A network meta-analysis of efficacy and safety for first-line and second/further-line therapies in postmenopausal women with hormone receptor-positive, HER2-negative, advanced breast cancer.

BACKGROUND: Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR + /HER2 -) advanced breast cancer is a prevalent subtype among postmenopausal women. Despite the growing number of randomized clinical trials (RCTs) exploring this topic, the efficacy and safety of first-line and second/further-line treatments remain uncertain. Accordingly, our aim was to conduct a comprehensive evaluation of the efficacy and safety of these therapies through network meta-analysis. METHODS: RCTs were identified by searching Pubmed, Embase, and major cancer conferences. The efficacy of interventions was assessed using the hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS), while safety was indicated by the incidence of any grade adverse events (AEs), grade 3-5 AEs, AEs leading to treatment discontinuation, and AEs leading to death. Both time-variant HRs fractional polynomial models and time-invariant HRs Cox-proportional hazards models were considered for handling time-to-event data. Safety indicators were analyzed using Bayesian network meta-analysis. Additionally, subgroup analyses were conducted based on patient characteristics. RESULTS: A total of 41 RCTs (first-line 17, second/further-lines 27) were included in the analysis. For first-line treatment, the addition of Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors to endocrine therapy significantly improved therapeutic efficacy in terms of both PFS and OS, demonstrating the best performance across all mechanisms. Specifically, the combination of Abemaciclib and Letrozole demonstrated the most favorable performance in terms of PFS, while Ribociclib plus Fulvestrant yielded the best outcomes in OS. Incorporating the immune checkpoint inhibitor Avelumab into the regimen with CDK4/6 inhibitors and selective estrogen receptor degraders significantly enhanced both PFS and OS in second-line or later treatments. Regarding safety, endocrine monotherapy performed well. Regarding safety, endocrine monotherapy performed well. There is mounting evidence suggesting that most CDK4/6 inhibitors may demonstrate poorer performance with respect to hematologic AEs. However, additional evidence is required to further substantiate these findings. CONCLUSIONS: CDK4/6 inhibitors, combined with endocrine therapy, are pivotal in first-line treatment due to their superior efficacy and manageable AEs. For second/further-line treatment, adding immune checkpoint inhibitors to CDK4/6 inhibitors plus endocrine therapy may produce promising results. However, to reduce the results' uncertainty, further trials comparing these novel treatments are warranted. TRIAL REGISTRATION: Registration number: PROSPERO (CRD42022377431).

C-type lectin 4 of Toxocara canis activates NF-ĸB and MAPK pathways by modulating NOD1/2 and RIP2 in murine macrophages in vitro.

Toxocara canis is a parasitic zoonose that is distributed worldwide and is one of the two pathogens causing toxocariasis. After infection, it causes serious public health and safety problems, which pose significant veterinary and medical challenges. To better understand the regulatory effects of T. canis infection on the host immune cells, murine macrophages (RAW264.7) were incubated with recombinant T. canis C-type lectin 4 (rTc-CTL-4) protein in vitro. The quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to analyze the nucleotide-binding oligomerization domain-containing protein 1/2 (NOD1/2), receptor-interacting protein 2 (RIP2), nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB), and mitogen-activated protein kinase (MAPK) on mRNA level and protein expression level in macrophages. Our results indicated that 10 µg/mL rTc-CTL-4 protein could modulate the expression of NOD1, NOD2, and RIP2 at both the transcriptional and translational levels. The protein translation levels of NF-κB, P-p65, p38, and P-p38 in macrophages were also modulated by rTc-CTL-4 protein. Macrophages were co-incubated with rTc-CTL-4 protein after siRNA silencing of NOD1, NOD2, and RIP2. The expression levels of NF-κB, P-p65, p38, and P-p38 were significantly changed compared with the negative control groups (Neg. Ctrl.). Taken together, rTc-CTL-4 protein seemed to act on NOD1/2-RIP2-NF-κB and MAPK signaling pathways in macrophages and might activate MAPK and NF-κB signaling pathways by regulating NOD1, NOD2, and RIP2. The insights from the above studies could contribute to our understanding of immune recognition and regulatory mechanisms of T. canis infection in the host animals.

Predictors of disease severity in SARS-CoV-2 omicron variant XBB sublineages and variants of interest.

