The effects of treating GERD on the outcomes of otitis media with effusion: A systematic review and meta-analysis.

OBJECTIVE: Gastroesophageal reflux disease (GERD) may cause otitis media with effusion (OME). However, whether treating GERD can benefit patients with OME has not been well studied. METHODS: We systematically searched PubMed, Embase, Cochrane Library, and Wanfang databases. The search period was from the establishment of the databases until December 31, 2022. Clinical studies related to GERD treatment on the outcomes of OME were included. Two reviewers independently conducted literature screening and data extraction according to the inclusion and exclusion criteria. To evaluate the quality of the included studies, we used the NOS assessment tool and the RevMan 5.4. Subgroup analysis was conducted to reduce the risk of heterogeneity, and Egger and Begg funnel plots were used to evaluate publication bias. Meta-analysis was performed using Stata14.0 and Review Manager 5.4 software. RESULTS: Finally, 21,744 patients from 16 studies were included. The results showed that the rate of GERD in OME patients was 0.56 (95 % confidence interval (CI): 0.33, 0.79), while it was 0.04 (95 % CI: 0.03, 0.05) in the adult GERD population. The combined risk ratio (RR) of OME in patients with versus without GERD was 1.58 (95 % CI: 1.35, 1.85; p < 0.01). The efficacy rate of GERD treatment in OME patients was 0.59 (95 % CI: 0.44, 0.74), especially for those with chronic OME (0.64, 95 % CI: 0.36, 0.92). Compared to the control group, treatment with GERD improved the symptoms and efficacy of OME (OR = 1.65; 95 % CI: 0.95, 2.85; p > 0.05). The hearing loss cure rate was 0.70 (95 % CI: 0.57, 0.82). CONCLUSION: GERD has been suggested to be a high-risk factor for OME. Treatment of GERD can improve the symptoms of OME. However, further studies are required to verify these findings.

IGF2 deficiency promotes liver aging through mitochondrial dysfunction and upregulated CEBPB signaling in D-galactose-induced aging mice.

BACKGROUND: Liver aging, marked by cellular senescence and low-grade inflammation, heightens susceptibility to chronic liver disease and worsens its prognosis. Insulin-like growth factor 2 (IGF2) has been implicated in numerous aging-related diseases. Nevertheless, its role and underlying molecular mechanisms in liver aging remain largely unexplored. METHODS: The expression of IGF2 was examined in the liver of young (2-4 months), middle-aged (9-12 months), and old (24-26 months) C57BL/6 mice. In vivo, we used transgenic IGF2f/f; Alb-Cre mice and D-galactose-induced aging model to explore the role of IGF2 in liver aging. In vitro, we used specific short hairpin RNA against IGF2 to knock down IGF2 in AML12 cells. D-galactose and hydrogen peroxide treatment were used to induce AML12 cell senescence. RESULTS: We observed a significant reduction of IGF2 levels in the livers of aged mice. Subsequently, we demonstrated that IGF2 deficiency promoted senescence phenotypes and senescence-associated secretory phenotypes (SASPs), both in vitro and in vivo aging models. Moreover, IGF2 deficiency impaired mitochondrial function, reducing mitochondrial respiratory capacity, mitochondrial membrane potential, and nicotinamide adenine dinucleotide (NAD)+/NADH ratio, increasing intracellular and mitochondrial reactive oxygen species levels, and disrupting mitochondrial membrane structure. Additionally, IGF2 deficiency markedly upregulated CCAAT/enhancer-binding protein beta (CEBPB). Notably, inhibiting CEBPB reversed the senescence phenotypes and reduced SASPs induced by IGF2 deficiency. CONCLUSIONS: In summary, our findings strongly suggest that IGF2 deficiency promotes liver aging through mitochondrial dysfunction and upregulated CEBPB signaling. These results provide compelling evidence for considering IGF2 as a potential target for interventions aimed at slowing down the process of liver aging.

High-normal free thyroxine level is related with decreased bone mineral density in nonobese male patients with type 2 diabetes over 50 years old.

