ObjectiveTo evaluate the effects of Tongnaoyin on the blood-brain barrier status and neurological impairment in acute ischemic stroke （AIS） patients with the syndrome of phlegm-stasis blocking collaterals by dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI）. MethodsA total of 63 patients diagnosed with AIS in the Jiangsu Province Hospital of Chinese Medicine from October 2022 to December 2023 were enrolled in this study. According to random number table method，the patients were assigned into a control group （32 cases） and an observation group （31 cases）. The control group received conventional Western medical treatment，and the observation group took 200 mL Tongnaoyin after meals，twice a day from day 2 of admission on the basis of the treatment in the control group. After 7 days of treatment，the patients were examined by DCE-MRI. The baseline data for two groups of patients before treatment were compared. The National Institute of Health Stroke Scale （NIHSS） score and modified Rankin Scale （mRS） score were recorded before treatment and after 90 days of treatment for both groups. The rKtrans，rKep，and rVe values were obtained from the region of interest （ROI） of the infarct zone/mirror area and compared between the two groups. ResultsThere was no significant difference in the NIHSS or mRS score between the two groups before treatment. After 90 days of treatment，the NIHSS and mRS scores declined in both groups，and the observation group had lower scores than the control group （P<0.05）. After treatment，the rKtrans and rVe in the observation group were lower than those in the control group （P<0.01）. ConclusionCompared with conventional Western medical treatment alone，conventional Western medical treatment combined with Tongnaoyin accelerates the repair of the blood-brain barrier in AIS patients，thereby ameliorating neurological impairment after AIS to improve the prognosis.

This study aimed to investigate the correlation between changes in intestinal toxicity and compositional alterations of Euphorbiae Ebracteolatae Radix(commonly known as Langdu) before and after milk processing, and to explore the detoxification mechanism of milk processing. Mice were intragastrically administered the 95% ethanol extract of raw Euphorbiae Ebracteolatae Radix, milk-decocted(milk-processed), and water-decocted(water-processed) Euphorbiae Ebracteolatae Radix. Fecal morphology, fecal water content, and the release levels of inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in different intestinal segments were used as indicators to evaluate the effects of different processing methods on the cathartic effect and intestinal inflammatory toxicity of Euphorbiae Ebracteolatae Radix. LC-MS/MS was employed to analyze the small-molecule components in the raw product, the 95% ethanol extract of the milk-processed product, and the milky waste(precipitate) formed during milk processing, to assess the impact of milk processing on the chemical composition of Euphorbiae Ebracteolatae Radix. The results showed that compared with the blank group, both the raw and water-processed Euphorbiae Ebracteolatae Radix significantly increased the fecal morphology score, fecal water content, and the release levels of TNF-α and IL-1β in various intestinal segments(P<0.05). Compared with the raw group, all indicators in the milk-processed group significantly decreased(P<0.05), while no significant differences were observed in the water-processed group, indicating that milk, as an adjuvant in processing, plays a key role in reducing the intestinal toxicity of Euphorbiae Ebracteolatae Radix. Mass spectrometry results revealed that 29 components were identified in the raw product, including 28 terpenoids and 1 acetophenone. The content of these components decreased to varying extents after milk processing. A total of 28 components derived from Euphorbiae Ebracteolatae Radix were identified in the milky precipitate, of which 27 were terpenoids, suggesting that milk processing promotes the transfer of toxic components from Euphorbiae Ebracteolatae Radix into milk. To further investigate the effect of milk adjuvant processing on the toxic terpenoid components of Euphorbiae Ebracteolatae Radix, transmission electron microscopy(TEM) was used to observe the morphology of self-assembled casein micelles(the main protein in milk) in the milky precipitate. The micelles formed in casein-terpenoid solutions were characterized using particle size analysis, fluorescence spectroscopy, ultraviolet spectroscopy, and Fourier-transform infrared(FTIR) spectroscopy. TEM observations confirmed the presence of casein micelles in the milky precipitate. Characterization results showed that with increasing concentrations of toxic terpenoids, the average particle size of casein micelles increased, fluorescence intensity of the solution decreased, the maximum absorption wavelength in the UV spectrum shifted, and significant changes occurred in the infrared spectrum, indicating that interactions occurred between casein micelles and toxic terpenoid components. These findings indicate that the cathartic effect of Euphorbiae Ebracteolatae Radix becomes milder and its intestinal inflammatory toxicity is reduced after milk processing. The detoxification mechanism is that terpenoid components in Euphorbiae Ebracteolatae Radix reassemble with casein in milk to form micelles, promoting the transfer of some terpenoids into the milky precipitate.
