Myositis Autoantibody Profiles and Clinical Significance in Patients with Inflammatory Myopathies in Southwest China.

BACKGROUND: The purpose of this study is to analyze the distribution of myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs) in patients with idiopathic inflammatory myopathies (IIMs) in southwest China and to explore the relevance between each subtype, each clinical feature, and to explore the relevance between the laboratory indexes. METHODS: For this study, 200 patients with IIMs were tested for myositis autoantibodies. Clinical manifestations and laboratory metrics were collected and the correlations between autoantibodies and clinical phenotypes were analyzed. RESULTS: MSAs were found in 73.5% of the patients. The most frequently MSAs were anti-MDA5 (26.8%), followed by anti-ARS (18.5%). Anti-Ro52 was the most prevalent in MAAs (46.2%). Interstitial lung disease (ILD) and arthralgia were more frequent in anti-MDA5 and anti-Jo-1 positive groups (each p < 0.05). Anti-TIF1-γ and anti-NXP2 were associated with dysphagia (each p < 0.05). Different antibody subtypes were associated with laboratory indicators of response to muscle damage and immune status. Logistic regression showed that anti-MDA5 and anti-Jo-1 were independent risk factors for ILD (OR = 4.542, p = 0.004; OR = 4.290, p = 0.018, respectively) and arthralgia (OR = 7.856, p = 0.000; OR = 5.731, p = 0.004, respectively), whereas anti-TIF1-γ and anti-NXP2 were independent risk factors for dysphagia (OR = 4.521, p = 0.009; OR = 6.889, p = 0.017, respectively). CONCLUSIONS: Different antibody subtypes were associated with specific clinical features. Anti-MDA5 and anti-Jo-1 were independent risk factors for ILD and arthralgia. Anti-TIF1-γ and anti-NXP2 were independent risk factors for dysphagia.

Long-term risks of cardiovascular death in a population-based cohort of 1,141,675 older patients with cancer.

BACKGROUND: previous studies have focused on the risk of cardiovascular disease (CVD)-related death in individual cancers, adolescents or all cancers. OBJECTIVE: to evaluate the risk of CVD-related death in older patients with cancer. METHODS: older patients with cancer (over 65 years) of 16 cancers diagnosed between 1975 and 2018 were screened out from the Surveillance, Epidemiology and End Results program. The proportion of deaths, competing risk regression models, standardized mortality ratios (SMRs) and absolute excess risks (AERs) were used to assess the risk of CVD-related death. RESULTS: this study included 1,141,675 older patients (median follow-up: 13.5 years). Of the 16 individual cancers, the risk of CVD death exceeded primary neoplasm death in older patients with cancers of the breast, endometrium, vulva, prostate gland, penis and melanoma of the skin over time (high competing risk group). Compared to the general older population, older patients with cancer had higher SMR and AER of CVD-related death (SMR: 1.58-4.23; AER: 21.16-365.89), heart disease-related death (SMR: 1.14-4.16; AER: 16.29-301.68) and cerebrovascular disease-related death (SMR: 1.11-4.66; AER: 3.02-72.43), with the SMR trend varying with CVD-related death competing risk classifications. The risk of CVD-related death in the high-competing risk group was higher than in the low-competing risk group. CONCLUSIONS: for older patients with cancer, six of 16 individual cancers, including breast, endometrium, vulva, prostate gland, penis and melanoma of the skin was at high risk of CVD-related death. Management for long-term cardiovascular risk in older patients with cancer is needed.

The Value of Hematological Indexes in Evaluating the Risk of Hip Involvement in Patients with Ankylosing Spondylitis.

BACKGROUND: The goal was to explore the value of neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) in evaluating the risk of hip involvement in patients with ankylosing spondylitis (AS). METHODS: The study included 188 AS patients (Based on BASRI-hip score, patients were classified as hip involvement group (BASRI-hip ≥ 2; n = 84) and non-hip involvement group (BASRI-hip ≤ 1; n = 104), 173 patients with osteoarthritis (OA) of the hip and 181 age- and gender-matched healthy controls (HCs). The value of NLR and MLR in different groups were observed. RESULTS: The NLR and MLR in AS patients with hip involvement were significantly higher than in the non-hip involvement group (p < 0.05), and patients with moderate and severe hip involvement were significantly higher than mild hip involvement (p < 0.05). The analysis of receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) of NLR, MLR, and the combination of NLR and MLR for AS patients with hip involvement were 0.817, 0.840, and 0.863, respectively (each p < 0.001) and the AUC values for predicting AS patients with moderate and severe hip involvement in patients with AS were 0.862, 0.847, and 0.889, respectively (each p < 0.001), which showed their significance in clinical settings. Also, NLR and MLR of AS patients were positively correlated with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) (each p < 0.01). CONCLUSIONS: Therefore, NLR and MLR may be diagnostic hematological indexes in evaluating AS patients with hip involvement, particularly in the patients with moderate and severe hip involvement and higher diagnostic efficiency when combined analysis is done.

