Plasmid-mediated azithromycin resistance in non-typhoidal Salmonella recovered from human infections.

OBJECTIVES: Mechanisms of non-typhoidal Salmonella (NTS) resistance to azithromycin have rarely been reported. Here we investigate the epidemiology and genetic features of 10 azithromycin-resistant NTS isolates. METHODS: A total of 457 NTS isolates were collected from a tertiary hospital in Guangzhou. We performed antimicrobial susceptibility tests, conjugation experiments, efflux pump expression tests, whole-genome sequencing and bioinformatics analysis to conduct the study. RESULTS: The results showed that 10 NTS isolates (2.8%) were resistant to azithromycin with minimum inhibitory concentration values ranging from 128 to 512 mg/L and exhibited multidrug resistance. The phylogenetic tree revealed that 5 S. London isolates (AR1-AR5) recognized at different times and departments were closely related [3-74 single-nucleotide polymorphisms (SNPs)] and 2 S. Typhimurium isolates (AR7 and AR8) were clones (<3 SNPs) at 3-month intervals. The azithromycin resistance was conferred by mph(A) gene found on different plasmids, including IncFIB, IncHI2, InFII, IncC and IncI plasmids. Among them, IncFIB, InFII and IncHI2 plasmids carried different IS26-class 1 integron (intI1) arrangement patterns that mediated multidrug resistance transmission. Conjugative IncC plasmid encoded resistance to ciprofloxacin, ceftriaxone and azithromycin. Furthermore, phylogenetic analysis demonstrated that mph(A)-positive plasmids closely related to 10 plasmids in this study were mainly discovered from NTS, Escherichia coli, Klebsiella pneumonia and Enterobacter hormaechei. The genetic environment of mph(A) in 10 NTS isolates was IS26-mph(A)-mrx(A)-mphR(A)-IS6100/IS26 that co-arranged with intI1 harbour multidrug-resistant (MDR) gene cassettes on diverse plasmids. CONCLUSIONS: These findings highlighted that the dissemination of these plasmids carrying mph(A) and various intI1 MDR gene cassettes would seriously restrict the availability of essential antimicrobial agents for treating NTS infections.

4,5-Dimethoxycanthin-6-one Inhibits Glioblastoma Stem Cell and Tumor Growth by Inhibiting TSPAN1 Interaction with TM4SF1.

Glioblastoma stem cells (GSCs) have been implicated in the self-renewal and treatment resistance of glioblastoma (GBM). Our previous study found that 4,5-dimethoxycanthin-6-one has the potential to inhibit GBM cell proliferation. This current study aims to elucidate the molecular mechanism underlying the effects of 4,5-dimethoxycanthin-6-one in GBM development. The effect of 4,5-dimethoxycanthin-6-one on GSC formation and differentiation was explored in human GBM cell lines U251 and U87. Subsequently, 4,5-dimethoxycanthin-6-one binding to tetraspanin 1 (TSPAN1) / transmembrane 4 L six family member 1 (TM4SF1) was analyzed by molecular simulation docking. Co-immunoprecipitation (Co-IP) and immunofluorescence (IF) were used to assess the interactions between TSPAN1 and TM4SF1 in GSCs. Cell proliferation was detected by cell counting kit-8 (CCK-8) and colony formation assay. To evaluate cell migration, invasion and apoptosis, we employed wound healing assay, transwell and flow cytometry, respectively. Furthermore, subcutaneous xenograft tumor models in nude mice were constructed to evaluate the impact of 4,5-dimethoxycanthin-6-one on GSCs in vivo by examining tumor growth and histological characteristics. 4,5-Dimethoxycanthin-6-one inhibited GSC formation and promoted stem cell differentiation in a concentration-dependent manner. Molecular docking models of 4,5-dimethoxycanthin-6-one with TM4SF1 and TSPAN1 were constructed. Then, the interaction between TSPAN1 and TM4SF1 in GSC was clarified. Moreover, 4,5-dimethoxycanthin-6-one significantly inhibited the expressions of TM4SF1 and TSPAN1 in vitro and in vivo. Overexpression of TSPAN1 partially reversed the inhibitory effects of 4,5-dimethoxycanthin-6-one on GSC formation, proliferation, migration and invasion. 4,5-Dimethoxycanthin-6-one inhibited GBM progression by inhibiting TSPAN1/TM4SF1 axis. 4,5-Dimethoxycanthin-6-one might be a novel and effective drug for the treatment of GBM.

