Tag: statistics

Chin Med. 2025 Jan 3;20(1):1. doi: 10.1186/s13020-024-01053-2.

ABSTRACT

BACKGROUND: This research aims to explore the anti-obesity potential of Wu-Mei-Wan (WMW), particularly its effects on adipose tissue regulation in obese mice induced by a high-fat diet (HFD). The study focuses on understanding the role of heat shock factor 1 (HSF1) in mediating these effects.

METHODS: HFD-induced obese mice were treated with WMW. Body weight, food intake, and histopathological analysis of adipose tissue were conducted. Brown adipose tissue (BAT) activity was evaluated using Positron Emission Tomography, and ultrastructural changes were examined via transmission electron microscopy. Proteomic analysis identified targets of WMW in obesity treatment. HSF1 expression was inhibited to confirm its role. Molecular docking studied interactions between WMW and HSF1. Short-chain fatty acids (SCFAs) in the intestines were measured to determine if WMW’s effects on HSF1 are mediated through SCFAs. Protein expression was assessed using western blot, immunohistochemistry, immunofluorescence and RT-qPCR were employed to detect the mRNA levels. Statistical analyses included t-tests, ANOVA, and non-parametric tests like the Mann-Whitney U test or Kruskal-Wallis test.

RESULTS: WMW significantly mitigates the adverse effects of a HFD on body weight and glucose metabolism in obese mice. Both low-dose WMW and high-dose WMW treatments led to reduced weight gain and improved glucose tolerance, with low-dose WMW showing more pronounced effects. WMW also reversed structural damage in BAT, enhancing mitochondrial integrity and thermogenic function, particularly at the low dose. Additionally, WMW treatment promoted the browning of WAT, evidenced by increased expression of key thermogenic proteins such as UCP1 and PGC-1α. The increase in HSF1 expression in both BAT and WAT, observed with WMW treatment, was crucial for these beneficial effects, as inhibition of HSF1 negated the positive outcomes. Furthermore, WMW treatment led to elevated levels of short-chain fatty acids SCFAs in the intestines, which are associated with increased HSF1 expression.

CONCLUSIONS: WMW represents a potent therapeutic strategy for obesity, promoting metabolic health and beneficial modulation of adipose tissue through an HSF1-dependent pathway.

PMID:39754217 | DOI:10.1186/s13020-024-01053-2

J Orthop Surg Res. 2025 Jan 3;20(1):5. doi: 10.1186/s13018-024-05434-z.

ABSTRACT

OBJECTIVE: To investigate the application value of arthroscopic channel modification in meniscal injury repair.

METHODS: We retrospectively analyzed the data of 100 patients with meniscus injuries treated with knee arthroscopy from December 2022 to December 2023 and divided them into a control group and a modified group according to the application of “arthroscopic access modification technology”. We compared the operation time, postoperative hospitalization time, VAS score, Lysholm knee function score, postoperative complications, and postoperative images of the patients in these two groups. We compared the operation time, postoperative hospitalization time, pre- and postoperative VAS scores, Lysholm knee function scores, postoperative complications and postoperative imaging indices of the patients in the two groups.

RESULTS: All patients successfully underwent surgery and were followed up without intraoperative vascular or nerve injury or postoperative complications such as infection, wound necrosis or thrombosis. The average follow-up time was 16.03 ± 3.69 months; the average operation time and postoperative hospitalization time of the modified group were significantly better than those of the control group were (P < 0.05); the pain and knee function of the two groups significantly improved over time (P < 0.05); and, compared with those of the control group, the modified group could obtain a more satisfactory score at an early stage of the postoperative period (P < 0.05), and the comparison of the intermediate and long-term scores of the two groups was not statistically significant (P > 0.05). There was no statistically significant difference (P > 0.05).

CONCLUSION: The improved arthroscopic access technique can make the entry and exit of instruments into and out of the joint cavity smoother, improve the surgical field of view, significantly shorten the operation time, reduce the occurrence of intraoperative complications, improve the function of patients’ knee joints earlier, and increase their satisfaction with the operation.

PMID:39754209 | DOI:10.1186/s13018-024-05434-z

Diabetol Metab Syndr. 2025 Jan 3;17(1):1. doi: 10.1186/s13098-024-01543-1.

ABSTRACT

BACKGROUND: To identify the relationship between BMI or lipid metabolism and diabetic neuropathy using a Mendelian randomization (MR) study.