ALAS1 associated with goat kidding number trait was regulated by the transcription factor ASCL2 to affect granulosa cell proliferation.

ALAS1 is a member of the α-oxoamine synthase family, which is the first rate-limiting enzyme for heme synthesis and is important for maintaining intracellular heme levels. In the ovary, ALAS1 is associated with the regulation of ovulation-related mitochondrial P450 cytochromes, steroid metabolism, and steroid hormone production. However, there are few studies on the relationship between ALAS1 and reproductive traits in goats. In this study, a mutation located in the promoter region of ALAS1 (g.48791372C>A) was found to be significantly (p < 0.05) associated with the kidding number of Yunshang black goats. Specifically, the mean kidding number in the first three litters and the kidding numbers of all three litters were significantly (p < 0.05) higher in individuals with the CA genotype or AA genotype than in those with the CC genotype. To further investigate the regulatory mechanism of ALAS1, the expression of ALAS1 in goat ovarian tissues with different genotypes was verified by real-time quantitative PCR. The results showed that the expression of ALAS1 was significantly higher in the ovaries of individuals with AA genotype than those with AC and CC genotypes (p < 0.01), and the expression trend of transcription factor ASCL2 was consistent with ALAS1. Additionally, the ALAS1 g.48791372C>A mutation created a new binding site for the transcription factor ASCL2. The luciferase activity assay indicated that the mutation increased the promoter activity of ALAS1. Overexpression of the transcription factor ASCL2 induced increased expression of ALAS1 in goat granulosa cells (p < 0.05). The opposite trend was shown for the inhibition of ASCL2 expression. The results of real-time quantitative PCR, EdU and Cell Counting Kit-8 assays indicated that the transcription factor ASCL2 increased the proliferation of goat granulosa cells by mediating the expression of ALAS1. In conclusion, the transcription factor ASCL2 positively regulated the transcriptional activity and expression levels of ALAS1, altering granulosa cell proliferation and the kidding number in goats.

Association between KRAS gene polymorphisms and genetic susceptibility to breast cancer in a Chinese population.

OBJECTIVE: The KRAS gene has a pathophysiological role in the development of many cancers. This study aims to investigate the relationship between KRAS polymorphisms and genetic susceptibility to breast cancer. METHOD: The rs712, rs12587 and rs9266 gene loci in the KRAS gene of 421 subjects (141 breast cancer patients, 141 benign breast tumours and 139 healthy controls) were analysed by the polymerase chain reaction and SNaPshot sequencing. Transcriptomic information on KRAS and corresponding clinical information was downloaded from the TCGA and GTEx databases. Differences in KRAS expression between breast cancer tissues and control tissues were analysed. RESULTS: We found no significant association between KRAS rs712 and rs12587 locus gene polymorphisms and an increased risk of developing benign breast tumours and breast cancer (p > 0.05). The KRAS rs9266 locus mutation heterozygous model CT and dominant model CT + TT were significantly associated with an increased risk of breast cancer (both p < 0.05). In addition, the TAT haplotype was expressed at an increased frequency, and the GAC haplotype was expressed at a reduced frequency in breast cancer compared with controls (both p < 0.05). We found that KRAS was over expressed in breast cancer tumour tissues compared with the control tissues (p < 0.0001). CONCLUSION: The KRAS rs9266 gene polymorphism and the TAT haplotype may be associated with an increased risk of breast cancer in Chinese women. The GAC haplotype may be a protective factor against breast cancer.

Rapid PFOS mineralization with peroxydisulfate activation process mediated by N modified Fe-based catalyst.

