Leprosy: treatment, prevention, immune response and gene function.

Since the leprosy cases have fallen dramatically, the incidence of leprosy has remained stable over the past years, indicating that multidrug therapy seems unable to eradicate leprosy. More seriously, the emergence of rifampicin-resistant strains also affects the effectiveness of treatment. Immunoprophylaxis was mainly carried out through vaccination with the BCG but also included vaccines such as LepVax and MiP. Meanwhile, it is well known that the infection and pathogenesis largely depend on the host's genetic background and immunity, with the onset of the disease being genetically regulated. The immune process heavily influences the clinical course of the disease. However, the impact of immune processes and genetic regulation of leprosy on pathogenesis and immunological levels is largely unknown. Therefore, we summarize the latest research progress in leprosy treatment, prevention, immunity and gene function. The comprehensive research in these areas will help elucidate the pathogenesis of leprosy and provide a basis for developing leprosy elimination strategies.

Mutational signature and prognosis in adenocarcinoma of the bladder.

Adenocarcinoma of the bladder is a rare urinary bladder carcinoma with limited therapy options due to lack of molecular characterization. Here, we aimed to reveal the mutational and transcriptomic landscapes of adenocarcinoma of the bladder and assess any relationship with prognosis. Between February 2015 and June 2021, a total of 23 patients with adenocarcinoma of the bladder were enrolled. These included 16 patients with primary bladder adenocarcinomas and seven patients with urachal adenocarcinoma. Whole exome sequencing (16 patients), whole genome sequencing (16 patients), bulk RNA sequencing (RNA-seq) (19 patients), and single-cell RNA-seq (5 patients) were conducted for the specimens. Correlation analysis, survival analysis, and t-tests were also performed. Prevalent T>A substitutions were observed among somatic mutations, and major trinucleotide contexts included 5'-CTC-3' and 5'-CTG-3'. This pattern was mainly contributed by COSMIC signature 22 related to chemical carcinogen exposure (probably aristolochic acid), which has not been reported in bladder adenocarcinoma. Moreover, genes with copy number changes were also enriched in the KEGG term 'chemical carcinogenesis'. Transcriptomic analysis suggested high immune cell infiltration and luminal-like features in the majority of samples. Interestingly, a small fraction of samples with an APOBEC-derived mutational signature exhibited a higher risk of disease progression compared with samples with only a chemical carcinogen-related signature, confirming the molecular and prognostic heterogeneity of bladder adenocarcinoma. This study presents mutational and transcriptomic landscapes of bladder adenocarcinoma, and indicates that a chemical carcinogen-related mutational signature may be related to a better prognosis compared with an APOBEC signature in adenocarcinoma of the bladder. © 2024 The Pathological Society of Great Britain and Ireland.

Self-Care Ability and Life Quality of Cured Leprosy Patients: The Mediating Effects of Social Support.

OBJECTIVES: The study explores the relationship between social support, self-care ability, and life quality of cured leprosy patients (CLPs), aiming to develop strategies to enhance their overall well-being. METHODS: From July to December 2021, we investigated the social support, self-care ability, and life quality of CLPs through three scales and analyzed the correlation between them. In addition, structural estimation modeling (SEM) was employed to analyze their correlation. RESULTS: A total of 9245 CLPs were recruited, with a male-to-female ratio of 2.19:1, and 94.04% of cured patients was 60 years or above, with predominantly home-cured patients. The scores of WHOQOL-BREF, SSRS, and ESCA were (51.39 ± 9.89), (31.87 ± 8.76), and (100.95 ± 19.75), respectively. The results indicate a poorer quality of life and social support for CLPs compared to the general population in China. Furthermore, the home group had higher scores on these scales than the leprosarium group. The correlation analysis showed significant interactions between life quality, social support, self-care ability, and various domains (p < 0.05). SEM results revealed that the direct effect of self-care ability on life quality was 0.13, and the indirect effect on quality of life through social support was 0.08. The mediating effect of social support accounted for 22.86% of the total effect in the home group. In the leprosarium group, the effect of self-care ability on quality of life was 0.14. CONCLUSIONS: Most CLPs in Jiangsu Province are concentrated in the central region, with a high disease burden. We found that CLPs have a poorer life quality than the general population, with the leprosarium group being worse than the home group. The government and society should pay more attention to and support these cured patients.

Rosemary extract improves egg quality by altering gut barrier function, intestinal microbiota and oviductal gene expressions in late-phase laying hens.

