Survival outcomes of neoadjuvant versus adjuvant therapy in patients with T1c, node-negative, human epidermal growth factor receptor 2-positive breast cancer: A Surveillance, Epidemiology, and End Results population-based study.

BACKGROUND: Persistent debates exist regarding the superiority of neoadjuvant therapy (NAT) over adjuvant therapy (AT) for patients with T1c, node-negative, human epidermal growth factor receptor 2-positive (HER2+) breast cancer, and relevant guidelines for these patients are lacking. METHODS: Data on patients with T1cN0M0-stage HER2+ breast cancer who received chemotherapy and surgery were extracted from 2010 to 2020 from the Surveillance, Epidemiology, and End Results database. Propensity score matching (PSM) was used to create well-balanced cohorts for the NAT and AT groups. Kaplan-Meier (KM) analysis and Cox proportional hazards models were used to assess the differences between NAT and AT in terms of overall survival (OS) and breast cancer-specific survival (BCSS). Additionally, logistic regression models were used to explore factors associated with response to NAT. RESULTS: After PSM, 2140 patient pairs were successfully matched, which achieved a balanced distribution between the NAT and AT groups. KM curves revealed similar OS and BCSS between patients receiving NAT and those undergoing AT. A multivariate Cox model identified achieving pathological complete response (pCR) after NAT, compared with AT, as a protective prognostic factor for OS (hazard ratio, 0.52; 95% CI, 0.35-0.77; p < .001) and BCSS (hazard ratio, 0.60; 95% CI, 0.37-0.98; p = .041). A logistic regression model revealed that White race and hormone receptor-negative status independently predicted pCR. CONCLUSIONS: For patients with T1cN0M0-stage HER2+ breast cancer, NAT demonstrated comparable OS and BCSS to AT. Patients who achieved pCR after NAT exhibited significantly better survival outcomes compared with those who received AT.

Overexpressing S100A9 ameliorates NK cell dysfunction in estrogen receptor-positive breast cancer.

BACKGROUND: Estrogen receptor (ER) positive human epidermal growth factor receptor 2 (HER2) negative breast cancer (ER+/HER2-BC) and triple-negative breast cancer (TNBC) are two distinct breast cancer molecular subtypes, especially in tumor immune microenvironment (TIME). The TIME of TNBC is considered to be more inflammatory than that of ER+/HER2-BC. Natural killer (NK) cells are innate lymphocytes that play an important role of tumor eradication in TME. However, studies focusing on the different cell states of NK cells in breast cancer subtypes are still inadequate. METHODS: In this study, single-cell mRNA sequencing (scRNA-seq) and bulk mRNA sequencing data from ER+/HER2-BC and TNBC were analyzed. Key regulator of NK cell suppression in ER+/HER2-BC, S100A9, was quantified by qPCR and ELISA in MCF-7, T47D, MDA-MB-468 and MDA-MB-231 cell lines. The prognosis predictability of S100A9 and NK activation markers was evaluated by Kaplan-Meier analyses using TCGA-BRAC data. The phenotype changes of NK cells in ER+/HER2-BC after overexpressing S100A9 in cancer cells were evaluated by the production levels of IFN-gamma, perforin and granzyme B and cytotoxicity assay. RESULTS: By analyzing scRNA-seq data, we found that multiple genes involved in cellular stress response were upregulated in ER+/HER2-BC compared with TNBC. Moreover, TLR regulation pathway was significantly enriched using differentially expressed genes (DEGs) from comparing the transcriptome data of ER+/HER2-BC and TNBC cancer cells, and NK cell infiltration high/low groups. Among the DEGs, S100A9 was identified as a key regulator. Patients with higher expression levels of S100A9 and NK cell activation markers had better overall survival. Furthermore, we proved that overexpression of S100A9 in ER+/HER2-cells could improve cocultured NK cell function. CONCLUSION: In conclusion, the study we presented demonstrated that NK cells in ER+/HER2-BC were hypofunctional, and S100A9 was an important regulator of NK cell function in ER+BC. Our work contributes to elucidate the regulatory networks between cancer cells and NK cells and may provide theoretical basis for novel drug development.

