Deficiency of UCHL1 results in insufficient decidualization accompanied by impaired dNK modulation and eventually miscarriage.

BACKGROUND: Miscarriage is a frustrating complication of pregnancy that is common among women of reproductive age. Insufficient decidualization which not only impairs embryo implantation but disturbs fetomaternal immune-tolerance, has been widely regarded as a major cause of miscarriage; however, the underlying mechanisms resulting in decidual impairment are largely unknown. METHODS: With informed consent, decidual tissue from patients with spontaneous abortion or normal pregnant women was collected to detect the expression profile of UCHL1. Human endometrial stromal cells (HESCs) were used to explore the roles of UCHL1 in decidualization and dNK modulation, as well as the mechanisms involved. C57/BL6 female mice (7-10 weeks old) were used to construct pregnancy model or artificially induced decidualization model to evaluate the effect of UCHL1 on mice decidualization and pregnancy outcome. RESULTS: The Ubiquitin C-terminal hydrolase L1 (UCHL1), as a deubiquitinating enzyme, was significantly downregulated in decidua from patients with miscarriage, along with impaired decidualization and decreased dNKs. Blockage of UCHL1 led to insufficient decidualization and resultant decreased expression of cytokines CXCL12, IL-15, TGF-ß which were critical for generation of decidual NK cells (dNKs), whereas UCHL1 overexpression enhanced decidualization accompanied by increase in dNKs. Mechanistically, the promotion of UCHL1 on decidualization was dependent on its deubiquitinating activity, and intervention of UCHL1 inhibited the activation of JAK2/STAT3 signaling pathway, resulting in aberrant decidualization and decreased production of cytokines associated with dNKs modulation. Furthermore, we found that inhibition of UCHL1 also disrupted the decidualization in mice and eventually caused adverse pregnancy outcome. CONCLUSIONS: UCHL1 plays significant roles in decidualization and dNKs modulation during pregnancy in both humans and mice. Its deficiency indicates a poor pregnancy outcome due to defective decidualization, making UCHL1 a potential target for the diagnosis and treatment of miscarriage.

Diagnostic accuracy and cellular origin of pleural fluid CXCR3 ligands for tuberculous pleural effusion.

BACKGROUND: Pleural biomarkers represent potential diagnostic tools for tuberculous pleural effusion (TPE) due to their advantages of low cost, short turnaround time, and less invasiveness. This study evaluated the diagnostic accuracy of two CXCR3 ligands, C-X-C motif chemokine ligand 9 (CXCL9) and CXCL11, for TPE. In addition, we investigated the cellular origins and biological roles of CXCL9 and CXCL11 in the development of TPE. METHODS: This double-blind study prospectively enrolled patients with undiagnosed pleural effusion from two centers (Hohhot and Changshu) in China. Pleural fluid on admission was obtained and levels of CXCL9 and CXCL11 were measured by an enzyme-linked immunosorbent assay (ELISA). The receiver operating characteristic (ROC) curve and the decision curve analysis (DCA) were used to evaluate their diagnostic accuracy and net benefit, respectively. THP-1 cell-derived macrophages were treated with Bacillus Calmette-Guérin (BCG), and quantitative real-time PCR (qRT-PCR) and ELISA were used to determine the mRNA and protein levels of CXCL9 and CXCL11. The chemoattractant activities of CXCL9 and CXCL11 for T helper (Th) cells were analyzed by a transwell assay. RESULTS: One hundred and fifty-three (20 TPEs and 133 non-TPEs) patients were enrolled in the Hohhot Center, and 58 (13 TPEs and 45 non-TPEs) were enrolled in the Changshu Center. In both centers, we observed increased CXCL9 and CXCL11 in TPE patients. The areas under the ROC curves (AUCs) of pleural CXCL9 and CXCL11 in the Hohhot Center were 0.70 (95 % CI: 0.55-0.85) and 0.68 (95 % CI: 0.52-0.84), respectively. In the Changshu Center, the AUCs of CXCL9 and CXCL11 were 0.96 (95 % CI: 0.92-1.00) and 0.97 (95 % CI: 0.94-1.00), respectively. The AUCs of CXCL9 and CXCL11 decreased with the advancement of age. The decision curves of CXCL9 and CXCL11 showed net benefits in both centers. CXCL9 and CXCL11 were upregulated in BCG-treated macrophages. Pleural fluid from TPE and conditioned medium from BCG-treated macrophages were chemotactic for Th cells. Anti-CXCL9 or CXCL11 neutralizing antibodies could partly block the chemotactic activity. CONCLUSIONS: Pleural CXCL9 and CXCL11 are potential diagnostic markers for TPE, but their diagnostic accuracy is compromised in elderly patients. CXCL9 and CXCL11 can promote the migration of peripheral Th cells, thus representing a therapeutic target for the treatment of TPE.

