Gypensapogenin A-Liposomes Efficiently Ameliorates Hepatocellular Lipid Accumulation via Activation of FXR Receptor.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common metabolic diseases encountered in clinical practice, which is characterized by the excessive accumulation of triglycerides (steatosis), and a variety of metabolic abnormalities including lipid metabolism and bile acid metabolism are closely related to NAFLD. In China, Gynostemma pentaphyllum is used as functional food and Chinese medicine to treat various diseases, especially NAFLD, for a long time. However, the active components that exert the main therapeutic effects and their mechanisms remain unclear. In this study, Gypensapogenin A was isolated from the total saponins of G. pentaphyllum and prepared as a liposomal delivery system. Gypensapogenin A liposomes could activate FXR, inhibit the expression of CYP7A1 and CYP8B1, increase the expression of CYP27A1, modulate the ratio of CA and CDCA, decrease the content of CA, and increase the content of CDCA, thus forming a virtuous cycle of activating FXR to play a role in lowering blood lipid levels.

Endometriosis is a disease of immune dysfunction, which could be linked to microbiota.

Background: Endometriosis, characterized by extrauterine endometrial tissue, leads to irregular bleeding and pelvic pain. Menstrual retrograde theory suggests fragments traverse fallopian tubes, causing inflammation and scar tissue. Prevalent among infertile women, risk factors include fewer pregnancies, delayed childbirth, irregular cycles, and familial predisposition. Treatments, medication, and surgery entail side effects. Studies link gut microbiota alterations to endometriosis, necessitating research to establish causation. We used Mendelian randomization to investigate the potential link between endometriosis and gut microbiota through genetic variants. Methods: Two-sample Mendelian randomization analyzed gut microbiota's potential causal effects on endometriosis. Instrumental variables, robustly associated with exposures, leveraged GWAS data from MiBioGen for gut microbiota and FinnGen R8 release for endometriosis. SNPs strongly associated with exposures were instrumental variables. Rigorous assessments ensured SNP impact scrutiny on endometriosis. Results: At the genus level, Anaerotruncus, Desulfovibrio, Haemophilus, and Holdemania showed causal association with endometriosis. Specific gut microbiota exhibited causal effects on different endometriosis stages. Holdemania and Ruminococcaceae UCG002 exerted reversible, stage-specific impacts. Conclusion: Mendelian randomization provides evidence for the causal link between specific gut microbiotas and endometriosis, emphasizing the pivotal role of gut microbiota dysbiosis. Modulating gut microbiota emerges as a promising strategy for preventing and treating endometriosis.

Functional characterization of Fagopyrum tataricum ZIP gene family as a metal ion transporter.

The zinc/iron-regulated transporter-like proteins (ZIP) family acts as an important transporter for divalent metal cations such as Zn, Fe, Mn, Cu, and even Cd. However, their condition is unclear in Tartary buckwheat (Fagopyrum tataricum). Here, 13 ZIP proteins were identified and were predicted to be mostly plasma membrane-localized. The transient expressions of FtZIP2 and FtZIP6 in tobacco confirmed the prediction. Multiple sequence alignment analysis of FtZIP proteins revealed that most of them had 8 putative transmembrane (TM) domains and a variable region rich in histidine residues between TM3 and TM4, indicating the reliable affinity to metal ions. Gene expression analysis by qRT-PCR showed that FtZIP genes were markedly different in different organs, such as roots, stems, leaves, flowers, fruits and seeds. However, in seedlings, the relative expression of FtZIP10 was notably induced under the CdCl2 treatment, while excessive Zn2+, Fe2+, Mn2+ and Cd2+ increased the transcript of FtZIP5 or FtZIP13, in comparison to normal conditions. Complementation of yeast mutants with the FtZIP family genes demonstrate that FtZIP7/10/12 transport Zn, FtZIP5/6/7/9/10/11 transport Fe, FtZIP12 transports Mn and FtZIP2/3/4/7 transport Cd. Our data suggest that FtZIP proteins have conserved functions of transportation of metal ions but with distinct spatial expression levels.

Comprehensive analysis revealed P4Hs as new biomarkers for prognosis and immunotherapy in head and neck cancer.

