The 90% effective dose (ED90) of remimazolam for inhibiting responses to the insertion of a duodenoscope during ERCP.

BACKGROUND: Compared to midazolam, remimazolam has a faster onset and offset of hypnotic effect, as well as cardiorespiratory stability, this study aims to determine the 90% effective dose (ED90) of remimazolam to inhibit responses to insertion of a duodenoscope during endoscopic retrograde cholangiopancreatography (ERCP). METHODS: A dose-response study was carried out undergoing ERCP who received remimazolam-alfentanil anesthesia using 10 µg/kg of alfentanil between September 2021 and November 2021. The initial dose of remimazolam was 0.2 mg/kg. The dose was then decided based on the responses of earlier patients by exploiting the sequential ascend and descend according to a 9: 1 biased coin design. Upon failure, the dose of remimazolam was increased by 0.025 mg/kg in the next patient. When the insertion was successful, the succeeding patient was randomized to an identical dose or a dose that was lower by 0.025 mg/kg.The ED90 of remimazolam for inhibiting responses to the insertion of a duodenoscope during ERCP was calculated. Adverse events and complications of remimazolam were recorded. RESULTS: A total of 55 elderly patients (age > 65) were included in the study. 45 successfully anesthetized patients, and 10 unsuccessfully. The ED90 of remimazolam was 0.300 mg/kg (95% CI = 0.287-0.320). ED95 was 0.315 (95% CI = 0.312-0.323) and ED99 was 0.323 (95% CI = 0.323-0.325). Among the patients, 9 patients developed hypotension, 2 patients developed bradycardia and 1 patient developed tachycardia, and hypoxia occurred in 2 patients. CONCLUSIONS: A loading dose of 0.300 mg / kg of remimazolam for elderly patients undergoing ERCP can safely, effectively, and quickly induce patients to fall asleep and inhibit responses to the insertion of a duodenoscope. TRIAL REGISTRATION: The study protocol was registered at the website ClinicalTrials.gov on 22/09/2021(NCT05053763).

Draconibacterium aestuarii sp.nov., a Glycolipid-Producing Bacterium Isolated from Tidal Flat Sediment and Emended Description of the Genus Draconibacterium.

A facultatively anaerobic, Gram-negative, curved rod-shaped bacterium (4.0-17.0 µm long, 0.6-0.9 µm wide), designated Z1-6T, was obtained from tidal flat sediment collected from YueAo village in Zhoushan, Zhejiang, People's Republic of China. Strain Z1-6T occurred at 15-45 °C (optimum 28-32 °C), pH 6.0-9.0 (optimum 7.0-7.5), and in the presence of 1-5% (w/v) NaCl (optimum 1-2%). The strain contained iso-C15:0 and antesio-C15:0 as the major fatty acids. An unsaturated menaquinone with seven isoprene units (MK-7) was the predominant respiratory quinone. The polar lipids included phosphatidylethanolamine (PE), one aminophospholipid (APL), two phospholipids (PL1 and PL2), three glycolipids (GL1, GL2, and GL3), and two unidentified lipids (L1 and L2). The genomic DNA G+C content of strain Z1-6T was 39.2%, and the genome size was 6.4 Mb. The strain showed the highest average nucleotide identity (ANI) value of 73.5-74.6%, digital DNA-DNA hybridization (dDDH) value of 19.3-20%, average amino acid identity (AAI) value of 72.0-73.1% with the members of genus Draconibacterium. Phylogenetic analysis based on 16S rRNA gene sequences and genome revealed that strain Z1-6T formed a distinct branch in the clade of the genus Draconibacterium. Based on the phenotypic, phylogenetic, chemotaxonomic analyses and genomic data, strain Z1-6T represents a novel species of the genus Draconibacterium, for which the name Draconibacterium aestuarii sp. nov. (The type strain Z1-6T = MCCC 1K07533T = KCTC 92310T) is proposed.

Photoinduced Palladium-Catalyzed Radical Heck-Type Coupling of Cyclobutanone Oxime Esters with Vinyl Arenes.

A palladium-catalyzed radical Heck-type coupling reaction of cyclobutanone oxime esters with olefins under visible-light irradiation has been developed. The cyanoalkyl/Pd(I) hybrid species generated by selected ring-opening C-C bond cleavage of imino/Pd(I) species reacted smoothly with vinyl arenes, delivering the cyanoalkylation olefins under mild conditions. This elegant strategy has a broad scope and functional group tolerance. Subsequently, late-stage functionalization of bioactive molecules and synthetic transformations of the product further confirm the practicality.

