Impact of childhood socioeconomic status on depression among postdoctoral researchers in universities: The chain mediating role of current subjective socioeconomic status and perceived stress. / ç«¥å¹´ç¤¾ä¼šç»æµŽåœ°ä½å¯¹é«˜æ ¡åšå£«åŽæŠ‘éƒçš„å½±å“ï¼šå½“ä¸‹ä¸»è§‚ç¤¾ä¼šç»æµŽåœ°ä½å’ŒåŽ‹åŠ›æ„ŸçŸ¥çš„é“¾å¼ä¸­ä»‹ä½œç”¨.

OBJECTIVES: Postdoctoral researchers in Chinese universities commonly face a high risk of mental health issues, such as depression, yet the underlying causes and mechanisms remain unclear. This study aims to explore the influence of childhood socioeconomic status (SES) on depression among postdoctoral researchers and the mediating roles of current subjective SES and perceived stress in this process. METHODS: An online survey was conducted among postdoctoral researchers at a university. The survey included a general information questionnaire, the Childhood Socioeconomic Status Scale, the Subjective Socioeconomic Status Scale, the Perceived Stress Scale, and the Patient Health Questionnaire. A total of 505 valid responses were collected. Pearson correlation analysis was used to analyze the data, and the PROCESS macro was employed for chain mediation analysis. RESULTS: Childhood SES was significantly positively correlated with current subjective SES (P<0.05) and significantly negatively correlated with postdoctoral tenure, perceived stress, and depression (all P<0.05). Current subjective SES was significantly negatively correlated with perceived stress and depression (both P<0.05), while perceived stress was significantly positively correlated with depression (P<0.05). The chain mediation effect of childhood SES → current subjective SES → perceived stress → depression was significant (P<0.05). CONCLUSIONS: Childhood socioeconomic status can influence depression among postdoctoral researchers through the mediating roles of current subjective socioeconomic status and perceived stress. These findings provide a target for the prevention and intervention of depression in postdoctoral populations and offer a reference for the development of mental health promotion strategies for young university faculty.

Understanding the Role of Spin State in Cobalt Oxyhydroxides for Water Oxidation.

Although the electronic state of catalysts is strongly corrected with their oxygen evolution reaction (OER) performances, understanding the role of spin state in dynamic electronic structure evolution during OER process is still challenging. Herein, we developed a spin state regulation strategy to boost the OER performance of CoOOH through elemental doping (CoMOOH, M = V, Cr, Mn, Co and Cu). Experimental results including magnetic characterization, in situ X-ray absorption spectroscopy, in situ Raman and density functional theory calculations unveil that Mn doping could successfully increase the Co sites from low spin state to intermediate spin state, leading to the largest lattice distortion and smallest energy gap between dxy and dz2 orbitals among the obtained CoMOOH electrocatalysts. Benefiting from the promoted electron transfer from dxy to dz2 orbital, facilitated formation of active high-valent *O-Co(IV) species at applied potential, and reduced energy barrier of rate-determining step, the CoMnOOH exhibits the highest OER performance. Our work provides significant insight into the correction between dynamic electronic structure evolution and OER performance by understanding the role of spin state regulation in metal oxyhydroxides, paving a new avenue for rational design of high-activity electrocatalysts.

Construction of a nomogram with IrAE and clinic character to predict the survival of advanced G/GEJ adenocarcinoma patients undergoing anti-PD-1 treatment.