Prolyl 4-hydroxylases (P4Hs) are a family of key modifying enzymes in collagen synthesis. P4Hs have been confirmed to be closely associated with tumor occurrence and development. However, the expression of P4Hs in head and neck cancer (HNSC) as well as its relationship with prognosis and tumor immunity infiltration has not yet been analyzed. We investigated the transcriptional expression, survival data, and immune infiltration of P4Hs in patients with HNSC from multiple databases. P4H1-3 expression was significantly higher in HNSC tumor tissues than in normal tissues. Moreover, P4HA1 and P4HA2 were associated with tumor stage, patient prognosis, and immune cell infiltration. P4HA3 was related to patient prognosis and immune cell infiltration. Correlation experiments confirmed that P4HA1 may serve as a prognosis biomarker and plays a role in the progression of nasopharyngeal carcinoma. These findings suggest that P4HA1-3 may be a novel biomarker for the prognosis and treatment of HNSC, which is expected to support the development of new therapies for patients with head and neck tumors and improve patient outcomes.

Predictive Factor of Tumor Aggressiveness in Patients with Extrahepatic Cholangiocarcinoma Based on Diffusion-weighted MRI.

BACKGROUND: Extrahepatic cholangiocarcinoma (EHCC), an exceedingly malignant neoplasm, often eludes early detection, culminating in a dire prognosis. Accurate cancer staging systems and pathological differentiation are designed to guide adjuvant interventions and predict postoperative prognoses. OBJECTIVE: This study sought to investigate the predictive capacity of DW-MRI in discerning T stages, lymph node metastasis, and pathological differentiation grades in patients with EHCC. METHODS: Eighty-five patients were pathologically diagnosed with EHCC and underwent abdominal MRI within two weeks before surgery at our hospital from Aug 2011 to Aug 2021. Tumor axial maximum area (AMA) and apparent diffusion coefficient (ADC) values for diverse T stages, N stages, and differentiation grades were retrospectively analyzed. RESULTS: The Mann-Whitney U test displayed significantly higher lesion AMA values (P =0.006) and lower tumor ADC values (P = 0.001) in the nodepositive group (median ADC and AMA value: 1.220×10-3 mm2/s, 82.231 mm2) than in the node-negative group (median ADC and AMA value: 1.316×10-3 mm2/s, 51.174 mm2). A tumor ADC value<1.249×10-3 mm2/s from the receiver operating characteristic curve (AUC=0.725, P=0.001) exhibited the capability to predict node-positive EHCC with a sensitivity of 64.29%, and specificity of 73.68%. Furthermore, a progressive decrease in the degree of EHCC differentiation was associated with a reduction in the tumor ADC value (P=0.000). CONCLUSION: The N stage and differentiation of EHCC can be evaluated non-invasively using diffusion-weighted MRI.

Complementary and alternative medicine in relation to chemotherapy-induced peripheral neuropathy: A narrative review.

PURPOSE: To summarizes the available evidence on the effectiveness, safety, and feasibility of complementary and alternative medicine (CAM) in the management of chemotherapy-induced peripheral neuropathy (CIPN). METHODS: We searched for systematic reviews, and meta-analyzes published up to April 2023 in the Pubmed and Web of Science databases. The latest original research on related topics was also reviewed. The search was restricted to English-language papers. Two independent reviewers performed a quality assessment of the identified literature. RESULTS: The results of 35 systematic reviews and meta-analyzes were included in this study. Preliminary evidence suggests that CAM, including acupuncture, physical activity (PA), herbal and nutritional supplements, mind-body therapies, touch therapy, and non-invasive neuromodulation techniques, have shown tremendous potential for the prevention and treatment of CIPN. Of these, there is strong evidence supporting acupuncture, PA, and herbal medicine. However, existing clinical studies are also limited by the heterogeneity of study methods, insufficient sample size, and poor study design. Further studies are needed to validate the efficacy of CAM in patients with CIPN and to elucidate potential therapeutic mechanisms. CONCLUSIONS: Current research has reached a preliminary conclusion suggesting the potential efficacy of certain CAMs in the management of CIPN. Future clinical trials should incorporate more robust study design protocols and larger sample sizes to enhance the validity of findings.

Molecular Classification of Endometrial Endometrioid Carcinoma With Microcystic Elongated and Fragmented Pattern.

