The hidden impact: the rate of nicotine metabolism and kidney health.

Objectives: The effects of nicotine metabolism on the kidneys of healthy individuals have not been determined. The nicotine metabolite ratio (NMR) indicates the rate of nicotine metabolism and is linked to smoking behaviors and responses to tobacco treatments. We conducted this study in order to investigated the relationship between nicotine metabolite ratio (NMR) and kidney function. Methods: An analysis of cross-sectional data of adults was conducted using a population survey dataset (National Health and Nutrition Examination Survey Data 2013/2018 of the United States). A weighted multivariate regression analysis was conducted to estimate the correlation between NMR and kidney function. Furthermore, we apply fitting smooth curves to make the relationship between NMR and estimated glomerular filtration rate (eGFR) more visualized. Results: The research included a total of 16153 participants. Weighted multivariate regression analyses adjusted for possible variables showed a negative relationship between NMR and estimated glomerular filtration rate (eGFR).The ß (95%CI) of the regression equation between NMR and eGFR was -2.24 (-2.92, -1.55), the trend testing showed consistent results. NMR is positively correlated with urinary albumin creatinine ratio (uACR), but it is not statistically significant. A stratified analysis found a negative correlation between NMR and eGFR in all age, gender and diabetes subgroups, the results were not statistically significant among Mexican Americans and other races. Notably, each unit rise in NMR corresponded to a 4.54 ml/min·1.73m² lower eGFR in diabetic participants and a 6.04 ml/min·1.73m² lower eGFR in those aged 60 and above. Conclusions: Our study shows that nicotine metabolite ratio is negatively associated with kidney function among most adults. It will be necessary to conduct more well-designed prospective clinical trials in order to determine the exact causal interactions between NMR and kidney function. Specific mechanisms also need to be further explored in basic experiments.

Reliability and validity of the Chinese version of the Structured Interview of Personality Organization-Revised (STIPO-R).

With the publication of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, a set of dimensional criteria was added as an emerging alternative model to the diagnosis of personality disorder (PD; American Psychiatric Association, 2013). Parallel to this, within the object relations conceptualization of personality pathology, a structured interview, the Structured Interview of Personality Organization (STIPO), was developed to assess pathological personality and then revised (STIPO-R). In this study, the reliability and validity of the Chinese version of the STIPO-R were tested on a sample of 236 Chinese participants, including both psychiatric patients and healthy individuals. Overall, the STIPO-R showed good internal consistency, interrater and test-retest reliability, and generally satisfactory results in structure and convergent validity. The STIPO-R also demonstrated discriminant validity (healthy individuals vs. psychiatric patients with PD vs. psychiatric patients without PD). Results are also discussed in light of cultural differences between Chinese and Western cultures. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

3-methyladenine ameliorates acute lung injury by inhibiting oxidative damage and apoptosis.

Background: Acute lung injury (ALI) is a condition characterized by inflammation and oxidative damage. 3-methyladenine (3-MA) has great potential for regulating apoptosis, but its regulatory role in ALI is unknown. Methods: Lipopolysaccharide (LPS)-treated mice and tert-butyl hydroperoxide (TBHP)-treated bronchial epithelial cells were used to simulate in vivo and in vitro ALI models, respectively. In vivo, lung injury was assessed by histopathological analysis and lung injury scoring. The total cell count, protein content, and inflammatory factors in bronchoalveolar lavage fluid (BALF) were examined. The level of apoptosis in lung tissue was assessed through TUNEL staining. In the vitro ALI model, cell viability and levels of reactive oxygen species and apoptosis were assessed. Results: 3-MA pretreatment ameliorated lung injury, including intra-alveolar hemorrhage and inflammatory cell accumulation, both in vitro and in vivo. 3-MA pretreatment also decreased inflammatory factor levels in the BALF. 3-MA pretreatment alleviated oxidative damage, decreased reactive oxygen species levels, and attenuated morphological changes. TUNEL and Annexin V-FITC/PI staining revealed that pretreatment with 3-MA reduced the level of apoptosis. 3-MA pretreatment significantly decreased the expression of caspase-3 and Bax but increased the expression of Bcl-2 in ALI. Mechanistically, 3-MA pretreatment also affected the PKCα/NOX4 and Nrf2 pathways, which decreased the level of apoptosis in ALI. Conclusions: 3-MA pretreatment inhibited inflammation and oxidative damage in ALI and inhibited apoptosis to mitigate ALI in part by inhibiting the PKCα/NOX4 pathway and activating the Nrf2 pathway. Based on these results, 3-MA might be a viable medication to treat with ALI.

