A cross-sectional study on the impact of hemodialysis duration on retinal nerve fiber layer thinning in hemodialysis patients.

This study aimed to investigate the relationship between hemodialysis duration (HDD) and retinal nerve fiber layer (RNFL) thickness. A total of 60 patients receiving maintenance hemodialysis and 67 healthy controls were analyzed. Spectral domain optical coherence tomography (SD-OCT) was employed to measure annular RNFL thicknesses. The hemodialysis group exhibited reduced temporal and inferior RNFL thicknesses relative to the control group. In hemodialysis patients, the inferior RNFL thickness was negatively correlated with HDD and positively correlated with intraocular pressure (IOP). Moreover, IOP was positively correlated with HDD. Mediation analysis showed that the negative correlation between HDD and inferior RNFL thickness was mediated by IOP. In conclusion, hemodialysis leads to temporal and inferior RNFL thinning, and the thickness reduction is proportional to hemodialysis duration. However, such changes are not induced by an increase in IOP.

WNT2B high­expressed fibroblasts induce the fibrosis of IBD by promoting NK cells secreting IL-33.

Fibrosis is an important pathological change in inflammatory bowel disease (IBD), but the mechanism has yet to be elucidated. WNT2B high­expressed fibroblasts are enriched in IBD intestinal tissues, although the precise function of this group of fibroblasts remains unclear. This study investigated whether WNT2B high­expressed fibroblasts aggravated intestinal tissue damage and fibrosis. Our study provides evidence that WNT2B high­expressed fibroblasts and NK cells were enriched in colitis tissue of patients with IBD. WNT2B high­expressed fibroblasts secreted wnt2b, which bound to FZD4 on NK cells and activated the NF-κB and STAT3 pathways to enhance IL-33 expression. TCF4, a downstream component of the WNT/ß-catenin pathway, bound to p65 and promoted binding to IL-33 promoter. Furthermore, Salinomycin, an inhibitor of the WNT/ß-catenin pathway, inhibited IL-33 secretion in colitis, thereby reducing intestinal inflammation.Knocking down WNT2B reduces NK cell infiltration and IL-33 secretion in colitis, and reduce intestinal inflammation and fibrosis. In conclusion, WNT2B high­expressed fibroblasts activate NK cells by secreting wnt2b, which activates the WNT/ß-catenin and NF-κB pathways to promote IL-33 expression and secretion, potentially culminating in the induction of colonic fibrosis in IBD. KEY MESSAGES: WNT2B high-expressed fibroblasts and NK cells are enriched in colitis tissue, promoting NK cells secreting IL-33. Wnt2b activates NF-κB and STAT3 pathways promotes IL-33 expression by activating p65 and not STAT3. syndrome TCF4 binds to p65 and upregulates the NF- κB pathway. Salinomycin reduces NK cell infiltration and IL-33 secretion in colitis. Knocking down WNT2B mitigates inflammation and fibrosis in chronic colitis.

Thrombo-inflammatory prognostic score can predict the outcome of stroke: a retrospective cohort study.

Introduction: Inflammatory and thrombotic biomarkers are simple prognostic indicators of adverse clinical outcomes in patients with ischemic stroke (IS). However, isolated assessment of inflammatory or thrombus biomarkers in patients with IS is limited in clinical practice. Methods: This study aimed to evaluate the predictive value of a novel, simplified thrombo-inflammatory prognostic score (TIPS) that combines both inflammatory and thrombus biomarkers in the early phase of IS and to identify high-risk patients at the time of admission. The study population comprised 915 patients with a primary diagnosis of IS in the emergency departments of five grade A tertiary hospitals in China. Results: Patients were divided into two groups based on the modified Rankin Scale (mRS): <3 and ≥3. TIPS with a value of "2" indicates biomarkers for high inflammation and thrombosis, "1" represents a biomarker, and "0" signals the absence of a biomarker. Multivariate logistic regression analysis was employed to identify the association between TIPS and clinical outcomes. TIPS was an independent predictor of unfavorable functional outcomes and mortality. It had a superior predictive value for clinical outcomes compared to the National Institutes of Health Stroke Scale (NIHSS) (effect ratio, 37.5%), D-dimer (effect ratio, 12.5%), and neutrophil-to-lymphocyte ratio (effect ratio, 25%). Conclusion: The survival probability of TIPS with a score of 0 is twice as high as that of TIPS with a score of 2. The survival rate for TIPS with a score of 1 is one time higher than that for TIPS with a score of 2. The predictive value of TIPS for unfavorable functional outcomes is represented by an AUC of 0.653. TIPS is associated with an increased risk of death and unfavorable functional outcomes in patients with IS and may be a useful tool for identifying high-risk patients at the time of admission.

