Dual-Region Computed Tomography Radiomics-Based Machine Learning Predicts Subcarinal Lymph Node Metastasis in Patients with Non-small Cell Lung Cancer.

BACKGROUND: Noninvasively and accurately predicting subcarinal lymph node metastasis (SLNM) for patients with non-small cell lung cancer (NSCLC) remains challenging. This study was designed to develop and validate a tumor and subcarinal lymph nodes (tumor-SLNs) dual-region computed tomography (CT) radiomics model for predicting SLNM in NSCLC. METHODS: This retrospective study included NSCLC patients who underwent lung resection and SLNs dissection between January 2017 and December 2020. The radiomic features of the tumor and SLNs were extracted from preoperative CT, respectively. Ninety machine learning (ML) models were developed based on tumor region, SLNs region, and tumor-SLNs dual-region. The model performance was assessed by the area under the curve (AUC) and validated internally by fivefold cross-validation. RESULTS: In total, 202 patients were included in this study. ML models based on dual-region radiomics showed good performance for SLNM prediction, with a median AUC of 0.794 (range, 0.686-0.880), which was superior to those of models based on tumor region (median AUC, 0.746; range, 0.630-0.811) and SLNs region (median AUC, 0.700; range, 0.610-0.842). The ML model, which is developed by using the naive Bayes algorithm and dual-region features, had the highest AUC of 0.880 (range of cross-validation, 0.825-0.937) among all ML models. The optimal logistic regression model was inferior to the optimal ML model for predicting SLNM, with an AUC of 0.727. CONCLUSIONS: The CT radiomics showed the potential for accurately predicting SLNM in NSCLC patients. The ML model with dual-region radiomic features has better performance than the logistic regression or single-region models.

Effectiveness of Very Brief Advice on Tobacco Cessation: A Systematic Review and Meta-Analysis.

BACKGROUND: Very brief advice (VBA; ≤ 3 min) on quitting is practical and scalable during brief medical interactions with patients who smoke. This study aims to synthesize the effectiveness of VBA for smoking cessation and summarize the implementation strategies. METHODS: We searched randomized controlled trials aiming at tobacco abstinence and comparing VBA versus no smoking advice or no contact from Medline, Embase, CINAHL, Cochrane Library, PsycInfo databases, six Chinese databases, two trial registries ClinicalTrials.gov and WHO-ICTRP from inception to September 30, 2023. Grading of Recommendations, Assessment, Development, and Evaluations framework was used to assess the certainty of the evidence of the meta-analytic findings. The outcomes were self-reported long-term tobacco abstinence at least 6 months after treatment initiation, earlier than 6 months after treatment initiation, and quit attempts. Effect sizes were computed as risk ratio (RR) with 95% CI using frequentist random-effect models. DATA SYNTHESIS: Thirteen randomized controlled trials from 15 articles (n = 26,437) were included. There was moderate-certainty evidence that VBA significantly increased self-reported tobacco abstinence at ≥ 6 months in the adjusted model (adjusted risk ratio ARR 1.17, 95% CI: 1.07-1.27) compared with controls. The sensitivity analysis showed similar results when abstinence was verified by biochemical validation (n = 6 studies, RR 1.53, 95% CI 0.98-2.40). There was high-certainty evidence that VBA significantly increased abstinence at < 6 months (ARR 1.22, 95% CI: 1.01-1.47). Evidence of effect on quit attempts (ARR 1.03, 95% CI 0.97-1.08) was of very low certainty. DISCUSSION: VBA delivered in a clinical setting is effective in increasing self-reported tobacco abstinence, which provides support for wider adoption in clinical practice.

Design, synthesis, and evaluation of benzodioxolane compounds for antitumor activity.

This study reports the design, synthesis, and comprehensive biological evaluation of 13 benzodioxolane derivatives, derived from the core structure of piperine, a natural product with established antitumor properties. Piperine, primarily found in black pepper, has been noted for its diverse pharmacological activities, including anti-inflammatory, antioxidant, and anticancer effects. Leveraging piperine's antitumor potential, we aimed to enhance its efficacy through structural modifications. Among the synthesized compounds, HJ1 emerged as the most potent, exhibiting a 4-fold and 10-fold increase in inhibitory effects on HeLa and MDA-MB-231 cell lines, respectively, compared to piperine. Furthermore, HJ1 demonstrated a favorable safety profile, characterized by significantly lower cytotoxicity towards the human normal cell line 293T. Mechanistic investigations revealed that HJ1 markedly inhibited clonogenicity, migration, and adhesion of HeLa cells. In vivo studies utilizing the chick embryo chorioallantoic membrane (CAM) model substantiated the robust antitumor activity of HJ1, evidenced by its ability to suppress tumor angiogenesis and reduce tumor weight. These results suggest that HJ1 holds significant promise as a lead compound for the development of novel antitumor therapies.

