Identification of seven variants in the col4a1 gene that alter RNA splicing by minigene assay.

Type IV collagen is an integral component of basement membranes. Mutations in COL4A1, one of the key genes encoding Type IV collagen, can result in a variety of diseases. It is clear that a significant proportion of mutations that affect splicing can cause disease directly or contribute to the susceptibility or severity of disease. Here, we analyzed exonic mutations and intronic mutations described in the COL4A1 gene using bioinformatics programs and identified candidate mutations that may alter the normal splicing pattern through a minigene system. We identified seven variants that induce splicing alterations by disrupting normal splice sites, creating new ones, or altering splice regulatory elements. These mutations are predicted to impact protein function. Our results help in the correct molecular characterization of variants in COL4A1 and may help develop more personalized treatment options.

A novel heterozygous variant of the SALL1 gene with atypical Townes-Brocks syndrome phenotypes in Chinese family.

Townes-Brocks syndrome (TBS) is an autosomal dominant disorder characterised by the triad of anorectal, thumb, and ear malformations. It may also be accompanied by defects in kidney, heart, eyes, hearing, and feet. TBS has been demonstrated to result from heterozygous variants in the SALL1 gene, which encodes zinc finger protein believed to function as a transcriptional repressor. The clinical characteristics of an atypical TBS phenotype patient from a Chinese family are described, with predominant manifestations including external ear dysplasia, unilateral renal hypoplasia with mild renal dysfunction, and hearing impairment. A novel heterozygous variant c.3060T>A (p.Tyr1020*) in exon 2 of the SALL1 gene was identified in this proband. Pyrosequencing of the complementary DNA of the proband revealed that the variant transcript accounted for 48% of the total transcripts in peripheral leukocytes, indicating that this variant transcript has not undergone nonsense-mediated mRNA decay. This variant c.3060T > A is located at the terminal end of exon 2, proximal to the 3' end of the SALL1 gene, and exerts a relatively minor impact on protein function. We suggest that the atypical TBS phenotype observed in the proband may be attributed to the truncated protein retaining partial SALL1 function.

Impression life with pulmonary hypertension: clinically relevant characteristics and quality of life among patients in Gansu, China.

BACKGROUND: The adverse effects of pulmonary arterial hypertension (PAH) on physical, emotional, and health-related quality of life (HRQoL) remain primarily unrecognized, especially in resource-limited settings. OBJECTIVES: This study aims to characterize the HRQoL of patients with PAH in this area and also identify the potential role of clinically relevant characteristics, including the 6-min walk distance test (6MWD), WHO-Functional Classification (WHO-FC), and mental health in the occurrence of lowering quality of life. DESIGN: This was a cross-sectional observational study. METHODS: Inpatients with PAH were chosen from a tertiary hospital located in Gansu province, China. All participants were interviewed face-by-face by using questionnaires, including items from the 36-Item Short Form Health Survey (SF-36), the self-rating anxiety scale, and the self-rating depression scale. Data on demographic and clinically relevant characteristics, including WHO-FC and 6MWD, were also collected by tracing medical recorders. Multiple linear regression analysis was used to determine the association between demographic, clinically relevant characteristics data, and physical component summary (PCS) or mental component summary (MCS) in SF-36. RESULTS: Of the 152 participants, SF-36 differed significantly from Chinese norms in all eight domains, with role-physical (21.55 ± 9.87) less than one-third of the norm (88.79 ± 28.49). Multiple linear regression results showed that the factors with the greatest impact on PCS were anxiety scores (ß = -0.22, p = 0.001), followed by WHO-FC (ß = -0.16, p = 0.014) and 6MWD (ß = 0.15, p = 0.036). The factors with the greatest impact on MCS were WHO-FC (ß = -0.30, p < 0.001), followed by anxiety (ß = -0.23, p = 0.001) and depression scores (ß = -0.16, p = 0.013). CONCLUSION: HRQoL was substantially reduced among PAH patients in the resource-limited area, mainly the physiological functions. WHO-FC and anxiety scores were independently associated with both PCS and MCS in SF-36. Clinicians should make reasonable rehabilitation programs and plans for patients according to their cardiac function grade and the severity of clinical symptoms. In addition, psychological interventions should also be taken, especially for those with anxiety symptoms, so as to improve their HRQoL.