The Omicron variant has been reported to present with milder disease compared with Delta, although this may be due to immunity from vaccination and prior exposure. Predictors of severity with recent strains have not been well characterized. We retrospectively examined consecutive cases of moderate-to-severe COVID-19 (defined as requiring supplemental oxygenation, intensive care or mortality) admitted to seven tertiary hospitals across Singapore in April 2023. Whole genome sequencing was performed on each isolate to determine the sublineage, while baseline clinical, laboratory data and outcomes were tabulated. We reviewed 182 patients with moderate-to-severe illness and 466 controls hospitalized at the same time. Advanced age and presence of chronic kidney disease predicted adverse outcome. Previously reported markers such as radiographic evidence of pneumonia, elevated C-reactive protein and serum creatinine levels at presentation also correlated with adverse outcomes. There were no observable differences in outcomes with any specific Omicron XBB sublineage. We did not find any specific Omicron XBB sublineage that was associated with worse outcomes. Larger multinational studies would be important to track the clinical evolution of the virus in its current endemic state.

Sphingopyxis yananensis sp. nov., a novel 2-nitropropane degrading bacterium isolated from a microbial fermentation bed substrate.

A rod-shaped, Gram-negative staining strain, FBM22T, was isolated from a microbial fermentation bed substrate from a pig farm. Its colonies appeared yellow and were 0.5-1.2 mm in diameter. Cells were 0.3-0.5 µm wide, 0.5-0.83 µm long. Optimal growth occurred at 30 °C and pH 7.0-8.0; NaCl was not required for growth. The strain performed denitrification and nitrate reduction functions. And it could produce catalase. FBM22-1T utilized the following organic substrates for growth: tyrosine, glutamic acid, D-glucose, and galactose. The novel isolate could degrade 2-nitropropane as carbon and nitrogen source. The dominant respiratory quinone was Q-10. The major polar lipids were diphosphatidylglycerol, phosphatidylcholine and phosphatidylethanolamine. C18:1 ω7c, C16:1 ω7c and/ or C16:1 ω6c, and C14:0 2-OH were the major (≥ 8%) fatty acids. The G+C content was 56.8 mol%. FBM22T was found to be a member of the genus Sphingopyxis in the family Sphingomonadaceae of the class Alphaproteobacteria. It had the highest sequence similarity with the type strains Sphingopyxis terrae subsp. ummariensis UI2T (96.47%) and Sphingopyxis terrae subsp. terrae NBRC 15098T (96.40%). Furthermore, FBM22T had 18.7% and 18.4% relatedness (based on digital DNA-DNA hybridization) with its two relatives (S. terrae subsp. ummariensis UI2T and S. terrae subsp. terrae NBRC 15098T). The morphological, physiological, and genotypic differences identified in this study support the classification of FBM22T as a novel species within the genus Sphingopyxis, for which the name Sphingopyxis yananensis sp. nov. is proposed. The type strain is FBM22T (= KCTC 82290T = CCTC AB2020286T).

Study on microbes and antibiotic resistance genes in karst primitive mountain marshes - A case study of Niangniang Mountain in Guizhou, China.

Previous research on antibiotic resistance genes and microorganisms centered on those in urban sewage treatment plants, breeding farms, hospitals and others with serious antibiotic pollution. However, at present, there are evident proofs that antibiotic resistance genes (ARGs) indeed exist in a primitive environment hardly without any human's footprints. Accordingly, an original karst mountain swamp ecosystem in Niangniang Mountain, Guizhou, China, including herbaceous swamp, shrub swamp, sphagnum bog and forest swamp, was selected to analyze the physical and chemical parameters of sediments. Moreover, microbial compositions, functions, as well as their connections with ARGs were assayed and analyzed using metagenomic technology. The results showed that there was no significant difference in the dominant microorganisms and ARGs in the four marshes, in which the dominant bacteria phyla were Proteobacteria (37.82 %), Acidobacteriota (22.17 %) and Actinobacteriota (20.64 %); the dominant archaea Euryarchaeota. (1.00 %); and the dominant eukaryotes Ascomycota (0.07 %), with metabolism as their major functions. Based on the ARDB database, the number of ARGs annotated reached 209 including 30 subtypes, and the dominant ARGs were all Bacitracin resistance genes (bacA, 84.77 %). In terms of the diversity of microorganisms and ARGs, the herbaceous swamp ranked the top, and the shrub swamp were at the bottom. Correlation analysis between microorganisms and resistance genes showed that, apart from aac2ic, macB, smeE, tetQ, and tetL, other ARGs were positively correlated with microorganisms. Among them, baca coexisted with microorganisms. Pearson correlation analysis results showed that contrary to ARGs, microorganisms were more affected by environmental factors.