Mixed Metal Components in PM2.5 Contribute to Chemokine Receptor CCR5-Mediated Neuroinflammation and Neuropathological Changes in the Mouse Olfactory Bulb.

Particulate matter, especially PM2.5, can invade the central nervous system (CNS) via the olfactory pathway to induce neurotoxicity. The olfactory bulb (OB) is the key component integrating immunoprotection and olfaction processing and is necessarily involved in the relevant CNS health outcomes. Here we show that a microglial chemokine receptor, CCR5, is the target of environmentally relevant PM2.5 in the OB to trigger neuroinflammation and then neuropathological injuries. Mechanistically, PM2.5-induced CCR5 upregulation results in the pro-inflammatory paradigm of microglial activation, which subsequently activates TLR4-NF-κB neuroinflammation signaling and induces neuropathological changes that are closely related to neurodegenerative disorders (e.g., Aß deposition and disruption of the blood-brain barrier). We specifically highlight that manganese and lead in PM2.5 are the main contributors to CCR5-mediated microglial activation and neuroinflammation in synergy with aluminum. Our results uncover a possible pathway of PM2.5-induced neuroinflammation and identify the principal neurotoxic components, which can provide new insight into efficiently diminishing the adverse health effects of PM2.5.

Effects and mechanisms of endocrine disruptor bisphenol AF on male reproductive health: A mini review.

Bisphenol AF (BPAF), an analogue of bisphenol A (BPA), is commonly found in manufacturing industries and known for its endocrine-disrupting properties. Despite potential similarities in adverse effects with BPA, limited toxicological data exist specifically for BPAF and its impact on male reproductive physiology. This mini-review aims to elucidate the influence of BPAF on the male reproductive system, focusing on estrogenic effects, effects on the hypothalamus-pituitary-gonad (HPG) axis, steroidogenesis, spermatogenesis, and transgenerational reproductive toxicity. Additionally, we outline the current insights into the potential mechanisms underlying BPAF-induced male reproductive disorders. BPAF exposure, either directly or maternally, has been associated with detrimental effects on male reproductive functions, including damage to the blood-testis barrier (BTB) structure, disruptions in steroidogenesis, testis dysfunction, decreased anogenital distance (AGD), and defects in sperm and semen quality. Mechanistically, altered gene expression in the HPG axis, deficits in the steroidogenesis pathway, activation of the aromatase pathway, cascade effects induced by reactive oxygen species (ROS), activation of ERK signaling, and immunological responses collectively contribute to the adverse effects of BPAF on the male reproductive system. Given the high prevalence of male reproductive issues and infertility, along with the widespread environmental distribution of bisphenols, this study provides valuable insights into the negative effects of BPAF. The findings underscore the importance of considering the safe use of this compound, urging further exploration and regulatory attention to decrease potential risks associated with BPAF exposure.

Calycosin decreases cerebral ischemia/reperfusion injury by suppressing ACSL4-dependent ferroptosis.