Analysis of the initial orbital MRI in aquaporin-4 antibody-positive optic neuritis (AQP4-ON): lesion location and lesion length can be predictive of visual prognosis.

PURPOSE: Despite mounting evidence indicating that aquaporin-4 antibody-positive optic neuritis (AQP4-ON) presents a less favorable prognosis than other types of optic neuritis, there exists substantial heterogeneity in the prognostic outcomes within the AQP4-ON cohort. Considering the persistent debate over the role of MRI in assessing the prognosis of optic neuritis, we aim to investigate the correlation between the MRI appearance and long-term visual prognosis in AQP4-ON patients. METHODS: We retrospectively reviewed the ophthalmological and imaging data of AQP4-ON patients admitted to our Neuro-ophthalmology Department from January 2015 to March 2018, with consecutive follow-up visits for a minimum of 3 years. RESULTS: A total of 51 AQP4-ON patients (59 eyes) meeting the criteria were enrolled in this research. After assessing the initial orbital MR images of each patient at the first onset, we observed the involvement of the canalicular segment (p < 0.001), intracranial segment (p = 0.004), optic chiasm (p = 0.009), and the presence of LEON (p = 0.002) were significantly different between recovery group and impairment group. For quantitative measurement, the length of the lesions is significantly higher in the impairment group (20.1 ± 9.3 mm) than in the recovery group (12.5 ± 5.3 mm) (p = 0.001). CONCLUSION: AQP4-ON patients with involvement of canalicular, intracranial segment and optic chiasm of the optic nerve, and the longer range of lesions threaten worse vision prognoses. Timely MR examination during the initial acute phase can not only exclude the intracranial or orbital mass lesions but also indicate visual prognosis in the long term.

Phocaeicola vulgatus alleviates diet-induced metabolic dysfunction-associated steatotic liver disease progression by downregulating histone acetylation level via 3-HPAA.

Diet-induced metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder with limited effective interventions available. A novel approach to address this issue is through gut microbiota-based therapy. In our study, we utilized multi-omics analysis to identify Phocaeicola vulgatus (P. vulgatus) as a potential probiotic for the treatment of MASLD. Our findings from murine models clearly illustrate that the supplementation of P. vulgatus mitigates the development of MASLD. This beneficial effect is partly attributed to the metabolite 3-Hydroxyphenylacetic acid (3-HPAA) produced by P. vulgatus, which reduces the acetylation levels of H3K27 and downregulates the transcription of Squalene Epoxidase (SQLE), a rate-limiting enzyme in steroid biosynthesis that promotes lipid accumulation in liver cells. This study underscores the significant role of P. vulgatus in the development of MASLD and the critical importance of its metabolite 3-HPAA in regulating lipid homeostasis. These findings offer a promising avenue for early intervention therapy in the context of MASLD.

A 3-hour time interval may not be sufficient for delayed enhancement magnetic resonance imaging with intravenous gadoteridol injection based on 3d-real IR sequence of the inner ear in Meniere's disease patient.

BACKGROUND: Magnetic resonance imaging (MRI) can be applied to visualize endolymphatic hydrops (EH). AIMS/OBJECTIVES: To explore whether a 3-h time interval was feasible for clinical practice. MATERIALS AND METHODS: We prospectively enrolled 15 patients with unilateral Meniere's disease, each of whom underwent delayed enhancement MRI scan of the inner ear after intravenous gadoteridol injection at a 3-h interval. The ears of these patients were divided into two groups (group A: the affected ears; group B: the unaffected ears). Among the two groups, the signal intensity in perilymphatic area of the basal turn of cochlea, the results of visual evaluations in the vestibule, cochlea and semicircular canal and the detection results of EH were compared. RESULTS: Regarding the signal intensity, a difference was found between group A and group B (p = .016). Besides, no difference was found between the visual evaluations in the vestibule, cochlea and semicircular canal of the two groups. Regarding the detection results of EH, group A (6 vestibules were undiagnosable; 8 cochleae were undiagnosable); group B (9 vestibules were undiagnosable; 10 cochleae were undiagnosable). CONCLUSIONS AND SIGNIFICANCE: In the clinical application of gadoteridol for the inner ear, 3-h delayed MR imaging may not be sufficient.