As the cheap and efficient catalysts, the iron-based catalysts have been considered as one of the most promising catalysts for peroxydisulfate (PDS) activation and the development of high-performance iron-based catalysts are attracting growing attentions. In this work, a magnetic Fe-based catalysts (Fe/NC-1000) was obtained by using Fe modified ZIF-8 as the precursor and used to activate the PDS for the degradation of perfluorooctane sulphonate (PFOS). Morphology and structure analysis showed that the resulted Fe/NC-1000 catalyst was displayed porous spheres (40-60 nm) and mainly composed of Fe0, FeNx and carbon. When Fe/NC-1000 was employed to activate the PDS (0.1 g/L of catalyst dosage, 0.5 g/L of PDS dosage and at initial pH of 4.6), the Fe/NC-1000/PDS system exhibited excellent efficiency (97.9 ± 0.1) % for PFOS (10 mg/L) degradation within 30 min. The quenching tests and EPR results revealed that the Fe/NC-1000/PDS system degraded PFOS primarily through singlet oxygen (1O2) evolution and electron-transfer process. Besides, based on the degradation byproducts determined by LC-MS-MS, the PFOS first occurred de-sulfonation to form PFOA, and then the resulted PFOA underwent stepwise defluorination in the Fe/NC-1000/PDS system. Density Functional Theory (DFT) calculations and electrochemistry tests strongly confirmed that Fe/NC-1000 exhibited high electron transfer efficiency, resulting in promoted performance on activating PDS. Importantly, the results of Ecological Structure-Activity Relationship (ECOSAR) analysis showed that the intermediates were lowly toxic during the PFOS degradation, manifesting a green process for PFOS removal. This study would provide more understandings for the persulfate activation process mediated by Fe-based catalysts for Perfluorinated alkyl substances (PFAS) elimination.

Clinical significance of serum ferritin in patients with systemic sclerosis.

OBJECTIVE: The purpose of this study was to explore the clinical significance of serum ferritin (SF) in patients with systemic sclerosis (SSc). METHODS: The levels of SF were measured in 115 patients with SSc and 117 healthy controls (HCs). Clinical characteristics and laboratory indexes between the high ferritin SSc group and the normal ferritin SSc group were analyzed. RESULTS: The level of SF in SSc patients was significantly higher than that in HCs (319.78 [179, 554.33] ng/ml vs. 99 [49.03, 164.29] ng/ml, p < 0.01). Compared with the normal ferritin SSc group, the high ferritin SSc group was more likely to develop skin diffuse cutaneous SSc, fingertip arthralgia, and cardiac involvement. In addition, the levels of glutamine transaminase (GGT), alanine aminotransferase (ALT), creatine kinase (CK), creatine kinase isoenzyme-MB (CK-MB), lactate dehydrogenase (LD), immunoglobulin G (IgG), immunoglobulin A (IgA), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and the positive rate of anti-Scl70 antibody in the high ferritin SSc group were significantly higher (each p < 0.05). SF was positively correlated with GGT, ALT, CK, CK-MB, LD, IgA, CRP, and ESR (each p < 0.05). Multiple linear regression analysis showed that cardiac involvement, ALT, and ESR were independent influencing factors of SF in SSc. CONCLUSION: Our study shows that the level of SF in patients with SSc is increased, and the elevated SF is related to abnormal liver function, myocardial involvement, inflammatory status, and production of autoantibodies in SSc. Cardiac involvement, ALT, and ESR are independent factors affecting SF in SSc.

Integrated analyses of miRNA-mRNA expression profiles of ovaries reveal the crucial interaction networks that regulate the prolificacy of goats in the follicular phase.

BACKGROUND: Litter size is an important index of mammalian prolificacy and is determined by the ovulation rate. The ovary is a crucial organ for mammalian reproduction and is associated with follicular development, maturation and ovulation. However, prolificacy is influenced by multiple factors, and its molecular regulation in the follicular phase remains unclear. METHODS: Ten female goats with no significant differences in age and weight were randomly selected and divided into either the high-yielding group (n = 5, HF) or the low-yielding group (n = 5, LF). Ovarian tissues were collected from goats in the follicular phase and used to construct mRNA and miRNA sequencing libraries to analyze transcriptomic variation between high- and low-yield Yunshang black goats. Furthermore, integrated analysis of the differentially expressed (DE) miRNA-mRNA pairs was performed based on their correlation. The STRING database was used to construct a PPI network of the DEGs. RT-qPCR was used to validate the results of the predicted miRNA-mRNA pairs. Luciferase analysis and CCK-8 assay were used to detect the function of the miRNA-mRNA pairs and the proliferation of goat granulosa cells (GCs). RESULTS: A total of 43,779 known transcripts, 23,067 novel transcripts, 424 known miRNAs and 656 novel miRNAs were identified by RNA-seq in the ovaries from both groups. Through correlation analysis of the miRNA and mRNA expression profiles, 263 negatively correlated miRNA-mRNA pairs were identified in the LF vs. HF comparison. Annotation analysis of the DE miRNA-mRNA pairs identified targets related to biological processes such as "estrogen receptor binding (GO:0030331)", "oogenesis (GO:0048477)", "ovulation cycle process (GO:0022602)" and "ovarian follicle development (GO:0001541)". Subsequently, five KEGG pathways (oocyte meiosis, progesterone-mediated oocyte maturation, GnRH signaling pathway, Notch signaling pathway and TGF-ß signaling pathway) were identified in the interaction network related to follicular development, and a PPI network was also constructed. In the network, we found that CDK12, FAM91A1, PGS1, SERTM1, SPAG5, SYNE1, TMEM14A, WNT4, and CAMK2G were the key nodes, all of which were targets of the DE miRNAs. The PPI analysis showed that there was a clear interaction among the CAMK2G, SERTM1, TMEM14A, CDK12, SYNE1 and WNT4 genes. In addition, dual luciferase reporter and CCK-8 assays confirmed that miR-1271-3p suppressed the proliferation of GCs by inhibiting the expression of TXLNA. CONCLUSIONS: These results increase the understanding of the molecular mechanisms underlying goat prolificacy. These results also provide a basis for studying interactions between genes and miRNAs, as well as the functions of the pathways in ovarian tissues involved in goat prolificacy in the follicular phase.