Objective: This study aimed to develop and validate a survival prediction model and nomogram to predict survival in patients with advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma undergoing treatment with anti-programmed cell death 1 receptor (PD-1). This model incorporates immune-related adverse events (irAEs) alongside common clinical characteristics as predictive factors. Method: A dataset comprising 255 adult patients diagnosed with advanced G/GEJ adenocarcinoma was assembled. The irAEs affecting overall survival (OS) to a significant degree were identified and integrated as a candidate variable, together with 12 other candidate variables. These included gender, age, Eastern cooperative oncology group performance status (ECOG PS) score, tumor stage, human epidermal growth factor receptor 2 (HER2) expression status, presence of peritoneal and liver metastases, year and line of anti-PD-1 treatment, neutrophil-to-lymphocyte ratio (NLR), controlling nutritional status (CONUT) score, and Charlson comorbidity index (CCI). To mitigate timing bias related to irAEs, landmark analysis was employed. Variable selection was performed using the least absolute shrinkage and selection operator (LASSO) regression to pinpoint significant predictors, and the variance inflation factor was applied to address multicollinearity. Subsequently, a Cox regression analysis utilizing the forward likelihood ratio method was conducted to develop a survival prediction model, excluding variables that failed to satisfy the proportional hazards (PH) assumption. The model was developed using the entire dataset, then internally validated through bootstrap resampling and externally validated with a cohort from another Hospital. Furthermore, a nomogram was created to delineate the predictive model. Results: After consolidating irAEs from the skin and endocrine systems into a single protective irAE category and applying landmark analysis, variable selection was conducted for the prognostic prediction model along with other candidate variables. The finalized model comprised seven variables: ECOG PS score, tumor stage, HER2 expression status in tumor tissue, first-line anti-PD-1 treatment, peritoneal metastasis, CONUT score, and protective irAE. The overall concordance index for the model was 0.66. Calibration analysis verified the model's accuracy in aligning predicted outcomes with actual results. Clinical decision curve analysis indicated that utilizing this model for treatment decisions could enhance the net benefit regarding 1- and 2-year survival rates for patients. Conclusion: This study developed a prognostic prediction model by integrating common clinical characteristics of irAEs and G/GEJ adenocarcinoma. This model exhibits good clinical practicality and possesses accurate predictive ability for overall survival OS in patients with advanced G/GEJ adenocarcinoma.

Impact of the number of lymph node dissections and a novel risk stratification on the prognosis in elderly locally advanced esophageal adenocarcinoma.

Background: Elderly patients with locally advanced esophageal adenocarcinoma (EAC) have a poor prognosis. The purpose of this study was to identify prognostic factors and construct a risk stratification for assessing the prognosis of elderly (≥ 70 years old) EAC patients who receiving neoadjuvant chemoradiotherapy (NCRT) and esophagectomy. Methods: A total of 688 patients with non-metastatic locally advanced EAC who underwent NCRT and esophagectomy were selected from the Surveillance Epidemiology and End Results (SEER) database. Multivariable Cox analysis was used to identify prognostic factors of overall survival (OS). Restricted Cubic Splines (RCS) was used to examine the linear relationship between the number of lymph node dissection (LND) and OS. Result: RCS showed a linear relationship between LND and OS (P = 0.690). As the number of LND increased, the risk of death decreased. Multivariable analysis demonstrated that LND > 23, grade III/IV, and regional node positive were independent prognostic factors. Subgroup analysis indicated that enlarged lymph node dissection (LND > 23) did not improve OS in patients with grade I/II or T1-2 stage, whereas enlarged lymph node dissection significantly improved OS in patients with grade III/IV or T3-4 stage. Furthermore, we constructed a novel risk score based on LND, grade, and regional node status, which stratified patients into low-, medium-, and high-risk groups. Patients in the high-risk group (risk score = 3) had a worse prognosis. Conclusions: Enlarged lymph node dissection (LND > 23) improved OS in patients with grade III/IV or T3-4 stage. Moreover, a novel risk score was constructed, which facilitated risk stratification and postoperative surveillance in elderly EAC patients.

Coriolopsis strumosa as an Orchid Endophytic Fungus and Its Spatial Distribution in Epidendrum sp. (Orchidaceae).