'Fear, uncertain, tired ...' psychological distress among pulmonary hypertension patients: a qualitative interview study.

BACKGROUND: Patient-centered health care for patients with pulmonary hypertension (PH) is important and requires an understanding of patient experiences. However, there is a lack of approaches to examine what's the effects and how the disease impact patients' psychological well-beings. METHODS: We conducted qualitative interviews with PH patient representatives to understand patient psychological experiences and inform patient-centered research and care. Participants were chosen from a tertiary hospital located in northwest China. 20 patients with PH who be treated at the hospital (13 participants were women, aged 18-74 years) were strategically selected and individually interviewed. We used qualitative analysis to identify themes relating to existential psychological distress that would clarify the nature of such concerns. RESULTS: We found that patients experience tremendous psychological distress throughout the treatment process. Four categories that describe patients' psychological experiences emerged: burden of PH treatment, fear and uncertainty about the disease, frustration in social and family role, and lack of recognition of the condition. CONCLUSIONS: Existential concerns are salient in PH and involve the experience of loss and disruptions to the sense of self and relationships. Healthcare practitioners must work more in collaboration to detect patients' need for support and to develop the patient's own skills to manage daily life. The PH teams should tailor interventions to provide emotional, informational and instrumental support and guidance to patients.

Three exonic variants in the COL4A5 gene alter RNA splicing in a minigene assay.

BACKGROUND: X-linked Alport syndrome (XLAS) is an inherited renal disease caused by rare variants of COL4A5 on chromosome Xq22. Many studies have indicated that single nucleotide variants (SNVs) in exons can disrupt normal splicing process of the pre-mRNA by altering various splicing regulatory signals. The male patients with XLAS have a strong genotype-phenotype correlation. Confirming the effect of variants on splicing can help to predict kidney prognosis. This study aimed to investigate whether single nucleotide substitutions, located within three bases at the 5' end of the exons or internal position of the exons in COL4A5 gene, cause aberrant splicing process. METHODS: We analyzed 401 SNVs previously presumed missense and nonsense variants in COL4A5 gene by bioinformatics programs and identified candidate variants that may affect the splicing of pre-mRNA via minigene assays. RESULTS: Our study indicated three of eight candidate variants induced complete or partial exon skipping. Variants c.2678G>C and c.2918G>A probably disturb classic splice sites leading to corresponding exon skipping. Variant c.3700C>T may disrupt splicing enhancer motifs accompanying with generation of splicing silencer sequences resulting in the skipping of exon 41. CONCLUSION: Our study revealed that two missense variants positioned the first nucleotides of the 5' end of COL4A5 exons and one internal exonic nonsense variant caused aberrant splicing. Importantly, this study emphasized the necessity of assessing the effects of SNVs at the mRNA level.

Functional analysis of the CTNS gene exonic variants predicted to affect splicing.

Cystinosis is a severe, monogenic systemic disease caused by variants in CTNS gene. Currently, there is growing evidence that exonic variants in many diseases can affect pre-mRNA splicing. The impact of CTNS gene exonic variants on splicing regulation may be underestimated due to the lack of routine studies at the RNA level. Here, we analyzed 59 exonic variants in the CTNS gene using bioinformatics tools and identified candidate variants that may induce splicing alterations by minigene assays. We identified six exonic variants that induce splicing alterations by disrupting the ratio of exonic splicing enhancers/exonic splicing silencers (ESEs/ESSs) or by interfering with the recognition of classical splice sites, or both. Our results help in the correct molecular characterization of variants in cystinosis and inform emerging therapies. Furthermore, our work suggests that the combination of in silico and in vitro assays facilitates to assess the effects of DNA variants driving rare genetic diseases on splicing regulation and will enhance the clinical utility of variant functional annotation.

