Transglutaminase 2 serves as a pathogenic hub gene of KRAS mutant colon cancer based on integrated analysis.

BACKGROUND: Colon cancer is acknowledged as one of the most common malignancies worldwide, ranking third in United States regarding incidence and mortality. Notably, approximately 40% of colon cancer cases harbor oncogenic KRAS mutations, resulting in the continuous activation of epidermal growth factor receptor signaling. AIM: To investigate the key pathogenic genes in KRAS mutant colon cancer holds considerable importance. METHODS: Weighted gene co-expression network analysis, in combination with additional bioinformatics analysis, were conducted to screen the key factors driving the progression of KRAS mutant colon cancer. Meanwhile, various in vitro experiments were also conducted to explore the biological function of transglutaminase 2 (TGM2). RESULTS: Integrated analysis demonstrated that TGM2 acted as an independent prognostic factor for progression-free survival. Immunohistochemical analysis on tissue microarrays revealed that TGM2 was associated with an elevated probability of perineural invasion in patients with KRAS mutant colon cancer. Additionally, biological roles of the key gene TGM2 was also assessed, suggesting that the downregulation of TGM2 attenuated the proliferation, invasion, and migration of the KRAS mutant colon cancer cell line. CONCLUSION: This study underscores the potential significance of TGM2 in the progression of KRAS mutant colon cancer. This insight not only offers a theoretical foundation for therapeutic approaches but also highlights the need for additional clinical trials and fundamental research to support our preliminary findings.

A phase 4 multicentre, 2×2 factorial randomised, double-blind, placebo-controlled trial to investigate the efficacy and safety of tobramycin inhalation solution for Pseudomonas aeruginosa eradication in bronchiectasis: ERASE.

Chronic Pseudomonas aeruginosa (PA) infection significantly contributes to morbidity and mortality in bronchiectasis patients. Initiating antibiotics early may lead to the eradication of PA. Here we outline the design of a trial (ERASE; NCT06093191) assessing the efficacy and safety of inhaled tobramycin, alone or with oral ciprofloxacin, in bronchiectasis patients with a new isolation of PA. This multicentre, 2×2 factorial randomised, double-blind, placebo-controlled, parallel-group trial includes a 2-week screening period, a 12-week treatment phase (with a combination of ciprofloxacin or a placebo at initial 2 weeks) and a 24-week follow-up. 364 adults with bronchiectasis and a new PA isolation will be randomly assigned to one of four groups: placebo (inhaled saline and ciprofloxacin placebo twice daily), ciprofloxacin alone (750 mg ciprofloxacin and inhaled saline twice daily), inhaled tobramycin alone (inhaled 300 mg tobramycin and ciprofloxacin placebo twice daily) or a combination of both drugs (inhaled 300 mg tobramycin and 750 mg ciprofloxacin twice daily). The primary objective of this study is to assess the proportion of patients successfully eradicating PA in each group by the end of the study. Efficacy will be evaluated based on the eradication rate of PA at other time points (12, 24 and 36 weeks), the occurrence of exacerbations and hospitalisations, time to first pulmonary exacerbations, patient-reported outcomes, symptom measures, pulmonary function tests and the cost of hospitalisations. To date no randomised trial has evaluated the benefit of different PA eradication strategies in bronchiectasis patients. The ERASE trial will therefore generate crucial data to inform future clinical guidelines.

Risk factors and predicting nomogram for the clinical deterioration of non-severe community-acquired pneumonia.

