COVID-19: the CaMKII-like system of S protein drives membrane fusion and induces syncytial multinucleated giant cells.

The SARS-CoV-2 S protein on the membrane of infected cells can promote receptor-dependent syncytia formation, relating to extensive tissue damage and lymphocyte elimination. In this case, it is challenging to obtain neutralizing antibodies and prevent them through antibodies effectively. Considering that, in the current study, structural domain search methods are adopted to analyze the SARS-CoV-2 S protein to find the fusion mechanism. The results show that after the EF-hand domain of S protein bound to calcium ions, S2 protein had CaMKII protein activities. Besides, the CaMKII_AD domain of S2 changed S2 conformation, facilitating the formation of HR1-HR2 six-helix bundles. Apart from that, the Ca2+-ATPase of S2 pumped calcium ions from the virus cytoplasm to help membrane fusion, while motor structures of S drove the CaATP_NAI and CaMKII_AD domains to extend to the outside and combined the viral membrane and the cell membrane, thus forming a calcium bridge. Furthermore, the phospholipid-flipping-ATPase released water, triggering lipid mixing and fusion and generating fusion pores. Then, motor structures promoted fusion pore extension, followed by the cytoplasmic contents of the virus being discharged into the cell cytoplasm. After that, the membrane of the virus slid onto the cell membrane along the flowing membrane on the gap of the three CaATP_NAI. At last, the HR1-HR2 hexamer would fall into the cytoplasm or stay on the cell membrane. Therefore, the CaMKII_like system of S protein facilitated membrane fusion for further inducing syncytial multinucleated giant cells.

COVID-19: captures iron and generates reactive oxygen species to damage the human immune system.

Currently, the novel coronavirus pneumonia has been widespread globally, and there is no specific medicine. In response to the emergency, we employed bioinformatics methods to investigate the virus's pathogenic mechanism, finding possible control methods. We speculated in previous studies that E protein was associated with viral infectivity. The present study adopted the domain search techniques to analyse the E protein. According to the results, the E protein could bind iron or haem. The iron and haem bound by the E protein came from the attacked haemoglobin and phagocytes. When E protein was attached to haem, it synthesised oxygen and water into superoxide anions, hydrogen peroxide and hydroxyl radicals. When the iron-bound E protein and the haem-bound E protein worked together, they converted superoxide anions and hydrogen peroxide into oxygen and water. These were the "ROS attack" and "ROS escape" of the virus. "ROS attack" damaged the tissues or cells exposed on the surface of the virus, and "ROS escape" decomposed the superoxide anion and hydrogen peroxide that attacked the virus. When NK cells were exposed to infected cells, viruses that had not shed from the infected cells' surface damaged them through "ROS attack". In addition, lymphocytes such as T cells and B cells, which could be close to the antigen of the virus surface, were also easily damaged or killed by the "ROS attack", generating a decrease in lymphocytes. When memory B cells were exposed to the virus's surface antigen, they were also damaged by "ROS attack", resulting in the patient's re-infection. The virus applied the "ROS escape" to decompose hydrogen peroxide released by phagocytes into oxygen and water. The surrounding cells were replenished with oxygen, and the patient was in a "happy hypoxia" state. When the phagocytes swallowed the virus, the E protein converted superoxide anions into oxygen and water. In this way, the virus parasitized in the vesicles of the phagocyte. While virus was in the lysosome, the E protein generated ROS to damage nearby hydrolases. In this way, the virus parasitized the lysosome. Excessive hydroxyl free radicals destroyed the membrane structure of the lysosome, causing the hydrolase release from lysosome, autophagy of phagocytic cells and subsequent cell death. As a result, the colonizing phagocytes of the virus was associated with asymptomatic infection or retest-positive. Briefly, the virus inhibited the immune system through "ROS escape", and damaged the immune system by "ROS attack". The destruction instigated a strong cytokine storm, leading to organ failure and complications.

