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Imported cutaneous leishmaniasis (CL) is a growing problem with increasing global travel to endemic areas. Returned travelers with CL are easy to be misdiagnosed and mistreated due to the lack of awareness for the disease to the physicians in non-endemic region that may lead to unfavorable outcome. Our study intends to summarize the characteristics of Leishmania infection imported from Iraq, so as to help Chinese physicians diagnose and treat the disease. All CL patients were treated with intralesional injection of antimony. The definitive diagnosis of CL is based on the parasite identification by microscopic examination directly on lesion smear or parasite culture, PCR amplification of Leishmania-specific internal transcribed spacer 1 (ITS-1). The phylogenetic analysis, the immunopathological examination and the cytokine detection were proceeded after the diagnosis. We have identified 25 CL cases in migrant Chinese workers returned from Iraq for the first time with L. major as the major species of infected Leishmania parasite. Clinical features of the Iraq-imported CL include the history of skin exposure to sandflies bite and the lesions mostly on the exposed limbs. More ulcerative wet lesion was observed than nodular dry lesion. PCR is not only used to detect Leishmania parasite with high sensitivity, but also to identify the species of infected parasite through sequencing the amplified Leishmania-specific ITS-1 gene. The phylogenetic analysis based on the amplified ITS-1 sequences revealed that the infected Leishmania was closed related to the species and strains endemic in Iraq. The immunopathological examination revealed the T-cell filtrated cellular immune response with less B cells and NK cells involved. The cytokine profile measured in the skin lesion also confirmed the Th1 cellular response with higher expression levels of IFN-γ, IL-6 and IL-8. The skin lesions in CL patients were healed after being treated locally with antimony. The clinical and parasitological features of these Chinese CL cases imported from Iraq provide useful information for the diagnosis and treatment of CL that is not commonly seen in Chinese local population.

Background Loiasis is one of the significant filarial diseases for people living in West and Central Africa with wide endemic area but is not seen in China. As economy booms and international traveling increase, China faces more and more imported parasitic diseases that are not endemic locally. Loiasis is one of the parasitic diseases that enter China by travelers infected in Africa. The better understanding of the clinical and laboratory features of loa loa infection will facilitate the diagnosis and treatment of loiasis in China. Methods The study targeted travelers who were infected with L. loa in endemic Africa regions and returned to Beijing between 2014 and 2023. Epidemiological, clinical, and biological data as well as treatment of these patients were collected. Results Total 21 cases were identified as L. loa infection based on their typical clinical manifestations and parasite finding. All cases had a history of travel to Africa for more than 6 months, most of them are the construction workers dispatched to West Africa with outdoor activities. Calabar swelling ( n  = 19; 90.5%) and pruritus ( n  = 11; 52.4%) were among the most common clinical symptoms followed by muscle pain ( n  = 7; 33.3%) and skin rash ( n  = 2; 9.5%). The adult worms were observed in the eyelid or subconjunctiva ( n  = 2; 9.5%) and subcutaneous tissues ( n  = 2; 9.5%). Although all patients presented with a high eosinophil count (> 0.52 × 10 9 /L), only two cases displayed microfilariae in fresh venous blood and positive for filarial antigen. A cut section of adult worm was observed through biopsy on a skin nodule surrounded by lymphocytes, plasma cells and eosinophils. All subjects were positive in PCR targeting L. loa ITS-1. The constructed phylogenetic tree based on the amplified ITS-1 sequences identified their genetical relation to the L. Loa from Africa. All patients treated with albendazole and diethylcarbamazine were recovered without relapse. Conclusion This study provides useful information and guideline for physicians and researchers in non-endemic countries to diagnose and treat loiasis and L. loa infections acquired from endemic regions.