The Significance of Blood Index and Biochemistry Index in Patients with Rheumatoid Arthritis.

BACKGROUND: The aim of this study is to demonstrate the clinical significance of the platelet-to-lymphocyte ratio (PLR) and the ratio of aspartate aminotransferase (AST) to alanine aminotransferase (ALT) in patients with rheumatoid arthritis (RA). METHODS: A total of 215 patients with RA, 115 patients with osteoarthritis (OA), and 303 healthy controls (HCs) were included in this study. Data on the AST and ALT levels were collected from liver function test reports, and data on the number of platelets and lymphocytes were obtained from a routine blood analysis. Moreover, all the laboratory parameters of patients with RA, patients with OA, and HCs were retrospectively analyzed. RESULTS: The results obtained in this study showed that patients with RA had the highest PLR and AST/ALT ratio, whereas HCs had the lowest ratios (p < 0.05). Receiver operating characteristic (ROC) analysis showed that PLR + AST/ALT can produce high sensitivity and moderate specificity, distinguishing patients with RA from HCs, with a sensitivity of 91.1%, specificity of 75.3%, and area under the ROC curve (AUC) of 0.907. Spearman's analysis showed the PLR is negatively correlated with the erythrocyte sedimentation rate and C-reactive protein levels (p < 0.005). CONCLUSIONS: Combined detection of PLR and AST/ALT is better than each indicator individually and can improve the diagnostic efficiency of RA.

The presence of synthetic polymers in the maturation medium affects the cryotolerance and developmental capacity after parthenogenic activation of vitrified goat oocytes.

The purpose of this present study is to assess if addition of the synthetic polymers in maturation medium can influence cryotolerance and subsequently embryonic development of mammalian oocytes. We examined the roles of two polymers, including polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP), on in vitro maturation (IVM), embryonic developmental capacity, and cryotolerance of goat oocytes. The present study includes two parts. At first, goat cumulus-oocyte complexes (COCs) were matured in a medium supplemented with 10% fetal bovine serum (FBS), 3 mg/ml PVP, or 1 mg/ml PVA, respectively. Data of oocyte with first polar body, cleavage, and blastocyst following parthenogenetic activation (PA) were recorded. Secondly, after maturation in the above medium, oocytes were vitrified using the Cryotop technique and then the morphology, cleavage and blastocyst formation of vitrified oocytes have been checked. The results demonstrated that the adding of PVP or PVA in maturation medium can't affect IVM of goat oocytes in comparison with FBS, as concern cumulus cell expansion, first polar body formation, and embryonic development. Additionally, without plunging into liquid nitrogen, only exposure to the vitrification and warming solutions cannot also influence the quality of oocytes, in terms of morphology, cleavage, and blastocyst formation. However, after IVM with synthetic polymers and vitrification, the ratio of oocytes with standard morphology in PVP or PVA group was only 59.47% ± 3.56% or 54.86% ± 5.19%, respectively, and was significantly less than that in the FBS group (89.37% ± 4.52%, P < 0.05). Furthermore, the cleavage ratio of oocytes in PVP or PVA group was 37.41% ± 4.17% or 27.71% ± 3.91% and was considerably less than that in the FBS group (64.97% ± 4.69%, P < 0.05). In addition, the cleavage ratio in PVP group was statistically higher than that in PVA group (P < 0.05). In terms of blastocyst development, a significant difference was observed between the synthetic polymer group and the FBS group (24.96% ± 3.62%, P < 0.05). However, the blastocyst ratio in the PVA group (7.51% ± 1.68%) was statistically less than the PVP groups (13.20% ± 4.59%, P < 0.05) and the FBS group (P < 0.05). In conclusion, two potential serum replacements, either PVP or PVA, can support IVM and embryonic development of goat oocytes at the concentration used in this study. But IVM with synthetic polymers supplemented to maturation medium may reduce the cryotolerance of oocytes. Additionally, the supportive function of PVP on embryonic development of vitrified oocytes might be better than that of PVA.