Management of Refractory Helicobacter pylori Infection: Consensus and Controversy / 胃肠病学

The harm of Helicobacter pylori (Hp) infection has been fully recognized, and the eradication of Hp to prevent and treat Hp-associated diseases is highly cost-effective. Now, the statement "Hp infected individuals should be offered eradication therapy, unless there are competing considerations" has been widely accepted. However, the eradication rate of Hp in clinical practice is gradually decreasing, which affects negatively the prevention and control of Hp infection. The goals are unified, but difficulties are encountered in the implementation. Therefore, the treatment of "refractory Hp infection" has become a hot research spot today. In this paper, the controversy over the definition of "refractory Hp infection", the causes for "refractory" infection and related countermeasures are described in detail.

Interpretation of "Management of Helicobacter pylori Infection: the Maastricht /Florence Consensus Report" / 胃肠病学

The recently published paper titled "Management of Helicobacter pylori infection: the Maastricht /Florence consensus report" reached consensus on 87 statements concerning management of Helicobacter pylori infection in following 5 aspects: (1) indications/associations, (2) diagnosis, (3) treatment, (4) prevention/gastric cancer and (5) Helicobacter pylori and the gut microbiota. Detailed interpretations of this consensus were presented in this paper.

Role of Citric Acid in Improving the Accuracy of Urea Breath Test for Diagnosis of Helicobacter pylori Infection / 胃肠病学

Urea breath test (UBT) is the most important non-invasive method for diagnosis of Helicobacter pylori (Hp) infection. Citric acid in UBT reagents can increase the acidity of stomach and the detection value of delta over baseline (DOB), thereby reducing the false positive and false negative rates of UBT in patients with gastric hypochlorhydria (moderate-to-severe gastric mucosal atrophy/intestinal metaplasia, taking proton pump inhibitors), thus improving the diagnostic accuracy of Hp infection.

Interpretation of "Screening and Eradication of Helicobacter pylori for Gastric Cancer Prevention: the Taipei Global Consensus" / 胃肠病学

Recently published paper titled "Screening and eradication of Helicobacter pylori for gastric cancer prevention: the Taipei global consensus" reached consensus in the following 5 aspects: (1) Disease burden of Helicobacter pylori (Hp) infection associated gastric cancer; (2) Implementation of Hp screening and eradication programs at population level; (3) Treatment of Hp infection in mass eradication programs; (4) Potentially adverse consequences of Hp eradication; (5) Endoscopic surveillance for gastric cancer after Hp eradication. Detailed interpretations of these 5 aspects were performed in this paper.

Rational Management of Unintentional Weight Loss / 胃肠病学

Unintentional weight loss is one of the common clinical symptoms with potential serious clinical implications. There are a variety of potential etiologies and special factors to be considered. Comprehensive evaluation of these patients should be based on the relevant results found in the medical history,physical examination,and laboratory tests. The purpose of this paper is to discuss the clinical importance,underlying etiologies,and rational management of unintentional weight loss.

Screening and Early Detection of Gastric Cancer / 胃肠病学

Gastric cancer is one of the most common malignant tumors in China. The 5-year survival rate of advanced gastric cancer is less than 30%,while the 10-year survival rate of early gastric cancer can reach 90%. Gastric cancer screening is the primary means of detecting early gastric cancer and reducing its mortality. Helicobacter pylori(H. pylori) infection is the most important cause of gastric cancer. Eradication of H. pylori can reduce the incidence of gastric cancer and its mortality. This review summarized recent advances in screening methods,screening subjects,screening procedures, and the combination of gastric cancer screening with H. pylori detection/eradication strategy.

