A novel multi-component protein vaccine ECP001 containing a protein polypeptide antigen nPstS1 riching in T-cell epitopes showed good immunogenicity and protection in mice.

Tuberculosis (TB) is an infectious disease that seriously affects human health. Until now, the only anti-TB vaccine approved for use is the live attenuated Mycobacterium bovis (M. bovis) vaccine - BCG vaccine, but its protective efficacy is relatively low and does not provide satisfactory protection against TB in adults. Therefore, there is an urgent need for more effective vaccines to reduce the global TB epidemic. In this study, ESAT-6, CFP-10, two antigens full-length and the T-cell epitope polypeptide antigen of PstS1, named nPstS1, were selected to form one multi-component protein antigens, named ECP001, which include two types, one is a mixed protein antigen named ECP001m, the other is a fusion expression protein antigen named ECP001f, as candidates for protein subunit vaccines. were prepared by constructing one novel subunit vaccine by mixing or fusing the three proteins and combining them with aluminum hydroxide adjuvant, and the immunogenicity and protective properties of the vaccine was evaluated in mice. The results showed that ECP001 stimulated mice to produce high titre levels of IgG, IgG1 and IgG2a antibodies; meanwhile, high levels of IFN-γ and a broad range of specific cytokines were secreted by mouse splenocytes; in addition, ECP001 inhibited the proliferation of Mycobacterium tuberculosis in vitro with a capacity comparable to that of BCG. It can be concluded that ECP001 is a novel effective multicomponent subunit vaccine candidate with potential as BCG Initial Immunisation-ECP001 Booster Immunisation or therapeutic vaccine for M. tuberculosis infection.

Analysis on the Effect of Metformin Hydrochloride Combined with Insulin Pump for Gestational Diabetes Mellitus.

BACKGROUND: U To analyze the effect of metformin hydrochloride combined with insulin pump for gestational diabetes mellitus (GDM). METHODS: Overall, 216 patients with GDM in Zhangqiu Maternity and Child Care Hospital, Jinan, China from Aug 2018 to Dec 2020 were enrolled and randomized into research and control groups. Patients in the control group were treated with insulin pump, while those in the research group were treated with metformin hydrochloride combined with insulin pump. The clinical efficacy, blood glucose levels, serum Betatrophin, C reactive protein (CRP), Cystatin C (Cys-C), homocysteine (Hcy), adiponectin, tumor necrosis factor (TNF-α), interleukin-6 (IL-6) content, incidence of adverse pregnancy outcomes and incidence of adverse newborns of patients in the two groups were compared. RESULTS: After treatment, the total clinical efficiency of the research group was 84.26%, significantly higher than that of the control group (68.52%). The levels of FPG, 2hPG, HbAlc, serum Betatrophin, CRP, CysC, Hcy, adiponectin factors, TNF-α, and IL-6 in the research group were lower than those in the control group, with statistically significant differences (P<0.05). The overall incidence of adverse pregnancy outcomes was 10.19% in the research group, and 25.93% in the control group. The comparative differences between the two groups were statistically significant (P<0.05). The overall incidence of adverse newborns was 9.26% in the research group, and 21.30% in the control group. The comparative differences between the two groups were statistically significant as well (P<0.05). CONCLUSION: Metformin hydrochloride combined with insulin pump for GDM can significantly reduce blood glucose level, regulate serum protein factor levels, and improve adverse outcomes for mother and child, which deserves clinical promotion.

A newly identified linear epitope on non-RBD region of SARS-CoV-2 spike protein improves the serological detection rate of COVID-19 patients.

BACKGROUND: Serological test is helpful in confirming and tracking infectious diseases in large population with the advantage of fast and convenience. Using the specific epitope peptides identified from the whole antigen as the detection antigen is sensitive and relatively economical. The development of epitope peptide-based detection kits for COVID-19 patients requires comprehensive information about epitope peptides. But the data on B cell epitope of SARS-CoV-2 spike protein is still limited. More importantly, there is a lack of serological data on the peptides in the population. In this study, we aimed to identify the B cell epitope peptides of spike protein and detect the reactivity in serum samples, for further providing data support for their subsequent serological applications. RESULTS: Two B cell linear epitopes, P104 and P82, located in non-RBD region of SARS-CoV-2 S protein were identified by indirect ELISA screening of an overlapping peptide library of the S protein with COVID-19 patients' convalescent serum. And the peptides were verified by testing with 165 serum samples. P104 has not been reported previously; P82 is contained in peptide S21P2 reported before. The positive reaction rates of epitope peptides S14P5 and S21P2, the two non-RBD region epitopes identified by Poh et al., and P82 and P104 were 77.0%, 73.9%, 61.2% and 30.3%, respectively, for 165 convalescent sera, including 30 asymptomatic patients. Although P104 had the lowest positive rate for total patients (30.3%), it exhibited slight advantage for detection of asymptomatic infections (36.7%). Combination of epitopes significantly improved the positive reaction rate. Among all combination patterns, (S14P5 + S21P2 + P104) pattern exhibited the highest positive reaction rate for all patients (92.7%), as well as for asymptomatic infections (86.7%), confirming the feasibility of P104 as supplementary antigen for serological detection. In addition, we analyzed the correlation between epitopes with neutralizing antibody, but only S14P5 had a medium positive correlation with neutralizing antibody titre (rs = 0.510, P < 0.01). CONCLUSION: Our research proved that epitopes on non-RBD region are of value in serological detection especially when combination more than one epitope, thus providing serological reaction information about the four epitopes, which has valuable references for their usage.