Coronary Artery Tree Description and Lesion Evaluation (CatLet) score for functional evaluation of coronary stenosis: a comparison study with pressure wire fractional flow reserve.

Background: Pressure wire fractional flow reserve (FFR) and its derivatives, such as quantitative flow ratio (QFR), computational pressure flow-derived FFR (caFFR), coronary angiography-derived FFR (FFRangio), and computed tomography-derived FFR (FFRCT), have been validated for identifying functionally significant stenosis and guiding revascularization strategy. The limitations of using these methods include the side effects of hyperemia-induced agents, additional costs, and vulnerability to microvascular resistance. FFR is related both to the degree of a stenotic coronary artery and to its subtended myocardial territory. Coronary Artery Tree Description and Lesion Evaluation (CatLet) score (also known as Hexu) is a product of the degree of a stenosis and the weighting of the affected coronary artery (myocardial territory). Hence, we hypothesized that the CatLet score could predict hemodynamically significant coronary stenosis. Methods: We retrospectively enrolled consecutive patients with stable coronary artery disease. They attended Sichuan Science City Hospital with at least one lesion of 50-90% diameter stenosis in a coronary artery of 2 mm or larger. FFR measurement was obtained during invasive coronary angiography. The CatLet score was obtained by multiplying a fixed value of 2.0 (for non-occlusive lesions) and the weight of the affected coronary artery. The primary endpoint was the CatLet score's diagnostic accuracy in identifying hemodynamically significant coronary stenosis, with a pressure wire FFR of ≤0.80 being used as reference. Results: We analyzed the FFR and CatLet scores from 206 vessels in 175 patients with stable coronary disease and intermediate coronary lesions. The per-vessel analysis revealed an overall good correlation between the CatLet score and the FFR [r=-0.61; 95% confidence interval (95% CI): -0.69 to -0.52; P<0.01]. We also noted a significant CatLet score-FFR correlation for each of the left anterior descending artery (LAD), left circumflex (LCX), and right coronary artery (RCA). With a CatLet score ≥10 as a predictor of FFR ≤0.80, the overall diagnostic accuracy included a sensitivity of 78.80% (95% CI: 67.00-87.90%), a specificity of 85.00% (95% CI: 78.00-90.50%), a positive likelihood ratio of 5.25, a negative likelihood ratio of 0.25, and an area under the curve of 0.90 (95% CI: 0.85-0.94). Equivalent vessel-specific results were also achieved for each of the LAD, LCX, and RCA. Conclusions: The CatLet score, solely based on visual estimation of the results of coronary angiography, demonstrated good diagnostic performance with respect to myocardial ischemia. Its clinical values in guiding revascularization warrant further investigation.

WNT2B activates macrophages via NF-κB signaling pathway in inflammatory bowel disease.

Inflammation is a significant pathological manifestation of inflammatory bowel disease (IBD), yet its mechanism has remained unclear. Although WNT2B is enriched in the intestinal inflammatory tissue of IBD patients, the specific mechanism of WNT2B in the formation of intestinal inflammation remains unclear. This study was aimed to investigate whether macrophages expressing WNT2B can aggravate intestinal tissue inflammation. Samples were collected from both normal individuals and patients with IBD at multiple colon sites. Macrophages were identified using tissue immunofluorescence. IκB kinase (IKK)-interacting protein (IKIP), which interacts with WNT2B, was found by protein cross-linking and protein mass spectrometry. The expression of WNT2B, IKIP, the NF-κB pathway, and downstream molecules were analyzed. An acute colitis model of C57BL/6J mice was established using an adeno-associated virus (AAV)-mediated WNT2B knockdown system and 3% dextran sulfate sodium (DSS). The degree of intestinal inflammation in mice was assessed upon WNT2B knockdown in macrophages. Macrophages expressing WNT2B were found to be enriched in the colitis tissues of IBD patients. WNT2B in macrophages activated the NF-κB pathway and enhanced the expression of downstream inflammatory cytokines. By competitively binding IKIP, WNT2B reduced the binding of IKIP to IKKß and promoted the activation of the NF-κB pathway. Using an AAV-mediated WNT2B knockdown system, WNT2B expression in intestinal macrophages was suppressed, leading to a reduction in intestinal inflammation. WNT2B activated the NF-κB pathway and enhanced the expression of downstream inflammatory cytokines by competitively binding to IKIP, potentially contributing to colon inflammatory injury in IBD.