The network structures of depressive and insomnia symptoms among cancer patients using propensity score matching: Findings from the Health and Retirement Study (HRS).

OBJECTIVE: Both depression and insomnia are found to be more prevalent in cancer patients compared to the general population. This study compared the network structures of depression and insomnia among cancer patients versus cancer-free participants (controls hereafter). METHOD: The 8-item Center for Epidemiological Studies Depression Scale (CESD-8) and the 4-item Jenkins Sleep Scale (JSS-4) were used to measure depressive and insomnia symptoms, respectively. Propensity score matching (PSM) was used to construct the control group using data from the Health and Retirement Study (HRS). In total, a sample consisting of 2216 cancer patients and 2216 controls was constructed. Central (influential) and bridge symptoms were estimated using the expected influence (EI) and bridge expected influence (bridge EI), respectively. Network stability was assessed using the case-dropping bootstrap method. RESULT: The prevalence of depression (CESD-8 total score ≥ 4) in cancer patients was significantly higher compared to the control group (28.56 % vs. 24.73 %; P = 0.004). Cancer patients also had more severe depressive symptoms relative to controls, but there was no significant group difference for insomnia symptoms. The network structures of depressive and insomnia symptoms were comparable between cancer patients and controls. "Felt sadness" (EI: 6.866 in cancer patients; EI: 5.861 in controls), "Felt unhappy" (EI: 6.371 in cancer patients; EI: 5.720 in controls) and "Felt depressed" (EI: 6.003 in cancer patients; EI: 5.880 in controls) emerged as the key central symptoms, and "Felt tired in morning" (bridge EI: 1.870 in cancer patients; EI: 1.266 in controls) and "Everything was an effort" (bridge EI: 1.046 in cancer patients; EI: 0.921 in controls) were the key bridge symptoms across both groups. CONCLUSION: Although cancer patients had more frequent and severe depressive symptoms compared to controls, no significant difference was observed in the network structure or strength of the depressive and insomnia symptoms. Consequently, psychosocial interventions for treating depression and insomnia in the general population could be equally applicable for cancer patients who experience depression and insomnia.

Inter-relationships of depression and insomnia symptoms with life satisfaction in stroke and stroke-free older adults: Findings from the Health and Retirement Study based on network analysis and propensity score matching.

BACKGROUND: Depression and insomnia are common co-occurring psychiatric problems among older adults who have had strokes. Nevertheless, symptom-level relationships between these disorders remain unclear. OBJECTIVES: In this study, we compared inter-relationships of depression and insomnia symptoms with life satisfaction among older stroke patients and stroke-free peers in the United States. METHODS: The study included 1026 older adults with a history of stroke and 3074 matched controls. Data were derived from the US Health and Retirement Study. Depression, insomnia and life satisfaction were assessed. Propensity score matching was employed to identify demographically-similar groups of stroke patients and controls. Central and bridge symptoms were assessed using Expected influence (EI) and bridge EI, respectively. RESULTS: The prevalence of depression in the stroke group (25.0 %) was higher than that of controls (14.3 %, P < 0.001). In stroke group, "Feeling depressed" (CESD1; EI: 5.80), "Feeling sad" (CESD7; EI: 4.67) and "Not enjoying life" (CESD6; EI: 4.51) were the most central symptoms, while "Feeling tired in the morning" (JSS4; BEI: 1.60), "Everything was an effort" (CESD2; BEI: 1.21) and "Waking up during the night" (JSS2; BEI: 0.98) were key bridge symptoms. In controls, the most central symptoms were "Lack of happiness" (CESD4; EI: 6.45), "Feeling depressed" (CESD1; EI: 6.17), and "Feeling sad" (CESD7; EI: 6.12). Furthermore, "Feeling tired in the morning" (JSS4; BEI: 1.93), "Everything was an effort" (CESD2; BEI: 1.30), and "Waking up too early" (JSS3; BEI: 1.12) were key bridge symptoms. Life satisfaction had the most direct associations with "Not enjoying life" (CESD6) and "Feeling lonely" (CESD5) in the two groups, respectively. CONCLUSION: Older adults with stroke exhibited more severe depression and insomnia symptoms. Interventions targeting central and bridge symptoms may help to mitigate the co-occurrence of these symptoms.