BACKGROUND: Currently, there remains insufficient focus on non-severe community-acquired pneumonia (CAP) patients who are at risk of clinical deterioration, and there is also a dearth of research on the related risk factors. Early recognition of hospitalized patients at risk of clinical deterioration will be beneficial for their clinical management. METHOD: A retrospective study was conducted in The First Affiliated Hospital of Wenzhou Medical University, China, spanning from January 1, 2018 to April 30, 2022, and involving a total of 1,632 non-severe CAP patients. Based on whether their condition worsened within 72 h of admission, patients were divided into a clinical deterioration group and a non-clinical deterioration group. Additionally, all patients were randomly assigned to a training set containing 75% of patients and a validation set containing 25% of patients. In the training set, risk factors for clinical deterioration in patients with non-severe CAP were identified by using LASSO regression analysis and multivariate logistic regression analysis. A nomogram was developed based on identified risk factors. The effectiveness of the nomogram in both the training and validation sets was assessed using Receiver Operating Characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). RESULTS: Age, body mass index (BMI), body temperature, cardiovascular comorbidity, respiratory rate, LDH level, lymphocyte count and D-dimer level were identified as risk factors associated with the clinical deterioration of non-severe CAP within 72 h of admission. The area under curve (AUC) value of the nomogram was 0.78 (95% CI: 0.74-0.82) in the training set and 0.75 (95% CI: 0.67-0.83) in the validation set. Furthermore, the calibration curves for both the training and validation sets indicated that the predicted probability of clinical deterioration aligned with the actual probability. Additionally, DCA revealed clinical utility for the nomogram at a specific threshold probability. CONCLUSION: The study successfully identified the risk factors linked to the clinical deterioration of non-severe CAP and constructed a nomogram for predicting the probability of deterioration. The nomogram demonstrated favorable predictive performance and has the potential to aid in the early identification and management of non-severe CAP patients at elevated risk of deterioration.

Genome-Wide Identification of Detoxification Genes in Wild Silkworm Antheraea pernyi and Transcriptional Response to Coumaphos.

For a half-century, the commercial wild silkworm, Antheraea pernyi, has been protected by coumaphos, which is an internal organophosphorus insecticide used to kill the potential parasitic fly larvae inside. Knowledge about the detoxification genes of A. pernyi as well as the detoxification mechanism for this species remains severely limited. In this study, we identified 281 detoxification genes (32 GSTs, 48 ABCs, 104 CYPs, and 97 COEs) in the genome of this insect, which are unevenly distributed over 46 chromosomes. When compared to the domesticated silkworm, Bombyx mori, a lepidopteran model species, A. pernyi has a similar number of ABCs, but a greater number of GSTs, CYPs, and COEs. By transcriptome-based expression analysis, we found that coumaphos at a safe concentration level significantly changed the pathways related to ATPase complex function and the transporter complex in A. pernyi. KEGG functional enrichment analysis indicated that protein processing in the endoplasmic reticulum was the most affected pathway after coumaphos treatment. Finally, we identified four significantly up-regulated detoxification genes (ABCB1, ABCB3, ABCG11, and ae43) and one significantly down-regulated detoxification gene (CYP6AE9) in response to coumaphos treatment, suggesting that these five genes may contribute to detoxification of coumaphos in A. pernyi. Our study provides the first set of detoxification genes for wild silkworms from Saturniidae and highlights the importance of detoxification gene repertoire in insect pesticide tolerance.

Endovascular treatment achieves better outcomes than best medical management in patients with M2 occlusion and high stroke severity: a meta-analysis.

BACKGROUND: The lack of randomized evidence makes it difficult to establish reliable treatment recommendations for patients with M2 occlusion. This study aims to compare the efficacy and safety of endovascular treatment (EVT) with best medical management (BMM) in patients with M2 occlusion, and to investigate whether the optimal treatment varies according to stroke severity. METHODS: Comprehensive literature retrieval was conducted to identify studies that directly compared the outcomes of EVT and BMM. According to stroke severity, the study population were classified into those with moderate-severe stroke and those with mild stroke. National Institute of Health Stroke Scale (NIHSS) scores ≥ 6 was defined as moderate-severe stroke, and NIHSS scores 0-5 as mild stroke. Random-effects meta-analyses were performed to measure the symptomatic intracranial hemorrhage (sICH) within 72 h, and the modified Rankin Scale (mRS) scores 0-2 and the mortality at 90 days. RESULTS: Totally, 20 studies were identified, including 4358 patients. In the moderate-severe stroke population, the EVT had 82% higher odds for mRS scores 0-2 (OR 1.82, 95% CI 1.34-2.49) and a 43% lower odds for mortality (OR 0.57, 95% CI 0.39-0.82) compared with the BMM. However, no difference was found in the sICH rate (OR 0.88, 95% CI 0.44-1.77). In the mild stroke population, no differences were observed in the mRS scores 0-2 (OR 0.81, 95% CI 0.59-1.10) or mortality (OR 1.23, 95% CI 0.72-2.10) between EVT and BMM, whereas EVT was associated with higher sICH rate (OR 4.21, 95% CI 1.86-9.49). CONCLUSION: EVT may be only beneficial for patients with M2 occlusion and high stroke severity, but not for those with NIHSS scores 0-5.