Effect and Potential Mechanism of Immunotherapy on Cognitive Deficits in Animal Models of Alzheimer's Disease: A Systematic Review and Meta-Analysis.

OBJECTIVE: Immunotherapy has been reported to ameliorate Alzheimer's disease (AD) in the animal model; however, the immunologic approaches and mechanisms have not been specifically described. Thus, the systematic review and meta-analysis were conducted to explore the effect and potential mechanism of immunotherapy on AD animal experiments based on behavioral indicators. METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Cochrane Collaboration guidelines and the inclusion/exclusion criteria of immunotherapy in animal studies, 15 studies were systematically reviewed after extraction from a collected database of 3,742 publications. Finally, the effect and mechanism of immunotherapy on AD models were described by performing multiple subgroup analyses. RESULTS: After immunotherapy, the escape latency was reduced by 18.15 seconds and the number of crossings over the platform location was increased by 1.60 times in the Morris Water Maze. Furthermore, compared to the control group, active and passive immunization could markedly ameliorate learning and memory impairment in 3 × Tg AD animal models, and active immunization could ameliorate the learning and memory ability of the APPswe/PS1ΔE9 AD animal model. Meanwhile, it could be speculated that cognitive dysfunction was improved by immunotherapy, perhaps mainly via reducing Aß40, Aß42, and Tau levels, as well as increasing IL-4 levels. CONCLUSION: Immunotherapy significantly ameliorated the cognitive dysfunction of AD animal models by assessing behavioral indicators.

Screening of candidate genes related to differences in growth and development between Chinese indigenous and Western pig breeds.

Neijiang (NJ) and Yacha (YC) are two indigenous pig breeds in the Sichuan basin of China, displaying higher resistance to diseases, lower lean ratio, and slower growth rate than the commercial Western pig breed Yorkshire (YS). The molecular mechanisms underlying the differences in growth and development between these pig breeds are still unknown. In the present study, five pigs from NJ, YC, and YS breeds were subjected to the whole genome resequencing, and then the differential single-nucleotide polymorphisms (SNPs) were screened using a 10-kb window sliding in 1-kb step using the Fst method. Finally, 48,924, 48,543, and 46,228 nonsynonymous single-nucleotide polymorphism loci (nsSNPs) were identified between NJ and YS, NJ and YC, and YC and YS, which highly or moderately affected 2,490, 800, and 444 genes, respectively. Moreover, three nsSNPs were detected in the genes of acetyl-CoA acetyltransferase 1 (ACAT1) insulin-like growth factor 2 receptor (IGF2R), insulin-like growth factor 2 and mRNA-binding protein 3 (IGF2BP3), which potentially affected the transformation of acetyl-CoA to acetoacetyl-CoA and the normal functions of the insulin signaling pathways. Moreover, serous determinations revealed significantly lower acetyl-CoA content in YC than in YS, supporting that ACAT1 might be a reason explaining the differences in growth and development between YC and YS breeds. Contents of phosphatidylcholine (PC) and phosphatidic acid (PA) significantly differed between the pig breeds, suggesting that glycerophospholipid metabolism might be another reason for the differences between Chinese and Western pig breeds. Overall, these results might contribute basic information to understand the genetic differences determining the phenotypical traits in pigs.

AflQ1-Q2 represses lincomycin biosynthesis via multiple cascades in Streptomyces lincolnensis.