BACKGROUND: Rosemary extract (RE) has been reported to exert antioxidant property. However, the application of RE in late-phase laying hens on egg quality, intestinal barrier and microbiota, and oviductal function has not been systematically studied. This study was investigated to detect the potential effects of RE on performance, egg quality, serum parameters, intestinal heath, cecal microbiota and metabolism, and oviductal gene expressions in late-phase laying hens. A total of 210 65-week-old "Jing Tint 6" laying hens were randomly allocated into five treatments with six replicates and seven birds per replicate and fed basal diet (CON) or basal diet supplemented with chlortetracycline at 50 mg/kg (CTC) or RE at 50 mg/kg (RE50), 100 mg/kg (RE100), and 200 mg/kg (RE200). RESULTS: Our results showed that RE200 improved (P < 0.05) Haugh unit and n-6/n-3 of egg yolk, serum superoxide dismutase (SOD) compared with CON. No significant differences were observed for Haugh unit and n-6/n-3 of egg yolk among CTC, RE50, RE100 and RE200 groups. Compared with CTC and RE50 groups, RE200 increased serum SOD activity on d 28 and 56. Compared with CON, RE supplementation decreased (P < 0.05) total cholesterol (TC) level. CTC, RE100 and RE200 decreased (P < 0.05) serum interleukin-6 (IL-6) content compared with CON. CTC and RE200 increased jejunal mRNA expression of ZO-1 and Occludin compared with CON. The biomarkers of cecal microbiota and metabolite induced by RE 200, including Firmicutes, Eisenbergiella, Paraprevotella, Papillibacter, and butyrate, were closely associated with Haugh unit, n-6/n-3, SOD, IL-6, and TC. PICRUSt2 analysis indicated that RE altered carbohydrate and amino acid metabolism of cecal microbiota and increased butyrate synthesizing enzymes, including 3-oxoacid CoA-transferase and butyrate-acetoacetate CoA-transferase. Moreover, transcriptomic analysis revealed that RE200 improved gene expressions and functional pathways related to immunity and albumen formation in the oviductal magnum. CONCLUSIONS: Dietary supplementation with 200 mg/kg RE could increase egg quality of late-phase laying hens via modulating intestinal barrier, cecal microbiota and metabolism, and oviductal function. Overall, RE could be used as a promising feed additive to improve egg quality of laying hens at late stage of production.

Host genetic backgrounds: the key to determining parasite-host adaptation.

Parasitic diseases pose a significant threat to global public health, particularly in developing countries. Host genetic factors play a crucial role in determining susceptibility and resistance to infection. Recent advances in molecular and biological technologies have enabled significant breakthroughs in understanding the impact of host genes on parasite adaptation. In this comprehensive review, we analyze the host genetic factors that influence parasite adaptation, including hormones, nitric oxide, immune cells, cytokine gene polymorphisms, parasite-specific receptors, and metabolites. We also establish an interactive network to better illustrate the complex relationship between host genetic factors and parasite-host adaptation. Additionally, we discuss future directions and collaborative research priorities in the parasite-host adaptation field, including investigating the impact of host genes on the microbiome, developing more sophisticated models, identifying and characterizing parasite-specific receptors, utilizing patient-derived sera as diagnostic and therapeutic tools, and developing novel treatments and management strategies targeting specific host genetic factors. This review highlights the need for a comprehensive and systematic approach to investigating the underlying mechanisms of parasite-host adaptation, which requires interdisciplinary collaborations among biologists, geneticists, immunologists, and clinicians. By deepening our understanding of the complex interactions between host genetics and parasite adaptation, we can develop more effective and targeted interventions to prevent and treat parasitic diseases. Overall, this review provides a valuable resource for researchers and clinicians working in the parasitology field and offers insights into the future directions of this critical research area.

Clinical characteristics of 32 cases of diffuse panbronchiolitis. / 32例弥漫性泛细支气管炎的临床特征.

OBJECTIVES: Diffuse panbronchiolitis (DPB) is a chronic airway inflammation with low specificity and its diagnosis is often missed or delayed. This study aims to summarize the clinical characteristics and treatment of DPB in order to improve the understanding and diagnosis of the disease. METHODS: The clinical data of 32 DPB patients were collected, analyzed and summarized from March 1, 2013 to March 1, 2022 in the Second Xiangya Hospital of Central South University. The basic information, clinical manifestations, laboratory tests, pulmonary function, imaging tests, treatment, and regression of patients were analyzed. RESULTS: A total of 32 patients were enrolled in the final analysis, with a male-to-female ratio at 1.67. The median age at symptom onset was 26.5 (11.0-69.0) years, and the median age of diagnosis was 47.5 (16.0-77.0) years. All patients presented with chronic cough and copious sputum production. A total of 26 patients had post activity shortness of breath and 14 patients had a positive result (blood cold agglutination test titer≥1꞉64). Pulmonary function examination was performed in 31 patients, 18 patients showed mixed pulmonary ventilation dysfunction, 12 patients showed obstructive pulmonary ventilation, and 1 patient had normal pulmonary ventilation function. A total of 31 patients had a bilateral, diffuse, small nodule pattern on chest CT. All patients were treated with macrolides. A total of 31 patients showed improvement, and 20 patients showed improvement in partial pressure of oxygen and blood oxygen saturation compared with before at discharge. A total of 12 patients were re-examined by chest CT after completing macrolides treatment, 6 cases showed less diffuse nodules, 5 cases showed no significant changes, and 1 case showed more diffuse nodules, which indicated the disease progression. Seven patients received pulmonary function tests after completing macrolides treatment, forced expiratory volume in one second (FEV1) and FEV1/forced vital capacitywere improved, but forced expiratory flow at 25% of vital capacity did not change significantly. CONCLUSIONS: The clinical manifestations of DPB are nonspecific. Early diagnosis and treatment are very important for the prognosis of patients.