BMX deletion mitigates neuroinflammation induced by retinal ischemia/reperfusion through modulation of the AKT/ERK/STAT3 signaling cascade.

Aims: Retinal ischemia/reperfusion (I/R) injury is implicated in the etiology of various ocular disorders. Prior research has demonstrated that bone marrow tyrosine kinase on chromosome X (BMX) contributes to the advancement of ischemic disease and inflammatory reactions. Consequently, the current investigation aims to evaluate BMX's impact on retinal I/R injury and clarify its implied mechanism of action. Main methods: This study utilized male and female systemic BMX knockout (BMX-/-) mice to conduct experiments. The utilization of Western blot assay and immunofluorescence labeling techniques was employed to investigate variations in the expression of protein and tissue localization. Histomorphological changes were observed through H&E staining and SD-OCT examination. Visual function changes were assessed through electrophysiological experiments. Furthermore, apoptosis in the retina was identified using the TUNEL assay, as well as the ELISA technique, which has been utilized to determine the inflammatory factors level. Key findings: Our investigation results revealed that the knockdown of BMX did not yield a significant effect on mouse retina. In mice, BMX knockdown mitigated the negative impact of I/R injury on retinal tissue structure and visual function. BMX knockdown effectively reduced apoptosis, suppressed inflammatory responses, and decreased inflammatory factors subsequent to I/R injury. The outcomes of the current investigation revealed that BMX knockdown partially protected the retina through downregulating phosphorylation of AKT/ERK/STAT3 pathway. Significance: Our investigation showed that BMX-/- reduces AKT, ERK, and STAT3 phosphorylation, reducing apoptosis and inflammation. Thus, this strategy protected the retina from structural and functional damage after I/R injury.

Solid-state high harmonic spectroscopy for all-optical band structure probing of high-pressure quantum states.

High pressure has triggered various novel states/properties in condensed matter, as the most representative and dramatic example being near-room-temperature superconductivity in highly pressured hydrides (~200 GPa). However, the mechanism of superconductivity is not confirmed, due to the lacking of effective approach to probe the electronic band structure under such high pressures. Here, we theoretically propose that the band structure and electron-phonon coupling (EPC) of high-pressure quantum states can be probed by solid-state high harmonic generation (sHHG). This strategy is investigated in high-pressure Im-3m H3S by the state-of-the-art first-principles time-dependent density-functional theory simulations, where the sHHG is revealed to be strongly dependent on the electronic structures and EPC. The dispersion of multiple bands near the Fermi level is effectively retrieved along different momentum directions. Our study provides unique insights into the potential all-optical route for band structure and EPC probing of high-pressure quantum states, which is expected to be helpful for the experimental exploration of high-pressure superconductivity in the future.

The Accuracy of Guided Implant Surgery With Different Fields of View of Cone-Beam Computerized Tomography.

Although a smaller size field of view (FOV) of cone-beam computerized tomography (CBCT) reduces radiation exposure, its effect on the accuracy of static computer-aided implant surgery (s-CAIS) remains unknown. This study aimed to evaluate the impact of the size of FOV on the accuracy of s-CAIS and to investigate if the arch affects this effect. A total of 32 implant sites on 8 identical scannable models (maxillae and mandibles) were randomly allocated to 2 FOV sizes: test (5 × 5 cm) and control (10 × 10 cm). All models were scanned with an intraoral scanner (IOS). With the registration of the surface scan and CBCT image, a prosthetic-driven implant position was planned. Following the fabrication of surgical templates, a single-blinded surgeon placed all implants with the fully guided s-CAIS protocol. IOS captured the implant positions with the scan body attached. Implant-planning software measured the angular deviation, 3-dimensional (3D) deviation at the crest, and 3D deviation at the apex between preplanned and actual implant positions. Two-way analysis of variance was used to analyze the effect of FOV and arch on the deviations. The size of FOV did not show a significant effect (P > .198) on angular deviation, 3D deviation at the crest, or 3D deviation at the apex. No significant difference was found when comparing the effect of the size of FOV between the maxillary and mandibular implants. In conclusion, the use of small FOV CBCT demonstrated comparable accuracy of s-CAIS to the use of medium FOV CBCT.