Lincomycin is a broad-spectrum antibiotic and particularly effective against Gram-positive pathogens. Albeit familiar with the biosynthetic mechanism of lincomycin, we know less about its regulation, limiting the rational design for strain improvement. We therefore analyzed two-component systems (TCSs) in Streptomyces lincolnensis, and selected eight TCS gene(s) to construct their deletion mutants utilizing CRISPR/Cas9 system. Among them, lincomycin yield increased in two strains (Δ3900-3901 and Δ5290-5291) while decreased in other four strains (Δ3415-3416, Δ4153-4154, Δ4985, and Δ7949). Considering the conspicuous effect, SLINC_5291-5290 (AflQ1-Q2) was subsequently studied in detail. Its repression on lincomycin biosynthesis was further proved by gene complementation and overexpression. By binding to a 16-bp palindromic motif, the response regulator AflQ1 inhibits the transcription of its encoding gene and the expression of eight operons inside the lincomycin synthetic cluster (headed by lmbA, lmbJ, lmbK, lmbV, lmbW, lmbU, lmrA, and lmrC), as demonstrated by quantitative RT-PCR and electrophoretic mobility shift assays. Besides, the regulatory genes including bldD, glnR, lcbR1, and ramR are also regulated by the TCS. According to the screening towards nitrogen sources, aspartate affects the regulatory behavior of histidine kinase AflQ2. And in return, AflQ1 accelerates aspartate metabolism via ask-asd, asd2, and thrA. In summary, we acquired six novel regulators related to lincomycin biosynthesis, and elucidated the regulatory mechanism of AflQ1-Q2. This highly conserved TCS is a promising target for the construction of antibiotic high-yield strains. KEY POINTS: • AflQ1-Q2 is a repressor for lincomycin production. • AflQ1 modulates the expression of lincomycin biosynthetic and regulatory genes. • Aspartate affects the behavior of AflQ2, and its metabolism is promoted by AflQ1.

Does the application of biogas slurry reduce soil N2O emissions and increase crop yield?-A systematic review.

The use of organic fertilizer for agricultural production can reduce the use of chemical fertilizer (CF), reduce greenhouse gas emissions, and maintain crop production. However, biogas slurry (BS), a liquid with a high moisture content and a low C/N ratio, differs from commercial organic fertilizer and manure in terms of its impact on the soil N cycle. Replacing CF with BS needs to be reconsidered regarding soil nitrous oxide (N2O) emissions and crop production in terms of fertilization, agricultural land type, and soil characteristics. For this systematic review, the results of 92 published studies worldwide were collected. Based on the findings, the combined application of BS and CF can significantly increase soil total N (TN), microbial biomass N (MBN), and soil organic matter (SOM) levels. The Chaol and ACE index values of soil bacteria were increased by 13.58% and 18.53%, whereas those of soil fungi were decreased by 10.45% and 14.53%, respectively. At a replacement ratio (rr) ≤ 70%, crop yield was promoted by 2.20%-12.17%, and soil N2O emissions were reduced by 1.94%-21.81%. A small rr (≤30%) was more conducive to growth, and a moderate rr (30% < rr ≤ 70%) was more favorable for N2O emission reduction, especially in the dryland crop system. However, at rr = 100%, soil N2O emissions in neutral and alkaline dryland soil were increased by 28.56%-32.22%. The importance analysis of the influencing factors showed that the proportion of BS, the N application rate, and the temperature were the factors affecting soil N2O emissions. Our results provide a scientific basis for the safe use of BS in agricultural systems.

Developmental regulator RamRsl controls both morphological development and lincomycin biosynthesis in Streptomyces lincolnensis.

