Arachidonic acid metabolism CYP450 pathway is deregulated in hepatocellular carcinoma and associated with microvascular invasion.

Arachidonic acid metabolism plays a crucial role in the development and progression of inflammatory and metabolic liver diseases. However, its role in hepatocellular carcinoma (HCC) remains unclear. In this study, we investigated the expression of key genes involved in the arachidonic acid metabolism pathway in HCC using a combination of bioinformatics, proteomics and immunohistochemistry analyses. Through a comprehensive analysis of publicly available datasets, clinical HCC tissues, and tissue microarrays, we compared the expression of hepatic arachidonic acid metabolic genes. We observed significant downregulation of cytochrome P450 (CYP450) pathway genes at both the messenger RNA and protein levels in HCC tissues compared to normal liver tissues. Furthermore, we observed a strong correlation between the deregulation of the arachidonic acid metabolism CYP450 pathway and the pathological features and prognosis of HCC. Specifically, the expression of CYP2C8/9/18/19 was significantly correlated with pathological grade (r = -.484, p < .0001), vascular invasion (r = -.402, p < .0001), aspartate transaminase (r = -.246, p = .025), gamma-glutamyl transpeptidase (r = -.252, p = .022), alkaline phosphatase (r = -.342, p = .002), alpha-fetoprotein (r = -.311, p = .004) and carbohydrate antigen 19-9 (r = -.227, p = .047). Moreover, we discovered a significant association between CYP450 pathway activity and vascular invasion in HCC. Collectively, these data indicate that arachidonic acid CYP450 metabolic pathway deregulation is implicated in HCC progression and may be a potential predictive factor for early recurrence in patients with HCC.

Contralateral needling at the foot of unaffected side combining with rehabilitation treatment for motor dysfunction of hand after ischemic stroke: study protocol for a randomized controlled pilot trial.

This pilot study is to assess the feasibility and the effect of a combination therapy of rehabilitation treatment and contralateral needling, which is manipulated at the foot of the unaffected side, for the recovery of the paretic hand post-stroke. This prospective pilot clinical trial will recruit 72 stroke patients with paretic hands and a disease course of 14 to 90 d. Patients will be randomized into two groups: the control group will receive conventional Xingnao Kaiqiao acupuncture and basic treatment for the stroke; based on the control group, the observation group will receive the contralateral needling at the foot of the unaffected side combined with the rehabilitation movement of the paretic hand. 12 sessions will be administrated for 2 weeks. The primary outcome, Fugl-Meyer Assessment, and the secondary outcomes, the handgrip strength, the range of motion, the modified Barthel index, and the Brunnstrom recovery stages, will be measured the recovery of the hand motor function during the 2 weeks' intervention. This study aims to investigate the instant effect of contralateral needling at the foot of the unaffected side combined with the rehabilitation treatment movement for patients with the paretic hand of Poststroke motor dysfunction and provide the previous evidence for the future large sample studies.

[Ecological Toxic Effect of Perfluorinated Compounds on Fish Based on Meta-analysis].

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are refractory organic pollutants, which are characterized by ubiquity, bioaccumulation, and biological toxicity. To explore the biotoxic effects of PFAS on fish, this study reviewed 64 publications. The toxicity of PFAS on functional traits of fish exposed to PFAS was analyzed based on Meta-analysis combined with effect sizes, which provided reference for the toxicity assessment of PFAS and was conducive to the priority control and management of PFAS pollution. The results showed that:① of the 12 functional traits studied, seven were found to be vulnerable in fish; the order of toxicity response was malformation (lnRR=-2.5599), development (lnRR=-0.4103), cell damage (lnRR=-0.3962), reproduction (lnRR=-0.3724), thyroid response (lnRR=-0.2492), growth (lnRR=-0.2194), and survival (lnRR=-0.2192). ② The aquatic toxicity of PFAS was significantly affected by the sex and developmental stage of fish. PFAS tended to have adverse effects on female fish (lnRR=-0.1628), and the physiological function of embryos was most significantly affected by PFAS (lnRR=-0.3553). ③ A total of 13 PFAS were involved in the study, among which PFAS with sulfonate groups and long-chains were more likely to have significant toxicity to the functional traits of fish (P<0.05).④ Existing data revealed that PFAS tended to produce acute toxicity to fish at medium and low concentrations (0.01-10 mg·L-1, P<0.05).

