Nomogram for assistant diagnosing acute suppurative cholangitis: a case-control study.

BACKGROUND: Acute suppurative cholangitis (ASC) lacks sensitive and specific preoperative diagnostic criteria. Some researchers suggest treating ASC as severe cholangitis. This study aimed to explore the relationship between the Tokyo Guidelines 2018 (TG18) grading system for acute cholangitis (AC) and the diagnosis of acute suppurative cholangitis (ASC), searching for independent risk factors of ASC and develop a nomogram to discriminate ASC from acute nonsuppurative cholangitis (ANSC) accurately. METHODS: After applying the inclusion and exclusion criteria, 401 patients with acute cholangitis (AC) were retrospectively analyzed at Nanjing First Hospital between January 2015 and June 2023. SPSS version 27.0 and R studio software were used to analyze data obtained from medical records. The results were validated in a prospective cohort of 82 AC patients diagnosed at Nanjing First Hospital between July 2023 and February 2024. RESULTS: Among the 401 patients, 102 had suppurative bile (the ASC group; AC grade I: 40 [39.2%], AC grade II: 27 [26.5%], AC grade III: 35 [34.3%]), whereas 299 did not have (the ANSC group; AC grade I: 157 [52.5%], AC grade II: 92 [30.8%], AC grade III: 50 [16.7%]). The specificity of ASC for diagnosing moderate-to-severe cholangitis is 79.7%. Multivariate logistic regression analysis identified concurrent cholecystitis, CRP, PCT, TBA, and bile duct diameter as independent risk factors for suppurative bile, and all of these factors were included in the nomogram. The calibration curve exhibited consistency between the nomogram and the actual observation, and the area under the curve was 0.875 (95% confidence interval: 0.835-0.915), sensitivity was 86.6%, and specificity was 75.5%. CONCLUSION: Suppurative bile is a specific indicator for diagnosing moderate-to-severe cholangitis. However, diagnosing ASC with AC grade II and AC grade III has the risk of missed diagnosis as the sensitivity is only 60.8%. To improve the diagnostic rate of ASC, this study identified concurrent cholecystitis, CRP, PCT, TBA, and preoperative bile duct diameter as independent risk factors for ASC, and a nomogram was developed to help physicians recognize patients with ASC.

Association between single-point insulin sensitivity estimator and heart failure in older adults: A cross-sectional study.

BACKGROUND: Heart failure (HF) is a condition caused by a malfunction of the heart's pumping function. The single-point insulin sensitivity estimator (SPISE) index is a novel indicator for assessing insulin resistance in humans. However, the connection between the SPISE index and the risk of HF in the elderly is unknown. Therefore, our study aims to evaluate the connection between the SPISE index and HF in older adults. METHODS: The study was based on data collected from the 1999-2020 National Health and Nutrition Examination Survey database and included 6165 participants aged ≥60 years. The multivariable linear regression model and the smooth fitting curve model were applied to investigate the connection between the SPISE index and HF in the elderly. Furthermore, the subgroup analysis was performed to investigate the interactive factors. RESULTS: In this study, the mean age of the population was 69.38 years. After adjusting for all covariates, we observed that the SPISE index was inversely related to the prevalence of HF (OR = 0.87, 95 % CI = 0.80-0.94, P < 0.001) in older adults. The interaction analysis showed that the association might be affected by diabetes mellitus and smoking status. Additionally, an inflection point between the SPISE index and HF was found among older women. CONCLUSIONS: An inverse correlation was detected between the SPISE index and HF in the elderly. This could provide new insight into the prevention and management of HF in the elderly population.

Ultra-low dose estradiol and dydrogesterone for the treatment of menopausal symptoms in a pooled, multi-ethnic population.

