Hospital of Hebei Province

To establish an integrated in vitro evaluation platform for identifying effective antibiotic combinations against rifampicin-resistant Mycobacterium tuberculosis (RR-TB), by simultaneously assessing synergistic drug interactions, intracellular bactericidal activity, macrophage apoptosis, and cytokine responses. Using this platform, we investigated the combinatory potential of linezolid (LZD) with five second-line antitubercular agents. The minimum inhibitory concentrations (MICs) of LZD and five second-line drugs were determined using the Alamar Blue microplate assay. Drug–drug interactions between LZD and cycloserine (CS), clofazimine (CFZ), bedaquiline (BDQ), moxifloxacin (MFX), or levofloxacin (LFX) were evaluated using checkerboard microdilution analysis. Drug pairs demonstrating in vitro synergy were further examined in a macrophage infection model. Intracellular bacterial burden was quantified by colony-forming unit (CFU) enumeration. Macrophage apoptosis was assessed using flow cytometry, and cytokine production (IL-12/23 p40, TNF-α, IL-6, and IL-10) was analyzed to characterize immune modulation. LZD demonstrated synergistic interactions with CS and CFZ, whereas no synergy was observed with BDQ, MFX, or LFX. The synergistic combinations LZD + CS and LZD + CFZ significantly reduced intracellular CFU counts, enhanced macrophage apoptosis, and altered cytokine responses, characterized by increased TNF-α and decreased IL-10 levels in infected macrophages. This study presents a comprehensive and mechanistically informative in vitro methodology for evaluating antibiotic combinations against RR-TB. The platform effectively integrates drug synergy testing with assessments of intracellular killing, apoptosis induction, and immune modulation, offering a promising approach for preclinical screening of novel anti-TB therapeutic strategies.

Infectious uveitis can be induced by a variety of factors, including viral, bacterial, and parasitic infections, among others. Among these, viral infections are the most common cause of infectious uveitis. Traditional diagnostic methods have limited sensitivity and are often cumbersome, which restricts their ability to accurately identify the viral pathogens responsible. As a result, there is still no gold-standard diagnostic tool for detecting uveitis. With advancements in molecular diagnostic technologies, metagenomic next-generation sequencing (mNGS) has become widely used in clinical sample detection, molecular sequencing, and microbial analysis. This article reports a case of an elderly male patient who presented with a one-month history of left eye vision deterioration. The patient had a generally healthy status, with a 17-year history of hypertension, and denied any other underlying conditions. Ophthalmic examination showed planktonic cells (+++) in the anterior chamber of the left eye, partial posterior adhesion of the iris, lens opacity, visible attachment of iris pigments in front, severe vitreous opacity, visible flocculent yellow white floating material, and faintly visible optic disc structure in the fundus. These findings led to a diagnosis of left eye uveitis. Given the severity of the ocular condition, a decision was made to perform vitreous cavity puncture for smear culture and metagenomic mNGS to identify the pathogen. mNGS promptly detected 9939 sequence counts of Varicella-zoster virus (VZV), confirming the pathogen. Following the identification, Acyclovir injection is used for systemic intravenous injection and local intravitreal injection of ganciclovir injection for antiviral therapy.After two weeks of treatment, the symptoms of anterior uveitis showed some improvement, but the vitreous inflammation remained largely unchanged. Consequently, a vitreous body removal (vitrectomy) was performed, postoperative fundus examination showed the refractive interstitium is clear, and Kyrieleis plaques along the inner wall of the paraoptic artery can be seen. Postoperatively, the patient’s vision improved rapidly. Previous reports typically emphasize the importance of antiviral therapy. However, in this case, the authors discuss the use of vitrectomy in a VZV infection-induced pan-uveitis and retinal vasculitis patient, where antiviral therapy alone was insufficient, resulting in a satisfactory outcome post-surgery. Intraocular fluid metagenomic testing is an effective method for diagnosing unexplained uveitis. For patients with VZV-associated uveitis and severe vitreous opacity, early vitrectomy is an effective therapeutic approach.

ABSTRACTEndobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) plays an important role in the diagnosis of benign and malignant mediastinal lesions. However, it is mostly used for the biopsy of consolidated lesions and enlarged lymph nodes. This paper presents a case of mediastinal abscess diagnosed by endobronchial ultrasound‐guided puncture.