Association of gene polymorphisms and the decreased expression of long non-coding RNA LOC553103 with rheumatoid arthritis.

BACKGROUND: Long non-coding RNAs (lncRNAs) are involved in many key bioprocesses, including the occurrence and development of rheumatoid arthritis (RA). We aimed to analyze the association of genetic variants of long non-coding RNA LOC553103 and its peripheral blood mononuclear cells (PBMC) expression with RA. METHODS: We enrolled 457 RA patients and 551 healthy controls and conducted a case-control study to analyze the relationship between LOC553103 gene rs272879 and the susceptibility of RA by TaqMan single nucleotide polymorphism genotyping. Among them, we sampled 92 cases and 92 controls, respectively, to detect the PBMC level of LOC553103 using quantitative real-time polymerase chain reaction technology. We explored the association between LOC553103 rs272879 and its PBMC expression levels in 71 RA patients. Mann-Whitney, Chi-square, and Spearman correlation analysis were used for statistical analysis and P-value <.05 was considered statistically significant. RESULTS: The genotype frequency of LOC553103 rs272879 CC was increased, and CG was decreased in RA patients compared to the control group (χ2 = 6.772, P = .034). The LOC553103 expression level in PBMC of RA patients was downregulated compared to healthy control (Z = -4.497, P < .001). Moreover, negative correlations were observed between the PBMC level of LOC553103 and erythrocyte sedimentation rate (rs = -0.262, P = .018), white blood cell count (rs = -0.382, P = .004), platelet (rs = -0.293, P = .030), and disease activity score in 28 joints (rs = -0.271, P = .016) in RA patients. CONCLUSIONS: This study provides the first evidence supporting an association between LOC553103 gene polymorphisms and susceptibility of RA and a relationship of PBMC level of LOC553103 with clinical manifestations and laboratory indicators of RA patients.

Phytoplankton-derived polysaccharides and microbial peptidoglycans are key nutrients for deep-sea microbes in the Mariana Trench.

BACKGROUND: The deep sea represents the largest marine ecosystem, driving global-scale biogeochemical cycles. Microorganisms are the most abundant biological entities and play a vital role in the cycling of organic matter in such ecosystems. The primary food source for abyssal biota is the sedimentation of particulate organic polymers. However, our knowledge of the specific biopolymers available to deep-sea microbes remains largely incomplete. One crucial rate-limiting step in organic matter cycling is the depolymerization of particulate organic polymers facilitated by extracellular enzymes (EEs). Therefore, the investigation of active EEs and the microbes responsible for their production is a top priority to better understand the key nutrient sources for deep-sea microbes. RESULTS: In this study, we conducted analyses of extracellular enzymatic activities (EEAs), metagenomics, and metatranscriptomics from seawater samples of 50-9305 m from the Mariana Trench. While a diverse array of microbial groups was identified throughout the water column, only a few exhibited high levels of transcriptional activities. Notably, microbial populations actively transcribing EE genes involved in biopolymer processing in the abyssopelagic (4700 m) and hadopelagic zones (9305 m) were primarily associated with the class Actinobacteria. These microbes actively transcribed genes coding for enzymes such as cutinase, laccase, and xyloglucanase which are capable of degrading phytoplankton polysaccharides as well as GH23 peptidoglycan lyases and M23 peptidases which have the capacity to break down peptidoglycan. Consequently, corresponding enzyme activities including glycosidases, esterase, and peptidases can be detected in the deep ocean. Furthermore, cell-specific EEAs increased at 9305 m compared to 4700 m, indicating extracellular enzymes play a more significant role in nutrient cycling in the deeper regions of the Mariana Trench. CONCLUSIONS: Transcriptomic analyses have shed light on the predominant microbial population actively participating in organic matter cycling in the deep-sea environment of the Mariana Trench. The categories of active EEs suggest that the complex phytoplankton polysaccharides (e.g., cutin, lignin, and hemicellulose) and microbial peptidoglycans serve as the primary nutrient sources available to deep-sea microbes. The high cell-specific EEA observed in the hadal zone underscores the robust polymer-degrading capacities of hadal microbes even in the face of the challenging conditions they encounter in this extreme environment. These findings provide valuable new insights into the sources of nutrition, the key microbes, and the EEs crucial for biopolymer degradation in the deep seawater of the Mariana Trench. Video Abstract.