Differentiation of Sinonasal NKT From Diffuse Large B-Cell Lymphoma Using Machine Learning and MRI-Based Radiomics.

PURPOSE: The aim of this study was to construct and validate a noninvasive radiomics method based on magnetic resonance imaging to differentiate sinonasal extranodal natural killer/T-cell lymphoma from diffuse large B-cell lymphoma. METHODS: We collected magnetic resonance imaging scans, including contrast-enhanced T1-weighted imaging and T2-weighted imaging, from 133 patients with non-Hodgkin lymphoma (103 sinonasal extranodal natural killer/T-cell lymphoma and 30 diffuse large B-cell lymphoma) and randomly split them into training and testing cohorts at a ratio of 7:3. Clinical characteristics and image performance were analyzed to build a logistic regression clinical-image model. The radiomics features were extracted on contrast-enhanced T1-weighted imaging and T2-weighted imaging images. Maximum relevance minimum redundancy, selectKbest, and the least absolute shrinkage and selection operator algorithms (LASSO) were applied for feature selection after balancing the training set. Five machine learning classifiers were used to construct the single and combined sequences radiomics models. Sensitivity, specificity, accuracy, precision, F1score, the area under receiver operating characteristic curve, and the area under precision-recall curve were compared between the 15 models and the clinical-image model. The diagnostic results of the best model were compared with those of 2 radiologists. RESULTS: The combined sequence model using support vector machine proves to be the best, incorporating 7 features and providing the highest values of specificity (0.903), accuracy (0.900), precision (0.727), F1score (0.800), and area under precision-recall curve (0.919) with relatively high sensitivity (0.889) in the testing set, along with a minimum Brier score. The diagnostic results differed significantly ( P < 0.05) from those of radiology residents, but not significantly ( P > 0.05) from those of experienced radiologists. CONCLUSIONS: Magnetic resonance imaging based on machine learning and radiomics to identify the type of sinonasal non-Hodgkin lymphoma is effective and has the potential to help radiology residents for diagnosis and be a supplement for biopsy.

Identification of exosomal miR-484 role in reprogramming mitochondrial metabolism in pancreatic cancer through Wnt/MAPK axis control.

The microRNAs (miRNAs) are potent regulators of tumorigenesis in various cancers, especially pancreatic cancer. The abnormal expression of miRNAs can be observed in tumor cells. Noteworthy, miRNAs could be transferred by exosomes as small extracellular vesicles in regulation of carcinogenesis. This research focused on exploring the roles and mechanisms of exosomal miR-484, derived from human bone marrow mesenchymal stem cells (hBMSCs), in the context of molecular interactions and regulation of mitochondrial metabolism. Exosomes were isolated for the examination of miR-484 expression. The impacts of hBMSCs-derived exosomal miR-484 on pancreatic cancer cells were studied using various assays. Evaluation of mitochondrial function and metabolism was performed. Wnt/MAPK pathway-related protein expression was assessed, and an in vivo tumor xenograft model was utilized to examine the functions. Our findings demonstrated a decreased miR-484 expression in pancreatic cancer cells. However, hBMSCs-derived exosomal miR-484 inhibited the proliferation and migration of these cells, while inducing apoptosis. Moreover, miR-484 led to an upsurge in reactive oxygen species production, a decrease in ATP levels, and a disruption in mitochondrial metabolism. In vivo analyses showed that hBMSCs-derived exosomal miR-484 lessened tumor size and weight, while also suppressing the expression of mitochondrial biomarkers. Further, there was a decline in ß-catenin and p-p38 protein levels both in vitro and in vivo. The addition of LiCl restored the disrupted mitochondrial metabolism. Conclusively, our results suggest that hBMSCs-derived exosomal miR-484 mitigates the malignant transformation and mitochondrial metabolism of pancreatic cancer by deactivating the Wnt/MAPK pathway.