Genetic polymorphisms of PRKAA1 (AMPKα1) and postherpetic pain susceptibility: Multicenter, randomized control, and haplotype analysis study.

Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is a pivotal regulatory protein in energy metabolism. In a pilot study, we found that AMPK-associated energy metabolism imbalance in neurons contributes to the occurrence and maintenance of neuropathic pain (NeP). This study aimed to explore the relationship between genetic polymorphisms of AMPK gene (Rs13361707, rs3792822, and rs10074991) in PRKAA1 and postherpetic neuralgia (PHN) in Chinese individuals. Hundred and thirty two patients with PHN and 118 control individuals were enrolled in this study. All blood samples were shuffled and blinded to the person performing the haplotype analysis. Rs13361707, rs3792822, and rs10074991 PRKAA1 genotypes were identified in all participants. Dominant and recessive models were used for evaluating the association between these nucleotide polymorphisms and PHN susceptibility. A haplotype analysis of PHN patients and healthy controls was performed. Clinical characteristics between the two groups were not significantly different (p > 0.05) except that the ages in control subjects were younger than the PHN patients (p < 0.05). Genotypes and allele frequencies are significantly different between the PHN patients and control subjects for the rs13361707 and rs10074991 polymorphisms (p < 0.05), but not for rs3792822 (p > 0.05). In addition, the CCG haplotype of rs13361707-rs3792822-rs10074991 correlated negatively with PHN occurrence, but TCA was positively correlated with PHN (p < 0.05). Our results indicate that PRKAA1 gene polymorphisms rs13361707 and rs10074991 were associated with a risk of PHN, and that the CCG haplotype of rs13361707-rs3792822-rs10074991 correlated negatively with PHN occurrence in haplotype analysis. TCA was positively associated with PHN in Chinese individuals.

The Clinical Impact of Metagenomic Next-Generation Sequencing (mNGS) Test in Hospitalized Patients with Suspected Sepsis: A Multicenter Prospective Study.

Background: Metagenomic Next Generation Sequencing (mNGS) has the potential to detect pathogens rapidly. We aimed to assess the diagnostic performance of mNGS in hospitalized patients with suspected sepsis and evaluate its role in guiding antimicrobial therapy. Methods: A multicenter, prospective cohort study was performed. We enrolled patients with suspected sepsis, collected clinical characteristics and blood samples, and recorded the 30-day survival. Diagnostic efficacy of mNGS test and blood culture was compared, and the clinical impact of mNGS on antibiotic regimen modification was analyzed. Results: A total of 277 patients were enrolled, and 162 were diagnosed with sepsis. The mortality was 44.8% (121/270). The mNGS test exhibited shorter turn-out time (27.0 (26.0, 29.0) vs. 96.0 (72.0, 140.3) hours, p < 0.001) and higher sensitivity (90.5% vs. 36.0%, p < 0.001) compared with blood culture, especially for fungal infections. The mNGS test showed better performance for patients with mild symptoms, prior antibiotic use, and early stage of infection than blood culture, and was capable of guiding antibiotic regimen modification and improving prognosis. Higher reads of pathogens detected by mNGS were related to 30-day mortality (p = 0.002). Conclusions: Blood mNGS testing might be helpful for early etiological diagnosis of patients with suspected sepsis, guiding the antibiotic regimen modification and improving prognosis.

Micropyrones A and B, two new α-pyrones from the actinomycete Microbacterium sp. GJ312 isolated from Glycyrrhiza uralensis Fisch.

Two new α-pyrones, micropyrones A (1) and B (2), along with four known γ-pyrones, nocapyrone D (3), nocapyrone A (4), marinactinone A (5), and nocapyrone H (6), were isolated from the culture extract of actinomycete Microbacterium sp. GJ312, which was isolated from Glycyrrhiza uralensis. The structures of these compounds were identified by analysis of spectral data. They are the first α- and γ-pyrones reported from the genus Microbacterium. The antibacterial activity of all compounds against Staphylococcus aureus and methicillin resistant S. aureus was evaluated. However, none of them showed significant activity. This study represents the first phytochemical example of a Glycyrrhiza-derived actinomycete.

Effect of AMPK Subunit Alpha 2 Polymorphisms on Postherpetic Pain Susceptibility in Southwestern Han Chinese.

