ObjectiveStroke poses a heavy burden due to its high mortality and morbidity rates. Accurate and real-time detection of lesions is pivotal for prompt clinical intervention and favorable prognosis. Electrical impedance tomography (EIT) and microwave tomography (MWT) have emerged as compelling alternatives for stroke screening, owing to their non-ionizing, non-invasive and portable nature. EIT provides information on tissue conductivity, and MWT offers high sensitivity to changes in dielectric properties. However, single-modality imaging is inherently limited, EIT suffers from low sensitivity to deep-seated tissues and severe ill-posedness of inverse problems, whereas MWT is challenged by strong nonlinearity in inverse scattering and susceptibility to modeling errors. Consequently, the clinical utility of standalone EIT or MWT for stroke diagnosis remains constrained by poor spatial resolution and imaging artifacts. To improve the accuracy and robustness of stroke imaging, a dual-modality fusion conditional denoising diffusion probabilistic model (DM-DDPM) was proposed for high-precision dual-modality image reconstruction. MethodsA dual-encoder network with a symmetric architecture and independently trained parameters was constructed to extract heterogeneous features separately from EIT boundary voltage measurements and MWT scattered field signals. Attentional feature fusion (AFF) is employed to integrate complementary information from the two modalities adaptively, generating robust fused priors that suppress redundant noise while preserving key physical characteristics. Subsequently, the fused priors are embedded into a Transformer-based diffusion model via a cross attention mechanism to guide the reverse denoising process. This approach effectively reduces artifacts and enhances the stability of conductivity distribution reconstruction. Time step embedding is introduced to enable the network to perceive the diffusion stage and further improve the accuracy of noise prediction. ResultsSimulated experiments demonstrated that DM-DDPM significantly outperforms single-modality and multi-modality networks under various noise levels. A head model simulation dataset was constructed based on COMSOL Multiphysics, and tests were carried out under 50 dB, 40 dB and 30 dB signal-to-noise ratio levels. At 30 dB, the average relative error (RE) was below 0.20, while the structural similarity index measure (SSIM) and correlation coefficient (CC) remained above 0.90 and 0.89, respectively. Compared with single-modality and multi-modality networks, artifacts were significantly reduced, lesion edges were clearer, and localization was more accurate. The model maintains high reconstruction quality and strong robustness for single, double, and triple lesions simultaneously. Furthermore, physical experiments were conducted using a 16-electrode EIT system and a 16-antenna MWT system with asynchronous data acquisition. These experiments confirmed the feasibility of the method in real-world scenarios and demonstrated that it can robustly reconstruct simulated lesions despite environmental interference and measurement noise, validating its reliability for practical clinical applications. ConclusionThe proposed method effectively combines complementary dual-modality information with a conditional diffusion model. Low accuracy and poor noise resistance in single-modality imaging were effectively addressed, while the noise amplification issue caused by direct multimodal data fusion was avoided. The proposed algorithm exhibits strong anti-noise interference ability and high imaging stability in both simulation and physical experiments. Precise localization of stroke lesions with different quantities was achieved, providing a high-precision, and practical technical support for clinical stroke detection.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

Reproductive system diseases are among the primary contributors to the decline in social fertility rates and the intensification of aging, posing significant threats to both physical and mental health, as well as quality of life. Recent research has revealed the substantial potential of the gut microbiota in improving reproductive system diseases. Under healthy conditions, the gut microbiota maintains a dynamic balance, whereas dysfunction can trigger immune-inflammatory responses, metabolic disorders, and other issues, subsequently leading to reproductive system diseases through the gut-gonadal axis. Reproductive diseases, in turn, can exacerbate gut microbiota imbalance. This article reviews the impact of the gut microbiota and its metabolites on both male and female reproductive systems, analyzing changes in typical gut microorganisms and their metabolites related to reproductive function. The composition, diversity, and metabolites of gut bacteria, such as Bacteroides, Prevotella, and Firmicutes, including short-chain fatty acids, 5-hydroxytryptamine, γ-aminobutyric acid, and bile acids, are closely linked to reproductive function. As reproductive diseases develop, intestinal immune function typically undergoes changes, and the expression levels of immune-related factors, such as Toll-like receptors and inflammatory cytokines (including IL-6, TNF-α, and TGF-β), also vary. The gut microbiota and its metabolites influence reproductive hormones such as estrogen, luteinizing hormone, and testosterone, thereby affecting folliculogenesis and spermatogenesis. Additionally, the metabolism and absorption of vitamins can also impact spermatogenesis through the gut-testis axis. As the relationship between the gut microbiota and reproductive diseases becomes clearer, targeted regulation of the gut microbiota can be