Targeting neoadjuvant chemotherapy-induced metabolic reprogramming in pancreatic cancer promotes anti-tumor immunity and chemo-response.

The molecular dynamics of pancreatic ductal adenocarcinoma (PDAC) under chemotherapy remain incompletely understood. The widespread use of neoadjuvant chemotherapy (NAC) provides a unique opportunity to investigate PDAC samples post-chemotherapy. Leveraging a cohort from Fudan University Shanghai Cancer Center, encompassing PDAC samples with and without exposure to neoadjuvant albumin-bound paclitaxel and gemcitabine (AG), we have compiled data from single-cell and spatial transcriptomes, proteomes, bulk transcriptomes, and metabolomes, deepening our comprehension of the molecular changes in PDACs in response to chemotherapy. Metabolic flux analysis reveals that NAC induces a reprogramming of PDAC metabolic patterns and enhances immunogenicity. Notably, NAC leads to the downregulation of glycolysis and the upregulation of CD36. Tissue microarray analysis demonstrates that high CD36 expression is linked to poorer survival in patients receiving postoperative AG. Targeting CD36 synergistically improves the PDAC response to AG both in vitro and in vivo, including patient-derived preclinical models.

A Novel Neutrophil Extracellular Traps Signature for Overall Survival Prediction and Tumor Microenvironment Identification in Gastric Cancer.

Background: Neutrophil extracellular traps (NETs) released by neutrophils are crucial for cancer development, metastasis, and can indicate gastric cancer (GC) patients' prognosis. This study reveals the relevance of NETs-related genes to GC through transcriptome analysis. Methods: We obtained transcriptome sequencing data of GC from UCSC Xena and screened prognostic NETs-related genes by GEPIA2 database. The signature for NETs was subsequently created using the LASSO-Cox regression. The clinical value of model was further explored using the nomogram and was externally validated by the GEO database. After that, we employed GO, KEGG, and GSEA enrichment analyses to evaluate the bio-functional enrichment and related pathways. Additionally, ESTIMATE, MCP counter, and ssGSEA scores were used to investigate the immunological microenvironment of GC patients. Finally, in the external cohort, neutrophil elastase (NE)-DNA complexes were measured by ELISA, and the prognostic value of NE-DNA in GC was investigated using Cox analysis. Results: Seven NETs-associated genes (PDE4B, CD93, CTSG, IL6, ELANE, KCNJ15, and CRISPLD2) were filtered to establish the signature and participated in building the nomogram. In comparison to the high-risk group, the overall survival (OS) was much longer in the low-risk group (P=0.005). The validation cohort demonstrated the acceptable predictive ability of the nomogram. The signature was enriched in biological features such as extracellular matrix organization, epithelial-mesenchymal transition and inflammatory response. Moreover, there were substantial differences in immune cell infiltration across the different risk groups (p<0.001), especially the high-risk group having more immune cells that are engaged in the antigen presentation process and associated functions. Finally, in the external cohort, NE-DNA levels were shown to be an independent factor affecting OS prognosis (p=0.006). Conclusion: Overall, this research identified a novel signature based on seven NETs-associated genes to predict prognosis and identify tumor microenvironment of GC. And high NE-DNA level may be a critical factor in the poor OS associated with NETs.

Influencing factors of hospital-acquired COVID-19 prevention and control status among emergency support frontline healthcare workers under closed-loop management: a cross-sectional study.