[Effect of gut microbiota homeostasis on hematopoiesis in a neonatal rat model of necrotizing enterocolitis]. / è‚ é“å¾®ç”Ÿç‰©ç¨³æ€å¯¹åæ­»æ€§å°è‚ ç»“è‚ ç‚Žæ–°ç”Ÿå¤§é¼ æ¨¡åž‹é€ è¡€ç³»ç»Ÿçš„å½±å“.

OBJECTIVES: To study the effect of gut microbiota on hematopoiesis in a neonatal rat model of necrotizing enterocolitis (NEC). METHODS: Neonatal Sprague-Dawley rats were randomly divided into a control group and a model group (NEC group), with 6 rats in each group. Formula milk combined with hypoxia and cold stimulation was used to establish a neonatal rat model of NEC. Hematoxylin and eosin staining was used to observe the pathological changes of intestinal tissue and hematopoiesis-related organs. Routine blood tests were conducted for each group. Immunohistochemistry was used to observe the changes in specific cells in hematopoiesis-related organs. Flow cytometry was used to measure the changes in specific cells in bone marrow. 16S rDNA sequencing was used to observe the composition and abundance of gut microbiota. RESULTS: Compared with the control group, the NEC group had intestinal congestion and necrosis, damage, atrophy, and shedding of intestinal villi, and a significant increase in NEC histological score. Compared with the control group, the NEC group had significantly lower numbers of peripheral blood leukocytes and lymphocytes (P<0.05), nucleated cells in the spleen, thymus, and bone marrow, and small cell aggregates with basophilic nuclei in the liver (P<0.05). The NEC group had significant reductions in CD71+ erythroid progenitor cells in the liver, CD45+ lymphocytes in the spleen and bone marrow, CD3+ T lymphocytes in thymus, and the proportion of CD45+CD3-CD43+SSChi neutrophils in bone marrow (P<0.05). There was a significant difference in the composition of gut microbiota between the NEC and control groups, and the NEC group had a significant reduction in the abundance of Ligilactobacillus and a significant increase in the abundance of Escherichia-Shigella (P<0.05), which replaced Ligilactobacillus and became the dominant flora. CONCLUSIONS: Multi-lineage hematopoietic disorder may be observed in a neonatal rat model of NEC, which may be associated with gut microbiota dysbiosis and abnormal multiplication of the pathogenic bacteria Escherichia-Shigella.

Sarcodonol A-D from fruiting bodies of Sarcodon imbricatus inhibits HCoV-OC43 induced apoptosis in MRC-5 cells.

Four new 26-carboxylated ergostane-type sterols (Sarcodonol A-D) were isolated from 70% ethanol extracts of dried fruiting bodies of Sarcodon imbricatus. Their chemical structures were elucidated using 1D- and 2D-nuclear magnetic resonance and high-resolution electrospray ionization mass spectrometry, and confirmed by comparison with previously reported data. As far as we know, this is the first instance of isolating a 26-carboxylated ergostane-type sterol from nature. The determined antiviral efficacy of sarcodonol A-D (1-4) against HCoV-OC43 in MRC-5 cells confirmed that sarcodonol D (4) had significant antiviral activity. Notably, sarcodonol D (4) potently blocked virus infection at low-micromolar concentration and showed high SI (IC50 = 2.26 µM; CC50 > 100 µM; SI > 44.2). In addition, this research shows that the antiviral effect of sarcodonol D (4) via reduced apoptosis increased by viral infection is through mitochondrial stress regulation. This suggests that sarcodonol D (4) is a potential candidate for use as an antiviral treatment.

Ag decoration on Na2Ti3O7 nanowires for improved SERS and PHE performance.

