Advances in Helicobacter pylori vaccine research: From candidate antigens to adjuvants-A review.

BACKGROUND: Helicobacter pylori is a Gram-negative, spiral-shaped bacterium that infects approximately 50% of the world's population and has been strongly associated with chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoma, and gastric cancer. The elimination of H. pylori is currently considered one of the most effective strategies for the treatment of gastric-related diseases, so antibiotic therapy is the most commonly used regimen for the treatment of H. pylori infection. Although this therapy has some positive effects, antibiotic resistance has become another clinically prominent problem. Therefore, the development of a safe and efficient vaccine has become an important measure to prevent H. pylori infection. METHODS: PubMed and ClinicalTrials.gov were systematically searched from January 1980 to March 2023 with search terms-H. pylori vaccine, adjuvants, immunization, pathogenesis, and H. pylori eradication in the title and/or abstract of literature. A total of 5182 documents were obtained. Based on the principles of academic reliability, authority, nearly publicated, and excluded the similar documents, finally, 75 documents were selected, organized, and analyzed. RESULTS: Most of the candidate antigens used as H. pylori vaccines in these literatures are whole-cell antigens and virulence antigens such as UreB, VacA, CagA, and HspA, and the main types of vaccines for H. pylori are whole bacteria vaccines, vector vaccines, subunit vaccines, nucleic acid vaccines, epitope vaccines, etc. Some vaccines have shown good immune protection in animal trials; however, few vaccines show good in clinical trials. The only H. pylori vaccine passed phase 3 clinical trial is a recombinant subunit vaccine using Urease subunit B (UreB) as the vaccine antigen, and it shows good prophylactic effects. Meanwhile, the adjuvant system for vaccines against this bacterium has been developed considerably. In addition to the traditional mucosal adjuvants such as cholera toxin (CT) and E. coli heat labile enterotoxin (LT), there are also promising safer and more effective mucosal adjuvants. All these advances made safe and effective H. pylori vaccines come into service as early as possible. CONCLUSIONS: This review briefly summarized the advances of H. pylori vaccines from two aspects, candidates of antigens and adjuvants, to provide references for the development of vaccine against this bacterium. We also present our prospects of exosomal vaccines in H. pylori vaccine research, in the hope of inspiring future researchers.

Return to the Essence of Doctor-patient Relationship / 中国医学伦理学

Doctor-patient relationship plays a crucial role in regulating medical behavior and medical ethics. The essence of doctor-patient relationship is the true practice of life created by mutual kindness and harmony, which expressed by love, sympathy, comfort and cooperation. From the perspective of economy, ethics, law, science and technology, this paper deeply analyzed the reasons and consequences of doctor-patient relationship’s deviation from the essence, and believed that effectively strengthening communication, actively enhancing empathy, and sincerely providing care are conducive to returning to the essence of the doctor-patient relationship and easing the tense situation of the doctor-patient relationship.

Epidemiological characteristics of 17 imported patients infected with SARS-CoV-2 Omicron variant / 中南大学学报(医学版)