This study aimed to assess the physicochemical stability and compatibility of butorphanol tartrate, nicardipine hydrochloride, urapidil, and tirofiban hydrochloride to support safe infusion practices in the ICU. Compatibility systems involving four-, three-, and two-drug combinations were prepared in 0.9% sodium chloride injection under simulated clinical conditions at room temperature in the absence of light. Evaluations included appearance, pH, and insoluble particle counts at 0, 2, 4, 8, 12, and 24hours. Quantitative analysis of drug concentrations was performed using high performance liquid chromatography (HPLC). All tested combinations retained physical stability within 24hours, showing no measurable variation in appearance, pH, or particle. Nicardipine concentrations declined significantly, reaching 74.35% of baseline in the nicardipine-urapidil-tirofiban mixture at 24hours, and decreasing to 76.29% at 12hours and 71.46% at 24hours in the nicardipine-tirofiban combination. The concentrations of active ingredients in the remaining mixtures remained stable, consistently exceeding 90% of initial values. Butorphanol demonstrated compatibility with the other agents under the tested conditions. In clinical application, infusion of nicardipine combined with tirofiban should be restricted to less than 8hours, and nicardipine combined with urapidil and tirofiban should not exceed 12hours. Other mixtures can be administered for up to 24hours with flexibility in infusion duration.

Abstract Objective: Exploring the value of non-invasive brain edema monitoring combined with bedside video electroencephalography in evaluating the short-term prognosis of children with severe encephalitis. Methods: This study retrospectively analyzed the clinical data of 136 children diagnosed with severe encephalitis in the Intensive Care Medicine Department of Hebei Children's Hospital from January 2021 to July 2024. According to the prognosis at discharge, patients were divided into a poor prognosis group (54 cases) and a good prognosis group (82 cases). Compare the clinical manifestations, modified GCS scores, early warning scores, clinical indicators monitored after admission, DC values, and video electroencephalography between two groups of children. Logistic regression was used to analyze the risk factors for poor prognosis, and receiver operating characteristic (ROC) curves were used to analyze the predictive value of DC, video EEG, and their combined evaluation of prognosis. Results: There was a statistically significant difference ( P <0.05) in the modified GCS score, early warning score, lactate dehydrogenase, blood ammonia, and abnormal cranial imaging between the two groups of patients. The DC values monitored at admission in the poor prognosis group were significantly lower than those in the good group, with 22 cases (40.7%) having severe EEG abnormalities, and the difference was statistically significant ( P <0.05). GCS score, early warning score DC、 Severe abnormal video electroencephalogram is a risk factor for poor prognosis in children with severe encephalitis. The area under the ROC curve for predicting the prognosis of children with severe encephalitis using DC values is 0.734, with an optimal cutoff value of 75, a sensitivity of 74.1%, and a specificity of 63.4%. The area under the ROC curve for predicting prognosis using video electroencephalogram is 0.701, with a sensitivity of 53.7% and specificity of 86.6%. The area under the combined prediction curve is 0.822, with a sensitivity of 77.8% and specificity of 75.6%. Conclusion: Severe encephalitis is the result of the interaction of multiple factors, and clinical attention should be paid to GCS score, early warning score, DC, and video electroencephalogram. The combined application of DC and bedside video EEG can significantly improve the evaluation efficiency of short-term prognosis in children with severe encephalitis. Classification number: R725.9

Rigid nasopharyngoscopy is a valuable diagnostic method for immune-mediated allergy conditions, particularly for children aged≤6 years. In addition to evaluating the structural characteristics of the nasal cavity, the procedure also reveals inflammatory activity in the nasopharyngeal framework. This study assessed 110 pediatric patients between 2 and 6 years old who presented with suspected allergic conditions. Rigid nasopharyngoscopy was performed, and its diagnostic performance was high with 85.45% sensitivity, 78.18% specificity, and an overall diagnostic accuracy of 83.00%, which supports its role in diagnosing and ruling out allergic disorders. The findings revealed strong associations between mucosal erythema, cobblestoning, and mucosal secretions with symptoms like nasal obstruction and postnasal drip. These signs have proven to be reliable indicators of inflammation and chronic irritation in this age group. The procedure was well tolerated, and over 85% of children experienced no adverse effects. Minor discomfort and nasal bleeding were reported in a small number of cases. Taken together, the results show that rigid nasopharyngoscopy is an essential diagnostic modality for early detection of allergy conditions in the pediatric population.