Habitual salt preference worsens blood pressure in hospitalized hypertensive patients with omicron infection under epidemic-related stress.

BACKGROUND: We investigated the synergistic effect of stress and habitual salt preference (SP) on blood pressure (BP) in the hospitalized Omicron-infected patients. METHODS: From 15,185 hospitalized Omicron-infected patients who reported having high BP or hypertension, we recruited 662 patients. All patients completed an electronic questionnaire on diet and stress, and were required to complete morning BP monitoring at least three times. RESULTS: The hypertensive group (n = 309) had higher habitual SP (P = 0.015) and COVID-19 related stress (P < 0.001), and had longer hospital stays (7.4 ± 1.5 days vs. 7.2 ± 0.5 days, P = 0.019) compared with controls (n = 353). After adjusting for a wide range of covariates including Omicron epidemic-related stress, habitual SP was found to increase both systolic (4.9 [95% confidence interval (CI), 2.3-7.4] mmHg, P < 0.001) and diastolic (2.1 [95%CI, 0.6-3.6] mmHg, P = 0.006) BP in hypertensive patients, and increase diastolic BP (2.0 [95%CI, 0.2-3.7] mmHg, P = 0.026) in the control group. 31 (8.8%) patients without a history of hypertension were discovered to have elevated BP during hospitalization, and stress was shown to be different in those patients (P < 0.001). In contrast, habitual SP was more common in hypertensive patients with uncontrolled BP, compared with patients with controlled BP (P = 0.002). CONCLUSIONS: Habitual SP and psychosocial stress were associated with higher BP in Omicron-infected patients both with and without hypertension. Nonpharmaceutical intervention including dietary guidance and psychiatric therapy are crucial for BP control during the long COVID-19 period.

Left Ventricular Vortex Characteristics in Fetuses With Coarctation of the Aorta by Blood Speckle-Tracking Echocardiography.

OBJECTIVES: The aims of this study were to assess the vortex characteristics of left ventricle (LV) in fetuses with coarctation of the aorta (CoA) using high-frame rate ultrasound with blood speckle-tracking (BST) and explore its relationships with cardiac function and morphology parameters. METHODS: Thirty fetuses with CoA and 30 gestational-age matched normal fetuses were included in this cross-sectional study. The area, length, width, and position of the vortex in the LV were recorded and quantitatively analyzed by BST echocardiography. The associations of vortex properties with ventricular function and morphology were also determined. RESULTS: Based on BST imaging, the LV vortex can be observed in 93% of the fetuses. The fetuses with CoA exhibited significantly larger and wider vortex than the controls (P < .05). Linear regression analysis indicated that vortex area was positively related to sphericity index of LV as well as isovolumic relaxation time (r = .52, P = .003 and r = .42, P = .021). There was a negative correlation between vortex area and mitral valve size (r = -.443, P = .014). No significant association was found between vortex area and myocardial performance index and aortic isthmus size. CONCLUSIONS: It is feasible to quantitatively evaluate the left ventricular vortex in fetuses by BST. The fetuses with CoA exhibited greater vortex area and width, and the altered vortex property is associated with geometry of LV. This will facilitate our comprehension of the unique flow patterns and early cardiac remodeling in fetuses with CoA.

Assessment of Pulmonary Arterial Vascular Impedance in Fetuses With Tetralogy of Fallot.

OBJECTIVE: To evaluate the vascular impedance of the pulmonary arteries in fetuses with tetralogy of Fallot (TOF) by Doppler echocardiography. METHODS: A total of 42 fetuses with TOF (TOF group) and 84 gestational age-matched normal fetuses (control group) were prospectively collected from the Second Xiangya Hospital of Central South University from August 2022 to January 2023. The severity of TOF was classified into mild TOF (z score ≥-2), moderate TOF (-4 < z score < -2), or severe TOF (z score ≤-4) according to the z score value of the pulmonary annulus diameter. The pulsatility index (PI) of the main pulmonary artery (MPA), distal left pulmonary artery (DLPA), and distal right pulmonary artery (DRPA) were measured by pulsed-wave Doppler. The differences in clinical data and echocardiographic parameters between TOF group, control group, and TOF subgroups were compared. RESULTS: Compared with the control group, MPA-PI increased significantly, whereas DLPA-PI and DRPA-PI decreased in TOF group (all P < .001). There were no significant differences in MPA-PI and DRPA-PI among mild TOF, moderate TOF, and severe TOF (all P > .05). However, DLPA-PI decreased significantly in severe TOF compared with mild TOF (P < .05). CONCLUSION: Fetuses with TOF presented increased vascular impedance in the pulmonary trunk and decreased impedance in distal pulmonary artery branches. Further large and follow-up studies are needed to demonstrate the associations between those changed vascular impedances and the development of PA in patients with TOF.