Fluorescence sensor based on optimized quantum yield manganese-carbon polymer dots and smartphone-integrated sensing platform for tetracycline detection.

The one-step synthesis of Mn-doped carbon quantum dots (Mn-CPDs) with a high quantum yield (QY = 45%) is reported using the microwave-assisted method. Subsequently, Mn-CPDs were successfully combined with Eu3+ ions to construct an Eu3+@Mn-CPDs fluorescence sensor. The presence of tetracycline (TC) induced a transition of fluorescence emission from blue (434 nm) to red (618 nm), and a robust linear relationship was observed between the ratio of F618 nm / F434 nm and the TC concentration (5 - 50 nmol/L), with a limit of detection (LOD) of 5.76 nmol/L. The underlying mechanism of Eu3+@Mn-CPDs and TC sensing is unveiled as a synergistic effect involving inner filter effect (IFE) and concurrent interactions. Notably, the smartphone-integrated sensing platform based on Eu3+@Mn-CPDs enables rapid and quantitative TC detection within a short time (< 30 s) by monitoring fluorescence color changes, achieving high-detection sensitivities (with a LOD of 6.18 nmol/L). This versatile and efficient sensing platform demonstrates its potential for the determination of TC concentrations in milk, honey, and tap water samples.

A commentary regarding the article 'A meta-analysis of atrial septal defect closure in patients with severe pulmonary hypertension: Is there a room for poking holes amidst debate?'

Atrial septal defects (ASD) are a common congenital heart defect. The majority of patient with ASDs often follow an uncomplicated course of events. However, a proportion of patients with ASDs, may have their condition complicated by pulmonary hypertension (PH), with a subsequent significant impact on management, morbidity, and mortality. The presence of PH influences the suitability for defect closure. Suitability for ASD closure when PVR is between 2.3 and 4.6 WU (PVRi 4-8 WU/m2) is not straightforward and clinical decision-making is individualized. Considerations include, whether to intervene with a complete defect closure, fenestrated closure or the 'treat and repair' strategy. However, it is difficult to determine the outcomes for ASD closure in patients with moderately-to-severely elevated PVR. A "treat and repair strategy" might be an option. In addition, the patient should be carefully selected by the observation of PVR change through vasoreactivity and balloon occlusion tests, and then closure should be considered. For patients with a predictable poor prognosis, research on the risk assessment of ASD closure in patients with PAH will be needed for a more individualized treatment plan.

Effects of Electroacupuncture on Skeletal Muscle Mitochondrial Dynamics in SAMP8 Mice / 中国中医药信息杂志

Objective To observe the effects of electroacupuncture on the motor function and mitochondrial dynamics of skeletal muscle of SAMP8 mice;To explore the mechanism of electroacupuncture in improving the motor dysfunction of Alzheimer disease(AD)from the perspective of mitochondrial dynamics.Methods Totally 18 SAMP8 mice were divided into model group and electroacupuncture group,with 9 mice in each group,and the SAMR1 mice with the same age were set as control group."Baihui","Dazhui"and"Shenshu"were selected in the electroacupuncture group,and electroacupuncture was performed daily for 20 min,8 d as a course of treatment.Each course of treatment was separated by 2 d,for a total of 3 courses of treatment.The model group and the control group were not intervened.The motor function of mice was tested by grip strength test,suspension test,hind limb extension test and Morris water maze experiment.The morphology and structure of gastrocnemius were observed by HE staining,ATP content in gastrocnemius was determined by colorimetry,the mRNA expression of optic atrophy 1(OPA1),mitofusin 2(MFN2)and dynamin-related protein 1(DRP1)in gastrocnemius were detected by real-time quantitative PCR,the expressions of OPA1,MFN2 and DRP1 in gastrocnemius were detected by Western blot.Results Compared with the control group,the grip strength,the score in suspension test,and the average speed and maximum speed of Morris water maze experiment of mice in model group significantly decreased(P<0.01);the arrangement of fibers in the gastrocnemius muscle tissue was disordered,the gaps become wider,and the distribution of nuclei was uneven;the ATP content in the gastrocnemius muscle tissue was significantly decreased(P<0.01),the mRNA and protein expressions of OPA1 and MFN2 were significantly decreased(P<0.01),and the expression of DRP1 mRNA and protein significantly increased(P<0.01).Compared with the model group,the grip strength,the score in suspension test,and the average speed and maximum speed of Morris water maze experiment in electroacupuncture group significantly increased(P<0.01);the arrangement of gastrocnemius muscle tissue was relatively neat,the gaps become narrower,and the distribution of nuclei was more uniform;the ATP content in gastrocnemius muscle tissue significantly increased(P<0.01),while the mRNA and protein expressions of OPA1 and MFN2 significantly increased(P<0.05,P<0.01),the expression of DRP1 mRNA and protein significantly decreased(P<0.01).Conclusion Electroacupuncture can improve the skeletal muscle morphological structure and motor dysfunction of SAMP8 mice,and the mechanism may be related to the correction of skeletal muscle mitochondrial dynamic imbalance and the increase of skeletal muscle ATP content.