Background: This study aimed to understand the hospital-acquired COVID-19 infection rate and infection prevention and control status of emergency support frontline healthcare workers (ESFHCWs) under closed-loop management, and to explore the related factors affecting hospital-acquired COVID-19 prevention and control status. Methods: The study site was a provincial-level tertiary hospital in the Xinjiang Uygur Autonomous Region specializing in treating COVID-19 patients. ESFHCWs were assigned from different hospitals in Zhejiang Province to provide emergency medical support in this specialized hospital. All ESFHCWs were managed using a closed loop. A self-designed questionnaire was used to estimate basic information, work experience, and the status of infection prevention and control (SIPC). A total of 269 ESFHCWs responded to the questionnaire. A generalized linear regression model was used to estimate the factors influencing SIPC. Results: There were six hospital-acquired COVID-19 cases, with an infection rate of 2.23%. The independent risk factors influencing COVID-19 prevention and control status were work seniority, anxiety disorder, and consumption of gastrointestinal, anti-inflammatory and anti-asthmatic, and hypnotic sedative drugs. Compared with ESFHCWs with more than 10 years of work seniority, ESFHCWs with less than 5 years of work seniority and 5-10 years of work seniority had lower COVID-19 SIPC scores. Among ESFHCWs with anxiety disorder, the SIPC score was significantly lower than that of ESFHCWs without anxiety disorder. The SIPC scores of ESFHCWs taking other medications (gastrointestinal, anti-inflammatory and anti-asthmatic, and hypnotic sedative drugs) were lower than those of ESFHCWs who did not. Conclusion: The closed-loop management method may be effective in reducing the infection rate of hospital-acquired COVID-19 among ESFHCWs. HCWs with less than 10 years of work seniority, anxiety disorder, and other medications (gastrointestinal, anti-inflammatory and anti-asthmatic, and hypnotic sedative drugs) were probably not suitable for participating in emergency assistant actions because of their poor SIPC scores. Further studies are needed to develop the selection criteria for ESFHCWs.

Prevalence and Determinants of Delay in Time-to-Diagnosis for Pulmonary Arterial Hypertension Patients in Gansu China: A Observational Cohort Study.

Current studies of patients with pulmonary arterial hypertension (PAH) have shown a significant diagnostic delay. However, the causes and risk factors for this delay are not been well explored in Chinese population. This study aimed to assess the status of diagnostic delay in patients with PAH in China. Additionally, we identified factors associated with the delay. Demographic and clinical data were collected from 153 PAH patients admitted to three tertiary hospitals in Gansu, China, from March 2020 to October 2022. Based on the recorded date, the diagnostic delay was divided into patient delay and health system delay. For analysis, we divided diagnostic delay into 2 groups (≤3 years and >3 years). Factors associated with delay were identified by binary logistic regression. The median diagnostic delay was 3 years (IQR: 0.25-5.88). Binary logistic regression analysis showed that male (OR = 2.48, 95% CI: 1.10-5.58), those with junior high school or below (OR = 3.65, 95% CI: 1.36-9.78), living far away from the tertiary hospital (OR = 2.66, 95% CI: 1.14-6.18), initially visit hospital before 2018 (OR = 3.82, 95% CI: 1.68-8.71), and visit hospital at county level or below (OR = 3.80, 95% CI: 1.42-10.18) were risk factor for diagnostic delay (>3 years). Despite increased awareness, most patients with PAH in Gansu, China still experienced a delay in diagnosis of more than 3 years. Male sex, lower educational background, and being away from tertiary hospitals are risk factors for delay. Furthermore, factors impacting time-to-diagnosis and its impact should be continuously evaluated as therapeutic strategies continue to evolve and improve.