Short-term culture for rapid identification by mass spectrometry and automated antimicrobial susceptibility testing from positive bottles.

BACKGROUND: Early and appropriate antibiotic treatment improves the clinical outcome of patients with sepsis. There is an urgent need for rapid identification (ID) and antimicrobial susceptibility testing (AST) of bacteria that cause bloodstream infection (BSI). Rapid ID and AST can be achieved by short-term incubation on solid medium of positive blood cultures using MALDI-TOF mass spectrometry (MS) and the BD M50 system. The purpose of this study is to evaluate the performance of rapid method compared to traditional method. METHODS: A total of 124 mono-microbial samples were collected. Positive blood culture samples were short-term incubated on blood agar plates and chocolate agar plates for 5 ∼ 7 h, and the rapid ID and AST were achieved through Zybio EXS2000 MS and BD M50 System, respectively. RESULTS: Compared with the traditional 24 h culture for ID, this rapid method can shorten the cultivation time to 5 ∼ 7 h. Accurate organism ID was achieved in 90.6% of Gram-positive bacteria (GP), 98.5% of Gram-negative bacteria (GN), and 100% of fungi. The AST resulted in the 98.5% essential agreement (EA) and 97.1% category agreements (CA) in NMIC-413, 99.4% EA and 98.9% CA in PMIC-92, 100% both EA and CA in SMIC-2. Besides, this method can be used for 67.2% (264/393) of culture bottles during routine work. The mean turn-around time (TAT) for obtaining final results by conventional method is approximately 72.6 ± 10.5 h, which is nearly 24 h longer than the rapid method. CONCLUSIONS: The newly described method is expected to provide faster and reliable ID and AST results, making it an important tool for rapid management of blood cultures (BCs). In addition, this rapid method can be used to process most positive blood cultures, enabling patients to receive rapid and effective treatment.

Luteolin ameliorates hypoxic pulmonary vascular remodeling in rat via upregulating KV1.5 of pulmonary artery smooth muscle cells.

BACKGROUND: Hypoxic pulmonary vascular remodeling (HPVR) is a key pathological feature of hypoxic pulmonary hypertension (HPH). Oxygen-sensitive potassium (K+) channels in pulmonary artery smooth muscle cells (PASMCs) play a crucial role in HPVR. Luteolin (Lut) is a plant-derived flavonoid compound with variety of pharmacological actions. Our previous study found Lut alleviated HPVR in HPH rat. PURPOSE: To elucidate the mechanism by which Lut mitigated HPVR, focusing on oxygen-sensitive voltage-dependent potassium channel 1.5 (Kv1.5). METHODS: HPH rat model was established using hypobaric chamber to simulate 5000 m altitude. Isolated perfused/ventilated rat lung, isolated pulmonary arteriole ring was utilized to investigate the impact of Lut on K+ channels activity. Kv1.5 level in lung tissue and pulmonary arteriole of HPH rat was assessed. CyclinD1, CDK4, PCNA, Bax, Bcl-2, cleaved caspase-3 levels in lung tissue of HPH rat were tested. The effect of Lut on Kv1.5, cytoplasmic free calcium concentration ([Ca2+]cyt), CyclinD1, CDK4, PCNA, Bax/Bcl-2 was examined in PASMCs under hypoxia, with DPO-1 as a Kv1.5 specific inhibitor. The binding affinity between Lut and Kv1.5 in PASMCs was detected by drug affinity responsive target stability (DARTS). The overexpression of KCNA5 gene (encoding Kv1.5) in HEK293T cells was utilized to confirm the interaction between Lut and Kv1.5. Furthermore, the impact of Lut on mitochondrial structure, SOD, GSH, GSH-Px, MDA and HIF-1α levels were evaluated in lung tissue of HPH rat and PASMCs under hypoxia. RESULTS: Lut dilated pulmonary artery by directly activating Kv and Ca2+-activated K+ channels (KCa) in smooth muscle. Kv1.5 level in lung tissue and pulmonary arteriole of HPH rat was upregulated by Lut. Lut downregulated CyclinD1, CDK4, PCNA while upregulating Bax/Bcl-2/caspase-3 axis in lung tissue of HPH rat. Lut decreased [Ca2+]cyt, reduced CDK4, CyclinD1, PCNA, increased Bax/Bcl-2 ratio, in PASMCs under hypoxia, by upregulating Kv1.5. The binding affinity and the interaction between Lut and Kv1.5 was verified in PASMCs and in HEK293T cells. Lut also decreased [Ca2+]cyt and inhibited proliferation via targeting Kv1.5 of HEK293T cells under hypoxia. Furthermore, Lut protected mitochondrial structure, increased SOD, GSH, GSH-Px, decreased MDA, in lung tissue of HPH rat. Lut downregulated HIF-1α level in both lung tissue of HPH rat and PASMCs under hypoxia. CONCLUSION: Lut alleviated HPVR by promoting vasodilation of pulmonary artery, reducing cellular proliferation, and inducing apoptosis through upregulating of Kv1.5 in PASMCs.