A germline mutation in Rab43 gene identified from a cancer family predisposes to a hereditary liver-colon cancer syndrome.

BACKGROUND: Hereditary cancer syndromes have inherited germline mutations which predispose to benign and malignant tumors. Understanding of the molecular causes in hereditary cancer syndromes has advanced cancer treatment and prevention. However, the causal genes of many hereditary cancer syndromes remain unknown due to their rare frequency of mutation. METHODS: A large Chinese family with a history of hereditary liver-colon cancer syndrome was studied. The genomic DNA was extracted from the blood samples of involved family members, whole-exome sequencing was performed to identify genetic variants. Functional validation of a candidate variant was carried out using gene expression, gene knockout and immunohistochemistry. RESULTS: The whole-exome of the proband diagnosed with colon cancer was sequenced in comparison with his mother. A total of 13 SNVs and 16 InDels were identified. Among these variants, we focused on a mutation of Rab43 gene, a GTPase family member involving in protein trafficking, for further validation. Sanger DNA sequencing confirmed a mutation (c: 128810106C > T, p: A158T) occurred in one allele of Rab43 gene from the proband, that heterozygous mutation also was verified in the genome of the proband's deceased father with liver cancer, but not in his healthy mother and sister. Ectopic expression of the Rab43 A158T mutant in Huh7 cells led to more enhanced cell growth, proliferation and migration compared to the expression of wild type Rab43. Conversely, knockout of Rab43 in HepG2 cells resulted in slow cell growth and multiple nuclei formation and impaired activation of Akt. Finally, a positive correlation between the expression levels of Rab43 protein and cancer development in that family was confirmed. CONCLUSIONS: A germline mutation of Rab43 gene is identified to be associated with the onset of a familial liver-colon cancer syndrome. Our finding points to a potential role of protein trafficking in the tumorigenesis of the familial cancer syndrome, and helps the genetic counseling to the affected family members.

Case report: Envafolimab combined with Endostar in the treatment of advanced non-small cell lung cancer with malignant pleural effusion.

Malignant pleural effusion (MPE) is one of the common complications of lung cancer. The quality of life and prognoses for MPE patients are significantly compromised. Controlling the production of MPE can relieve patients' symptoms, improve their quality of life, and prolong their survival. This article presents a case of advanced non-small cell lung cancer (NSCLC) with MPE and negative driver genes. The patient received envafolimab and Endostar in combination, resulting in a complete reduction of MPE and durable clinical benefits. The exploratory use of this treatment method improved the quality of life of this patient and has the potential to prolong the survival of this patient.

A Population-Based and Propensity Score-Matched Investigation of the Occurrence, Management, and Prognosis of Anal Mucinous Adenocarcinoma Patients.

BACKGROUND: Anal mucinous adenocarcinoma (AMAC) is an extremely rare form of anal cancer. Our objective was to examine the incidence, management, and prognostic factors of AMAC. MATERIALS AND METHODS: We analyzed age-adjusted incidence rates (AAI) over time and compared the prognosis of AMAC with anal squamous cell carcinoma (ASCC) and adenocarcinoma (AAC) using propensity score matching (PSM) and Kaplan-Meier analysis. Patients were classified based on summary stage and treatments to determine cancer-specific survival (CSS). RESULTS: AAI of AMAC fluctuated within a narrow range (0.082-0.237 per million person-years) from 2000 to 2018. AMAC had a slight non-significant trend of worse prognosis than ASCC (p=0.348) and a better prognosis than AAC (p<0.01). Females made up a larger proportion of patients diagnosed with the distant disease (p<0.05) and unmarried (p<0.05), and somewhat less probably to need surgical removal (p<0.01) and radiotherapy (p<0.01). Elderly patients, with regional stage, distant-stage disease, no surgery tended to have lower rates of survival (all p<0.05). Localized stage was associated with better prognosis (p<0.05). Surgery was associated with a tendency towards better survival (p=0.095). CONCLUSIONS: The incidence of AMAC is consistently low. AMAC demonstrates a more favorable prognosis compared to typical AAC and a slightly worse prognosis compared to ASCC. Females with AMAC were less likely to undergo surgical removal or receive radiotherapy. AMAC exhibits a low incidence yet favorable prognosis compared to typical AAC and slightly worse compared to ASCC. Elderly age is associated with poorer prognosis, while localized stage indicates better prognosis. Surgery demonstrates a trend towards improved survival.

Performance and mechanistic studies of rapid atenolol degradation through peroxymonosulfate activation by V, Co, and bamboo carbon catalyst.