Recurrent pembrolizumab-induced mechanical small bowel obstruction in a patient with metastatic cervical cancer.

•Adverse events of pembrolizumab have been documented, but more severe gastrointestinal effects are not as well described.•We report a case of a patient with cervical cancer treated with pembrolizumab who developed small bowel obstruction (SBO)•Histological analysis and gastrointestinal workup points to pembrolizumab as likely cause of SBO.

Effects of extracorporeal diaphragm pacing combined with inspiratory muscle training on respiratory function in people with stroke: a randomized controlled trial.

OBJECTIVES: To evaluate the effect of external diaphragmatic pacing (EDP) combined with inspiratory muscle training on respiratory function in post-stroke patients. METHODS: Patients with stroke were enrolled from the First Affiliated Hospital of Soochow University in China between 2021 and 2022. The patients were randomized into an EDP treatment group (control group) or an EDP treatment plus inspiratory muscle training group (experimental group). Each therapy was administered once a day for 6 days per week. The peak inspiratory flow (PIF), maximal inspiratory pressure (MIP), forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC% ratio, and diaphragm thickness and mobility were measured and compared between the two groups after 4 weeks. RESULTS: After 4 weeks of intervention, respiratory muscle function indicators including PIF (95% CI: 0.21-1.28, p = 0.008) and MIP (95% CI: 6.92-25.44, p = 0.001) significantly improved in the experimental group. Diaphragmatic thickness also significantly increased in the experimental group (p < 0.05), while diaphragmatic excursion showed no significant difference between the two groups. Additionally, FVC (95% CI: 0.14-1.14, p = 0.013) and FEV1 (95% CI: 0.20-1.06, p = 0.005) demonstrated a significant increase in the experimental group, whereas FEV1/FVC% (95% CI: -0.84 to 9.36, p = 0.099) exhibited no significant group difference. CONCLUSION: EDP combined with inspiratory muscle training in individuals with stroke provides greater benefits than EDP alone in terms of respiratory function recovery, except for the parameters of diaphragmatic excursion and FEV1/FVC%.

Isthmin-1 alleviates cardiac ischemia/reperfusion injury through cGMP-PKG signaling pathway.

AIMS: Ischemia/reperfusion (I/R) injury is an important complication of reperfusion therapy for acute myocardial infarction, extremely compromising the cardiac benefits of revascularization, however, specific and efficient treatment for cardiac I/R injury is still lacking. Isthmin-1 (ISM1) is a novel adipokine, and plays indispensable roles in regulating glycolipid metabolism and cell survival. The present study aims to investigate the potential role and molecular mechanism of ISM1 in cardiac I/R injury using gain- and loss-of-function approaches. METHODS AND RESULTS: Cardiac-specific ISM1 overexpression and silence were achieved using an adeno-associated virus serotype 9 system, and then these mice were subjected to I/R surgery, followed by biochemical test, echocardiography and histopathologic examinations, etc. Meanwhile, neonatal rat cardiomyocytes (NRCMs) with ISM1 silence or overexpression also received simulated I/R (sI/R) injury to further verify its role in vitro. The potential downstream pathways and molecular targets of ISM1 were screened by RNA-sequencing. We also treated injured mice and NRCMs with recombinant ISM1 (rISM1) to explore whether supplementation with ISM1 was sufficient to protect against I/R injury. Furthermore, acute myocardial infarction patients with percutaneous coronary intervention (PCI) and paired healthy controls were included to reveal the clinical relevance of circulating ISM1. Cardiac-specific ISM1 silencing aggravated while ISM1 overexpression alleviated I/R-induced acute cardiac injury and cardiac remodeling and dysfunction. Mechanistically, ISM1 targeted αvß5 integrin to facilitate the nuclear accumulation of nuclear transcription factor Y subunit alpha, transcriptionally increased soluble guanylyl cyclase beta subunit expression, and eventually enhanced cGMP generation. Besides, we confirmed that treatment with rISM1 before or after reperfusion could confer cardioprotective effects in mice. Clinically, lower ISM1 levels post-PCI was associated with worse outcome in patients. CONCLUSION: ISM1 can protect against cardiac I/R injury through cGMP-PKG signaling pathway, and it is a promising therapeutic and predictive target of cardiac I/R injury.

