Objective To explore the predictive effect of serum 25-hydroxyvitamin D3 [25(OH)D3] and blood lipid metabolism indexes on the occurrence of osteoporosis in type 2 diabetes mellitus (T2DM). Methods Totally 98 patients with T2DM in the hospital from January 2022 to January 2024 were classified into osteoporosis group (38 cases) and non-osteoporosis group (60 cases) by means of concurrent osteoporosis status. The levels of serum 25(OH)D3 and blood lipid metabolism indexes [high density lipoprotein (HDL), total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), VLDL] were measured in study subjects. The association of serum 25(OH)D3 and blood lipid metabolism indexes with osteoporosis was explored by Logistic regression analysis. The predictive value of serum 25(OH)D3 and blood lipid metabolism indexes on osteoporosis was analyzed by receiver operating characteristic curve (ROC). Results Serum 25(OH)D3 and HDL levels in the osteoporosis group were lower while TG and LDL levels were higher than those in the non-osteoporosis group (P<0.05). The differences in the levels of TC and VLDL were insignificant between groups (P>0.05). After logistic regression analysis, the levels of serum 25(OH)D3, HDL, TG and LDL were closely related to the occurrence of osteoporosis (P<0.05). ROC curve indicated that the area under the curve (AUC), sensitivity and specificity of combined prediction of osteoporosis by serum 25(OH)D3, HDL, TG, and LDL were 0.943, 92.11% and 85.00%, and the efficiency of combined prediction was better than that of each index alone (P<0.05). Conclusion The levels of serum 25(OH)D3, HDL, TG and LDL in T2DM are closely related to osteoporosis. Early combined monitoring of the indicators can provide reference value for clinical prediction of osteoporosis occurrence in patients with T2DM.

Plant-derived exosome-like nanovesicles (PELNs), characterized by a natural lipid bilayer membrane, have rapidly emerged as a prominent research frontier in medicine owing to their unique biological properties and robust therapeutic potential. This review comprehensively examines the biological profiles, mechanistic functions, and recent engineering advancements of PELNs. In terms of composition, PELNs are uniquely enriched in plant-specific glycolipids, phosphatidylserine, secondary metabolites, and highly stable 2'-O-methylated miRNAs. This distinct molecular makeup endows them with exceptional biocompatibility, negligible immunogenicity, and the capacity for cross-species molecular communication. Mechanistically, PELNs demonstrate profound anti-inflammatory efficacy by suppressing the NF-κB and NLRP3 inflammasome pathways. They also serve as potent immune modulators, driving macrophage M1/M2 polarization and regulating T cell activity. Additionally, PELNs exhibit promising antitumor capabilities, targeting malignancies via reactive oxygen species (ROS) induction, TRAIL pathway activation, and tumor microenvironment remodeling. Crucially, the plant miRNAs encapsulated within PELNs remain highly stable in the gastrointestinal tract, allowing them to selectively alter gene expression in specific gut microbiota communities. This interaction deeply influences host immunity and metabolism, highlighting the vital role in cross-species regulation. Advancements in bioengineering have further expanded the clinical utility of PELNs. Targeted delivery efficiency can be significantly amplified via surface functionalization (e.g., folate and RGD sequences) and state-of-the-art drug loading technologies such as sonication and electroporation. Consequently, engineered PELNs surpass traditional synthetic nanocarriers in penetrating natural physiological barriers, particularly for oral and transdermal drug administration. Despite these advantages, clinical translation is currently hindered by the lack of standardized isolation protocols, challenges in scalable manufacturing, and the need for robust quality control frameworks. Looking forward, the integration of multi-omics approaches and AI-driven “molecular fingerprinting”—coupled with the design of synthetic biomimetic vesicles—will be instrumental in overcoming these bottlenecks, ultimately establishing PELNs as a next-generation platform for precision medicine and targeted nanotherapeutic delivery.