OBJECTIVES: Evidence suggests ethnicity-specific differences in postmenopausal symptoms, highlighting the need for therapies that are efficacious across different ethnicities. We evaluated the efficacy of an ultra-low dose combination of 0.5 mg estradiol and 0.25 mg dydrogesterone (E 0.5 mg/D 2.5 mg) in alleviating vasomotor symptoms across a multi-ethnic population. STUDY DESIGN: Data from two controlled trials were pooled to form a dataset of 583 postmenopausal women from across Europe and China. Participants were randomized to receive treatment with E 0.5 mg/D 2.5 mg or placebo for 12 weeks. MAIN OUTCOME MEASURES: The main efficacy variable was absolute change in the number of hot flushes from baseline to end of treatment. Health-related quality of life and safety were also assessed. RESULTS: Change in the number of hot flushes per day was greater with E 0.5 mg/D 2.5 mg versus placebo (mean difference - 1.5, 95 % confidence interval - 2.1, -1.0; p < 0.001). Participants treated with E 0.5 mg/D 2.5 mg reported improvement in health-related quality of life (including psychological symptoms, vaginal dryness), and high amenorrhea rates. Combined E 0.5 mg/D 2.5 mg was well tolerated: there were no differences between groups in the percentage of participants with at least one serious adverse event or treatment-emergent serious adverse events. Analysis of change in body weight indicated no differences between groups. CONCLUSIONS: This pooled analysis demonstrates the consistent efficacy of E 0.5 mg/D 2.5 mg in the treatment of menopause-related symptoms across a multi-ethnic population of postmenopausal women.

HIF-1α knockdown attenuates inflammation and oxidative stress in ischemic stroke male rats via CXCR4/NF-κB pathway.

BACKGROUND: Hypoxia inducible factor-1α (HIF-1α) is a sensitive indicator of oxygen homeostasis, of which the expression elevates following hypoxia/ischemia. This study reveals the specific mechanisms underlying the effects of HIF-1α on ischemic stroke (IS). METHODS: IS model was established using middle cerebral artery occlusion (MCAO)-modeled male rats and oxygen glucose deprivation/reoxygenation (OGD/R)-treated mice hippocampal cells HT22, followed by the silencing of HIF-1α and the overexpression of C-X-C motif chemokine receptor 4 (CXCR4) and nuclear factor-kappa B (NF-κB). Following the surgery, Garcia's grading scale was applied for neurological evaluation. Cerebral infarcts and injuries were visualized using 2,3,5-triphenyltetrazolium chloride and hematoxylin-eosin staining. The levels of tumor necrosis factor-α, Interleukin (IL)-6, IL-1ß, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine, were calculated via ELISA. MTT assay and lactate dehydrogenase (LDH) assay kit were adopted to determine the viability and cytotoxicity of OGD/R-modeled cells. Reactive oxygen species (ROS) generation was evaluated using a 2'-7'dichlorofluorescin diacetate (DCFH-DA) probe. The levels of HIF-1α, CXCR4, and NF-κB p65 were quantified via Western blot and immunofluorescence, respectively. RESULTS: HIF-1α knockdown improved Garcia's score, attenuated the cerebral infarct, inflammation, and ROS generation, and alleviated the levels of inflammatory cytokines and CXCR4/NF-κB p65 in MCAO-modeled rats. Such effects were reversed following the overexpression of CXCR4 and NF-κB. Also, in OGD/R-treated HT22 cells, HIF-1α silencing diminished the cytotoxicity and ROS production and reduced the expressions of CXCR4/NF-κB p65, while promoting viability. However, CXCR4/NF-κB p65 overexpression did the opposite. CONCLUSION: HIF-1α knockdown alleviates inflammation and oxidative stress in IS through the CXCR4/NF-κB pathway.

Analysis of Clinical Diagnosis and Treatment Modes for Congenital Branchial Cleft Anomalies.