Feasibility of occipital condyle screw placement in patients with Chiari malformation type I: a computed tomography-based morphometric study.

BACKGROUND: The occipital condyle (OC) screw is an alternative technique for occipitocervical fixation that is especially suitable for revision surgery in patients with Chiari malformation type I (CMI). This study aimed to investigate the feasibility and safety of this technique in patients with CMI. METHODS: The CT data of 73 CMI patients and 73 healthy controls were retrospectively analyzed. The dimensions of OCs, including length, width, height, sagittal angle, and screw length, were measured in the axial, sagittal, and coronal planes using CT images. The OC available height was measured in the reconstructed oblique parasagittal plane of the trajectory. RESULTS: The mean length, width, and height of OCs in CMI patients were 17.79 ± 2.31 mm, 11.20 ± 1.28 mm, and 5.87 ± 1.29 mm, respectively. All OC dimensions were significantly smaller in CMI patients compared with healthy controls. The mean screw length and sagittal angle were 19.13 ± 1.97 mm and 33.94° ± 5.43°, respectively. The mean OC available height was 6.36 ± 1.59 mm. According to criteria based on OC available height and width, 52.1% (76/146) of OCs in CMI patients could safely accommodate a 3.5-mm-diameter screw. CONCLUSIONS: The OC screw is feasible in approximately half of OCs in CMI patients. Careful morphometric analyses and personalized surgical plans are necessary for the success of this operation in CMI patients.

Development and validation of an instrument to assess work support needs of adults with intellectual disabilities in sheltered employment.

BACKGROUND: The Work Support Profile (WSP) is a brief assessment instrument that enables staff supporting adults with disabilities to provide calibrated and individualized support for specific work tasks. This paper sought to examine the psychometric properties of WSP for people with disabilities. METHOD: A pilot study was conducted with 239 sheltered workshop employees diagnosed mainly with intellectual disability to explore the structure of this assessment tool, and provide initial evidence of its psychometric properties. Subsequently, a larger-scale study captured a nationwide profile of 761 sheltered workshop employees with intellectual disability. RESULTS: Across both studies, factor analyses yielded a conceptually acceptable 5-factor structure with 33 items accounting for approximately 65% of the variance. Furthermore, the reliability, convergent and discriminant validity of WSP can be considered adequate. CONCLUSION: Results provide preliminary evidence that WSP is a psychometrically adequate tool for assessing the work support needs of adults with disabilities on given work tasks.

[Genome-wide analysis of LBD(lateral organ boundaries domain) gene family in Cannabis sativa of traditional Chinese medicine hemp seed].

LBD(lateral organ boundaries)transcription factors play an important role in the regulation of plant growth, development and secondary metabolism. In order to explore the function of LBD genes in cannabis, the Cannabis sativa genome and transcriptome were used to identify the C. sativa LBD gene family, and analyzed their expression patterns. Our results showed that the cannabis LBD contains 32 members, which were divided into two major categories, seven sub-families. Class Ⅰ was divided into 5 sub-families, named Class Ⅰ_a to Class Ⅰ_e, while Class Ⅱ was divided into 2 sub-families, including Class Ⅱ_a and Class Ⅱ_b. Analysis showed that the number of amino acids encoded LBDs was between 172 and 356, and the isoelectric point was between 4.92 and 9.43. The mole-cular weight of LBD was between 18 862.92 Da and 40 081.33 Da, and most members are located in the nucleus. Chromosome positioning of LBD showed that 32 members were unevenly distributed on 10 chromosomes of C. sativa LBD transcription factor domain, gene structure and motifs are relatively conservative, and the characteristics of different class members are similar. The upstream promoter region of the gene contains a variety of cis-acting elements related to plant hormones and environmental factors, C. sativa LBD genes have different expression patterns in the stems, leaves, and flowers of ZYS varieties(low tetrahydrocannabinol, high cannabidiol). The members of the LBD gene family are mainly expressed in the flowers and stems of ZYS varieties, while members expressed in the leaves very few; Class Ⅱ members CsLBD21 and CsLBD23 are expressed in flowers and stems, and CsLBD8 and CsLBD18 are expressed in flowers, stems and leaves. These genes may participate in the growth and development of cannabis and affect the biosynthesis of cannabinoids. This study laid the foundation for the subsequently functional research of the cannabis LBD gene family.