Clinical characteristics of IgG4-related disease with lung involvement in 14 patients. / 14例累及肺部的IgG4ç›¸å ³æ€§ç–¾ç— çš„ä¸´åºŠç‰¹å¾.

OBJECTIVES: Immunoglobulin G4-related diseases (IgG4-RD) is a rare autoimmune disease, and there is no specific diagnostic test for patients with lung involvement yet. This study aims to summarize the clinical characteristics of IgG4-RD with lung involvement and improve the understanding and diagnosis of this disease. METHODS: All patients diagnosed with IgG4-RD in the Second Xiangya Hospital from December 2014 to February 2022 were re-diagnosed according to the recommendations of Chinese Expert Consensus on the Diagnosis and Treatment of IGG4-Related Diseases in 2021. The clinical data of 14 IgG4-RD patients with pulmonary abnormalities were collected and analyzed. RESULTS: Among the 14 patients, 11 were males and 3 were females, and the median age of diagnosis was 66 (22-82) years old. Six cases had respiratory symptoms such as cough, sputum and short breath. Extrapulmonary involvement was the most common in the glands of head and neck (6/14), followed by pancreas and bile duct (4/14). Elevated serum IgG4 level was found in all patients, and most (11/14) were accompanied by abnormal inflammatory markers. Patients' pulmonary imaging findings were diverse, the most common performances were mediastinal/hilar lymphadenopathy (12/14), followed by multiple pulmonary nodules (9/14), patchy density enhancement (7/14) and the increased broncho vascular bundles (6/14). Lung biopsy was performed in 9 patients, their pathology results showed lymphoplasmic cell infiltration, 5 cases of them had interstitial fibrosis, 2 cases with phlebitis, and extrapulmonary biopsy was performed in 8 patients. Immunohistochemical results of all the patients showed that the number of IgG4+ plasma cells was more than 10 per high magnification, and the ratio of IgG4/IgG was more than 40%. For treatment, 12 patients received hormone therapy, and 5 patients combined immunosuppressive therapy with hormone. 10 patients were in remission after treatment, while 2 patients were progressed. CONCLUSIONS: IgG4-RD with lung involvement is rare and has no specific clinical manifestation. Its pulmonary imaging is diverse. Diagnosis for it should combine with serum IgG4 level and pathological examination. Glucocorticoid is the first line treatment, and combination with immunosuppressant can help prevent disease recurrence.

In vivo detection of circulating tumor cells predicts high-risk features in patients with bladder cancer.

Previous studies have suggested the potential diagnostic value of circulating tumor cells (CTCs). This study aims to validate the efficacy of in vivo detection of CTCs in bladder cancer (BC) patients. A total of 216 BC patients were enrolled in this study. All patients had one in vivo detection of CTCs before initial treatment as a baseline parameter. The results of CTCs were associated with different clinicopathological features including molecular subtypes. PD-L1 expression on CTCs was also assessed and compared with its expression on tumors. CTC positive was defined as > 2 CTCs detected. Among all 216 patients, 49 (23%) were detected as CTC positive (> 2 CTCs) at baseline. Positive detection of CTCs was associated with multiple high-risk clinicopathological features including the multiplicity of the tumor (P = 0.02), tumor size (P < 0.01), tumor stage (P < 0.01), tumor grade (P < 0.01) and tumor PD-L1 expression (P = 0.01). The expression of PD-L1 on tumor and CTCs were not coordinated. Only 55% (74/134) matched the same status of PD-L1 expression on tumor and CTCs, along with 56 CTC (+) Tissue (-) and 4 CTC (-) Tissue (+) (P < 0.01). Our study has demonstrated the efficacy of in vivo detection of CTCs. The positive detection of CTCs is associated with multiple clinicopathological features. PD-L1 expression on CTCs has the potential to be a supplementary biomarker for immunotherapy.

In vivo detection demonstrates circulating tumor cell reduction instead of baseline number has prognostic value in bladder cancer patients receiving neoadjuvant chemotherapy.