Ischemic stroke is the second leading cause of death globally. Calycosin is a typical phytoestrogen that protects against cerebral ischemia/reperfusion (I/R) injury. However, the role of ferroptosis in this effect remains unknown. In the present study, we investigated the ferroptosis mechanism of calycosin against cerebral I/R injury using transient middle cerebral artery occlusion/reperfusion (tMCAO/R)-exposed rats and oxygen-glucose deprivation/reperfusion (OGD/R)-stimulated PC12 cells. We found that calycosin treatment significantly improved neurological deficits, brain edema, blood-brain barrier (BBB) breakdown, infarction volume, and neuronal injuries in rats that underwent tMCAO/R; similar to ferrostatin-1 (a ferroptosis inhibitor), calycosin prevented cell viability loss in PC12 cells exposed to OGD/R stimulation. In addition, calycosin intervention decreased ferroptosis, as assessed by iron accumulation, malondialdehyde (MDA), superoxide dismutase (SOD), ceramide, and reactive oxygen species (ROS) levels, as well as ferroptosis-related protein expression (ACSL4, TfR1, FTH1, and GPX4). Furthermore, overexpression of ACSL4 reversed calycosin-induced beneficial efficacy in OGD/R-stimulated PC12 cells. The molecular docking analysis demonstrated that calycosin binds to ACSL4 by forming stable hydrogen bonds at G465, K690, and D573. Collectively, these findings indicate that calycosin ameliorates cerebral I/R injury by depressing ACSL4-dependent ferroptosis.

Age affects the diagnostic accuracy of the cancer ratio for malignant pleural effusion.

BACKGROUND AND OBJECTIVE: Cancer ratio (CR), which is defined as serum lactate dehydrogenase (LDH) to pleural fluid adenosine deaminase (ADA) ratio, has been reported to be a useful diagnostic marker for malignant pleural effusion (MPE). Whether its diagnostic accuracy is affected by age remains unknown. This study aimed to investigate the effects of age on the diagnostic accuracy of CR. METHODS: The participants in this study were from a prospective cohort (SIMPLE cohort, n = 199) and a retrospective cohort (BUFF cohort, n = 158). All participants were patients with undiagnosed pleural effusion (PE). We used receiver operating characteristic (ROC) curves to evaluate the diagnostic accuracy of CR. The effect of age on the diagnostic accuracy of CR was investigated by adjusting the upper limit of age for participant enrolment. RESULTS: Eighty-eight MPE patients were verified in the SIMPLE cohort, and thirty-five MPE patients were verified in the BUFF cohort. The AUCs of CR in the SIMPLE and BUFF cohorts were 0.60 (95% CI: 0.52-0.68) and 0.63 (95% CI: 0.54-0.71), respectively. In both cohorts, the AUCs of CR decreased with the advancement of age. CONCLUSION: Age can affect the diagnostic accuracy of CR for MPE. CR has limited diagnostic value in older patients. KEY MESSAGE: Cancer ratio is a promising diagnostic marker for malignant pleural effusion. This study revealed that its diagnostic accuracy decreased in older patients. Its diagnostic accuracy is overestimated by previous studies using tuberculosis and pneumonia patients as controls.

Clinical Study on Gonococcal Infection of the Penile Raphe.

INTRODUCTION: Gonococcal infection of the penile raphe is rarely encountered in the clinical setting. The study aimed to understand the incidence, sites, clinical manifestations, and treatment of gonococcal infection of the penile raphe. METHODS: We enrolled men with gonococcal infection of the penile raphe and men with urethral gonorrhea from January 2010 to December 2021. All patients' demographic data and clinical characteristics were recorded. All patients were treated with ceftriaxone. Incision and drainage were performed in patients with non-ruptured abscesses. Nodules and sinus tract-like lesions that did not resolve after 1 month of treatment were excised. RESULTS: Among 2,736 men who presented with urethral gonorrhea from January 2010 to December 2021, 5 (0.18%) had accompanying gonococcal infection of the penile raphe. An additional two men presented with gonococcal infection of the penile raphe without urethritis. Thus, 7 (0.26%; confidence interval, 0.11-0.56%) of 2,738 men had urethral gonorrhea or gonococcal infection of the penile raphe confirmed both clinically and by laboratory testing. Lesions were present in the frenulum of the prepuce and at the median aspect, proximal end, distal end, and both the proximal and distal ends of the penile raphe. The lesions manifested as abscesses, ulcers, a nodule, and a nodule with a sinus-like lesion. All lesions exhibited tenderness. All seven patients were cured after treatment. CONCLUSION: Gonococcal infection of the penile raphe is a rare, atypical type of involvement of the male urogenital tract by Neisseria gonorrhoeae. It may be a local complication of urethral gonorrhea or an independent primary infection. The proximal end, distal end, and median aspect of the penile raphe can be infected by N. gonorrhoeae. Cutaneous lesions present as abscesses, ulcers, nodules, and sinus-like lesions. Ceftriaxone is effective, but sinus-like lesions require surgery.