[A case report of lymphomatoid granulomatosis and review of the literature].

To explore the clinical manifestation of lymphomatoid granulomatosis (LG) and the early diagnosis. Retrospective analyses of the clinical features of LG and pathology features by open lung biopsies were conducted. The patient was a 42-year-old female with irregular fever, and her chest X-ray and computed tomography showed nodules with cavity and pleural effusion. Open lung biopsy proved LG. LG is seldom seen in clinic. Open lung biopsy is very important for pathology diagnosis. Early diagnosis and treatment are the key to improving survival in these patients. The therapeutic effect is good.

[Clinical feature analysis of 190 patients with anti-neutrophil cytoplasmic antibodies associated vasculitis].

OBJECTIVE: To explore the clinical features and disease spectrums for ANCA (anti-neutrophil cytoplasmic antibodies)-associated vasculitis (AAV) and to improve its cognition. METHODS: Clinical features of 190 cases of patients with AAV hospitalized from 1998 to 2008 were reviewed retrospectively. According to the result of ANCA test, the patients were divided into two groups, cytoplasmic ANCA (C-ANCA) positive and perinuclear ANCA (P-ANCA) positive. The authors compared the differences of disease spectrums, clinical manifestations and laboratory tests between two groups. The relative mortality factors were also analyzed. RESULTS: The authors studied 92 males and 98 females with an age range of 8 - 89 (59 +/- 18) years old. There were 156 cases aged 40 - 80 years old (82.1%) and 162 patients (85.3%) were of primary AAV including 146 cases of P-ANCA positive and 16 cases of C-ANCA positive. There were 28 patients with secondary AAV including 18 cases of connective tissue disease, 7 cases of propylthiouracil induction, 1 case each of idiopathic thrombocytopenic purpura, lung cancer and endometrial carcinoma. There were 25 cases of P-ANCA positive and 3 cases of C-ANCA positive in secondary AAV. There were 171 cases (90.0%) in P-ANCA group and 19 cases (10.0%) in C-ANCA group. The number of organ involvement was 2.53 in C-ANCA group and 1.92 in P-ANCA group. Gastrointestinal tract, joint, upper respiratory tract and ocular involvement was more in C-ANCA group than in P-ANCA group. Oral and auricular involvement was more in P-ANCA group than in C-ANCA group. The involvement difference was of statistic significance in upper respiratory tract, joint and eye (all P < 0.05). Renal and pulmonary involvement in P-ANCA group was similar to C-ANCA group. There were 3 mortality cases in C-ANCA group and 22 in P-ANCA group. Respiratory failure and multiple organ dysfunctions were relative mortality factors. CONCLUSIONS: AAV is observed in elders with multiple organ involvement. The number of organ involvement in C-ANCA group is more than that in P-ANCA group. P-ANCA positive patients are more than c-ANCA patients. The disease spectrum is different in these two groups. Secondary AAV is more in P-ANCA group than in C-ANCA group. Clinical manifestations, laboratory tests and type of ANCA are helpful for the diagnosis of AAV.

[Retrospective analysis of three cases of pulmonary mucormycosis].

OBJECTIVE: To describe the clinical characteristics of pulmonary mucormycosis and to evaluate the approaches to its diagnosis and treatment. METHODS: Three cases of pulmonary mucormycosis were successfully diagnosed by histopathologic examination of infected tissues obtained by fiberoptic bronchoscopy in this hospital. The clinical features of the cases were analyzed and the literature reviewed. RESULTS: Three patients were all farmers and two of them had had diabetic ketoacidosis. The first patient died from massive hemoptysis one day after the diagnosis was confirmed. The second patient was cured by large doses of intravenous amphotericin B (total dosage 2 g). The third patient presented with right middle bronchial stenosis after right upper lobectomy because of squamous carcinoma, and was cured by amphotericin B (1.5 g) combined with interventional therapy under fiberoptic bronchoscopy. The two patients were followed for 0.5 - 1 year without relapse. CONCLUSIONS: The mortality of pulmonary mucormycosis is high. Fiberoptic bronchoscopy is a useful diagnostic method for histopathologic examination. Successful treatment of pulmonary mucormycosis includes early diagnosis, control of underlying diseases and surgical intervention of isolated lesions combined with large dosage of amphotericin B.