This study systematically examined the effects of atomization as a transdermal permeation enhancer on the transdermal delivery of active ingredients with different physicochemical properties and investigated the underlying mechanisms. Porcine ear skin served as an in vitro model, and skin permeation experiments were conducted using Franz diffusion cells. Receptor fluids were collected at specific time points, and samples of the stratum corneum and viable epidermis–dermis were separated and prepared. Quantitative and visualization methods, including high-performance liquid chromatography, fluorescence derivatization, and confocal laser scanning microscopy, were used to compare skin retention and transdermal permeation of adenosine (AD), tranexamic acid (TXA), calcein (CAL), and tocopheryl acetate (TA) under atomized and non-atomized conditions. Additionally, transepidermal water loss (TEWL) measurements and attenuated total reflectance–Fourier transform infrared spectroscopy (ATR-FTIR) were employed to analyze the mechanism behind the penetration enhancement caused by atomization. The findings showed that atomization increased skin retention within the stratum corneum and viable epidermis–dermis, as well as the transdermal permeation of all four active ingredients to varying degrees. The most significant enhancement was observed for TXA, which has a relatively low molecular weight and moderate lipophilicity, while the enhancement effects for highly hydrophilic AD and highly lipophilic TA were comparatively limited; however, atomization significantly increased the skin retention of TA. TEWL results indicated that skin permeability increased within 4 hours after atomization and largely recovered within 8 hours. ATR-FTIR analysis suggested that atomization may facilitate transdermal delivery by disrupting the lipid order and keratin conformation in the stratum corneum.This study provides theoretical support and experimental references for the advancement of atomization transdermal delivery technology, as well as the design and development of related atomization products.

Stem cell treatment may enhance erectile dysfunction (ED) in individuals with cavernous nerve injury (CNI). Nevertheless, no investigations have directly ascertained the implications of varying amounts of human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) on ED. We compare the efficacy of three various doses of HUC-MSCs as a therapeutic strategy for ED. Sprague-Dawley rats (total = 175) were randomly allocated into five groups. A total of 35 rats underwent sham surgery and 140 rats endured bilateral CNI and were treated with vehicles or doses of HUC-MSCs (1 × 10 6 cells, 5 × 10 6 cells, and 1 × 10 7 cells in 0.1 ml, respectively). Penile tissues were harvested for histological analysis on 1 day, 3 days, 7 days, 14 days, 28 days, 60 days, and 90 days postsurgery. It was found that varying dosages of HUC-MSCs enhanced the erectile function of rats with bilateral CNI and ED. Moreover, there was no significant disparity in the effectiveness of various dosages of HUC-MSCs. However, the expression of endothelial markers (rat endothelial cell antigen-1 [RECA-1] and endothelial nitric oxide synthase [eNOS]), smooth muscle markers (alpha smooth muscle actin [α-SMA] and desmin), and neural markers (neurofilament [RECA-1] and neurogenic nitric oxide synthase [nNOS]) increased significantly with prolonged treatment time. Masson's staining demonstrated an increased in the smooth muscle cell (SMC)/collagen ratio. Significant changes were detected in the microstructures of various types of cells. In vivo imaging system (IVIS) analysis showed that at the 1 st day, the HUC-MSCs implanted moved to the site of damage. Additionally, the oxidative stress levels were dramatically reduced in the penises of rats administered with HUC-MSCs.
Male ; Animals ; Erectile Dysfunction/metabolism* ; Rats, Sprague-Dawley ; Mesenchymal Stem Cell Transplantation/methods* ; Rats ; Penis/pathology* ; Humans ; Disease Models, Animal ; Umbilical Cord/cytology* ; Peripheral Nerve Injuries/complications* ; Mesenchymal Stem Cells ; Nitric Oxide Synthase Type III/metabolism* ; Actins/metabolism* ; Nitric Oxide Synthase Type I/metabolism*

