Effects of Lactobacillus paracasei N1115 on gut microbial imbalance and liver function in patients with hepatitis B-related cirrhosis

BACKGROUND Hepatitis B cirrhosis(HBC)is a chronic disease characterized by irreversible diffuse liver damage and aggravated by intestinal microbial imbalance and metabolic dysfunction.Although the relationship between certain single probiotics and HBC has been explored,the impact of the complex ready-to-eat Lactobacillus paracasei N1115(LP N1115)supplement on patients with HBC has not been determined.AIM To compare the changes in the microbiota,inflammatory factor levels,and liver function before and after probiotic treatment in HBC patients.METHODS This study included 160 HBC patients diagnosed at the General Hospital of Ningxia Medical University between October 2018 and December 2020.Patients were randomly divided into an intervention group that received LP N1115 supplementation and routine treatment and a control group that received routine treatment only.Fecal samples were collected at the onset and conclusion of the 12-wk intervention period.The structure of the intestinal microbiota and the levels of serological indicators,such as liver function and inflammatory factors,were assessed.RESULTS Following LP N1115 intervention,the intestinal microbial diversity significantly increased in the intervention group(P<0.05),and the structure of the intestinal microbiota was characterized by an increase in the proportions of probiotic microbes and a reduction in harmful bacteria.Additionally,the intervention group demonstrated notable improvements in liver function indices and significantly lower levels of inflammatory factors(P<0.05).CONCLUSION LP N1115 is a promising treatment for ameliorating intestinal microbial imbalance in HBC patients by modulating the structure of the intestinal microbiota,improving liver function,and reducing inflammatory factor levels.

Deciphering resistancemechanisms and novel strategies to overcome drug resistance in ovarian cancer:a comprehensive review

Ovarian cancer is among the most lethal gynecological cancers,primarily due to the lack of specific symptoms leading to an advanced-stage diagnosis and resistance to chemotherapy.Drug resistance(DR)poses the most significant challenge in treating patients with existing drugs.The Food and Drug Administration(FDA)has recently approved three new therapeutic drugs,including two poly(ADP-ribose)polymerase(PARP)inhibitors(olaparib and niraparib)and one vascular endothelial growth factor(VEGF)inhibitor(bevacizumab)for maintenance therapy.However,resistance to these new drugs has emerged.Therefore,understanding the mechanisms of DR and exploring new approaches to overcome them is crucial for effective management.In this review,we summarize the major molecular mechanisms of DR and discuss novel strategies to combat DR.

Circulating tumor cells and circulating tumor DNA in breast cancer diagnosis and monitoring

Liquid biopsy,including both circulating tumor cells and circulating tumor DNA,is becoming more popular as a diagnostic tool in the clinical management of breast cancer.Elevated concentrations of these biomarkers during cancer treatment may be used as markers for cancer progression as well as to understand the mechanisms underlying metastasis and treatment resistance.Thus,these circulating markers serve as tools for cancer assessing and monitoring through a simple,non-invasive blood draw.However,despite several study results currently noting a potential clinical impact of ctDNA mutation tracking,the method is not used clinically in cancer diagnosis among patients and more studies are required to confirm it.This review focuses on understanding circulating tumor biomarkers,especially in breast cancer.

草酸盐摄入量及个人习惯与肾结石风险的关系

肾结石是一种易复发的泌尿系统疾病。大多数肾结石是钙结石,通常由草酸钙或磷酸钙组成。尿液中可溶性钙、草酸盐、磷酸盐和柠檬酸盐过饱和是钙结石形成的基础。遗传、饮食、缺乏体力活动和个人习惯都会导致肾结石的形成。在这篇综述中,我们总结了肾结石风险与草酸盐摄入量和一些个人习惯(如吸烟、饮酒和吸毒)的关系。

Regulation of microRNA by hepatitis B virus infection and their possible association with control of innate immunity

Hepatitis B virus(HBV)chronically infects more than350 million people worldwide.HBV causes acute and chronic hepatitis,and is one of the major causes of cirrhosis and hepatocellular carcinoma.There exist complex interactions between HBV and the immune system including adaptive and innate immunity.Tolllike receptors(TLRs)and TLR-signaling pathways are important parts of the innate immune response in HBV infections.It is well known that TLR-ligands could suppress HBV replication and that TLRs play important roles in anti-viral defense.Previous immunological studies demonstrated that HBV e antigen(HBeAg)is more efficient at eliciting T-cell tolerance,including production of specific cytokines IL-2 and interferon gamma,than HBV core antigen.HBeAg downregulates cytokine production in hepatocytes by the inhibition of MAPK or NF-κB activation through the interaction with receptor-interacting serine/threonine protein kinase.MicroRNAs(miRNAs)are also able to regulate various biological processes such as the innate immune response.When the expressions of approximately 1000 miRNAs were compared between human hepatoma cells HepG2 and HepG2.2.15,which could produce HBV virion that infects chimpanzees,using real-time RT-PCR,we observed several different expression levels in miRNAs related to TLRs.Although we and others have shown that HBV modulates the host immune response,several of the miRNAs seem to be involved in the TLR signaling pathways.The possibility that alteration of these miRNAs during HBV infection might play a critical role in innate immunity against HBV infection should be considered.This article is intended to comprehensively review the association between HBV and innate immunity,and to discuss the role of miRNAs in the innate immune response to HBV infection.