Clinicopathological features of Langerhans cell histiocytosis involving thyroid gland / 复旦学报（医学版）

Objective To summarize the clinical and pathological characteristics of Langerhans cell histiocytosis(LCH)involving thyroid gland.Methods We reviewed 5 cases of histologically confirmed LCH with thyroid gland involvement in Huashan Hospital,Fudan University from Jun 2017 to Nov 2022 and analyzed their clinicopathological features.Results There were 1 male and 4 females aged from 29 to 54 years,with a median age of 31 years.Ultrasound showed hypoechoic nodules of thyroid.Morphologically,there were a large number of Langerhans cells,which contained abundant eosinophilic cytoplasm.The nucleus was oval,or had deeply grooved nuclei,which was like coffee beans.The nucleolus was not obvious,accompanied by a variable number of lymphocytes and eosinophils infiltration.The lesional cells were positive for CD1α,S100,Langerin,and Ki67 proliferation index was more than 15%,of which the highest was 70%.The tested 4 cases were all BRAF V600E and MAP2K1 gene mutation negative.Conclusion Cases limited to the thyroid were exceedingly rare.Most cases occurred in patients with multifocal disease.The clinical manifestations were painless enlargement of the thyroid gland.Surgical resection was a common treatment.Pathological manifestations included a large number of Langerhans cells and eosinophils diffused with the destruction of normal thyroid follicular structures.There was a characteristic of low mutation rates in BRAF V600E and MAP2K1 genes.

Study of effects of cognitive reserve on brain networks based on rest state functional magnetic resonance imaging / 医疗卫生装备

Objective To explore the effects of cognitive reserve on brain networks based on rest state functional magnetic resonance imaging(rsfMRI).Methods Firstly,7 973 healthy middle-aged and elderly individuals were selected for rsfMRI images at UK Biobank(UKB),and 21 resting-state networks were obtained through group independent component analysis.Secondly,the parameters of network node efficiency,shortest path length and node degree centrality were extracted using graph theory analysis.Finally,four indicators of resting-state networks including activeness,network node efficiency,node shortest path length and node degree centrality were compared and analyzed,whose relationships with five cognitive reserve proxies such as education level,early fluid intelligence,sports,leisure activities and socialization level.Results The education level,early fluid intelligence and sports,and the activity correlated positively with the activeness of multi resting-state networks and the node efficiency and node degree centrality of most of cognitive control networks and default mode networks,while negatively with the shortest path length of most of cognitive control networks and default mode networks.Leisure activities,socialization level and sports had negative correlations with the activeness of the resting-state network,and had little effects on the overall topological properties of the functional network.Conclusion Resting-state networks may be affected positively by education level,early fluid intelligence and sports,while negatively by two cognitive reserve proxies including leisure activities and socialization level.[Chinese Medical Equipment Journal,2024,45(1):1-8]

Detection of 14 sulfonate esters impurities of active pharmaceutical ingredients based on GC-MS/MS and LC-MS/MS / 药学学报