Mitochondrial dysfunction is closely associated with the pathogenesis of Parkinson's disease (PD). Lutein has been shown to exert protective effects in neurological disorders. This study aimed to investigate the ameliorative effects of lutein on mitochondrial function in PD and its underlying molecular mechanisms. Animal and cellular PD models were established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice and treatment of SH-SY5Y cells with 1-methyl-4-phenylpyridinium ion (MPP+), respectively. Motor function was assessed using the rotarod, adhesive removal, and pole tests. Mitochondrial function was evaluated using MitoSOX Red staining, JC-1 staining, and adenosine triphosphate (ATP) content measurement. Western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to measure the levels of relevant proteins and mRNA. Lutein significantly ameliorated MPTP-induced motor dysfunction in PD mice, increased the number of tyrosine hydroxylase (TH)-positive neurons, and alleviated damage to striatal brain tissue. At the cellular level, lutein significantly suppressed MPP+-induced apoptosis of SH-SY5Y cells, upregulated the expression of B-cell lymphoma-2 (Bcl-2), and downregulated the expression of Bcl-2-associated X protein (Bax) and cleaved caspase-3. Additionally, lutein significantly reduced reactive oxygen species (ROS) levels, restored mitochondrial membrane potential, increased ATP levels, and increased the activity of mitochondrial respiratory chain complex I. At the molecular level, lutein promoted the ubiquitination of dynamin-related protein 1 (Drp1), whose degradation was impaired in the PD model. This effect was mediated by the E3 ubiquitin ligase Tripartite Motif-containing protein 31 (TRIM31), whose expression was downregulated in the disease state. Functional experiments confirmed that overexpression of TRIM31 enhanced Drp1 ubiquitination and improved mitochondrial function, whereas TRIM31 knockdown partially attenuated the therapeutic effects of lutein. In summary, this study revealed, for the first time, that lutein alleviates PD progression by increasing Drp1 ubiquitination and degradation via TRIM31 transcription and translation, ultimately improving neuronal mitochondrial function. These findings not only elucidate a novel mechanism underlying lutein's neuroprotective effect but also identify a potential therapeutic target and offer a new strategy for PD treatment.

BackgroundOptical genome mapping (OGM) is an emerging cytogenetic method for concurrently detecting structural variants (SVs) and copy number variants (CNVs). However, its clinical application in prenatal diagnosis remains underexplored.MethodsThis study retrospectively evaluated the clinical validity of OGM in prenatal diagnosis by comparing with two routine genetic testing methods: karyotyping and chromosomal microarray analysis (CMA). Both positive and negative cases detected by routine genetic methods were enrolled to evaluate the technical concordance of OGM and its capability to improve diagnostic rate in negative cases. The exclusion criteria were balanced centromeric translocations, mosaic cases with cellular fractions < 20%, and loss of heterozygosity (LOH) < 25 Mb. All samples subjected to OGM testing were anonymized and analyzed blindly. The results from OGM were compared with those from routine genetic testing, and statistical analyses were performed to assess technical concordance and diagnostic rate.ResultsOf 217 samples (166 positive samples and 51 negative samples for routine genetic testing), all were successfully tested with OGM, including 2 umbilical cord blood samples, 4 chorionic villi samples, and 211 cultured amniotic fluid samples. Of the 207 reportable chromosomal aberrations from 166 positive samples, the blinded concordance between OGM and CMA, karyotyping, and combination of karyotyping plus CMA was 97.81%, 96.36%, and 97.10%, respectively. OGM missed six aberrations initially, including one LOH, two marker chromosomes, and three microdeletions. However, after reanalysis, its concordance improved to 100% with CMA and 99.03% with karyotyping plus CMA. OGM also diagnosed one additional case of a 3-kb deletion in 51 negative samples, improving the diagnostic rate by 1.96%. Moreover, OGM reclassified the pathogenicity of two microdeletions from pathogenic to uncertain significance in 2 positive cases. Furthermore, OGM clarified the diagnosis suspected by routine genetic testing and improved diagnostic accuracy in some cases.ConclusionAs far as we know, this is the largest retrospective study on OGM in prenatal diagnosis, and it includes a broad range of sample types. The results showed that OGM exhibits high concordance among the tested methods and increases the diagnostic rate. Thus, OGM has the potential to become a first-line technique for prenatal diagnosis in the future.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12967-025-06901-9.