Na2Ti3O7 (NTO) is recognized as an authenticated promising photocatalyst and surface-enhanced Raman scattering (SERS) active material, although its performance is limited by its high carrier recombination rate, wide band gap and inadequate utilization of visible light. In this study, to solve these issues, sea urchin-shaped NTO nanowires directly grown on a substrate were fabricated, and then Ag nanoparticles were decorated on NTO nanowires using sputtering equipment. The as-prepared Ag-NTO substrates exhibited different morphologies and high SERS activity, which was confirmed by finite-difference time-domain (FDTD) simulations, showing that appropriate Ag decoration can bring more nanogaps and thus enhance the electromagnetic field (EM) contribution. We visualized the charge transfer (CT) mechanism in SERS and further investigated the catalytic hydrogen production process similarly induced by photogenerated CT. The optimal SERS substrate (Ag-NTO-3) was adopted to verify the photocatalytic hydrogen evolution (PHE) activity, and the hydrogen evolution rate of Ag-NTO-3 was 106.7 µmol h-1 (twice that of pristine NTO). Photoelectrochemical measurements and photoluminescence (PL) analysis were used to elucidate the potential enhancement mechanisms for the photocatalytic performance and CT process. This study can provide a valuable reference for performance and mechanism studies of SERS substrates and photocatalysts.

International expert consensus on diagnosis and treatment of lung cancer complicated by chronic obstructive pulmonary disease.

Background: Lung cancer combined by chronic obstructive pulmonary disease (LC-COPD) is a common comorbidity and their interaction with each other poses significant clinical challenges. However, there is a lack of well-established consensus on the diagnosis and treatment of LC-COPD. Methods: A panel of experts, comprising specialists in oncology, respiratory medicine, radiology, interventional medicine, and thoracic surgery, was convened. The panel was presented with a comprehensive review of the current evidence pertaining to LC-COPD. After thorough discussions, the panel reached a consensus on 17 recommendations with over 70% agreement in voting to enhance the management of LC-COPD and optimize the care of these patients. Results: The 17 statements focused on pathogenic mechanisms (n=2), general strategies (n=4), and clinical application in COPD (n=2) and lung cancer (n=9) were developed and modified. These statements provide guidance on early screening and treatment selection of LC-COPD, the interplay of lung cancer and COPD on treatment, and considerations during treatment. This consensus also emphasizes patient-centered and personalized treatment in the management of LC-COPD. Conclusions: The consensus highlights the need for concurrent treatment for both lung cancer and COPD in LC-COPD patients, while being mindful of the mutual influence of the two conditions on treatment and monitoring for adverse reactions.

Clinical Utility of Sero-Immunological Responses Against SARS-CoV-2 Nucleocapsid Protein During Subsequent Prevalence of Wild-Type, Delta Variant, and Omicron Variant.

As nucleocapsid protein of severe acute respiratory syndrome coronavirus 2 is immunogenic but not targeted in vaccines, it could be useful in distinguishing natural infection from vaccination. We aimed to investigate the clinical utility of sero-immunological responses against the nucleocapsid protein. Nucleocapsid antibody immunoassay study with 302 coronavirus disease 2019 (COVID-19) patients showed lower titers in immunocompromised patients (P < 0.001), higher titers in higher severity (P = 0.031), and different seroconversion rates and titers according to variants of concern. Longitudinal evaluation of nucleocapsid antibodies using 513 samples from 291 COVID-19 patients revealed that it could persist up to 556 days from symptom onset. Interferon gamma release assay against the nucleocapsid protein showed poor response, precluding the deduction of a cut-off for the nucleocapsid protein. In conclusion, nucleocapsid antibody provides instructive clues about the immunogenicity of nucleocapsid proteins by different seroconversion rates and titers according to the severity of infection, host immune status, and different variants of concern.

Efficacy and safety of zonisamide as the first additional treatment in Chinese patients with focal or secondary bilateral tonic-clonic seizures: An observational ,prospective study.