Naringin has been reported to have an anti-atherosclerosis effect but the underlying mechanism is not fully understood. The aim of this study is to investigate the impact of naringin on the TNF-α-induced expressions of cell adhesion molecules, chemokines and NF-κB signaling pathway in human umbilical vein endothelial cells (HUVECs). The experiments revealed that naringin, at concentrations without cytotoxicity, dose-dependently inhibited the adhesion of THP-1 monocytes to the TNF-α-stimulated HUVECs. The TNF-α-induced expressions of cell adhesion molecules, including VCAM-1, ICAM-1 and E-selectin, at both the mRNA and protein levels, were significantly suppressed by naringin in a dose dependent manner. In addition, the TNF-α-induced mRNA and protein levels of chemokines, including fractalkine/CX3CL1, MCP-1 and RANTES, were also reduced by naringin. Naringin significantly inhibited TNF-α-induced nuclear translocation of NF-κB, which resulted from the inhibited phosphorylation of IKKα/β, IκB-α and NF-κB. Altogether, we proposed that naringin modulated TNF-α-induced expressions of cell adhesion molecules and chemokines through the inhibition of TNF-α-induced activation of IKK/NF-κB signaling pathway to exert the anti-atherosclerotic effect.

Our previous studies showed that Trichinella spiralis paramyosin (TsPmy) is an immunomodulatory protein that inhibits complement C1q and C8/C9 to evade host complement attack. Vaccination with recombinant TsPmy protein induced protective immunity against T. spiralis larval challenge. Due to the difficulty in producing TsPmy as a soluble recombinant protein, we prepared a DNA vaccine as an alternative approach in order to elicit a robust immunity against Trichinella infection. The full-length TsPmy coding DNA was cloned into the eukaryotic expression plasmid pVAX1, and the recombinant pVAX1/TsPmy was transformed into attenuated Salmonella typhimurium strain SL7207. Oral vaccination of mice with this attenuated Salmonella-delivered TsPmy DNA vaccine elicited a significant mucosal sIgA response in the intestine and a systemic IgG antibody response with IgG2a as the predominant subclass. Cytokine analysis also showed a significant increase in the Th1 (IFN-γ, IL-2) and Th2 (IL-4, 5, 6, 10) responses in lymphocytes from the spleen and MLNs of immunized mice upon stimulation with TsPmy protein. The expression of the homing receptors CCR9/CCR10 on antibody secreting B cells may be related to the translocation of IgA-secreted B cells to local intestinal mucosa. The mice immunized with Salmonella-delivered TsPmy DNA vaccine produced a significant 44.8% reduction in adult worm and a 46.6% reduction in muscle larvae after challenge with T. spiralis larvae. Our results demonstrated that oral vaccination with TsPmy DNA delivered by live attenuated S. typhimurium elicited a significant local IgA response and a mixed Th1/Th2 immune response that elicited a significant protection against T. spiralis infection in mice.

Trichinella spiralis infection induces protective immunity against re-infection in animal models. Identification of the antigens eliciting acquired immunity during infection is important for vaccine development against Trichinella infection and immunodiagnosis. The T. spiralis adult cDNA library was immunoscreened with sera from pigs experimentally infected with 20,000 infective T. spiralis larvae. Total 43 positive clones encoding for 28 proteins were identified; one of the immunodominant proteins was 20 kDa Ts-ES-1 secreted by Trichinella stichocytes and existing in the excretory/secretory (ES) products of T. spiralis adult and muscle larval worms. Ts-ES-1 contains 172 amino acids with a typical signal peptide in the first 20 amino acids. The expression of Ts-ES-1 was detected in both the adult and muscle larval stages at the mRNA and protein expression levels. Mice immunized with recombinant Ts-ES-1 (rTs-ES-1) formulated with ISA50v2 adjuvant exhibited a significant worm reduction in both the adult worm (27%) and muscle larvae burden (42.1%) after a challenge with T. spiralis compared to the adjuvant control group (p<0.01). The rTs-ES-1-induced protection was associated with a high level of specific anti-Ts-ES-1 IgG antibodies and a Th1/Th2 mixed immune response. The newly identified rTs-ES-1 is an immunodominant protein secreted by Trichinella stichocytes during natural infection and enables to the induction of partial protective immunity in vaccinated mice against Trichinella infection. Therefore, rTs-ES-1 is a potential candidate for vaccine development against trichinellosis.