Organic Fluorescent Probes for Monitoring Micro-Environments in Living Cells and Tissues.

As a vital parameter in living cells and tissues, the micro-environment is crucial for the living organisms. Significantly, organelles require proper micro-environment to achieve normal physiological processes, and the micro-environment in organelles can reflect the state of organelles in living cells. Moreover, some abnormal micro-environments in organelles are closely related to organelle dysfunction and disease development. So, visualizing and monitoring the variation of micro-environments in organelles is helpful for physiologists and pathologists to study the mechanisms of the relative diseases. Recently, a large variety of fluorescent probes was developed to study the micro-environments in living cells and tissues. However, the systematic and comprehensive reviews on the organelle micro-environment in living cells and tissues have rarely been published, which may hinder the research progress in the field of organic fluorescent probes. In this review, we will summarize the organic fluorescent probes for monitoring the microenvironment, such as viscosity, pH values, polarity, and temperature. Further, diverse organelles (mitochondria, lysosome, endoplasmic reticulum, cell membrane) about microenvironments will be displayed. In this process, the fluorescent probes about the "off-on" and ratiometric category (the diverse fluorescence emission) will be discussed. Moreover, the molecular designing, chemical synthesis, fluorescent mechanism, and the bio-applications of these organic fluorescent probes in cells and tissues will also be discussed. Significantly, the merits and defects of current microenvironment-sensitive probes are outlined and discussed, and the development tendency and challenges for this kind of probe are presented. In brief, this review mainly summarizes some typical examples and highlights the progress of organic fluorescent probes for monitoring micro-environments in living cells and tissues in recent research. We anticipate that this review will deepen the understanding of microenvironment in cells and tissues and facilitate the studies and development of physiology and pathology.

Gonococcal tysonitis, a rare local complication of gonorrhea: a clinical study of 15 cases.

To investigate the incidence, clinical manifestations, and treatments of gonococcal tysonitis in men. We enrolled men with gonococcal tysonitis and men with gonococcal urethritis from January 2000 to December 2020. Demographic data, interval from non-marital sexual contact to the onset of symptoms of gonococcal tysonitis, occurrence sites, and manifestations were recorded for all patients. Ceftriaxone (1 g) was injected intramuscularly once daily for 5 days in patients with lesions comprising abscesses or nodules. A single dose of ceftriaxone (1 g) was injected intramuscularly in patients with sinus-like lesions. Incision and drainage were performed in patients with non-ruptured abscesses. Fifteen patients with gonococcal tysonitis (0.29%; 95% confidence interval: 0.15-0.44%) were observed among 5087 patients with gonococcal urethritis. The mean age was 38.64 years (range, 17-74 years). The mean gonococcal tysonitis incubation period was 6.02 ± 1.37 days (range, 2-11 days). Lesions were present in the right side of the preputial frenulum in seven patients (46.67%), in the left side of the preputial frenulum in six patients (40%), and in both sides of preputial frenulum in two patients (13.33%). The lesions manifested as abscesses in 7 patients (46.67%), nodules in six patients (40%), and sinus-like lesions in two patients (13.33%); all lesions exhibited tenderness. All 15 patients were cured after treatment. Gonococcal tysonitis is a rare local complication of gonorrhea. Gonococcal urethritis with concurrent gonococcal tysonitis was less common than gonococcal urethritis with concurrent paraurethral gonococcal infection or gonococcal urethritis with concurrent gonococcal epididymitis. Gonococcal tysonitis lesions manifest as abscesses, nodules, and sinus-like lesions. Treatment with ceftriaxone is effective for gonococcal tysonitis.