Background: To evaluate the efficacy and safety of zonisamide (ZNS) as the first additional treatment for focal or secondarily bilateral tonic-clonic seizure (sBTCS). Methods: A total of 118 patients between 18 and 75 years of age with focal or sBTCS were recruited from multiple hospitals in Shandong province between May 13, 2021, and February 16, 2022. All received ZNS as the first additional treatment after clinical judgment. Seizure frequency, retention, and adverse events (AEs) were assessed 2 and 5 months after the introduction of ZNS. Results: Overall response rates at 2 and 5 months were 79.5% and 75.5%, respectively, whereas seizure-free rates at the same point were 53.6% and 51%, respectively. The review's retention rates at 2 and 5 months were 95% and 86%, respectively. The most common AEs were anorexia with weight loss (11.8%), dizziness (6.9%), and headache (3.9%). Conclusions: Our real-world study confirmed the efficacy and safety of ZNS as a first-additional treatment for focal or sBTCS in Chinese patients, with a high short-term retention rate.

Clinical application of a body area network-based smart bracelet for pre-hospital trauma care.

Objective: This study aims to explore the efficiency and effectiveness of a body area network-based smart bracelet for trauma care prior to hospitalization. Methods: To test the efficacy of the bracelet, an observational cohort study was conducted on the clinical data of 140 trauma patients pre-admission to the hospital. This study was divided into an experimental group receiving smart bracelets and a control group receiving conventional treatment. Both groups were randomized using a random number table. The primary variables of this study were as follows: time to first administration of life-saving intervention, time to first administration of blood transfusion, time to first administration of hemostatic drugs, and mortality rates within 24 h and 28 days post-admission to the hospital. The secondary outcomes included the amount of time before trauma team activation and the overall length of patient stay in the emergency room. Results: The measurement results for both the emergency smart bracelet as well as traditional equipment showed high levels of consistency and accuracy. In terms of pre-hospital emergency life-saving intervention, there was no significant statistical difference in the mortality rates between both groups within 224 h post-admission to the hospital or after 28-days of treatment in the emergency department. Furthermore, the treatment efficiency for the group of patients wearing smart bracelets was significantly better than that of the control group with regard to both the primary and secondary outcomes of this study. These results indicate that this smart bracelet has the potential to improve the efficiency and effectiveness of trauma care and treatment. Conclusion: A body area network-based smart bracelet combined with remote 5G technology can assist the administration of emergency care to trauma patients prior to hospital admission, shorten the timeframe in which life-saving interventions are initiated, and allow for a quick trauma team response as well as increased efficiency upon administration of emergency care.

Comparative effectiveness and safety of Chinese medicine belly button application for childhood diarrhea: a Bayesian network meta-analysis of randomized controlled trials.

Background: Chinese medicine belly button application (CMBBA) has been used to treat childhood diarrhea (CD) in several randomized controlled trials (RCTs), but its effectiveness and combination strategy still need to be clarified. Therefore, we aimed to evaluate the effectiveness, safety, and the optimal combination strategy of CMBBA in treating CD. Methods: Up until January 2023, we searched for studies that met our inclusion criteria in six databases, including PubMed, the Cochrane Library, Chinese SinoMed, CNKI, VIP, and Wanfang. Heterogeneity was quantified using I2 statistics. A methodological evaluation was performed using the Cochrane Risk Bias Tool 2.0. The Confidence in Network Meta-Analysis online software was employed to evaluate evidence grading. A minimally contextualized framework was used to provide a comprehensive conclusion for the network meta-analysis. This study protocol was registered with PROSPERO. Results: We analyzed data from 33 RCTs that included 4,490 children with diarrhea. In terms of clinical effectiveness, CMBBA plus montmorillonite powder plus anti-infectives may be the most effective treatment option for children with diarrhea and concurrent infection according to a minimally contextualized framework. Either exclusive use of CMBBA or CMBBA in combination with modern medicine was beneficial in reducing the time to diarrhea disappearance (MD = -1.33 days, 95% CI: -1.59 to -1.08, Z = -10.103, p < 0.001) compared to modern medicine exclusively, and the difference was statistically significant. The combined usage of CMBBA could shorten the recovery time of dehydration by an average of 0.74 days (MD = -0.74 days, 95% CI: -1.10 to -0.37, Z = -3.931.103, p < 0.001). While some studies have reported mild allergic reactions and mild abdominal pain after CMBBA use, these symptoms can be cured in a relatively short period of time. Conclusions: The combination of CMBBA, montmorillonite powder, and anti-infectives may provide superior clinical effectiveness for children with diarrhea and concurrent infection. To treat CD, CMBBA can be used effectively and safely. However, the findings must be interpreted with cautiously due to the limited number of clinical trials and the low quality of the studies. In addition, the choice of treatment plan should also be based on the specific conditions of each patient. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022380694.