Background The differential diagnosis between adult systemic EBV-positive T-cell lymphoproliferative disorders (EBV + T-LPD) and angioimmunoblastic T-cell lymphoma (AITL) with multiple EBV infections is difficult, and distinguishing between the two has become a diagnostic challenge for pathologists. Given that the clinical treatment plans are different, an accurate diagnosis is a prerequisite to ensure effective treatment, therefore, it is extremely necessary and meaningful to find effective pathological indicators for distinguishing between two diseases. Methods We present a retrospective study comparing 7 cases of adult EBV + T-LPD and 16 cases of AITL with multiple EBV infections diagnosed at our institution from 2017 to 2022. Differences in immunophenotype, type of EBV-infected cells, clonality and gene mutations between the two groups of cases were compared by immunohistochemical staining, double-label staining, TCR gene rearrangement and next-generation sequencing analysis. Results 7 cases of adult EBV + T-LPD: all cases had no more than 1 T follicular helper (THF) marker was expressed, and there were significantly more EBER+/CD3 + cells than EBER+/CD20 + cells; 5 cases had mutation detection results, in which only 1 had the characteristic KMT2D mutation, 2 had TET2 mutations, and no common mutations such as DDX3X were detected.16 cases of AITL with multiple EBV infections: all cases were found to express at least 2 TFH markers, with 87% of them expressing at least 3 TFH markers., and had significantly more EBER+/CD20 + cells than EBER+/CD3 + cells; 4 cases had mutation test results, with mutated high-frequency genes being TET2 (100%, and all of them had 2 or more TET2 mutations) and RHOA G17V (100%), DNMT3A mutation occurred in 2 cases (50%), and IDH2 R172 mutation occurred in 1 case (25%). Conclusions We found that the expression pattern of TFH markers, the types of cells predominantly infected by EBV and the different mutations can all be used as effective pathological indicators for distinguishing between two diseases.

ObjectivesTumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is a member of the TNF super-family, which is involved in the regulation of immune response and pathogenesis of autoimmune diseases, including polymyositis (PM) and dermatomyositis (DM). In this study, we examined the level and origin of serum-soluble TRAIL (sTRAIL) in patients with PM and DM and analyzed its association with disease activity and clinical features. Method11 PM patients, 33 DM patients, and 20 healthy controls were enrolled in this study. Clinical features were recorded when admitted, and disease activity was evaluated by myositis disease activity assessment visual analogue scale (MYOACT). TRAIL expression in muscle tissues was detected by immunohistochemistry. Serum sTRAIL levels were measured by enzyme-linked immunosorbent assay. The expression of membrane TRAIL (mTRAIL) and its receptors, including DR4 and DR5, on circulating T cells was analyzed by flow cytometry.ResultsTRAIL was expressed in infiltrated inflammatory cells in muscle tissues from patients. The serum sTRAIL level was markedly increased in patients and was positively correlated with the disease activity. Serum sTRAIL was decreased after therapy in patients and was specifically higher in patients with dysphagia, but lower in patients with autoantibody Jo-1 positive. The frequency of mTRAIL and its receptors on circulating T cells from patients were significantly elevated than that from healthy controls. ConclusionsThe serum sTRAIL could be a biomarker for evaluating the disease activity of PM and DM, and targeting the generation of TRAIL in T cells might be a potential approach in the treatment of PM and DM.