[Mechanism of astragaloside â £ combined with Panax notoginseng saponins in regulating angiogenesis to treat cerebral ischemia based on network pharmacology and experimental verification].

Network pharmacology and animal and cell experiments were employed to explore the mechanism of astragaloside Ⅳ(AST Ⅳ) combined with Panax notoginseng saponins(PNS) in regulating angiogenesis to treat cerebral ischemia. The method of network pharmacology was used to predict the possible mechanisms of AST Ⅳ and PNS in treating cerebral ischemia by mediating angiogenesis. In vivo experiment: SD rats were randomized into sham, model, and AST Ⅳ(10 mg·kg~(-1)) + PNS(25 mg·kg~(-1)) groups, and the model of cerebral ischemia was established with middle cerebral artery occlusion(MCAO) method. AST Ⅳ and PNS were administered by gavage twice a day. the Longa method was employed to measure the neurological deficits. The brain tissue was stained with hematoxylin-eosin(HE) to reveal the pathological damage. Immunohistochemical assay was employed to measure the expression of von Willebrand factor(vWF), and immunofluorescence assay to measure the expression of vascular endothelial growth factor A(VEGFA). Western blot was employed to determine the protein levels of vascular endothelial growth factor receptor 2(VEGFR2), VEGFA, phosphorylated phosphatidylinositol 3-kinase(p-PI3K), and phosphorylated protein kinase B(p-AKT) in the brain tissue. In vitro experiment: the primary generation of rat brain microvascular endothelial cells(rBEMCs) was cultured and identified. The third-generation rBMECs were assigned into control, model, AST Ⅳ(50 µmol·L~(-1)) + PNS(30 µmol·L~(-1)), LY294002(PI3K/AKT signaling pathway inhibitor), 740Y-P(PI3K/AKT signaling pathway agonist), AST Ⅳ + PNS + LY294002, and AST Ⅳ + PNS + 740Y-P groups. Oxygen glucose deprivation/re-oxygenation(OGD/R) was employed to establish the cell model of cerebral ischemia-reperfusion injury. The cell counting kit-8(CCK-8) and scratch assay were employed to examine the survival and migration of rBEMCs, respectively. Matrigel was used to evaluate the tube formation from rBEMCs. The Transwell assay was employed to examine endothelial cell permeability. Western blot was employed to determine the expression of VEGFR2, VEGFA, p-PI3K, and p-AKT in rBEMCs. The results of network pharmacology analysis showed that AST Ⅳ and PNS regulated 21 targets including VEGFA and AKT1 of angiogenesis in cerebral infarction. Most of these 21 targets were involved in the PI3K/AKT signaling pathway. The in vivo experiments showed that compared with the model group, AST Ⅳ + PNS reduced the neurological deficit score(P<0.05) and the cell damage rate in the brain tissue(P<0.05), promoted the expression of vWF and VEGFA(P<0.01) and angiogenesis, and up-regulated the expression of proteins in the PI3K/AKT pathway(P<0.05, P<0.01). The in vitro experiments showed that compared with the model group, the AST Ⅳ + PNS, 740Y-P, AST Ⅳ + PNS + LY294002, and AST Ⅳ + PNS + 740Y-P improved the survival of rBEMCs after OGD/R, enhanced the migration of rBEMCs, increased the tubes formed by rBEMCs, up-regulated the expression of proteins in the PI3K/AKT pathway, and reduced endothelial cell permeability(P<0.05, P<0.01). Compared with the LY294002 group, the AST Ⅳ + PNS + LY294002 group showed increased survival rate, migration rate, and number of tubes, up-regulated expression of proteins in the PI3K/AKT pathway, and decreased endothelial cell permeability(P<0.05,P<0.01). Compared with the AST Ⅳ + PNS and 740Y-P groups, the AST Ⅳ + PNS + 740Y-P group presented increased survival rate, migration rate, and number of tubes and up-regulated expression of proteins in the PI3K/AKT pathway, and reduced endothelial cell permeability(P<0.01). This study indicates that AST Ⅳ and PNS can promote angiogenesis after cerebral ischemia by activating the PI3K/AKT signaling pathway.

Longitudinal associations of polypharmacy and frailty with major cardiovascular events and mortality among more than half a million middle-aged participants of the UK Biobank.