The studies on the molecular classification of endometrioid carcinoma (EC) with microcystic, elongated, and fragmented (MELF) pattern invasion are limited. In this study, 77 cases of ECs with MELF patterns in Chinese women were collected. The molecular classification of the fifth edition of the World Health Organization was used to classify the molecular subtypes using immunohistochemistry staining (mismatch repair [MMR]-immunohistochemistry: MSH2, MSH6, MLH1, and PMS2; p53) and Sanger sequencing targeted POLE . The results showed that the prevalence of the 4 molecular subtypes in EC with MELF pattern was 6.5% (5/77) for POLE mutation, 20.8% (16/77) for MMR deficient, 11.7% (9/77) for p53-mutant, and 61.0% (47/77) for no specific molecular profile. The clinicopathological characteristics of each subtype were compared. The p53-mutant and no specific molecular profile subgroups were associated with higher International Federation of Gynecology and Obstetrics stage and International Federation of Gynecology and Obstetrics grade, deeper myometrial invasion, lymphovascular space invasion, lymph node metastasis, and absence of tumor-infiltrating lymphocytes, whereas the POLE mutation and MMR deficient subgroups were associated with lower aggressive features and prominent tumor-infiltrating lymphocytes. Progression-free survival showed that the p53-mutant and no specific molecular profile subgroups had a poorer prognosis than the POLE mutation and MMR deficient subgroups. However, lymph node metastasis was an independent factor associated with a higher risk of disease recurrence in multivariate analysis. In conclusion, ECs with MELF patterns can be divided into 4 molecular subtypes with discrepancies in aggressive clinicopathological characteristics and tumor-infiltrating lymphocytes. Molecular classification has clinical significance in a morpho-molecular approach for ECs with MELF patterns.

DNAJA1 promotes proliferation and metastasis of breast cancer by activating mutant P53/NF-κB pathway.

PURPOSE: Breast cancer is one of the most common tumors with high malignancy and metastatic rate. DNAJA1 is closely related to tumor progress in several tumors. However, the role and mechanisms of DNAJA1 in the metastasis and proliferation of breast cancer are unknown. METHODS: Immunohistochemistry and western blot were used to detect the protein expression genes. In vivo and vitro experiments were performed to evaluate the proliferation, invasive and metastatic abilities of breast cancer cells. RESULTS: DNAJA1 was high expressed in 234 cases of breast cancer tissues and associated with metastasis, p53 expression and poor survival for patients. Knock down of DNAJA1 decreased the number of plate clone formation and the OD value of CCK8 assays in breast cancer cells. Depletion of DNAJA1 also in decreased the invasive abilities of breast cancer cells. In vivo, knock down DNAJA1 decreased the growth of subcutaneous tumor and lung metastatic nodes. Mechanically, DNAJA1 could bind with P53-R175H and reduced its degradation. Up regulation of DNAJA1 in mutant P53-R175H breast cancer cell promoted the nuclear translocation of p65, activated NF-κB pathway and enhanced the transcription of its downstream genes such as MMP9, CXCL10 et al. Blockade of NF-κB pathway effectively rescued the effects of DNAJA1 on proliferation and metastasis in breast cancer. CONCLUSION: Our study reveals that DNAJA1 is up regulated in breast cancer and promotes breast cancer cells proliferation and metastasis via P53-R175H/NF-κB pathway. It might be a potential prognosis marker for the breast cancer patients.

Comparative analysis of serum and saliva samples using Raman spectroscopy: a high-throughput investigation in patients with polycystic ovary syndrome and periodontitis.

BACKGROUND: Polycystic ovary syndrome (PCOS) and periodontitis significantly affect women's oral and systemic health worldwide, and yet increase the risk of cardiovascular-metabolic diseases like diabetes and coronary heart disease. Regarding the PCOS-periodontitis connection, whether sex hormones, metabolic and inflammatory mediators could account for the underlying linking mechanism needs to be further investigated. This case-control study evaluated the hormonal, metabolic and inflammatory profiles in PCOS and non-PCOS subjects with various periodontal conditions, via assessing serum and saliva samples by Raman spectroscopy. METHODS: A total of 66 females with PCOS and 22 systemically healthy female volunteers were recruited in a single hospital. Full-mouth periodontal examination was undertaken for identifying the subjects with periodontal health, gingivitis or periodontitis. The datasets of sex hormones and metabolic indicators were retrieved from the hospital information system. Both serum and saliva samples were collected for detecting inflammatory mediators and Raman spectroscopic assessment. The subjects were categorized into four groups according to their conditions of PCOS and periodontitis for Raman spectroscopic analysis. Partial least squares discriminant analysis was performed to examine the inter-group differences in Raman spectra. RESULTS: PCOS patients exhibited greater mean probing depth (P < 0.05) and higher serum levels of triglycerides (P < 0.05) and matrix metalloproteinase-8 (P < 0.05) than those in non-PCOS participants. Both probing depth and triglyceride level were positively correlated with PCOS (P < 0.05). There was a significant difference in mean Raman spectra of saliva samples among the four groups with different conditions of PCOS and periodontitis (P < 0.05), while no significant inter-group difference existed in serum samples. CONCLUSIONS: The present study shows that periodontal condition may affect the biomolecular profiles of Raman spectra in serum and saliva of PCOS patients. It underscores the importance of the collaborative teamwork of dentists and gynecologists for enhancing women's oral health, general wellbeing and quality of life.