Anti-inflammatory properties and characterization of water extracts obtained from Callicarpa kwangtungensis Chun using in vitro and in vivo rat models.

Callicarpa kwangtungensis Chun (CK) is a common remedy exhibits anti-inflammatory properties and has been used in Chinese herbal formulations, such as KangGongYan tablets. It is the main component of KangGongYan tablets, which has been used to treat chronic cervicitis caused by damp heat, red and white bands, cervical erosion, and bleeding. However, the anti-inflammatory effects of CK water extract remains unknown. This study assessed the anti-inflammatory effects of CK in vivo and in vitro, characterized its main components in the serum of rats and verified the anti-inflammatory effects of serum containing CK. Nitric oxide (NO), tumour necrosis factor α (TNF-α) and interleukin-6 (IL-6) release by RAW264.7 cells was examined by ELISA and Griess reagents. Inflammation-related protein expression in LPS-stimulated RAW264.7 cells was measured by western blotting. Furthermore, rat model of foot swelling induced by λ-carrageenan and a collagen-induced arthritis (CIA) rat model were used to explore the anti-inflammatory effects of CK. The components of CK were characterized by LC-MS, and the effects of CK-containing serum on proinflammatory factors levels and the expression of inflammation-related proteins were examined by ELISA, Griess reagents and Western blotting. CK suppressed IL-6, TNF-α, and NO production, and iNOS protein expression in LPS-stimulated RAW264.7 cells. Mechanistic studies showed that CK inhibited the phosphorylation of ERK, P38 and JNK in the MAPK signaling pathway, promoted the expression of IκBα in the NF-κB signaling pathway, and subsequently inhibited the expression of iNOS, thereby exerting anti-inflammatory effects. Moreover, CK reduced the swelling rates with λ-carrageenan induced foot swelling, and reduced the arthritis score and incidence in the collagen-induced arthritis (CIA) rat model. A total of 68 compounds in CK water extract and 31 components in rat serum after intragastric administration of CK were characterized. Serum pharmacological analysis showed that CK-containing serum suppressed iNOS protein expression and NO, TNF-α, and IL-6 release. CK may be an anti-inflammatory agent with therapeutic potential for acute and chronic inflammatory diseases, especially inflammatory diseases associated with MAPK activation.

Multimodal ultrasound imaging: a method to improve the accuracy of sentinel lymph node diagnosis in breast cancer.

Aim: This study assessed the utility of multimodal ultrasound in enhancing the accuracy of breast cancer sentinel lymph node (SLN) assessment and compared it with single-modality ultrasound. Methods: Preoperative examinations, including two-dimensional ultrasound (2D US), intradermal contrast-enhanced ultrasound (CEUS), intravenous CEUS, shear-wave elastography (SWE), and surface localization, were conducted on 86 SLNs from breast cancer patients. The diagnostic performance of single and multimodal approaches for detecting metastatic SLNs was compared to postoperative pathological results. Results: Among the 86 SLNs, 29 were pathologically diagnosed as metastatic, and 57 as non-metastatic. Single-modality ultrasounds had AUC values of 0.826 (intradermal CEUS), 0.705 (intravenous CEUS), 0.678 (2D US), and 0.677 (SWE), respectively. Intradermal CEUS significantly outperformed the other methods (p<0.05), while the remaining three methods had no statistically significant differences (p>0.05). Multimodal ultrasound, combining intradermal CEUS, intravenous CEUS, 2D US, and SWE, achieved an AUC of 0.893, with 86.21% sensitivity and 84.21% specificity. The DeLong test confirmed that multimodal ultrasound was significantly better than the four single-modal ultrasound methods (p<0.05). Decision curve analysis and clinical impact curves demonstrated the superior performance of multimodal ultrasound in identifying high-risk SLN patients. Conclusion: Multimodal ultrasound improves breast cancer SLN identification and diagnostic accuracy.