PURPOSE: Previous studies have suggested the potential prognostic value of circulating tumor cells (CTCs) in bladder cancer (BC) patients. This study aims to validate the prognostic value of in vivo detection of CTCs in muscle invasive bladder cancer (MIBC) patients receiving neoadjuvant chemotherapy (NAC). METHODS: A total of 107 MIBC patients were enrolled in this study. All patients had one in vivo detection of CTCs before initial treatment as baseline, and those who received neoadjuvant chemotherapy (NAC) had a second detection after NAC and before radical cystectomy. CTCs dynamic change after NAC was analyzed. Prognostic value of in vivo CTCs detection was investigated. RESULTS: Among 68 patients who received NAC, 45 patients (66%) had a CTC reduction after NAC. CTC reduction instead of baseline CTC positivity was a key prognostic factor for better progression free survival (PFS) among all MIBC patients receiving NAC in Kaplan-Meier analysis (P < 0.01) and in both crude (HR 6.14, 95%CI 1.63-23.21) and adjusted regression model (HR 6.76, 95% CI 1.59-28.88). The AUC was 0.85. CONCLUSION: Our study demonstrated the prognostic value of in vivo detection of CTCs. The dynamic change of CTCs count may help evaluate the efficacy of NAC.

Potential Effects of 25-Hydroxycholecalciferol on the Growth Performance, Blood Antioxidant Capacity, Intestinal Barrier Function and Microbiota in Broilers under Lipopolysaccharide Challenge.

Our experiment was to detect the effects of 25-hydroxycholecalciferol (25OHD3) on antioxidant capacity, immune status and gut health of broilers under lipopolysaccharide (LPS) challenge. In total, 108 male Arbor Acre broilers (48.5 ± 0.4 g) were allotted to three treatment groups containing six replicates for each group with six birds per replicate: (1) corn-soybean basal diet + injection of sterile saline (CON group); (2) corn-soybean basal diet + an injection of LPS (LPS group); (3) corn-soybean basal diet with 50 µg/kg 25OHD3 + injection of LPS (LPS + 25-D group). At the end of the experiment, birds were intraperitoneally injected with LPS in the LPS and LPS + 25-D groups based on the dosage of 5.0 mg/kg BW, or the equivalent volume of 0.9% sterile saline in the CON group. At 4 h postinjection, blood samples, jejunal and ileal tissues and cecal digesta were collected to analyze blood antioxidant capacity, intestinal barrier function and microbiota. The results showed that broilers challenged with LPS had significantly higher BW loss than the CON group, and 25OHD3 alleviated BW loss induced by the LPS challenge. 25OHD3 alleviated the LPS-induced decline (p < 0.05) in serum activities of superoxide dismutase (SOD) and immunoglobulin G (IgG), as well as prevented the LPS-induced increase (p < 0.05) in serum content of tumor necrosis factor-α (TNF-α). 25OHD3 significantly increased villus height in the jejunum and the relative mRNA abundance of Occludin in the jejunum and ileum, as well as prevented the LPS-induced increase in the jejunal content of interferon-γ (IFN-γ) compared with the LPS group. Compared with the LPS group, 25OHD3 significantly increased Lactobacillus abundance and decreased Lachnoclostridium abundance in the cecal digesta, as well as had the potential to enhance metabolite contents including propionate, isobutyrate, butyrate and total SCFA. The correlation analysis revealed that BW loss and serum contents of TNF-α, IL-1ß and D-lactate were positively correlated with Lachnoclostridium and negatively correlated with Lactobacillus (p < 0.05). Overall, 25OHD3 partially improves the antioxidant status, immunity, intestinal barrier and microbial composition of broilers under the LPS challenge.

Dietary Oregano Essential Oil Supplementation Influences Production Performance and Gut Microbiota in Late-Phase Laying Hens Fed Wheat-Based Diets.

This study aimed to investigate the potential effects of OEO on production performance, egg quality, fatty acid composition in yolk, and cecum microbiota of hens in the late phase of production. A total of 350 58-week-old Jing Tint Six laying hens were randomly divided into five groups: (1) fed a basal diet (control); (2) fed a basal diet + 5 mg/kg flavomycin (AGP); (3) fed a basal diet + 100 mg/kg oregano essential oil + 20 mg/kg cinnamaldehyde (EO1); (4) fed a basal diet + 200 mg/kg oregano essential oil + 20 mg/kg cinnamaldehyde (EO2); (5) fed a basal diet + 300 mg/kg oregano essential oil + 20 mg/kg cinnamaldehyde (EO3). Compared to the control group, group EO2 exhibited higher (p < 0.05) egg production during weeks 5−8 and 1−8. EO2 had a lower feed conversion ratio than the control group during weeks 1−8. The content of monounsaturated fatty acid (MUFA) in EO2 was higher (p < 0.05) than that of the control and AGP groups. EO2 increased (p < 0.05) the abundance of Actinobacteriota and decreased the abundance of Desulfovibri in the cecum. The abundances of Anaerofilum, Fournierella, Fusobacterium, and Sutterella were positively correlated with egg production, feed conversion ratio, and average daily feed intake, while the abundances of Bacteroides, Desulfovibrio, Lactobacillus, Methanobrevibacter, and Rikenellaceae_RC9_gut_group were negatively correlated with egg production, feed conversion ratio, and average daily feed intake. Dietary supplementation with 200 mg/kg OEO and 20 mg/kg cinnamaldehyde could improve egg-production performance, decrease feed conversion ratio, and alter the fatty acid and microbial composition of eggs from late-phase laying hens.