Coriolopsis spp. are wood-decaying fungi that inhabit forests. They are mainly distributed in tropical and subtropical areas. Strain Epi910 was isolated from the asymbiotically germinated protocorm of Epidendrum sp. and identified as Coriolopsis strumosa. Symbiotic germination and high-throughput sequencing of the endophytic fungal communities of different parts were performed to characterize the function and spatial distribution of the Epi910 isolate. Under symbiotic germination, Epi910 promoted seed germination and seedling formation as an endophytic native fungus of Epidendrum sp. Endophytic fungal communities from seven different parts of Epidendrum sp. were characterized. In total, 645 OTUs were identified; 30 OTUs were shared among all seven parts. The internal transcribed spacer sequence of Epi910 was identical to that of a dominant shared OTU (OTU6). The relative abundance of OTU6 in the seven parts was identified as follows: capsule pericarp > seed > root > asymbiotically germinated protocorm > epiphytic root > ovary > rachis. Our results suggest that the isolate belonging to Coriolopsis strumosa could promote the germination of Epidendrum sp. There may, therefore, be endophytic fungi other than common orchid mycorrhizal fungi with the ability to enhance germination in orchids.

Stabilizing atomic Ru species in conjugated sp2 carbon-linked covalent organic framework for acidic water oxidation.

Suppressing the kinetically favorable lattice oxygen oxidation mechanism pathway and triggering the adsorbate evolution mechanism pathway at the expense of activity are the state-of-the-art strategies for Ru-based electrocatalysts toward acidic water oxidation. Herein, atomically dispersed Ru species are anchored into an acidic stable vinyl-linked 2D covalent organic framework with unique crossed π-conjugation, termed as COF-205-Ru. The crossed π-conjugated structure of COF-205-Ru not only suppresses the dissolution of Ru through strong Ru-N motifs, but also reduces the oxidation state of Ru by multiple π-conjugations, thereby activating the oxygen coordinated to Ru and stabilizing the oxygen vacancies during oxygen evolution process. Experimental results including X-ray absorption spectroscopy, in situ Raman spectroscopy, in situ powder X-ray diffraction patterns, and theoretical calculations unveil the activated oxygen with elevated energy level of O 2p band, decreased oxygen vacancy formation energy, promoted electrochemical stability, and significantly reduced energy barrier of potential determining step for acidic water oxidation. Consequently, the obtained COF-205-Ru displays a high mass activity with 2659.3 A g-1, which is 32-fold higher than the commercial RuO2, and retains long-term durability of over 280 h. This work provides a strategy to simultaneously promote the stability and activity of Ru-based catalysts for acidic water oxidation.

Efficacy and safety of PD-1 inhibitors plus chemotherapy with or without endostatin for stage IV lung squamous cancer: a retrospective study.

Backgroud: The study aimed to analyze the efficacy and safety of PD-1 inhibitors plus chemotherapy with or without endostatin for stage IV lung squamous cell carcinoma (LUSC). Methods: A total of 219 patients with stage IV LUSC were included. 120 received PD-1 inhibitors plus chemotherapy with or without endostatin (IC ± A), of which 39 received endostatin (IC+A) and 81 did not receive endostatin (IC-A). 99 received chemotherapy with or without endostatin (C ± A). Endpoints included overall survival (OS), progression-free survival (PFS), adverse events (AEs), and immune-related adverse events (irAEs). Results: The median PFS in the IC ± A group versus the C ± A group was 8 and 4 months (P < 0.001), and the median OS was 17 and 9 months (P < 0.001). There was no significant difference in any grade AEs between the IC ± A and C ± A groups (P > 0.05). The median PFS in the IC+A group versus the IC-A group was 11 and 7 months (P = 0.024), and the median OS was 34 and 15 months (P = 0.01). There was no significant difference between the IC+A group and the IC-A group for all grade AEs and irAEs (P > 0.05). The subgroup analysis showed that patients with LIPI = 0 had significant OS and PFS benefits in IC+A group, while for patients with LIPI = 1-2, there was no significant difference in OS and PFS benefits between the IC+A group and IC-A group. Conclusions: PD-1 inhibitors plus chemotherapy with endostatin might be first-line treatment for patients with stage IV LUSC.

The Carthamus tinctorius L. genome sequence provides insights into synthesis of unsaturated fatty acids.