Risk factors and predicting nomogram for the clinical deterioration of non-severe community-acquired pneumonia.

BACKGROUND: Currently, there remains insufficient focus on non-severe community-acquired pneumonia (CAP) patients who are at risk of clinical deterioration, and there is also a dearth of research on the related risk factors. Early recognition of hospitalized patients at risk of clinical deterioration will be beneficial for their clinical management. METHOD: A retrospective study was conducted in The First Affiliated Hospital of Wenzhou Medical University, China, spanning from January 1, 2018 to April 30, 2022, and involving a total of 1,632 non-severe CAP patients. Based on whether their condition worsened within 72 h of admission, patients were divided into a clinical deterioration group and a non-clinical deterioration group. Additionally, all patients were randomly assigned to a training set containing 75% of patients and a validation set containing 25% of patients. In the training set, risk factors for clinical deterioration in patients with non-severe CAP were identified by using LASSO regression analysis and multivariate logistic regression analysis. A nomogram was developed based on identified risk factors. The effectiveness of the nomogram in both the training and validation sets was assessed using Receiver Operating Characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). RESULTS: Age, body mass index (BMI), body temperature, cardiovascular comorbidity, respiratory rate, LDH level, lymphocyte count and D-dimer level were identified as risk factors associated with the clinical deterioration of non-severe CAP within 72 h of admission. The area under curve (AUC) value of the nomogram was 0.78 (95% CI: 0.74-0.82) in the training set and 0.75 (95% CI: 0.67-0.83) in the validation set. Furthermore, the calibration curves for both the training and validation sets indicated that the predicted probability of clinical deterioration aligned with the actual probability. Additionally, DCA revealed clinical utility for the nomogram at a specific threshold probability. CONCLUSION: The study successfully identified the risk factors linked to the clinical deterioration of non-severe CAP and constructed a nomogram for predicting the probability of deterioration. The nomogram demonstrated favorable predictive performance and has the potential to aid in the early identification and management of non-severe CAP patients at elevated risk of deterioration.

Effect of 7-ketocholesterol incorporation on substrate binding affinity and turnover rate of the organic cation transporter 2 (OCT2).

The organic cation transporter 2 (OCT2) is pivotal in the renal elimination of several positively charged molecules. OCT2 mode of transport is profoundly influenced by the level of membrane cholesterol. The aim of this study was to investigate the effect of oxidized cholesterol on OCT2 transport activity in human embryonic kidney 293 cells stably transfected with OCT2 (OCT2-HEK293) and in primary renal proximal tubular epithelial cells (RPTEC). Cholesterol was exchanged with 7-ketocholesterol, the main product of cholesterol auto-oxidation, by exposing cells to sterol-saturated methyl-ß-cyclodextrin (mßcd). After a 30 min-exposure, approximately 50% of the endogenous cholesterol was replaced by 7-ketocholesterol without significant changes in total sterol level. In the presence of 7-ketocholesterol, [3H]1-methyl-4-phenylpyridinium (MPP+) uptake was significantly reduced in both cell lines. 7-ketocholesterol incorporation did not affect lipid raft integrity, nor OCT2 surface expression and spatial organization. The inhibitory effect of 7-ketocholesterol on MPP+ uptake was abolished by the presence of MPP+ in the trans-compartment. In the presence of 7-ketocholesterol, both Kt and Vmax of MPP+ influx decreased. Molecular docking using OCT2 structure in outward occluded conformation showed overlapping poses and similar binding energies between cholesterol and 7-ketocholesterol. The thermal stability of OCT2 was not changed when cholesterol was replaced with 7-ketocholesterol. We conclude that 7-ketocholesterol confers a higher rigidity to the carrier by reducing its conformational entropy, arguably as a result of changes in plasma membrane physical properties, thereby facilitating the achievement of a higher affinity state at the expense of the mobility and overall cycling rate of the transporter.