Background: The prevalence of 'low bone mineral density (BMD)' in Type 2 diabetes (T2DM), especially stratified by body mass index, is seldom reported. The relation of the euthyroid range and low BMD in T2DM remains to be further elucidated. Objectives: We aim to investigate the thyroid hormones' impact on BMD among euthyroid patients with T2DM. Design and methods: A total of 1452 hospitalized T2DM patients with normal thyroid function (43.6% males aged over 50 and 56.4% postmenopausal females) were enrolled in this cross-sectional study. BMD was measured at lumbar spine by GE lunar dual-energy X-ray absorptiometry system, and 'low BMD' was defined as T-score <-1.0 SD. The prevalence of 'low BMD' was compared between obese and nonobese (body mass index < 25 kg/m2) groups for both sexes, and the relation of low BMD and free T4 quartiles was explored by multiple logistic regression. Results: The general prevalence of 'low BMD' was 12.3% for male patients aged over 50 (15.5% in the nonobese group and 8.0% in the obese group) and 49.8% for postmenopausal females (56.7% in the nonobese group and 48.9% in the obese group). After adjustment in multiple linear regression, free T4 level remained significantly related to decreased BMD in nonobese male subgroup. Multiple logistic regression revealed that BMD of the highest free T4 quartile (1.12-1.48 ng/dL) decreased significantly than other three quartiles after adjusting for confounding factors including age, body mass index, serum calcium and creatinine level, fasting glucose, alkaline phosphatase, glycosylated hemoglobin, total cholesterol, and smoking history (OR = 2.724, 95% CI = 1.085-6.840, p = 0.033). No significant relation was found in obese male or postmenopausal female groups. Conclusion: High-normal free T4 is a potential independent risk factor for 'low BMD' in nonobese male T2DM patients aged over 50. Close attention should be paid to thyroid function profile, even within normal range, in nonobese men with underlying higher fracture risks on diabetes status.

Case Report: Recurrent Autoimmune Hypoglycemia Induced by Non-Hypoglycemic Medications.

We present a case of recurrent autoimmune hypoglycemia induced by non-hypoglycemic agents. We review reported cases of autoimmune hypoglycemia related to non-hypoglycemic agents, and discuss the effects of different detection methods for insulin autoantibodies on the results obtained. We aim to provide information for clinicians and a warning for medication usage. Considering the increasing number of clopidogrel-induced AIH cases and the hypoglycemia-induced increase in the risk of cardiovascular events, we recommend that cardiovascular disease patients being treated with clopidogrel be informed of this rare side effect and that clinicians be vigilant for the possibility of autoimmune hypoglycemia in this patient population.

The Different Effects of Skeletal Muscle and Fat Mass on Height Increment in Children and Adolescents Aged 6-11 Years: A Cohort Study From China.

Objective: This study aimed to investigate the contribution of body composition including skeletal muscle mass (SMM) and body fat mass (BFM) to longitudinal growth among children and adolescents aged 6-11 years old. Methods: This cohort study was conducted from the annual health examination between 2019 and 2020. Annual height gain and weight gain and changes in SMM and BFM were calculated and compared between sexes, different nutritional status, and growth curve shifting mode. Spearman analyses and multiple linear regression analysis were performed to identify the impact of SMM, BFM, or body mass index (BMI) on height gain. Results: Of the 584 subjects, the annual height gains of boys (4.76 cm in the 6-9-year group and 4.63 cm in the 10-11-year group) were significantly lower than those of girls (5.48 and 5.74 cm, respectively). Spearman analysis showed that SMM gain and height gain were positively and significantly correlated in each examination of all children (r = 0.535 for boys and 0.734 for girls, p < 0.001). Conversely, BFM and height gains were negatively (r = -0.5240 for boys and -0.232 for girls, p < 0.001) correlated. Multiple linear regression analysis identified SMM gain as an independent predictor (95% CI: 1.20,1.44) of height gain after adjusting for age, gender, BMI, BFM gain, and percentage of body fat (PBF). Conclusion: SMM gains, rather than BFM gains, were associated with height gains in children and adolescents aged 6-11 years. Monitoring SMM changes in routine healthcare might motivate children and adolescents to achieve dietary and exercise recommendations, thereby growing taller without gaining excessive weight.

Combining CRISPR-Cas12a-Based Technology and Metagenomics Next Generation Sequencing: A New Paradigm for Rapid and Full-Scale Detection of Microbes in Infectious Diabetic Foot Samples.