Pulmonary artery stiffness in fetuses with tetralogy of Fallot.

PURPOSE: This study evaluated the elastic characteristics of the pulmonary trunk and distal branches in fetuses diagnosed with tetralogy of Fallot (TOF) using Doppler echocardiography. METHODS: Data on 42 fetuses diagnosed with TOF and 84 gestational age-matched normal fetuses were prospectively collected from the Second Xiangya Hospital of Central South University between August 2022 and January 2023. The severity of TOF was classified into three categories based on the z-score of the pulmonary annulus diameter: mild (z-score ≥-2), moderate (-40.05). CONCLUSION: Fetuses diagnosed with TOF exhibited increased vascular stiffness in the MPA and reduced stiffness in the distal pulmonary artery (PA). Larger-scale follow-up studies are required to elucidate the relationships between these changes in vascular stiffness and PA development in patients with TOF.

Efficacy of flexible ureterorenoscopy with holmium laser in the management of calyceal diverticular calculi.

The purpose of this study was to evaluate the efficacy and safety of flexible ureteroscopy with holmium laser lithotripsy in the management of calyceal diverticular calculi. In this study, we retrospectively analyzed the clinical data of 27 patients with calyceal diverticular calculi admitted to the Department of Urology of the Zigong First People's Hospital from May 2018 to May 2021. Intraoperatively, the diverticular neck was found in all 27 patients, but flexible ureterorenoscopy lithotripsy was not performed in 2 cases because of the slender diverticular neck, and the success rate of the operation was 92.6%. Of the 25 patients with successful lithotripsy, the mean operative time was 76.9 ± 35.5 (43-200) min. There were no serious intraoperative complications such as ureteral perforation, mucosal avulsion, or hemorrhage. Postoperative minor complications (Clavien classification I-II) occurred in 4 (16%) patients. The mean hospital stay was 4.4 ± 1.7 (3-12) days. The stone-free rate was 80% at the 1-month postoperative follow-up. After the second-stage treatment, the stone-free rate was 88%. In 22 cases with complete stone clearance, no stone recurrence was observed at 5.3 ± 2.6 (3-12) months follow-up. This retrospective study demonstrated that flexible ureterorenoscopy with holmium laser is a safe and effective choice for the treatment of calyceal diverticular calculi, because it utilizes the natural lumen of the human body and has the advantages of less trauma, fewer complications, and a higher stone-free rate.

New evidence that vitamin D prevents headache: a bidirectional two-sample Mendelian randomization analysis.

Background: Previous observational clinical studies and meta-analyses have yielded inconsistent results regarding the relationship between vitamin D and headache, and the causal relationship remains unclear. The aim of this study was to investigate the causal relationship between vitamin D and headache by bidirectional two-sample Mendelian randomisation (MR) analysis. Methods: The relationship between high levels of vitamin D and headache was investigated by two-sample MR analysis using publicly available genome-wide association study (GWAS) data. The primary method was inverse variance weighting (IVW), and secondary methods were weighted median and MR-Egger methods. No heterogeneity or horizontal multidirectionality was found in the MR results. The robustness and validity of the findings were assessed using the leave-behind method. Results: A significant causal relationship was found between high vitamin D levels and headache using the IVW method (OR = 0.848; p = 0.007; 95% CI = 0.752-0.956). However, in a reverse analysis, no evidence of a causal relationship between headache and high levels of vitamin D was found using the IVW method (OR = 1.001; p = 0.906; 95% CI = 0.994-1.006). Our MR analyses showed no significant horizontal multidimensionality or heterogeneity (p > 0.05). Sensitivity analyses confirmed that MR estimates were not affected by single nucleotide polymorphisms (SNPs). Confirmation that our results are robust and valid has been obtained by the leave-one-out method. Conclusion: Our study suggests that high levels of vitamin D prevent the risk of headache. However, there is no evidence of a causal relationship between headache and high levels of vitamin D. Vitamin D may reduce the risk of headache.

An integrative model with HLA-DR, CD64, and PD-1 for the diagnostic and prognostic evaluation of sepsis.