Developing the Co-based catalysts with high reactivity for the sulfate radical (SO4-·)-based advanced oxidation processes (SR-AOPs) has been attracting numerous attentions. To improve the peroxymonosulfate (PMS) activation process, a novel Co-based catalyst simultaneously modified by bamboo carbon (BC) and vanadium (V@CoO-BC) was fabricated through a simple solvothermal method. The atenolol (ATL) degradation experiments in V@CoO-BC/PMS system showed that the obtained V@CoO-BC exhibited much higher performance on PMS activation than pure CoO, and the V@CoO-BC/PMS system could fully degrade ATL within 5 min via the destruction of both radicals (SO4-· and O2-··) and non-radicals (1O2). The quenching experiments and electrochemical tests revealed that the enhancing mechanism of bamboo carbon and V modification involved four aspects: (i) promoting the PMS and Co ion adsorption on the surface of V@CoO-BC; (ii) enhancing the electron transfer efficiency between V@CoO-BC and PMS; (iii) activating PMS with V3+ species; (iv) accelerating the circulation of Co2+ and Co3+, leading to the enhanced yield of reactive oxygen species (ROS). Furthermore, the V@CoO-BC/PMS system also exhibited satisfactory stability under broad pH (3-9) and good efficiency in the presence of co-existing components (HCO3-, NO3-, Cl-, and HA) in water. This study provides new insights to designing high-performance, environment-friendly bimetal catalysts and some basis for the remediation of antibiotic contaminants with SR-AOPs.

Association of litter size with the ruminal microbiome structure and metabolomic profile in goats.

The Yunshang black goat is a renowned mutton specialist breed mainly originating from China that has excellent breeding ability with varying litter sizes. Litter size is an important factor in the economics of goat farming. However, ruminal microbiome structure might be directly or indirectly regulated by pregnancy-associated factors, including litter sizes. Therefore, the current experiment aimed to evaluate the association of different litter sizes (low versus high) with ruminal microbiome structure by 16S rRNA gene sequencing and metabolomic profiling of Yunshang black does. A total of twenty does of the Yunshang Black breed, approximately aged between 3 and 4 years, were grouped (n = 10 goats/group) into low (D-l) and high (D-h) litter groups according to their litter size (the lower group has ≤ 2 kids/litter and the high group has ≧ 3 kids/litter, respectively). All goats were sacrificed, and collected ruminal fluid samples were subjected to 16S rRNA sequencing and LC-MS/MC Analysis for ruminal microbiome and metabolomic profiling respectively. According to PCoA analysis, the ruminal microbiota was not significantly changed by the litter sizes among the groups. The Firmicutes and Bacteroidetes were the most dominant phyla, with an abundance of 55.34% and 39.62%, respectively. However, Ruminococcaceae_UCG-009, Sediminispirochaeta, and Paraprevotella were significantly increased in the D-h group, whereas Ruminococcaceae_UCG-010 and Howardella were found to be significantly decreased in the D-l group. The metabolic profiling analysis revealed that litter size impacts metabolites as 29 and 50 metabolites in positive and negative ionic modes respectively had significant differences in their regulation. From them, 16 and 24 metabolites of the D-h group were significantly down-regulated in the positive ionic mode, while 26 metabolites were up-regulated in the negative ionic mode for the same group. The most vibrant identified metabolites, including methyl linoleate, acetylursolic acid, O-desmethyl venlafaxine glucuronide, melanostatin, and arginyl-hydroxyproline, are involved in multiple biochemical processes relevant to rumen roles. The identified differential metabolites were significantly enriched in 12 different pathways including protein digestion and absorption, glycerophospholipid metabolism, regulation of lipolysis in adipocytes, and the mTOR signaling pathway. Spearman's correlation coefficient analysis indicated that metabolites and microbial communities were tightly correlated and had significant differences between the D-l and D-h groups. Based on the results, the present study provides novel insights into the regulation mechanisms of the rumen microbiota and metabolomic profiles leading to different fertility in goats, which can give breeders some enlightenments to further improve the fertility of Yunshang Black goats.

A Convenient and Effective Preoxygenation Technique for Prolonging Deep Inspiration Breath-Hold Duration With a Venturi Mask With a 50% Oxygen Concentration.