Potential of Aromatic Plant-Derived Essential Oils for the Control of Foodborne Bacteria and Antibiotic Resistance in Animal Production: A Review.

Antibiotic resistance has become a severe public threat to human health worldwide. Supplementing antibiotic growth promoters (AGPs) at subtherapeutic levels has been a commonly applied method to improve the production performance of livestock and poultry, but the misuse of antibiotics in animal production plays a major role in the antibiotic resistance crisis and foodborne disease outbreaks. The addition of AGPs to improve production performance in livestock and poultry has been prohibited in some countries, including Europe, the United States and China. Moreover, cross-resistance could result in the development of multidrug resistant bacteria and limit therapeutic options for human and animal health. Therefore, finding alternatives to antibiotics to maintain the efficiency of livestock production and reduce the risk of foodborne disease outbreaks is beneficial to human health and the sustainable development of animal husbandry. Essential oils (EOs) and their individual compounds derived from aromatic plants are becoming increasingly popular as potential antibiotic alternatives for animal production based on their antibacterial properties. This paper reviews recent studies in the application of EOs in animal production for the control of foodborne pathogens, summarizes their molecular modes of action to increase the susceptibility of antibiotic-resistant bacteria, and provides a promising role for the application of nanoencapsulated EOs in animal production to control bacteria and overcome antibiotic resistance.

Clinical characteristics of eosinophilic granulomatosis with polyangiitis involving the lung in 13 patients. / 13ä¾‹ç´¯åŠè‚ºéƒ¨çš„å—œé ¸æ€§è‚‰èŠ½è‚¿æ€§å¤šè¡€ç®¡ç‚Žçš„ä¸´åºŠç‰¹å¾.

OBJECTIVES: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis, which often starts with respiratory symptoms such as asthma, and it is difficult to make early clinical diagnosis.This study aims to improve the therapeutic level of EGPA with lung involvement via analyzing the clinical characteristics, diagnosis, and treatment . METHODS: We retrospectively analyzed the clinical data of 13 EGPA patients with lung involvement who were diagnosed from February 1, 2014 to July 31, 2021 in the Second Xiangya Hospital, Central South University. RESULTS: The ratio of male to female in 13 patients was 7꞉6. The patients were diagnosed at median age 52 (46-68) years old and 6 had been diagnosed as "bronchial asthma". Pulmonary clinical manifestations mainly included cough, expectoration, wheezing, and shortness of breath; while extra-pulmonary manifestations mainly included rash and subcutaneous mass, fever, limb numbness, muscle and joint pain, abdominal pain, etc. Peripheral blood tests of all patients showed that 11 patients had eosinophils ≥10%, 10 had elevated inflammatory indicators, and 3 were anti-neutrophil cytoplasmic antibody (ANCA) positive. The major lung imaging features were patches or strips of increased density, multiple nodules, bronchiectasis, bronchial wall thickening, exudation, mediastinal lymph nodes, and so on. Eight patients had sinusitis and 9 with abnormal electromyography. Extravascular eosinophil infiltration was found in 9 patients. Six patients with lung biopsy showed eosinophil, lymphocyte, and plasma cell infiltration, 3 patients were involved in small blood vessels, and 1 had granuloma. Pulmonary function tests were performed in 7 patients, 5 of them showed different degrees of pulmonary ventilation dysfunction, and 4 of them had diffusion dysfunction. Almost all patients respond well to glucocorticoid and immunosuppressant. CONCLUSIONS: EGPA is rare in clinical, often involving multiple systems with great harm and may combine with asthmatic manifestations. Pulmonary involvement is relatively common. However, due to insufficient recognition of this disease and huge heterogeneity of pulmonary imaging manifestations, misdiagnosis and missed diagnosis are easy to occur. Relevant laboratory, imaging, and biopsy examination should be performed as early as possible with comprehensive consideration of extrapulmonary involvement. Early identification has great significance to improve the diagnosis rate and prognosis of diseases.

NLRP3 Inflammasome Activation in MΦs-CRC Crosstalk Promotes Colorectal Cancer Metastasis.