Objective To investigate the changes in eosinophil counts and the activation of microglial cells in the brain tissues of mice at different stages of Angiostrongylus cantonensis infection, and to examine the role of microglia in regulating the progression of angiostrongyliasis and unravel the possible molecular mechanisms. Methods Fifty BALB/c mice were randomly divided into the control group and the 7-d, 14-d, 21-day and 25-d infection groups, of 10 mice in each group. All mice in infection groups were infected with 30 stage III A. cantonensis larvae by gavage, and animals in the control group was given an equal amount of physiological saline. Five mice were collected from each of infection groups on days 7, 14, 21 d and 25 d post-infection, and 5 mice were collected from the control group on the day of oral gavage. The general and focal functional impairment was scored using the Clark scoring method to assess the degree of mouse neurological impairment. Five mice from each of infection groups were sacrificed on days 7, 14, 21 d and 25 d post-infection, and 5 mice from the control group were sacrificed on the day of oral gavage. Mouse brain tissues were sampled, and the pathological changes of brain tissues were dynamically observed using hematoxylin and eosin (HE) staining. Immunofluorescence staining with eosinophilic cationic protein (ECP) and ionized calcium binding adaptor molecule 1 (Iba1) was used to assess the degree of eosinophil infiltration and the counts of microglial cells in mouse brain tissues in each group, and the morphological parameters of microglial cells (skeleton analysis and fractal analysis) were quantified by using Image J software to determine the morphological changes of microglial cells. In addition, the expression of M1 microglia markers Fcγ receptor III (Fcgr3), Fcγ receptor IIb (Fcgr2b) and CD86 antigen (Cd86), M2 microglia markers Arginase 1 (Arg1), macrophage mannose receptor C-type 1 (Mrc1), chitinase-like 3 (Chil3), and phagocytosis genes myeloid cell triggering receptor expressed on myeloid cells 2 (Trem2), CD68 antigen (Cd68), and apolipoprotein E (Apoe) was quantified using real-time quantitative reverse transcription PCR (RT-qPCR) assay in the mouse cerebral cortex of mice post-infection. Results A large number of A. cantonensis larvae were seen on the mouse meninges surface post-infection, and many neuronal nuclei were crumpled and deeply stained, with a large number of bleeding points in the meninges. The median Clark scores of mouse general functional impairment were 0 (interquartile range, 0), 0 (interquartile range, 0.5), 6 (interquartile range, 1.0), 14 (interquartile range, 8.5) points and 20 (interquartile range, 9.0) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.45, P < 0.01), and the median Clark scores of mouse focal functional impairment were 0 (interquartile range, 0), 2 (interquartile range, 2.5), 7 (interquartile range, 3.0), 18 (interquartile range, 5.0) points and 25 (interquartile range, 6.5) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.72, P < 0.01). The mean scores of mice general and focal functional impairment were all higher in the infection groups than in the control group (all P values < 0.05). Immunofluorescence staining showed a significant difference in the eosinophil counts in mouse brain tissues among the five groups (F = 40.05, P < 0.000 1), and the eosinophil counts were significantly higher in mouse brain tissues in the 14-d (3.08 ± 0.78) and 21-d infection groups (5.97 ± 1.37) than in the control group (1.00 ± 0.28) (both P values < 0.05). Semi-quantitative analysis of microglia immunofluorescence showed a significant difference in the counts of microglial cells among the five groups (F = 17.66, P < 0.000 1), and higher Iba1 levels were detected in mouse brain tissues in 14-d (5.75 ± 1.28), 21-d (6.23 ± 1.89) and 25-d infection groups (3.70 ± 1.30) than in the control group (1.00 ± 0.30) (all P values < 0.05). Skeleton and fractal analyses showed that the branch length [(162.04 ± 34.10) μm vs. (395.37 ± 64.11) μm; t = 5.566, P < 0.05] and fractal dimension of microglial cells (1.30 ± 0.01 vs. 1.41 ± 0.03; t = 5.266, P < 0.05) were reduced in mouse brain tissues in the 21-d infection group relative to the control group. In addition, there were significant differences among the 5 groups in terms of M1 and M2 microglia markers Fcgr3 (F = 48.34, P < 0.05), Fcgr2b (F = 55.46, P < 0.05), Cd86 (F = 24.44, P < 0.05), Arg1 (F = 31.18, P < 0.05), Mrc1 (F = 15.42, P < 0.05) and Chil3 (F = 24.41, P < 0.05), as well as phagocytosis markers Trem2 (F = 21.19, P < 0.05), Cd68 (F = 43.95, P < 0.05) and Apoe (F = 7.12, P < 0.05) in mice brain tissues. Conclusions A. cantonensis infections may induce severe pathological injuries in mouse brain tissues that are characterized by massive eosinophil infiltration and persistent activation of microglia cells, thereby resulting in progressive deterioration of neurological functions.