Spinal cord injury effectively ameliorated by neuroprotective effects of rosmarinic acid.

OBJECTIVE: Pathophysiology of spinal cord injury (SCI) causes primary and secondary effects leading to loss of neuronal function. The aim of the present study was to investigate the role of rosmarinic acid (RA) in protection against SCI. METHODS: The experimental study was carried out in male wistar rats categorized into three groups. Group I - sham operated rats; Group II - SCI; Group III - SCI followed by RA treatment (10 mg/kg). The spinal tissues after treatment schedule were analyzed for oxidative stress status through determination of reactive oxygen species (ROS), lipid peroxidation, protein damage (carbonyl and sulfhydryl contents), and antioxidant enzyme activities. The expression of oxidative stress factors NF-κB and Nrf-2 was determined by Western blot analysis. Further pro-inflammatory cytokines (TNF-α, IL-6, MCP-1, and IL-1ß) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The results show that treatment with RA significantly enhances the antioxidant status and decrease the oxidative stress in wistar rats post-SCI. RA effectively ameliorated inflammatory mechanisms by downregulation of NF-κB and pro-inflammatory cytokines post-SCI. CONCLUSION: The study demonstrates for the first time on the role of RA in protecting the spinal cord from injury and demonstrates its neuroprotection in wistar rats.

Dysregulation of clathrin promotes thyroid cell growth and contributes to multinodular goiter pathogenesis.

A germline mutation (A339V) in thyroid transcription factor-1 (TITF1/NKX2.1) was shown to be associated with multinodular goiter (MNG) and papillary thyroid carcinoma (PTC) pathogenesis. The overexpression of A339V TTF1 significantly promoted hormone-independent growth of the normal thyroid cells, representing a cause of MNG and/or PTC. Nevertheless, the underlying mechanism still remains unclear. In this study, we used liquid chromatography (LC)-tandem mass spectrometry (MS/MS)-based shotgun proteomics comparing the global protein expression profiles of normal thyroid cells (PCCL3) that overexpressed the wild-type or A339V TTF1 to identify key proteins implicated in this process. Proteomic pathway analysis revealed that the aberrant activation of epidermal growth factor (EGF) signaling is significantly associated with the overexpression of A339V TTF1 in PCCL3, and clathrin heavy chain (Chc) is the most significantly up-regulated protein of the pathway. Intriguingly, dysregulated Chc expression facilitated a nuclear accumulation of pStat3, leading to an enhanced cell proliferation of the A339V clones. Down-regulation and abrogation of Chc-mediated cellular trafficking, respectively, by knocking-down Chc and ectopic expression of a dominant-negative (DN) form of Chc could significantly reduce the nuclear pStat3 and rescue the aberrant cell proliferation of the A339V clones. Subsequent expression analysis further revealed that CHC and pSTAT3 are co-overexpressed in 66.7% (10/15) MNG. Taken together, our results suggest that the A339V TTF1 mutant protein up-regulates the cellular expression of Chc, resulting in a constitutive activation of Stat3 pathway, and prompting the aberrant growth of thyroid cells. This extensive growth signal may promote the development of MNG.

Identification of GLI Mutations in Patients With Hirschsprung Disease That Disrupt Enteric Nervous System Development in Mice.

BACKGROUND & AIMS: Hirschsprung disease is characterized by a deficit in enteric neurons, which are derived from neural crest cells (NCCs). Aberrant hedgehog signaling disrupts NCC differentiation and might cause Hirschsprung disease. We performed genetic analyses to determine whether hedgehog signaling is involved in pathogenesis. METHODS: We performed deep-target sequencing of DNA from 20 patients with Hirschsprung disease (16 men, 4 women), and 20 individuals without (controls), and searched for mutation(s) in GLI1, GLI2, GLI3, SUFU, and SOX10. Biological effects of GLI mutations were tested in luciferase reporter assays using HeLa or neuroblastoma cell lines. Development of the enteric nervous system was studied in Sufu(f/f), Gli3(Δ699), Wnt1-Cre, and Sox10(NGFP) mice using immunohistochemical and whole-mount staining procedures to quantify enteric neurons and glia and analyze axon fasciculation, respectively. NCC migration was studied using time-lapse imaging. RESULTS: We identified 3 mutations in GLI in 5 patients with Hirschsprung disease but no controls; all lead to increased transcription of SOX10 in cell lines. SUFU, GLI, and SOX10 form a regulatory loop that controls the neuronal vs glial lineages and migration of NCCs. Sufu mutants mice had high Gli activity, due to loss of Sufu, disrupting the regulatory loop and migration of enteric NCCs, leading to defective axonal fasciculation, delayed gut colonization, or intestinal hypoganglionosis. The ratio of enteric neurons to glia correlated inversely with Gli activity. CONCLUSIONS: We identified mutations that increase GLI activity in patients with Hirschsprung disease. Disruption of the SUFU-GLI-SOX10 regulatory loop disrupts migration of NCCs and development of the enteric nervous system in mice.