METHODS: Body constitution-related phenotypes, namely BMI (kg/m²), total cholesterol (TC), and triglyceride (TG), were investigated in this study. Despite the disparate origins of these data, all were accessible through the IEU OPEN GWAS database ( https://gwas.mrcieu.ac.uk/ ). Instrumental variables and F-statistics for each exposure-outcome pair were determined in weighted mode, weighted median, MR-Egger and Inverse-Variance Weighted (IVW) MR analyses. The p-value threshold was consistently set at 5.00E-08, following established methodology. The preliminary analysis utilized the IVW method to explore potential causal relationships between body constitution-related phenotypes and diabetic neuropathy. Inverse variance weighting, a technique amalgamating random variables, assigns weights inversely proportional to each variable’s variance, commonly used for merging findings from independent studies. The weighted median method provides a causal estimate even when up to 50% of the instruments are invalid, enhancing robustness. The weighted mode method identifies the most common causal effect, reducing bias when some instruments exhibit horizontal pleiotropy. The Wald ratio method was utilized to calculate exposure-outcome effects, employing a range of methodologies to ensure result accuracy across different scenarios. This study addresses the critical gap in understanding the causal relationship between BMI, lipid metabolism, and diabetic neuropathy (DN). Employing a MR approach, it highlights BMI as a predictive factor for DN progression, providing insights into potential risk management strategies.

RESULTS: IVW analysis showed that BMI (P = 0.033, OR = 2.53, 95% CI 1.08-5.96) and triglycerides level (P = 0.593, OR = 1.11, 95% CI 0.77-1.60) were positively associated with the initiation of DN, indicating that the values of BMI and triglycerides are potentially the risk factors in DN development. Additionally, TC was negatively associated with the DN (P = 0.069, OR = 0.72, 95% CI = 0.50-1.03).The forest plot of advanced analysis between BMI and DN relationship indicated a positive correlation between increasing BMI and the risk of DN. In addition, it is evident that with the increase in BMI, the risk of diabetic polyneuropathy also rises. This research demonstrates a positive association between BMI and DN risk (P = 0.033, OR = 2.53, 95% CI = 1.08-5.96). However, no significant correlation was observed between triglycerides (P = 0.593) or total cholesterol (P = 0.069) and DN development, underscoring the complex interplay between lipid metabolism and DN.

CONCLUSION: This research demonstrates a positive association between the risk of DN and BMI, while no significant correlation exists between TG or TC and the development of DN. These results imply that BMI may serve as a predictive factor for the progression of DN.

PMID:39754202 | DOI:10.1186/s13098-024-01543-1

Trials. 2025 Jan 3;26(1):5. doi: 10.1186/s13063-024-08626-4.

ABSTRACT

BACKGROUND: Breast cancer is the most diagnosed cancer in women worldwide and carries a considerable psychosocial burden. Interventions based on Acceptance and Commitment Therapy (ACT) and compassion-based approaches show promise in improving adjustment and quality of life in people with cancer. The Mind programme is an integrative ACT and compassion-based intervention tailored for women with breast cancer, which aims to prepare women for survivorship by promoting psychological flexibility and self-compassion. A pilot study of the Mind programme has shown acceptability and preliminary efficacy in improving quality of life and psychological health. This paper presents the study protocol of two randomised controlled trials that aim to test the efficacy and cost-effectiveness of an optimised version of the Mind programme in women with breast cancer.

METHODS: Participants will be women diagnosed with breast cancer randomly assigned to the Mind programme or a support group intervention (active control) in a 1:1 ratio for study 1, while study 2 includes one more arm (treatment as usual; inactive control) and a 2:2:1 ratio. Both interventions will be delivered weekly via an 8-session face-to-face or online group format. Data will be collected at baseline, post-treatment and 6-month follow-up. The efficacy and cost-effectiveness of the two interventions will be assessed. Treatment outcomes will comprise cancer-specific quality of life (primary outcome), anxiety and depressive symptoms, psychological flexibility, self-compassion, health-related quality of life, resource use, and intervention’s acceptability and feasibility. Study 1 will also include immunological and epigenetic markers associated with breast cancer prognosis and mental health. Outcome assessors will be blind to group allocation. Statistical analyses will be conducted using an intention-to-treat approach. Analyses of moderators and mediators of change will also be performed.

DISCUSSION: These trials examine the efficacy and cost-effectiveness of an integrative ACT and compassion-based intervention tailored for women with breast cancer. Greater improvements in psychosocial, biological and resource use are expected in the Mind group, when compared to the control group(s). Results will likely support the potential benefits of the Mind programme for breast cancer patients and highlight the clinical relevance of integrative and holistic interventions in oncology. TRIALS REGISTRATION {2A, 2B}: ClinicalTrials.gov NCT05642897 and NCT06212414. Registered on December 8, 2022, and January 18, 2024.

