Sterilizing immunity against SARS-CoV-2 in hamsters conferred by a novel recombinant subunit vaccine

A safe and effective SARS-CoV-2 vaccine is essential to avert the on-going COVID-19 pandemic. Here, we developed a subunit vaccine, which is comprised of CHO-expressed spike ectodomain protein (StriFK) and nitrogen bisphosphonates-modified zinc-aluminum hybrid adjuvant (FH002C). This vaccine candidate rapidly elicited the robust humoral response, Th1/Th2 balanced helper CD4 T cell and CD8 T cell immune response in animal models. In mice, hamsters, and non-human primates, 2-shot and 3-shot immunization of StriFK-FH002C generated 28- to 38-fold and 47- to 269-fold higher neutralizing antibody titers than the human COVID-19 convalescent plasmas, respectively. More importantly, the StriFK-FH002C immunization conferred sterilizing immunity to prevent SARS-CoV-2 infection and transmission, which also protected animals from virus-induced weight loss, COVID-19-like symptoms, and pneumonia in hamsters. Vaccine-induced neutralizing and cell-based receptor-blocking antibody titers correlated well with protective efficacy in hamsters, suggesting vaccine-elicited protection is immune-associated. The StriFK-FH002C provided a promising SARS-CoV-2 vaccine candidate for further clinical evaluation.

Virus-free and live-cell visualizing SARS-CoV-2 cell entry for studies of neutralizing antibodies and compound inhibitors

The ongoing COVID-19 pandemic, caused by SARS-CoV-2 infection, has resulted in hundreds of thousands of deaths. Cellular entry of SARS-CoV-2, which is mediated by the viral spike protein and host ACE2 receptor, is an essential target for the development of vaccines, therapeutic antibodies, and drugs. Using a mammalian cell expression system, we generated a recombinant fluorescent protein (Gamillus)-fused SARS-CoV-2 spike trimer (STG) to probe the viral entry process. In ACE2-expressing cells, we found that the STG probe has excellent performance in the live-cell visualization of receptor binding, cellular uptake, and intracellular trafficking of SARS-CoV-2 under virus-free conditions. The new system allows quantitative analyses of the inhibition potentials and detailed influence of COVID-19-convalescent human plasmas, neutralizing antibodies and compounds, providing a versatile tool for high-throughput screening and phenotypic characterization of SARS-CoV-2 entry inhibitors. This approach may also be adapted to develop a viral entry visualization system for other viruses.

Application of a novel nanoemulsion adjuvant for rabies vaccine which stabilizes a Krebs cycle intermediate (SDH) in an animal model.

Rabies is the most lethal zoonotic, vaccine-preventable viral disease in the world. Its treatment is complicated by insufficient vaccine supply and the requirement for four to five repeated injections, as commercially available inactivated rabies lack adjuvant and have low immunogenicity. In this study, we focused on the role of a Krebs cycle intermediate, succinate dehydrogenase (SDH), in the innate immune response to cytokine production. We formulated a novel nanoemulsion adjuvant, Golden03, which stabilizes mouse SDH activity and contains more coenzyme Q10 and succinic acid than the classic MF59 adjuvant. Mice were immunized on days 1, 3, and 7, with seroconversion rate results suggesting that Golden03 significantly enhanced vaccine-stimulated antibody production against the rabies virus. Neutralizing antibody concentration testing by RFFIT indicated that treatment with Golden03 could result in antibody levels of up to 0.74 IU/mL 5 days post infection (DPI). ELISPOT for IFN-γ in mouse spleen cells showed that Golden03 enhanced immune responses at 14 DPI, inducing a rapid and powerful cellular response compared to the control group. Furthermore, the Vaccine-Golden03 group displayed no obvious weight loss or death after intracranial injection with CVS-11. An additional advantage is that Golden03 allowed for a three-quarter reduction in dose, while maintaining its efficacy and rapid stimulation effect. We suggest that Golden03 could be developed as a potential adjuvant for use in human rabies vaccine.

Laparoscopic transabdominal ultra-low anastomosis for rectal cancer: experience of 54 cases / 中国肿瘤临床

Objectives: To evaluate the safety and feasibility of ultra-low anastomosis for anal preservation in laparoscopic rectal can-cer surgery. Methods: The clinical data of 54 patients with low rectal cancer admitted to The Affiliated Hospital of Southwest Medical University from July 2014 to June 2017 were retrospectively analyzed. The short-term effect and complications were analyzed. Results:All patients underwent successful operations; conversion to laparotomy or death was not observed in any of the patients. The mean operative time was (165 ± 31) minutes, and the intraoperative bleeding volume was (12 ± 5) mL. There was no prophylactic ileostomy in all patients. Postoperative anastomotic bleeding and anastomotic leakage occurred in 2 and 3 cases, respectively; these complica-tions were managed with conservative treatment. Postoperative urination and sexual functions of the patients remained good, and most patients were satisfied with their anal function 1 year post-operation. No local recurrences or deaths were noted after follow-up for more than 2 years. However, liver metastases were detected in 3 patients 1 year post-surgery. Conclusions: Laparoscopic transab-dominal ultra-low anastomosis for rectal cancer has a good short-term effect; however, the long-term effect remains to be evaluated.