Association between polyunsaturated fatty acids and progression among patients with diabetic kidney disease.

AIMS: Diabetic kidney disease (DKD) is the major complication of diabetes mellitus (DM) and one of the leading causes of end-stage renal disease. Early detection and treatment are contributing to delay the progression of DKD. Dietary management has potential benefits for DKD, especially the intake of polyunsaturated fatty acids (PUFAs). However, there is a lack of sufficient evidence, so we aimed to explore the association between PUFAs intake and DKD progression. METHODS: In the National Heath and Nutrition Examination Survey (NHANES) between 2011-2018, a cross-sectional study was conducted among adults with T2DM. DKD was diagnosed with urine albumin to creatinine ratio (ACR) ≥ 30 mg/g or estimated glomerular filtration rate (eGFR) ＜60 ml/min/1.73 m2. Using Survey package of R to arrange the collected PUFAs intake data in order from small to large and divide them into four equal parts, which were expressed as Q1, Q2, Q3 and Q4 respectively. To investigate the association between PUFAs intake and DKD, a weighted univariate logistic regression analysis was performed and the odds ratio (OR) and 95% confidence interval (CI) were calculated for the association with DKD and PUFAs quartiles. RESULTS: The study involved 3287 participants with T2DM, including 2043 non-DKD and 1244 DKD patients. The results showed that the intake of PUFAs was a protective factor for DKD (p = 0.022), and with the increase of the PUFAs, renal function improved in DKD patients, the adjusted mean of eGFR and Scr changing from 57 (41, 86) in Q1 to 71 (55, 101) ml/min in Q4 (p 0.001), 103 (73, 131) in Q1 to 90 (68, 117) in Q4 (p = 0.031), respectively. CONCLUSION: Our study indicated that intake of more PUFAs may contribute to delay DKD progression, while different n-6/n-3 ratios need to be explored to protect the kidney.

In vivo pharmacokinetic study of vanillic acid in monocrotaline-induced pulmonary arterial hypertension rats and its tissue distribution.

Vanillic acid (VA) is a bioactive chemical present in many food plants and fruits. It has been shown to have a protective effect on pulmonary tissues in monocrotaline-induced pulmonary arterial hypertension, as well as an intervention effect on right ventricular remodeling. The purpose of this study was to develop and test a reliable method for assessing VA utilizing ultra-performance liquid chromatography-high resolution mass spectrometry using caffeic acid as the internal standard. Across diverse substrates, the correlation coefficient for VA ranged from 0.9992 to 0.9995. The method's intraday precision was <13.53% (RSD), and its accuracy (RE) ranged from -9.88 to 4.35%. The precision across days was <13.69% (RSD), while the accuracy ranged from 2.16 to 10.94% (RE). The extraction recoveries ranged from 80.30 to 118.81%, with a lower limit of quantification of 20 ng/mL. The approach was successfully applied to pharmacokinetic and tissue distribution studies of VA in rat plasma after gavage administration, and the pharmacokinetic parameters of VA in the plasma of the monocrotaline-induced pulmonary arterial hypertension were significantly different from those of the control group.

Assessing Swallowing Dysfunction Aggravation in Chronic Obstructive Pulmonary Disease Patients Using Ultrasonic Measurements With Swallowing Movement Parameters.