Introduction: Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) can influence energy metabolism. Energy metabolism imbalance is closely associated with the occurrence of neuropathic pain (NeP). Rs10789038 and rs2796498 are genetic polymorphisms of PRKAA2, the gene encoding AMPK, which is closely related to energy metabolism imbalance. This study aimed to explore the relationship between PRKAA2 and postherpetic neuralgia (PHN) in the southwestern Chinese Han population. Methods: This study enrolled 132 PHN patients and 118 healthy subjects. The rs10789038 and rs2796498 PRKAA2 genotypes were identified in all participants. The association between these single nucleotide polymorphisms and PHN susceptibility was evaluated in the dominant and recessive models. Haplotype analysis of patients with PHN and healthy controls was performed. Results: The PHN patients were older than the healthy subjects (P < 0.05); however, the other clinical characteristics between two groups were not significantly different (all P >0.05). Genotypes and allele frequencies differed significantly between PHN patients and healthy subjects in the rs10789038 polymorphism (P < 0.05), but not in rs2796498 (P > 0.05). In addition, the GG haplotype of rs10789038-rs2796498 correlated negatively with PHN occurrence in haplotype analysis (P < 0.05). Conclusion: PHN occurrence may be related to the PRKAA2 rs10789038 A>G genetic polymorphism in the southwestern Chinese Han population.

Effectiveness and safety of bedaquiline-containing regimens for treatment on patients with refractory RR/MDR/XDR-tuberculosis: a retrospective cohort study in East China.

OBJECTIVE: Refractory rifampicin-resistant/multidrug resistant/extensively-drug resistant tuberculosis (RR/MDR/XDR-TB) were defined as patients infected with Mycobacterium tuberculosis (MTB) resistant to rifampicin(RR-TB), or at least resistant to rifampicin and isoniazid (MDR-TB) or added resistant to fluoroquinolones (FQs) and one of second line injectable agents (XDR-TB), a patient for whom an effective regimen (fewer than 4 effective agents due to adverse events (AEs) or multiple drug resistances) cannot be developed. To compare the effectiveness and safety of bedaquiline (BDQ)-containing and BDQ-free regimens for treatment of patients with refractory RR/MDR/XDR-TB. METHODS: Patients with refractory RR/MDR/XDR-TB receiving BDQ-containing regimens (BDQ group, n = 102) and BDQ-free regimens (non-BDQ group, n = 100) satisfied with included criteria were strictly included in this retrospective historical control study across East China. Culture conversion, treatment outcome, cavity closing rate, and AEs were compared between two groups. RESULTS: The baseline characteristics involved all possible aspects of patients were well balanced between two groups (p > 0.05). Culture conversion rates in the BDQ group at month 3 (89.2% vs. 66.0%), month 6 (90.2% vs 72.0%), month 9 (91.2% vs. 66.0%), and month 12 (94.1% vs 65.0%) were all significantly higher than those in non-BDQ group (p < 0.001). Similar results were observed in the cavity closing rate at month 9 (19.6% vs 8.0%, p = 0.0) and month 12 (39.2% vs 15.0%, p < 0.001). Patients receiving BDQ-containing regimens had more treatment success than those receiving BDQ-free regimens (p < 0.001; cure rate, 69.6% vs. 45.0%; complete the treatment, 22.5% vs. 18.0%; treatment success, 92.2% vs. 63.0%); the use of BDQ and combined with Linezolid or Clofazimine or Cycloserine were identified as independent predictors of treatment success and no culture reversion (P < 0.05). AEs were similarly reported in 26.5% of patients in the BDQ group and 19.0% in the non-BDQ group (p = 0.2). CONCLUSIONS: BDQ-containing regimens resulted in better treatment outcomes and similar safety relative to BDQ-free regimens for patients with refractory pulmonary RR/MDR/XDR-TB.

Dynamic interaction nursing intervention on functional rehabilitation and self-care ability of patients after aneurysm surgery.