Clinical value of intraoperative interorganizational targeted injection chemotherapy for Dixon operation of advanced rectal cancer / 中国医师杂志

Objective To explore the clinical value of intraoperative interorganizational targeted injection chemotherapy (IITIC) in Dixon operation of advanced rectal cancer (ARC).Methods From June 2013 to December 2013,53 patients who suffered from ARC and were treated by operation in our hospital were divided into group A and group B randomly.29 patients in group A were carried out Dixon operation and IITIC,while 24 patients in group B were carried out Dixon operation only.Serum levels of tumor necrosis factoroα (TNF-ot),carcinoembryonic antigen (CEA) and carbohydrate antigen 242 (CA242) were measured and compared for all the patients in perioperative period.Also,Serum levels of white blood cell (WBC),platelet (PLT),alanine aminotransferase (ALT),aspartate aminotransferase (AST) and creatinine (Cr) were measured and compared for all the patients in perioperative period.Postoperative anastomotic fistula,intra-abdominal hemorrhage,intra-abdominal abscess and death were observed and compared between group A and group B.Postoperative follow-up and survival analysis were carried out for patients in both groups.Results The serum levels of TNF-α,CEA and CA242 at each time point were significantly different both in group A and group B (P ＜ 0.05).Furthermore,The serum levels of TNF-α and CA242 were statistically different between group A and group B (P ＜ 0.05),while there was no statistically significant difference in the serum levels of CEA (P ＞ 0.05).The serum levels of WBC,ALT,AST and Cr were not statistically significant difference between group A and group B (P ＞ 0.05),while the serum levels of PLT were statistically significant difference (P ＜ 0.05).All of the 53 patients were not encountered anastomotic fistula,intra-abdominal hemorrhage,intra-abdominal abscess and death.According to survival analysis,the postoperative1-,2-and 3-year cumulative survival rates of the patients in group A were 93.1％,85.9％ and 71.1％,respectively,while those of the patients in group B were 91.5％,78.4％ and 61.0％,respectively.The median survival times of the Patients in group A and group B were 40.0 months and 39.0 months,respectively,the difference was not statistical significant (P ＞ 0.05).Conclusions It is safe and feasible to carry out IITIC in Dixon operation for ARC.IITIC can increase the treatment effect to operation of ARC,which also can improve patients' prognosis.

Clinical analysis of colorectal cancer combined with active tuberculosis / 肿瘤研究与临床

Objective To explore the treatment methods for colorectal cancer patients combined with active tuberculosis. Methods The clinical data of 8 cases of colorectal cancer combined with active tuberculosis from September 2011 to January 2017 in the Affiliated Hospital of Southwest Medical University were analyzed retrospectively. Results All the patients received tumor radical resection after given intensive anti-tuberculotherapy for 2 to 3 weeks. From the second day after surgery, isonicotinyl hydrazide was done through intravenous infusion. When gastrointestinal function was restored, the preoperative anti-tuberculosis treatment was reused. After 2 mouths, consolidation therapy was done. There were 3 cases of complicating pneumonia and 1 case of complicating anastomotic fistula after surgery.Six courses of FOLFOX4 chemotherapy combined with anti-tuberculosis consolidation treatment were carried out for all the patients. No tuberculosis dissemination or death case occurred. Conclusions After given anti-tuberculotherapy for 2 to 3 weeks, the colorectal cancer patients combined with active tuberculosis could receive tumor radical resection. It is safe and feasible to carry out assisted chemotherapy for tumor during the consolidation anti-tuberculotherapy.

Clinical value of combined detection of serum CD4 + T cells and CD8 + T cells for advanced gastric cancer / 中国医师杂志

Objective To explore the clinical value of combined detection of serum CD4 + T cells and CD8 + T cells for advanced gastric cancer (AGC).Methods Serum levels of CI4 + T cells and CD8 + T cells were measured by flow cytometry and compared in 20 patients with AGC (experimental group) and 20 healthy adults (control group).Also,serum levels of CD4 + T cells and CD8 + T cells were measured by flow cytometry and compared before and after surgical treatment in the patients of experimental group.Results The serum levels of CD4 + T cells were decreased and CD8 + T cells were increased in patients with AGC.However,the serum levels of CD4 +T cells were increased and CD8 +T cells were decreased after surgical treatment (P ＜ 0.05).Conclusions The serum levels of CD4 + T cells and CD8 + T cell help to assess the immune status of patients with AGC,which contributes to the illness monitoring for AGC.