OBJECTIVE: To investigate the correlation between ultrasonic measurements of swallowing movement parameters and aggravation of swallowing dysfunction in patients with chronic obstructive pulmonary disease (COPD). METHODS: COPD patients with swallowing dysfunction (n = 120) and COPD patients with normal swallowing function (n = 100) treated in our hospital between January 2020 and January 2023 were included in observation and control groups, respectively. The correlation between ultrasonic measurements of swallowing movement parameters and COPD with swallowing dysfunction was analyzed. The observation group was divided into mild and severe groups according to their Gugging Swallowing Screen (GUSS) scores. The correlation between ultrasonic measurements of swallowing movement parameters and COPD exacerbation combined with swallowing dysfunction was analyzed. RESULTS: In the observation group, Hyoid muscle thickness, hyoid bone displacement, geniohyoid muscle movement distance, HLAS, and CSR were lower compared to the control group, negatively associated with COPD-related swallowing issues. Conversely, geniohyoid muscle movement time and minimum hyohyoid distance (NHLA) were higher in the observation group, positively correlated with COPD-related swallowing dysfunction. In COPD patients with swallowing problems, the severe group exhibited lower values for lingual muscle thickness, hyoid bone displacement, geniohyoid muscle movement distance, HLAS, and CSR compared to the mild group, while geniohyoid muscle movement time and NHLA were higher in the severe group. Receiver operating characteristic (ROC) curves were created, indicating the promising diagnostic utility of these parameters for assessing the presence and severity of swallowing dysfunction in COPD patients. CONCLUSION: The ultrasonic measurement of swallowing motion parameters can effectively assess swallowing dysfunction in COPD patients.

Progesterone improved the behavior of PC12 cells under OGD/R by reducing FABP5 expression and inhibiting TLR4/NF-κB signaling pathway.

Herein, PC12 cells were applied to detect the impact of progesterone under oxygen glucose deprivation/reperfusion (OGD/R) stimulation. The cell proliferation of PC12 cells was evaluated by cell counting kit-8 assay, and the concentrations of MDA, ROS and SOD were examined by their corresponding Enzyme Linked Immunosorbent Assay kits. The invasion and migration properties of PC12 cells were evaluated by transwell and wound healing assays, respectively. The expression patterns of related genes were evaluated by western blot and qPCR. Under OGD/R stimulation, progesterone treatment could elevate the viability of PC12 cells, reduce the levels of MDA and ROS, and elevate the concentration of SOD. Moreover, progesterone treatment could strengthen the invasion and migration abilities of PC12 cells under OGD/R condition, as well as decrease the apoptosis and inflammation. FABP5 expression was significantly increased in PC12 cells under OGD/R stimulation, which was reversed after progesterone stimulation. Under OGD/R stimulation, the protective effects of progesterone on PC12 cells were strengthened after si-FABP5 treatment. The protein levels of TLR4, p-P65 NF-κB, and P65 NF-κB in OGD/R-induced PC12 cells were increased, which were inhibited after progesterone treatment. Progesterone exerted protective effects on PC12 cells by targeting FABP5 under OGD/R stimulation.

Supramolecular Integration of Multifunctional Nanomaterial by Mannose-Decorated Azocalixarene with Ginsenoside Rb1 for Synergistic Therapy of Rheumatoid Arthritis.

The complexity and progressive nature of diseases require the exploitation of multifunctional materials. However, introducing a function inevitably increases the complexity of materials, which complicates preparation and decreases reproducibility. Herein, we report a supramolecular integration of multifunctional nanomaterials based on mannose-modified azocalix[4]arene (ManAC4A) and ginsenoside Rb1 (Rb1), which showed advances of simplicity and reproducibility. ManAC4A possesses reactive oxygen species (ROS) scavenging capacity and hypoxia-responsiveness, together with macrophage-targeting and induction functionality. Collectively, the Rb1@ManAC4A assembly simply prepared by two components is integrated with multifunction, including triple targeting (ELVIS targeting, macrophage-targeting, and hypoxia-targeted release) and triple therapy (ROS scavenging, macrophage polarization, and the anti-inflammatory effect of Rb1). The spontaneous assembly and recognition of ManAC4A, with its precise structure and molecular weight, facilitated the simple and straightforward preparation of Rb1@ManAC4A, leading to excellent batch consistency. Progress in simplicity and reproducibility, as directed by this research, will catalyze the clinical translation of multifunctional materials.

Association between the modified lung immune predictive index and clinical outcomes of advanced non-small cell lung cancer treated with first-line immune checkpoint inhibitors combined with chemotherapy.