OBJECTIVES@#With the continuous generation of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pressure of epidemic prevention and control continues to increase in China. Omicron with stronger infectiousness, immune escape ability and repeated infection ability spread to many countries and regions around the world in a short period of time. China has also successively reported cases of imported Omicron infections. This study aims to understand the epidemiological characteristics of Omicron variant via analyzing the epidemiological characteristics of imported patients with Omicron in Hunan Province, and to provide reference for preventing and controlling the imported epidemics.@*METHODS@#The clinical data of imported patients with coronavirus disease 2019 admitted to Hunan Province from December 16 to December 31, 2021 were retrospectively collected. The epidemiological information, general information, clinical classification, clinical symptoms, vaccination status, and lung CT were analyzed. Nasopharyngeal swabs and blood samples were collected. Virus nucleic acid was detected by magnetic beads method using SARS-CoV-2 detection kit. Ct values of ORF1ab gene and N gene were compared between asymptomatic infected patients and confirmed patients. The specific IgM and IgG antibodies were detected by chemiluminescence assay using SARS-CoV-2 IgM test kit and SARS-CoV-2 IgG test kit, respectively. Ct values of IgM and IgG antibodies were compared between asymptomatic infected patients and confirmed patients.@*RESULTS@#Seventeen patients with Omicron variant infection were treated in Hunan, including 15 confirmed patients (5 common type and 10 mild type) and 2 asymptomatic infection patients. The 17 patients were all Chinese, they were generally young, and 16 were male. There were 9 patients with diseases. Of them 3 patients had respiratory diseases. All 17 patients had completed the whole process of vaccination, but only one person received a booster shot of SARS-CoV-2 vaccine. The clinical manifestations of the patients were mild, mainly including dry/painful/itchy throat, cough, and fatigue. The total protein and creatine in the asymptomatic infection and confirmed cases infected with Omicron variant were all within the normal range, but other biochemical indicators were abnormal. There were the significant differences in C-reactive protein and fibrinogen between asymptomatic infection and confirmed patients (both P<0.05). There were more patients with elevated C-reactive protein in confirmed patients than without confirmed ones. The detection rate of specific IgM and IgG antibodies on admission was 100%, and there was no significant difference in the specific antibody levels between asymptomatic infection and confirmed patients (P>0.05). There were no significant differences in Ct values of ORF1ab gene and N gene (21.35 and 18.39 vs 19.22 and 15.67) between the asymptomatic infection and the confirmed patients (both P>0.05). Only 3 patients had abnormal lung CT, showing a small amount of patchy and cord-like shadows. One of them had no abnormality on admission but had pulmonary lesions and migratory phenomenon after admission.@*CONCLUSIONS@#The patients with Omicron variant tend to be young people and have milder clinical symptoms, but the viral load is high and the infectiveness is strong. Therefore, the timely identification and effective isolation and control for asymptomatic infections and confirmed patients with mild symptoms are extremely important. In terms of epidemic prevention and control, the government still needs to strengthen the risk control of overseas input, adhere to normalized epidemic prevention and control measures, to effectively control the source of infection, cut off the route of transmission, and protect vulnerable people.

Retrospective and cost-effective analysis of the result of Changsha Municipal Public Welfare Program by Noninvasive Prenatal Testing / 中华医学遗传学杂志

OBJECTIVE@#To assess the practical and health economical values of non-invasive prenatal test (NIPT) in Changsha Municipal Public Welfare Program.@*METHODS@#A retrospective analysis was carried out on 149 165 women undergoing NIPT test from April 9, 2018 to December 31, 2019. For pregnant women with high risks, invasive prenatal diagnosis and follow-up of pregnancy outcome were conducted. The cost-benefit of NIPT for Down syndrome was analyzed.@*RESULTS@#NIPT was carried out for 149 165 pregnant women and succeeded in 148 749 cases (99.72%), for which outcome were available in 148 538 (99.86%). 90% of pregnant women from the region accepted the screening with NIPT. 415 (0.27%) were diagnosed as high risk. Among these, 381 (91.81%) accepted amniocentesis, which led to the diagnosis of 212 cases of trisomy 21 (PPV=85.14%), 41 cases with trisomy 18 (PPV=48.81%) and 10 cases with trisomy 13 (PPV=20.83%). The sensitivity and specificity of NIPT for trisomy 21, trisomy 18 and trisomy 13 were (97.70%, 99.98%), (97.62%, 9.97%) and (100%, 99.97%), respectively. In addition, 213 and 30 cases were diagnosed with sex chromosomal aneuploidies (PPV=46.2%) and other autosomal anomalies (PPV=16.57%), respectively. For Down syndrome screening, the cost and benefit of the project was 120.79 million yuan and 1,056.95 million yuan, respectively. The cost-benefit ratio was 1: 8.75, and safety index was 0.0035.@*CONCLUSION@#NIPT is a highly accurate screening test for trisomy 21, which was followed by trisomy 18 and sex chromosomal aneuploidies, while it was less accurate for other autosomal aneuploidies. The application of NIPT screening has a high health economical value.

Economic burden of Down syndrome patients and psychological and social discrimination to female caregivers in Changsha, China / 中华医学遗传学杂志

OBJECTIVE@#To estimate the social and economic burden of Downs syndrome for patients and their families residing in Changsha, China.@*METHODS@#An 160-item self-administered questionnaire was designed and distributed to the primary caregivers of the patients in March 2020. A total of 81 eligible participants had completed the questionnaire, among which 20 were excluded for incomplete data. A patient perspective was taken to estimate the economic burden of the disease. The social impact of the disease on the patient's family was evaluated through questions adapted from the Stanford Psychological Wellbeing (PWB) Scale.@*RESULTS@#The estimated life-course cost of a Downs syndrome patient in Changsha is 4 985 659 RMB, with the patient and caregiver's loss of income taking the greater proportion. In addition, as the majority of the patients' primary caregivers, female caregivers experienced not only considerable financial hardship caused by the care provision, but also a significant amount of psychological pressure and social discrimination.@*CONCLUSION@#Increased level of social welfare for the patients and social support for their female caregivers are essential for reducing economic burden and improving their quality of life in the area. In addition, prenatal screening and diagnosis for Downs syndrome are important for reducing both the social and economic burden of the disease by preventing its occurrence.