OBJECTIVE: The objective of this study was to investigate and assess the clinical data of 123 patients diagnosed with congenital branchial cleft anomalies (CBCAs), to summarize pivotal aspects concerning their clinical diagnosis and treatment process. MATERIALS AND METHODS: The authors conducted a retrospective analysis of 123 patients who underwent surgical intervention for CBCAs at our institution between August 2005 and September 2021. The clinical demographic characteristics of the patients, primary symptoms, treatment chronology, preoperative diagnostic assessments, surgical strategies, occurrences of postoperative complications, and rates of recurrence were subjected to statistical analysis. RESULTS: Among the enrolled patients, there were 43 cases (34.9%) of congenital first branchial cleft anomalies (CFBCA), 76 cases (61.8%) of congenital second branchial cleft anomalies (CSBCA), and 4 cases (3.3%) of congenital third branchial cleft anomalies (CTBCA), with no cases of congenital fourth branchial anomalies (CFBA). Notably, among all cases, 43 anomalies were situated in the upper one-third of the sternocleidomastoid muscle, while 80 anomalies were located in the lower one-third. Different surgical approaches were selected for patients based on the specific type of anomaly presented. Following surgery, there was recurrence in 14 cases, with factors such as patient age, clinical categorization, lesion type, and history of preoperative infection and surgical intervention identified as primary risk factors for it. CONCLUSION: CBCAs represent comparatively uncommon disorders affecting the head and cervical regions in clinical practice. Diagnostic modes such as ultrasonography and lipiodol contrast radiography can be used for accurate diagnosis, with surgical intervention serving as the primary therapeutic method.

Molecular Evidence for the Axial Coordination Effect of Atomic Iodine on Fe-N4 Sites in Oxygen Reduction Reaction.

We present a molecular-scale investigation of the axial coordination effect of atomic iodine on Fe-N4 sites in the oxygen reduction reaction (ORR) by electrochemical scanning tunneling microscopy (ECSTM). A well-defined model catalytic system with explicit and uniform iodine-coordinated Fe-N4 sites was constructed facilely by the self-assembly of iron(II) phthalocyanine (FePc) on an I-modified Au(111) surface. The electrocatalytic activity of FePc for the ORR shows a tremendous enhancement with axial iodine ligands. The ingenious modulation of the electronic structure of Fe sites to evoke a higher spin configuration by axial iodine was evidenced. In addition, the interaction strength between reactive oxygen species and active centers becomes weaker due to the presence of iodine ligands, and the reaction is thermodynamically preferable. Moreover, the facilitated reaction dynamics of FePc on I/Au(111) were explicitly determined via in-situ ECSTM potential pulse experiments. Noteworthily, axial atomic iodine was found inefficacious for improving the activity of Co-N4 sites, and electron rearrangement was not detected, demonstrating that adequate interactions between axial ligands and metal sites for optimizing electronic structures and catalytic behaviors are prerequisites for the impactful role of axial ligands.

Predicting all-cause mortality and premature death using interpretable machine learning among a middle-aged and elderly Chinese population.

Objective: To develop machine learning-based prediction models for all-cause and premature mortality among the middle-aged and elderly population in China. Method: Adults aged 45 years or older at baseline of 2011 from the China Health and Retirement Longitudinal Study (CHARLS) were included. The stacked ensemble model was built utilizing five selected machine learning algorithms. These models underwent training and testing using the CHARLS 2011-2015 cohort (derivation cohort) and subsequently underwent external validation using the CHARLS 2015-2018 cohort (validation cohort). SHapley Additive exPlanations (SHAP) was introduced to quantify the importance of risk factors and explain machine learning algorithms. Result: In derivation cohort, a total of 10,677 subjects were included, 478 died during the follow-up. The stacked ensemble model demonstrated the highest efficacy in terms of its discrimination capability for predicting all-cause mortality and premature death, with an AUC[95 % CI] of 0.826[0.792-0.859] and 0.773[0.725-0.821], respectively. In validation cohort, the corresponding AUC[95 % CI] were 0.803[0.743-0.864] and 0.791[0.719-0.863], respectively. Risk factors including age, sex, self-reported health, activities of daily living, cognitive function, ever smoker, levels of systolic blood pressure, Cystatin C and low density lipoprotein were strong predictors for both all-cause mortality and premature death. Conclusion: Stacked ensemble models performed well in predicting all-cause and premature death in this Chinese cohort. Interpretable techniques can aid in identifying significant risk factors and non-linear relationships between predictors and mortality.