AIMS: Assessing the role of ramRsl , a gene absent in a lincomycin over-producing strain, in the regulation of morphological development and lincomycin biosynthesis in Streptomyces lincolnensis. METHODS AND RESULTS: The gene ramRsl was deleted from the wild-type strain NRRL 2936 and the ΔramR mutant strain was characterized by a slower growth rate and a delayed morphological differentiation compared to the original strain NRRL 2936. Furthermore, the ΔramR produced 2.6-fold more lincomycin than the original strain, and consistently the level of expression of all lincomycin cluster located genes was enhanced at 48 and 96 h in the ΔramR. Complementation of ΔramR with an intact copy of ramRsl restored all wild-type features, whereas the over-expression of ramRsl led to a reduction of 33% of the lincomycin yield. Furthermore, the level of expression of glnR, bldA and SLCG_2919, three of known lincomycin biosynthesis regulators, was lower in the ΔramR than in the original strain at the early stage of fermentation and we demonstrated, using electrophoretic mobility shift assay and XylE reporter assay, that glnR is a novel direct target of RamR. CONCLUSIONS: Altogether, these results indicated that, beyond promoting the morphological development, RamR regulates negatively lincomycin biosynthesis and positively the expression of the nitrogen regulator GlnR. SIGNIFICANCE AND IMPACT OF THE STUDY: We demonstrated that RamR plays a negative role in the regulation of lincomycin biosynthesis in S. lincolnensis. Interestingly, the deletion of this gene in other antibiotic-producing Streptomyces strains might also increase their antibiotic-producing abilities.

Human health risk visualization of potentially toxic elements in farmland soil: A combined method of source and probability.

Human health is adversely affected by potentially toxic elements (PTEs) in the topsoil, entering the bodies via inhalation, ingestion, and dermal contact. To visualize human health risks, we investigated five PTEs (Cd, As, Pb, Hg, and Cr) in 72 farmland topsoil samples from a town in Chongqing City, southwest China. Based on the human health risk assessment model, sequential indicator simulation (SIS) and the positive matrix factorization model (PMF) were used to construct the spatial health risks and to analyze the sources of PTEs; finally, health risks were combined with the source by ArcGIS. Based on our results, the use of SIS is feasible for the prediction of the spatial distribution of PTEs. Among the risks, the non-cancer risk of As for children most likely exceeded the accepted level in some areas, making As a priority pollutant. Although the health risks of soil Cd were acceptable in the region, the spatial probability distribution of Cd> 0.3 mg/kg represents a threat as Cd enters the human food chain. Even if the industrial discharge was the lowest individual contributor (29.33%), due to the impact of industrial discharge, the total non-cancer risk with a high probability (>0.85) for children still exceeded the accepted level in the northwestern area, which should be regarded as the priority pollution source. The combined method was useful to reduce efforts in environmental management, thus providing a basis for soil remediation and pollution source control.

[Association of fetal cardiac structural abnormalities and chromosomal aneuploidies and copy number variations].

OBJECTIVE: To investigate the association of fetal cardiac structural abnormalities with chromosomal aneuploidies and copy number variations (CNVs) in amniocytes. METHODS: 328 pregnant women were subjected to fetal ultrasonography and chromosomal microarray analysis (CMA). Based on the fetal heart structure, the subjects were divided into normal (n=273) and abnormal groups (n=55). The detection rates of chromosomal aneuploidies and CNVs were compared between the two groups. Spearman method was used to assess the association between the results and fetal cardiac structural abnormalities. RESULTS: The detection rates for chromosomal aneuploidies and CNVs in the abnormal group were significantly higher than that in the normal group (P< 0.05), and the incidence of fetal cardiac structural abnormalities was strongly associated with chromosomal aneuploidies and CNVs (P< 0.05). CONCLUSION: Fetal chromosomal aneuploidies and CNVs are strongly associated with cardiac structural abnormalities.

A Prospective Study of Maternal Plasma Concentrations of Retinol-Binding Protein 4 and Risk of Gestational Diabetes Mellitus.