Two methods including gas chromatography tandem mass spectrometry (GC-MS/MS) and high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) were established to detect common alkyl sulfonates and aryl sulfonates genotoxic impurities. Four alkyl sulfonates and methyl benzenesulfonate were determined by GC-MS/MS using butyl methanesulfonate as the internal standard, the chromatographic column was HP-5MS UI (30 mm × 0.25 mm, 0.25 µm), the carrier gas was helium, the flow rate was 1.0 mL·min-1 in a constant flow mode, the sample inlet temperature was set to 250 ℃, the split ratio was 10∶1, and the initial temperature of the heating program was 80 ℃, maintained for 1 minute, and then increased to 240 ℃ at a heating rate of 30 ℃·min-1 for 2 minutes. The mass spectrometry detector was an electron bombardment ion source (EI source), the data collection condition was multi reaction monitoring mode (MRM), and method validation using the raw material of clinical drug citalopram hydrobromide as a sample. The results showed that the linear range of four alkyl sulfonates and methyl benzenesulfonate were good at 3-50 ng·mL-1 and 9-150 ng·mL-1, with a correlation coefficient of r > 0.999, The spiked recovery was 80%-120%. The detection limits were 1 and 3 ng·mL-1; Ten aryl sulfonates determined by LC-MS/MS, the chromatographic column was CSH Fluoro phenyl (100 mm × 2.1 mm, 1.7 µm), the mobile phase was methanol (B)-5 mmol·L-1 ammonium formate (D), with a flow rate of 0.2 mL·min-1, and gradient elution was performed. The gradient program (T/% B) was set as 0/20, 25/90, 35/90, 42/20. The mass spectrometer detector was electro spray ionization with positive ionization mode (ESI+), the data collection was in dynamic multi reaction monitoring mode (dMRM), and the method was validated using the raw material of the clinical drug citalopram hydrobromide as a sample. The results showed that the linear range of aryl sulfonates were good at 9-2 000 ng·mL-1, 3-100 ng·mL-1 and 0.9-30 ng·mL-1, respectively. The correlation coefficient r > 0.999, the spiked recovery was 80%-120%. The detection limits were 30, 1 and 0.3 ng·mL-1. Two detection methods did not detect potential sulfonate genotoxicity impurities in the above APIs. The established analytical methods are reliable and effective, which can provide reference for drug quality control and detection.

Enhancing Emergency Nurses' Disaster Nursing Ability and Psychological Resilience: A Randomized Controlled Trial.

Objective: This study aimed to investigate emergency nurses' disaster nursing ability and psychological resilience, validate the effectiveness of a training system for disaster nursing ability based on psychological resilience, and verify the relationship between psychological resilience and disaster nursing ability among emergency nurses. Methods: A training system was developed to enhance psychological resilience and disaster nursing ability. A multicenter, randomized controlled experiment was conducted in five Grade III hospitals in Sichuan Province. A total of 93 emergency nurses were randomly assigned to the following three groups: the blank group, intervention group, and control group. The corresponding interventions were as follows: no intervention, psychological resilience, and nurses' disaster nursing ability training. Personal information forms, the Connor-Davidson Resiliency Scale, and the Nurses' Disaster Nursing Ability Assessment Scale were used in the survey. Results: There was no significant difference in the scores of psychological resilience and disaster nursing ability in the blank group in the pretest and posttest (P > 0.05). The disaster nursing ability of both the intervention and control groups significantly improved in the posttest (P < 0.05). Compared with the control group, the intervention group demonstrated significant improvement in psychological resilience in the posttest (P < 0.05). However, there was no statistical difference in psychological resilience scores in the control group in the pretest and posttest (P > 0.05). Conclusion: The study concluded that the psychological resilience and disaster nursing ability of emergency nurses could be enhanced through the implemented training system.

[Saikosaponin D regulates apoptosis and autophagy of pancreatic cancer Panc-1 cells via Akt/mTOR pathway].