PMID:39754194 | DOI:10.1186/s13063-024-08626-4

J Transl Med. 2025 Jan 4;23(1):8. doi: 10.1186/s12967-024-06035-4.

ABSTRACT

BACKGROUND: Anti-CD19 chimeric antigen receptor (CAR) T cell therapy is a common, yet highly efficient, cellular immunotherapy for lymphoma. However, many recent studies have reported on its cardiovascular (CV) toxicity. This study analyzes the cardiotoxicity of CD19 CAR T cell therapy in the treatment of lymphoma for providing a more valuable reference for clinicians.

METHODS: The PubMed, Embase, Cochrane library, and Web of Science databases were comprehensively searched from the time of their establishment to May 2024. The ClinicalTrials.gov English database is a comprehensive repository of the original studies of CD19 CAR T cell therapy and associated adverse outcomes, such as arrhythmia, CV events, and hypotension, in patients with lymphoma. The Cochrane Collaboration tool and the Newcastle-Ottawa Scale (NOS) were used to assess the quality of the included original studies. For RCTs, the Cochrane Collaboration tool was used to assess the risk of bias. For non-randomized studies, the risk of bias was assessed using the NOS quality assessment scale.

RESULTS: A risk analysis of two randomized controlled trials and nine cohort studies, totaling 1379 patients with lymphoma receiving CD19 CAR-T, is conducted. The incidences for all-cause mortality, CV events, and hypotension were found to be 17.8%, 17.8%, and 52.8%, respectively. Additionally, the incidences of heart failure (HF), cardiomyopathy, cardiac arrest, and other CV events are 3%, 0.6%, 1.3%, and 2.5%, respectively. In addition to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) as adverse events, patients treated with CD19 CAR T cells are also at risk of CV events. The most common CV events are arrhythmia and HF. Our further analysis showed that the incidence of CV events was 28.7% in the elderly and 13.5% in adults. The incidence of CV events in the elderly was higher than that in adults, and it was statistically significant. Furthermore, the incidence of CV events and hypotension is strongly associated with patients with CRS.

CONCLUSION: Therefore, clinicians should pay close attention to the occurrence of such CV events and take timely prevention and intervention measures to further improve the safety of CD19 CAR T cell therapy.

PMID:39754193 | DOI:10.1186/s12967-024-06035-4

Lipids Health Dis. 2025 Jan 4;24(1):2. doi: 10.1186/s12944-024-02422-4.

ABSTRACT

BACKGROUND: Prior research indicates a potential link between dyslipidemia and endometriosis (EMs). However, the relationship between remnant cholesterol (RC) and EMs has not been thoroughly investigated. Consequently, looking into and clarifying the connection between RC and EMs was the primary goal of this study.

METHODS: Following the screening of participants from the NHANES dataset spanning 2001 to 2006, a total of 1,840 individuals were incorporated into this research. A weighted multivariable logistic regression analysis was first performed to investigate the relation between RC and the likelihood of encountering EMs. To assess the degree of consistency in the link between RC and EMs across different populations, additional subgroup analyses were performed. In addition, the researchers used the extreme gradient boosting (XGBoost) technique and the area under the receiver operating characteristic curve (ROC) to evaluate how well RC recognized EMs. Lastly, both linear and nonlinear relationships were validated using generalized additive models (GAM), while dose-response connections were investigated through restricted cubic spline models.

RESULTS: After accounting for all potential confounders, a strong correlation between RC and EMs was identified. In particular, an increase of one unit in RC was linked to a 135% rise in the likelihood of developing EMs. Analyses of subgroups revealed that these relationships remained stable across the majority of subgroups (interaction P-value > 0.05). Multivariable logistic regression demonstrated RC’s independent predictive value, maintaining statistical significance after adjusting for confounders. The AUC of 0.614 suggests RC’s moderate ability to discriminate EMs, outperforming traditional markers like LDL-C in sensitivity and specificity. Furthermore, XGBoost analysis identified RC as the most critical predictor among lipid-related and demographic variables. The relationship was further validated through GAM, which visually confirmed a linear trend, and RCS, which provided statistical evidence of linearity.

CONCLUSION: This study reveals a clear connection between RC and the likelihood of having EMs within the US population, suggesting RC as a potential marker for further investigation in understanding endometriosis risk.

PMID:39754185 | DOI:10.1186/s12944-024-02422-4

BMC Oral Health. 2025 Jan 3;25(1):14. doi: 10.1186/s12903-024-05401-4.