Expression and regulation of HIF-1a in hypoxic pulmonary hypertension: Focus on pathological mechanism and Pharmacological Treatment.

Hypoxia inducible factor-1(HIF-1), a heterodimeric transcription factor, is composed of two subunits (HIF-1α and HIF-1ß). It is considered as an important transcription factor for regulating oxygen changes in hypoxic environment, which can regulate the expression of various hypoxia-related target genes and play a role in acute and chronic hypoxia pulmonary vascular reactions. In this paper, the function and mechanism of HIF-1a expression and regulation in hypoxic pulmonary hypertension (HPH) were reviewed, and current candidate schemes for treating pulmonary hypertension by using HIF-1a as the target were introduced, so as to provide reference for studying the pathogenesis of HPH and screening effective treatment methods.

Curriculum vitae of CUG binding protein 1 (CELF1) in homeostasis and diseases: a systematic review.

RNA-binding proteins (RBPs) are kinds of proteins with either singular or multiple RNA-binding domains (RBDs), and they can assembly into ribonucleic acid-protein complexes, which mediate transportation, editing, splicing, stabilization, translational efficiency, or epigenetic modifications of their binding RNA partners, and thereby modulate various physiological and pathological processes. CUG-BP, Elav-like family 1 (CELF1) is a member of the CELF family of RBPs with high affinity to the GU-rich elements in mRNA, and thus exerting control over critical processes including mRNA splicing, translation, and decay. Mounting studies support that CELF1 is correlated with occurrence, genesis and development and represents a potential therapeutical target for these malignant diseases. Herein, we present the structure and function of CELF1, outline its role and regulatory mechanisms in varieties of homeostasis and diseases, summarize the identified CELF1 regulators and their structure-activity relationships, and prospect the current challenges and their solutions during studies on CELF1 functions and corresponding drug discovery, which will facilitate the establishment of a targeted regulatory network for CELF1 in diseases and advance CELF1 as a potential drug target for disease therapy.

Short-chain fatty acids mitigate Methamphetamine-induced hepatic injuries in a Sigma-1 receptor-dependent manner.

Methamphetamine (Meth) is a potent psychostimulant with well-established hepatotoxicity. Gut microbiota-derived short-chain fatty acids (SCFAs) have been reported to yield beneficial effects on the liver. In this study, we aim to further reveal the mechanisms of Meth-induced hepatic injuries and investigate the potential protective effects of SCFAs. Herein, mice were intraperitoneally injected with 15 mg/kg Meth to induce hepatic injuries. The composition of fecal microbiota and SCFAs was profiled using 16 S rRNA sequencing and Gas Chromatography/Mass Spectrometry (GC/MS) analysis, respectively. Subsequently, SCFAs supplementation was performed to evaluate the protective effects against hepatic injuries. Additionally, Sigma-1 receptor knockout (S1R-/-) mice and fluvoxamine (Flu), an agonist of S1R, were introduced to investigate the mechanisms underlying the protective effects of SCFAs. Our results showed that Meth activated S1R and induced hepatic autophagy, inflammation, and oxidative stress by stimulating the MAPK/ERK pathway. Meanwhile, Meth disrupted SCFAs product-related microbiota, leading to a reduction in fecal SCFAs (especially Acetic acid and Propanoic acid). Accompanied by the optimization of gut microbiota, SCFAs supplementation normalized S1R expression and ameliorated Meth-induced hepatic injuries by repressing the MAPK/ERK pathway. Effectively, S1R knockout repressed Meth-induced activation of the MAPK/ERK pathway and further ameliorated hepatic injuries. Finally, the overexpression of S1R stimulated the MAPK/ERK pathway and yielded comparable adverse phenotypes to Meth administration. These findings suggest that Meth-induced hepatic injuries relied on the activation of S1R, which could be alleviated by SCFAs supplementation. Our study confirms the crucial role of S1R in Meth-induced hepatic injuries for the first time and provides a potential preemptive therapy.

