The Study on Immunological Response of Long－term Release System hCG Microsphere in C_(57） Black Mouse

This paper describes the study of the immunological response of C57 Black mouse to hCG by multiple inoculations with hCG and single injection with a long-term release system of hCG/poly(lactide-co-glycolide) microsphere(hCG/PGLA).Three parameters including1)the dynamic variation of hCG antibody titres,2)the capacity of biological neutralization by hCG antibodies in vitro and in vivo,and3)assay of the binding affinity constants of hCG antibodies,are compared.The results showed that the single injection with hCG/PGLA was capable of producing high titres of anti-hCG antibodies.The analyses of three parameters of antisera from C57 Black mouse showed that the properties of the antisera elicited using a single injection with hCG/PGLA were generally similar to those of the antisera raised by the multiple inoculations with hCG,and concentration of the antibodies was directly proportional to hCG bioneutralization capacity. Meanwhile,all of these results suggest us that a further long-term release system of β-hCG/PGLA as a vaccine may substitute for conventional vaccine and it also provides a new convenient inoculative method for widespread clinical application and research of hCG vaccine and other vaccines.

The Study on Immuno-response and Antisera Properties of Recombinant β-subunit of Human Chorionic Gonadotropin in C57 Black Mouse

In this study, the immuno-response of recombinant hCG-β and natural hCGβ was comparatively investigated by using Freund's adjuvant. The results showed that, the properties and merits of the antibodies elicited by both kinds of hCG-β were similar. The antisera had high affinity for binding with hCG (Kαγβ≈5.86×108/mol/L, Kαβ≈8.18×108/mol/L), and were found to be effective in inhibiting the binding of 125I-hCG to receptors in rat testes. Results also indicated that, similar to the antisera induced by natural hCG-β, the recombinant hCG-β induced antisera had capacity of neutralizing the biological activities of hCG. Recombinant hCG-β could be used as an immunogen for contraceptive vaccine.

Microbiota regulation in constipation and colorectal cancer

The relevance of constipation to the development and progression of colorectal cancer(CRC)is currently a controversial issue.Studies have shown that changes in the composition of the gut microbiota,a condition known as ecological imbalance,are correlated with an increasing number of common human diseases,including CRC and constipation.CRC is the second leading cause of cancerrelated deaths worldwide,and constipation has been receiving widespread attention as a risk factor for CRC.Early colonoscopy screening of constipated patients,with regular follow-ups and timely intervention,can help detect early intestinal lesions and reduce the risks of developing colorectal polyps and CRC.As an important regulator of the intestinal microenvironment,the gut microbiota plays a critical role in the onset and progression of CRC.An increasing amount of evidence supports the thought that gut microbial composition and function are key determinants of CRC development and progression,with alterations inducing changes in the expression of host genes,metabolic regulation,and local and systemic immunological responses.Furthermore,constipation greatly affects the composition of the gut microbiota,which in turn influences the susceptibility to intestinal diseases such as CRC.However,the crosstalk between the gut microbiota,constipation,and CRC is still unclear.

Intestinal-borne dermatoses significantly improved by oral application of Escherichia coli Nissle 1917

AIM: To evaluate the effect of oral Escherichia coli (E. coli) Nissle application on the outcome of intestinal-borne dermatoses.METHODS: In a randomized, controlled, non-blinded prospective clinical trial 82 patients with intestinal-borne facial dermatoses characterized by an erythematous papular-pustular rash were screened. At the initiation visit 37 patients entered the experimental arm and 20 patients constituted the control arm. All 57 patients were treated with a vegetarian diet and conventional topical therapy of the dermatoses with ointments containing tetracycline, steroids and retinoids. In the experimental arm patients received a one month therapy with oral E. coli Nissle at a maintenance dose of 2 capsules daily. The experimental group was compared to a non-treatment group only receiving the diet and topical therapy. The primary outcome parameter was improvement of the dermatoses, secondary parameters included life quality and adverse events. In addition the immunological reaction profile (IgA, interleucin-8 and interferon-α) was determined. Furthermore the changes of stool consistency and the microbiota composition over the time of intervention were recorded.RESULTS: Eighty-nine percent of the patients with acne, papular-pustular rosacea and seborrhoic dermatitis responded to E. coli Nissle therapy with significant amelioration or complete recovery in contrast to 56% in the control arm (P < 0.01). Accordingly, in the E. coli Nissle treated patients life quality improved significantly (P < 0.01), and adverse events were not recorded. The clinical improvement was associated with a significant increase of IgA levels to normal values in serum as well as suppression of the proinflammatory cytokine IL-8 (P < 0.01 for both parameters). In the E. coli Nissle treated group a shift towards a protective microbiota with predominance of bifidobacteria and lactobacteria (> 107 CFU/g stool) was observed in 79% and 63% of the patients, respectively (P < 0.01), compared to no change in the control group without E. coli Nissle. Moreover, the detection rate of a pathogenic flora dropped from 73% to 14 % of the patients in the experimental arm (P < 0.01) with no significant change in the control arm (accounting 80% before and 70% after the observation period, P > 0.05). Accordingly, stool consistency, color and smell normalized in the E. coli Nissle treated patients.CONCLUSION: E. coli Nissle protects the mucus barrier by overgrowth of a favorable gut microbiota with less immunoreactive potential which finally leads to clinical improvement of intestinal borne dermatoses.