Background: As revealed by previous studies, the modified lung immune predictive index (mLIPI) can predict outcomes in patients with lung cancer receiving single-agent immunotherapy. However, the application value of the mLIPI for patients treated with combination immunotherapy requires further investigation. In this study, we aimed to explore the relationship between the mLIPI and the efficacy of treatment together with the prognosis of patients with advanced non-small cell lung cancer (NSCLC) receiving first-line immune checkpoint inhibitors (ICIs) combined with platinum-based chemotherapy. Methods: In this retrospective study, we enrolled patients with advanced NSCLC treated with ICIs plus chemotherapy from March 2019 to June 2022. The patients were classified into good, intermediate, and poor/very poor groups according to their mLIPI before treatment. We further calculated the disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) of the three groups. The predictive ability of the mLIPI was evaluated by plotting a time-dependent receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Results: A total of 209 patients were included in this study. There were 75 patients in the good group, 114 patients in the intermediate group, and 20 patients in the poor/very poor group. The median PFS was 11.2 months [95% confidence interval (CI): 8.763-13.704] in the good group; 8.1 months (95% CI: 7.354-8.846) in the intermediate group; and 5.4 months (95% CI: 2.142-8.658) in the poor/very poor group. The median OS was not reached in the good group, 29.5 months (95% CI: 23.555-35.512) in the intermediate group, and 14.5 months (95% CI: 8.567-20.366) in the poor/very poor group (P<0.05). Multivariate analysis showed that the mLIPI was independently associated with PFS and OS (P<0.05); the AUC values of the mLIPI for predicting PFS at 3, 6, and 9 months were 0.673, 0.637, and 0.614, respectively, and for predicting OS at 6, 12, and 24 months were 0.715, 0.655, and 0.625, respectively. Conclusions: The pretreatment mLIPI could be used to predict outcomes in patients with NSCLC receiving first-line ICIs plus chemotherapy.

Effects and mechanisms of intrauterine chronic hypoxia on ovarian reserve function of zygotic rats.

Chronic intrauterine hypoxia (ICH) may lead to permanent alterations in the offspring's body structure, function, and metabolism through the "developmental programming" pathway, resulting in lasting changes in physiology and metabolism, as well as the onset of adult-onset diseases. The aim was to investigate intrauterine growth restriction caused by ICH and its effect on ovarian reserve function in female offspring at different developmental stages after birth. Healthy female Sprague-Dawley rats (n = 20) were pregnant by normal mating, and the rats in the ICH group were treated with chronic intrauterine hypoxia twice a day for 04 h00 each time from day 4 to 21 of gestation. After the first hypoxic treatment, four pregnant rats were randomly selected from the ICH and natural control groups for arterial blood gas analysis. In the ICH group, birth weight and body weight on the 5th day after birth were less than in the control group, the total number of follicles and the number of primordial follicles in the offspring of the ICH group were significantly reduced on postnatal days 5, 20, and 40 (p < 0.05). ICH decreases ovarian reserve function in female offspring rats and programmatically regulates the differential expression of ovarian miRNAs in female offspring rats.

Risk estimation for postoperative nausea and vomiting: development and validation of a nomogram based on point-of-care gastric ultrasound.

BACKGROUND: We aimed to develop a nomogram that can be combined with point-of-care gastric ultrasound and utilised to predict postoperative nausea and vomiting (PONV) in adult patients after emergency surgery. METHODS: Imaging and clinical data of 236 adult patients undergoing emergency surgery in a university hospital between April 2022 and February 2023 were prospectively collected. Patients were divided into a training cohort (n = 177) and a verification cohort (n = 59) in a ratio of 3:1, according to a random number table. After univariate analysis and multivariate logistic regression analysis of the training cohort, independent risk factors for PONV were screened to develop the nomogram model. The receiver operating characteristic curve, calibration curve, decision curve analysis (DCA) and clinical impact curve (CIC) were used to evaluate the prediction efficiency, accuracy, and clinical practicability of the model. RESULTS: Univariate analysis and multivariate logistic regression analysis showed that female sex, history of PONV, history of migraine and gastric cross-sectional area were independent risk factors for PONV. These four independent risk factors were utilised to construct the nomogram model, which achieved significant concordance indices of 0.832 (95% confidence interval [CI], 0.771-0.893) and 0.827 (95% CI, 0.722-0.932) for predicting PONV in the training and validation cohorts, respectively. The nomogram also had well-fitted calibration curves. DCA and CIC indicated that the nomogram had great clinical practicability. CONCLUSIONS: This study demonstrated the prediction efficacy, differentiation, and clinical practicability of a nomogram for predicting PONV. This nomogram may serve as an intuitive and visual guide for rapid risk assessment in patients with PONV before emergency surgery.

Stress-induced red nucleus attenuation induces anxiety-like behavior and lymph node CCL5 secretion.