Numerical Simulation of Layered Bimetallic ZChSnSb8Cu4/Steel TIG-MIG Hybrid Welding Based on Simufact.

Considering the problem of the weak bonding interface structure between the rolling mill oil and film bearing bushings of Babbitt alloy and steel substrate, a numerical simulation of the layered bimetallic ZChSnSb8Cu4/steel by tungsten inert gas (TIG)-metal inert gas (MIG) hybrid welding process was carried out using Simufact Welding software (version 2020). In this study, the TIG-MIG hybrid welding process was simulated to obtain the temperature field and the stress field distributions. The residual stress and the deformation of the weldment were also analyzed using the calculated results. The results showed that the temperature gradient and the thermal stress were reduced in TIG-MIG hybrid welding compared to the conventional MIG welding preparation of layered bimetal ZChSnSb8Cu4/steel, which resulted in an improvement in the structural stability of the weldment. The temperature field and deformation of TIG-MIG hybrid welding of Babbitt alloy were studied under different controlled electrode spacings and TIG welding currents, and it was found that as electrode spacing increased, so did heat loss. Furthermore, with increased TIG welding current, compressive stress increased and tensile stress at the weld decreased, and the maximum thermal efficiency of welding was with a preheating current of 60 A.

Post-marketing surveillance for the safety of the 9-valent human papillomavirus vaccine: a retrospective real-world study in China.

BACKGROUND: The 9-valent human papillomavirus (9vHPV) vaccine was introduced in China in 2018. This study was conducted to monitor the occurrence of new-onset autoimmune diseases (AIs) in Chinese women vaccinated with the 9vHPV vaccine and adverse pregnancy outcomes in infants born to mothers with inadvertent pregnancy exposure. RESEARCH DESIGN AND METHODS: Women who received the first dose of the 9vHPV vaccine at age 16-26 years in Ningbo between January 2019 and March 2021 were monitored in the Ningbo Regional Health Information Platform. New-onset cases of seven pre-specified AIs diagnosed within six months after vaccination were collected. Cases of stillbirth and 23 major congenital anomalies diagnosed within three months of birth in target infants were collected. RESULTS: A total of 102,670 doses of the 9vHPV vaccine were administered to 41,609 women who had received no other HPV vaccine. New-onset AIs were diagnosed in 36 women, comprising 21 Hashimoto's, 11 Graves', and 4 uveitis disease cases. Among 50 women with maternal vaccination exposure, no stillbirths were observed. One case of microtia was observed. CONCLUSIONS: In this first post-marketing surveillance of the 9vHPV vaccine in China, no safety signals were identified when putting the results in context to published data.

SDPR Inhibits TGF-ß Induced Cancer Metastasis Through Fatty Acid Oxidation Regulation in Gastric Cancer.

Our previous studies have confirmed that transforming growth factor-ß (TGF-ß) plays an important role in tumor metastasis, and the serum deprivation protein response (SDPR) is a potential downstream target of TGF-ß. However, the role and mechanism of SDPR in gastric cancer are still unclear. We performed gene microarray, bioinformation analysis, combined with in vivo and in vitro experimental verification, we identified that SDPR is significantly downregulated in gastric cancer, and participates in TGF-ß-mediated tumour metastasis. Mechanically, SDPR interacts with extracellular signal-regulated kinase (ERK) and inhibits fatty acid metabolism key gene Carnitine palmitoyl transferase 1A (CPT1A) at transcriptional level by supressing ERK/PPAR pathway. Our findings suggest that the TGF-ß/SDPR/CPT1A axis play an important role in the fatty acid oxidation of gastric cancer, and provides a new insight into the crosstalk of tumour microenvironments and metabolism reprogramming and suggest that strategies to intervene the fatty acid metabolism may therapy gastric cancer metastasis.