Diagnostic accuracy of pleural fluid lactate dehydrogenase to adenosine deaminase ratio for tuberculous pleural effusion: an analysis of two cohorts.

BACKGROUND: This study aimed to evaluate the diagnostic accuracy of pleural fluid (PF) lactate dehydrogenase (LDH) to adenosine deaminase (ADA) (LDH/ADA) ratio for tuberculous pleural effusion (TPE). Especially to explore whether the LDH/ADA ratio provides added diagnostic value to ADA. METHODS: The diagnostic accuracy of PF LDH/ADA ratio and ADA for TPE was evaluated in two cohorts, named the BUFF (Biomarkers for patients with Undiagnosed pleural eFFusion) cohort (62 with TPE and 194 with non-TPE) and the SIMPLE (a Study Investigating Markers in PLeural Effusion) cohort (33 with TPE and 177 with non-TPE). Receiver operating characteristic (ROC) curve and decision curve were used to measure the diagnostic accuracy of the PF LDH/ADA ratio. The added diagnostic value of the LDH/ADA ratio to ADA was evaluated with net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: The area under the ROC curves (AUCs) of PF ADA and LDH/ADA ratio in the BUFF cohort were 0.76 and 0.74, respectively. In the SIMPLE cohort, the AUCs of PF ADA and LDH/ADA ratio were 0.80 and 0.85, respectively. The decision curves of PF LDH/ADA and ADA were close in both the BUFF and SIMPLE cohorts. The NRI and IDI analyses did not reveal any added diagnostic value of LDH/ADA to ADA. CONCLUSIONS: PF LDH/ADA ratio has moderate diagnostic accuracy for TPE. It does not provide added diagnostic value beyond ADA. The current evidence does not support LDH/ADA ratio for diagnosing TPE.

Inhibition of autophagy-dependent pyroptosis attenuates cerebral ischaemia/reperfusion injury.

Autophagy is closely associated with cerebral ischaemia/reperfusion injury, but the underlying mechanisms are unknown. We investigated whether Spautin-1 ameliorates cerebral ischaemia/reperfusion injury by inhibiting autophagy and whether its derived pyroptosis is involved in this process. We explored the mechanism of Spautin-1 in cerebral ischaemia/reperfusion. To answer these questions, healthy male Sprague-Dawley rats were exposed to middle cerebral artery occlusion for 60 minutes followed by reperfusion for 24 hours. We found that cerebral ischaemia/reperfusion increased the expression levels of autophagy and pyroptosis-related proteins. Treatment with Spautin-1 reduced the infarct size and water content and restored some neurological functions. In vitro experiments were performed using oxygen-glucose deprivation/reoxygenation to model PC12 cells. The results showed that PC12 cells showed a significant decrease in cell viability and a significant increase in ROS and autophagy levels. Spautin-1 treatment reduced autophagy and ROS accumulation and attenuated NLRP3 inflammasome-dependent pyroptosis. However, these beneficial effects were greatly blocked by USP13 overexpression, which significantly counteracted the inhibition of autophagy and NLRP3 inflammasome-dependent ferroptosis by Spautin-1. Together, these results suggest that Spautin-1 may ameliorate cerebral ischaemia-reperfusion injury via the autophagy/pyroptosis pathway. Thus, inhibition of autophagy may be considered as a promising therapeutic approach for cerebral ischaemia-reperfusion injury.

Prevalence and Clinical Manifestations of Penile Gonococcal Cutaneous and Accessory Gland Infections in Men With Gonorrhea.