Epidemiological and clinical features of 291 cases with coronavirus disease 2019 in areas adjacent to Hubei, China: a double-center observational study

BackgroundThe clinical outcomes of COVID-19 patients in Hubei and other areas are different. We aim to investigate the epidemiological and clinical characteristics of patient with COVID-19 in Hunan which is adjacent to Hubei. MethodsIn this double-center, observational study, we recruited all consecutive patients with laboratory confirmed COVID-19 from January 23 to February 14, 2020 in two designated hospitals in Hunan province, China. Epidemiological and clinical data from patients electronic medical records were collected and compared between mild, moderate and severe/critical group in detail. Clinical outcomes were followed up to February 20, 2020. Findings291 patients with COVID-19 were categorized into mild group (10.0%), moderate group (72.8%) and severe/critical group (17.2%). The median age of all patients was 46 years (49.8% were male). 86.6% patients had an indirect exposure history. The proportion of patients that had been to Wuhan in severe/critical group (48.0% vs 17.2%, p=0.006) and moderate group (43.4% vs 17.2%, p=0.007) were higher than mild group. Fever (68.7%), cough (60.5%), and fatigue (31.6%) were common symptoms especially for severe and critical patients. Typical lung imaging finding were bilateral and unilateral ground glass opacity or consolidation. Leukopenia, lymphopenia and eosinopenia occurred in 36.1%, 22.7% and 50.2% patients respectively. Increased fibrinogen was detected in 45 of 58 (77.6%) patients with available results. 29 of 44 (65.9%) or 22 of 40 (55.0%) patients were positive in Mycoplasma pneumonia or Chlamydia pneumonia antibody test respectively. Compared with mild or moderate group, severe/critical group had a relative higher level of neutrophil, Neutrophil-to-Lymphocyte Ratio, h-CRP, ESR, CK, CK-MB, LDH, D-dimer, and a lower level of lymphocyte, eosinophils, platelet, HDL and sodium (all p<0.01). Most patients received antiviral therapy and Chinese Medicine therapy. As of February 20, 2020, 159 (54.6%) patients were discharged and 2 (0.7%) patients died during hospitalization. The median length of hospital stay in discharged patients was 12 days (IQR: 10-15). InterpretationThe epidemiological and clinical characteristics of COVID-19 patients in Hunan is different from patients in Wuhan. The proportion of patients that had been to Wuhan in severe/critical group and moderate group were higher than mild group. Laboratory and imaging examination can assist in the diagnosis and classification of COVID-19 patients.

Result of Sanger sequencing for newborn carriers of single heterozygous variants of GJB2 or SLC26A4 gene by genechip analysis / 中华医学遗传学杂志

OBJECTIVE@#To detect additional variants for newborn carriers of single heterozygous variants of the GJB2 or SLC26A4 gene by genechip analysis in Changsha area, and explore the variation spectrum of deafness-related genes in this region.@*METHODS@#For 462 newborns carrying single heterozygous variants of the GJB2 or SLC26A4 gene, all exons of the genes were subjected to Sanger sequencing. The pathogenicity of the variants was analyzed by database and literature search.@*RESULTS@#For 305 newborns carrying a heterozygous GJB2 variant, 143 (46.49%) were found to carry additional variants, including 29 (9.51%) with c.109G>A likely pathogenic variant, and 1 (6.48%) with c.551G>A pathogenic variant. Among 153 newborns carrying single heterozygous variant of the SLC26A4 gene, 2 (1.31%) were found with a c.281C>T variant, and 1 (0.65%) with a c.1547_1548ins pathogenic variant. Among 4 newborns simultaneously carrying GJB2 and SLC26A4 variants, two were found to carry c.109G>A and c.844T>C variants (clinical significance unknown), respectively.@*CONCLUSION@#For newborns carrying single heterozygous variants of the GJB2 or SLC26A4 gene by genechip analysis, the detection rate for other variants is quite high. Sanger sequencing can significantly improve the detection rate of high-risk newborns and enrich the variant spectrum of deafness genes.