ABSTRACT

BACKGROUND: Molar incisor hypomineralization (MIH) is estimated to affect more than 800 million people worldwide. The clinical management of MIH can be challenging. For dentists, to provide effective and high-quality dental care to people affected by MIH, it is essential that they improve their awareness, ability to describe the clinical situation, and knowledge of treatment modalities. Previous surveys conducted with students showed that only a limited number are confident in diagnosing MIH. The aim of the study was to assess the clinical knowledge and perceptions of 4th- and 5th-year dental students regarding the distribution, severity, etiology and treatment modalities of MIH.

METHODS: In this cross-sectional study, a total of 194 students studying in the 4th- (85 students) and 5th- (109 students) years participated in the survey. The survey had 23 questions and two sections, the first of which was intended to gather demographic information about the students. The second part consisted of questions about the diagnosis, etiology, and treatment of MIH. The independent t test and the chi-square test was used to compare qualitative data.

RESULTS: The majority of students (78.87%) stated that they had known about MIH. 5th-year students had known about MIH at a statistically significantly higher rate compared to 4th-year students (p = 0.0001). While only 19.69% of the participants stated that they could diagnose a patient with MIH, the proportion of 5th-year students who could make such a diagnosis was statistically significantly higher (p = 0.0001). The majority of the participants (96.39%) stated that they wanted MIH-related practices to be included more in their clinical education. The most desired topic to be included was diagnosis (91.98%).

CONCLUSIONS: The current study showed that students have some knowledge about MIH, but this knowledge is not sufficient, especially in terms of diagnosis and treatment. The students clearly wanted to develop their knowledge of MIH both theoretically and practically.

PMID:39754180 | DOI:10.1186/s12903-024-05401-4

J Orthop Surg Res. 2025 Jan 3;20(1):8. doi: 10.1186/s13018-024-05345-z.

ABSTRACT

AIMS: Which is the best extensile lateral (ELA) or sinus tarsi (STA) approach for osteosynthesis displaced intraarticular calcaneal fracture (DIACF) is still debatable. The current RCT’s primary objective was to compare the complications incidence after open reduction and internal fixation of DIACFs through STA vs. ELA. The secondary objectives were the differences in intraoperative radiation exposure, time to fracture union, functional and radiological outcomes.

METHODS: Between August 2020 and February 2023, 157 patients with Sanders type II and III fractures were randomly assigned to either ELA (81 patients with 95 fractures) or STA (76 patients with 91 fractures). The primary outcome was the incidence of complications. The secondary outcomes were Böhler’s and Gissane angles angle, fracture union, and American Orthopaedic Foot and Ankle Society (AOFAS) score.

RESULTS: No statistical differences between both groups regarding basic demographic data, injury characteristics, and fracture classification; however, patients in the STA group were operated upon significantly earlier (4.43 ± 7.37 vs. 7 ± 6.42 days, p = 0.001). STA’s operative time was significantly shorter (55.83 ± 7.35 vs. 89.66 ± 7.12 min, p < 0.05), and no statistical difference regarding intraoperative radiation exposure. The time to fracture union was significantly shorter in STA (6.33 ± 0.8 vs. 7.13 ± 0.7 weeks, p = 0.000). Skin complications (superficial or deep infection) and Subtalar osteoarthritis were significantly higher in ELA (18.9% vs. 3.3%, p = 0.001) and (32.6% vs. 9.9%, p = 0.001), respectively. The radiological parameters were significantly better in STA postoperatively and at the last follow up. The AOFAS scores were significantly better in STA (83.49 ± 7.71 vs. 68.62 ± 7.05, respectively, p = 0.000).

CONCLUSION: During osteosynthesis of Sanders type II and III DIACFs, STA is superior to ELA in terms of operating earlier, shorter operative time, fewer complications, and better radiological and functional outcomes.

PMID:39754179 | DOI:10.1186/s13018-024-05345-z

BMC Psychiatry. 2025 Jan 3;25(1):8. doi: 10.1186/s12888-024-06399-3.

ABSTRACT

BACKGROUNDS: Dissociative experiences are described as crucial psychological mechanisms involving the organism’s responses to severe psychological traumas and unpleasant past experiences. This research was conducted to examine the psychometric properties of the Dissociative Experiences Measure, Oxford (DEMO) in the Iranian general population.