BACKGROUND: No studies have focused on the prevalence and clinical manifestations of penile gonococcal cutaneous and accessory gland infections in men with gonorrhea. METHODS: We enrolled patients with penile gonococcal cutaneous and accessory gland infections and patients with urethral gonorrhea from January 2014 to February 2020. Demographic data, occurrence sites, and manifestations of all patients were recorded. RESULTS: Fifty-one patients with penile gonococcal cutaneous and accessory gland infections were observed among 1994 (2.6%; 95% confidence interval, 1.9%-3.4%) patients with urethral or penile gonorrhea. Lesions were present at the external urethral orifice in 22 (43%) patients, at the glans in 11 (21%), in the side of the frenulum of the prepuce in 7 (14%), in the penile raphe in 5 (10%), in the inner plate of the prepuce in 1 (2%), in the external urethral orifice and side of the frenulum of the prepuce in 3 (6%), and in the glans and side of the frenulum of the prepuce in 2 (4%). The lesions manifested as sinus-like lesions in 22 (43%) patients, abscesses in 14 (27%), nodules in 10 (20%), pustules in 3 (6%), nodules with sinus tracts in 1 (2%), and ulcers in 1 (2%). CONCLUSIONS: Penile gonococcal cutaneous and accessory gland infections in men probably are more common than previously understood. They mainly involve the paraurethral duct, glans, Tyson's gland, and penile raphe. Lesions mainly present as sinus-like lesions, abscesses, and nodules.

[Correlation between the genotypes and clinical symptoms of human papilloma virus in male outpatients at STD clinics].

OBJECTIVE: To investigate the distribution of the human papilloma virus (HPV) and its genotypes in the male outpatients at the clinics of sexually transmitted diseases (STD) in Changshu and analyze its association with the primary clinical symptoms so as to provide some evidence for the prevention and treatment of HPV infection in men. METHODS: We collected exfoliated cell samples from the external genitals of 602 male outpatients at the STD clinics in Changshu from February 2016 to February 2018, extracted and amplified nucleic acids from the samples, and detected the HPV genotypes using the gene chip technique. We performed statistical analyses on the types of symptoms in clinical diagnosis and their correlation with the genotypes of HPV using the chi-square test. RESULTS: The HPV positive rate in the male STD clinics was 48.2%, of which 47.2 % fell into the low-risk type, 30.0% with multiple infections. The main genotypes included HPV types 6, 11, 39, and 52, and the main HPV-related clinical symptoms were verruca (43.1%) and erythra (41.0%). Low-risk types 6 and 11 accounted for a significantly higher percentage than the high-risk types in the verruca patients (60.0% vs 15.0%, , P < 0.05), but showed no statistically significant difference from the latter in the erythra patients (38.7% vs 38.7%, P > 0.05). The incidence of low-risk infection was remarkably higher than that of high-risk infection in the acrobystitis and balanitis patients (P < 0.05), while the high-risk types constituted a markedly higher percentage than the low-risk and high- and low-risk mixed types in the asymptomatic men at physical examination (84.6% vs 0.0% and 15.4%, P < 0.05). CONCLUSIONS: The HPV positive rate was as high as 48.2% in the males at the STD clinics in Changshu, and the main infection type was low-risk genotype single infection. The clinical symptoms of low-risk infection were mainly verruca and prepuce balanitis, and the high-risk type was mostly asymptomatic at physical examination.

Metabolomic profiles delineate the effect of Sanmiao wan on hyperuricemia in rats.

A serum metabolomic method based on ultra-high-performance liquid chromatography coupled with mass spectrometry was developed to characterize hyperuricemia-related metabolic profiles and delineate the mechanism of Sanmiao wan (SMW), a traditional Chinese medicine (TCM), in treating hyperuricemic rats. With partial least-squares discriminant analysis for classification and selection of biomarkers, 13 potential biomarkers in mouse serum were identified in the screen, primarily involved in purine metabolism, arginine and proline metabolism, citrate cycle, phenylalanine metabolism, tryptophan metabolism and glycerophospholipid metabolism. Taking these potential biomarkers as screening indexes, SMW could reverse the pathological process of hyperuricemia through partially regulating the perturbed metabolic pathway except for glycerophospholipid metabolism. Our results showed that a metabolomic approach offers a useful tool to identify hyperuricemia-related biomarkers and provides a new methodological cue for systematically dissecting the underlying efficacies and mechanisms of TCM in treating hyperuricemia.

