK， LC3Ⅱ/LC3Ⅰ， and Beclin1 in the spleen （P<0.05， P<0.01）， and down-regulated mRNA expression of mTOR， ULK1， and p62 and protein expression of p-mTOR， p-ULK1， and p62 （P<0.05， P<0.01）. Compared with the results in the model group， high- and low-dose QHYQSX and prednisone could down-regulate the mRNA expression of AMPK， LC3， and Beclin1 and protein expression of p-AMPK/AMPK， LC3Ⅱ/LC3Ⅰ， and Beclin1 in the spleen （P<0.05， P<0.01）， and up-regulate the mRNA expression of mTOR， ULK1， and p62 and protein expression of p-mTOR， p-ULK1， and p62 （P<0.05， P<0.01）. ConclusionQHYQSX may inhibit excessive autophagy by regulating the AMPK/mTOR/ULK1 signaling pathway， thereby regulating immune intolerance and playing a role in the treatment of ITP.

Portopulmonary hypertension (POPH) is an increase in pulmonary artery pressure that occurs on the basis of portal hypertension. As a member of the BMP family, bone morphogenetic protein 9 (BMP9) not only has the osteogenic activity, but can also protect endothelial integrity and maintain vascular homeostasis. This article reviews the pathogenesis of POPH, the physiological expression and role of BMP9, and related research advances in the BMP9 signaling pathway and its involvement in pulmonary hypertension and vascular remodeling, thereby exploring the possibility of BMP9 as a new biomarker for POPH to assist in the diagnosis of POPH.

Objective:To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for early hypopharyngeal carcinoma and precancerous lesions.Methods:Clinical data of 41 patients who received ESD for early hypopharyngeal carcinoma and precancerous lesions from August 2013 to August 2019 in the Department of Endoscopy of Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College were retrospectively analyzed. Main outcome measurements included operation completion rate, operation time, en bloc resection rate, R0 resection rate, complication rate and recurrence.Results:ESD was successfully completed in all 41 cases, with a success rate of 100.0% and a mean time of 49.1 min (ranged 10-110 min). Fifty-four lesions underwent en bloc resection, with an en bloc resection rate of 98.2% (54/55), of which 41 had negative horizontal and vertical margins, and the R0 resection rate was 74.5% (41/55). During the operation of 55 lesions, there was a small amount of blood oozing on the wound surface, and electrocoagulation with thermal biopsy forceps could successfully stop the bleeding. No perforation occurred, and 2 cases (4.3%) had delayed bleeding after ESD, and hemostasis was successful under emergency endoscopy. Postoperative endoscopy showed that 1 case (2.2%) had esophageal entrance stenosis, and the obstruction was relieved after repeated water balloon dilatation. The follow-up period ranged from 3 to 72 months, and the median time was 18 months. One case was found to have mucosal lesions in the same part of the hypopharynx and received ESD treatment again. Follow-up to October 2020, no residual lesions and recurrence were found.Conclusion:ESD is a safe and effective option for the treatment of early hypopharyngeal carcinoma and precancerous lesions, which is worthy of clinical application.

Objective:To analyze the incidence and epidemiological characteristics of traumatic spinal cord injury in China in 2018.Methods:Multi-stage stratified cluster sampling was used to randomly select hospitals capable of treating patients with spinal cord injury from 3 regions，9 provinces and 27 cities in China to retrospectively investigate eligible patients with traumatic spinal cord injury admitted in 2018. National and regional incidence rates were calculated. The data of cause of injury，injury level，severity of injury，segment and type of fracture，complications，death and other data were collected by medical record questionnaire，and analyzed according to geographical region，age and gender.Results:Medical records of 4，134 patients were included in this study，with a male-to-female ratio of 2.99∶1. The incidence of traumatic spinal cord injury in China in 2018 was 50.484 / 1 million （95% CI 50.122-50.846）. The highest incidence in the Eastern region was 53.791 / 1 million （95% CI 53.217-54.365）. In the whole country，the main causes of injury were high falls （29.58%），as well as in the Western region （40.68%），while the main causes of injury in the Eastern and Central regions were traffic injuries （31.22%，30.10%）. The main injury level was cervical spinal cord in the whole country （64.49%），and the proportion of cervical spinal cord injury in the Central region was the highest （74.68%），and the proportion of lumbosacral spinal cord injury in the Western region was the highest （32.30%）. The highest proportion of degree of injury was incomplete quadriplegia （55.20%），and the distribution pattern was the same in each region. A total of 65.87% of the patients were complicated with fracture or dislocation，77.95% in the Western region and only 54.77% in the Central region. In the whole country，the head was the main combined injury （37.87%），as well as in the Eastern and Central regions，while the proportion of chest combined injury in the Western region was the highest （38.57%）. A total of 32.90% of the patients were complicated with respiratory complications. There were 23 patients （0.56%） died in hospital，of which 17（73.91%） died of respiratory dysfunction. Conclusions:The Eastern region of China has a high incidence of traumatic spinal cord injury. Other epidemiological features include high fall as the main cause of injury cervical spinal cord injury as the main injury level，incomplete quadriplegia as the main degree of injury，head as the main combined injury，and respiratory complications as the main complication.