BACKGROUND: Studies of the associations of polypharmacy and frailty with adverse health outcomes in middle-aged adults are limited. Furthermore, a potentially stronger association of polypharmacy with adverse health outcomes in frail than in non-frail adults is of interest. OBJECTIVE: To evaluate associations of frailty (assessed using a frailty index) and polypharmacy (defined as taking five or more drugs) with major cardiovascular events, cancer incidence, all-cause, cardiovascular disease-specific, and cancer-specific mortality. METHODS: Cox proportional hazards regression models were used to analyze 501,548 participants of the UK Biobank cohort study aged 40-69 years who were followed up for an average of 12 years. RESULTS: The prevalence of pre-frailty and frailty were 43.2 % and 2.3 %, respectively, and that of polypharmacy was 18.3 %. Although strongly associated with each other, frailty and polypharmacy were independently, statistically significantly associated with major cardiovascular events, cardiovascular disease-specific, and all-cause mortality. In addition, the hazard ratios of polypharmacy were stronger among (pre-)frail than non-frail study participants. No profound associations with cancer incidence and cancer mortality were observed. No sex and age differences were observed. CONCLUSIONS: This large cohort study showed that polypharmacy and frailty are independent risk factors for major cardiovascular events, cardiovascular disease-specific and all-cause mortality in both middle-aged (40-64 years) and older people (≥ 65 years). In addition, the hazard ratios of polypharmacy were stronger among (pre-)frail than non-frail study participants. This underlines the need to avoid polypharmacy as far as possible not only in older but also in middle-aged subjects (40-64 years), especially if they are pre-frail or frail.

Challenging pitfalls in frozen section pathology: a case of mandible ghost cell odontogenic carcinoma and the literature review.

BACKGROUND: Ghost cell odontogenic carcinoma (GCOC) is a rare malignancy characterized by the presence of ghost cells, preferably in the maxilla. Only slightly more than 50 case reports of GCOC have been documented to date. Due to the rarity of this tumor and its nonspecific clinical criteria, there is a heightened risk of misdiagnosis in clinical examination, imaging findings, and pathology interpretation. CASE PRESENTATION: A 50-year-old male patient presented to the hospital due to experiencing pain in his lower front teeth while eating for the past 2 months. Upon examination, a red, hard, painless mass was found in his left lower jaw, measuring approximately 4.0 cm × 3.5 cm. Based on the malignant histological morphology of the tumor and the abundant red-stained keratinized material, the preoperative frozen section pathology misdiagnosed it as squamous cell carcinoma (SCC). The surgical resection specimen pathology via paraffin section revealed that the tumor was characterized by round-like epithelial islands within the fibrous interstitium, accompanied by a large number of ghost cells and some dysplastic dentin with infiltrative growth. The malignant components displayed marked heterogeneity and mitotic activity. Additionally, a calcified cystic tumor component of odontogenic origin was observed. Hemorrhage, necrosis, and calcifications were present, with a foreign body reaction around ghost cells. Immunoreactivity for ß-catenin showed strong nuclear positivity in tumor cells, while immunostaining was completely negative for p53. The Ki67 proliferation index was approximately 30-40%. The tumor cells exhibited diffuse CK5/6, p63, and p40 immunoreactivity, with varying immunopositivity for EMA. Furthermore, no BRAFV600E mutation was identified by ARMS-PCR. The final pathology confirmed that the tumor was a mandible GCOC. CONCLUSION: We have reported and summarized for the first time the specific manifestations of GCOC in frozen section pathology and possible pitfalls in misdiagnosis. We also reviewed and summarized the etiology, pathological features, molecular characteristics, differential diagnosis, imaging features, and current main treatment options for GCOC. Due to its rarity, the diagnosis and treatment of this disease still face certain challenges. A correct understanding of the pathological morphology of GCOC, distinguishing the ghost cells and the secondary stromal reaction around them, is crucial for reducing misdiagnosis rates.