Clinical value of combined detection of serum CA724, CEA and TNF-α for advanced gastric cancer / 中国医师杂志

Objective To explore the clinical value of combined detection of serum carbohydrate antigen 724 (CA724),carcinoembryonic antigen (CEA),and tumor necrosis factor-α (TNF-α) for the diagnosis,assessment of curative effect,and illness monitoring for advanced gastric cancer (AGC).Methods Serum levels of CA724,CEA and TNF-α were measured by the methods of chemiluminescence and compared in 20 patients with AGC (Group A),20 patients with benign gastric disease (Group B),and 20 healthy adults (Group C).Also,serum levels of CA724,CEA and TNF-α in peripheral blood as well as in portal vein were measured and compared before and after surgical treatment in patients of group A.Results The serum levels of CA724,CEA and TNF-α in patients of group A were significantly higher than groups B and C (P ＜ 0.05).In addition,the serum levels of CA724,CEA and TNF-α in patients of group A were decreased after surgical treatment and increased slightly after one month (P ＜ 0.05).Conclusions The serum levels of CA724,CEA and TNF-α in most patients of AGC are significantly elevated and the combined detection of serum CA724,CEA and TNF-α contributes to the diagnosis,assessment of curative effect,and illness monitoring for AGC.

Clinical value of gastric bare area for the prognosis of gastric fundus and cardia carcinoma / 肿瘤研究与临床

Objective To explore the clinical value of gastric bare area (GBA) for the prognosis of gastric fundus and cardia carcinoma.Methods The data of 82 patients with gastric fundus and cardia carcinoma from January 2010 to December 2011 were retrospectively analyzed.The patients were divided into group A (49 cases) with cancer cell invasion in GBA and group B (33 cases) without invasion in GBA.All the patients underwent D2 gastrectomy plus surgical resection of GBA and were treated by 6 cycles of postoperative FOLFOX-4 chemotherapy scheme.Postoperative follow-up and survival analysis were carried out for patients in both groups.Results According to survival analysis (Kaplan-Meier method),the postoperative 1-,2-and 3-year cumulative survival rates of the patients in group A were 91.8 ％,57.3 ％ and 29.0 ％,respectively,while those of the patients in group B were 93.9 ％,75.0 ％ and 48.2 ％,respectively.The median survival times of the patients in group A and group B were 27.0 months and 36.0 months,respectively,which was demonstrated existing statistical significance(X2 =4.972,P =0.026).Conclusions The prognosis of gastric fundus and cardia carcinoma patients with invasion in GBA by cancer cells is poor.Surgical resection of GBA may help to improve the prognosis of the patients with gastric fundus and cardia carcinoma.

Disinfection Methods for Dental Instruments and Their Dynamic Trends:An Investigation / 中华医院感染学杂志

OBJECTIVE To learn the disinfection and sterilization for dental instruments and to provide scientific basis for related regulations according to the scheme made by Beijing Center for Disease Prevention and Control.METHODS To investigate some dental medical units by adopting investigation form,inquirement,checking about the record for disinfection equipment including such items as air,the surface of used material,hands,etc.RESULTS Altogether 39 dental medical units including 9 hospitals,21 joint clinics and 9 private medical units were investigated with 96.11%,88.79%,and 70.97% qualified rates,respectively.CONCLUSIONS In private dental units the qualified rate for disfection is poor,disinfection instruments are short,and the professionals knowledge related to disfection is little.As a result,strengthening monitoring and guidance to prevent hospital infection should be carried out at once.

Problem in the Medical Humanistic Curriculum and the Counter-Measures / 中国医学伦理学

With the developmetn of the medical humanistic education,more and more problems appear.The casualness of the medical humanistic curriculum,the monotony of the method of the evaluation,the insufficiency of the content,the inadequacy of the quality of the teachers,and the poor effect of the education are the factors affecting the development of our medical humanistic education.Through comparison of the humanistic education home and abroad,we find the key to these problems are the innovation of the curriculum and evaluation.

Disinfection Effectiveness at Medical Care Units in Dongcheng District,Beijing in 2005 / 中华医院感染学杂志

OBJECTIVE To monitor disinfection effectiveness at medical care units in Dongcheng District,Beijing,and therefore,analyze the existing problems in the process and how to solve them.METHODS Air monitoring was conducted by means of plate vessel exposure,hands and article inspection by daubing,steamed pressure disinfection by biological-bacterial piece examination and the using disinfection liquid was examined by fixed suspended liquid tests from Jan to Nov 2005.RESULTS After monitoring and inspecting 23 hospitals,103 clinics,etc,the results showed the disinfection effectiveness was of significant variety.CONCLUSIONS Medical workers should be trained about knowledge related to disinfection and medical management and disinfection control should be strengthened.