BACKGROUND: The aim of this study was to investigate whether retinol-binding protein 4 (RBP4) concentrations, measured at the first prenatal visit, are associated with risk of gestational diabetes mellitus (GDM). METHODS: From July 2015 to June 2016, consecutive women who admitted to the obstetrics center of our hospital were included. At the first prenatal visit (the median gestational age was 6 [interquartile range 4-10] weeks) in the hospital, involved subjects were tested for fasting plasma glucose (FPG) and RBP4 using venous plasma samples collected after at least 8 h of fasting in the morning. Data for FPG and RBP4 concentrations at the first prenatal visit and one-step GDM screening with 75-g oral glucose tolerance test performed between 24 and 28 weeks of gestation were collected and analyzed. RESULTS: Blood at first prenatal visit was available for 827 women, among whom GDM developed in 101 (12.2%). In multivariate models comparing the second (Q2), third, and fourth quartiles against the first quartile of RBP4, concentrations of RBP4 in Q2, Q3, and Q4 were associated with GDM later developed, and increased risk of GDM by 54, 205, and 536%. There was a significant statistical difference in the area under the curve between the established risk factors alone and the addition of RBP4 concentrations (difference, 0.039 [95% CI 0.030-0.052]; p = 0.03). In the subgroup of women combined with obesity and FABP4 ≥median, the measured OR was 9.83 (95% CI [4.76-16.13]; p < 0.001) for GDM compared to those without obesity and FABP4

Overexpression of Populus trichocarpa CYP85A3 promotes growth and biomass production in transgenic trees.

Brassinosteroids (BRs) are essential hormones that play crucial roles in plant growth, reproduction and response to abiotic and biotic stress. In Arabidopsis, AtCYP85A2 works as a bifunctional cytochrome P450 monooxygenase to catalyse the conversion of castasterone to brassinolide, a final rate-limiting step in the BR-biosynthetic pathway. Here, we report the functional characterizations of PtCYP85A3, one of the three AtCYP85A2 homologous genes from Populus trichocarpa. PtCYP85A3 shares the highest similarity with AtCYP85A2 and can rescue the retarded-growth phenotype of the Arabidopsis cyp85a2-2 and tomato dx mutants. Constitutive expression of PtCYP85A3, driven by the cauliflower mosaic virus 35S promoter, increased the endogenous BR levels and significantly promoted the growth and biomass production in both transgenic tomato and poplar. Compared to the wild type, plant height, shoot fresh weight and fruit yield increased 50%, 56% and 43%, respectively, in transgenic tomato plants. Similarly, plant height and stem diameter increased 15% and 25%, respectively, in transgenic poplar plants. Further study revealed that overexpression of PtCYP85A3 enhanced xylem formation without affecting the composition of cellulose and lignin, as well as the cell wall thickness in transgenic poplar. Our finding suggests that PtCYP85A3 could be used as a potential candidate gene for engineering fast-growing trees with improved wood production.

InDel marker detection by integration of multiple softwares using machine learning techniques.

BACKGROUND: In the biological experiments of soybean species, molecular markers are widely used to verify the soybean genome or construct its genetic map. Among a variety of molecular markers, insertions and deletions (InDels) are preferred with the advantages of wide distribution and high density at the whole-genome level. Hence, the problem of detecting InDels based on next-generation sequencing data is of great importance for the design of InDel markers. To tackle it, this paper integrated machine learning techniques with existing software and developed two algorithms for InDel detection, one is the best F-score method (BF-M) and the other is the Support Vector Machine (SVM) method (SVM-M), which is based on the classical SVM model. RESULTS: The experimental results show that the performance of BF-M was promising as indicated by the high precision and recall scores, whereas SVM-M yielded the best performance in terms of recall and F-score. Moreover, based on the InDel markers detected by SVM-M from soybeans that were collected from 56 different regions, highly polymorphic loci were selected to construct an InDel marker database for soybean. CONCLUSIONS: Compared to existing software tools, the two algorithms proposed in this work produced substantially higher precision and recall scores, and remained stable in various types of genomic regions. Moreover, based on SVM-M, we have constructed a database for soybean InDel markers and published it for academic research.

Single-dose intra-articular bupivacaine after knee arthroscopic surgery: a meta-analysis of randomized placebo-controlled studies.