Domesticated safflower (Carthamus tinctorius L.) is a widely cultivated edible oil crop. However, despite its economic importance, the genetic basis underlying key traits such as oil content, resistance to biotic and abiotic stresses, and flowering time remains poorly understood. Here, we present the genome assembly for C. tinctorius variety Jihong01, which was obtained by integrating Oxford Nanopore Technologies (ONT) and BGI-SEQ500 sequencing results. The assembled genome was 1,061.1 Mb, and consisted of 32,379 protein-coding genes, 97.71% of which were functionally annotated. Safflower had a recent whole genome duplication (WGD) event in evolution history and diverged from sunflower approximately 37.3 million years ago. Through comparative genomic analysis at five seed development stages, we unveiled the pivotal roles of fatty acid desaturase 2 (FAD2) and fatty acid desaturase 6 (FAD6) in linoleic acid (LA) biosynthesis. Similarly, the differential gene expression analysis further reinforced the significance of these genes in regulating LA accumulation. Moreover, our investigation of seed fatty acid composition at different seed developmental stages unveiled the crucial roles of FAD2 and FAD6 in LA biosynthesis. These findings offer important insights into enhancing breeding programs for the improvement of quality traits and provide reference resource for further research on the natural properties of safflower.

Safflower CtFLS1-Induced Drought Tolerance by Stimulating the Accumulation of Flavonols and Anthocyanins in Arabidopsis thaliana.

Flavonol synthase gene (FLS) is a member of the 2-oxoglutarate-dependent dioxygenase (2-ODD) superfamily and plays an important role in plant flavonoids biosynthetic pathways. Safflower (Carthamus tinctorius L.), a key source of traditional Chinese medicine, is widely cultivated in China. Although the flavonoid biosynthetic pathway has been studied in several model species, it still remains to be explored in safflower. In this study, we aimed to elucidate the role of CtFLS1 gene in flavonoid biosynthesis and drought stress responses. The bioinformatics analysis on the CtFLS1 gene showed that it contains two FLS-specific motifs (PxxxIRxxxEQP and SxxTxLVP), suggesting its independent evolution. Further, the expression level of CtFLS1 in safflower showed a positive correlation with the accumulation level of total flavonoid content in four different flowering stages. In addition, CtFLS1-overexpression (OE) Arabidopsis plants significantly induced the expression levels of key genes involved in flavonol pathway. On the contrary, the expression of anthocyanin pathway-related genes and MYB transcription factors showed down-regulation. Furthermore, CtFLS1-OE plants promoted seed germination, as well as resistance to osmotic pressure and drought, and reduced sensitivity to ABA compared to mutant and wild-type plants. Moreover, CtFLS1 and CtANS1 were both subcellularly located at the cell membrane and nucleus; the yeast two-hybrid and bimolecular fluorescence complementation (BiFC) assay showed that they interacted with each other at the cell membrane. Altogether, these findings suggest the positive role of CtFLS1 in alleviating drought stress by stimulating flavonols and anthocyanin accumulation in safflower.

Effects of perceived stress on turnover intention of female healthcare staff: a serial multiple mediation model.

BACKGROUND: Healthcare staff in China, especially females, work in a high-pressure, high-load, and high-risk environment, which affects the physical and mental health, the efficiency and quality of work, and increases turnover intention. The present study investigated the relationship between perceived stress and turnover intention in female healthcare staff, and the effects of future-oriented coping and work-family balance on this relationship. METHODS: Four hundred thirty-five female medical workers were recruited to perform a perceived stress scale, future-oriented coping inventory, work-family balance scale and turnover intention scale. Meanwhile, serial multiple mediation analysis was performed using PROCESS. RESULTS: 1) Perceived stress positively predicted the level of turnover intention in female healthcare staff; 2) Preventive coping and proactive coping showed mediation effects on the relationship between perceived stress and turnover intention, and preventive coping positively related to proactive coping; 3) The work-family balance also showed mediation effects on the relationship between perceived stress and turnover intention; 4) Preventive coping, proactive coping and work-family balance showed a serial multiple mediation on the relationship between perceived stress and turnover intention in female healthcare workers. CONCLUSIONS: Perceived stress affects the level of turnover intention in female healthcare staff through preventive coping, proactive coping, and work-family balance. In addition, the sequential model of future-oriented coping was validated among female healthcare staff.