Alkali Metal Cations Induce Structural Evolution on Au(111) During Cathodic Polarization.

The activity of the electrocatalytic CO2 reduction reaction (CO2RR) is substantially affected by alkali metal cations (AM+) in electrolytes, yet the underlying mechanism is still controversial. Here, we employed electrochemical scanning tunneling microscopy and in situ observed Au(111) surface roughening in AM+ electrolytes during cathodic polarization. The roughened surface is highly active for catalyzing the CO2RR due to the formation of surface low-coordinated Au atoms. The critical potential for surface roughening follows the order Cs+ > Rb+ > K+ > Na+ > Li+, and the surface proportion of roughened area decreases in the order of Cs+ > Rb+ > K+ > Na+ > Li+. Electrochemical CO2RR measurements demonstrate that the catalytic activity strongly correlates with the surface roughness. Furthermore, we found that AM+ is critical for surface roughening to occur. The results unveil the unrecognized effect of AM+ on the surface structural evolution and elucidate that the AM+-induced formation of surface high-activity sites contributes to the enhanced CO2RR in large AM+ electrolytes.

PDIA3 defines a novel subset of adipose macrophages to exacerbate the development of obesity and metabolic disorders.

Adipose tissue macrophages (ATMs) play important roles in maintaining adipose tissue homeostasis and orchestrating metabolic inflammation. Given the extensive functional heterogeneity and phenotypic plasticity of ATMs, identification of the authentically pathogenic ATM subpopulation under obese setting is thus necessitated. Herein, we performed single-nucleus RNA sequencing (snRNA-seq) and unraveled a unique maladaptive ATM subpopulation defined as ATF4hiPDIA3hiACSL4hiCCL2hi inflammatory and metabolically activated macrophages (iMAMs), in which PDIA3 is required for the maintenance of their migratory and pro-inflammatory properties. Mechanistically, ATF4 serves as a metabolic stress sensor to transcribe PDIA3, which then imposes a redox control on RhoA activity and strengthens the pro-inflammatory and migratory properties of iMAMs through RhoA-YAP signaling. Administration of Pdia3 small interfering RNA (siRNA)-loaded liposomes effectively repressed adipose inflammation and high-fat diet (HFD)-induced obesity. Together, our data support that strategies aimed at targeting iMAMs by suppressing PDIA3 expression or activity could be a viable approach against obesity and metabolic disorders in clinical settings.

Metabolic profiling and spatial metabolite distribution in wild soybean (G. soja) and cultivated soybean (G. max) seeds.

Wild soybeans retain many substances significantly reduced or lost in cultivars during domestication. This study utilized LC-MS to analyze metabolites in the seed coats and embryos of wild and cultivated soybeans. 866 and 815 metabolites were identified in the seed extracts of both soybean types, with 35 and 10 significantly differing metabolites in the seed coat and embryos, respectively. The upregulated metabolites in wild soybeans are linked to plant defense, stress responses, and nitrogen cycling. MALDI-MSI results further elucidated the distribution of these differential metabolites in the cotyledons, hypocotyls, and radicles. In addition to their role in physiological processes like growth and response to environmental stimuli, the prevalent terpenoids, lipids, and flavonoids present in wild soybeans exhibit beneficial bioactivities, including anti-inflammatory, antibacterial, anticancer, and cardiovascular disease prevention properties. These findings underscore the potential of wild soybeans as a valuable resource for enhancing the nutritional and ecological adaptability of cultivated soybeans.

The implementation of low instantaneous dose rate total body irradiation with linear accelerator in small-size treatment rooms.