[High-intensity laser therapy combined with targeted hand function training for the treatment of grade 1-2 thumb carpometacarpal osteoarthritis].

OBJECTIVE: To explore clinical effect of high-intensity laser therapy(HILT) combined with targeted hand function training on pain and lateral pinch force in grade 1-2 thumb carpometacarpal(CMC) osteoarthritis(OA). METHODS: From April 2020 and April 2022, 42 female patients with thumb CMC OA grade 1 to 2, aged from 58 to 80 years old with an everage of (68.90±7.58) years old were divided into observation group of 21 patients who received HILT and targeted hand function training for 4 weeks, and 21 patients in control group who received ultrashort wave therapy combined with using of an orthosis for 4 weeks. Visual analogue scale(VAS) was applied to evaluate degree of pain, function of finger was evaluated by dynamometer to measure lateral pinch force at baseline, immediately following intervention at 4 and 12 weeks following intervention. RESULTS: VAS and lateral pinch force at immediately and 12 weeks after intervention betwwen two groups were better than that of before intervention(P<0.05). Compared with control group, the degree of pain in observation group improved more(immediately after intervention t=3.37, P<0.05, 12 weeks after intervention t=9.05, P<0.05), lateral pinch force higher than that of control group (immediately after intervention t=-2.55, P<0.05, 12 weeks after intervention t=9.51, P<0.05). CONCLUSION: High-intensity laser therapy combined with targeted hand function training is more effective than traditional methods in improving pain and lateral pinch force in grade 1-2 thumb carpometacarpal osteoarthritis.

Impact of human serum albumin level on symptomatic cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVE: To investigate the impact of human serum albumin (HSA) levels on symptomatic cerebral vasospasm (SCVS) in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: We retrospectively reviewed the medical records. SCVS was defined as the development of a new neurological deterioration when the cause was considered to be ischemia attributable to vasospasm after other possible causes of worsening had been excluded. The aSAH patients were divided into two groups: those with SCVS (group 1) and those without SCVS (group 2). The HSA level data on the 1st, 2nd, and 3rd day after admission was collected. Multivariate logistical regression and receiver operating characteristic (ROC) analysis were performed to evaluate the ability of HSA level to predict the development of SCVS. RESULTS: A total of 270 patients were included in our study, of which 74 (27.4%) developed SCVS. The average and lowest HSA levels were lower in group 1 (P < 0.001). In univariate logistic regression, white blood cell count, neutrophil count, and average and lowest HSA levels were associated with SCVS. After adjustment for age, CT Fisher grade, Hunt-Hess grade, and WFNS grade, both the average and lowest HSA levels remained independent predictors of SCVS (P < 0.001). The CT Fisher grade was confirmed to be an independent predictor of SCVS across each model. ROC analysis revealed that the lowest HSA level was a better predictor for SCVS than average HSA level and CT Fisher grade. CONCLUSION: Clinicians are encouraged to measure HSA levels for the first 3 days after admission to predict the occurrence of SCVS after aSAH.

Lobosteroids A-F: Six New Highly Oxidized Steroids from the Chinese Soft Coral Lobophytum sp.