Ribosomal protein L22 like 1: a promising biomarker for lung adenocarcinoma.

No studies have reported the effect of ribosomal protein L22 like 1 (RPL22L1) in lung adenocarcinoma (LUAD). Therefore, we aimed to systematically investigate the role of RPL22L1 in LUAD. The expression of RPL22L1 was analyzed using TCGA, GEO, TIMER, UALCAN databases, and validated by immunohistochemistry (IHC). Gene methylation analysis was performed using the UALCAN, GSCA and MethSurv databases. The immune infiltrates were investigated using the Single Sample Gene Set Enrichment Analysis (ssGSEA), TIMER database, and TISCH database. The results demonstrated that RPL22L1 was up-regulated in LUAD, and verified by IHC. Kaplan-Meier analysis suggested that patients with high RPL22L1 expression had poor prognosis. Multivariate analysis confirmed that RPL22L1 was an independent prognostic factor. Furthermore, RPL22L1 overexpression was associated with hypomethylation, and two CpGs of RPL22L1 were significantly associated with prognosis. Up-regulated RPL22L1 was enriched in MYC targets, E2F targets, G2M checkpoint, mTORC1 signaling, cell cycle, and so on. Moreover, RPL22L1 expression was negatively correlated with immune cell infiltration, and patients with high RPL22L1 expression had lower immune, stromal, and estimate scores. Single-cell analysis suggested that RPL22L1 might have a potential function in the tumor microenvironment (TME) of LUAD. In conclusion, RPL22L1 may be a promising biomarker for LUAD.

Analysis of the treatment and prognosis of 266 cases of extranodal natural killer/T-cell lymphoma, nasal type in a single medical center.

Objective: To assess the impact of different treatment strategies and risk factors on the prognosis of patients with extranodal NK/T-cell lymphoma, nasal type (ENKTL) in a single medical center. Methods and analysis: The clinical features of 266 patients with ENKTL were retrospectively analyzed, among whom those in stages I and II received sandwich therapy, while those in stages III and IV underwent chemotherapy plus autologous hematopoietic stem cell transplantation. The Kaplan-Meier curves, univariate and multivariate Cox regression analyses were employed for survival and prognosis analysis. Statistical significance was set at P<0.05. Results: Following treatment, the post-intervention outcomes demonstrated a complete remission (CR) rate of 71.05% and a partial remission (PR) rate of 3.76%. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 70.4% and 70.9%, respectively. In addition, the PFS for patients in stage I/II was 79.8%, with an OS of 81.1%, whereas for those in stage III/IV, the PFS was 41.7% and the OS was 40.9%. Notably, the achievement of CR immediately after treatment was an independent prognostic factor (P<0.001). Patients in stage I/II depicted a favorable 5-year OS rate, while those in stage III/IV manifested a less favorable prognosis. Conclusion: Stages of the disease and whether CR was achieved following treatment are important factors determining the survival and prognosis of patients with ENKTL. Further researches focusing on disease onset and mechanisms of drug resistance will contribute to better management of ENKTL.

Exploring inter-ethnic and inter-patient variability and optimal dosing of osimertinib: a physiologically based pharmacokinetic modeling approach.