Purpose: Coronavirus disease 2019 (COVID-19) infection may affect serum hormones levels and male sexual function. This study aims to provide evidence for the causal relationship between COVID-19 infection, serum testosterone levels and the risk of erectile dysfunction (ED) using a two-sample Mendelian randomization (MR) approach. Materials and Methods: Summary-level data for serum testosterone levels (199,569 samples and 12,321,875 single nucleotide polymorphisms [SNPs]) were obtained from Rebecca’s study, while data for ED (6,175 cases and 217,630 controls) were sourced from Bovijn’s study. Genetic variations linked to COVID-19 were used as instrumental variables (IVs) in meta-analyses of genome-wide association studies (GWASs) involving 6,406 cases and 902,088 controls from the COVID-19 Host Genetics Initiative.The inverse-variance weighted (IVW) method was primarily employed to evaluate the potential associations between COVID-19 infection, serum testosterone levels, and the risk of ED. The weighted mode, weighted-median and simple-median method were employed to evaluate the sensitivity. Heterogeneity and pleiotropic outlier were assessed using Cochran’s Q test and MREgger regression. Results: The MR analysis demonstrated that COVID-19 infection was associated with reduced serum testosterone levels (odds ratio [OR] 0.966, 95% confidence interval [CI] 0.938–0.993, p=0.016) and an increased risk of ED (OR 1.205, 95% CI 1.063–1.367, p=0.004) when using IVW methods. Sensitivity analyses utilizing various IV sets and MR approach remained consistent. Conclusions COVID-19 infection is associated with a decrease in serum testosterone levels and an increased risk of ED. Male patients recovering from COVID-19 need to pay special attention to their sex hormone levels and sexual health.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

OBJECTIVES: To explore the synthesis of high-quality CT (sCT) from cone-beam CT (CBCT) using PE-CycleGAN for adaptive radiotherapy (ART) for nasopharyngeal carcinoma. METHODS: A perception-enhanced CycleGAN model "PE-CycleGAN" was proposed, introducing dual-contrast discriminator loss, multi-perceptual generator loss, and improved U-Net structure. CBCT and CT data from 80 nasopharyngeal carcinoma patients were used as the training set, with 7 cases as the test set. By quantifying the mean absolute error (MAE), peak signal-to-noise ratio (PSNR), structural similarity index (SSIM), as well as the dose gamma pass rate and the relative dose deviations of the target area and organs at risk (OAR) between sCT and reference CT, the image quality and dose calculation accuracy of sCT were evaluated. RESULTS: The MAE of sCT generated by PE-CycleGAN compared to the reference CT was (56.89±13.84) HU, approximately 30% lower than CBCT's (81.06±15.86) HU (P<0.001). PE-CycleGAN's PSNR and SSIM were 26.69±2.41dB and 0.92±0.02 respectively, significantly higher than CBCT's 21.54±2.37dB and 0.86±0.05 (P<0.001), indicating substantial improvements in image quality and structural similarity. In gamma analysis, under the 2 mm/2% criterion, PE-CycleGAN's sCT achieved a pass rate of (90.13±3.75)%, significantly higher than CBCT's (81.65±3.92)% (P<0.001) and CycleGAN's (87.69±3.50)% (P<0.05). Under the 3 mm/3% criterion, PE-CycleGAN's sCT pass rate of (90.13±3.75)% was also significantly superior to CBCT's (86.92±3.51)% (P<0.001) and CycleGAN's (94.58±2.23)% (P<0.01). The mean relative dose deviation of the target area and OAR between sCT and planned CT was within ±3% for all regions, except for the Lens Dmax (Gy), which had a deviation of 3.38% (P=0.09). The mean relative dose deviations for PTVnx HI, PTVnd HI, PTVnd CI, PTV1 HI, PRV_SC, PRV_BS, Parotid, Larynx, Oral, Mandible, and PRV_ON were all less than ±1% (P>0.05). CONCLUSIONS PE-CycleGAN demonstrates the ability to rapidly synthesize high-quality sCT from CBCT, offering a promising approach for CBCT-guided adaptive radiotherapy in nasopharyngeal carcinoma.
Humans ; Cone-Beam Computed Tomography/methods* ; Nasopharyngeal Neoplasms/diagnostic imaging* ; Nasopharyngeal Carcinoma/radiotherapy* ; Radiotherapy Planning, Computer-Assisted/methods* ; Radiotherapy Dosage ; Signal-To-Noise Ratio ; Radiotherapy, Intensity-Modulated