PURPOSE: This paper describes the implementation of an instantaneous low-dose-rate total body irradiation (TBI) technique using block-filtered 6 MV X-rays with a linear accelerator (LINAC) to reduce pulmonary toxicity. METHODS: In the absence of dedicated TBI-specific meter-set dose rates in LINAC and sufficient treatment room size, a 2-cm-thick transmission block was used together with a 200-cm source-to-surface distance (SSD) to reduce the instantaneous dose rates of 6 MV x-rays down to 10 cGy/min, thus alteration to the beam properties. A TBI-specific dose calculation model was built with data acquired at the treatment planning system (TPS)-permitted maximum 140-cm SSD and was validated in phantoms at a 180-cm SSD. As for planning strategies, we adopted large anterior-to-posterior/posterior-to-anterior (AP/PA) open fields with multi-leaf collimator shielding for lungs to achieve target coverage, lung protection, and efficient dose delivery. A custom-designed sliding couch (Patent No. ZL202123085880.1) was manufactured to support patients during treatment. Measures to control the quality and safety of TBI treatment include machine interlocks, pretreatment checklists, and in-vivo dose monitoring. RESULTS: The instantaneous dose rate of block-filtered 6MV X-ray was reduced to approximately 7.0 cGy/min at 12.5-7.5 cm depth with a 185-200 cm SSD. The dose calculated by TPS differs from the measurements by 0.15%-1.55% in the homogeneous phantom and 1.2%-4.85% in the CIRS thorax phantom. The open-field TBI technique achieved V90% (PTV) ≈ 96.8% and MLD = 6.6 Gy with 1-h planning and 50-min beam delivery in a single fraction. From February 2021 to July 2023, 30 patients received TBI treatments in our center, and in-vivo monitoring results differed from TPS calculations by -1.49%-2.10%. After 6-12 months of follow-ups, all the patients treated in our center showed no pulmonary toxicities of grade 2 or higher. CONCLUSION: A low instantaneous dose rate TBI technique can be implemented in the clinic.

Electroacupuncture reduces inflammatory damage following cerebral ischemia-reperfusion by enhancing ABCA1-mediated efferocytosis in M2 microglia.

Ischemic stroke (IS) is a severe cerebrovascular disease with high disability and mortality rates, where the inflammatory response is crucial to its progression and prognosis. Efferocytosis, the prompt removal of dead cells, can reduce excessive inflammation after IS injury. While electroacupuncture (EA) has been shown to decrease inflammation post-ischemia/reperfusion (I/R), its link to efferocytosis is unclear. Our research identified ATP-binding cassette transporter A1 (Abca1) as a key regulator of the engulfment process of efferocytosis after IS by analyzing public datasets and validating findings in a mouse model, revealing its close ties to IS progression. We demonstrated that EA can reduce neuronal cell death and excessive inflammation caused by I/R. Furthermore, EA treatment increased Abca1 expression, prevented microglia activation, promoted M2 microglia polarization, and enhanced their ability to phagocytose injured neurons in I/R mice. This suggests that EA's modulation of efferocytosis could be a potential mechanism for reducing cerebral I/R injury, making regulators of efferocytosis steps a promising therapeutic target for EA benefits.

Sevoflurane anesthesia during late gestation induces cognitive disorder in rat offspring via the TLR4/BDNF/TrkB/CREB pathway.