Purpose: This study aimed to develop and validate a physiologically based pharmacokinetic (PBPK) model for osimertinib (OSI) to predict plasma trough concentration (Ctrough) and pulmonary EGFRm+ (T790M and L858R mutants) inhibition in Caucasian, Japanese, and Chinese populations. The PBPK model was also utilized to investigate inter-ethnic and inter-patient differences in OSI pharmacokinetics (PK) and determine optimal dosing regimens. Methods: Population PBPK models of OSI for healthy and disease populations were developed using physicochemical and biochemical properties of OSI and physiological parameters of different groups. And then the PBPK models were validated using the multiple clinical PK and drug-drug interaction (DDI) study data. Results: The model demonstrated good consistency with the observed data, with most of prediction-to-observation ratios of 0.8-1.25 for AUC, Cmax, and Ctrough. The PBPK model revealed that plasma exposure of OSI was approximately 2-fold higher in patients compared to healthy individuals, and higher exposure observed in Caucasians compared to other ethnic groups. This was primarily attributed to a lower CL/F of OSI in patients and Caucasian. The PBPK model displayed that key factors influencing PK and EGFRm+ inhibition differences included genetic polymorphism of CYP3A4, CYP1A2 expression, plasma free concentration (fup), albumin level, and auto-inhibition/induction on CYP3A4. Inter-patient PK variability was most influenced by CYP3A4 variants, fup, and albumin level. The PBPK simulations indicated that the optimal dosing regimen for patients across the three populations of European, Japanese, and Chinese ancestry was OSI 80 mg once daily (OD) to achieve the desired range of plasma Ctrough (328-677 nmol/L), as well as 80 mg and 160 mg OD for desirable pulmonary EGFRm+ inhibition (>80%). Conclusion: In conclusion, this study's PBPK simulations highlighted potential ethnic and inter-patient variability in OSI PK and EGFRm+ inhibition between Caucasian, Japanese, and Chinese populations, while also providing insights into optimal dosing regimens of OSI.

Case Report: Gas in the esophagus, stomach wall and portal vein with congenital hypertrophic pyloric stenosis.

Background: CHPS dramatically affects infant growth and development and can even cause aspiration resulting from esophageal reflux. There is potential danger. CHPS is common, while CHPS with gas in the stomach wall and portal vein is rare. Gas in the stomach wall and portal vein are often the key features of more serious disease. It can be easily mistaken as a serious disease when patients with CHPS have gas in the stomach wall and portal vein. Case presentation: A 56-day-old baby was hospitalized for aspiration pneumonia after vomiting without bile for 20 days. Compared with vomiting, which is the most common symptom, pneumonia tends to attract more attention. Because of pneumonia, a chest CT scan was performed and revealed massive gas accumulation in the walls of the esophagus, stomach, and portal vein. Therefore, NEC was considered first and was treated conservatively for one week. However, the vomiting continued, and CHPS was confirmed by ultrasound. The delay in CHPS diagnosis was due to insufficient recognition of the signs of gas accumulation. Because of inexperience and lack of knowledge about CHPS with gastrointestinal pneumatosis, physicians failed to make an early accurate diagnosis. Case 2 was a 29-day-old male who was admitted to the hospital with vomiting without bile. He was examined by ultrasound, which revealed gas in the stomach wall and portal vein after admission to the hospital. No peritonitis was found after a detailed and comprehensive physical examination. Emergency life-threatening diseases such as NEC were quickly ruled out. He received surgery as soon as possible and had an uneventful recovery with no complications. Conclusion: CHPS may present with gas in the gastric or esophageal wall and portal vein, which is not a contraindication to surgery.

Prediction of ROS1 and TRKA/B/C occupancy in plasma and cerebrospinal fluid for entrectinib alone and in DDIs using physiologically based pharmacokinetic (PBPK) modeling approach.

PURPOSE: Entrectinib (ENT) is a potent c-ros oncogene 1(ROS1) and neurotrophic tyrosine receptor kinase (NTRKA/B/C) inhibitor. To determine the optimum dosage of ENT using ROS1 and NTRKA/B/C occupancy in plasma and cerebrospinal fluid (CSF) in drug-drug interactions (DDIs), physiologically-based pharmacokinetic (PBPK) models for healthy subjects and cancer population were developed for ENT and M5 (active metabolite). METHODS: The PBPK models were built using the modeling parameters of ENT and M5 that were mainly derived from the published paper on the ENT PBPK model, and then validated by the observed pharmacokinetics (PK) in plasma and CSF from healthy subjects and patients. RESULTS: The PBPK model showed that AUC, Cmax, and Ctrough ratios between predictions and observations are within the range of 0.5-2.0, except that the M5 AUC ratio is slightly above 2.0 (2.34). Based on the efficacy (> 75% occupancy for ROS1 and NTRKA/B/C) and safety (AUC < 160 µM·h and Cmax < 8.9 µM), the appropriate dosing regimens were identified. The appropriate dosage is 600 mg once daily (OD) when administered alone, reduced to 200 mg and 400 mg OD with itraconazole and fluconazole, respectively. ENT is not recommended for co-administration with rifampicin or efavirenz, but is permitted with fluvoxamine or dexamethasone. CONCLUSION: The PBPK models can serve as a powerful approach to predict ENT concentration as well as ROS1 and NTRKA/B/C occupancy in plasma and CSF.