Multiple mycotoxins in commonly used edible oils: Occurrence and evaluation of potential health risks.

In this study, the contamination of 51 mycotoxins in 416 edible oils were determined by UPLC-MS/MS. Totally, twenty-four mycotoxins were detected and nearly half of the samples (46.9%, n = 195) were contaminated simultaneously with six to nine kinds of mycotoxins. The predominant mycotoxins and contamination characteristics varied depending on the type of oils. More specifically, four enniatins, alternariol monomethyl ether (AME) and zearalenone were the most frequent combination. Overall, peanut and sesame oils (10.7-11.7 mycotoxins on average) were found to be the most contaminated matrices whereas camellia and sunflower seed oils (1.8-2.7 species) were the opposite. Dietary exposure risks of mycotoxins were acceptable in most cases, however, the ingestion of aflatoxins (especially aflatoxin B1) through peanut and sesame oil (margin of exposure: 239.4-386.3 < 10000) exceeded the acceptable carcinogenic risk level. Meanwhile, the risks of cumulative ingestion through the food chain should be of great concern, especially sterigmatocystin, ochratoxin A, AME and zearalenone.

Stress granules: functions and mechanisms in cancer.

Stress granules (SGs) are non-enveloped structures formed primarily via protein and RNA aggregation under various stress conditions, including hypoxia and viral infection, as well as oxidative, osmotic, and heat-shock stress. SGs assembly is a highly conserved cellular strategy to reduce stress-related damage and promote cell survival. At present, the composition and dynamics of SGs are well understood; however, data on the functions and related mechanisms of SGs are limited. In recent years, SGs have continued to attract attention as emerging players in cancer research. Intriguingly, SGs regulate the biological behavior of tumors by participating in various tumor-associated signaling pathways, including cell proliferation, apoptosis, invasion and metastasis, chemotherapy resistance, radiotherapy resistance, and immune escape. This review discusses the roles and mechanisms of SGs in tumors and suggests novel directions for cancer treatment.

Development and validation of a radiopathomic model for predicting pathologic complete response to neoadjuvant chemotherapy in breast cancer patients.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has become the standard therapeutic option for early high-risk and locally advanced breast cancer. However, response rates to NAC vary between patients, causing delays in treatment and affecting the prognosis for patients who do not sensitive to NAC. MATERIALS AND METHODS: In total, 211 breast cancer patients who completed NAC (training set: 155, validation set: 56) were retrospectively enrolled. we developed a deep learning radiopathomics model(DLRPM) by Support Vector Machine (SVM) method based on clinicopathological features, radiomics features, and pathomics features. Furthermore, we comprehensively validated the DLRPM and compared it with three single-scale signatures. RESULTS: DLRPM had favourable performance for the prediction of pathological complete response (pCR) in the training set (AUC 0.933[95% CI 0.895-0.971]), and in the validation set (AUC 0.927 [95% CI 0.858-0.996]). In the validation set, DLRPM also significantly outperformed the radiomics signature (AUC 0.821[0.700-0.942]), pathomics signature (AUC 0.766[0.629-0.903]), and deep learning pathomics signature (AUC 0.804[0.683-0.925]) (all p < 0.05). The calibration curves and decision curve analysis also indicated the clinical effectiveness of the DLRPM. CONCLUSIONS: DLRPM can help clinicians accurately predict the efficacy of NAC before treatment, highlighting the potential of artificial intelligence to improve the personalized treatment of breast cancer patients.

[Cloning, identification and functional analysis of the goat transcription factor c-fos].