Accumulation of Hydrogen Bonds and van der Waals Interactions Determines Force Response between Two Parallel Cellulose Chains: Steered Molecular Dynamics Simulations.

We investigated the response forces between two parallel cellulose chains during the shearing and tearing processes by using steered molecular dynamics simulations. It was found that there are two logarithmic dependencies between response force and pulling speed in shearing processes but only one in tearing, according to Bell's equation by fitting the f-ln v curve. The mechanism is that there are 2-fold interactions determining the force response between two parallel cellulose chains resisting chain separation during a shearing process. Our results indicate that hydrogen bonds dominate the interchain interactions in the fast pull mode (FPM) for shearing, while van der Waals interactions dominate in the slow pull mode (SPM). For tearing, the one-by-one breaking of hydrogen bonds and van der Waals interactions plays a main role.

Long noncoding RNA TMPO-AS1 upregulates BCAT1 expression to promote cell proliferation in nasopharyngeal carcinoma via microRNA let-7c-5p.

BACKGROUND: Long non-coding RNA (lncRNA) is a group of RNA transcripts that contribute to tumor development by post-transcriptionally regulating cancer-related genes. Nasopharyngeal carcinoma (NPC) is an epithelial tumor that occurs in the nasopharynx and is common in North Africa and Southeast Asia. The study investigated the functions of lncRNA TMPO-AS1 in NPC cell proliferation and apoptosis as well as its related competing endogenous RNA (ceRNA) mechanism. METHODS: Candidate microRNA and genes that may regulated by TMPO-AS1 were predicted with the bioinformatic tool starBase. TMPO-AS1 expression in NPC tissue, cells, nuclear part, and cytoplasmic part was measured by RT-qPCR. MTT assay, EdU assay, and flow cytometry analysis were carried out to evaluate NPC cell viability, proliferation, and apoptosis, respectively. RNA immunoprecipitation assay and luciferase reporter assay were conducted to detect the binding between TMPO-AS1 and let-7c-5p or that between let-7c-5p and BCAT1. RESULTS: TMPO-AS1 and BCAT1 showed high expression in NPC tissue and cells, while let-7c-5p was downregulated in NPC. The silencing of TMPO-AS1 suppressed NPC cell proliferation while promoting cell apoptosis. Moreover, TMPO-AS1 interacted with let-7c-5p and negatively regulated let-7c-5p expression. BCAT1 was a target of let-7c-5p and was inversely regulated by let-7c-5p in NPC cells. The repressive impact of TMPO-AS1 knockdown on NPC cell growth was countervailed by overexpressed BCAT1. CONCLUSION: TMPO-AS1 accelerates NPC cell proliferation and represses cell apoptosis by interacting with let-7c-5p to regulate BCAT1 expression.

Role of mitophagy in pulmonary hypertension: Targeting the mechanism and pharmacological intervention.

Mitophagy, a crucial pathway in eukaryotic cells, selectively eliminates dysfunctional mitochondria, thereby maintaining cellular homeostasis via mitochondrial quality control. Pulmonary hypertension (PH) refers to a pathological condition where pulmonary arterial pressure is abnormally elevated due to various reasons, and the underlying pathogenesis remains elusive. This article examines the molecular mechanisms underlying mitophagy, emphasizing its role in PH and the progress in elucidating related molecular signaling pathways. Additionally, it highlights current drug regulatory pathways, aiming to provide novel insights into the prevention and treatment of pulmonary hypertension.

The effectiveness of booster vaccination of inactivated COVID-19 vaccines against susceptibility, infectiousness, and transmission of omicron BA.2 variant: a retrospective cohort study in Shenzhen, China.