Anesthetic Management of a Patient With Hemoglobin M Disease Undergoing Laparoscopic Uterine Myomectomy: A Case Report.

Hemoglobin M (Hb M) is a group of abnormal Hb variants that form methemoglobin, which leads to cyanosis. Patients with Hb M appear cyanotic but are usually asymptomatic. Cyanosis with low peripheral oxygen saturation is unresponsive to oxygen therapy despite normal partial pressure of oxygen. As such, close attention should be paid during anesthesia. We report the first case of a Hb M patient undergoing laparoscopic uterine myomectomy under general anesthesia.

Novel nomogram for predicting survival in advanced non-small cell lung cancer receiving anti-PD-1 plus chemotherapy with or without antiangiogenic therapy.

Background: This study aimed to develop and validate a novel nomogram to predict survival in advanced non-small cell lung cancer (NSCLC) receiving programmed cell death 1 (PD-1) inhibitor plus chemotherapy with or without antiangiogenic therapy. Methods: A total of 271 patients with advanced NSCLC who received anti-PD-1 plus chemotherapy with or without antiangiogenic therapy were enrolled in our center and randomized into the training cohort (n = 133) and the internal validation cohort (n = 138). Forty-five patients from another center were included as an independent external validation cohort. The nomogram was created based on the multivariate Cox regression analysis to predict overall survival (OS) and progression-free survival (PFS). The performance of the nomogram was assessed using the concordance index (C-index), the time-dependent area under the receiver operating (ROC) curves (AUCs), calibration curves, and decision curve analysis (DCA). Results: Four factors significantly associated with OS were utilized to create a nomogram to predict OS: Eastern Cooperative Oncology Group performance status (ECOG PS), programmed cell death-ligand 1 (PD-L1) expression, chemotherapy cycle, and pretreatment lactate dehydrogenase-albumin ratio (LAR). Six variables significantly associated with PFS were incorporated into the development of a nomogram for predicting PFS: ECOG PS, histology, PD-L1 expression, chemotherapy cycle, pretreatment platelet to lymphocyte (PLR), and pretreatment LAR. The C-indexes of the nomogram for predicting OS and PFS were 0.750 and 0.747, respectively. The AUCs for predicting the 6-month, 12-month, and 18-month OS and PFS were 0.847, 0.791, and 0.776 and 0.810, 0.787, and 0.861, respectively. The calibration curves demonstrated a good agreement between predictions and actual observations. The DCA curves indicated that the nomograms had good net benefits. Furthermore, the nomogram model was well-validated in the internal and external cohorts. Conclusion: The novel nomogram for predicting the prognosis of advanced NSCLC receiving anti-PD-1 plus chemotherapy with or without antiangiogenic therapy may help guide clinical treatment decisions.

An emerging role of arecoline on growth performance, intestinal digestion and absorption capacities and intestinal structural integrity of adult grass carp (Ctenopharyngodon idella).