Animals ; Mice ; Milk/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Male ; Tumor Necrosis Factor-alpha/immunology* ; Intestines/drug effects* ; Interleukin-1beta/immunology* ; Tandem Mass Spectrometry ; Female

OBJECTIVE: To explore clinical efficacy of different technical combinations in treating ischemic diabetic foot (DF). METHODS: A retrospective analysis was conducted on 35 patients with DF who were treated with vascular interventional opening technique, periosteal distraction technique and bone cement coverage technique from January 2024 to November 2024. They were divided into comprehensive group and periosteal distraction group according to whether the vascular interventional opening technique was used in combination or not. There were 5 patients in comprehensive group, including 4 males and 1 female, aged from 59 to 73 years old with an average of (64.40±5.46) years old;the duration of diabetes ranged from 0.17 to 30.00 years with an average of (14.63±12.02) years;the courses of DF ranged from 30 to 150 days with an average of (84.00±61.48) days;2 patients were grade 2, 2 patients were grade 3, and 1 patient was grade 4 according to Wagner classification;combined vascular interventional opening, periosteal distraction and bone cement coverage surgery for treatment. There were 30 patients in periosteal stretch group, including 22 males and 8 females, aged from 58 to 86 years old with an average of (72.63±7.84) years old;the duration of diabetes was 10.00 (6.75, 16.75) years;the courses of DF was 30.00 (15.00, 37.50) days;14 patients were grade 2, 11 patients were grade 3, and 5 patients were grade 4 according to Wagner classification; combined periosteal distraction and bone cement coverage surgery for treatment. Changes of C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT), toe skin temperature, peripheral capillary oxygen saturation (SpO₂), and visual analogue scale (VAS) for pain were compared between two groups before operation and 1 week after operation. The number of operations, healing period, healing number, toe amputation number, preoperative fever situation and the number of complications were compared between two groups. RESULTS: Both groups were followed up for at least 6 months. There were no statistically significant differences in the number of operations, healing period, toe amputation rate, wound healing rate and complications between two groups (P>0.05). Before operation, the toe skin temperature of comprehensive group (26.98±0.88) ℃ was lower than that of periosteal distraction group (28.17±1.45) ℃, and the difference was statistically significant (P<0.05);while there were no statistically significant difference in CRP, IL-6, PCT, toe SpO2 and VAS between two groups (P>0.05). At 1 week after operation, IL-6, toe skin temperature, toe SpO₂ and VAS in comprehensive group were 12.29(7.92, 22.15) pg·ml-1, (36.02±0.23) ℃, (95.80±0.84) % and(1.40±0.55) respectively, while those in periosteal distraction group were 5.49(4.36, 7.45) pg·ml^-1, (31.36±1.57) ℃, (84.53±6.38) %, (2.20±0.81);and there were statistically significant differences between two groups(P<0.05). CRP, IL-6 and VAS at 1 week after operation in both groups were decreased compared with those before operation, and the differences were statistically significant(P<0.05). The toe skin temperature and SpO₂ were increased compared with those before operation, and the differences were statistically significant(P<0.001). CONCLUSION The multi-technique combination therapy, including vascular interventional opening technique, periostealdistraction technique and bone cement covering technique, could protect each other, enhance efficacy, effectively promote the wound healing of ischemic diabetic foot ulcer, and reduce the toe amputation rate. For moderate to severe ischemic DF, the combined use of periosteal distraction and bone cement coverage techniques has a satisfactory effect. For extremely severe ischemic DF with inflow tract lesions, vascular interventional opening techniques need to be added.