OBJECTIVES: To propose a new method for optimizing radiotherapy planning for lung cancer by incorporating prognostic models that take into account individual patient information and assess the feasibility of treatment planning optimization directly guided by minimizing the predicted prognostic risk. METHODS: A mixed fluence map optimization objective was constructed, incorporating the outcome-based objective and the physical dose constraints. The outcome-based objective function was constructed as an equally weighted summation of prognostic prediction models for local control failure, radiation-induced cardiac toxicity, and radiation pneumonitis considering clinical risk factors. These models were derived using Cox regression analysis or Logistic regression. The primary goal was to minimize the outcome-based objective with the physical dose constraints recommended by the clinical guidelines. The efficacy of the proposed method for optimizing treatment plans was tested in 15 cases of non-small cell lung cancer in comparison with the conventional dose-based optimization method (clinical plan), and the dosimetric indicators and predicted prognostic outcomes were compared between different plans. RESULTS: In terms of the dosemetric indicators, D_95% of the planning target volume obtained using the proposed method was basically consistent with that of the clinical plan (100.33% vs 102.57%, P=0.056), and the average dose of the heart and lungs was significantly decreased from 9.83 Gy and 9.50 Gy to 7.02 Gy (t=4.537, P<0.05) and 8.40 Gy (t=4.104, P<0.05), respectively. The predicted probability of local control failure was similar between the proposed plan and the clinical plan (60.05% vs 59.66%), while the probability of radiation-induced cardiac toxicity was reduced by 1.41% in the proposed plan. CONCLUSIONS The proposed optimization method based on a mixed objective function of outcome prediction and physical dose provides effective protection against normal tissue exposure to improve the outcomes of lung cancer patients following radiotherapy.
Humans ; Lung Neoplasms/radiotherapy* ; Radiotherapy Planning, Computer-Assisted/methods* ; Prognosis ; Radiotherapy, Intensity-Modulated/methods* ; Carcinoma, Non-Small-Cell Lung/radiotherapy* ; Radiotherapy Dosage ; Female ; Male ; Middle Aged

OBJECTIVE: To explore the association between acupuncture during controlled ovarian hyperstimulation (COH) and the live birth rate (LBR) using different propensity score methods. METHODS: In this retrospective cohort study, eligible women who underwent a COH were divided into acupuncture and non-acupuncture groups. The primary outcome was LBR, as determined by propensity score matching (PSM). LBR was defined as the delivery of one or more living infants that reached a gestational age over 28 weeks after embryo transfer. The propensity score model encompassed 16 confounding variables. To validate the results, sensitivity analyses were conducted using three additional propensity score methods: propensity score adjustment, inverse probability weighting (IPW), and IPW with a "doubly robust" estimator. RESULTS: The primary cohort encompassed 9751 patients (1830 [18.76%] in the acupuncture group and 7921 [81.23%] in the non-acupuncture group). Following 1:1 PSM, a higher LBR was found in the acupuncture cohort (41.4% [755/1824] vs 36.4% [664/1824], with an odds ratio of 1.23 [95% confidence interval, 1.08-1.41]). Three additional propensity score methods produced essentially similar results. The risk of serious adverse events did not significantly differ between the two groups. CONCLUSION This retrospective study revealed an association between acupuncture and an increased LBR among patients undergoing COH, and that acupuncture is a safe and valuable treatment option. Please cite this article as: Zheng XY, Jiang ZY, Li YT, Li CL, Zhu H, Yu Z, Yu SY, Yang LL, Tang SY, Lü XY, Liang FR, Yang J. Association between acupuncture and live birth rates after fresh embryo transfer: A cohort study based on different propensity score methods. J Integr Med. 2025; 23(5):528-536.
Humans ; Female ; Propensity Score ; Embryo Transfer ; Adult ; Acupuncture Therapy ; Retrospective Studies ; Pregnancy ; Live Birth ; Birth Rate ; Cohort Studies

OBJECTIVE: To explore and quantify the association of hot night exposure during the sperm development period (0-90 lag days) with semen quality. METHODS: A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014-2020 were recruited in this multicenter study. Two indices (i.e., hot night excess [HNE] and hot night duration [HND]) were used to estimate the heat intensity and duration during nighttime. Linear mixed models were used to examine the association between hot nights and semen quality parameters. RESULTS: The exposure-response relationship revealed that HNE and HND during 0-90 days before semen collection had a significantly inverse association with sperm motility. Specifically, a 1 °C increase in HNE was associated with decreased sperm progressive motility of 0.0090 (95% confidence interval [ CI]: -0.0147, -0.0033) and decreased total motility of 0.0094 (95% CI: -0.0160, -0.0029). HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021 (95% CI: -0.0040, -0.0003) and 0.0023 (95% CI: -0.0043, -0.0002), respectively. Consistent results were observed at different temperature thresholds on hot nights. CONCLUSION Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.
Humans ; Male ; Semen Analysis ; Adult ; Sperm Motility ; Hot Temperature/adverse effects* ; China ; Middle Aged ; Spermatozoa/physiology* ; Young Adult