Ni-catalyzed highly chemo-, regio-, and enantioselective decarboxylative aldol reaction of ß,γ-unsaturated α-ketoesters with ß-ketoacids.

A novel Ni-catalyzed decarboxylative aldol reaction of ß,γ-unsaturated α-ketoesters with ß-ketoacids is reported. The reaction proceeds smoothly with high chemo-, regio-, and enantioselectivity. This protocol provides a convenient approach to access enantioenriched chiral tertiary alcohols.

Transsylvian-transinsular approach to large lateral thalamus hemorrhages.

Here, we aimed to evaluate the experience of transsylvian-transinsular microsurgical approach (TTH) to the huge lateral thalamic hemorrhages (THs). A total of 37 patients with huge lateral TH (hematoma volumes between 30 and 90 cm) who underwent surgical treatment through middle or distal TTH at the Bayi Brain Hospital from January 2007 to May 2012 were included in this series. By using TTH, near-complete (99%) evacuation was achieved in 29 patients (78.4%). Glasgow Coma Scale (GOS) scores were significantly improved at discharge compared with admission scores (P < 0.001). The overall survival rate at 3 months was 81.08% (30/37), including 51.35% (19/37) with good function (GOS, 4-5), 13.51% (5/37) with disability (GOS, 3), and 16.22% (6/37) in a vegetative state (GOS, 2). The mortality rate (GOS, 1) was 18.92% (7/37). Our series showed that, according to the extension direction of hematomas, to select middle or distal TTH is effective and safe for TH.

Hedgehog and Notch signaling in enteric nervous system development.

The enteric nervous system (ENS) in mammals is derived from a small pool of progenitor cells, namely enteric neural crest cells (NCCs). These precursor cells proliferate extensively to expand, migrate over a long distance to fully colonize the developing gut and differentiate into millions of neurons and glia to form a functional ENS for regulating the complex behaviors of the gut. This developmental process relies on a precise regulation of the neuronal and glial differentiation and requires an appropriate balance between the migration, proliferation and differentiation of enteric NCCs and their progeny. Hedgehog (Hh) and Notch signalings are essential for almost every aspect of ENS development, and they confer both the long- and short-range signals to coordinate these seemingly diverse cellular processes. In this review, we summarize the roles of Hh and Notch signaling, particularly in the context of gut organogenesis and ENS development and emphasize how combinatory Hh and Notch signaling renders functional diversity as well as specificity.

[Progress in the study of Velvet and LaeA proteins and their relation to the development and bioactive compounds in medicinal fungi].

The medicinal fungi, which are of great importance in traditional medicine, are facing the problems of wild resources scarcity and low concentration of bioactive compounds. Velvet family and LaeA global regulator play a vital role in secondary metabolism and developmental programs, which are found in a wide variety of fungi ranging from Chytridiomycota to Basidiomycota. This review elaborates the structures and functions between Velvet family and LaeA protein. The Velvet family which shares the Velvet protein domain, including VeA (Velvet), VelB (Velvet like B), VosA (viability of spores A) and VelC (Velvet like C), acts on the regulation function is secondary metabolism and developmental programs such as asexual and sexual development. Furthermore, the function is affected by environmental factors such as light and temperature. LaeA protein which owns S-adenosylmethionine-dependent methyltransferase domain, coordinately regulates development and secondary metabolism by regulating and modifying the Velvet proteins. The regulation of LaeA is mediated by light receptor proteins. Therefore, clarifying the mechanism of Velvet and LaeA proteins in medicinal fungi will pave the way for nurturing medicinal fungi and improving production of bioactive compounds.

[Reasons that seedless fruits of Siraitia grosvenorii become small].