C-fos is a transcription factor that plays an important role in cell proliferation, differentiation and tumor formation. The aim of this study was to clone the goat c-fos gene, clarify its biological characteristics, and further reveal its regulatory role in the differentiation of goat subcutaneous adipocytes. We cloned the c-fos gene from subcutaneous adipose tissue of Jianzhou big-eared goats by reverse transcription-polymerase chain reaction (RT-PCR) and analyzed its biological characteristics. Using real-time quantitative PCR (qPCR), we detected the expression of c-fos gene in the heart, liver, spleen, lung, kidney, subcutaneous fat, longissimus dorsi and subcutaneous adipocytes of goat upon induced differentiation for 0 h to 120 h. The goat overexpression vector pEGFP-c-fos was constructed and transfected into the subcutaneous preadipocytes for induced differentiation. The morphological changes of lipid droplet accumulation were observed by oil red O staining and bodipy staining. Furthermore, qPCR was used to test the relative mRNA level of the c-fos overexpression on adipogenic differentiation marker genes. The results showed that the cloned goat c-fos gene was 1 477 bp in length, in which the coding sequence was 1 143 bp, encoding a protein of 380 amino acids. Protein structure analysis showed that goat FOS protein has a basic leucine zipper structure, and subcellular localization prediction suggested that it was mainly distributed in the nucleus. The relative expression level of c-fos was higher in the subcutaneous adipose tissue of goats (P < 0.05), and the expression level of c-fos was significantly increased upon induced differentiation of subcutaneous preadipocyte for 48 h (P < 0.01). Overexpression of c-fos significantly inhibited the lipid droplets formation in goat subcutaneous adipocytes, significantly decreased the relative expression levels of the AP2 and C/EBPß lipogenic marker genes (P < 0.01). Moreover, AP2 and C/EBPß promoter are predicted to have multiple binding sites. In conclusion, the results indicated that c-fos gene was a negative regulatory factor of subcutaneous adipocyte differentiation in goats, and it might regulate the expression of AP2 and C/EBPß gene expression.

miR-199a-3p promotes gastric cancer progression by promoting its stemness potential via DDR2 mediation.

BACKGROUND: Peritoneal metastasis (PM) is an independent prognostic factor in gastric cancer (GC), however, the underlying mechanisms of PM occurrence remain unclear. METHOD: The roles of DDR2 were investigated in GC and its potential relationship to PM, and orthotopic implants into nude mice were performed to assess the biological effects of DDR2 on PM. RESULTS: Herein, DDR2 level is more significantly observed to elevate in PM lesion than the primary lesion. GC with DDR2-high expression evokes a worse overall survival (OS) in TCGA, similar results of the gloomy OS with high DDR2 levels are clarified via the stratifying stage of TNM. The conspicuously increased expression of DDR2 was found in GC cell lines, luciferase reporter assays verified that miR-199a-3p directly targeted DDR2 gene, which was correlated to tumor progression. We ulteriorly observed DDR2 participated in GC stemness maintenance via mediating pluripotency factor SOX2 expression and implicated in autophagy and DNA damage of cancer stem cells (CSCs). In particular, DDR2 dominated EMT programming through recruiting NFATc1-SOX2 complex to Snai1 in governing cell progression, controlling by DDR2-mTOR-SOX2 axis in SGC-7901 CSCs. Furthermore, DDR2 promoted the tumor peritoneal dissemination in gastric xenograft mouse model. CONCLUSION: Phenotype screens and disseminated verifications incriminating in GC exposit the miR-199a-3p-DDR2-mTOR-SOX2 axis as a clinically actionable target for tumor PM progression. The herein-reported DDR2-based underlying axis in GC represents novel and potent tools for studying the mechanisms of PM.

Effects of PD-1 inhibitor combined with anti-angiogenic drugs on efficacy and immune function of non-small cell lung cancer.

OBJECTIVE: To investigate the effect of PD-1 inhibitor combined with anti-angiogenic drugs on the therapeutic efficacy and immune function of patients with non-small cell lung cancer (NSCLC). METHODS: Clinical data of 60 NSCLC patients who admitted to a regional Hospital of Traditional Chinese Medicine from May 2020 to August 2021 were analyzed retrospectively. Among them, 23 patients who received sintilimab and anlotinib were in group A, 20 patients treated with sintilimab were in group B, and 17 patients intervened by anlotinib alone were in group C. The changes of clinical efficacy, objective remission rate (ORR) and disease control rate (DCR) among the three groups were compared. The levels of cluster of differentiation 4 (CD4)+, cluster of differentiation 8 (CD8)+ and CD4+/CD8+ were assessed before and 6 weeks after treatment. The progression-free survival (PFS) was calculated and the prognostic factors were analyzed by Cox regression. The adverse reactions of immunotherapy in three groups were evaluated. RESULTS: There was no obvious difference in ORR among the three groups (P>0.05). The proportion of DCR in group A was dramatically higher than that in group B and C (P<0.05). After treatment, the CD4+ and CD4+/CD8+ levels were markedly higher, while the CD8+ level in group A was lower in group A than those in the other two groups (P<0.05). There was no obvious difference in the incidence of immune-related adverse reactions among the three groups (P>0.05). The median PFS of patients was 6.03 months. Cox regression analysis revealed that Eastern Cooperative Oncology Group score, tumor metastasis and treatment regimen were independent prognostic factors affecting PFS. CONCLUSION: Sintilimab combined with anlotinib can effectively improve DCR and prolong PFS in NSCLC patients, and this regimen does not increase immune-related adverse reactions during treatment.