Humans ; Male ; Female ; Middle Aged ; Aged ; Diabetic Foot/surgery* ; Retrospective Studies ; Aged, 80 and over ; Ischemia/surgery* ; Interleukin-6/metabolism*

BACKGROUND: Low serum albumin levels are established predictors of adverse outcomes in various cardiovascular conditions. However, the role of serum albumin in mortality among elderly patients with chronic aortic regurgitation (AR) has not been thoroughly investigated. This study aims to assess the relationship between serum albumin levels and mortality in this specific patient population. METHODS: Our analysis included 873 elderly AR patients from the China Valvular Heart Disease study, with baseline serum albumin measured at enrollment. Mortality outcomes were monitored for two years post-enrollment, employing a Cox proportional hazards model with a two-piecewise Cox proportional hazards framework to investigate the nonlinear relationship between serum albumin levels and all-cause mortality. RESULTS: During the 2-year follow-up period, we observed 63 all-cause deaths. The association between serum albumin levels and all-cause mortality displayed an approximating L-shaped curve, indicating a mortality threshold at 35 g/L. For serum albumin levels below 35 g/L, each 1 g/L decrease was associated with a 25% higher risk of all-cause mortality (HR = 1.25, 95% CI: 1.07-1.45). In contrast, no significant change in mortality risk was observed when serum albumin levels were greater than or equal to 35 g/L. Moreover, when serum albumin is classified as hypoproteinemia (serum albumin < 35 g/L), the higher risks of all-cause death were observed in hypoproteinemic patients (HR = 2.93, 95% CI: 1.50-5.74). More importantly, the association between serum albumin and death was significantly stronger in overweight/obese patients (≥ 24 kg/m² vs. < 24 kg/m², P _interaction = 0.006). CONCLUSIONS In elderly patients with AR, serum albumin levels showed an approximating L-shaped relationship with all-cause death, with thresholds of 35 g/L. Body mass index was significant effect modifiers of the association. These results suggest that serum albumin, as an inexpensive and readily available biochemical marker, may further improve the stratified risk of mortality in older AR patients.

Intervertebral disc degeneration (IDD) is largely attributed to impaired endogenous repair. Nucleus pulposus-derived stem cells (NPSCs) senescence leads to endogenous repair failure. Small extracellular vesicles/exosomes derived from mesenchymal stem cells (mExo) have shown great therapeutic potential in IDD, while whether mExo could alleviate NPSCs senescence and its mechanisms remained unknown. We established a compression-induced NPSCs senescence model and rat IDD models to evaluate the therapeutic efficiency of mExo and investigate the mechanisms. We found that mExo significantly alleviated NPSCs senescence and promoted disc regeneration while knocking down thioredoxin (TXN) impaired the protective effects of mExo. TXN was bound to various endosomal sorting complex required for transport (ESCRT) proteins. Autocrine motility factor receptor (AMFR) mediated TXN K63 ubiquitination to promote the binding of TXN on ESCRT proteins and sorting of TXN into mExo. Knocking down exosomal TXN inhibited the transcriptional activity of nuclear factor erythroid 2-related factor 2 (NRF2) and activator protein 1 (AP-1). NRF2 and AP-1 inhibition reduced endogenous TXN production that was promoted by exosomal TXN. Inhibition of NRF2 in vivo diminished the anti-senescence and regenerative effects of mExo. Conclusively, AMFR-mediated TXN ubiquitination promoted the sorting of TXN into mExo, allowing exosomal TXN to promote endogenous TXN production in NPSCs via TXN/NRF2/AP-1 feed-forward circuit to alleviate NPSCs senescence and disc degeneration.