Arecoline is an alkaloid with important pharmacological effects in the plant areca nut, which has been demonstrated to be an agonist of muscarinic receptors (M receptor). This study explored the influences of dietary arecoline on growth performance, intestinal digestion and absorption abilities, antioxidant capacity, and the apical junction complex (AJC) of adult grass carp (Ctenopharyngodon idella). Adult grass carp (608 to 1512 g) were fed at 6 graded levels of dietary arecoline (0, 0.5, 1.0, 1.5, 2.0, and 2.5 mg/kg diet) for 9 weeks. The results suggested that appropriate dietary supplementation of arecoline (1.0 mg/kg) increased growth parameters and intestinal growth in adult grass carp (P < 0.05), enhanced digestion and absorption capacities (P < 0.05), up-regulated muscarinic receptor 3 (M3) mRNA level (P < 0.05), increased the content of neuropeptide fish substance P (P < 0.05), improved antioxidant capacity by activating the Keap1a/Nrf2 signaling pathway (P < 0.05), reduced intestinal mucosal permeability (P < 0.05), and increased mRNA levels of tight junction (TJ) and adherent junction AJ-related proteins in fish by inhibiting the RhoA/ROCK signaling pathway (RhoA/ROCK/MLCK/NMII) (P < 0.05). In addition, the appropriate arecoline supplementation for adult grass carp was determined to be 1.20, 1.21, 1.07, and 1.19 mg/kg based on percentage weight gain, lipase activity, serum diamine oxidase, and protein carbonyl, respectively. Overall, to the best of our knowledge, we investigated for the first time the effects and possible mechanisms of dietary arecoline on intestinal digestive and absorptive capacities and structural integrity in fish and evaluated the appropriate level of supplementation.

The multi-kingdom microbiome of the goat gastrointestinal tract.

BACKGROUND: Goat is an important livestock worldwide, which plays an indispensable role in human life by providing meat, milk, fiber, and pelts. Despite recent significant advances in microbiome studies, a comprehensive survey on the goat microbiomes covering gastrointestinal tract (GIT) sites, developmental stages, feeding styles, and geographical factors is still unavailable. Here, we surveyed its multi-kingdom microbial communities using 497 samples from ten sites along the goat GIT. RESULTS: We reconstructed a goat multi-kingdom microbiome catalog (GMMC) including 4004 bacterial, 71 archaeal, and 7204 viral genomes and annotated over 4,817,256 non-redundant protein-coding genes. We revealed patterns of feeding-driven microbial community dynamics along the goat GIT sites which were likely associated with gastrointestinal food digestion and absorption capabilities and disease risks, and identified an abundance of large intestine-enriched genera involved in plant fiber digestion. We quantified the effects of various factors affecting the distribution and abundance of methane-producing microbes including the GIT site, age, feeding style, and geography, and identified 68 virulent viruses targeting the methane producers via a comprehensive virus-bacterium/archaea interaction network. CONCLUSIONS: Together, our GMMC catalog provides functional insights of the goat GIT microbiota through microbiome-host interactions and paves the way to microbial interventions for better goat and eco-environmental qualities. Video Abstract.

Effect of acute normovolemic hemodilution on anesthetic effect, plasma concentration, and recovery quality in elderly patients undergoing spinal surgery.

OBJECTIVE: To explore the effect of acute normovolemic hemodilution (ANH) on the anesthetic effect, plasma concentration, and postoperative recovery quality in elderly patients undergoing spinal surgery. METHODS: A total of 60 cases of elderly patients aged 65 to 75 years who underwent elective multilevel spinal surgery were assigned randomly into the ANH group (n = 30) and control group (n = 30). Hemodynamic and blood gas analysis indexes were observed and recorded before ANH (T1), after ANH (T2), immediately after postoperative autologous blood transfusion (T3), 10 min (T4), 20 min (T5), 30 min (T6), 40 min (T7), and 50 min (T8) after the transfusion, and at the end of the transfusion (i.e., 60 min; T9). At T3 ~ 9, bispectral index (BIS) and train-of-four (TOF) stimulation were recorded and the plasma propofol/cisatracurium concentration was determined. The extubation time and recovery quality were recorded. RESULTS: The ANH group presented a lower MAP value and a higher SVV value at T2, and shorter extubation and orientation recovery time (P < 0.05) compared with the control group. BIS values at T8 and T9 were lower in the ANH group than those in the control group (P < 0.05). TOF values at T7 ~ 9 were lower in the ANH group than those in the control group (P < 0.05). There were no statistically significant differences in the postoperative plasma concentrations of propofol and cisatracurium between the groups (P > 0.05). CONCLUSION: During orthopedic surgery, the plasma concentration of elderly patients is increased after autologous blood transfusion of ANH, and the depth of anesthesia and muscle relaxant effect are strengthened, thus leading to delayed recovery of respiratory function and extubation.