Prognostic value of ABO blood group in patients with gastric cancer.

BACKGROUND: Previous studies have shown a link between the ABO blood groups and prognoses for several types of malignancies. However, little is known about the relationship between the ABO blood groups and prognosis in patients with gastric cancer (GC). The aim of this study was to investigate the prognostic performance of ABO blood groups in patients with GC. METHODS: A total of 1412 GC patients who had undergone curative intent surgery between January 2005 and January 2010 participated in the present study. A prognostic nomogram was constructed to improve the predictive capacity for patients with gastrectomy using R software, and its predictive accuracy was determined by the concordance index (c-index). RESULTS: The median follow-up period of the 1412 GC patients was 44 mo with 809 alive. Non-AB blood groups were associated with significantly decreased overall survival in GC patients (hazard ratio = 2.59; 95% confidence interval = 1.74-3.86, P < 0.001), but patients in the group AB had a better prognosis than those in the non-AB blood groups. Meanwhile, group A had the worst prognosis among all the blood groups (hazard ratio = 3.14; 95% confidence interval = 2.09-4.72; P < 0.001). In addition, our constructed nomogram, superior to that of the traditional AJCC stage system (c-index: 0.69), could more accurately predict overall survival (c-index: 0.78) in GC patients who had undergone gastrectomy. CONCLUSIONS: The blood group AB is a favorable prognostic factor for GC patients, but the blood group A is an adverse prognostic factor for patients with gastrectomy. Further prospective studies are warranted to confirm this relationship.

Role of IL-10-Producing Regulatory B Cells in Chronic Hepatitis B Virus Infection.

BACKGROUND: A subset of interleukin (IL)-10-producing regulatory B (Breg) cells that suppress T-cell-mediated immunity was recently identified; however, their role in chronic hepatitis B (CHB) remains elusive. AIM: To explore the possible role of Breg in the interaction with Th cells and consequent pathogenesis of CHB. METHODS: The prevalence of Breg as well as 3 major effector T-cell subsets--CD4(+)CD25(high)Foxp3(+) regulatory T (Treg) cells, T helper 1 cells (Th1), and T helper 2 cells (Th2)--was assessed in the peripheral blood of 31 patients with CHB, 28 patients with acute hepatitis B (AHB), and 25 healthy controls (HC). RESULTS: Compared to patients with AHB and HC, the prevalence of Breg and Treg cells and the concentration of IL-10 in the supernatant of cultured peripheral blood mononuclear cells (PBMCs) were greatly increased in patients with CHB. A significantly decreased proportion of Th1 cells was also observed in patients with CHB and was demonstrated to have a negative correlation with the prevalence of Breg. Furthermore, depletion of Treg cells in the PBMCs of patients with CHB did not alter the frequency of Breg cells or their ability to produce IL-10, indicating little, if any, impact of Treg cells on the generation and maintenance of Breg cells. CONCLUSIONS: Our data indicate that increased Breg cells might be a major source of elevated IL-10 in CHB and represent a critical and independent regulatory force in the development of impaired anti-HBV immunity, consequently contributing to the pathogenesis of CHB.

Pathogen profile in men with inflammation of paraurethral glands.

OBJECTIVE: To investigate the pathogen profile in men with inflammation of the paraurethral glands. METHODS: We enrolled 40 patients with first-onset, drug-naive inflammation of the paraurethral glands. Discharge from the lesions was collected for Gram staining. Microscopy was performed for screening for trichomonads and detecting Gram-negative intracellular diplococci within phagocytes. Cultures for detection of Neisseria gonorrhoeae, Ureaplasma urealyticum and other bacteria, and Chlamydia-trachomatis-associated antigens were performed. PCR was conducted for herpes simplex virus type 1 or 2. RESULTS: From these 40 patients, there were nine microbial species, which included Gram-negative bacteria (23 cases, 54.8%), Gram-positive bacteria (15 cases, 35.7%) and other pathogens (4 cases, 9.5%). The top three pathogens were gonococci (38.1%), Staphylococcus aureus (16.7%) and Escherichia coli (14.3%). CONCLUSIONS: Inflammation of paraurethral glands in men may be caused by a variety of pathogens and not just by gonococcal infection.