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) can result in fatigue and post-exertional malaise; however, whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection exacerbates lower urinary tract symptoms (LUTS) is unclear. This study investigated the association between prenatal SARS-CoV-2 infection and postpartum LUTS. METHODS: A multicenter, retrospective cohort study was conducted at two tertiary hospitals in China from November 1, 2022, to November 1, 2023. Participants were classified into infected and uninfected groups based on SARS-CoV-2 antigen results. LUTS prevalence and severity were assessed using self-reported symptoms and the Incontinence Impact Questionnaire-Short Form (IIQ-7). Pelvic floor muscle activity was measured using electromyography following the Glazer protocol. Group comparisons were performed to evaluate the association of SARS-CoV-2 infection with LUTS and electromyography parameters, with stratified analyses conducted using SPSS version 26.0. RESULTS: Among 3,652 participants (681 infected, 2,971 uninfected), no significant differences in LUTS prevalence or IIQ-7 scores were observed. However, SARS-CoV-2 infection was an independent factor influencing the electromyographic activity of the pelvic floor muscles (mean tonic contraction amplitudes), regardless of delivery mode ( P = 0.001). CONCLUSION Prenatal SARS-CoV-2 infection was not significantly associated with an increased risk of postpartum LUTS but independently altered pelvic floor muscle electromyographic activity, suggesting potential neuromuscular effects.
Humans ; Female ; COVID-19/epidemiology* ; Retrospective Studies ; Adult ; Pregnancy ; Lower Urinary Tract Symptoms/virology* ; Postpartum Period ; Pregnancy Complications, Infectious/virology* ; China/epidemiology* ; Electromyography ; SARS-CoV-2/physiology* ; Pelvic Floor/physiopathology* ; Prevalence

Objective:To prepare a novel ginseng polypeptide thermosensitive hydrogel,and to investigate its repair effect on heat-induced skin injury in the rats and explore the underlying mechanisms.Methods:Thermosensitive hydrogels were formulated using Pluronic F127 and β-sodium glycerophosphate(β-GP),and their phase transition temperatures,spatial structures,elemental compositions,and water retention capacities were evaluated.The rat models of heat-induced skin injury were established and the model rats were divided into PBS group,Gel group,and ginseng polypeptide gel(GP-Gel)group.After 11 d of treatment,the morphological changes of wound and collagen deposition in the wound of the rats in various groups were observed by HE and Masson staining.Immunohistochemistry was used to detect the expression levels of α-smooth muscle actin(α-SMA),connective tissue growth factor(CTGF),basic fibroblast growth factor(bFGF),proliferating cell nuclear antigen(PCNA),cell proliferation marker Ki67,epidermal growth factor(EGF),CD31,vascular endothelial growth factor(VEGF),P50 and P65 proteins in the skin wound tissue of the rats in various groups.Western blotting method was used to detect the expression levels of Toll-like receptor 4(TLR4)in the skin wound tissue of the rats in various groups.ELISA method was used to measure the levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),interleukin-15(IL-15),and interleukin-10(IL-10)in the serum of the rats in various groups.Results:Compared with PBS and Gel groups,the wound area of the rats in GP-Gel group was reduced(P＜0.01),the expression levels of PCNA,Ki67,EGF,CD31,VEGF,α-SMA,and CTGF proteins in the skin wound tissue were increased(P＜0.05 or P＜0.01),and the expression levels of P65 and TLR4 proteins were decreased(P＜0.01);the level of anti-inflammatory factor IL-10 in serum was increased(P＜0.01),while the levels of pro-inflammatory factors TNF-α,IL-1β,IL-6 and IL-15 were decreased(P＜0.05 or P＜0.01).Conclusion:The ginseng polypeptide thermosensitive hydrogel promotes the repair of heat-induced skin injury by enhancing cell proliferation,collagen synthesis,angiogenesis,and reducing inflammatory responses.