Vogt-Koyanagi-Harada disease after SARS-CoV-2 infection: Case report and literature review.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for coronavirus disease 2019 (COVID-19), a complex and multifaceted illness. COVID-19 is associated with various ocular manifestations including conjunctivitis, retinal vein occlusion and optic neuritis. However, the case of Vogt-Koyanagi-Harada (VKH) disease associated with SARS-CoV-2 is infrequent, and the specific association is still unclear. CASE PRESENTATION: In the present study, a 35-year-old female patient without any significant medical history presented with 1 week of bilateral blurred vision, occurring 2 weeks after a clinical course of COVID-19. Upon examination, both eyes exhibited bullous serous retinal detachments. She was diagnosed with incomplete VKH disease. Early diagnosis and treatment of VKH disease are essential for the visual prognosis of this aggressive disease. In this particular patient, ocular inflammatory signs and visual acuity improved via corticosteroid therapy. It is worth noting that the occurrence of VKH disease associated with SARS-CoV-2 is uncommon, and the specific connection between the two remains unknown. We review and summarize the clinical characteristics of VKH disease following SARS-CoV-2 infection, and discuss the potential mechanisms that may explain this phenomenon, based on similar studies previously reported. CONCLUSION: Despite the unclear causality, it is important for ophthalmologists and physicians to be recognizant of the possible association between VKH disease and COVID-19. SARS-CoV-2 may play a potential immunological triggering role in VKH disease. However, further in-depth research is necessary to investigate the clinical and epidemiological features, as well as the underlying mechanisms of this association.

Further clarification of cognitive processes of prospective memory in schizophrenia by comparing eye-tracking and ecologically-valid measurements.

The aim of this study is to compare ecologically-valid measure (the Cambridge Prospective Memory Test, CAMPROMPT) and laboratory measure (eye-tracking paradigm) in assessing prospective memory (PM) in individuals with schizophrenia spectrum disorders (SSDs). In addition, eye-tracking indices are used to examine the relationship between PM and other cognitive domains in SSDs patients. Initially, the study sample was formed by 32 SSDs patients and 32 healthy control subjects (HCs) who were matched in sociodemographic profile and the performance on CAMPROMPT. An eye-tracking paradigm was employed to examine the differences in PM accuracy and key cognitive processes (e.g., cue monitoring) between the two groups. Additional 31 patients were then recruited to investigate the relationship between PM cue monitoring, other cognitive functions, and the severity of clinical symptoms within the SSDs group. The monitoring of PM cue was reflected in total fixation time and total fixation counts for distractor words. Cognitive functions were assessed using the Chinese version of the MATRICS Consensus Cognitive Battery (MCCB). The Positive and Negative Syndrome Scale (PANSS) was applied to assess psychopathology. SSDs patients exhibited fewer total fixation counts for distractor words and lower PM accuracy compared to HCs, even though they were priori matched on CAMPROMPT. Correlation analysis within the SSDs group (63 cases) indicated a negative correlation between PM accuracy and PANSS total score, and a positive correlation with working memory and attention/vigilance. Regression analysis within the SSDs group revealed that higher visual learning and lower PANSS total scores independently predicted more total fixation counts on distractor words. Impairment in cue monitoring is a critical factor in the PM deficits in SSDs. The eye-tracking laboratory paradigm has advantages over the ecologically-valid measurement in identifying the failure of cue detection, making it a more sensitive tool for PM deficits in patients with SSDs.

Polar alcohol guest molecules regulate the stacking modes of 2-D MOF nanosheets.

The modulation of two-dimensional metal-organic framework (2-D MOF) nanosheet stacking is an effective means to improve the properties and promote the application of nanosheets in various fields. Here, we employed a series of alcohol guest molecules (MeOH, EtOH and PrOH) to modulate Zr-BTB (BTB = benzene-1,3,5-tribenzoate) nanosheets and to generate untwisted stacking. The distribution of stacking angles was statistically analyzed from high-angle annular dark-field (HAADF) and fast Fourier transform (FFT) images. The ratios of untwisted stacking were calculated, such as 77.01% untwisted stacking for MeOH, 83.45% for EtOH, and 85.61% for PrOH. The obtained untwisted Zr-BTB showed good separation abilities for different substituted benzene isomers, superior para selectivity and excellent column stability and reusability. Control experiments of 2-D Zr-TCA (TCA = 4,4',4''-tricarboxytriphenylamine) and Zr-TATB (TATB = 4,4',4''-(1,3,5-triazine-2,4,6-triyl)tribenzoic acid) nanosheets with similar pore sizes and stronger polarity regulated by the alcohol guests exhibited moderate separation performance. The electron microscopy images revealed that polar alcohol regulation dominantly generated the twisted stacking of Zr-TCA and Zr-TATB with various Moiré patterns. Polar guest molecules, such as alcohols, provide strong host-guest interactions during the regulation of MOF nanosheet stacking, providing an opportunity to design new porous Moiré materials with application prospects.