employed to address reproductive system issues in both humans and animals. This article discusses the regulation of the gut microbiota and intestinal immune function through microecological preparations, fecal microbiota transplantation, and drug therapy to treat reproductive diseases. Microbial preparations and drug therapy can help maintain the intestinal barrier and reduce chronic inflammation. Fecal microbiota transplantation involves transferring feces from healthy individuals into the recipient’s intestine, enhancing mucosal integrity and increasing microbial diversity. This article also delves into the underlying mechanisms by which the gut microbiota influences reproductive capacity through the gut-gonadal axis and explores the latest research in diagnosing and treating reproductive diseases using gut microbiota. The goal is to restore reproductive capacity by targeting the regulation of the gut microbiota. While the gut microbiota holds promise as a therapeutic target for reproductive diseases, several challenges remain. First, research on the association between gut microbiota and reproductive diseases is insufficient to establish a clear causal relationship, which is essential for proposing effective therapeutic methods targeting the gut microbiota. Second, although gut microbiota metabolites can influence lipid, glucose, and hormone synthesis and metabolism via various signaling pathways—thereby indirectly affecting ovarian and testicular function—more in-depth research is required to understand the direct effects of these metabolites on germ cells or granulosa cells. Lastly, the specific efficacy of gut microbiota in treating reproductive diseases is influenced by multiple factors, necessitating further mechanistic research and clinical studies to validate and optimize treatment regimens.

Circadian rhythm is an endogenous biological clock mechanism that enables organisms to adapt to the earth’s alternation of day and night. It plays a fundamental role in regulating physiological functions and behavioral patterns, such as sleep, feeding, hormone levels and body temperature. By aligning these processes with environmental changes, circadian rhythm plays a pivotal role in maintaining homeostasis and promoting optimal health. However, modern lifestyles, characterized by irregular work schedules and pervasive exposure to artificial light, have disrupted these rhythms for many individuals. Such disruptions have been linked to a variety of health problems, including sleep disorders, metabolic syndromes, cardiovascular diseases, and immune dysfunction, underscoring the critical role of circadian rhythm in human health. Among the numerous systems influenced by circadian rhythm, the skin—a multifunctional organ and the largest by surface area—is particularly noteworthy. As the body’s first line of defense against environmental insults such as UV radiation, pollutants, and pathogens, the skin is highly affected by changes in circadian rhythm. Circadian rhythm regulates multiple skin-related processes, including cyclic changes in cell proliferation, differentiation, and apoptosis, as well as DNA repair mechanisms and antioxidant defenses. For instance, studies have shown that keratinocyte proliferation peaks during the night, coinciding with reduced environmental stress, while DNA repair mechanisms are most active during the day to counteract UV-induced damage. This temporal coordination highlights the critical role of circadian rhythms in preserving skin integrity and function. Beyond maintaining homeostasis, circadian rhythm is also pivotal in the skin’s repair and regeneration processes following injury. Skin regeneration is a complex, multi-stage process involving hemostasis, inflammation, proliferation, and remodeling, all of which are influenced by circadian regulation. Key cellular activities, such as fibroblast migration, keratinocyte activation, and extracellular matrix remodeling, are modulated by the circadian clock, ensuring that repair processes occur with optimal efficiency. Additionally, circadian rhythm regulates the secretion of cytokines and growth factors, which are critical for coordinating cellular communication and orchestrating tissue regeneration. Disruptions to these rhythms can impair the repair process, leading to delayed wound healing, increased scarring, or chronic inflammatory conditions. The aim of this review is to synthesize recent information on the interactions between circadian rhythms and skin physiology, with a particular focus on skin tissue repair and regeneration. Molecular mechanisms of circadian regulation in skin cells, including the role of core clock genes such as Clock, Bmal1, Per and Cry. These genes control the expression of downstream effectors involved in cell cycle regulation, DNA repair, oxidative stress response and inflammatory pathways. By understanding how these mechanisms operate in healthy and diseased states, we can discover new insights into the temporal dynamics of skin regeneration. In addition, by exploring the therapeutic potential of circadian biology in enhancing skin repair and regeneration, strategies such as topical medications that can be applied in a time-limited manner, phototherapy that is synchronized with circadian rhythms, and pharmacological modulation of clock genes are expected to optimize clinical outcomes. Interventions based on the skin’s natural rhythms can provide a personalized and efficient approach to promote skin regeneration and recovery. This review not only introduces the important role of circadian rhythms in skin biology, but also provides a new idea for future innovative therapies and regenerative medicine based on circadian rhythms.