PURPOSE: The purpose of this meta-analysis was to examine the efficacy and safety of single-dose intra-articular bupivacaine in the management of pain after knee arthroscopic surgery. METHOD: The comprehensive literature search, using MEDLINE, the Cochrane Central Register of Controlled Trials, and Embase databases, was conducted to identify randomized controlled trials that used single-dose intra-articular bupivacaine for postoperative pain. The relative risk (RR), weighted mean difference (WMD), and their corresponding 95 % confidence intervals (CIs) were calculated using RevMan(®) statistical software. RESULT: Twenty-three studies (n = 1287) were included (647 subjects in bupivacaine group and 640 subjects in the control group). Statistically significant differences were observed in the VAS values (WMD -1.1; 95 % CI -1.7 to -0.5), number of patients requiring supplementary analgesia (RR 0.83; 95 % CI 0.74-0.94), and time to first analgesic request (WMD 129.3; 95 % CI 15.4-243.1) among the bupivacaine group when compared to the control group. However, short-term side effects had no significant difference between these two groups (RR 0.73; 95 % CI 0.44-1.24). CONCLUSIONS: On the basis of the currently available literature, single-dose intra-articular bupivacaine was shown to be significantly better than placebo at relieving pain after knee arthroscopic surgery. More high-quality randomized controlled trials with long follow-up are highly required for examining the safety of single-dose intra-articular bupivacaine. Besides, routine use of single-dose intra-articular bupivacaine is still an effective way for pain management after knee arthroscopic surgery.

The CUSUM analysis of the learning curve for endoscopic thyroidectomy by the breast approach.

OBJECTIVES: To evaluate the learning curve for endoscopic thyroidectomy by the breast approach (ETBBA) based on the cumulative summation (CUSUM) technique. METHODS: The study included 110 consecutive patients who underwent ETBBA by a single surgeon between January 2009 and May 2012 at the Xiangya Hospital of Central South University, Changsha, China. The learning curve was evaluated using the CUSUM technique. The patients were chronologically arranged into 3 phases by the CUSUM analysis for operative time. Demographic data and operative parameters were also analyzed. RESULTS: The mean operative time (OT) was 125.3 minutes. The conversion rate for technical difficulties and the definitive complication rate were 6.4% and 10%, respectively. The learning curve was analyzed mainly by OT using the CUSUM technique. There was a significant improvement in the average OT (P < .05) after the first 27 patients and again after the first 67 patients (P < .05). A downward trend in OT was found up to the last patient. There were similarities in gender, tumor size, extent of surgery, blood loss, histology, hospital stay, conversion rate, and complications among the 3 phases. Comparison of 2 neighboring phases also showed no significant differences in age. CONCLUSIONS: ETBBA performed by surgeons has a remarkable learning curve. There were 27 cases in the early stage of the learning curve, whereas mastery level could be achieved with 67 cases.

Knowledge domains and emerging trends of Genome-wide association studies in Alzheimer's disease: A bibliometric analysis and visualization study from 2002 to 2022.

OBJECTIVES: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive decline in cognitive and behavioral function. Studies have shown that genetic factors are one of the main causes of AD risk. genome-wide association study (GWAS), as a novel and effective tool for studying the genetic risk of diseases, has attracted attention from researchers in recent years and a large number of studies have been conducted. This study aims to summarize the literature on GWAS in AD by bibliometric methods, analyze the current status, research hotspots and future trends in this field. METHODS: We retrieved articles on GWAS in AD published between 2002 and 2022 from Web of Science. CiteSpace and VOSviewer software were applied to analyze the articles for the number of articles published, countries/regions and institutions of publication, authors and cited authors, highly cited literature, and research hotspots. RESULTS: We retrieved a total of 2,751 articles. The United States had the highest number of publications in this field, and Columbia University was the institution with the most published articles. The identification of AD-related susceptibility genes and their effects on AD is one of the current research hotspots. Numerous risk genes have been identified, among which APOE, CLU, CD2AP, CD33, EPHA1, PICALM, CR1, ABCA7 and TREM2 are the current genes of interest. In addition, risk prediction for AD and research on other related diseases are also popular research directions in this field. CONCLUSION: This study conducted a comprehensive analysis of GWAS in AD and identified the current research hotspots and research trends. In addition, we also pointed out the shortcomings of current research and suggested future research directions. This study can provide researchers with information about the knowledge structure and emerging trends in the field of GWAS in AD and provide guidance for future research.