Acaricidal activity of Cymbopogon citratus and Azadirachta indica against house dust mites

Objective:To examine the acaricidal effects of the essential oil of Cymbopogon citratits leaf extract(lemongrass)and ethanolic Azadirachta indica leaf extract(neem)against house dust mites Dermatophagoides farinae(D.farinae)and Dermalophagoides pteronyssinus(D.pteronyssinus).Methods:Twenty-five adults mites were placed onto treated filter paper that is soaked with plant extract and been tested at different concentrations(50.00%,25.00%,12.50%,6.25%and 3.13%)and exposure times(24hrs,48hrs,72hrs and 96 hrs).All treatments were replicated 7 times,and the experiment repeated once.The topical and contact activities of the two herbs were investigated.Results:Mortalities from lemongrass extract were higher than neem for both topical and contact activities.At 50%concentration,both 24 hrs topical and contact exposures to lemongrass resulted in more than 91%mortalities for both species of inites.At the same concentration and exposure time,neem resulted in topical mortalities of 40.3%and 15.7%against D.pteronyssinus and D.farinae respectively;contact mortalities were 8.0%and 8.9%against the 2 mites,respectively.There was no difference in topical mortalities of D.pteronyssinus from exposure to concentrations oflemongrass and neem up to 12.50%;lemongrass was more effective than neem at the higher concentrations.Conclusions:Generally,topical mortalities of D.farinae due to lemongrass are higher than that due to neem.Contact mortalities of lemongrass are always higher that neem against both species of mites.

Knowledge,attitude,and practices related to cutaneous leishmaniasis in an endemic focus of cutaneous leishmaniasis,Southern Iran

Objective:To assess knowledge,attitudes,and practices(KAP)of inhabitants of an endemic area it)Fars province toward cutaneous leishmaniasis(CI).Methods:the study was carried out in Lapui district in Fars province,south of Iran,one of the most important foci of CL in this province.Sample size(237 residents)was calculated based on population.House-to-house survey was done to collect the data regarding knowledge,attitudes,and practices of the inhabitants.The head of each household was interviewed by a trained staff to assess his/her KAP related to CL.A semi-structured KAP questionnaire was used for data collection.Results:Mean age of participants was 39 and more titan half of the respondents were in the age group of 31-40.Males constituted 172(72.5%)of subjects.Most of the respondents(84.3%)were literate.The majority of the study poulation(83%)had heard about SalaJc(local name for CL)and most of these respondents(91%)were aware that CL is presented with a cutaneous lesion.Nearly two-third of the participants(63.5%)stated the bite of mosquito(not specifically sandflies)for CL transmission.The respondents'attitude regarding the treatment of CL was not satisfactory since Only 48%believed that CL can be treated by medicine.A noticeable proportion of respondents(21%)believed in indigenous medicine for the treatment of CL.A small proportion of respondents(14%)stated that traditional healers are good at treating this disease.More than two-third(69%)of respondents believed that the disease is preventable although most of interviewees did not know about preventive measures.Conclusions:In this study,insufficient knowledge of community about infection nature,vector,transmission mode and preventive measures of CL,highlights the needs for a health education initiative to enhance the awareness of people about CL.This would improve inhabitants'contribution in control program of CL in this area.

Effect of tranexamic acid on the treatment of patients with upper gastrointestinal bleeding: A double-blinded randomized controlled clinical trial

Objective:To determine the efficacy of tranexamic acid(TXA)in the management of acute upper gastrointestinal(GI)bleeding.Methods:A total of 70 patients with acute upper GI bleeding were included in this double-blinded randomized controlled clinical trial from September 2018 to December 2018.Patients were divided into the control group(received fluid therapy and intravenous infusion of pantoprazole,35 cases)and the TXA group(received intravenous TXA besides the treatment of control group,35 cases).Rebleeding,admission duration,and need for blood transfusion were compared between the two groups.Results:Fifteen patients(42.9%)in the TXA group and 10 patients(28.6%)in the control group stayed in hospital for more than 3 days during their admission(P=0.21).Rebleeding occurred in 8 patients(22.9%)and 5 patients(14.3%)of the TXA group and the control group,respectively(P=0.35).More patients in the TXA group(21 cases,60%)received blood transfusion than the control group(8 cases,22.9%)(P=0.02).Conclusions:TXA did not improve the outcome of patients with acute upper GI bleeding.