Study on the metastatic sequence of cervix lymph node in hypopharyngeal carcinoma / 中华肿瘤杂志

Objective@#To investigate the metastatic sequence of cervical lymph node in hypopharyngeal carcinoma aimed at guiding neck exploration.@*Methods@#Seventy-five serial sections of integrally dissected lateral neck specimens from 67 patients of hypophayryngeal carcinoma were histopathologically observed, and the metastatic sequence of cervical lymph node of hypophayryngeal carcinoma were analysed.@*Results@#In 75 integrally dissected lateral neck specimens, 63 laterals were found to occur cervical lymph node metastases, the metastatic ratio was 84.0%. The analytic result of 63 dissected lateral neck specimens with positive lymph nodes showed that the metastatic lymph node ratio in descending order was level Ⅱ (90.5%), level Ⅲ (76.2%), level Ⅳ (41.3%), level Ⅴ (15.9%), level Ⅰ (7.9%) and level Ⅵ (3.2%). The metastatic ratio of lymph node between level Ⅰ~Ⅵ were significantly different from each other (P<0.01). When the tumor metastasized to one cervical lymph node, this could be found in levels Ⅱ or Ⅲ, when metastasized to two cervical lymph nodes, these could be found in levels Ⅱ, Ⅲ, Ⅳ, and when metastasized to more than 5 of cervical lymph nodes, these could be found in levels Ⅱ, Ⅲ, Ⅳ, Ⅴ, Ⅰand Ⅵ. According to the occurring sequence, metastatic ratio and number of cervical lymph node metastasis (LNM), levels Ⅱ and Ⅲ were identified as the first station, level Ⅳ was the second station and levels Ⅴ, Ⅰ and Ⅵ were the third station of cervical LNM in hypopharyngeal carcinoma.@*Conclusion@#The confirmation of metastatic sequence of cervical lymph node in hypophayryngeal carcinoma provides a reliable evidence for neck lymph node dissection and reference value for clinic therapy.

Pay Attention to Eradication of Helicobacter pylori for Prevention of Gastric Cancer / 胃肠病学

Gastric cancer ranks second among the most common causes of cancer death in China. More than 90% of gastric cancer are considered as the ultimate consequence of a longstanding mucosal inflammation. Helicobacter pylori (H. pylori)infection is the leading etiological cause of gastritis,which may result in atrophy,intestinal metaplasia and dysplasia of the gastric mucosa,and finally the occurrence of gastric cancer (Correa's Cascade of intestinal type of gastric cancer). This well-understood natural history provides the rationale for primary and secondary cancer prevention strategies. A large body of evidence demonstrates that combined strategies of primary (H. pylori eradication) and secondary (endoscopic screening and surveillance)prevention may prevent or limit the progress of gastric oncogenesis. In this article, the importance of primary prevention of gastric cancer is emphasized.

Interpretation of the Fifth Chinese National Consensus Report on Management of Helicobacter pylori Infection / 胃肠病学

The Fifth Chinese National Consensus Report on Management of Helicobacter pylori Infection has been published.Contents of the consensus consist of six parts, including indications for Helicobacter pylori eradication, diagnosis, treatment, Helicobacter pylori and gastric cancer, Helicobacter pylori infection in special populations, Helicobacter pylori and gastrointestinal microbiota.Most of the contents are understandable, and this paper mainly explains 7 controversial issues.

Strive to Improve the Eradication Rate of Helicobacter pylori:Part Ⅰ / 胃肠病学

The indication for eradication of Helicobacter pylori( Hp)has been gradually expanded from peptic ulcer to“confirmed Hp infection”. Kyoto global consensus report on Hp gastritis has defined Hp gastritis as an infectious disease, and proposed that eradication therapy should be given to Hp infected individuals unless there are competing considerations. Currently the issue of Hp infection is no longer whether it should be eradicated,but rather how it can be effectively eradicated. With the rise of antibiotic resistance,Hp eradication is much more difficult than beforehand. This series of lectures on how to improve the eradication rate of Hp has been elaborated in detail in following aspects:current status of Hp eradication therapy,how to improve the eradication rate of drug-resistant strains of Hp,and to explore suitable eradication regimens for Chinese patients in reference with international consensus.