BACKGROUND: Nursing practices based on the dynamic interaction model have been shown to be superior to generic nursing practices. However, whether this model is effective in patients recovering from intracranial aneurysm surgery is not well studied. AIM: To investigate the effect of nursing based on a dynamic interaction model on functional rehabilitation of patients after aneurysm surgery. METHODS: A total of 86 cases in our hospital with intracranial aneurysm from April 2019 to April 2021, were selected and divided into the study group and the control group, with 43 patients in each group. The control group received routine nursing, and the research group received nursing intervention based on a dynamic interaction model. The daily living ability (activities of daily living, ADL), cognitive function (Simple Intelligent Mental State Scale, MMSE), quality of life (Generic Quality of Life Inventory-74, GQOL-74), self-care ability (Exercise of Self-Care Agency scale), incidence of complications, and nursing satisfaction were recorded before and after intervention. RESULTS: Before intervention, ADL (52.09 ± 6.44), MMSE (18.03 ± 4.11), and GQOL-74 (53.68 ± 4.34) scores in the study group were not significantly different from those in the control group (ADL: 50.97 ± 7.32, MMSE: 17.59 ± 3.82, GQOL-74: 55.06 ± 3.98) (P > 0.05). After intervention, ADL (86.12 ± 5.07), MMSE (26.64 ± 2.66), and GQOL-74 (83.13 ± 5.67) scores in the study group were higher than those in the control group (ADL: 79.81 ± 6.35, MMSE: 24.51 ± 3.00, and GQOL-74: 77.96 ± 6.27) (P < 0.05). Before intervention, self-concept (17.46 ± 4.44), self-care skills (25.22 ± 4.20), self-care knowledge (22.35 ± 4.74), and self-care responsibility (15.06 ± 3.29) scores in the study group was similar to those in the control group (self-concept: 16.89 ± 5.53, self-care skills: 24.59 ± 4.46, self-care knowledge: 21.80 ± 3.61, and self-care responsibility: 14.83 ± 3.11) (P > 0.05). After the intervention, self-concept (26.01 ± 3.18), self-care skills (37.68 ± 6.05), self-care knowledge (45.56 ± 5.83), and self-care responsibility (22.01 ± 3.77) scores in the study group were higher than those in the control group (self-concept: 22.97 ± 3.46, self-care skills: 33.02 ± 5.65, self-care skills knowledge: 36.81 ± 5.54, and self-care responsibility: 17.97 ± 3.56 points) (P < 0.05). The incidence of complications in the study group (4.65%) was lower than that in the control group (18.60%) (P < 0.05). Nursing satisfaction in the study group (95.35%) was higher than that in the control group (81.40%) (P < 0.05). CONCLUSION: Nursing intervention based on a dynamic interaction model can improve postoperative cognitive function, daily living ability, self-care ability, quality of life, and patient satisfaction, while reducing the risk of complications.

Metabolic Dysfunction-associated Fatty Liver Disease is Associated with Greater Impairment of Lung Function than Nonalcoholic Fatty Liver Disease.

Background and Aims: We compared lung function parameters in nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD), and examined the association between lung function parameters and fibrosis severity in MAFLD. Methods: In this cross-sectional study, we randomly recruited 2,543 middle-aged individuals from 25 communities across four cities in China during 2016 and 2020. All participants received a health check-up including measurement of anthropometric parameters, biochemical variables, liver ultrasonography, and spirometry. The severity of liver disease was assessed by the fibrosis (FIB)-4 score. Results: The prevalence of MAFLD was 20.4% (n=519) and that of NAFLD was 18.4% (n=469). After adjusting for age, sex, adiposity measures, smoking status, and significant alcohol intake, subjects with MAFLD had a significantly lower predicted forced vital capacity (FVC, 88.27±17.60% vs. 90.82±16.85%, p<0.05) and lower 1 s forced expiratory volume (FEV1, 79.89±17.34 vs. 83.02±16.66%, p<0.05) than those with NAFLD. MAFLD with an increased FIB-4 score was significantly associated with decreased lung function. For each 1-point increase in FIB-4, FVC was diminished by 0.507 (95% CI: -0.840, -0.173, p=0.003), and FEV1 was diminished by 0.439 (95% CI: -0.739, -0.140, p=0.004). The results remained unchanged when the statistical analyses was performed separately for men and women. Conclusions: MAFLD was significantly associated with a greater impairment of lung function parameters than NAFLD.

Diagnostic performance of the metagenomic next-generation sequencing in lung biopsy tissues in patients suspected of having a local pulmonary infection.