Immunodiagnosis of human hydatid disease: Where do we stand?

Cystic echinococcosis(CE) is a zoonotic parasitic infection caused by the larval stage of Echinococcus granulosus. Diagnosis of CE mainly relies on a combination of serological testing along with imaging approaches. A variety of serological methods, mainly based on hydatid cyst fluid, antigen B(Ag B) and antigen 5, have been developed and used for immunodiagnosis of CE, yet their performances are not satisfactory. Although utilizing of recombinant or synthetic antigens, improved the performance of serological tests, it has not applicably overcome the problem of low sensitivity and cross reactivity, seen in the diagnosis of CE. Performances of immunodiagnostic tests based on Ag B subunits are promising. The 8 k Da subunit of Ag B is the most studied antigen in native, synthetic or recombinant form for diagnosis of CE. From the 5 subunits of Ag B, antigen B8/1 and B8/2 provided the highest diagnostic sensitivity and specificity. Moreover, detecting of specific antibodies of Ig G subclasses has improved the efficacy of immunodiagnostic tests. Among the Ig G subclasses, both Ig G2 and Ig G4 are considered as good markers for diagnosis and Ig G4 as a suitable marker for follow up of the patients. In this review an overview of immunodiagnostic methods, related antigens and their performances in the diagnosis of CE are given. The paper highlights pitfall and challenges in the serological diagnosis of CE. Moreover, limitation of currently available immunodiagnostic tests and the most recent development in the designing and application of serological assays for diagnosis of CE in human are addressed.

Association between community-acquired pneumonia and platelet indices: A case-control study

Objective:To examine whether the platelet index would be applicable for the diagnosis of community-acquired pneumonia(CAP).Methods:In this study,64 CAP patients(the case group)and 68 healthy children(the control group)were included from 2017 to 2018.Baseline variables were recorded including total white blood cells,neutrophils,lymphocytes,red blood cells,platelet,mean platelet volume,platelet distribution width,erythrocyte sedimentation rate,and C-reactive protein,and compared between the case group and the control group.The cutoff value,sensitivity,and specificity of neutrophil-to-lymphocyte ratio,platelet,neutrophils,lymphocytes,and platelet larger cell ratio were calculated by receiver-operating characteristic curves.Results:The median platelet count of the case group and the control group were(411.09±67.40)mm3 and(334.48±78.15)mm3,respectively(P=0.000).The median neutrophil count of the case group was higher than that of the control group,while the lymphocyte level of the case group was lower.Differences in other variables including the mean platelet volume,platelet distribution width,C-reactive protein,and erythrocyte sedimentation rate were not statistically significant between the two groups.Conclusions:Due to the different levels of platelet,neutrophil and lymphocyte indices in the case and the control group,these indices can be used simultaneously for the diagnosis of CAP.

Environmental characteristics of anopheline mosquito larval habitats in a malaria endemic area in Iran

Objective:To determine the effects of environmental parameters of lanal habitats on distribution and abundance of anopheline mosquitoes in Rudan county of Iran.Methods:This cross-sectional study was conducted during the mosquito breeding season from February 2010 to October 2011. The anopheline larvae were collected using the standard dipping method,the specimens were identified using a morphological-based key.Simultaneously with larvay collection,environmental parameters of the larval habitats including water current and turbidity,sunlight situation,and substrate type of habitats were recorded.Water samples were taken from breeding sites during lanal collection.Before collection of samples,the water temperature was measured.The water samples were analysed for turbidity,conductivity,total alkalinity,total dissolved solid.pH and ions including chloride,sulphate,calcium,and magnesium.Statistical correlation analysis and ANOVA test were used to analyze the association between environmental parameters and larval mosquito abundance.Results:In total 2 973 lanae of the genus Anopheles were collected from 25 larval habitats and identified using morphological characters.They comprised of six species: An.dthali(53.21%),An.stephensi(24.22%),An.culicifacies(14.06%),An.superpictus(4.07%),An. turkhudi(3.30%),and An.apoci(1.14%).The most abundant species was An.dthali which were collected from all of the study areas.Larvae of two malaria vectors.An.dthali and An.stephensi, co-existed and collected in a wide range of habitats with different physico-chemical parameters. The most common larval habitats were man-made sites such as sand mining pools with clean and still water.The anopheline mosquitoes also preferred permanent habitats in sunlight with sandy substrates.The results indicated that there was a significant relationship between mean physicochemical parameters such as water temperature,conductivity,total alkalinity,sulphate,chloride, and mosquito distribution and abundance.Conclusions:The results of this study showed a correlation between certain environmental parameters and mosquito lanae abundance,and these parameters should be considered in planning and implementing larval control programs.