Little studies evaluated the effectiveness of booster vaccination of inactivated COVID-19 vaccines against being infected (susceptibility), infecting others (infectiousness), and spreading the disease from one to another (transmission). Therefore, we conducted a retrospective cohort study to evaluate the effectiveness of booster vaccination of inactivated COVID-19 vaccines against susceptibility, infectiousness, and transmission in Shenzhen during an Omicron BA.2 outbreak period from 1 February to 21 April 2022. The eligible individuals were classified as four sub-cohorts according to the inactivated COVID-19 vaccination status of both the close contacts and their index cases: group 2-2, fully vaccinated close contacts seeded by fully vaccinated index cases (reference group); group 2-3, booster-vaccinated close contacts seeded by fully vaccinated index cases; group 3-2, fully vaccinated close contacts seeded by booster-vaccinated index cases; and group 3-3, booster-vaccinated close contacts seeded by booster-vaccinated index cases. Univariate and multivariate logistic regression analyses were applied to estimate the effectiveness of booster vaccination. The sample sizes of groups 2-2, 2-3, 3-2, and 3-3 were 846, 1,115, 1,210, and 2,417, respectively. We found that booster vaccination had an effectiveness against infectiousness of 44.9% (95% CI: 19.7%, 62.2%) for the adults ≥ 18 years, 62.2% (95% CI: 32.0%, 78.9%) for the female close contacts, and 60.8% (95% CI: 38.5%, 75.1%) for the non-household close contacts. Moreover, booster vaccination had an effectiveness against transmission of 29.0% (95% CI: 3.2%, 47.9%) for the adults ≥ 18 years, 38.9% (95% CI: 3.3%, 61.3%) for the female close contacts, and 45.8% (95% CI: 22.1%, 62.3%) for the non-household close contacts. However, booster vaccination against susceptibility did not provide any protective effect. In summary, this study confirm that booster vaccination of the inactivated COVID-19 vaccines provides low level of protection and moderate level of protection against Omicron BA.2 transmission and infectiousness, respectively. However, booster vaccination does not provide any protection against Omicron BA.2 susceptibility.

Reconfigurable Microlens Array Enables Tunable Imaging Based on Shape Memory Polymers.

Microlens arrays (MLAs) with a tunable imaging ability are core components of advanced micro-optical systems. Nevertheless, tunable MLAs generally suffer from high power consumption, an undeformable rigid body, large and complex systems, or limited focal length tunability. The combination of reconfigurable smart materials with MLAs may lead to distinct advantages including programmable deformation, remote manipulation, and multimodal tunability. However, unlike photopolymers that permit flexible structuring, the fabrication of tunable MLAs and compound eyes (CEs) based on transparent smart materials is still rare. In this work, we report reconfigurable MLAs that enable tunable imaging based on shape memory polymers (SMPs). The smart MLAs with closely packed 200 × 200 microlenses (40.0 µm in size) are fabricated via a combined technology that involves wet etching-assisted femtosecond laser direct writing of MLA templates on quartz, soft lithography for MLA duplication using SMPs, and the mechanical heat setting for programmable reconfiguration. By stretching or squeezing the shape memory MLAs at the transition temperature (80 °C), the size, profiles, and spatial distributions of the microlenses can be programmed. When the MLA is stretched from 0 to 120% (area ratio), the focal length is increased from 116 to 283 µm. As a proof of concept, reconfigurable MLAs and a 3D CE with a tunable field of view (FOV, 160-0°) have been demonstrated in which the thermally triggered shape memory deformation has been employed for tunable imaging. The reconfigurable MLAs and CEs with a tunable focal length and adjustable FOV may hold great promise for developing smart micro-optical systems.

Deficiency of the HGF/Met pathway leads to thyroid dysgenesis by impeding late thyroid expansion.

The mechanisms of bifurcation, a key step in thyroid development, are largely unknown. Here we find three zebrafish lines from a forward genetic screening with similar thyroid dysgenesis phenotypes and identify a stop-gain mutation in hgfa and two missense mutations in met by positional cloning from these zebrafish lines. The elongation of the thyroid primordium along the pharyngeal midline was dramatically disrupted in these zebrafish lines carrying a mutation in hgfa or met. Further studies show that MAPK inhibitor U0126 could mimic thyroid dysgenesis in zebrafish, and the phenotypes are rescued by overexpression of constitutively active MEK or Snail, downstream molecules of the HGF/Met pathway, in thyrocytes. Moreover, HGF promotes thyrocyte migration, which is probably mediated by downregulation of E-cadherin expression. The delayed bifurcation of the thyroid primordium is also observed in thyroid-specific Met knockout mice. Together, our findings reveal that HGF/Met is indispensable for the bifurcation of the thyroid primordium during thyroid development mediated by downregulation of E-cadherin in thyrocytes via MAPK-snail pathway.

Polystyrene nanoplastics exacerbate aflatoxin B1-induced hepatic injuries by modulating the gut-liver axis.

