Background: Adrenocortical hormones, particularly 11-oxygenated androgens, are pivotal in female reproductive health and fertility. Standardized detection kits and population-specific reference intervals are lacking in China, hindering related clinical applications. Methods: A HPLC-tandem mass spectrometry (HPLC-MS/MS) pipeline was developed, rigorously validated, and applied to simultaneously quantify corticosterone, cortisone, cortisol, 18-OH cortisol, androstenedione (A4), 11β-hydroxyandrostenedione (11-OH A4), dehydroepiandrosterone, and dehydroepiandrosterone sulfate in serum samples from 455 reproductive-aged women (18–45 yrs) in Guangxi, China. Age-dependent concentration trends were analyzed, and reference intervals stratified by age (2.5th to 97.5th percentiles) were established. Correlations with body-composition metrics, ethnicity, and the menstrual cycle were investigated. Results: The HPLC-MS/MS method demonstrated high precision (intra- and inter-assay CVs < 15%), accuracy, and sensitivity. All eight hormones exhibited significant age-related declines (P < 0.001 for seven hormones; P = 0.001 for 11-OH A4). Notably, 11-OH A4 levels were significantly lower in the 35–45-yr (3.05 nmol/L) and 25–34-yr (3.09 nmol/L) age groups than in the 18–24-yr (3.57 nmol/L) age group, whereas no significant difference was observed between the 35–45-yr and 25–34-yr age groups. Weak negative correlations were observed between the body mass index and corticosterone and cortisone levels, whereas ethnicity and the menstrual cycle showed no significant associations with hormone levels. Conclusions We developed an HPLC-MS/MS-based method for simultaneously quantifying eight adrenocortical hormones, including 11-OH A4, and defined age-specific reference intervals for reproductive-aged Chinese women. These findings advance the clinical utility of adrenocortical hormones in diagnosing and managing reproductive disorders.

Purpose: We aimed to compare broad-spectrum antibiotic use between hospice and nonhospice patients with cancer at the end of life using nationwide data from Korea. Methods: In this retrospective cohort study, we analyzed the Korean National Health Insurance Service data of adult patients with cancer who died between 2018 and 2021. Hospice users were defined as patients who received inpatient, home-based, or consultation-based hospice care before death. We applied propensity score matching (1:2) to balance the baseline characteristics of the hospice and non-hospice groups. Broad-spectrum antibiotic use, including anti-pseudomonal penicillins, anti-pseudomonal cephalosporins, carbapenems, and glycopeptides, was assessed during the last 3 months of life using prescription proportions and days of therapy per 1,000 patient-days. Results: After matching, 38,102 hospice and 75,736 non-hospice users were analyzed. During the last 3 months of life, 74.6% of hospiceand 79.0% of non-hospice users received at least one broad-spectrum antibiotic (P＜0.001).The proportion of patients receiving broad-spectrum antibiotics was generally lower amonghospice users across all time intervals (P＜0.001), and the number of days of therapy wasalso lower, with the largest differences observed during the final week and last 3 days of life.Subgroup analyses showed the highest antibiotic exposure among patients with hematologic and pancreatobiliary cancers, particularly in the non-hospice group. Conclusion Hospice involvement was associated with lower use and reduced exposure to broad-spectrum antibiotics among patients with cancer near the end of life. These findings support the alignment of end-of-life treatment decisions with the comfort-oriented goals of hospice care.

Purpose: This study aimed to explore the practices, perceptions, and barriers related to specialty palliative care (SPC) referrals among oncologists in Korea, highlighting the clinical implications of early integration. Materials and Methods: A cross-sectional online survey targeting board-certified hemato-oncology specialists was conducted between August 1-25, 2024. The survey assessed referral practices, attitudes toward early SPC integration, referral criteria, barriers, and institutional characteristics. Results: A total of 227 oncologists participated (response rate, 36.7%). Among them, 68.7% reported frequent SPC referrals, with higher referral rates observed among younger physicians, those in tertiary hospitals, and institutions with in-house SPC teams (p < 0.001). Although 74.9% supported early SPC integration, referrals were often inconsistently timed, frequently occurring after disease progression or at the discontinuation of chemotherapy. For time-based referrals, the most commonly endorsed triggers were disease progression despite palliative second-line treatment and a prognosis of expected mortality within 6-12 months. Need-based referral triggers such as patient or family requests (96.5%), psychological distress (89.9%), or uncontrolled symptoms (83.3%), were also widely endorsed. The major barriers to early SPC integration included patient and family resistance (70.0%) and limited availability of SPC teams (34.4%). Conclusion This study emphasizes the importance of systematic efforts to promote timely SPC integration in Korea, including education to raise patient awareness, improved referral systems, and enhanced infrastructure. The positive attitudes toward early SPC among oncologists reflect a growing recognition of its value, highlighting the need for strategies that align with international standards.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.