PURPOSE: This study aims to evaluate the diagnostic application and performance of the metagenomic next-generation sequencing (mNGS) in patients suspected of local pulmonary infection by comparing it to the traditional pathogen detection methods in lung tissue specimens obtained by a computerized tomography-guided biopsy (CT-guided biopsy). METHODS: We retrospectively reviewed patients, admitted to the First Affiliated Hospital of Wenzhou Medical University, China from May 2018 to December 2020, who were suspected of local pulmonary infection. All cases received a CT-guided lung biopsy, tissue samples were sent both for conventional examinations (CE) and mNGS tests. The sensitivity and specificity of the two diagnostic approaches were compared. RESULTS: 106 patients enrolled, 76 patients were diagnosed with a pulmonary infection. Among 49 patients with identified pathogens, CE confirmed pathogenic infections in 32 cases. Mycobacterium spp. and fungi accounted for 37.5% (12/32) and 28.1% (9/32), respectively, with bacteria 34.4% (11/32). The mNGS examination detected extra pathogenic microorganisms in 22 patients that were consistent with the patients' clinical and radiographic pictures. The sensitivity of mNGS was 53.9% vs. 42.1% for the CE, while the specificity was 56.7% versus 96.7%. For detection rate, mNGS was significantly superior to CE in bacterial (96.3% vs. 40.7%, p < 0.05), and mixed infections (100% vs. 50%, p < 0.05), but inferior to CE in fungal (60% vs. 90%, p > 0.05) and Mycobacterium spp. infections (66.7% vs. 100%, p > 0.05) with no significant difference. Among 31 cases diagnosed with lung abscess, the diagnostic performance of the detection rate was 67.7% (21/31) in favour of mNGS compared to 29.0% (9/31) for CE (p < 0.05). Most polymicrobial infections were induced by anaerobic species that coexisted with Streptococcus constellatus. And Klebsiella pneumoniae was the most common isolated monomicrobial infection. CONCLUSIONS: The most commonly detected causative pathogens for local pulmonary infections were bacteria, Mycobacterium spp. and fungi. Compared with the CE, the advantages of mNGS in the pathogens detection lie in the discovery of bacterial and mixed infections, as well as in the detection of lung abscess. Conversely, mNGS is not good enough to be recommendable for the detection of Mycobacterium spp. and fungi.

Mitochondrial Genome Architecture and Evolutionary Origin of the Yao Silkworm, a Living Fossil of the Domestic Silkworm Bombyx mori (Lepidoptera: Bombycidae).

The Yao silkworm is a unique silkworm resource producing yellow flat plate silk that has only been reared by the Baiku Yao ethnic group in Nandan County, Guangxi Province, China for a thousand years. Here, we report the mitochondrial genomes (mitogenomes) of five Yao silkworm strains and 10 local Guangxi strains of the domestic silkworm (Bombyx mori) L. (Lepidoptera: Bombycidae), and use the resulting mitogenomes and the available Bombyx mitogenomes to characterize their genome architecture and trace the evolutionary origin of the Yao silkworm. The five Yao silkworm mitogenomes exhibited genome architectures identical to typical set of 37 mitochondrial genes (13 protein-coding genes, 22 transfer RNAs, and two ribosomal RNAs) and a high level of genome sequence similarity with the domestic silkworm. Mitogenome-based phylogenetic reconstruction provided solid evidence that the Yao silkworm shares a common ancestor with the domestic silkworm. Sliding window analysis uncovered a distinct variation pattern in the mitogenome between the Yao silkworm and the other domestic silkworm strains. The phylogenetic analyses revealed a basal placement of the Yao silkworm among all available domestic silkworm strains, indicating that the Yao silkworm is an ancient population of the domestic silkworm. Our data indicated that the Yao silkworm (B. mori) is a lineage of the domestic silkworm, which for the first time provides insights into the origin of the Yao silkworm.

Interpretation of ischiofemoral impingement via a clinical test using hip triaxial dynamic magnetic resonance imaging.