Objective To comparatively analyze the clinical characteristics of primary bilateral macronodular adrenal hyperplasia(PBMAH)and adrenal cortisol-producing Adenoma(CPA),and enhance the understanding of two diseases.Methods The clinical data of 85 PBMAH patients(PBMAH group)and 195 CPA patients(CPA group)diagnosed at Department of Endocrinology,the First Medical Center of Chinese PLA General Hospital,from September 2014 to August 2024 were retrospectively analyzed.The demographic characteristics,comorbidities,biochemical indicators,adrenocorticotropic hormone-cortisol(ACTH-F)levels,and adrenal imaging features and treatment conditions were compared between the two groups.Results(1)General characteristics:Compared with CPA group,PBMAH group had older age at diagnosis and a higher proportion of male patients.(2)Clinical characteristics:Compared with CPA group,PBMAH group had a longer disease duration,a higher proportion of subclinical Cushing's syndrome(CS),and a higher proportion of hypertension,impaired glucose tolerance/diabetes,bone mass reduction or osteoporosis,with higher serum potassium levels,and the differences were statistically significant(P<0.01).(3)Hormone levels:Both PBMAH and CPA groups showed ACTH-F rhythm disorder,significantly increased cortisol levels and suppressed ACTH.Compared with PBMAH group,CPA group had stronger autonomous cortisol secretion ability,manifested by increased midnight serum cortisol(F0:00),16:00 serum cortisol(F16:00),24-hour urinary free cortisol(24 h UFC)levels and lower 8:00 serum ACTH(ACTH8:00)and 16:00 serum ACTH(ACTH16:00)(P<0.01).After low-dose dexamethasone suppression test(LDDST),CPA group showed lower suppression rates of ACTH and cortisol,and higher proportions of paradoxical elevation in serum cortisol and 24 h UFC compared with PBMAH(P<0.01).Conclusions PBMAH has a longer disease course and higher proportions of comorbid metabolic disorders than CPA,mostly manifested as subclinical Cushing's syndrome.CPA has stronger autonomous cortisol secretion ability,with cortisol less likely to be suppressed after LDDST and more obvious paradoxical elevation of cortisol and 24 h UFC.

Objective To investigate the clinical and pathological characteristics of adrenal cortical carcinoma(ACC),compare differences between hypercortisolism and non-functional ACC,and assess the diagnostic value of indicators such as Ki-67 index.Methods The clinical data of 57 ACC patients admitted to the First Medical Center of Chinese PLA General Hospital from January 2015 to March 2025 were retrospectively analyzed.According to the results of endocrine function assessment,47 of these patients were divided into hypercortisolism group(n=19)and non-functional group(n=28).The differences in clinical and pathological characteristics between the two groups were compared,and non-parametric tests and Spearman correlation analysis were used to explore the relationship between Ki-67 index and tumor stage as well as imaging features.Results Among the 57 patients,there were 20 males and 37 females,with a male-to-female ratio of 1:1.85.The age ranged from 16 to 76 years,and the age at diagnosis was(48.7±13.3)years.The tumor diameter was(10.53±4.14)cm.The tumors were located on the right side in 12 cases(21.1%),on the left side in 34 cases(59.6%),and bilaterally in 11 cases(19.3%).Among them,16 cases(28.1%)were complicated with glucose metabolism disorders,31 cases(54.3%)had hypertension,and 20 cases(35.1%)had hypokalemia.According to ENSAT staging,there were 0 cases in stage Ⅰ,15 cases(26.3%)in stage Ⅱ,24 cases(42.1%)in stage Ⅲ,and 18 cases(31.6%)in stage Ⅳ.Endocrine function assessment was completed in 47 of the 57 patients,including 28 cases(59.6%)of non-functional ACC and 19 cases(40.4%)of hypercortisolism(including 1 case of hypercortisolism combined with increased sex hormone secretion).Compared with non-functional group,hypercortisolism group had a significantly higher prevalence of hypertension(P=0.014),later ENSAT stage(P=0.010),and a higher proportion of hypervascularization(P=0.048).The median Ki-67 index was 20%(10%-40%),showing no significant correlation with either the maximum tumor diameter or SUVmax value,but it was related to ENSAT staging,with Ki-67 index in stageⅣ patients being significantly higher than that in stage Ⅱ(P=0.032).Immunohistochemistry results showed that the positive rate of Inhibin-α was 84.8%,and the positive rate of Melan-A was 40.9%.Conclusions ACC is a rare malignant endocrine tumor.ACC patients with hypercortisolism are more likely to be complicated with hypertension,have later staging,and more common hypervascular manifestations.Clinically,their endocrine function should be prioritized for assessment,and more active treatment strategies should be adopted.Diagnosis should be combined with imaging characteristics(such as hypervascularization)and immunohistochemical indicators(Ki-67,Inhibin-α,Melan-A).The significant increase in Ki-67 is in the advanced stage can serve as an important prognostic indicator to guide individualized treatment.