CRIP1 fosters MDSC trafficking and resets tumour microenvironment via facilitating NF-κB/p65 nuclear translocation in pancreatic ductal adenocarcinoma.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is among the most immunosuppressive tumour types. The tumour immune microenvironment (TIME) is largely driven by interactions between immune cells and heterogeneous tumour cells. Here, we aimed to investigate the mechanism of tumour cells in TIME formation and provide potential combination treatment strategies for PDAC patients based on genotypic heterogeneity. DESIGN: Highly multiplexed imaging mass cytometry, RNA sequencing, mass cytometry by time of flight and multiplex immunofluorescence staining were performed to identify the pro-oncogenic proteins associated with low immune activation in PDAC. An in vitro coculture system, an orthotopic PDAC allograft tumour model, flow cytometry and immunohistochemistry were used to explore the biological functions of cysteine-rich intestinal protein 1 (CRIP1) in tumour progression and TIME formation. RNA sequencing, mass spectrometry and chromatin immunoprecipitation were subsequently conducted to investigate the underlying mechanisms of CRIP1. RESULTS: Our results showed that CRIP1 was frequently upregulated in PDAC tissues with low immune activation. Elevated CRIP1 expression induced high levels of myeloid-derived suppressor cell (MDSC) infiltration and fostered an immunosuppressive tumour microenvironment. Mechanistically, we primarily showed that CRIP1 bound to nuclear factor kappa-B (NF-κB)/p65 and facilitated its nuclear translocation in an importin-dependent manner, leading to the transcriptional activation of CXCL1/5. PDAC-derived CXCL1/5 facilitated the chemotactic migration of MDSCs to drive immunosuppression. SX-682, an inhibitor of CXCR1/2, blocked tumour MDSC recruitment and enhanced T-cell activation. The combination of anti-PD-L1 therapy with SX-682 elicited increased CD8+T cell infiltration and potent antitumor activity in tumour-bearing mice with high CRIP1 expression. CONCLUSIONS: The CRIP1/NF-κB/CXCL axis is critical for triggering immune evasion and TIME formation in PDAC. Blockade of this signalling pathway prevents MDSC trafficking and thereby sensitises PDAC to immunotherapy.

A Strong Adhesive Biological Hydrogel for Colon Leakage Repair and Abdominal Adhesion Prevention.

Colon leakage is one of the most severe complications in abdominal trauma or surgery cases. It can lead to severe abdominal infection and abdominal adhesions, resulting in prolonged hospital stays and increased mortality. In this study, a photosensitive hydrogel is proposed, which can swiftly form a strong adhesion coating on the damaged colon after UV irradiation, to realize quick cure and suture-free repair of colon leakage. The newly developed biological gel consists of hyaluronic acid methacryloyl (HAMA) and hyaluronic acid o-nitroso benzaldehyde (HANB) in the optimal ratio of 3: 1, which exerts both the rapid photocuring properties of HAMA and the strong tissue adhesion properties of HANB. HAMA/HANB shows excellent adhesion stability on wet surfaces, presenting controllable mechanical properties, ductility, adhesion stability, and chemical stability; it also evades foreign body response, which relieves the degree of abdominal adhesion. The underlying mechanism for HAMA/HANB promoting wound healing in colon leakage involves the reconstruction of the colon barrier, as well as the regulation of the immune reaction and neovascularization. In all, HAMA/HANB is a promising alternative suture-free approach for repairing colon leakage; it has a reliable healing effect and is expected to be extended to clinical application for other organ injuries.

Global Trends in Research of Antimicrobial Peptides for the Treatment of Drug-Resistant Bacteria from 1995 to 2021: A Bibliometric Analysis.

Background: Antimicrobial peptides (AMPs) can act on the bacterial cell membrane to play an antibacterial role in types of drug-resistant bacteria. Therefore, AMPs have attracted more and more attention in the treatment of drug-resistant bacteria. Methods: Bibliometric analysis was employed to sort out the development and trends in the research of AMPs in the treatment of drug-resistant bacteria and map the knowledge structure for scholars. Results: Since 2010, the publications and citations in this field have exploded, indicating a growing global interest in the field of AMPs for the treatment of drug-resistant bacteria. And as major countries in this field, China and the USA had conducted very in-depth exchanges and cooperation, which had injected a steady stream of impetus into this field. Both old and new scholars have made efforts, and related fields have developed rapidly, especially in the synthesis and improvement of novel AMPs. In recent years, research directions in the field of AMPs for the treatment of drug-resistant bacteria gradually focused on the practical application, optimization of drug delivery mode, optimization of synthesis mode, screening of new AMPs and other fields, indicating that the relevant research results of AMPs for the treatment of drug-resistant bacteria had entered the actual clinical stage, with higher practical significance. Conclusion: The research history, global research status, future research hotspots, and trends of the research of AMPs in the treatment of drug-resistant bacteria were discussed in depth in this study, which can provide research references and inspiration for researchers inside and outside the related field.