Ferroptosis,a novel form of programmed cell death driven by iron-dependent lipid peroxida-tion,plays a crucial role in both disease treatment and microbial control due to its multi-level regulatory mechanisms.It mainly involves iron metabolism,lipid peroxidation,and antioxidant systems.In the field of disease treatment,ferroptosis is regarded as a highly promising therapeutic target because of its key role in autoimmune diseases,cancer,and cardiovascular diseases.This review systematically summarizes the core regulatory factors of ferroptosis,such as glutathione peroxidase 4(GPX4)and long-chain acyl-CoA synthetase 4(ACSL4)and their interaction networks,and deeply explores the application prospects of targeted intervention strategies based on ferroptosis signaling pathways in disease treatment and micro-bial control.Additionally,we also summarize the current issues faced by ferroptosis in practical applica-tions and proposes strategies,such as nanodelivery,improved drug chemical stability and enhanced water solubility to optimize therapeutic efficacy.We aim to provide a theoretical basis and practical guidelines for exploring more targeted treatments using ferroptosis.

Objective To investigate the effect of butorphanol on lipopolysaccharide-induced chondrocyte injury by regulating the stromal cell-derived factor-1α(SDF-1α)/C-X-C chemokine receptor 4(CXCR4)pathway.Methods Human C28/12 chondrocytes were cultured in vitro and assigned to the following groups:control(normal culture),model(100 μmol/L lipopolysaccharide),model+low-dose butorphanol(100 μmol/L lipopolysaccharide+1μmol/L butorphanol),model+medium-dose butorphanol(100 μmol/L lipopolysaccharide+2 μmol/L butorphanol),model+high-dose butorphanol(100 μmol/L lipopolysaccharide+4 μmol/L butorphanol),and model+high-dose butorphanol+NUCC-390(100 μmol/L lipopolysaccharide+4 μmol/L butorphanol+500 nmol/L CXCR4 agonist NUCC-390).Cell viability,interleukin(IL)-6 and tumor necrosis factor-α(TNF-α)levels,apoptosis,and SDF-1α/CXCR4 pathway-related proteins were evaluated by MTT assay,enzyme-linked immunosorbent assay,flow cytometry,and Western blot,respectively.Results Chondrocyte survival rate and Bcl-2 protein expression were decreased while TNF-α,IL-6,apoptosis rate,Bax,Cleaved caspase-3,SDF-1α,and CXCR4 proteins were increased in the model group compared with the control group(P＜0.05).The above indicators were improved in the model+low-,medium-,and high-dose butorphanol groups compared with the model group,while the result for the model+high-dose butorphanol+NUCC-390 group were opposite to those of the model+high-dose butorphanol group.Conclusions Butorphanol may improve lipopolysaccharide-induced chondrocyte injury induced by inhibiting the SDF-1α/CXCR4 signaling pathway.