METHODS: This study used cross-sectional correlation, and the statistical population consisted of Iranians over 15 years old. Among them, 712 subjects were chosen as the study sample using the convenience sampling technique. Data were acquired between February and April 2022 using DEMO, Dissociative Experiences Scale II (DES-II), and Depression Anxiety and Stress Scale (DASS-21). In order to determine DEMO’s psychometric properties, Confirmatory Factor Analysis (CFA) was used to investigate the factorial structure, Cronbach’s alpha analyses to examine the internal consistency reliability, and Pearson correlation analyses to examine the relationships between DEMO’s subscales and the subscales of DES-II and DASS-21, indicating convergent validity. In order to analyze the data, LISREL 8.0 and SPSS-26 were used.

RESULTS: Based on the results of the CFA, the proposed five-factor structure of DEMO showed an acceptable fit to the data (χ² = 1939.81, SRMR = 0.078, CFI = 0.96, RMSEA = 0.074). The internal reliability was satisfactory for the total scale (Cronbach’s alpha = 0.93) and the five subscales (Cronbach’s alpha = 0.89 for unreality, 0.87 for numb and disconnected, 0.80 for memory blanks, 0.85 for zoned out, and 0.79 for vivid internal world). The CFA results indicated that the five factors explained 60.69% of the variance. Significant correlations were observed between the DEMO subscales and the respective subscales of DES-II and DASS-21, confirming the measure’s convergent validity.

CONCLUSION: It can be concluded from the results of this study that the DEMO has high reliability and validity among the Iranian general population.

PMID:39754178 | DOI:10.1186/s12888-024-06399-3

Biol Sex Differ. 2025 Jan 3;16(1):1. doi: 10.1186/s13293-024-00683-3.

ABSTRACT

BACKGROUND: X chromosome inactivation (XCI) is a female-specific process in which one X chromosome is silenced to balance X-linked gene expression between the sexes. XCI is initiated in early development by upregulation of the lncRNA Xist on the future inactive X (Xi). A subset of X-linked genes escape silencing and thus have higher expression in females, suggesting female-specific functions. One of these genes is the highly conserved gene Kdm6a, which encodes a histone demethylase that removes methyl groups at H3K27 to facilitate gene expression. KDM6A mutations have been implicated in congenital disorders such as Kabuki Syndrome, as well as in sex differences in development and cancer.

METHODS: Kdm6a was knocked out (KO) using CRISPR/Cas9 gene editing in hybrid female mouse embryonic stem (ES) cells derived either from a 129 × Mus castaneus (cast) cross or a BL6 x cast cross. In one of the lines a transcriptional stop signal inserted in Tsix results in completely skewed X silencing upon differentiation. The effects of both homozygous and heterozygous Kdm6a KO on Xist expression during the onset of XCI were measured by RT-PCR and RNA-FISH. Changes in gene expression and in H3K27me3 enrichment were investigated using allele-specific RNA-seq and Cut&Run, respectively. KDM6A binding to the Xist gene was characterized by Cut&Run.

RESULTS: We observed impaired upregulation of Xist and reduced coating of the Xi during early stages of differentiation in Kdm6a KO cells, both homozygous and heterozygous, suggesting a threshold effect of KDM6A. This was associated with aberrant overexpression of genes from the Xi after differentiation, indicating loss of X inactivation potency. Consistent with KDM6A having a direct role in Xist regulation, we found that the histone demethylase binds to the Xist promoter and KO cells show an increase in H3K27me3 at Xist, consistent with reduced expression.

CONCLUSIONS: These results reveal a novel female-specific role for the X-linked histone demethylase, KDM6A in the initiation of XCI through histone demethylase-dependent activation of Xist during early differentiation. X chromosome inactivation is a female-specific mechanism that evolved to balance sex-linked gene dosage between females (XX) and males (XY) by silencing one X chromosome in females. X inactivation begins with the upregulation of the long noncoding RNA Xist on the future inactive X chromosome. While most genes become silenced on the inactive X chromosome some genes escape inactivation and thus have higher expression in females compared to males, suggesting that escape genes may have female-specific functions. One such gene encodes the histone demethylase KDM6A which function is to turn on gene expression by removing repressive histone modifications. In this study, we investigated the role of KDM6A in the regulation of Xist expression during the onset of X inactivation. We found that KDM6A binds to the Xist gene to remove repressive histone marks and facilitate its expression in early development. Indeed, depletion of KDM6A prevents upregulation of Xist due to abnormal persistence of repressive histone modifications. In turn, this results in aberrant overexpression of genes from the inactive X chromosome. Our findings point to a novel mechanism of Xist regulation during the initiation of X inactivation, which may lead to new avenues of treatment to alleviate congenital disorders such as Kabuki syndrome and sex-biased immune disorders where X-linked gene dosage is perturbed.

PMID:39754175 | DOI:10.1186/s13293-024-00683-3