Steadily maintaining high intra-gastric PH is the major factor for successful eradication. It is important to search for a stronger PPI. Dexlansoprazole MR is a dual delayed release formulation PPI taken once daily which is capable of maintaining longer duration of high intra-gastric PH. It is very effective in treating gastroesophageal disease but reports on eradication is very rare. This study sought to compare dexlansoprazole MR-based concomitant treatment and lansoprazole-based concomitant treatment in infection and to investigate the factors that affect the eradication rates. Two hundred two participants with infection were included and randomly assigned to seven days of dexlansoprazole MR-based concomitant therapy (dexlansoprazole MR 60 mg once daily, clarithromycin 500 mg twice daily, amoxicillin 1 g twice daily and metronidazole 500 mg twice daily; DACM group) or a seven days of lansoprazole-based concomitant therapy (lansoprazole 30 mg twice daily, clarithromycin 500 mg twice daily, amoxicillin 1 g twice daily, and metronidazole 500 mg twice daily; LACM group). The participants were asked to perform urea breath tests eight weeks later. The eradication rates in the DACM group were 86.1% [95% confidence interval (CI): 77.8%-92.2%] in the ITT analysis and 90.6% (95% CI: 82.9%-95.6%) in the PP analysis, respectively, as compared with 90.1% (95% CI: 82.6%-95.2%) and 92.6% (95% CI: 85.5%-96.9%) ( =0.384 and =0.572, respectively) in the LACM group for the same analyses. The adverse event rates were 11.5% in the DACM group and 10.2% in the LACM group ( =0.779). As a first-line treatment regimen, dexlansoprazole MR-based concomitant therapy attained a successful eradication rate of 90%, which was non inferior to that of lansoprazole-based concomitant treatment. NCT03829150.

Background: Because of advances in medical treatment, the survival of cancer patients is prolonged. In line with the prolonged survival time of cancer the incidence of second primary cancer has increased. There is currently no effective way to prevent the occurrence of secondary primary cancer (SPC). Objectives: The aim of this study is to evaluate whether Chinese Herbal Medicine (CHM) is correlated with reduced occurrence of second primary cancer (SPC) of head and neck (H&N) in patients with esophageal cancer (EC). Method: We identified 15,546 patients who were diagnosed with esophageal cancer between Jan 1, 2000, and Dec 31, 2010. The patients with H&N cancer before receiving CHM were excluded. After the selection and matching process, both CHM and non-CHM cohorts each contained 850 individuals. We compared the cumulative incidence of SPC of H&N with or without CHM treatment in patients with EC by the Kaplan-Meier method. NodeXL is used to run a network analysis of CHM to examine the association between herbs and formulas. Results: Compared with non-CHM users, CHM-users showed a reduced incidence rate of SPC of H&N among the patients with EC. Reduced cumulative incidence of SPC of H&N among patients with EC was noted in the CHM cohort compared to the non-CHM cohort. The most commonly used single herbs and formulas were associated with reducing SPC occurrence. Conclusion: We propose that CHM as an adjuvant therapy may prevent the occurrence of SPC of H&N in patients with EC.

To assess the difference of the first-line therapy for in patients with or without type 2 diabetes (DM) and to investigate the clinical factors influencing treatment outcomes. In total, 719 patients with infection were treated with 7-day standard first-line triple therapy, of whom 182 did and 537 did not have DM. Propensity score matched at a 1:2 ratio - for age, sex and body mass index was performed for the two groups, yielding a DM group with 147 patients and a non-DM group with 249 matched controls for analysis. Urea breath test was performed 6-8 weeks after treatment. Clinical and laboratory parameters were collected for identifying factors associated with failed eradication. . was eradicated in 74.1% (95% confidence interval [CI] =66.2-81.0) of the DM group and 85.3% (95% CI =80.8-89.4) of the non-DM group ( =0.005). Of 51 gastric biopsy samples cultured for , 41 were positive. In the DM group, the rates of resistance to amoxicillin, clarithromycin, levofloxacin, and tetracycline were 0%, 50.0%, 50.0% and 0%, respectively. In the non-DM group, the comparable proportions were 2.9%, 17.1%, 22.9%, and 0%, respectively. Univariate analysis revealed that DM (Odds ratio [OR], 1.771, 95% CI, 1.167-2.668, =0.006), clarithromycin resistance (OR, 15.273; 95% CI, 1.687-138.269; =0.015), and amoxicillin resistance (OR, 4.672; 95% CI, 2.431-8.979; <0.001) were independently associated with failure to eradicate . Multivariate analysis showed that clarithromycin resistance was the major factor independently associated with failure of eradication (OR, 25.472; 95% CI, 1.549-418.956; =0.023). First-line eradication rates in patients with DM were significantly lower than in those without DM, although neither group achieved >90% eradication.