Ambient fine particulate matter exposures and human early placental inflammation.

The effect of fine particulate matter (PM2.5) on human early maternal-fetal interface is unknown. We explored the association between maternal exposure to ambient PM2.5 and inflammation in placental villus of 114 women with clinically recognized early pregnancy loss (CREPL) and 114 women with normal early pregnancy (NEP). Temporally-adjusted land use regression models were used to estimate maternal daily PM2.5 exposure during pregnancy. Villus interleukin-1beta (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were measured using multiplex cytokines detection platform. Single-day lag effect of PM2.5 exposure within ten days before early placental villus collection was estimated using multivariable linear regression model. Distributed lag and net cumulative effects of PM2.5 exposures within ten and 30 days before villus collection, as well as five single weeks during the periovulatory period, were estimated using distributed lag non-linear models. In all 228 subjects, after adjusting for group (CREPL or NEP), temporal confounders, and demographic characteristics, both single-day and distributed lag effects of PM2.5 exposure at lag 8 significantly increased villus IL-6; distributed lag effects of PM2.5 exposure in the first and second weeks before ovulation increased IL-1ß, and PM2.5 exposure in the third week after ovulation increased IL-6 and TNF-α. In CREPL, single-day lag effect significantly increased IL-1ß (at lag 1), IL-6 (at lag 8), and TNF-α (at lag 5); distributed lag effect increased IL-6 (at lag 4-lag 8) and TNF-α (at lag 4-lag 6); and cumulative effect within ten days before villus collection increased IL-6. There was no statistically significant cumulative effect in NEP. In summary, maternal PM2.5 exposure was associated with placental inflammation in human early pregnancy, particularly with increased villus IL-6 in CREPL. Whether maternal-fetal interface inflammation related to PM2.5 exposure during the periovulatory period or later contributes to CREPL or other adverse pregnancy outcomes requires further study.

Non-target metabolomics reveals the changes of small molecular substances in duck breast meat under different preservation time.

Poultry products are an essential animal source of protein for humans. Many factors could destroy the balance of the poultry production chain and cause an overstock of products, which need to be stored in the frozen storage warehouse for a long time. The long-term frozen storage may affect the quality of meat products. In this study, the changes of small molecular substances were revealed in duck meat during long-term storage using non-targeted metabolomics. The results showed that compared with fresh meat, even if the meat is stored under frozen storage conditions, the number of differential metabolites of frozen storage meat continues to increase with the prolongation of storage time, indicating that the meat composition has changed significantly with the storage time increased. With the increase in storage time, the nitrogen-containing small molecular compounds in duck meat increased (carnosine and anserine, aspartic acid, and tyrosine, 1H-indole-3-acetamide, 2-Hydroxyphenethylamine, 2-Naphylamine, allocystathionine, and O-phosphoethanolamine), the nucleotides decomposition process strengthened (IMP and AMP, GMP and UMP), and the content of organic acid increased (5-hydroxy indole acetic acid, 5-hydroxypentanoic acid and phenylacetate, taurine) and carbohydrate (1-O-sinapoyl-beta-d-glucose, 4-O-beta-d-glucopyranosyl-d-mannose, and alpha-d-glucose). These small molecular substances can be used as biomarkers to detect long-term stored duck meat deterioration. KEGG enrichment analysis showed that protein catabolism, nucleotide catabolism, fat decomposition and oxidation, and carbohydrate decomposition were the main metabolic processes of meat deterioration during the long-term storage of duck meat. In addition, Non-target metabolome technology is a powerful tool to reveal the meat deterioration process during long-term storage systematically. This study provided a reference for optimizing domestic poultry meat storage methods and ensuring food safety.