Enhanced proliferation and defective activation-induced cell death of CD4+ T cells in childhood asthma.

BACKGROUND: Hyperactivation of CD4+ T cells in peripheral blood and airway tissues has been suggested to play a key role in the development and maintenance of chronic inflammation in childhood asthma. However, the underlying mechanisms are not yet clear. OBJECTIVE: To investigate alterations in serum levels of T helper cell-related cytokines, mitogen-stimulated CD4+ T cell proliferation and activation-induced cell death (AICD) in childhood asthma. METHODS: 21 children with untreated asthma and 21 healthy volunteers (age and gender matched) participated in this study. Th1/Th2/Th17 cytokines in serum were analyzed by flow cytometry. CD4+ T cells were isolated from participants by using immuno-magnetic beads and were stimulated by phytohemagglutinin (PHA). Cell proliferation was evaluated with a Cell Counting Kit-8 (CCK-8). Activation induced cell death (AICD) of CD4+ T cells was also induced by PHA and apoptosis was assayed by annexin V/PI staining. Quantitative RT-PCR was carried out to analyze Fas and FasL mRNA expression. FLIPL, caspase-8 and Bcl-2 were detected by western blot analysis. RESULTS: In children with asthma, the proliferative capacity of CD4+ T cells was enhanced and AICD was inhibited significantly, while serum IL-4, IL-10 and TNF were markedly higher compared with the control group. Fas mRNA expression in the asthma group was obviously lower than that in the control group, while no change was detected in FasL mRNA expression. Western blot analysis showed that the levels of the anti-apoptotic proteins, FLIPL and Bcl-2 in CD4+ T cells of the asthma group were significantly higher than in the control group. Spearman's correlation tests showed that only IL-4 correlated positively with FLIPL and Bcl-2 expression, while IL-10 and TNF were unrelated to FLIPL and Bcl-2 expression. CONCLUSIONS: These results indicate that enhanced proliferation and defective AICD of CD4+ T cells influence the T cell-mediated inflammatory reaction in childhood asthma and that increased IL-4, FLIPL and Bcl-2 expression and decreased Fas expression jointly participate in these changes in cell proliferation and apoptosis.ression and decreased Fas expression jointly participate in these changes in cell proliferation and apoptosis.

Extrahepatic conditions of primary biliary cholangitis: A systematic review and meta-analysis of prevalence and risk.

BACKGROUND AND AIM: Many studies reported the prevalence of extrahepatic conditions (EHC) of primary biliary cholangitis (PBC), but the great heterogeneity existed across different studies. Therefore, we conducted the systematic review and meta-analyses to determine EHC prevalence and association with PBC. METHODS: We searched PUBMED and included observational, cross-sectional and case-controlled studies. A random or fixed effects model was used to estimate the pooled prevalence and odd ratio (OR) as appropriate. RESULTS: Of 5370 identified publications, 129 publications with 133 studies met the inclusion criteria. Sjögren's syndrome had the highest prevalence (21.4 % vs. 3 % in non-PBC individuals), followed by Raynaud's syndrome (12.3 % vs. 1 %), rheumatoid arthritis-like arthritis (5 % vs. 3 %), systemic sclerosis (3.7 % vs. 0 %) and systemic lupus erythematosus (2 % vs. 0 %). The prevalence of overall thyroid diseases (11.3 %), autoimmune thyroid diseases (9.9 %), osteoporosis (21.1 %), celiac disease (1 %) and chronic bronchitis (4.6 %) was also increased among PBC patients. CONCLUSION: This is the first exhaustive study on the old theme about EHC of PBC. Given increased prevalence of many EHCs in PBC patients, promptly recognizing these EHCs are of great importance for timely and precise diagnosis of PBC.