Objective To investigate the dosimetric effect of a biological optimization approach combining physical optimization with generalized equivalent uniform dose(gEUD)on hippocampus avoidance whole-brain radiotherapy(HA-WBRT).Methods A retrospective review was conducted of 20 patients with multiple brain metastases who underwent whole-brain radiotherapy at a certain hospital between May 2021 and December 2022.Two radiotherapy plans including plan_DV and plan_gEUD were designed for each patient by using Eclipse V15.6 planning system.Plan_DB used conven-tional dose-volume(DV)physical optimization,and plan_gEUD went through re-optimization with an Upper gEUD function applied to hippocampal region and hippocampal protection zone.Evaluation was carried out in accordance with RTOG 0933 guidance for the absolute values D2%,D98%and D50%received by 2%,98%,and 50%of the target volume in the planning target volume,conformity index(CI),homogeneity index(HI),gradient index(GI)and the dosimetric indexes of hippocampal region,hippocampal protection zone and other organs at risk(OARs).SPSS 26.0 software was used for statistical analysis.Results The two kinds of plans both had the target volume coverage meet the requirements of RTOG 0933 guidance.Plan_gEUD had the D98%,D2%and V105 of the planning target volume lower than those of plan_DV,with the differences being statistically significant(all P<0.05).The two kinds of plans had no significant differences in monitor unit,D50%and Dmax of PTV,HI,CI and GI(all P>0.05).Plan_gEUD had the Dmax and Dmean of hippocampal region and them of hippocampal pro-tection zone lower than those of plan_DV,and the optic nerve Dmax of plan_gEUD was higher than that of plan_DV,with the differences being statistically significant(all P<0.05).There were no statistically significant differences between the two kinds of plans in the Dmax of inner ear,optic chiasm,lens,and eyeball(all P>0.05).Conclusion Physical optimization in the HA-WBRT plan combined with gEUD optimization results in a greater dose reduction to the hippocampus while maintaining target coverage.

Aim To study the difference in hepatotox-icity of psoralen on normal rats and Yin-deficiency rats from the perspective of lipid metabolism,so as to help explain the mechanism of psoralen cautiously used in patients with Yin deficiency recorded in ancient books.Methods SD rats were randomly divided into the nor-mal control group(carboxymethyl cellulose-Na,CMC-Na),normal administration group(CMC-Na+psor-alen),Yin-deficiency control group(CMC-Na+thy-roxine)and Yin-deficiency administration group(CMC-Na+thyroxine+psoralen).The model of Yin-deficiency was established by thyroxine(1 mg·kg-1)for ten days,and then psoralen(200 mg·kg-1)was given for three days.The serum indexes related to liver injury were detected by automatic biochemical analy-zer,the morphological changes of liver tissue were ob-served using HE and oil red O staining,and the relative transcription levels of lipid metabolism related enzymes and mRNA of transporter and endoplasmic reticulum stress related factors were detected using Real-time PCR.Results After intragastric administration of psoralen for three days,compared with the normal group,the levels of serum alanine aminotransferase(ALT),aspartate transaminase(AST),total bile acid(TBA)and triglyeride(TG)in Yin deficiency group increased more significantly,while TC,ALB and TP de-creased more significantly,and liver HE and oil red O staining showed more obvious lipid degeneration.TG synthesis factors adrenocortical carcinoma(ACC),fatty acid synthase(FASN)and sterolregulatory element binding protein-1(SREBP-1)were down-regulated more significantly,TG transport factors mili-total pro-tein(MTP)and lipoprotein pipase(LPL)were down-regulated more evidently,fatty acid β-oxidation related factors carnitine palmitoyltransferase 1A(CPT1A),carnitine/organic cation transporter 2(OCTN2)and peroxisome proliferators-activated receptors-alpha(PPARα)were down-regulated more apparently,TC transporter adenosine triphosphate binding cassette transporter G8(ABCG8)and bile acid receptor farne-soid X receptor(FXR)were down-regulated more ob-viously,and endoplasmic reticulum stress factor activa-ting transcription factor 4(ATF4)was up-regulated more significantly.Conclusions Psoralen can cause more severe hepatotoxicity in Yin deficiency rats than that in normal administration group,and its mechanism may be related to the disorder of hepatic lipid metabo-lism,aggravation of hepatic cholestasis and steatosis,and activation of endoplasmic reticulum stress re-sponse.