The Treatment Outcomes of Radiotherapy and Surgical Treatment for Patients with Cavernous Sinus Hemangioma: A Meta-Analysis.

OBJECTIVE: Cavernous sinus hemangiomas (CSHs) are infrequent benign neoplasms. This meta-analysis was conducted with the objective of examining the prognostic outcomes of surgical interventions and radiotherapy (RT) in patients diagnosed with CSHs. METHODS: A comprehensive literature search was performed across PubMed, Embase, and Web of Science databases, with traceability up to June 22, 2021. The evaluation of continuous variables was conducted by applying the weighted mean difference (WMD) and 95% confidence interval. A one-arm meta-analysis was used to scrutinize the tumor control rate, clinical improvement rate, recovery rates of abducens nerve palsy and visual disturbance, total resection rate, and the incidence rate of permanent nerve palsy post-treatment. RESULTS: In total, 29 articles were incorporated into the meta-analysis. Post-RT for CSHs, a significant reduction in tumor volume was observed (WMD [95% confidence interval] = -17.16 [-21.52, -12.80] cm3). The tumor control rate, clinical improvement rate, recovery rate of abducens nerve palsy, and the recovery rate of visual disturbance were 97.1% (92.9, 99.7), 91.9% (82.3, 98.5), 95.6% (83.2, 100.0), and 86.3% (65.0, 99.5), respectively. Following surgical treatment, the total resection rate, mean intraoperative blood loss, recovery rate of visual disturbance, incidence rate of permanent nerve palsy, and recovery rate of abducens nerve palsy were 73.2% (57.1, 86.9), 971.17 mL (584.07, 1358.27), 66.4% (32.4, 0.942), 16.0% (4.6, 31.1), and 70.6% (51.0, 87.7), respectively. Notably, the recovery rate of abducens nerve palsy post-RT was markedly higher than postsurgical treatment. CONCLUSIONS: The results of this meta-analysis underscore that RT is an effective and safe treatment modality for CSHs. Furthermore, the prognostic outcomes of RT demonstrated superiority over surgical intervention.

Identified eleven exon variants in PKD1 and PKD2 genes that altered RNA splicing by minigene assay.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenic multisystem disease caused primarily by mutations in the PKD1 gene or PKD2 gene. There is increasing evidence that some of these variants, which are described as missense, synonymous or nonsense mutations in the literature or databases, may be deleterious by affecting the pre-mRNA splicing process. RESULTS: This study aimed to determine the effect of these PKD1 and PKD2 variants on exon splicing combined with predictive bioinformatics tools and minigene assay. As a result, among the 19 candidate single nucleotide alterations, 11 variants distributed in PKD1 (c.7866C > A, c.7960A > G, c.7979A > T, c.7987C > T, c.11248C > G, c.11251C > T, c.11257C > G, c.11257C > T, c.11346C > T, and c.11393C > G) and PKD2 (c.1480G > T) were identified to result in exon skipping. CONCLUSIONS: We confirmed that 11 variants in the gene of PKD1 and PKD2 affect normal splicing by interfering the recognition of classical splicing sites or by disrupting exon splicing enhancers and generating exon splicing silencers. This is the most comprehensive study to date on pre-mRNA splicing of exonic variants in ADPKD-associated disease-causing genes in consideration of the increasing number of identified variants in PKD1 and PKD2 gene in recent years. These results emphasize the significance of assessing the effect of exon single nucleotide variants in ADPKD at the mRNA level.