Objective:To explore the potential biomarkers for the metastasis and prognosis of uveal melanoma (UM) from molecular genetics.Methods:The data of 80 UM samples including 18 metastatic cases and 62 non-metastatic cases between 2007 and 2019 were downloaded from The Cancer Genome Atlas database.The tumor mutation burden and gene mutation information, including mutant genes, variant type, the proportion of single nucleotide variation (SNV) and mutation proportion, were analyzed using maftools package in R software, and the differentially expressed genes (DEGs) between the two groups were screened using edgeR package.The Kyoto Encyclopedia of Genes and Genomes enrichment analysis based on the DEGs was performed to screen prognosis-associated genes using KOBAS.Cox regression model was established using survival package in R software to verify the association between gene mutation and DEGs and the prognosis of UM patients.Results:The mutation analysis showed that missense mutation accounted for a large proportion in the mutation of UM samples, and the main variant type was SNV, and the mutation burden of UM was low.Compared with the non-metastatic UM samples, 562 DEGs were identified in the metastatic UM samples.Three pathways, including vitreoretinal degeneration, proteoglycans in cancer, and PI3K-Akt pathway, were significantly enriched.The expression levels of BAP1, FOXO3 and ITPR2 were 2 982.50 (1 251.50, 5 637.00), 1 223.00 (914.75, 2 706.25) and 2 201.50 (570.75, 4 814.00)in the metastatic group, and 5 225.00 (2 281.25, 8 784.00), 2 293.50 (1 254.25, 3 693.75) and 474.00 (153.00, 1 437.75) in the non-metastatic group, respectively.The expression of BAP1 and FOXO3 among the DEGs were significantly down-regulated and ITPR2 expression was significantly up-regulated in the metastatic group in comparison with the non-metastatic group ( Z=-1.786, -1.982, -3.065; all at P<0.10). The survival analysis revealed BAP1 mutation, decreased FOXO3 expression and increased ITPR2 expression were associated with inferior survival of UM patients (all at P<0.10). Conclusions:BAP1 mutation, up-regulation of FOXO3 and down-regulation of ITPR2 might be potential biomarkers for the metastasis and prognosis of UM.

Objective:To determine the potential risk factors of delayed hemorrhage after endoscopic submucosal dissection (ESD) in patients with early gastric carcinomas or precancerous lesions.Methods:The clinical data of 637 patients with early gastric carcinomas (EGC) who treated with ESD in Department of Endoscopy at Cancer Hospital, Chinese Academy of Medical Sciences, from August 2013 to August 2019, were retrospectively analyzed. Univariate analysis and multivariate logistic analysis were conducted to evaluate the risk factors associated with delayed bleeding.Results:A total of 699 lesions in 637 patients, of which 696 lesions were resected enbloc, the curative resection rate was 92.1% (644/699). The pathological diagnosis after ESD showed that 46 cases were low-grade intraepithelial neoplasia, 71 were high-grade intraepithelial neoplasia, and 582 were cancer. Delayed bleeding occurred in 74 lesions, while other 625 lesions without postoperative bleeding. The incidence was 10.6%. Compared with the non-bleeding group, there were statistically significant differences in the maximum length of the lesion, the gross shape of the lesion, the control of intra operative bleeding, and the operation time in the delayed bleeding group ( P<0.05). Multivariate logistic regression analysis showed that the maximum length of the lesion and the gross shape of the lesion were independent factors of delayed bleeding after ESD. Delayed bleeding was inclined to occur in patients with lesion size ≥3.0 cm ( OR=1.958, 95% CI: 1.162-3.299) and the superficial and flat lesion ( OR=10.598, 95% CI: 1.313-85.532) after ESD. Conclusions:The maximum length of the lesion and the gross shape of the lesion are independent impact factors of delayed bleeding occurring in patients with EGC and precancerous lesions after ESD. Patients with lesion size≥3 cm, or superficial flat lesion should be paid attention after ESD operation. It needs to take timely measures to prevent the very likely bleeding in order to ensure postoperative recovery and improve the quality of life for postoperative patients.