BACKGROUND:At present,a large number of studies have shown that mesenchymal stem cells can be combined with different strategies to more effectively improve liver fibrosis and inhibit its progression to end-stage liver disease.OBJECTIVE:To explore the mechanism of mesenchymal stem cells combined with different strategies to improve liver fibrosis compared with mesenchymal stem cells alone.METHODS:The first author used computers to search CNKI,WanFang,VIP,PubMed,Web of Science,and Nature databases involving mesenchymal stem cells combined with different strategies to improve liver fibrosis.The search terms were"mesenchymal stem cells,liver fibrosis,combination therapy,liver stellate cells"in Chinese,and"mesenchymal stem/stromal cells,liver/hepatic fibrosis/cirrhosis,combination therapy,hepatic stellate cells/HSCs"in English.By quickly browsing the title and abstract of the article,excluding the articles that are not closely related to the topic,104 articles were finally selected for review analysis.RESULTS AND CONCLUSION:Mesenchymal stem cells improve liver fibrosis by differentiating into hepato-like cells,inhibiting hepatic stellate cell activation,immune regulation,and other mechanisms.However,the low rate of liver colonization,low survival rate,and short action time of mesenchymal stem cells after transplantation limit their clinical application.Mesenchymal stem cells can improve liver fibrosis through a combination of drugs,gene modification,cytokines and other strategies,and the efficacy is better than that of mesenchymal stem cells alone.Moreover,the combination of mesenchymal stem cells and different strategies can effectively improve liver fibrosis by promoting mesenchymal stem cell homing,inhibiting hepatic stellate cell activation,regulating the microenvironment,and regulating signaling pathways.Mesenchymal stem cells can also show better liver-derived differentiation,homing and survival functions in reducing liver fibrosis through pretreatment,miRNA regulation and combination with other cells.The combination of mesenchymal stem cells and different strategies cannot avoid the potential risks of mesenchymal stem cells alone in the treatment of liver fibrosis,and the safety of these strategies(drugs,gene modifications,cytokines,etc.)is also worth considering.In addition,the number and route of mesenchymal stem cell transplantation need to be further studied.

Objective To investigate the coagulation effect of a cold atmospheric plasma(CAP)jet device with helium as the working gas and to study its coagulation mechanism preliminarily.Methods A CAP jet device treatment group,a helium airflow treatment group,a hot air treatment group(60℃)and a natural coagulation group were formed according to the treatment modes of the blood samples,with 10 μL of blood samples involved in each group,in order to validate the coagulation effect of the CAP jet device in vitro;the coagulation mechanism of the CAP jet device was explored by its application to the treatment of anticoagulated whole blood,platelet-rich plasma and platelet-depleted plasma;the coagulation effect of the CAP jet device in vivo was verified with a mouse liver punctate hemorrhage model and a rabbit mesenteric hemorrhage model.Results The CAP jet device can significantly accelerate the coagulation of anticoagulated blood droplets,and the coagulation time of anticoagulated blood droplets in the CAP jet device-treated group was shortened from 28 min in the natural coagulation group to(23±1.56)s,with the difference statistically significant(P<0.05),and the CAP jet device treatment group gained advantages significantly over the helium airflow treatment group(P<0.05)and the hot air(60℃)treatment group(P<0.05)in coagulation-promoting effect;the procoagulant effect of the CAP jet device rose with the increase of platelet content in blood droplets,and the coagulation effect of platelet-rich blood droplets was significantly better than that of whole blood(P<0.05),while no coagulation was observed in platelet-poor droplets.The CAP jet device could rapidly stop hemostasis of punctate hemorrhage in mouse liver and mesenteric hemorrhage in rabbits without delayed hemorrhage occurring within 10 min,and no obvious structural abnormality of the liver and thermal damage of the tissue were found microscopically.Conclusion The CAP jet device plays procoagulant and hemostatic effects in vivo and in vitro,and its effect is not dependent on temperature and airflow evaporation effects and is considered to be related to platelet activation,with low thermal damage to living tissue.[Chinese Medical Equipment Journal,2025,46(6):20-27]