To explore the steroidal constituents of the soft coral Lobophytum sp. at the coast of Xuwen County, Guangdong Province, China, a chemical investigation of the above-mentioned soft coral was carried out. After repeated column chromatography over silica gel, Sephadex LH-20, and reversed-phase HPLC, six new steroids, namely lobosteroids A-F (1-6), along with four known compounds 7-10, were obtained. Their structures were determined by extensive spectroscopic analysis and comparison with the spectral data reported in the literature. Among them, the absolute configuration of 1 was determined by X-ray diffraction analysis using Cu Kα radiation. These steroids were characterized by either the presence of an α,ß-α',ß'-unsaturated carbonyl, or an α,ß-unsaturated carbonyl moiety in ring A, or the existence of a 5α,8α-epidioxy system in ring B, as well as diverse oxidation of side chains. The antibacterial bioassays showed that all isolated steroids exhibited significant inhibitory activities against the fish pathogenic bacteria Streptococcus parauberis FP KSP28, Phoyobacterium damselae FP2244, and Streptococcus parauberis SPOF3K, with IC90 values ranging from 0.1 to 11.0 µM. Meanwhile, compounds 2 and 6-10 displayed potent inhibitory effects against the vancomycin-resistant Enterococcus faecium bacterium G7 with IC90 values ranging from 4.4 to 18.3 µM. Therefore, ten highly oxidized steroids with strong antibacterial activities were isolated from the Chinese soft coral Lobophytum sp., which could be developed as new chemotypes of antibacterial drug leads.

Population Pharmacokinetics of Difloxacin in Crucian Carp (Carassius auratus) after a Single Oral Administration.

This study aimed to investigate the population pharmacokinetics of difloxacin in crucian carp (Carassius auratus) orally provided a single dose of 20 mg/kg body weight (BW). To achieve this, fish were sampled at various intervals using a sparse sampling strategy, and plasma samples were analyzed using the high-performance liquid chromatography (HPLC) method. Subsequently, naïve average data were analyzed using a non-compartmental method, and a population model was developed based on the nonlinear mixed effects approach. The covariate of BW and the relationship between covariances were sequentially incorporated into the population model. However, it was found that only covariance and not BW affected the population parameters. Therefore, the covariance model was taken as the final population model, which revealed that the typical values of the absorption rate constant (tvKa), apparent volume of distribution per bioavailability (tvV), and clearance rate per bioavailability (tvCl) were 1.18 1/h, 14.18 L/kg, and 0.20 L/h/kg, respectively. Based on the calculated free AUC/MIC values, the current oral dose of difloxacin (20 mg/kg BW) cannot generate adequate plasma concentrations to inhibit pathogens with MIC values above 0.83 µg/mL. Further study should be carried out to collect the pathogens from crucian carp and determine the MIC data of difloxacin against them. Pharmacodynamic experiments must also be further carried out to determine the optimal therapeutic dose for the treatment of Aeromonas hydrophila infection.

[Content determination of seven active components of Eucommiae Cortex in aortic vascular endothelial cells of spontaneously hypertensive rats by UPLC-MS/MS].

In the present study, the contents of seven active components [genipinic acid(GA), protocatechuic acid(PCA), neochlorogenic acid(NCA), chlorogenic acid(CA), cryptochlorogenic acid(CCA),(+)-pinoresinol di-O-ß-D-glucopyranosid(PDG), and(+)-pinoresinol 4'-O-ß-D-glucopyranoside(PG)] of Eucommiae Cortex in aortic vascular endothelial cells of spontaneously hypertensive rats(SHR) were simultaneously determined by ultra-high liquid chromatography-triple quadrupole mass spectrometry(UPLC-MS/MS). The qualified SHR models were selected. The primary aortic endothelial cells(VECs) of rats were separated and cultured by ligation and adherence, followed by subculture. After successful identification, an UPLC-MS/MS method for simultaneously determining the contents of GA, PCA, NCA, CA, CCA, PDG, PG in seven components of Eucommiae Cortex in VECs was established, including specificity, linearity, matrix effect, recovery, accuracy, precision and stability. The established method had the lo-west limit of quantification of 0.97-4.95 µg·L~(-1), accuracy of 87.26%-109.6%, extraction recovery of 89.23%-105.3%, matrix effect of 85.86%-106.2%, and stability of 86.00%-112.5%. Therefore, the established accurate UPLC-MS/MS method could rapidly and simultaneously determine the contents of the seven active components of Eucommiae Cortex in VECs of SHRs, which provided a refe-rence for the study of cellular pharmacokinetics of active components of Eucommiae Cortex extract.