Previous studies have speculated that brain activity directly controls immune responses in lymphoid organs. However, the upstream brain regions that control lymphoid organs and how they interface with lymphoid organs to produce stress-induced anxiety-like behavior remain elusive. Using stressed human participants and rat models, we show that CCL5 levels are increased in stressed individuals compared to controls. Stress-inducible CCL5 is mainly produced from cervical lymph nodes (CLN). Retrograde tracing from CLN identifies glutamatergic neurons in the red nucleus (RN), the activities of which are tightly correlated with CCL5 levels and anxiety-like behavior in male rats. Ablation or chemogenetic inhibition of RN glutamatergic neurons increases anxiety levels and CCL5 expression in the serum and CLNs, whereas pharmacogenetic activation of these neurons reduces anxiety levels and CCL5 synthesis after restraint stress exposure. Chemogenetic inhibition of the projection from primary motor cortex to RN elicits anxiety-like behavior and CCL5 synthesis. This brain-lymph node axis provides insights into lymph node tissue as a stress-responsive endocrine organ.

The Value of Ultrasonic Elastography in Detecting Placental Stiffness for the Diagnosis of Preeclampsia: A Meta-Analysis.

This meta-analysis evaluated the diagnostic value of ultrasonic elastography in detecting placental stiffness in the diagnosis of preeclampsia (PE). A systematic search was conducted in the EMBASE, Web of Science, Cochrane Library, Scopus database, and PubMed databases to identify studies published before June 2023 using ultrasonic elastography to diagnose PE. The sensitivity, specificity, and diagnostic odds ratio of ultrasonic elastography for diagnosing PE were calculated, and a summary receiver operating characteristic curve model was constructed. The degree of heterogeneity was estimated using the I2 statistic, and a meta-regression analysis was performed to explore its sources. A protocol was determined previously (PROSPERO: CRD42023443646). We included 1188 participants from 11 studies, including 190 patients with PE and 998 patients without PE as controls. Overall sensitivity and specificity of ultrasonic elastography in detecting placental stiffness for the diagnosis of PE were 89% (95% CI: 85-93) and 74% (95% CI: 51-89), respectively. The I2 values for sensitivity and specificity were 59% (95% CI: 29-89) and 96% (95% CI: 95-98), respectively. The area under the receiver operating characteristic curve was 0.90 (95% CI: 0.87-0.92). The meta-regression analysis showed no significant heterogeneity. Ultrasonic elastography exhibits good diagnostic accuracy for detecting placental stiffness and can serve as a non-invasive tool for differentially diagnosing PE.

Shear wave elastography combined with two-dimensional ultrasonography for detecting optic nerve sheath: An effective tool for assessing preeclampsia.

PURPOSE/OBJECTIVE: This study aimed to investigate two-dimensional ultrasound and shear-wave elastography (SWE) in evaluating optic neuropathy in preeclampsia. METHODS: Ninety-one singleton pregnant women (51 with preeclampsia [observation group]; 40 without complications [control group]) admitted between January 2022 and April 2022 participated in this study. Optic nerve sheath diameter (ONSD) and optic nerve stiffness measurement (ONSM) were measured using two-dimensional ultrasound and SWE, respectively, and compared between the two groups. Receiver operating characteristic curves were employed to evaluate the performance of ONSD, ONSM, and combination (ONSD + ONSM) for diagnosing preeclampsia. RESULTS: The observation (preeclampsia) group ONSD and ONSM were significantly higher than those in the control group (p < 0.05). Optimal diagnostic values for ONSD and ONSM were 4.10 mm and 11.20 kPa, respectively. Areas under the curve for diagnosing preeclampsia were 0.958 (95% confidence interval [CI], 0.926-0.990) for ONSD, 0.939 (95% CI, 0.894-0.985) for ONSM, and 0.982 (95% CI, 0.962-1.000) for ONSD + ONSM. There was no significant difference between ONSD and ONSM in diagnosing preeclampsia (p = 0.436). However, ONSD + ONSM was significantly advantageous over ONSD or ONSM alone in diagnosing preeclampsia (p = 0.033; p = 0.014). CONCLUSIONS: Ultrasonic evaluation of the optic nerve can quantitatively assess optic nerve changes in pregnant women with preeclampsia.