This study was aimed at exploring novel auxiliary diagnostic biomarkers for brucellosis and their potential miR-NA-mRNA regulatory networks.High-throughput sequencing was used to compare miRNA expression differences in serum ex-osomes between patients with brucellosis and healthy controls.Subsequently,RT-qPCR was used to validate the expression of significantly upregulated exosomal miRNAs.The diagnostic value of these miRNAs was assessed with ROC curves,and bioin-formatics analyses were performed to investigate the potential roles of the miRNAs in brucellosis infection.The ROC curve a-nalysis indicated that the area under the curve for exosomal hsa-miR-11400(P＜0.05),hsa-miR-199a-5p(P＜0.05),and hsa-miR-148a-5p(P＜0.05)was 0.79,0.81,and 0.74,respectively.A total of 465 differentially expressed miRNAs and their tar-get genes were predicted,including 25 immune-related target genes,most of which were closely associated with cancer-related proteoglycans,NF-kappa B signaling pathways,and IL-17 signaling pathways.The constructed differentially expressed gene network indicated that the immune genes PLXNA2,IL17RA,PRKCA,CD22,ACVR1B,and CBL might be regulated by hsa-miR-199a-5p and hsa-miR-148a-5p.These findings suggest that exosomal miRNAs might serve as auxiliary diagnostic indicators for brucellosis.Our exosomal miRNA-mRNA regulatory network provides new insights into the pathogenesis and treatment of brucellosis.

Objective To investigate the coagulation effect of a cold atmospheric plasma(CAP)jet device with helium as the working gas and to study its coagulation mechanism preliminarily.Methods A CAP jet device treatment group,a helium airflow treatment group,a hot air treatment group(60℃)and a natural coagulation group were formed according to the treatment modes of the blood samples,with 10 μL of blood samples involved in each group,in order to validate the coagulation effect of the CAP jet device in vitro;the coagulation mechanism of the CAP jet device was explored by its application to the treatment of anticoagulated whole blood,platelet-rich plasma and platelet-depleted plasma;the coagulation effect of the CAP jet device in vivo was verified with a mouse liver punctate hemorrhage model and a rabbit mesenteric hemorrhage model.Results The CAP jet device can significantly accelerate the coagulation of anticoagulated blood droplets,and the coagulation time of anticoagulated blood droplets in the CAP jet device-treated group was shortened from 28 min in the natural coagulation group to(23±1.56)s,with the difference statistically significant(P<0.05),and the CAP jet device treatment group gained advantages significantly over the helium airflow treatment group(P<0.05)and the hot air(60℃)treatment group(P<0.05)in coagulation-promoting effect;the procoagulant effect of the CAP jet device rose with the increase of platelet content in blood droplets,and the coagulation effect of platelet-rich blood droplets was significantly better than that of whole blood(P<0.05),while no coagulation was observed in platelet-poor droplets.The CAP jet device could rapidly stop hemostasis of punctate hemorrhage in mouse liver and mesenteric hemorrhage in rabbits without delayed hemorrhage occurring within 10 min,and no obvious structural abnormality of the liver and thermal damage of the tissue were found microscopically.Conclusion The CAP jet device plays procoagulant and hemostatic effects in vivo and in vitro,and its effect is not dependent on temperature and airflow evaporation effects and is considered to be related to platelet activation,with low thermal damage to living tissue.[Chinese Medical Equipment Journal,2025,46(6):20-27]

This study was aimed at exploring novel auxiliary diagnostic biomarkers for brucellosis and their potential miR-NA-mRNA regulatory networks.High-throughput sequencing was used to compare miRNA expression differences in serum ex-osomes between patients with brucellosis and healthy controls.Subsequently,RT-qPCR was used to validate the expression of significantly upregulated exosomal miRNAs.The diagnostic value of these miRNAs was assessed with ROC curves,and bioin-formatics analyses were performed to investigate the potential roles of the miRNAs in brucellosis infection.The ROC curve a-nalysis indicated that the area under the curve for exosomal hsa-miR-11400(P＜0.05),hsa-miR-199a-5p(P＜0.05),and hsa-miR-148a-5p(P＜0.05)was 0.79,0.81,and 0.74,respectively.A total of 465 differentially expressed miRNAs and their tar-get genes were predicted,including 25 immune-related target genes,most of which were closely associated with cancer-related proteoglycans,NF-kappa B signaling pathways,and IL-17 signaling pathways.The constructed differentially expressed gene network indicated that the immune genes PLXNA2,IL17RA,PRKCA,CD22,ACVR1B,and CBL might be regulated by hsa-miR-199a-5p and hsa-miR-148a-5p.These findings suggest that exosomal miRNAs might serve as auxiliary diagnostic indicators for brucellosis.Our exosomal miRNA-mRNA regulatory network provides new insights into the pathogenesis and treatment of brucellosis.