Dietary pollution of Aflatoxin B1 (AFB1) poses a great threat to global food safety, which can result in serious hepatic injuries. Following the widespread use of plastic tableware, co-exposure to microplastics and AFB1 has dramatically increased. However, whether microplastics could exert synergistic effects with AFB1 and amplify its hepatotoxicity, and the underlying mechanisms are still unelucidated. Here, mice were orally exposed to 100 nm polystyrene nanoplastics (NPs) and AFB1 to investigate the influences of NPs on AFB1-induced hepatic injuries. We found that exposure to only NPs or AFB1 resulted in colonic inflammation and the impairment of the intestinal barrier, which was exacerbated by combined exposure to NPs and AFB1. Meanwhile, co-exposure to NPs exacerbated AFB1-induced dysbiosis of gut microbiota and remodeling of the fecal metabolome. Moreover, NPs and AFB1 co-exposure exhibited higher levels of systemic inflammatory factors compared to AFB1 exposure. Additionally, NPs co-exposure further exacerbated AFB1-induced hepatic fibrosis and inflammation, which could be associated with the overactivation of the TLR4/MyD88/NF-κB pathway. Notably, Spearman's correlation analysis revealed that the exacerbation of NPs co-exposure was closely associated with microbial dysbiosis. Furthermore, microbiota from NPs-exposed mice (NPsFMT) partly reproduced the exacerbation of NPs on AFB1-induced systemic and hepatic inflammation, but not fibrosis. In summary, our findings indicate that gut microbiota could be involved in the exacerbation of NPs on AFB1-induced hepatic injuries, highlighting the health risks of NPs.

Salvage surgery and conversion surgery for patients with non-small cell lung cancer: A narrative review.

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths. With the development of screening, patient selection and treatment strategies, patients' survival outcomes and living quality significantly improved. However, some patients still have local recurrence or residual tumors after receiving definitive therapies. Salvage surgery has been regarded as an effective option for recurrent or residual NSCLC, but its effectiveness remains undetermined. Furthermore, conversion surgery is a special type of salvage surgery for tumors converted from "initially unresectable" to "potentially resectable" status due to a favorable response to systemic treatments. Although conversion surgery is a promising curative procedure for advanced NSCLC, its concept and clinical value remain unfamiliar to clinicians. In this narrative review, we provided an overview of the safety and efficacy of salvage surgery, especially salvage surgery after sublobar resection in early-stage NSCLC. More importantly, we highlighted the concept and value of conversion surgery after systemic treatment in advanced NSCLC to gain some insights into its role in the treatment of lung cancer.

High-throughput mutagenesis and screening approach for the identification of drug-resistant mutations in the rifampicin resistance-determining region of mycobacteria.

Rifampicin is the most powerful first-line antibiotic for tuberculosis, which is caused by Mycobacterium tuberculosis. Although accumulating evidence from sequencing data of clinical M. tuberculosis isolates suggested that mutations in the rifampicin-resistance-determining region (RRDR) are strongly associated with rifampicin resistance, the comprehensive characterisation of RRDR polymorphisms that confer this resistance remains challenging. By incorporating I-SceI sites for I-SceI-based integrant removal and utilizing an L5 swap strategy, we efficiently replaced the integrated plasmid with alternative alleles, making mass allelic exchange feasible in mycobacteria. Using this method to establish a fitness-related gain-of function screen, we generated a mutant library that included all single-amino-acid mutations in the RRDR, and identified the important positions corresponding to some well-known rifampicin-resistance mutations (Q513, D516, S522, H525, R529, S531). We also detected a novel two-point mutation located in the RRDR confers a fitness advantage to M. smegmatis in the presence or absence of rifampicin. Our method provides a comprehensive insight into the growth phenotypes of RRDR mutants and should facilitate the development of anti-tuberculosis drugs.

Efficacy of simple and very brief handgrip and isometric exercises for reducing withdrawal symptoms in cigarette smokers: A pilot randomized controlled trial.