CAT Interruption as a Protective Factor in Chinese Patients with Spinocerebellar Ataxia Type 1.

Spinocerebellar ataxia type 1 (SCA1) is the third most common type of spinocerebellar ataxias in China. CAT interruptions in the pathogenic alleles of SCA1 patients had only been reported by limited documents and there was a lack of data based on the Chinese population. In this study, we detected CAT interrupted pathogenic alleles in SCA1 patients from 4 out of 79 (5.1%) Chinese families. Their total CAG repeats were larger (median 58 vs. 47, p < 0.001) but ages at onset were later (median 46 vs. 38, p = 0.020). The longest uninterrupted CAG repeats could explain 65.4% of the AAO variance, making an increase of 28.0% compared to the total CAG repeats. The interruption pattern was greatly different between Chinese cohort and Caucasian cohort, indicating the effect of race.

Loss of Neutralizing Activity of Tixagevimab/Cilgavimab (Evusheld™) Against Omicron BN.1, a Dominant Circulating Strain Following BA.5 During the Seventh Domestic Outbreak in Korea in Early 2023.

Tixagevimab/cilgavimab is a monoclonal antibody used to prevent coronavirus disease 2019 among immunocompromised hosts and maintained neutralizing activity against early omicron variants. Omicron BN.1 became a dominant circulating strain in Korea early 2023, but its susceptibility to tixagevimab/cilgavimab is unclear. We conducted plaque reduction neutralization test (PRNT) against BN.1 in a prospective cohort (14 patients and 30 specimens). BN.1 PRNT was conducted for one- and three-months after tixagevimab/cilgavimab administration and the average PRNT ND50 of each point was lower than the positive cut-off value of 20 (12.9 ± 4.5 and 13.2 ± 4.2, respectively, P = 0.825). In the paired analyses, tixagevimab/cilgavimab-administered sera could not actively neutralize BN.1 (PRNT ND50 11.5 ± 2.9, P = 0.001), compared with the reserved activity against BA.5 (ND50 310.5 ± 180.4). Unlike virus-like particle assay, tixagevimab/cilgavimab was not active against BN.1 in neutralizing assay, and would not be effective in the present predominance of BA.2.75 sublineages.

Urinary Tract Infections Caused by Uropathogenic Escherichia coli: Mechanisms of Infection and Treatment Options.

Urinary tract infections (UTIs) are common bacterial infections that represent a severe public health problem. They are often caused by Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumonia), Proteus mirabilis (P. mirabilis), Enterococcus faecalis (E. faecalis), and Staphylococcus saprophyticus (S. saprophyticus). Among these, uropathogenic E. coli (UPEC) are the most common causative agent in both uncomplicated and complicated UTIs. The adaptive evolution of UPEC has been observed in several ways, including changes in colonization, attachment, invasion, and intracellular replication to invade the urothelium and survive intracellularly. While antibiotic therapy has historically been very successful in controlling UTIs, high recurrence rates and increasing antimicrobial resistance among uropathogens threaten to greatly reduce the efficacy of these treatments. Furthermore, the gradual global emergence of multidrug-resistant UPEC has highlighted the need to further explore its pathogenesis and seek alternative therapeutic and preventative strategies. Therefore, a thorough understanding of the clinical status and pathogenesis of UTIs and the advantages and disadvantages of antibiotics as a conventional treatment option could spark a surge in the search for alternative treatment options, especially vaccines and medicinal plants. Such options targeting multiple pathogenic mechanisms of UPEC are expected to be a focus of UTI management in the future to help combat antibiotic resistance.