OBJECTIVE: To analyze the distribution of thalassemia (referred to as "thalassemia") gene variant types in the population of the Wuhan area, aiming to provide a genetic basis for the precise prevention and control as well as clinical diagnosis of thalassemia in the Wuhan region. METHODS: In this study, 2 133 suspected thalassemia patients and individuals undergoing prenatal screening who visited the Department of Hematology, Obstetrics and Gynecology, Reproductive Medicine, Pediatrics, and Neurology at Wuhan First Hospital from October 2022 to October 2024 were selected as the research subjects. Peripheral blood samples were collected from the patients. The common 27 thalassemia genotypes of α- and β-thalassemia were initially screened using fluorescence PCR melting curve analysis technology. For samples where the fluorescence PCR melting curve results indicated unknown variants or where the clinical phenotype was inconsistent with the common genotypes, Sanger sequencing technology was used for review and verification. RESULTS: Among the 2 133 specimens analyzed, common thalassemia gene variants were detected in 210 cases (9.85%, 210/2 133). A total of 156 cases (8.05%, 156/1 938) of thalassemia gene variants were detected in females and 54 cases (27.69%, 54/195) in males. A total of 94 cases (4.41%, 94/2 133) of α-thalassemia were detected, including 46 cases (2.16%, 46/2 133) of silent α-thalassemia, 47 cases (2.20%, 47/2 133) of mild α-thalassemia, and 1 case (0.05%, 1/2 133) of intermediate α-thalassemia. Additionally, 111 cases of β-thalassemia were identified (5.20%, 111/2 133), including 51 cases of β/β⁺ thalassemia (2.39%, 51/2 133), 59 cases of β/β⁰ thalassemia (2.77%, 59/2 133), and 1 case of β⁺/HbE thalassemia (0.05%, 1/2 133). αβ-composite thalassemia gene variants were detected in 5 cases (0.23%, 5/2 133), including 1 complex variant with a genotype of --^SEA/αα combined with CD41-42 (-TTCT) and 29(A>G), representing a heterozygous variant of three genotypes. Rare globin gene variants were detected in 3 cases, including HBB:c.60C>T, HBB:c.-146G>T, and HBA2:c.*12G>A. CONCLUSION The Wuhan region exhibits a relatively high prevalence of thalassemia genes with notable gender disparities. While maintaining focus on thalassemia screening for females, enhanced males screening efforts and genetic counseling should be implemented in future prevention programs.
Humans ; Female ; Male ; Genotype ; beta-Thalassemia/genetics* ; China ; Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Genetic Variation

AIM To investigate the effect of Fuzheng Hefu Zhiyang Formula(FZHFZY)on psoriasis-like skin lesions and immune regulation in mice.METHODS In the in vivo experiment,30 BALB/c mice were randomly divided into the blank group,the model group,the dexamethasone group(1.5 g/kg of compound dexamethasone acetate cream),and the low-dose(2.5 g/kg)and high-dose(5 g/kg)FZHFZY groups,with six mice in each group.The experiment groups were treated with respective FZHFZY and dexamethasone,and the other groups were given normal saline for 10 consecutive days,during which psoriatic skin lesions were induced with imiquimod cream for 7 consecutive days.The mice had their area and severity of psoriasis assessed by PASI score;their histological changes of skin lesions.observed with Hematoxylin-eosin(HE)staining;their F4/80 ratio of skin lesions observed with immunohistochemical(IHC)staining;their protein expressions of P38,p-P38,Erk,p-Erk,P65 and p-P65 detected by Western blot;and their mRNA expressions of tumor necrosis factor-α(TNF-α),IL-17,IL-23 and IL-1β detected by RT-qPCR.In the in vitro research,the cultured RAW264.7 cells were divided into the blank group,the LPS group,and the FZHFZY groups(1 200,600,300,150 μg/mL).The cells had their protein expressions of P38,p-P38,Erk,p-Erk,P65 and p-P65 detected with Western blot;and their mRNA expressions of IL-6,TNF-α,IL-23 and IL-8 detected by RT-qPCR.RESULTS The in vivo experiment showed that compared to the model group,the FZHFZY groups demonstrated decreased PASI score(P＜0.01);improved epidermal thickening and parakeratosis of skin lesions as revealed by HE staining result and increased expression of F4/80 in IHC staining sections;decreased protein expression ratios of p-P38/P38,p-ERK/Erk and p-P65/P65 in skin(P＜0.05,P＜0.01);and reduced mRNA expressions of TNF-α,IL-17,IL-23 and IL-1β in the skin(P＜0.01).FZHFZY(0～2 400 μg/mL)showed no significant cytotoxicity towards RAW264.7 cells in vitro(P＞0.05).Compared to those of the LPS group,the cells exposed to FZHFZ at concentrations of 1 200 and 600 μg/mL demonstrated decreased protein expression ratios of p-P38/P38,p-ERK/Erk,and p-P65/P65(P＜0.05,P＜0.01);and significantly decreased mRNA expressions of TNF-α,IL-17,IL-23 and IL-1β(P＜0.01).CONCLUSION FZHFZY alleviates imiquimod-induced psoriatic lesions in mice and suppresses inflammatory response in LPS-stimulated RAW264.7 cells by inhibiting P38/Erk/NF-κB signaling pathway.