Cryptosporidiosis-an overview

Apicomplexan protozoan parasites of the genus Cryptosporidium infect the gastrointestinal tract and lungs of a wide variety of animals, including humans. The majority of human infections are due to either Cryptosporidium hominis （C. hominis） and/or Cryptosporidium parvum （C. parvum）. The parasite has a complex life cycle that includes both asexual and sexual stages. While there are invasive free living stages, proliferation and differentiation take place within a unique parasitrophorous vacuole under the host cell brush border but outside the host cell cytoplasm. Infection is spread by environmentally resistant spores that primarily contaminate drinking water and occasionally food sources, which may cause significant outbreaks of diarrhea that generally lasts less than 2 w in immunocompetent individuals. In immunodeficient or immunosuppressed individuals, diarrhea may be copious and can result in significant morbidity and mortality, particularly in AIDS patients. Although diagnosis is relatively simple, effective drug treatment, particulary for infections in immunodeficient patients, has not been uniformly successful. This overview summarizes the species known to infect humans, aspects of the parasite life cycle, sources of infection, the pathophysiology of cryptosporidiosis, the immune response to infection, diagnosis, treatment and some aspects of cryptosporidiosis in China.

Transmembrane serine protease 2 and angiotensin-converting enzyme 2 anti-inflammatory receptors for COVID-19/inflammatory bowel diseases treatment

long-term,and relapsing inflammatory disorders.IBD may spontaneously grow in the colon,and in severe cases may result in tumor lesions such as invasive carcinoma in inflamed regions of the intestine.Recent epidemiological reports indicate that old age and underlying diseases such as IBD contribute to severity and mortality in patients with coronavirus disease 2019(COVID-19).Currently,the ongoing COVID-19 pandemic caused serious morbidity and mortality worldwide.It has also been shown that the transmembrane serine protease 2 is an essential factor for viral activation and viral engulfment.Generally,viral entry causes a'cytokine storm'that induces excessive generation of proinflammatory cytokines/chemokines including interleukin(IL)-6,IL-2,IL-7,tumor necrosis factor-α,and interferon-γ.Future research could concentrate on developing inflammatory immunological responses that are efficient to encounter COVID-19.Current analysis elucidates the role of inflammation and immune responses during IBD infection with COVID-19 and provides a list of possible targets for IBD-regulated therapies in particular.Data from clinical,in vitro,and in vivo studies were collected in English from PubMed,Google Scholar,Scopus,and the Cochrane library until May 2021.

Optimal Timing of Antiretroviral Therapy Initiation in Acquired Immunodeficiency Syndrome-Associated Toxoplasmic Encephalitis:A Prospective Observational Multicenter Study in China

Background:Toxoplasmic encephalitis(TE)is the most frequent cause of expansive brain lesions among patients with acquired immunodeficiency syndrome(AIDS).However,the optimal timing of antiretroviral therapy(ART)initiation in these patients remains controversial.This study aims to investigate the differences in outcomes of ART initiation at different times,in order to help clarify the treatment timing of AIDS-associated TE.Methods:This multicenter prospective observational study included 87 patients recruited from 11 research centers in China(from March 2019 to December 2022).Of the patients,38 were assigned to the early ART group(initiating ART within 2 weeks after anti-Toxoplasma treatment initiation),and the remaining 49 patients received deferred ART(initiating ART at least 2 weeks after anti-Toxoplasma treatment initiation).The main outcomes includedmortality and emergence of immune reconstitution inflammatory syndrome(IRIS).Human immunodeficiency virus(HIV)-1 viral load and CD4^(+)T-cell counts at weeks 24 and 48 were observed.Results:The number of deaths(1 vs.5,P=0.225)and incidence of IRIS(2.6%vs.0,P=0.437)were not significantly different between the early and deferred ART groups at week 48.Early ART initiation did not contribute significantly to HIV-1 viral load control(<50 copies/mL,n=8 vs.n=3 at week 24,P=0.142;n=7 vs.n=7 atweek 48,P=1.000).The median CD4^(+)T-cell counts between the two groups were not significantly different,either at week 24(155 vs.91 cells/mm^(3),P=0.837)or atweek 48(181 vs.146 cells/mm^(3),P=0.219).Conclusion:In patients with AIDS-associated TE,early ART initiation was not significantly different from deferred ART initiation in terms of incidence of mortality,IRIS,and HIV virological and immunological outcomes.Trial registration:This study was registered(registration number:ChiCTR1900021195)as one of 12 clinical trials under the title of a general project at the Chinese Clinical Trial Registry(chictr.gov)on February 1,2019.Enrollment for this study began inMarch 2019.