Controversial issues regarding the roles of IL-10 and IFN-γ in active/inactive chronic hepatitis B

According to the important roles played by cytokines in induction of appropriate immune responses against hepatitis B virus(HBV),Dimitropoulou et al have examined the important cytokines in their patients.They showed that the serum levels of interleukin 10(IL-10)and interferon-γ(IFN-γ)were decreased in patients with HBeAg-negative chronic active hepatitis B compared with the inactive hepatitis B virus carriers(Dimitropoulou et al 2013).The controversy can be considered regarding the decreased serum levels of IFN-γin the HBeAg-negative chronic active hepatitis B patients.They concluded that subsequent to decreased expression of IFN-γ,the process of HBV proliferation led to liver diseases.Previous studies stated that HBV is not directly cytopathic for the infected hepatocytes and immune responses are the main reason for destruction of hepatocytes(Chisari et al,2010).Scientists believe that immune responses against HBV are stronger in active forms of chronic HBV infected patients than inactive forms(Zhang et al,2012).Therefore,the findings from Dimitropoulou et al may deserve further attention and discussion.Additionally,downregulation of IL-10 inchronically active hepatitis B infected patients has also confirmed our claim.IL-10 is an anti-inflammatory cytokine and its expression is increased in inactive forms in order to downregulate immune responses(Arababadi et al,2012).Thus,based on the results from Dimitropoulou et al,it can be concluded that increased immune responses in chronically active hepatitis B infected patients are related to declined expression of IL-10 and interestingly IFN-γis not involved in induction of immune responses in these patients.

Impact of Indoor Residual-Sprayed Deltamethrin on Different Surfaces in a Malaria Endemic Area in Balai Ringin, Sarawak

Malaria control programme utilizing indoor residual spraying of chemical insecticide is only effective if a high coverage of targeted area is achieved. The effectiveness of the residual spraying, on the other hand, relies on the efficacy and residual activity of the insecticides applied, which to a certain extent are influenced by the nature of the sprayed surfaces. The bioefficacy of indoor residual-sprayed deltamethrin wettable granule (WG) formulation for the control of malaria was compared with the current dose of deltamethrin wettable powder (WP) in malaria endemic areas in Balai Ringin, Sarawak. Doses of 20 mg/m2 WP (control), 20 mg/m2 WG, 30 mg/m2 WG and 40 mg/m2 WG were sprayed separately on different surfaces namely, wooden, rough-bamboo, smooth-bamboo and brick surfaces. Residual activity of WP and WG formulations was tested against lab-bred Anopheles maculatus using WHO standard procedure. Deltamethrin at 30 mg/m2 WG exhibited the highest sustainable level of effectiveness against An. maculatus (An. maculatus mortality was between 95% - 100%) up to week 60 post-spraying when sprayed on smooth- bamboo surface. These results indicated that 30 mg/m2 WG could be an ideal concentration for controlling malaria vector effectively up to 15 months of which long-lasting residual spraying was envisaged. The usual two spraying cycles per year with 20 mg/m2 deltamethrin WP could be replaced with 30 mg/m2 deltamethrin WG since the long residual activity was achieved by employing a single spraying only.

Nocturnal man biting habits of mosquito species in Serian, Sarawak, Malaysia

Knowledge of the composition and biting habits of mosquito associated with endemic areas is important in establishing sound vector control programmes and understanding the epidemiology of vector borne diseases. The biting activity cycle of several mosquito species in Serian, Sarawak was observed and described. Collections were carried out indoors and outdoors for 12 hours from 6.00 pm to 6.00 am using human landing catch techniques. A total of 7271 mosquitoes comprising 27 species belonging to sixgenera were collected. Mansonia bonneae (23.6%) was the predominant species caught in the study areas followed by Culex vishnui (22.3%), Culex pseudovishnui (19.6%) and Culex tritaenorhynchus (13.7%). A high rate of human biting activity by Ma. bonneae was detected during November but the activity was low during January.The biting activity of Ma.bonneae was found higher outdoor compared to indoorand peaked at 7.00 pm-8.00 pm.Cx.vishnui also exhibited similar biting activity peak while Anopheles letiferex-hibited biting activity peaked at 12.00 am-1.00 am.Cx.pseudovishnui showed biting patterns which were almost similar between indoor and outdoor activity and could be considered active throughout the 12 hour period.