BACKGROUND: The present study aimed to use magnetic resonance (MR) to explore the dynamic changes of the ischiofemoral space (IFS) under the triaxial motion of the hip joint and verify the clinical test mechanism for ischiofemoral impingement (IFI). METHODS: A prospective design was used to screen 37 patients with clinically confirmed IFI, which included a total of 67 lateral hips, and 39 healthy controls with a total of 69 lateral hips. A dynamic MR examination was performed in positions designed by a simulated IFI test (adduction, adduction with 30° external rotation, 30° internal rotation, supine with 30° flexion, and prone with 30° backward extension). The IFS (mm) and quadratus femoris space (QFS, mm) were measured in different positions. All the data were evaluated independently by three musculoskeletal radiologists. The differences between the two groups were compared using the two-tailed t-test. RESULTS: The IFS and QFS in the case group were smaller than those in the control group. The IFS and QFS were significantly reduced in the prone with backward extension and adduction with external rotation positions of the hip. The correlation coefficients of the IFI test and long-stride walking (LSW) test were -0.621 and -0.715 for IFS and -0.653 and -0.696 for QFS, respectively. CONCLUSIONS: In this study, the mechanism of the IFI-specific clinical examination (IFI and LSW tests) was verified by triaxial dynamic MR imaging of the hip joint, which provided a dynamic imaging basis for the clinical application of the IFI-specific impingement test. The IFI impingement test can be used as a specific clinical test for IFI screening.

Transcriptomic analysis of Bombyx mori corpora allata with comparison to prothoracic glands in the final instar larvae.

The corpus allatum (CA) is an endocrine organ of insects that synthesizes juvenile hormone (JH). Yet little is known regarding the global gene expression profile for the CA, although JH signaling pathway has been well-studied in insects. Here, we report the availability of the transcriptome resource of the isolated CA from the final (fifth) instar larvae of the silkworm, Bombyx mori when the JH titer is low. We also compare it with prothoracic gland (PG) that produces the precursor of 20-hydroxyecdysone (20E), to find some common features in the JH and 20E related genes between the two organs. A total of 17,262 genes were generated using a combination of genome-guided assembly and annotation, in which 10,878 unigenes were enriched in 58 Gene Ontology terms, representing almost all expressed genes in the CA of the 5th instar larvae of B. mori. Transcriptome analysis confirmed that gene for Torso, the receptor of prothoracicotropic hormone (PTTH), is present in the PG but not in the CA. Transcriptome comparison and quantitative real time-PCR indicated that 11 genes related to JH biosynthesis and regulation and six genes for 20E are expressed in both the CA and PG, suggesting that the two organs may cross talk with each other through these genes. The temporal expression profiles of the two genes for the multifunctional neurohormonal factor sericotropin precursor and the uncharacterized protein LOC114249572, the most abundant in the CA and PG transcriptomes respectively, suggested that they might play important roles in the JH and 20E biosynthesis. The present work provides new insights into the CA and PG.

Characterization of algal organic matter as precursors for carbonaceous and nitrogenous disinfection byproducts formation: Comparison with natural organic matter.

Algal organic matter (AOM) and natural organic matter (NOM) from a typical eutrophic lake were comprehensively investigated in terms of their physico-chemical property, components and disinfection byproduct formation potentials (DBPFPs). The relationships between specific chemical properties of AOM and NOM with their corresponding DBPFPs were further evaluated during chlorination. Results indicated that AOM had lower specific UV absorbance (SUVA) but richer organic nitrogen contents than NOM. Fluorescence excitation emission matrix spectroscopy further demonstrated that AOM were chiefly composed of aromatic protein-like and soluble microbial byproduct-like matters, while NOM were mainly contributed from humic acid-like and soluble microbial byproduct-like substances. Although the molecular weight (MW) distribution of AOM and NOM showed no significant difference, size-exclusion chromatography with organic carbon as well as organic nitrogen detection (LC-OCD-OND) revealed that AOM were concentrated with the fraction of building blocks and NOM had higher concentrations of biopolymers and humics (HS). Moreover, AOM displayed higher DBPFPs than NOM, especially for nitrogenous DBPFP (N-DBPFP). MW < 1 kDa fractions both in AOM and NOM contributed the largest proportion to the formation of carbonaceous disinfection byproducts (C-DBPs). In addition, Pearson correlation analysis showed that bulk parameter SUVA was significantly relevant to the formation potentials of trihalomethane both in AOM and NOM, but was ineffective for carbonaceous DBPFP (C-DBPFP) prediction. Dissolved organic nitrogen contents in biopolymer and HS characterized by LC-OCD-OND had strong correlations with N-DBPFPs from AOM and NOM, indicating that LC-OCD-OND quantitative analysis could improve the prediction accuracy of the DBP formation than bulk parameters during NOM and AOM chlorination.

Spectrum of ß-Thalassemia Mutations in Some Areas of Guangxi Zhuang Autonomous Region of Southern China: A Study on a Pediatric Population Aged 0-15 Years.