This study aims to investigate the effect and mechanism of saikosaponin D on the proliferation, apoptosis, and autophagy of pancreatic cancer Panc-1 cells. The cell counting kit(CCK-8) was used to examine the effects of 7, 10, 13, 16, 19, 22, 25, and 28 µmol·L~(-1) saikosaponin D on the proliferation of Panc-1 cells. Three groups including the control(0 µmol·L~(-1)), low-concentration(10 µmol·L~(-1)) saikosaponin D, and high-concentration(16 µmol·L~(-1)) saikosaponin D groups were designed. The colony formation assay was employed to measure the effect of saikosaponin D on the colony formation rate of Panc-1 cells. The cells treated with saikosaponin D were stained with hematoxylin-eosin(HE), and the changes of cell morphology were observed. Hoechst 33258 fluorescent staining was used to detect the effect of saikosaponin D on the cell apoptosis. The autophagy staining assay kit with MDC was used to examine the effect of saikosaponin D on the autophagy of Panc-1 cells. Western blot and immunocytochemistry(ICC) were employed to examine the effect of saikosaponin D on the expression levels and distribution of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cysteine-aspartic acid protease-3(caspase-3), cleaved caspase-3, autophagy-associated protein Beclin1, microtubule-associated protein light chain 3(LC3), protein kinase B(Akt), phosphorylated protein kinase B(p-Akt), mammalian target of rapamycin(mTOR), and phosphorylated mammalian target of rapamycin(p-mTOR). The results showed that compared with the control group, saikosaponin D decreased the proliferation rate of Panc-1 cells in a dose-dependent and time-dependent manner. The colony formation rate of the cells significantly decreased after saikosaponin D treatment. Compared with the control group, the cells treated with saikosaponin D became small, accompanied by the formation of apoptotic bodies. The saikosaponin D groups showed increased apoptosis rate and autophagic vesicle accumulation. Compared with the control group, saikosaponin D up-regulated the expression of Bax, cleaved caspase3, Beclin1, LC3Ⅱ/LC3Ⅰ and down-regulated the expression of Bcl-2, caspase-3, p-Akt/Akt, and p-mTOR/mTOR. In addition, these proteins mainly existed in the cytoplasm. In conclusion, saikosaponin D can inhibit the proliferation and induce the apoptosis and autophagy of Panc-1 cells via inhibiting the Akt/mTOR pathway.

Prognostic accuracy of SOFA, MEWS, and SIRS criteria in predicting the mortality rate of patients with sepsis: A meta-analysis.

BACKGROUND: In recent years, some studies classified patients with sepsis and predicted their mortality by using some evaluation scales. Several studies reported significant differences in the predictive values of several tools, and the non-uniformity of the cut-off value. OBJECTIVE: To determine and compare the prognostic accuracy of Sequential Organ Failure Assessment (SOFA) score, Modified Early Warning Score (MEWS), and Systemic Inflammatory Response Syndrome (SIRS) criteria in predicting the mortality of patients with sepsis. METHODS: This study comprised of systematic literature review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. We searched PubMed, Embase, Web of Science and Cochrane Library databases from their establishment to July 31, 2022. The research articles published in the index journals provide sufficient data (true positive, false positive, true negative, and false negative results) for patients with sepsis. The combined sensitivity and specificity of the 95% confidence interval (CI) were calculated using the bivariate random effect model (BRM). The hierarchical overall subject working characteristics (HSROC) curve was drawn to evaluate the accuracy of the overall prognosis. RESULTS: Data of 55 088 patients from 32 studies were included in this meta-analysis. SOFA had an intermediate sensitivity of 0.73 (95% CI: 0.67-0.78) and a specificity of 0.70 (0.63-0.76). SIRS criteria had the highest sensitivity of 0.75 (0.66-0.82) and the lowest specificity of 0.40 (0.29-0.52). MEWS had the lowest sensitivity of 0.49 (0.40-0.59) and the highest specificity of 0.82 (0.78-0.86). CONCLUSIONS: Among SOFA, MEWS, and SIRS criteria, SOFA showed moderate sensitivity and specificity for predicting mortality in patients with sepsis, the highest sensitivity of SIRS and the strongest specificity of MEWS for predicting mortality in patients with sepsis. The future research direction is to combine the relevant indicators of MEWS and SIRS to develop a measurement tool with high reliability and validity. RELEVANCE TO CLINICAL PRACTICE: The review provides useful insights into the prognostic accuracy of different assessment tools in predicting mortality in sepsis patients, which will help clinicians choose the most appropriate tool for early identification and treatment of sepsis. The findings may also contribute to the development of more accurate and reliable prognostic models for sepsis.

MOF-Enhanced Chiral ECL Recognition System: Dual-Function in Phenylalanine Enantiomer Detection and Coreaction Acceleration.