Extending the Grading of Recommendations Assessment, Development and Evaluation (GRADE) in Traditional Chinese Medicine (TCM): The GRADE-TCM.

AIM: To extend and form the "Grading of Recommendations Assessment, Development and Evaluation in Traditional Chinese Medicine" (GRADE-TCM). METHODS: Methodologies were systematically reviewed and analyzed concerning evidence-based TCM guidelines worldwide. A survey questionnaire was developed based on the literature review and open-end expert interviews. Then, we performed expert consensus, discussion meeting, opinion collection, external examination, and the GRADE-TCM was formed eventually. RESULTS: 265 Chinese and English TCM guidelines were included and analyzed. Five experts completed the open-end interviews. Ten methodological entries were summarized, screened and selected. One round of consensus was conducted, including a total of 22 experts and 220 valid questionnaire entries, concerning 1) selection of the GRADE, 2) GRADE-TCM upgrading criteria, 3) GRADE-TCM evaluation standard, 4) principles of consensus and recommendation, and 5) presentation of the GRADE-TCM and recommendation. Finally, consensus was reached on the above 10 entries, and the results were of high importance (with voting percentages ranging from 50 % to 81.82 % for "very important" rating) and strong reliability (with the Cr ranging from 0.93 to 0.99). Expert discussion meeting (with 40 experts), opinion collection (in two online platforms) and external examination (with 14 third-party experts) were conducted, and the GRADE-TCM was established eventually. CONCLUSION: GRADE-TCM provides a new extended evidence-based evaluation standard for TCM guidelines. In GRADE-TCM, international evidence-based norms, characteristics of TCM intervention, and inheritance of TCM culture were combined organically and followed. This is helpful for localization of the GRADE in TCM and internationalization of TCM guidelines.

Serum 25-Hydroxyvitamin D Status and Vitamin D Supplements Use Are Not Associated with Low Back Pain in the Large UK Biobank Cohort.

Longitudinal studies assessing the association of vitamin D deficiency, defined by serum 25-hydroxyvitamin D levels < 30 nmol/L, and vitamin D supplement (VDS) use with low back pain (LBP) are sparse. This investigation assessed the cross-sectional and longitudinal association of vitamin D status and VDS use with LBP among 135,934 participants from the UK Biobank cohort. Approximately 21.6% of the participants had vitamin D deficiency, while only 4% regularly took VDS. In the month before study enrollment, 3.8% of the population reported experiencing LBP. An additional 3.3% of the population were diagnosed with LBP by their general practitioners for the first time during a median follow-up of 8.5 years. Vitamin D deficiency and VDS use were cross-sectionally associated with LBP in age- and sex-adjusted models, but these associations were not evident in comprehensively adjusted models. In longitudinal analyses, both vitamin D deficiency and VDS use were not associated with LBP in any model after correction for multiple testing. In conclusion, not unexpectedly due to the fact that LBP is multifactorial, our findings provide no evidence for the role of the vitamin D status in the etiology of LBP.

ABC2A: A Straightforward and Fast Method for the Accurate Backmapping of RNA Coarse-Grained Models to All-Atom Structures.

RNAs play crucial roles in various essential biological functions, including catalysis and gene regulation. Despite the widespread use of coarse-grained (CG) models/simulations to study RNA 3D structures and dynamics, their direct application is challenging due to the lack of atomic detail. Therefore, the reconstruction of full atomic structures is desirable. In this study, we introduced a straightforward method called ABC2A for reconstructing all-atom structures from RNA CG models. ABC2A utilizes diverse nucleotide fragments from known structures to assemble full atomic structures based on the CG atoms. The diversification of assembly fragments beyond standard A-form ones, commonly used in other programs, combined with a highly simplified structure refinement process, ensures that ABC2A achieves both high accuracy and rapid speed. Tests on a recent large dataset of 361 RNA experimental structures (30-692 nt) indicate that ABC2A can reconstruct full atomic structures from three-bead CG models with a mean RMSD of ~0.34 Å from experimental structures and an average runtime of ~0.5 s (maximum runtime < 2.5 s). Compared to the state-of-the-art Arena, ABC2A achieves a ~25% improvement in accuracy and is five times faster in speed.