BACKGROUND: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and progressive immunosuppression with high mortality. HLA-DR, CD64, and PD-1 were assumed to be useful biomarkers for sepsis prediction. However, the ability of a combination of these biomarkers has not been clarified. METHODS: An observational case-control study was conducted that included 30 sepsis patients, 30 critically ill patients without sepsis admitted to the intensive care unit (ICU), and 32 healthy individuals. The levels of HLA-DR, CD64, and PD-1 expression in peripheral blood immune cells and subsets was assayed on Days 1, 3, and 5, and the clinical information of patients was collected. We compared these biomarkers between groups and evaluated the predictive validity of single and combined biomarkers on sepsis mortality. RESULTS: The results indicate that PD-1 expression on CD4- CD8- T (PD-1+ CD4- CD8- T) (19.19% ± 10.78% vs. 9.88% ± 1.79%, p = .004) cells and neutrophil CD64 index (nCD64 index) (9.15 ± 5.46 vs. 5.33 ± 2.34, p = .001) of sepsis patients were significantly increased, and HLA-DR expression on monocytes (mHLA-DR+ ) was significantly reduced (13.26% ± 8.06% vs. 30.17% ± 21.42%, p = 2.54 × 10-4 ) compared with nonsepsis critically ill patients on the first day. Importantly, the expression of PD-1+ CD4- CD8- T (OR = 0.622, 95% CI = 0.423-0.916, p = .016) and mHLA-DR+ (OR = 1.146, 95% CI = 1.014-1.295, p = .029) were significantly associated with sepsis mortality. For sepsis diagnosis, the mHLA-DR+ , PD-1+ CD4- CD8- T, and nCD64 index showed the moderate individual performance, and combinations of the three biomarkers achieved greater diagnostic value (AUC = 0.899, 95% CI = 0.792-0.962). When adding PCT into the combined model, the AUC increased to 0.936 (95% CI = 0.840-0.983). For sepsis mortality, combinations of PD-1+ CD4- CD8- T and mHLA-DR+ , have a good ability to predict the prognosis of sepsis patients, with an AUC = 0.921 (95% CI = 0.762-0.987). CONCLUSION: These findings indicate that the combinations of HLA-DR, CD64, and PD-1 outperformed each of the single indicator in diagnosis and predicting prognosis of sepsis.

Phase separation of RNF214 promotes the progression of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and the expression and function of an uncharacterized protein RNF214 in HCC are still unknown. Phase separation has recently been observed to participate in the progression of HCC. In this study, we investigated the expression, function, and phase separation of RNF214 in HCC. We found that RNF214 was highly expressed in HCC and associated with poor prognosis. RNF214 functioned as an oncogene to promote the proliferation, migration, and metastasis of HCC. Mechanically, RNF214 underwent phase separation, and the coiled-coil (CC) domain of RNF214 mediated its phase separation. Furthermore, the CC domain was necessary for the oncogenic function of RNF214 in HCC. Taken together, our data favored that phase separation of RNF214 promoted the progression of HCC. RNF214 may be a potential biomarker and therapeutic target for HCC.

Flow-diverter stents combined with flow-T stenting-assisted coiling for the treatment of a large basilar apex aneurysm: a case report with a 9-month follow-up.

Background: Endovascular or surgical treatment of wide-neck, large basilar apex aneurysms is challenging. We present a novel concept for the treatment of complex basilar apex aneurysms using flow-diverter devices combined with the flow-T stenting-assisted coiling technique. Assess the efficacy and safety profile of the technique in this complex aneurysm. Case description: A patient with multiple unruptured intracranial aneurysms underwent staged treatment. A large basilar apex aneurysm was treated with a flow-diverter stent combined with a flow-T stenting-assisted coiling technique in the first stage, and a giant supraclinoid aneurysm was treated with a flow-diverter stent applied in the second stage. Clinical presentations, technical details, intra- and perioperative complications, and clinical and angiographic outcomes were recorded, with a 9-month follow-up. Results: The patient achieved full neurologic recovery postoperatively. Cerebral angiography performed postoperatively showed revascularization, good laminar flow, and no in-stent or adjacent stenosis. Conclusion: Flow-diverter stents combined with flow-T stenting-assisted coiling for the treatment of giant basilar apex aneurysms is a feasible technique with efficacy demonstrated at a 9-month follow-up. Staged endovascular treatment of multiple intracranial aneurysms may be a safe and viable option.