Sevoflurane (Sevo) is widely used for general anesthesia during pregnancy. Emerging evidence indicates that maternal Sevo exposure can trigger developmental neurotoxicity in the offspring. Nonetheless, the underlying mechanisms need further investigation. Pregnant Sprague-Dawley rats on gestational day 18 were exposed to 3.5% Sevo to induce the rat model of neurotoxicity. TAK-242, a TLR4 inhibitor, was administrated to inhibit the signaling transduction. Hippocampal tissues of rat offspring were harvested for immunohistochemical staining, TUNEL staining, Western blotting, ELISA, and measurement of oxidative stress-related markers. Serum samples were collected to evaluate lipid metabolism-associated factors. Morris water maze was implemented to test the cognitive function of offspring rats. Rat hippocampal neurons were isolated to elucidate the effect of TAK-242 on the BDNF/TrkB/CREB signaling in vitro. The results showed that maternal Sevo exposure during the third trimester induced neuroinflammation, lipid metabolism disturbance, and oxidative stress, and impaired the spatial learning and memory of rat offspring. Sevo upregulated TLR4 and impeded BDNF/TrkB/CREB signaling transduction in the hippocampus of rat offspring; TAK-242 administration reversed these effects. In conclusion, Sevo anesthesia during late gestation impairs the learning and memory ability of rat offspring possibly by promoting neuroinflammation and disturbing lipid metabolism via the TLR4/BDNF/TrkB/CREB pathway.

Glyphosate resistance and no fitness cost in backcross offspring of wild soybean and transgenic soybean with epsps gene.

BACKGROUND: The commercial utilization of genetically modified soybeans has yielded substantial economic advantages. Nevertheless, the genetic drift towards wild soybeans is one of the main ecological risks that needs to be addressed. Previous experiments demonstrated the absence of fitness cost or florescence overlap in hybrid offspring resulting from the crossbreeding of transgenic soybean GTS40-3-2 and Zhengzhou wild soybeans. In this study, hybrid progeny was systematically crossed with wild soybeans to establish a backcross progeny system. This system was employed to evaluate the ecological risk associated with the backcross progeny of transgenic and wild soybeans. RESULTS: The findings indicated that the offspring from the backcross exhibited glyphosate tolerance. Furthermore, the expression of foreign proteins in the backcross offspring was notably lower than in the transgenic soybean, and there was no significant difference when compared to the hybrid progeny. Parameters such as germination rate, aboveground biomass, pods per plant, full seeds per plant, and 100-grain weight exhibited no significant differences between the negative and positive lines of the backcross progenies, and no fitness cost was identified in comparison to wild soybeans. These results underscore the potential for foreign genes to propagate within other wild soybeans, which requires continuous attention. CONCLUSIONS: The widespread adoption of genetically modified soybeans has undeniably led to substantial economic gains. However, the research findings emphasize the critical importance of addressing the ecological risks posed by genetic drift towards wild soybeans. The backcross progeny system established in this study indicates that the potential for foreign gene dissemination to wild soybean populations warrants continued attention and mitigation strategies.

Exploring menopausal symptoms, attitudes, and behaviors among menopausal women in China: an online research perspective.

OBJECTIVE: The number of perimenopausal women in China is rising, but the population's concept of menopausal hormone therapy (MHT) is still relatively outdated. METHODS: In this study, we used the Knowledge-Attitude-Practice (KAP) theory and collected online questionnaires from 1,100 women aged 40 to 60 years nationwide to find out their menopausal symptom profiles; to learn about their perceptions, attitudes, and behaviors toward menopause and MHT; to explore the factors influencing the acceptance of hormone treatments; and to look for better ways to promote the dissemination of menopausal knowledge. RESULTS: The results revealed that among women aged 40 to 60 years, 82.36% experienced possible menopausal symptoms, with hot flushes/sweating, sleep disorders, mood disorders, and fatigue being the most prevalent; 55.90% reported moderate to severe symptoms, but only 46.99% of them sought healthcare services. Among those who sought medical care, 16.00% had their first visit to climacteric clinics/gynecological endocrinology, and 5.66% accepted MHT. Furthermore, 77.82% of participants never heard of MHT or were unaware of its existence. The healthcare-seeking behavior of menopausal women in response to symptoms and their willingness to accept MHT were found to be closely associated with their level of self-care. CONCLUSIONS: The prevalence of menopausal symptoms is higher in China than previous research findings, but due to a lack of relevant knowledge, the rate of seeking treatment from the appropriate medical department and accepting MHT is relatively low. Enhancing physicians' knowledge of the menopausal transition and using Internet tools might help improve Chinese women's knowledge of menopause and help them pass through this period smoothly.