Introduction: Diabetic foot infections (DFIs) pose a huge challenge for clinicians. Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), is one of the most significant pathogens of DFI. Early pathogen identification will greatly benefit the diagnosis and treatment of the disease. However, existing diagnostic methods are not effective in early detection. Methods: We developed an assay that coupled loop-mediated isothermal amplification (LAMP) and clustered regularly interspaced short palindromic repeats (CRISPR) techniques to enable quick and specific detection of Staphylococcus aureus and differentiate MRSA in samples from patients with DFI. Furthermore, the results were compared using a reference culture, quantitative real-time polymerase chain reaction (qRT-PCR), and metagenomics next generation sequencing (mNGS). Results: The CRISPR-LAMP assay targeting nuc and mecA successfully detected S. aureus strains and differentiated MRSA. The limit of detection (LoD) of the real-time LAMP for nuc and mecA was 20 copies per microliter reaction in comparison to two copies per µL reaction for the qRT-PCR assay. The specificity of the LAMP-CRISPR assay for nuc was 100%, without cross-reactions with non-S. aureus strains. Evaluating assay performance with 18 samples from DFI patients showed that the assay had 94.4% agreement (17/18 samples) with clinical culture results. The results of mNGS for 8/18 samples were consistent with those of the reference culture and LAMP-CRISPR assay. Conclusion: The findings suggest that the LAMP-CRISPR assay could be promising for the point-of-care detection of S. aureus and the differentiation of MRSA in clinical samples. Furthermore, combining the LAMP-CRISPR assay and mNGS provides an advanced platform for molecular pathogen diagnosis of DFI.

Knockdown of insulin-like growth factor 2 gene disrupts mitochondrial functions in the liver.

Even though insulin-like growth factor 2 (IGF2) has been reported to be overexpressed in nonalcoholic fatty liver disease (NAFLD), its role in the progression of NAFLD and the potential mechanism remain largely unclear. Using in vitro models, we found that IGF2 was the key overexpressed gene in steatosis, suggesting a possible association between IGF2 and NAFLD. Interestingly, loss-of-function experiments revealed that inhibition of IGF2 protein impaired mitochondrial biogenesis and respiration. It additionally disrupted the expression changes of mitochondrial fusion and fission-related proteins necessary in maintaining mitochondrial homeostasis. Consistently, IGF2 knockdown reduced the mitochondrial membrane potential and increased the production of reactive oxygen species. Mechanistically, IGF2 regulates mitochondrial functions by modulating the expression of SIRT1 and its downstream gene PGC1α. This research opens a new frontier on the role of IGF2 in energy metabolism, which potentially participates in the development of NAFLD. As such, IGF2 is a potential therapeutic target against NAFLD.

Relative Adrenocortical Insufficiency Following Radioactive Iodine Therapy for Graves' Disease: A Report of Two Cases.

INTRODUCTION: In recent years, radioactive iodine (RAI) therapy has become a main choice for Graves' disease. The rapid release of thyroid hormones following RAI may on occasion trigger severe events, such as thyroid storm or heart block. This study presents two cases of possible acute adrenocortical insufficiency precipitated by radioiodine therapy. CASE PRESENTATION: Two females aged 65 and 19 years with long-standing Graves' disease underwent radioiodine treatment at our clinical center. Both patients suffered nausea, fatigue, aggravated palpitation, and relative hypotension thereafter. Laboratory data showed severe thyrotoxicosis with free thyroxine higher than three times the upper limit, while basal serum cortisol (8 AM) was below the lower limit (5.08 µg/dL and 2.08 µg/dL respectively) under stress, indicating a potential relative adrenocortical insufficiency. There was then full recovery after adequate hydrocortisone therapy. As thyrotoxicosis resolved, the levels of basal cortisol were subsequently raised to normal. CONCLUSION: Post-RAI adrenocortical insufficiency might occur in patients with severe Graves' disease. Basal serum cortisol might be a cost-effective parameter for the identification of potential patients.

Clinical evaluation of a laboratory-developed test using clone E1L3N for the detection of PD-L1 expression status in non-small cell lung cancer.

BACKGROUND: Programmed death ligand 1 (PD-L1) has been used as a diagnostic marker to identify patients that will benefit from immune checkpoint inhibitors in non-small cell lung cancer (NSCLC). Immunohistochemistry with E1L3N clone is one of the most widely used and inexpensive laboratory-developed tests for PD-L1, but still need to be compared and validated with standard methods for clinical application. METHODS: We investigated the performance of E1L3N clone for PD-L1 testing in 299 tumor tissues of NSCLC patients and its comparability with FDA-approved 22C3 clone. RESULTS: The results show that the negative coincidence rate, weak positive coincidence rate, and positive coincidence rate were 97.4%, 92.2%, and 97.6% using the E1L3N assay relative to the 22C3 assay, respectively. An overall agreement of 96.3% was achieved between these two assays. We also found that the overall concordances were 97.8% and 93.9% for PD-L1 detection in large and small specimens, respectively, and no significant difference was obtained between these two assays (p = 0.076). In addition, the expression of PD-L1 was not detected in tumor tissues of benign lung disease using both the E1L3N and 22C3 assays. CONCLUSION: E1L3N can be used as a reliable alternative antibody clone to evaluate PD-L1 expression status for NSCLC patients.