OBJECTIVE To explore the characteristics and influential factors of pharmaceutical clinic service demands， providing evidence for optimizing pharmaceutical service models and facilitating pharmaceutical service models of pharmacist role transformation. METHODS A cross-sectional survey design was adopted， and 410 outpatient participants were selected from Fudan University Shanghai Cancer Center through convenience sampling for questionnaire administration from February to May 2025. Kano model was applied to analyze the demand attributes of 25 pharmaceutical services， while questionnaires were used to assess patients’ awareness and demand status. Subgroup analyses were conducted based on key demographic variables such as gender， age， educational attainment， and economic burdens， to SACA- systematically examine the differences in Kano attribute classification among patients in each subgroup. RESULTS The awareness rate of pharmaceutical outpatient services among patients was only 14.63%， yet those who were aware demonstrated a significantly higher demand rate for such services compared to those who were unaware （P＜0.001）. The demand for pharmaceutical clinic services exhibited a hierarchical characteristic： twelve items were identified as attractive attributes （e. g.， providing suggestions for more affordable treatment options， offering online consultation services， etc.）， five items as expected attributes （e.g.， having a good attitude and being able to patiently answer your questions， etc.）， three items as must-have attributes （e.g.， providing guidance on medication dosage and usage， providing guidance on medication precautions， etc.）， five items as indifferent attributes （e.g.， providing treatment plan recommendations based on the patient’s condition）. There were zero items classified as reverse attribute. Subgroup analysis revealed that female patients showed greater concern for “neat and clean attire of medical staff” than male patients （P＜0.001）； patients under 60 years of age demonstrated stronger demand for “providing treatment plan recommendations based on patients’ conditions” compared to patients aged 60 or above （P＝0.016）； those with below high school education placed greater emphasis on “providing guidance on medication precautions” compared to those with a high school education or above （P＝0.011）； patients with lower economic burdens exhibited stronger preferences for “neat and clean attire of medical staff ” （P＝0.002）. CONCLUSIONS The public awareness rate of pharmaceutical clinic services is considerably low； however， those who are aware of such services demonstrate significantly higher demand. The medication safety-related services and convenience-oriented demands should be prioritized in the development of pharmaceutical clinics. Moreover， the study also revealed that factors such as gender， age， educational level， and economic burdens exert significant influences on patients’ service demands.

OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

This paper explores the impacts of accelerated rehabilitation protocols following anterior cruciate ligament reconstruction(ACLR)on bone tunnel enlargement(BTE).While accelerated rehabilitation can shorten the recovery time and improve the knee function,it may increase the risk of BTE.In the early rehabilitation phase after ACLR,excessive early weight-bearing and rapid progression of knee flexion angles should be avoided,along with the proper use of braces.Continuous passive motion is not recommended in the early phase post-ACLR to prevent potential effects on BTE.Further research is needed to investigate the mechanisms of BTE and develop more effective rehabilitation strategies.This will help to select appropriate rehabilitation protocols for patients and balance functional recovery with the risk of BTE,thereby reducing the revision rate and improving postoperative outcomes.
Humans ; Anterior Cruciate Ligament Reconstruction/rehabilitation*

Objective:To compare the application of Micronutritional Risk Assessment(MNA),Universal Screening Tool for Malnutrition(MUST)and Nutritional Risk Screening 2002(NRS2002)in nutritional risk assessment among patients with digestive tract tumors during perichemotherapy,based on the Global Leadership Initiative on Malnutrition(GLIM)standard.Methods:A prospective cross-section study was conducted,including 114 patients with digestive tract tumors hospitalized by Department of General Surgery,Huangshan Shoukang Hospital from January 2020 to December 2021.All patients were evaluated by GLIM assessment,the correlation between GLIM and MNA,MUST and NRS 2002 screening results was compared,and the consistency among different methods was compared.Patients were divided into malnourished group(nutritional risk group)or normal nourished group according to the results of the three tools.The differences in single anthropometric or test indicators between the groups were compared.Results:According to GLIM,the proportion of malnutrition was 36.8%.The proportion of malnutrition evaluated by MNA,MUST,and NRS2002 were 63.2%,47.4%,and 32.5%,respectively.The sensitivity and negative predictive value of MNA in assessing nutrition-related risks were the highest,while the specificity,Jorden index,Kappa value and positive predictive value of NRS2002 were the highest.There were statistical differences in levels of body mass index,hemoglobin(Hb),triglyceride,total cholesterol,albumin,prealbumin(P-ALB),blood creatinine,lymphocyte counts,and hospitalization costs between two groups assessed by three different tools(P<0.05).Levels of Hb and P-ALB were statistically different between the two groups of the three screening tools.Conclusion:Based on GLIM evaluation results,MNA and other nutritional screening tools are applicable to the assessment of nutritional risks of patients with gastrointestinal cancer during perichemotherapy due to the joint evaluation of measurement indicators.The MNA is more recommended with the highest detection rate and sensitivity for nutritional risks assessment.

The bottom-up construction of artificial cells to mimic signal transduction is of great significance for a deep understanding of the communication networks of complex living systems.The dynamic coupling of signal secretion and response among artificial cells poses an important challenge.In this work,two types of artificial cells were constructed through a bio-artificial hybrid strategy.One was an artificial cell as an AI-2 signal sender(sender),which contained bacteria capable of autonomously synthesizing AI-2 signaling molecules.The other was an artificial cell as an AI-2 signal receiver(receiver),which contained bacteria expressing green fluorescent protein in response to the corresponding AI-2 signal.When the ratio of senders to receivers was 4∶1,the fluorescent signal of the receivers gradually increased over time and reached a plateau at 240 minutes.The artificial cells capable of sending and receiving quorum sensing signaling molecules constructed in this work laid a foundation for the study of complex signal communication within artificial cell populations.