INTRODUCTION: Withdrawal symptoms lead to smoking relapse and reduce the intention to quit. The present pilot RCT examined the effect of simple and very brief handgrip and isometric exercises on reducing withdrawal symptoms, measured by the strength of tobacco craving, Questionnaire of Smoking Urges-Brief (QSU-B), Mood and Physical Symptoms Scale (MPSS), and Positive and Negative Affect Schedule (PANAS). METHODS: In this 2-arm, open-labeled pilot RCT, 30 current smokers who had abstained from tobacco for at least 9 hours were randomly assigned (allocation ratio 1:1) to either the intervention group that watched a 5-minute video and did 5-minute handgrip and isometric exercises (pulling and pushing) or control group that watched 10-minute healthy-diet videos. Measurements were taken before, immediately after, and 10 minutes post-intervention. Outcomes were self-reported strength of tobacco craving, QSU-B, MPSS, and PANAS scores. The effect size for group-by-time interaction was assessed using Cohen's f2 (small=0.02, medium=0.15, large=0.35). RESULTS: Group-by-time interactions showed that the intervention group showed larger reductions than the control group in the strength of tobacco craving (Cohen's f2=0.54, 95% CI: 0.52-0.57), QSU-B (Cohen's f2=0.77; 95% CI: 0.74-0.80), and MPSS (Cohen's f2=0.51; 95% CI: 0.46-0.56) over the three measurement points. CONCLUSIONS: This RCT showed that simple and brief handgrip and isometric exercises could immediately reduce withdrawal symptoms and up to 10 minutes. CLINICAL TRIAL REGISTRATION: in https://clinicaltrials.gov/. IDENTIFIER: NCT04059497.

The effects of flow settings during high-flow nasal cannula oxygen therapy for neonates and young children.

BACKGROUND: During neonatal and paediatric high-flow nasal cannula therapy, optimising the flow setting is crucial for favourable physiological and clinical outcomes. However, considerable variability exists in clinical practice regarding initial flows and subsequent adjustments for these patients. Our review aimed to summarise the impact of various flows during high-flow nasal cannula treatment in neonates and children. METHODS: Two investigators independently searched PubMed, Embase, Web of Science, Scopus and Cochrane for in vitro and in vivo studies published in English before 30 April 2023. Studies enrolling adults (≥18 years) or those using a single flow setting were excluded. Data extraction and risk of bias assessments were performed independently by two investigators. The study protocol was prospectively registered with PROSPERO (CRD42022345419). RESULTS: 38 406 studies were identified, with 44 included. In vitro studies explored flow settings' effects on airway pressures, humidity and carbon dioxide clearance; all were flow-dependent. Observational clinical studies consistently reported that higher flows led to increased pharyngeal pressure and potentially increased intrathoracic airway pressure (especially among neonates), improved oxygenation, and reduced respiratory rate and work of breathing up to a certain threshold. Three randomised controlled trials found no significant differences in treatment failure among different flow settings. Flow impacts exhibited significant heterogeneity among different patients. CONCLUSION: Individualising flow settings in neonates and young children requires consideration of the patient's peak inspiratory flow, respiratory rate, heart rate, tolerance, work of breathing and lung aeration for optimal care.

Highly efficient capture approach for the identification of diverse inherited retinal disorders.

Our study presents a 319-gene panel targeting inherited retinal dystrophy (IRD) genes. Through a multi-center retrospective cohort study, we validated the assay's effectiveness and clinical utility and characterized the mutation spectrum of Taiwanese IRD patients. Between January 2018 and May 2022, 493 patients in 425 unrelated families, all initially suspected of having IRD without prior genetic diagnoses, underwent detailed ophthalmic and physical examinations (with extra-ocular features recorded) and genetic testing with our customized panel. Disease-causing variants were identified by segregation analysis and clinical interpretation, with validation via Sanger sequencing. We achieved a read depth of >200× for 94.2% of the targeted 1.2 Mb region. 68.5% (291/425) of the probands received molecular diagnoses, with 53.9% (229/425) resolved cases. Retinitis pigmentosa (RP) is the most prevalent initial clinical impression (64.2%), and 90.8% of the cohort have the five most prevalent phenotypes (RP, cone-rod syndrome, Usher's syndrome, Leber's congenital amaurosis, Bietti crystalline dystrophy). The most commonly mutated genes of probands that received molecular diagnosis are USH2A (13.7% of the cohort), EYS (11.3%), CYP4V2 (4.8%), ABCA4 (4.5%), RPGR (3.4%), and RP1 (3.1%), collectively accounted for 40.8% of diagnoses. We identify 87 unique unreported variants previously not associated with IRD and refine clinical diagnoses for 21 patients (7.22% of positive cases). We developed a customized gene panel and tested it on the largest Taiwanese cohort, showing that it provides excellent coverage for diverse IRD phenotypes.