OBJECTIVE: To study the reasons that the seedless fruits of Siraitia grosvenorii developed to smaller ones. METHODS: The differences of fruit expanding, gene expressing and cell development were investigated between the triploid and diploid fruits from two strains F050 and F049. RESULTS: The results showed the expanding of triploid fruits was stopped about 20 days after artificial pollination, 10 days earlier than the diploid fruits. Meanwhile, it was also investigated that aux expressing level in the triploid fruits was greatly higher than that in diploid fruits, while its ipt, cyt-p450, spds, cycB, cycD1, cycD3, cdkA, cdkB, exp and xth expressing level were greatly lower than that in diploid fruits. The majority of sarcocarp cells of the triploid fruits kept in the stage of small ones comparing with the diploid fruits. CONCLUSION: The expression of the genes of the proteins involving cell division and expansion was inhibited as the significant reduction of endogenous IAA, CTK, GA and SPDS after bad fertilization and the embryo abortion, which resulted in the end of division and extension of sarcocarp cells. Above reasons induce small fruits of triploid seedless Siraitia grosvenorii.

Nitrogen metabolism pathways and functional microorganisms in typical karst wetlands.

Aha Lake artificial reservoir wetland, Niangniang Mountain karst mountain wetland, and Caohai plateau lake wetland are typical karst wetlands in Guizhou Province with unique topography and geomorphic features. They were selected as research objects in this study to explore microorganisms and functional genes in nitrogen metabolism adopting macro-genome sequencing technology. It was found that Proteobacteria, Actinobacteria, and Acidobacteria were the dominant phyla in nitrogen metabolism in these three wetlands, similar to previous studies. However, at the genus level, there was a significant difference, with the dominant bacteria being Bradyrhizobium, Methylocystis, and Anaeromyxobacter. Six nitrogen metabolism pathways, including nitrogen fixation, nitrification, denitrification, dissimilatory nitrate reduction, assimilatory nitrate reduction, and complete nitrification, comammox, were revealed, but anaerobic ammonia oxidation genes were not detected. Nitrogen metabolism microorganisms and pathways were more affected by SOM, pH, NO3-, and EC in karst wetlands. This study further discussed microorganisms and functions of nitrogen metabolism in karst wetlands, which was of great significance to nitrogen cycles of karst wetland ecosystems.

Upcycling plastic waste into fully recyclable composites through cold sintering.

Plastics have substantial societal benefits, but their widespread use has led to a critical waste management challenge. While mechanical recycling dominates the reuse of post-consumer plastics, it is limited in efficacy, especially for composites. To address this, we propose a direct reprocessing approach that enables the creation of hybrid, long-lasting, and durable composites from difficult-to-recycle plastics. This approach utilizes cold sintering, a process that consolidates inorganic powders through fractional dissolution and precipitation at temperatures far below conventional sintering; these temperatures are compatible with plastic processing. We show that this process can create inorganic-matrix composites with significant enhancements in tensile strength and toughness over pure gypsum, which is commonly found in construction waste. These composites can be recycled multiple times through direct reprocessing with the addition of only water as a processing promoter. This approach to recycling leads to composites with orders of magnitude lower energy demand, global warming potential, and water demand, when compared against common construction products. Altogether, we demonstrate the potential for cold sintering to integrate waste into high-performance recyclable composites.

Study on the mechanisms of acupuncture combined with paroxetine in the treatment of mild to moderate depression based on DNA methylation analysis. / 基于DNA甲基化探讨针刺联合帕罗西汀治疗轻中度抑郁症的疗效机制.