The accurate discernment and separation of chiral isomers with high precision remain a significant challenge in various industries and biological fields. In this investigation, an electrochemiluminescent (ECL) chiral recognition platform was devised to ascertain the presence of phenylalanine (Phe). Notably, a homochiral [Ni2(l-asp)2(bipy)] (Ni-LAB) was established as a dual-function coreactant accelerator and chiral recognition substrate. Ni-LAB facilitates the reaction between the coreactant (K2S2O8) and the luminescent entity 3,4,9,10-perylenetetracar-boxylic-l-cysteine (PTCA-cys), thereby enhancing the ECL luminescence efficiency and improving the sensitivity of the chiral sensor. The chiral recognition potential of Ni-LAB was assessed to differentiate between Phe chiral isomers, and the underlying mechanism was comprehensively elucidated. This system exhibited remarkable proficiency in detecting Phe enantiomers and precisely differentiating a single Phe enantiomer within a mixture, showcasing exceptional levels of selectivity, stability, and reproducibility. This study paves the way for the development of advanced chiral recognition systems, potentially revolutionizing the field of chiral sensing and discrimination.

Chiral Discrimination of Penicillamine Enantiomers: The Role of Aggregation-Caused Quenching in Achieving High Selectivity.

The recognition and separation of chiral isomers are of great importance in both industrial and biological applications. In this study, a chiral recognition system based on electrochemiluminescence was established for the detection of penicillamine (PA) enantiomers. The system utilized a homochiral [Zn2(BDC)(d-lac)] (Zn-BL) platform for the uniform distribution of Ru(bpy)32+ nanoparticles, effectively mitigating aggregation-caused quenching. The chiral recognition ability of Zn-BL was tested to distinguish between PA enantiomers, and the results indicated a substantial increase in the chiral electrochemiluminescence (ECL) signal when l-PA was present, in contrast to d-PA. The mechanism underlying ECL chiral discrimination was investigated using water contact angle measurements, DFT calculations, and electrochemical characterization. The system exhibited high selectivity, stability, and reproducibility for PA enantiomer detection. Furthermore, the proposed method can accurately identify one enantiomer of PA in a mixture. This study provides a reliable and sensitive approach for achieving the highly selective detection of chiral molecules.

Utilizing directional preference in the management of cervicogenic headache: a case series.

BACKGROUND/PURPOSE: Headaches are among the most common complaints requiring medical care, and annual expenditures for this condition are estimated to be 14 billion US dollars. The International Headache Society (IHS) describes cervicogenic headache (CGH) as a secondary type of headache emanating from the cervical spine which may be referred to one or more regions of the head and/or face. Mechanical Diagnosis and Therapy (MDT) is an approach shown to be effective in the management of spinal musculoskeletal disorders; however, there is limited evidence as to its efficacy in the management of CGH. The purpose of this case series was to examine the MDT approach in the assessment, classification, and management of a sample of patients experiencing cervicogenic headache. CASE DESCRIPTION: This study was a prospective case series. Following IRB approval, 15 patients meeting the study inclusion criteria were recruited from a hospital-based outpatient physical therapy clinic. All subjects received a physical therapy examination by a Diploma trained MDT clinician which included but was not limited to patient self-report forms and the testing of repeated end range movements. The Numerical Pain Rating Scale (NPRS), Neck Disability Index (NDI), Headache Disability Index (HDI), Yellow Flag Risk Form (YFRF), Cervical Flexion Rotation Test (CFRT), and the Craniocervical Flexion Test (CCFT) were administered at the initial visit, 5th visit, and 10th visit or discharge, whichever occurred first. The NPRS, NDI, and HDI were re-administered at a 3 month follow up. Following the initial examination, patients were classified into the MDT categories of derangement, dysfunction, postural, or 'other' and then received intervention based on directional preference. OUTCOMES: Fifteen subjects (mean age, 45.9 years; F = 11, M = 4; symptom duration, 44.3 months; average visits, 8.8) received an examination and intervention and completed follow-up outcome measures. Based on MDT classification criteria, all 15 subjects in this case series were classified as derangements. A non-parametric Friedman test of Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation differences among repeated measures was conducted on all outcome measures revealing statistically significant improvements in NPRS (p < .01), NDI(p < .01), and HDI (p < .01) scores at visit 10 and 3 month follow up. The mean change scores exceeded the minimal clinical important difference (MCID) for NPRS (4.2), NDI (7.6), and HDI (28.5). CCFT scores improved significantly from the initial examination to visit 5 (p < .01) and YFRF scores improved significantly between visits 5 and 10 (p < .01). DISCUSSION/CONCLUSION: The diagnosis of CGH is difficult to determine based on pathoanatomical assessment. This case series suggests that the patient's response to repeated end range movements may indicate a directional preference for manual procedures and exercises which may be used in management of musculoskeletal conditions such as CGH.