Hypomethylation-associated ELF3 helps nasopharyngeal carcinoma to escape immune surveillance via MUC16-mediated glycolytic metabolic reprogramming.

Immune escape and metabolic reprogramming are two essential hallmarks of cancer. Mucin-16 (MUC16) has been linked to glycolysis and immune response in different cancers. However, its involvement in nasopharyngeal carcinoma (NPC) has not been well described. We seek to dissect the functions and detailed mechanisms of MUC16 in NPC. Bioinformatics prediction was performed to identify NPC-related molecules. MUC16 was significantly enhanced in NPC tissues, which was correlated with the advanced tumor stage of patients. Lentiviral plasmids-mediated MUC16 deletion inhibited the malignant behavior of NPC cells, and glycolysis inhibition by MUC16 deletion blocked immune escape in NPC cells. E74-like factor 3 (ELF3) bound to the MUC16 promoter to promote transcription of MUC16. MUC16 overexpression reversed the repressive effect of ELF3 silencing on glycolysis and immune escape in NPC and accelerated tumor growth in vivo. Overexpression of ELF3 in NPC was associated with reduced DNA methylation in its promoter. Our findings revealed the role of the ELF3/MUC16 axis in the immune escape and metabolic reprogramming of NPC, providing potential therapeutic targets for NPC.

Lipid profile in the aqueous humor of patients with myopia.

We examined the lipid profiles in the aqueous humor (AH) of myopic patients to identify differences and investigate the relationships among dissertating lipids. Additionally, we assessed spherical equivalents and axial lengths to explore the pathogenesis of myopia. Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was employed to qualitatively and quantitatively analyze the lipid composition of samples from myopic patients with axial lengths <26 mm (Group A) and >28 mm (Group B). Differences in lipid profiles between the two groups were determined using univariate and multivariate analyses. Receiver operator characteristic (ROC) curves were used to identify discriminating lipids. Spearman correlation analysis explored the associations between lipid concentrations and biometric parameters. Three hundred and nine lipids across 21 lipid classes have been identified in this study. Five lipids showed significant differences between Group B and Group A (VIP >1, P < 0.05): BMP (20:3/22:3), PG (22:1/24:0), PS (14:1/22:4), TG (44:2)_FA18:2, and TG (55:3)_FA18:1. The area under the curve (AUC) for these lipids was >0.75. Notably, the concentrations of BMP (20:3/22:3), PS (14:1/22:4), and TG (55:3)_FA18:1 were correlated with spherical equivalents, while BMP (20:3/22:3) and PS (14:1/22:4) correlated with axial lengths. Our study identified five differential lipids in myopic patients, with three showing significant correlations with the degree of myopia. These findings enhance our understanding of myopia pathogenesis through lipidomic alterations, emphasizing changes in cell membrane composition and function, energy metabolism and storage, and pathways involving inflammation, peroxisome proliferator-activated receptors (PPAR), and metabolic processes related to phosphatidylserine, phosphatidylglycerol, triglycerides, polyunsaturated fatty acids, and cholesterol.

[Effect of total saponins from Panacis Majoris Rhizoma on proliferation, apoptosis and autophagy of human cervical carcinoma HeLa cells].