Effect and Mechanism of Rapamycin on Cognitive Deficits in Animal Models of Alzheimer's Disease: A Systematic Review and Meta-analysis of Preclinical Studies.

Background: Alzheimer's disease (AD), the most common form of dementia, remains long-term and challenging to diagnose. Furthermore, there is currently no medication to completely cure AD patients. Rapamycin has been clinically demonstrated to postpone the aging process in mice and improve learning and memory abilities in animal models of AD. Therefore, rapamycin has the potential to be significant in the discovery and development of drugs for AD patients. Objective: The main objective of this systematic review and meta-analysis was to investigate the effects and mechanisms of rapamycin on animal models of AD by examining behavioral indicators and pathological features. Methods: Six databases were searched and 4,277 articles were retrieved. In conclusion, 13 studies were included according to predefined criteria. Three authors independently judged the selected literature and methodological quality. Use of subgroup analyses to explore potential mechanistic effects of rapamycin interventions: animal models of AD, specific types of transgenic animal models, dosage, and periodicity of administration. Results: The results of Morris Water Maze (MWM) behavioral test showed that escape latency was shortened by 15.60 seconds with rapamycin therapy, indicating that learning ability was enhanced in AD mice; and the number of traversed platforms was increased by 1.53 times, indicating that the improved memory ability significantly corrected the memory deficits. CONCLUSIONS: Rapamycin therapy reduced age-related plaque deposition by decreasing AßPP production and down-regulating ß-secretase and γ-secretase activities, furthermore increased amyloid-ß clearance by promoting autophagy, as well as reduced tau hyperphosphorylation by up-regulating insulin-degrading enzyme levels.

CHST4 associates with high-abundance immune infiltration in hormone receptor-positive breast cancer.

Hormone receptor-positive breast cancer (HR+ BRCA) with high-risk factors such as lymph node metastasis has a relatively poor prognosis. However, the biological basis of tumor cell migration is still poorly understood, especially as some of the metastatic events occur at an early stage. Here, we identified that carbohydrate sulfotransferase 4 (CHST4), which has an important role in lymphocyte homing, was abnormally down-regulated in HR+ BRCA and associated with lymph node metastasis. By enrichment analysis and immune infiltration evaluation, we predicted the potential ability of CHST4 to enhance immune cell infiltration. Then, IHC staining further demonstrated the contribution of CHST4 to the infiltration abundance of CD8+ T cells and CD4+ T cells in HR+ BRCA. IHC staining of MECA-79 further identified the correlation between CHST4 and sulfated perpheral lymphonode vascular addressin (PNAd). Finally, we demonstrated that CHST4 was connected to increased tumor-immune cell communication by analyzing single-cell sequencing data. In summary, our study provided novel insights into the regulation of HR+ BRCA immune infiltration by CHST4.

Comparing survival outcomes between neoadjuvant and adjuvant chemotherapy within T2N1M0 stage hormone receptor-positive, HER2-negative breast cancer: a retrospective cohort study based on SEER database.