Aim To explore the compatibility and po-tential mechanism of effective components of Biejia-Ezhu against triple negative breast cancer(TNBC)and verify it by experiments.Methods Effective compo-nents and targets of Biejia-Ezhu were obtained by TC-MSP and Swiss Target Prediction.Disease targets of TNBC were obtained from OMMI and GeneCards data-bases.The PPI network was constructed using STRING database.GO and KEGG path enrichment analysis was performed using DAVID database.Cytoscape3.9.1 software was used to construct the"drug-component-target-disease"network,screen key targets and compo-nents for molecular docking,and further verify the com-patibility of key components and targets in vitro.Re-sults ① A total of 71 effective components were iden-tified in the Biejia-Ezhu drug pair.There were 146 drug targets associated with the disease.A total of 113 signaling pathways were identified by KEGG analysis.The 71 potential active components of Biejia-Ezhu mainly acted on key targets such as mTORC1,ULK1,TNF,EGFR,ESR1,STAT3,HIF1A,and PTGS2.Mo-lecular docking results showed that glycine and curcu-min were the key active components of Biejia-Ezhu,and both had strong docking activity against key target proteins mTORC1 and ULK1.②The results of in vitro experiment showed that glycine combined with curcu-min significantly inhibited the proliferation and clonal formation ability of TNBC cells(P＜0.05),up-regula-ted the expression of autophagy marker LC3 Ⅱ/Ⅰ,down-regulated the expression of EGFR,down-regula-ted the expression of pathway protein mTORC1,p-mTOR,p-ULK1,and promoted the expression of path-way protein ULK1(P＜0.05).Conclusion The key component of Biejia-Ezhu against triple-negative breast cancer is glycine-curcumin,the mechanism of which may be related to the regulation of the mTORC1/ULK1 signaling pathway to promote autophagy.

Objective:To explore the clinical characteristics and identification of the independent risk factors for disease progression in patients with anti-gp210 antibody-positive primary biliary cholangitis (PBC).Methods:A retrospective cohort study was performed. A total of 323 cases with PBC diagnosed in Tianjin Medical University General Hospital from January 2013 to June 2023 (125 patients with anti-gp210 antibody-positive and 198 patients with anti-gp210 antibody-negative) were included. Baseline and follow-up data were collected. The independent sample t-test and Mann-Whitney U rank sum test were used for comparison between groups of continuous data. The χ2 test was used to compare the data between groups for the count data. The Pearson test was used for correlation analysis between continuous variables. The Kaplan-Meier method was used to analyze the disease progression-free survival rate. The Cox regression model was used to analyze the risk factors for disease progression. Results:The male proportion (11.2% vs. 5.1%, P=0.040) and IgM level [3.29(1.88, 4.80) g/L vs. 2.56(1.44, 3.87) g/L, P=0.019] were significantly higher in patients with PBC with positive anti-gp210 antibodies than those of the negative group. Histopathological analysis showed that the Scheuer score [1(0,3) vs. 0(0,2)], bile duct inflammation [(2(1,3) vs. 1(1,2)] and bile duct reaction score [(2(1,3) vs. 1(1,2)] were higher in the positive group than those of the negative group ( P<0.05), and the maturity of the tertiary lymphoid structure was higher ( P=0.011). Kaplan-Meier analysis showed that the 5-year disease-free survival rate was significantly lower in patients with positive anti-gp210 antibodies than that of the negative group (55.8% vs. 79.7%, P=0.006) at a median follow-up of 3(2,6) years. Multivariate Cox regression analysis showed that γ-glutamyl transferase [ HR=1.002 (95% CI: 1.000～1.003)] and platelet count [ HR=0.993 (95% CI: 0.988～0.999)] were the independent influencing factors for disease progression in patients with anti-gp210 antibody-positive PBC ( P=0.002, 0.017). Conclusion:Patients with anti-gp210 antibody-positive PBC have more severe clinical pathological manifestations and a higher risk of disease progression. Higher levels of γ-glutamyl transferase and lower platelet counts during the first visit are independent risk factors for disease progression in patients with anti-gp210 antibody-positive PBC, which can be used as dynamic monitoring indicators for this population, suggesting the need for early intensive intervention.