This paper investigated the effect of total saponins from Rhizoma Panacis Majoris on the proliferation, apoptosis, and autophagy of human cervical carcinoma HeLa cells. The saponin content was detected by ultraviolet-visible spectrophotometry. Cell coun-ting kit-8(CCK-8) assay, 4,6-diamidino-2-phenylindole(DAPI) staining, and flow cytometry were used to detect the effects of total saponins of Panacis Majoris Rhizoma on cell viability, morphology, cell cycle and apoptosis of HeLa cells. Western blot was used to detect the expression of apoptosis-related proteins B cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cleaved caspase-9, and cleaved caspase-3, autophagy-related proteins Beclin-1 and SQSTM1(p62), and the proteins related to the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR) and mitogen-activated protein kinase(MAPK) signaling pathways. It was found that the yield and saponin content of total saponins from Rhizoma Panacis Majoris were 6.3% and 78.3%, respectively. Total saponins from Rhizoma Panacis Majoris could significantly inhibit the proliferation(P<0.001), effect the nuclear morphology, block the G_0/G_1 cycle, and induce cell apoptosis in HeLa cells with a concentration-dependent manner. In addition, total saponins from Rhizoma Panacis Majoris up-regulated the expression of pro-apoptotic proteins Bax, cleaved caspase-9, and cleaved caspase-3, and autophagy-related protein p62(P<0.05), while down-regulated the expression of anti-apoptotic protein Bcl-2 and autophagy-related protein Beclin-1(P<0.01). Total saponins from Rhizoma Panacis Majoris could promote the expression of p-p38/p38, p-Jun N-terminal kinase(JNK)/JNK, p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR proteins in PI3K/Akt/mTOR and MAPK signaling pathways(P<0.05). In contrast, the effect on p-ERK/ERK expression was not obvious. Therefore, total saponins from Rhizoma Panacis Majoris may inhibit autophagy and promote apoptosis of HeLa cells through the activation of the PI3K/Akt/mTOR, c-JNK, and p38 MAPK signaling pathways, which indicates that total saponins from Rhizoma Panacis Majoris may have a potential role in cervical cancer treatment.

Evaluation of Phenazine Derivatives from the Lichen-Associated Streptomyces flavidovirens as Potent Antineuroinflammatory Agents In Vitro and In Vivo.

Eighteen nitrogen-containing compounds (1-18) were isolated from cultures of the lichen-associated Streptomyces flavidovirens collected from the Qinghai-Tibet Plateau, including seven phenazine derivatives with three new ones, named subphenazines A-C (2-4), two new furan pyrrolidones (8-9), and nine known alkaloids. The structures were elucidated by spectroscopic data analysis, and absolute configurations were determined by single-crystal X-ray diffraction and ECD calculations. The phenazine-type derivatives, in particular compound 3, exhibited significantly better antineuroinflammatory activity than other isolated compounds (8-18). Compound 3 inhibited the release of proinflammatory cytokines including IL-6, TNF-α, and PGE2, and the nuclear translocation of NF-κB; it also reduced the oxidative stress and activated the Nrf2 signaling pathway in LPS-induced BV2 microglia cells. In vivo anti-inflammatory activity in zebrafish indicated that 3 inhibited LPS-stimulated ROS generation. These findings suggested that compound 3 might be a potent antineuroinflammatory agent through the regulation of the NF-κB/Nrf2 signaling pathways.

Gefitinib (an EGFR tyrosine kinase inhibitor) plus anlotinib (an multikinase inhibitor) for untreated, EGFR-mutated, advanced non-small cell lung cancer (FL-ALTER): a multicenter phase III trial.

Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor (EGFR) signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy. In this phase 3 study (ClinicalTrial.gov: NCT04028778), 315 patients with treatment-naïve, EGFR-mutated, advanced non-small cell lung cancer (NSCLC) were randomized (1:1) to receive anlotinib or placebo plus gefitinib once daily on days 1-14 per a 3-week cycle. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS was observed for the anlotinib arm over the placebo arm (hazards ratio [HR] = 0.64, 95% CI, 0.48-0.80, P = 0.003). Particularly, patients with brain metastasis and those harboring EGFR amplification or high tumor mutation load gained significant more benefits in PFS from gefitinib plus anlotinib. The incidence of grade 3 or higher treatment-emergent adverse events was 49.7% of the patients receiving gefitinib plus anlotinib versus 31.0% of the patients receiving gefitinib plus placebo. Anlotinib plus gefitinib significantly improves PFS in patients with treatment-naïve, EGFR-mutated, advanced NSCLC, with a manageable safety profile.