OBJECTIVES: To explore the therapeutic effect of acupuncture combined with paroxetine for mild to moderate depression and the regulatory role of brain derived neurotrophic factor (BDNF) in patients based on DNA methylation. METHODS: A total of 66 patients with mild to moderate depression who met the inclusion and exclusion criteria were randomly divided into an observation (acupuncture+medication) group and a control (medication) group, with 33 patients in each group, and other 25 healthy volunteers were taken as the healthy group. The patients of the control group were treated by oral administration of paroxetine 20 mg/d for 4 weeks. The patients of the observation group were treated by acupuncture stimulation of Zhongwan (CV12), Qihai (CV6), Zusanli (ST36), Sanyinjiao (SP6), Shangxing (GV23), Shuigou (GV26), Shaoshang (LU11), Yinbai (SP1) and Daling (PC7) (for 20 min, 3 times a week for 4 weeks) on the basis of medication treatment (the same as that of the control group). Before treatment, 2 and 4 weeks of treatment, and 2 weeks of follow-up, the therapeutic effect was assessed using Hamilton Depression Scale 17 (HAMD-17). The SPSS25.0 software was used to form a randomized grouping and to randomly select 25 patients from the observation group and 25 patients from the control group for blood collecting and data analysis. The blood samples were taken for assaying serum BDNF content and the methylation degree of BDNF gene promotor I with ELISA and MassARRAY techniques, respectively. RESULTS: 1) In comparison with those before treatment, the total score of HAMD-17, sleep disorder factor score, and anxiety somatization factor score of both the observation and control groups were significantly decreased after 2 and 4 weeks of treatment, and 2 weeks of follow-up (P<0.05), except sleep disorder factor score in the control group after 2 weeks of the treatment. Compared with the same time-points of the control group, the HAMD-17 total score and sleep disorder factor score of the observation group were decreased after 2 and 4 weeks of treatment, and 2 weeks of follow-up (P<0.05), while the anxiety somatization factor score was evidently decreased after 2 weeks of treatment (P<0.05). 2) Following 2 weeks of treatment, the total effective rate and markedly effective rate of the observation group were 80%(24/30)and 36.67% (11/30), respectively, being significantly higher than those ï¼»(26.67% and 0 %)ï¼½ of the control group. After 4 weeks of treatment, the markedly effective rate of the observation group was 70.00% (21/30), being significantly higher than that 40% (12/30) of the control group (P<0.05), while the total effective rates of the observation and control groups were the same (100%). 3) Before the treatment, comparison among the healthy, observation and control groups showed no statistical significance in the methylation degree of each site (CpG1.2, CpG5.6, CpG8.9, CpG26, CpG27, CpG31, and CpG33.34) of BDNF gene promotor I, while after 4 weeks of the treatment, the methylation degree of CpG31 was considerably lower in the observation group than in the control group (P<0.05). 4) Before the treatment, the contents of serum BDNF of both observation and control group had no significant difference, but were evidently lower than that of the healthy group (P<0.05). Compared with that before treatment, the serum BDNF contents in both observation and control groups were significantly increased after the treatment (P<0.05), and was significantly higher in the observation group than in the control group (P<0.05). 5) The correlation analysis showed a negative correlation between the BDNF protein content and HAMD-17 score (correlation coefficient ρ=-0.686, P<0.01). CONCLUSIONS: Acupuncture may have an antidepressant role by decreasing CpG31 methylation of BDNF and increasing the serum content of BDNF protein in patients with depression. In addition, acupuncture combined with paroxetine has more advantages in treating mild to moderate depression than oral paroxetine alone, and can improve sleep disorders and anxiety somatization symptoms more quickly.

The impact of medium-chain triglycerides on weight loss and metabolic health in individuals with overweight or obesity: A systematic review and meta-analysis.

BACKGROUNDS: The efficacy of medium-chain triglycerides (MCTs) for weight management and mitigating metabolic disorders among individuals with overweight and obesity remains a topic of ongoing discussion. Notably, there is a gap in the distinction between pure MCTs and medium-long-chain triglycerides (MLCTs). METHODS: This meta-analysis investigates the efficacy of MCTs on weight loss and glucolipid metabolism in these populations, explicitly evaluating the differential effects of pure MCTs and MLCTs. We performed a random-effects meta-analysis on relevant studies examining weight loss and glucolipid parameters, incorporating a subgroup analysis conducted based on intervention types, pure MCTs versus MLCTs. RESULTS: Our findings revealed diets enriched with MCTs are more effective in achieving weight reduction (WMD: -1.53%; 95% CI: -2.44, -0.63; p < 0.01), particularly those containing pure MCTs (WMD: -1.62%; 95% CI: -2.78, -0.46; p < 0.01), compared to long-chain fatty acids (LCTs) enriched diets. However, our subgroup analysis indicates that an MLCTs-enriched diet did not significantly reduce weight loss. Additionally, MCTs-enriched diets were associated with significant reductions in blood triglyceride levels and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) scores, compared to LCTs-enriched diets. CONCLUSIONS: Hence, the authors recommend incorporating pure MCTs in dietary interventions for individuals with overweight and obesity, particularly those with comorbidities such as dyslipidemia and impaired glucose metabolism.