Long noncoding RNA small nucleolar RNA host gene 12 promotes papillary thyroid carcinoma cell growth and invasion by targeting miR-16-5p.

Emerging evidence has shown that long noncoding RNA (lncRNA) plays an important role in various types of malignant cancer. Small nucleolar RNA host gene 12 (SNHG12) was found to be upregulated and to act as an oncogene in several cancers. However, the function and regulatory mechanism of SNHG12 remain unclear in papillary thyroid carcinoma (PTC). In this study, SNHG12 was found to be increased in PTC tissues and cell lines using quantitative real-time PCR. Knockdown of SNHG12 significantly inhibited PTC cell proliferation, migration and invasion and induced apoptosis in vitro. Mechanistic investigations revealed that SNHG12 functions as a competing endogenous RNA (ceRNA) to sponge miR-16-5p, which was downregulated in PTC tissues. In addition, rescue assays further confirmed that SNHG12 contributed to the progression of PTC through regulating miR-16-5p expression. These results indicated that SNHG12 might contribute to tumor progression in PTC by acting as a ceRNA to sponge miR-16-5p.

Deciphering the biodiversity of Listeria monocytogenes lineage III strains by polyphasic approaches.

Listeria monocytogenes is a foodborne pathogen of humans and animals. The majority of human listeriosis cases are caused by strains of lineages I and II, while lineage III strains are rare and seldom implicated in human listeriosis. We revealed by 16S rRNA sequencing the special evolutionary status of L. monocytogenes lineage III, which falls between lineages I and II strains of L. monocytogenes and the non-pathogenic species L. innocua and L. marthii in the dendrogram. Thirteen lineage III strains were then characterized by polyphasic approaches. Biochemical reactions demonstrated 8 biotypes, internalin profiling identified 10 internal-in types clustered in 4 groups, and multilocus sequence typing differentiated 12 sequence types. These typing schemes show that lineage III strains represent the most diverse population of L. monocytogenes, and comprise at least four subpopulations IIIA-1, IIIA-2, HIB, and IIIC. The in vitro and in vivo virulence assessments showed that two lineage IIIA-2 strains had reduced pathogenicity, while the other lineage III strains had comparable virulence to lineages I and II. The HIB strains are phylogenetically distinct from other sub-populations, providing additional evidence that this sublineage represents a novel lineage. The two biochemical reactions L-rhamnose and L-lactate alkalinization, and 10 internalins were identified as potential markers for lineage III subpopulations. This study provides new insights into the biodiversity and population structure of lineage III strains, which are important for understanding the evolution of the L. mono-cytogenes-L. innocua clade.

Lmo0036, an ornithine and putrescine carbamoyltransferase in Listeria monocytogenes, participates in arginine deiminase and agmatine deiminase pathways and mediates acid tolerance.

Listeria monocytogenes is a foodborne pathogen causing listeriosis. Acid is one of the stresses that foodborne pathogens encounter most frequently. The ability to survive and proliferate in acidic environments is a prerequisite for infection. However, there is limited knowledge about the molecular basis of adaptation of L. monocytogenes to acid. Arginine deiminase (ADI) and agmatine deiminase (AgDI) systems are implicated in bacterial tolerance to acidic environments. Homologues of ADI and AgDI systems have been found in L. monocytogenes lineages I and II strains. Sequence analysis indicated that lmo0036 encodes a putative carbamoyltransferase containing conserved motifs and residues important for substrate binding. Lmo0036 acted as an ornithine carbamoyltransferase and putrescine carbamoyltransferase, representing the first example, to our knowledge, that catalyses reversible ornithine and putrescine carbamoyltransfer reactions. Catabolic ornithine and putrescine carbamoyltransfer reactions constitute the second step of ADI and AgDI pathways. However, the equilibrium of in vitro carbamoyltransfer reactions was overwhelmingly towards the anabolic direction, suggesting that catabolic carbamoyltransferase was probably the limiting step of the pathways. lmo0036 was induced at the transcriptional level when L. monocytogenes was subjected to low-pH stress. Its expression product in Escherichia coli exhibited higher catabolic carbamoyltransfer activities under acidic conditions. Consistently, absence of this enzyme impaired the growth of Listeria under mild acidic conditions (pH 4.8) and reduced its survival in synthetic human gastric fluid (pH 2.5), and corresponded to a loss in ammonia production, indicating that Lmo0036 was responsible for acid tolerance at both sublethal and lethal pH levels. Furthermore, Lmo0036 played a possible role in Listeria virulence.