OBJECTIVE: The NLRP3 inflammasome plays a key role in the progression and metastasis of colorectal cancer (CRC). METHODS: Macrophages (MΦs), as an important cellular component of the tumor microenvironment (TME), highly express the NLRP3 inflammasome. Rigorous investigation of the interaction and network between macrophages and colorectal cancer may help in understanding the role of the NLRP3 inflammasome in metastatic colorectal cancer. RESULTS: Herein, we demonstrated that NLRP3 inflammasome activation in MΦs-CRC crosstalk markedly promotes the invasion, migration, and epithelial-mesenchymal transition (EMT) of colorectal cancer cells in vitro. MΦs-CRC crosstalk activated the NLRP3 inflammasome to secrete the proinflammatory cytokine IL-1ß. Notably, IL-1ß neutralizing antibody (NA) weakened the invasion and migration promotion effects of MΦs-CRC crosstalk in vitro. Based on Spearman's rank correlation analysis, we found that the expression of NLRP3 was positively associated with the expression of the macrophage surface marker CD68 and the proinflammatory cytokine IL-1ß. Clinical investigations suggested that the expression of NLRP3 in patients with colorectal cancer was positively associated with advanced AJCC stage and poor prognosis. CONCLUSION: This study found that the activation of the NLRP3 inflammasome in macrophages can secrete the proinflammatory cytokine IL-1ß to promote the invasion and migration of colorectal cancer cells by regulating epithelial-mesenchymal transition (EMT). This research provides a new strategy for developing the NLRP3 inflammasome as a potential therapeutic target to prevent metastatic colorectal cancer.

Drug Resistance (Dapsone, Rifampicin, Ofloxacin) and Resistance-Related Gene Mutation Features in Leprosy Patients: A Systematic Review and Meta-Analysis.

Dapsone (DDS), Rifampicin (RIF) and Ofloxacin (OFL) are drugs recommended by the World Health Organization (WHO) for the treatment of leprosy. In the context of leprosy, resistance to these drugs occurs mainly due to mutations in the target genes (Folp1, RpoB and GyrA). It is important to monitor antimicrobial resistance in patients with leprosy. Therefore, we performed a meta-analysis of drug resistance in Mycobacterium leprae and the mutational profile of the target genes. In this paper, we limited the study period to May 2022 and searched PubMed, Web of Science (WOS), Scopus, and Embase databases for identified studies. Two independent reviewers extracted the study data. Mutation and drug-resistance rates were estimated in Stata 16.0. The results demonstrated that the drug-resistance rate was 10.18% (95% CI: 7.85-12.51). Subgroup analysis showed the highest resistance rate was in the Western Pacific region (17.05%, 95% CI:1.80 to 13.78), and it was higher after 2009 than before [(11.39%, 7.46-15.33) vs. 6.59% (3.66-9.53)]. We can conclude that the rate among new cases (7.25%, 95% CI: 4.65-9.84) was lower than the relapsed (14.26%, 95 CI%: 9.82-18.71). Mutation rates of Folp1, RpoB and GyrA were 4.40% (95% CI: 3.02-5.77), 3.66% (95% CI: 2.41-4.90) and 1.28% (95% CI: 0.87-1.71) respectively, while the rate for polygenes mutation was 1.73% (0.83-2.63). For further analysis, we used 368 drug-resistant strains as research subjects and found that codons (Ser, Pro, Ala) on RpoB, Folp1 and GyrA are the most common mutation sites in the determining region (DRDR). In addition, the most common substitution patterns of Folp1, RpoB, and GyrA are Pro→Leu, Ser→Leu, and Ala→Val. This study found that a higher proportion of patients has developed resistance to these drugs, and the rate has increased since 2009, which continue to pose a challenge to clinicians. In addition, the amino acid alterations in the sequence of the DRDR regions and the substitution patterns mentioned in the study also provide new ideas for clinical treatment options.

A Bibliometric Analysis of Leprosy during 2000-2021 from Web of Science Database.

In recent years, after the essential elimination of leprosy (the prevalence of which is <1/100,000), the trends, research hotpots, and frontiers of leprosy research are not clear. This study provides a detailed overview of leprosy in terms of papers, journal, language, year, citations, h-index, author keywords, institution, and country through bibliometrics. The results are as follows: (1) The publication rate has increased in recent years, and 8892 papers were obtained. Most of the publications are in English, and the subject categories are mainly focused on "Dermatology." The "leprosy review" published the most significant number of papers on leprosy, followed by "Plos Neglected Tropical Disease" and "International Journal of Leprosy and Other Mycobacterial Diseases." (2) Leprosy-related research was contributed to by 24,672 authors, and the ten authors with the most significant number of publications were identified. (3) The University of London (including the London School of Hygiene and Tropical Medicine) has the highest h-index, and Fundacao Oswaldo Cruz is the most productive institution. (4) Brazil, India, the United States, the United Kingdom, and the Netherlands are the most productive countries, and the collaborative network reveals that they have established close cooperation with other countries. France has the highest average number of citations. (5) The keyword co-occurrence network identifies five highly relevant clusters representing topical issues in leprosy research (public health, leprosy vaccine, immune mechanisms, treatment, and genomics research). Overall, these results provide valuable insights for scholars, research institutions, and policymakers to better understand developments in the field of leprosy.