PURPOSE: Voluntary deep inspiration breath-hold (DIBH) is commonly used in radiation therapy (RT), but the short duration of a single breath-hold, estimated to be around 20 to 40 seconds, is a limitation. This prospective study aimed to assess the feasibility and safety of using a simple preoxygenation technique with a Venturi mask to prolong voluntary DIBH. METHODS AND MATERIALS: The study included 33 healthy volunteers and 21 RT patients. Preoxygenation was performed using a Venturi mask with a 50% oxygen concentration. Paired t tests compared the duration of a single DIBH in room air and after 5, 15, and 30 minutes of preoxygenation in healthy volunteers. Sustainability of breath-hold and tolerability of heart rate and blood pressure were assessed for multiple DIBH durations in both volunteers and patients. RESULTS: In healthy volunteers, a 15-minute preoxygenation significantly prolonged the duration of a single DIBH by 24.95 seconds compared with 5-minute preoxygenation (89 ± 27.76 vs 113.95 ± 30.63 seconds; P < .001); although there was a statistically significant increase in DIBH duration after 30-minute preoxygenation, it was only extended by 4.95 seconds compared with 15-minute preoxygenation (113.95 ± 30.63 vs 118.9 ± 29.77 seconds; P < .01). After 15-minute preoxygenation, a single DIBH lasted over 100 seconds in healthy volunteers and over 80 seconds in RT patients, with no significant differences among 6 consecutive cycles of DIBH. Furthermore, there were no significant differences in heart rate or blood pressure after DIBHs, including DIBH in room air and 6 consecutive DIBHs after 15-minute preoxygenation (all P > .05). CONCLUSIONS: Preoxygenation with a 50% oxygen concentration for 15 minutes effectively prolongs the duration of 6 cycles of DIBH both in healthy volunteers and RT patients. The utilization of a Venturi mask to deliver 50% oxygen concentration provides a solution characterized by its convenience, good tolerability, and effectiveness.

Long-term and short-term cardiovascular disease mortality among patients of 21 non-metastatic cancers.

INTRODUCTION: Previous studies on cardiovascular disease (CVD) death risk in cancer patients mostly focused on overall cancer, age subgroups and single cancers. OBJECTIVES: To assess the CVD death risk in non-metastatic cancer patients at 21 cancer sites. METHODS: A total of 1,672,561 non-metastatic cancer patients from Surveillance, Epidemiology, and End Results (SEER) datebase (1975-2018) were included in this population-based study, with a median follow-up of 12·7 years. The risk of CVD deaths was assessed using proportions, competing-risk regression, absolute excess risks (AERs), and standardized mortality ratios (SMRs). RESULTS: In patients with localized cancers, the proportion of CVD death and cumulative mortality from CVD in the high-competing risk group (14 of 21 unique cancers) surpassed that of primary neoplasm after cancer diagnosis. The SMRs and AERs of CVD were found higher in patients with non-metastatic cancer than the general US population (SMR 1·96 [95 %CI, 1·95-1·97]-19·85[95 %CI, 16·69-23·44]; AER 5·77-210·48), heart disease (SMR 1·94[95 %CI, 1·93-1·95]-19·25[95 %CI, 15·76-23·29]; AER 4·36-159·10) and cerebrovascular disease (SMR 2·05[95 %CI, 2·02-2·08]-24·71[95 %CI, 16·28-35·96]; AER 1·01-37·44) deaths. In the high-competing risk group, CVD-related SMR in patients with localized stage cancer increased with survival time but followed a reverse-dipper pattern in the low-competing risk group (7 of 21 cancers). The high-competing risk group had higher CVD-related death risks than the low-competing risk group. CONCLUSION: The CVD death risk in patients with non-metastatic cancer varied by cancer stage, site and survival time. The risk of CVD mortality is higher in 14 out of 21 localized cancers (high-competing cancers). Targeted strategies for CVD management in non-metastatic cancer patients are needed.

Multiparametric magnetic resonance imaging (MRI)-based radiomics model explained by the Shapley Additive exPlanations (SHAP) method for predicting complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a multicenter retrospective study.

Background: Predicting the response to neoadjuvant chemoradiotherapy (nCRT) before initiating treatment is essential for tailoring therapeutic strategies and monitoring prognosis in locally advanced rectal cancer (LARC). In this study, we aimed to develop and validate radiomic-based models to predict clinical and pathological complete responses (cCR and pCR, respectively) by incorporating the Shapley Additive exPlanations (SHAP) method for model interpretation. Methods: A total of 285 patients with complete pretreatment clinical characteristics and T1-weighted (T1W) and T2-weighted (T2W) magnetic resonance imaging (MRI) at 3 centers were retrospectively recruited. The features of tumor lesions were extracted by PyRadiomics and selected using least absolute shrinkage and selection operator (LASSO) algorithm. The selected features were used to build multilayer perceptron (MLP) models alone or combined with clinical features. Area under the receiver operating characteristic curve (AUC), decision curve, and calibration curve were applied to evaluate performance of models. The SHAP method was adopted to explain the prediction models. Results: The radiomic-based models all showed better performances than clinical models. The clinical-radiomic models showed the best differentiation on cCR and pCR with mean AUCs of 0.718 and 0.810 in the validation set, respectively. The decision curves of the clinical-radiomic models showed its values in clinical application. The SHAP method powerfully interpreted the prediction models both at a holistic and individual levels. Conclusions: Our study highlights that the radiomic-based prediction models have more excellent abilities than clinical models and can effectively predict treatment response and optimize therapeutic strategies for patients with LARCs.