ß-Thalassemia (ß-thal), one of the most common form of single-gene inheritable blood diseases in the world, is highly prevalent in southern China, especially in the Guangxi Zhuang Autonomous Region. To update the ß-thal mutation spectrum in this region, we performed hematological and genetic analyses on 888 ß-thal major (ß-TM), ß-thal intermedia (ß-TI) and ß-thal carrier patients, aged 0-15 years old, from different parts of Guangxi Province. We identified 55 genotypes and 18 ß-thal mutations. The codons 41/42 (-TTCT) (HBB: c.126_129delCTTT) (43.97%), codon 17 (A>T) (HBB: c.52A>T) (25.43%), -28(A>G) (HBB: c.-78A>G) (8.18%), IVS-II-654 (C>T) (HBB: c.316-197C>T) (7.85%) and codon 26 (G>A) (HBB: c.79G>A) (5.02%) were the five most common, accounting for more than 90.0%. The results of our study are providing an up-to-date ß-thal mutation spectrum in the 0-15-year-old pediatric population, which will help genetic counseling and prevention of ß-TM in mainland China's most endemic region, Guangxi Zhuang Autonomous Region.

Potential use of glutathione as a treatment for Parkinson's disease.

The aim of the present study was to assess the efficacy and safety of glutathione (GSH) for the treatment of Parkinson's disease (PD). The PubMed, Cochrane Library, OvidSP, Web of Science, China Science and Technology Journal Database, Chinese National Knowledge Infrastructure and China Wanfang Standards Database databases were systematically searched from the inception dates to October 1st, 2019, using the key words'glutathione' or 'GSH' and 'Parkinson' or 'Parkinson's disease' or 'PD'. The quality of the included articles was assessed using the bias risk assessment tool of the Cochrane systematic evaluator manual (version 5.1.0). Pooled analysis of the relevant data was performed using RevMan 5.3 software and subgroup analysis was performed to determine the impact of the dosage (300 vs. 600 mg) on the outcome measures. A total of seven randomized controlled trials involving 450 participants were included in the meta-analysis. The results of the present study indicated a statistically significant difference between the GSH and control groups, in terms of the Unified Parkinson's Disease Rating Scale (UPDRS) III [standard mean difference (SMD), -0.48; 95% CI, -(0.88-0.08); P=0.02] and GSH peroxidase (SMD, 1.88; 95% CI, 0.52-3.24; P=0.007). However, the differences in the UPDRS I (SMD, -0.04; 95% CI, -0.25-0.16; P=0.70) and UPDRS II (SMD, 0.03; 95% CI, -0.17-0.24; P=0.77) score and in side effects were not statistically significant between the groups. Subgroup analyses revealed that the dosage (300 vs. 600 mg) was an influencing factor for UPDRS III. The present study demonstrated that GSH may mildly improve motor scores in PD, but not at the expense of increased adverse events.

Study on the Influencing Factors of Hypoglycemic Effect of Folate Targeted Polymersomes Encapsulating Insulin.

PURPOSE: To study the effects of the density of folic acid (FA) on the hypoglycemic ability of FA-targeted polymersomes as oral insulin carriers. Also to study the change of the hypoglycemic effect of FA-targeted mixed polymersomes added with various mass ratio of d-α-tocopherol polyethylene glycol 1000 succinate (TPGS). METHODS: The FA-targeted polymersomes with different FA molar contents were prepared. The in vitro insulin release experiments in different media for FA-targeted polymersomes with various FA contents were studied. Their quantitative cellular uptake in Caco-2 cells was examined. The in vivo hypoglycemic activity of FA-targeted polymersomes was also studied with diabetic rats. The polymersomes with the optimal FA molar content was chosen to prepare mixed polymersomes with various TPGS contents. RESULTS: Among insulin-loaded FA-targeted polymersomes with four different FA molar contents, insulin-loaded polymersomes with 10% FA molar content (insulin-loaded 10%FA-Ps) showed the hightest cellular uptake and the best hypoglycemic response. In addition, the insulin-loaded FA-Ps/TPGS5:1 mixed polymersomes exhibited higher cellular uptake and better hypoglycemic response than the other two insulin-loaded mixed polymersomes adding TPGS did. CONCLUSIONS: FA-Ps/TPGS5:1 could be a promising formulation for the oral administration of insulin.