Clinical analysis for 15 patients with pulmonary Langerhans cell histiocytosis and literature review. / 15ä¾‹æˆäººè‚ºæœ—æ ¼æ±‰æ–¯ç»†èƒžç»„ç»‡ç»†èƒžå¢žç”Ÿç—‡ä¸´åºŠåˆ†æžåŠæ–‡çŒ®å›žé¡¾.

OBJECTIVES: Pulmonary Langerhans cell histiocytosis (PLCH) is a clonal disease, characterized by proliferation of Langerhans cells that derived from bone marrow infiltrating the lungs and other organs. Due to the rarity of the disease, the current understanding of the disease is insufficient, often misdiagnosed or missed diagnosis. This study aims to raise clinicians' awareness for this disease via summarizing the clinical characteristics, imaging features, and treatment of PLCH. METHODS: We retrospectively analyzed clinical and follow-up data of 15 hospitalized cases of PLCH from September 2012 to June 2021 in the Second Xiangya Hospital of Central South University. RESULTS: The age of 15 patients (9 men and 6 women, with a sex ratio of 3 to 2) was 21-52 (median 33) years. Among them, 8 had a history of smoking and 5 suffered spontaneous pneumothorax during disease course. There were 3 patients with single system PLCH and 12 patients with multi-system PLCH, including 7 patients with pituitary involvement, 7 patients with lymph node involvement, 6 patients with bone involvement, 5 patients with liver involvement, 2 patients with skin involvement, 2 patients with thyroid involvement, and 1 patients with thymus involvement. The clinical manifestations were varied but non-specific. Respiratory symptoms mainly included dry cough, sputum expectoration, chest pain, etc. Constitutional symptoms included fever and weight loss. Patients with multi-system involvement experienced symptoms such as polyuria-polydipsia, bone pain, and skin rash. All patients were confirmed by pathology, including 6 by lung biopsy, 3 by bone biopsy, 2 by lymph node biopsy, and 4 by liver, skin, suprasternal fossa tumor, or pituitary stalk biopsy. The most common CT findings from this cohort of patients were nodules and/or cysts and nodular and cystic shadows were found in 7 patients. Three patients presented simple multiple cystic shadows, 3 patients presented multiple nodules, and 2 patients presented with single nodules and mass shadows. Pulmonary function tests were performed in 4 patients, ventilation dysfunction was showed in 2 patients at the first visit. Pulmonary diffusion function tests were performed in 4 patients and showed a decrease in 3 patients. Smoking cessation was recommended to PLCH patients with smoking history. Ten patients received chemotherapy while 2 patients received oral glucocorticoid therapy. Among the 11 patients with the long-term follow-up, 9 were in stable condition. CONCLUSIONS: PLCH is a neoplastic disease closely related to smoking. The clinical manifestations and laboratory examination are not specific. Pneumothorax could be the first symptom which is very suggestive of the disease. Definitive diagnosis relies on histology. There is no unified treatment plan for PLCH, and individualized treatment should be carried out according to organ involvement. Early smoking cessation is essential. Chemotherapy is the main treatment for rapidly progressing PLCH involved multiple organs. All diagnosed patients can be considered for the detection of BRAFV600E gene and relevant targeted therapies have been implemented recently.

Global epidemiology of leprosy from 2010 to 2020: A systematic review and meta-analysis of the proportion of sex, type, grade 2 deformity and age.

The objectives of this study were to explore global epidemiological characteristics of leprosy, and to provide reference for the construction of prevention strategies for leprosy. Computer retrieval of the study on the epidemiology of leprosy from 2010 to 2020 in Web of Science, PubMed, and SCOPUS databases were summarized. The included studies were assessed for the quality of the AHRQ; the proportions of the study indices were meta-analyzed with Stata 16.0. A random effects model was adopted to merge categories, including sex, type, grade 2 deformity (G2D) and age group for meta-analysis. The subgroup analysis used region as a stratification factor to analyze whether there were differences in the indicators. The meta-analysis included 30 studies totaling 11,353 cases. The global pooled proportion of male to female subjects with leprosy was 63% (95% CI 59%, 66%) to 37% (95% CI 34%, 41%), respectively. The pooled multibacillary proportion and paucibacillary proportion were 69% (95% CI 62%, 76%) and 31% (95% CI 24%, 38%), respectively. The pooled grade 2 deformity (G2D) proportion was 22% (95% CI 15%, 30%). Among age groups, the pooled children proportion was 11% (95% CI 8%, 13%), and the pooled adult proportion was 89% (95% CI 87%, 92%). The subgroup analysis indicated that epidemiological indicators varied from country to country. This study suggested that disparities existed between sex, type, grade 2 deformity (G2D) and age group characteristics of leprosy from country to country.