Diagnostic and Prognostic Value of Monocyte-to-Lymphocyte Ratio and Red Cell Distribution Width to Lymphocyte Ratio in Primary Biliary Cholangitis.

OBJECTIVE: The aim of this study is to assess levels of monocyte-to-lymphocyte ratio and red cell distribution width-to-lymphocyte ratio in primary biliary cholangitis patients and excavate their clinical significance. METHODS: The levels of monocyte-to-lymphocyte ratio and red cell distribution width-to-lymphocyte ratio in the primary biliary cholangitis, autoimmune hepatitis, and healthy controls were compared, and correlations between monocyte-to-lymphocyte ratio, red cell distribution width-to-lymphocyte ratio, and Mayo score were analyzed. The area under the receiver operating characteristic curve was utilized to analyze the diagnostic value of monocyte-to-lymphocyte ratio and red cell distribution width-to-lymphocyte ratio for primary biliary cholangitis. RESULTS: Monocyte-to-lymphocyte ratio and red cell distribution width-to-lymphocyte ratio in primary biliary cholangitis were higher than they were in autoimmune hepatitis and healthy controls (each, P < .05). Area under the s of monocyte-to-lymphocyte ratio and red cell distribution width-to-lymphocyte ratio in diagnosis of primary biliary cholangitis were 0.821 and 0.797, respectively (each, P < .001). The combination of monocyte-to-lymphocyte ratio and red cell distribution width-to-lymphocyte ratio increased the diagnostic value of primary biliary cholangitis (area under the receiver operating characteristic curve = 0.868, P < .001). The correlation analysis showed that monocyte-to-lymphocyte ratio and red cell distribution width-to-lymphocyte ratio were positively correlated with Mayo score (r-MLR = 0.459, r-RLR = 0.522, P < .001 for each). Red cell distribution width-to-lymphocyte ratio was independently associated with Mayo score (P = .036) by multiple linear regression. In primary biliary cholangitis patients with Child-Pugh classification, monocyte-to-lymphocyte ratio and red cell distribution width-to-lymphocyte ratio levels in class B and class C were significantly higher than in class A (each, P < .05). CONCLUSION: Elevated levels of monocyte-to-lymphocyte ratio and red cell distribution width-to-lymphocyte ratio may prove to be useful markers for estimating the prognosis of primary biliary cholangitis, and the combined detection of monocyte-to-lymphocyte ratio and red cell distribution width-to-lymphocyte ratio has some clinical diagnostic value in patients with primary biliary cholangitis.

The clinical value of the monocyte to high-density lipoprotein cholesterol ratio and alkaline phosphatase-to-platelet ratio in primary biliary cholangitis.

This study aimed to evaluate the clinical value of the monocyte to high-density lipoprotein cholesterol ratio (MHR) and alkaline phosphatase-to-platelet ratio (APPR) in the diagnosis and prognosis of primary biliary cholangitis (PBC). Clinical and laboratory data were retrospectively collected and analyzed from 92 PBC patients, 92 patients with autoimmune hepatitis (AIH), 120 patients with chronic hepatitis B (CHB) and 124 healthy controls (HCs). We compared the levels of MHR and APPR among the groups with PBC, AIH, CHB and HCs, and analyzed the correlations between MHR and APPR with laboratory indices including aspartate aminotransferase platelet ratio index, fibrosis index based on 4 factors, and Mayo score in PBC. Receiver operating characteristic curves were used to analyze the diagnostic performance of MHR and APPR for PBC, AIH, and CHB, respectively. MHR and APPR were significantly increased in PBC group than that in AIH, CHB and HCs groups (each P < .05). MHR and APPR were significantly higher in Child class B|C than that in class A in PBC patients. (P < .01, P < .05, respectively). MHR and APPR were positively related to the Mayo score [R = 0.508 (P < .001), R = 0.295 (P = .008), respectively]. The area under the receiver operating characteristic curves of MHR and APPR in diagnosing PBC were 0.764 (95% confidence interval [CI]: 0.699-0.821, P < .001) and 0.952 (95% CI: 0.915-0.977, P < .001), respectively, and the area under the curve of the combination of both was 0.974 (95% CI: 0.941-0.991, P < .001). MHR and APPR may prove to be useful prognostic biomarkers for PBC, and the combination of MHR and APPR have some clinical diagnostic value of PBC.