Predictive role of clinical features in patients with coronavirus disease 2019 for severe disease / 中南大学学报(医学版)

OBJECTIVES@#Since the outbreak of coronavirus disease 2019 (COVID-19), it has spread rapidly in China and many other countries. The rapid increase in the number of cases has caused widespread panic among people and has become the main public health problem in the world. Severe patients often have difficult breathing and/or hypoxemia after 1 week of onset. A few critically ill patients may not only rapidly develop into acute respiratory distress syndrome, but also may cause coagulopathy, as well as multiple organs failure (such as heart, liver and kidney) or even death. This article is to analyze the predictive role of clinical features in patients with COVID-19 for severe disease, so as to help doctor monitor the severity-related features, restrain the disease progress, and provide a reference for improvement of medical treatment.@*METHODS@#The clinical data of 208 patients with COVID-19 who were isolated and treated in Changsha Public Health Treatment Center from January 17, 2020 to March 14, 2020 were collected. All patients were the mild and ordinary adult patients on admission, including 105 males and 103 females from 19 to 84 (median age 44) years old. According to the "Program for the diagnosis and treatment of novel coronavirus (COVID-19) infected pneumonia (Trial version 7)" issued by the General Office of National Health Committee and Office of State Administration of Traditional Chinese Medicine as the diagnostic and typing criteria. According to progression from mild to severe disease during hospitalization, the patients were divided into a mild group (=183) and a severe transformation group (=25). The clinical features such as age, underlying disease, blood routine, coagulation function, blood biochemistry, oxygenation index, and so on were analyzed. Among them, laboratory tests included white blood cell (WBC), lymphocytes (LYM), neutrophil (NEU), hemoglobin (Hb), platelet (PLT), prothrombin time (PT), plasma fibrinogen (Fib), activated partial prothrombin time (APTT), thrombin time (TT), -dimer, total bilirubin (TBIL), albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), serum creatinine (Cr), creatine kinase (CK), creatine kinase isoenzyme-MB (CK-MB), lactate dehydrogenase (LDH), C-reactive protein (CRP), and oxygen partial pressure in arterial blood. Partial pressure of oxygen in arterial blood/fractional concentration of inspiratory oxygen (PaO/FiO) was calculated. The variables with statistical significance were analyzed by logistic regression analysis.@*RESULTS@#Patients in the severe transformation group had more combined underlying diseases than those in the mild group (<0.05). From the perspective of disease distribution, patients in the severe transformation group had more combined hypertension (<0.05). In the severe transformation group, PT was significantly longer, the levels of Fib, ALT, AST, CK, LDH, and CRP were significantly higher than those in the mild group (<0.05 or <0.001), while LYM, ALB, and PaO/FiO were significantly lower than those in the mild group (<0.05 or <0.001). Logistic regression analysis was performed on clinical features with statistically significant differences. Combined with hypertension, LYM, PT, Fib, ALB, ALT, AST, CK, LDH, and CRP as independent variables, and having severe disease or not was the dependent variable. The results show that combined hypertension, decreased LYM, longer PT, and increased CK level were independent risk factors that affected the severity of COVID-19 (<0.05).@*CONCLUSIONS@#The patients with mild COVID-19 who are apt to develop severe diseases may be related to combined hypertension, decreased LYM, and longer PT, and increased CK level. For the mild patients with these clinical features, early intervention may effectively prevent the progression to severe diseases.

Mental health status of patients with coronavirus disease 2019 in Changsha / 中南大学学报(医学版)

OBJECTIVES@#The epidemic of coronavirus disease 2019 (COVID-19) brought psychological stress to the public, especially to patients. This study aims to investigate the mental health of patients with COVID-19 in Changsha.@*METHODS@#We took cross-section investigation for the mental health of 112 patients with COVID-19 via questionnaires. Mann-Whitney test, Chi-square test, and Fisher's exact test were performed to compare general and clinical data between the slight-ordinary patients and severe patients. Single sample -tests were used to compare the difference between the factor scores of the Symptom Check-List 90 (SCL-90) in COVID-19 patients with the norm of 2015 and factor scores of SCL-90 in patients with the severe acute respiratory syndrome (SARS).@*RESULTS@#The obsessive-compulsive, depression, sleep and eating disorders had the highest frequency among the positive symptoms of SCL-90 in patients with COVID-19 in Changsha. The factor scores of somatization, depression, anxiety, phobia anxiety, sleep and eating disorders in patients with COVID-19 were higher than those of the norm (≤0.001 or 0.05).@*CONCLUSIONS@#The levels of somatization, depression, anxiety, phobia anxiety, sleep and eating disorders in patients with COVID-19 in Changsha are higher than those of the norm. However, the mental health of slight-ordinary patients with COVID-19 is better than that of patients with SARS. It needs to provide targeting psychological interventions depending on the severity of patients.