Fauna and some biological characteristics of Anopheles mosquitoes(Diptera:Culicidae) in Kalaleh County,Golestan Province,northeast of Iran

Objective:To determine fauna and some ecological aspects of Anopheles mosquitoes in northeast of Iran.Methods:In this descriptive study,3 villages in Kalaleh County were selected in different geographical zones.Anopheles mosquitoes were collected biweekly from May to October using standard dipping method for larvae,and hand catch,total catch,artificial pit shelter as well as night-biting collections on human and animal baits for adults.Results:Totally 399 larvae and 2 602 adults of Anopheles mosquitoes were collected and identified as 2 species:Anopheles superpictus s.l.(An.superpictus s.l.) and Anopheles maculipennis s.l.The dominant species was An.superpictus s.l.(92.1%).Activity of these mosquitoes found to be started from middle of May and extended till September with two peaks of activity in July and August.Conclusions:An.superpictus s.l.as one of the main malaria vectors in Iran as well as some other parts of the world is the dominant species in the study area.This species has high potential for transmission and possibility of establishing a transmission cycle with low abundance.Other species,Anopheles maculipennis s.l.also has introduced as a malaria vector in northern parts of Iran.As this Anopheles is a complex species,genetic studies are recommended to determine the members of this complex in the study area.

Leishmania tropica: The comparison of two frequently-used methods of parasite load assay in vaccinated mice

Objective:To compare limiting dilution assay and real-time PCR methods in Leishmania tropica parasite load measurement in vaccinated mice.Methods:BALB/c mice were vaccinated by Leishmania tropica soluble Leishmania antigen or recombinant Leishmania tropica stressinducible protein-1 with/without adjuvant.After three vaccinations,mice were challenged by Leishmania tropica promastigotes.Two months after challenge,the draining lymph nodes of mice footpad were removed and parasite load was assayed by limiting dilution assay and real-time PCR methods.Limiting dilution assay was done by diluting tissue samples to extinction in a biphasic medium.For real-time PCR,DNA of the lymph nodes was extracted,equal dilutions of each sample were prepared and hot-start real-time PCR was done using appropriate primers.The data of the two methods were compared by appropriate statistical methods.Results:Both methods were able to measure different levels of parasite load in vaccinated/unvaccinated mice.In addition,wherever parasite load of a group was estimated high(or low)by one method,the estimated parasite load by another method was the same,although statistically significant differences were found between some groups.Conclusions:Both methods lead to approximately similar results in terms of differentiating parasite load of the experimental groups.However,due to the lower errors and faster process,the real-time PCR method is preferred.

Zoonotic leishmaniasis and control in Ethiopia

Visceral leishmaniasis and cutaneous leishmaniasis are important public health problems in Ethiopian lowland and highland areas respectively. Failure of antimonial drugs to respond in some diffused cutaneous leishmaniasis and HIV/AIDS-leishmaniasis co-infected patients, side effects of these drugs, highly mutilating diagnostic procedures and high health care expense are among the problems associated with leishmaniasis. Control of leishmaniasis requires proper understanding of human parasites transmissions(anthroponotic or zoonotic or both). The aim of this review was to elaborate different ecologies of leishmaniasis based on evidences from previous researches and information from literatures obtained from different sources including PubMed to describe zoonotic leishmaniasis in Ethiopia with possible control methods.Although vectors of leishmaniasis in Ethiopia are not endophelic, night indoor visits of Phlebotomus vectors for possible blood meal on human have been indicated. Thus, application of indoor and domestic residual insecticides spraying, use of insecticide impregnated fine mashed bed net for visceral leishmaniasis, community based manipulation(destruction) and residual insecticide fogging of hyrax-sand fly habitats for cutaneous leishmaniasis are the visible vector and reservoir control methods that can be used for control of these diseases in Ethiopia. Use of repellants during night outdoor activities of people in the endemic areas requires further investigations.

A case report of cervicofacial actinomycosis

Actinomycosis is a rare chronic granulomatous disease.Here we reported a 23-year-old male presented with a neck mass in the antero-inferior part for 35 days,with increasing in size and appearing some new masses in various sizes on left side of neck.The masses improved to some extent,with an empirical therapy but relapsed after discontinuation of treatment.After further investigations in second admission,long-term treatment with penicillin was started with a diagnosis of cervicofacial actinomycosis.Bronchial cleft actinomycosis was proved in this patient, which is one of rare cases of actinomyces involvement.