BACKGROUND: Guideline recommendations for the application of neoadjuvant chemotherapy (NACT) in T2N1M0 stage hormone receptor-positive, HER2-negative (HR + /HER2-) breast cancer are ambiguous. The debate continues regarding whether NACT or adjuvant chemotherapy (ACT) offers superior survival outcomes for these patients. MATERIALS AND METHODS: Female patients diagnosed with HR + /HER2- breast cancer at T2N1M0 stage between 2010 and 2020, were identified from the Surveillance, Epidemiology, and End Results database and divided into two groups, the NACT group and the ACT group. Propensity score matching (PSM) was utilized to establish balanced cohorts between groups, considering baseline features. Kaplan-Meier (K-M) analysis and the Cox proportional hazards model were executed to assess the efficacy of both NACT and ACT in terms of overall survival (OS) and breast cancer-specific survival (BCSS). A logistic regression model was employed to examine the association between predictive variables and response to NACT. RESULTS: After PSM, 4,682 patients were finally included. K-M curves showed that patients receiving NACT exhibited significantly worse OS and BCSS when compared with patients undergoing ACT. Multivariable Cox analysis indicated that not achieving pathologic complete response (non-pCR) after NACT (versus ACT), was identified as an adverse prognostic factor for OS (HR 1.58, 95% CI 1.36-1.83) and BCSS (HR 1.70, 95% CI 1.44-2. 02). The logistic regression model revealed that low tumor grade independently predicted non-pCR. CONCLUSION: Among T2N1M0 stage HR + /HER2- patients, OS and BCSS of NACT were inferior to ACT. Patients who attained non-pCR after NACT demonstrated significantly worse survival outcomes compared with those who received ACT.

Oral contraceptive use and uterine leiomyoma risk: a meta-analysis based on cohort and case-control studies.

PURPOSE: To review the epidemiological and clinical evidence for the association between oral contraceptives (OCs) and uterine leiomyoma (UL). METHODS: Several databases (Pubmed, Cochrane Central, OVID, SpringerLink, Clinical Evidence, and Google scholar) and reference lists were searched through March 2012 with no restrictions. INCLUSION CRITERIA: cohort or case-control studies; the exposure of interest was OCs; the outcome of interest was UL; relative risk (RR) or odds ratio (OR) (or data to calculate them) were reported. Two independent reviewers assessed eligibility criteria and extracted data. RESULTS: Eleven literatures involving 8,990 UL patients and 1,31,055 participants were included from 3,017 studies initially found. The influence of OCs on UL risk was assessed by comparing "ever", "current" or "former" users and "never" users. Meta-analysis indicated that OCs use did not increase UL morbidity ("ever" vs "never": risk ratio [RR] 0.88; 95 % confidence interval [95 % CI] 0.75-1.04. "current" vs "never": RR 0.43; 95 % CI 0.25-0.73. "former" vs "never": RR 0.96; 95 % CI 0.84-1.08). Dose-response analysis showed the risk of UL morbidity was reduced by 17 % in "ever" users for 5 years or more (P trend = 0.006). However, the results have to be viewed with caution because there was significant heterogeneity (I (2): from 64 to 92 %). CONCLUSIONS: Although the role of potential bias and evidence of heterogeneity should be carefully evaluated, the present study suggests that UL should not be considered a contra-indication for OCs use.

Glucagon-like peptide 1 (GLP-1) receptor agonists in experimental Alzheimer's disease models: a systematic review and meta-analysis of preclinical studies.

Alzheimer's disease (AD) is a degenerative disease of the nervous system. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), a drug used to treat type 2 diabetes, have been shown to have neuroprotective effects. This systematic review and meta-analysis evaluated the effects and potential mechanisms of GLP-1 RAs in AD animal models. 26 studies were included by searching relevant studies from seven databases according to a predefined search strategy and inclusion criteria. Methodological quality was assessed using SYRCLE's risk of bias tool, and statistical analysis was performed using ReviewManger 5.3. The results showed that, in terms of behavioral tests, GLP-1 RAs could improve the learning and memory abilities of AD rodents; in terms of pathology, GLP-1 RAs could reduce Aß deposition and phosphorylated tau levels in the brains of AD rodents. The therapeutic potential of GLP-1 RAs in AD involves a range of mechanisms that work synergistically to enhance the alleviation of various pathological manifestations associated with the condition. A total of five clinical trials were retrieved from ClinicalTrials.gov. More large-scale and high-quality preclinical trials should be conducted to more accurately assess the therapeutic effects of GLP-1 RAs on AD.