Different dietary protein sources influence growth performance, antioxidant capacity, immunity, fecal microbiota and metabolites in weaned piglets.

The inclusion of high-quality proteins are commonly used in swine production. Our research investigated the effects of hydrolyzed wheat protein (HWP), fermented soybean meal (FSBM), and enzyme-treated soybean meal (ESBM) on growth performance, antioxidant capacity, immunity, fecal microbiota and metabolites of weaned piglets. A total of 144 piglets (weaned at 28 d) were allotted to 3 dietary treatments with 6 replicate pens per treatment and 8 piglets per pen. This study included 2 periods: d 0 to14 for phase 1 and d 15 to 28 for phase 2. Dietary treatments contained 15.90% HWP, 15.80% FSBM, and 15.10% ESBM in phase 1, and 7.90% HWP, 7.80% FSBM, and 7.50% ESBM in phase 2, respectively. The ADG of piglets in ESBM was increased (P < 0.05) compared with HWP and FSBM during d 1-28. Compared with HWP and FSBM, ESBM increased (P < 0.05) the ferric reducing ability of plasma (FRAP), and the serum level of superoxide dismutase (SOD) in piglets on d 14, as well as increased (P < 0.05) the serum FRAP level in piglets on d 28. ESBM decreased (P < 0.05) serum levels of DAO and IL-1ß in piglets compared with HWP on d 28. ESBM enhanced (P < 0.05) the relative abundance of Bacteroidetes, Oscillospiraceae and Christensenellaceae, as well as reduced the relative abundance of Clostridiaceae in the feces compared with HWP and FSBM. The PICRUSt analysis revealed that the number of gene tags related to degradation of valine, leucine and isoleucine, as well as lysine degradation in ESBM were lower (P < 0.05) than that in HWP and FSBM. ESBM increased (P < 0.05) the fecal butyrate level in piglets compared with FSBM, and ESBM tended to decrease (P = 0.076) the fecal cadaverine level. Overall, ESBM had advantages over HWP and FSBM in improving antioxidant status, immune function, fecal bacteria and metabolites for weaned piglets.

Epidemiological characteristics of leprosy during the period 2005-2020: A retrospective study based on the Chinese surveillance system.

Background: Jiangsu Province is located in the Yangtze River Delta region, with a total area of 107,200 square kilometers. Since 1949, over 55,000 cases have been registered, with Taixing accounting for the highest number of patients. The proportion of new cases with MB and G2D was higher compared to other regions. As a result, Jiangsu has been considered a priority area for public health interventions in China. Methods: This paper mainly described the population, time, and spatial distribution of the newly detected leprosy cases in Jiangsu Province between 2005 and 2020. In this study, all the data were entered into Microsoft Excel and SPSS for the descriptive analysis. ArcGIS was applied to create statistical maps, and Geoda was used to conduct spatial autocorrelation analysis with local Moran's I statistics (LISA). The epidemiological data were obtained from LEPMIS. In addition, population data were obtained from the Statistical Yearbook of Jiangsu Province. Results: During the study period, 363 new cases were reported. Of these, 232 were men and 131 were women (1.77:1). The mean age at diagnosis was 60.56 years, and no adolescent cases were identified. Three hundred and twenty-seven (90.08%) were diagnosed with MB and 36 (9.92%) with PB. 31.68% (115/363) of the patients presented with G2D. Farmers accounted for 74.9%, and most cases were identified in skin clinics (248, 68.32%). We observed a decreasing trend in detection rate, with a higher concentration of new cases diagnosed between July and October. Spatial analysis showed that the new cases were primarily distributed in the northwest of Jiangsu province, and Suqian has the highest incidence of leprosy. Special attention should be paid to Wuzhong, a county with a potential risk of inter-provincial transmission. Furthermore, 55 new cases came from other Chinese provinces but lived in Jiangsu. Conclusion: The NCDR of leprosy decreased, but the new cases showed disabilities, a sign of the late diagnosis. The results indicated that some regions were still suffering from the burden of leprosy. Thus, we recommend that the government should adopt effective strategies to promote leprosy control. The main priorities for eliminating new cases were to provide sustainable financial support, improve the quality of clinical services, strengthen preventive intervention and rehabilitation services for disabilities, provide health education among high-risk populations, and explore new approaches.