Acute severe hypoglycemia immediately after induction of anesthesia in an elderly patient with type 2 diabetes mellitus: A case report.

RATIONALE: Acute severe hypoglycemia immediately following anesthesia induction is a rare but life-threatening complication that is frequently underdiagnosed due to insufficient awareness. Among the various physiological processes influenced by opioids, alterations in blood glucose levels induced by opioids are a side effect that is commonly overlooked. The significance of this report lies in emphasizing the neglected association between opioids and hypoglycemia and highlighting the importance of close glucose monitoring to prevent hypoglycemic events in the perioperative setting. PATIENT CONCERNS: An 89-year-old man with type 2 diabetes mellitus experienced acute severe hypoglycemic episode immediately after general anesthesia induction. Baseline blood glucose level before starting anesthesia induction was 4.0 mmol/L. However, it decreased substantially to 0.96 mmol/L immediately after anesthesia induction. DIAGNOSIS: The patient exhibited normal serum insulin, C-peptide, and cortisol levels, alongside unremarkable renal and hepatic function. After excluding other causes of hypoglycemia, we speculate that opioids were the culprits due to the temporal association and the rapid decline in blood glucose levels. INTERVENTIONS: Forty milliliters of 50% dextrose were administered intravenously followed by an infusion of 5% dextrose. OUTCOMES: Recovery from anesthesia, extubation, and postoperative recovery were unremarkable. No further hypoglycemic episodes occurred during hospitalization. LESSONS: A precipitous and rapid decline in blood glucose following anesthesia induction is extremely uncommon. When a clinical anesthesiologist detects an abnormally low bispectral index during general anesthesia, hypoglycemia should be suspected. Instituting glucose monitoring in these situations can enable a timely diagnosis, forestalling the onset of life-threatening severe hypoglycemia.

Transmission characteristics and inactivated vaccine effectiveness against transmission of the SARS-CoV-2 Omicron BA.2 variant in Shenzhen, China.

We conducted a retrospective cohort study to evaluate the transmission risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 variant and the effectiveness of inactivated COVID-19 vaccine boosters in Shenzhen during a BA.2 outbreak period from 1 February to 21 April 2022. A total of 1,248 individuals were infected with the BA.2 variant, and 7,855 close contacts were carefully investigated. The risk factors for the high secondary attack rate of SARS-CoV-2 infection were household contacts [adjusted odds ratio (aOR): 1.748; 95% confidence interval (CI): 1.448, 2.110], younger individuals aged 0-17 years (aOR: 2.730; 95% CI: 2.118, 3.518), older persons aged ≥60 years (aOR: 1.342; 95% CI: 1.135, 1.588), women (aOR: 1.442; 95% CI: 1.210, 1.718), and the subjects exposed to the post-onset index cases (aOR: 8.546; 95% CI: 6.610, 11.050), respectively. Compared with the unvaccinated and partially vaccinated individuals, a relatively low risk of secondary attack was found for the individuals who received booster vaccination (aOR: 0.871; 95% CI: 0.761, 0.997). Moreover, a high transmission risk was found for the index cases aged ≥60 years (aOR: 1.359; 95% CI: 1.132, 1.632), whereas a relatively low transmission risk was observed for the index cases who received full vaccination (aOR: 0.642; 95% CI: 0.490, 0.841) and booster vaccination (aOR: 0.676; 95% CI: 0.594, 0.770). Compared with full vaccination, booster vaccination of inactivated COVID-19 vaccine showed an effectiveness of 24.0% (95% CI: 7.0%, 37.9%) against BA.2 transmission for the adults ≥18 years and 93.7% (95% CI: 72.4%, 98.6%) for the adults ≥60 years, whereas the effectiveness was 51.0% (95% CI: 21.9%, 69.3%) for the individuals of 14 days to 179 days after booster vaccination and 51.2% (95% CI: 37.5%, 61.9%) for the non-household contacts. The estimated mean values of the generation interval, serial interval, incubation period, latent period, and viral shedding period were 2.7 days, 3.2 days, 2.4 days, 2.1 days, and 17.9 days, respectively. In summary, our results confirmed that the main transmission route of Omicron BA.2 subvariant was household contact, and booster vaccination of the inactivated vaccines was relatively effective against BA.2 subvariant transmission in older people.