Interpretation of Japan“Evidence-based Clinical Practice Guidelines for Peptic Ulcer Disease 2015” / 胃肠病学

The Japanese Society of Gastroenterology revised the evidence-based clinical practice guidelines for peptic ulcer disease in 2015. The revised guidelines consist of the following items:bleeding gastric and duodenal ulcers, Helicobacter pylori(Hp)eradication therapy and non-eradication therapy,drug-induced ulcer,non-Hp/ non-nonsteroidal anti-inflammatory drug( NSAID)-induced ulcer,and surgical treatment. This guideline describes the abovementioned content in detail and is a good reference for clinical practice. A full interpretation of this guideline was performed in this paper.

Interpretation of“Management of Helicobacter pylori Infection - the Maastricht Ⅴ/Florence Consensus Report” / 胃肠病学

“Management of Helicobacter pylori infection — the Maastricht Ⅴ Consensus Conference”held in Florence, Italy,October 8-9th,2015 was convened for developing a new consensus on the management of Helicobacter pylori infection in following aspects:1. Indication/ Associations,2. Diagnosis,3. Treatment,4. Prevention/ Public Health,5. Helicobacter pylori and the Gastric Microbiota. A detailed interpretation of these contents was made in this paper.

Lentivirus-mediated knockdown of human E6 AP inhibits gastric cancer cell prolifera-tion and migration / 军事医学

Objective To detect the effect of E6AP on gastric cancer cell proliferation and migration.Methods The expression of E6AP in different gastric cancer cell lines and normal gastric mucosa epithelial cell lines was detected by Western blotting.Gastric cancer cells BGC-823 stably expressing E6AP short hairpan RNA(shRNA) were obtained by lentiviral vector of E6AP.The effect of E6AP on BGC-823 cell growth and migration was determined by CCK-8 kit, Tran-swell and wound healing assay.Results Gastric cancer cell line BGC-823 in which E6AP was stably knocked down was established.Knockdown of E6AP inhibited the proliferation and migration of BGC-823 cells.Conclusion E6AP plays a key role in gastric cancer proliferation and migration.

Management of Patients with Peptic Ulcer Bleeding / 胃肠病学

Peptic ulcer bleeding is a common emergency. Management of peptic ulcer bleeding needs prompt pre-endoscopy risk stratification,initiation of pharmacotherapy,endoscopic assessment and hemostasis if necessary. This article reviewed the proper management of patients with peptic ulcer bleeding based on the most recent relevant international guidelines and consensus.

Gastrointestinal Bleeding in Elderly / 胃肠病学

In patients with gastrointestinal bleeding,the elderly patients have the unique features in bleeding incidence,etiologic constitution,clinical manifestations,management and prognosis. The aging of population makes the evaluation and management of gastrointestinal bleeding in elderly a special and increasingly common clinical challenge. This paper reviewed this topic in detail.

Overview of Gastrointestinal Bleeding / 胃肠病学

Gastrointestinal(GI)bleeding is one of the commonly seen clinical problems in departments of emergency and gastroenterology. Acute massive bleeding may be life-threatening,and chronic blood loss can present symptoms of anemia. GI bleeding is the clinical manifestation of some serious diseases,including GI malignancies. Familiar with and mastering the clinical manifestations,classification and principles of management of GI bleeding will help to improve its prevention and treatment.

Interpretation of Kyoto Global Consensus on Helicobacter pylori Gastritis / 胃肠病学

A global consensus meeting on Helicobacter pylori(H. pylori)gastritis was held in Kyoto,Japan from January 31st to February 1st ,2014,which was convened to develop consensus on:(1)H. pylori gastritis is an infectious disease,(2)clinical distinction of dyspepsia caused by H. pylori from functional dyspepsia,(3)appropriate diagnostic assessment of gastritis and(4)when,whom and how to treat H. pylori gastritis. All 24 statements for 22 clinical questions achieved a consensus level of > 80% . In this paper,the statements were interpreted in detail.