This study aimed to investigate the protective effects of Huangqi Guizhi Wuwu decoction (HGWD) against cerebral ischemic injury and the underlying mechanisms. A middle cerebral artery occlusion (MCAO) model was established in C57BL/6 mice to evaluate the effects of HGWD on neurobehavioral scores, cerebral infarction rate, brain water content, and oxidative stress and inflammatory markers. The mRNA and protein expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) in brain tissue were assessed. In addition, Nrf2 knockout mice were used to verify the role of Nrf2 in the protective effects of HGWD against MCAO-induced injury. Additionally, an oxygen-glucose deprivation/reperfusion (OGD/R) model in primary neuronal cells was employed to further confirm the pharmacological effects of HGWD in vitro. The results showed that HGWD significantly ameliorated cerebral ischemic injury in MCAO mice, alleviated oxidative stress, suppressed the release of inflammatory factors, and markedly upregulated the expression of Nrf2, HO-1, and Bcl-2 while downregulating Bax expression, with consistent trends being observed at both mRNA and protein levels. The protective effects of HGWD were significantly attenuated in Nrf2 knockout mice, indicating the pivotal role of Nrf2 in HGWD-mediated protection against cerebral ischemic injury. In vitro experiments revealed that HGWD significantly increased neuronal cell viability, reduced lactate dehydrogenase(LDH) leakage, and decreased apoptosis in OGD/R-treated cells, accompanied by upregulation of Nrf2, HO-1, and Bcl-2 and downregulation of Bax. In conclusion, HGWD protects against cerebral ischemic injury by activating the Nrf2/HO-1 pathway to enhance antioxidant capacity and modulating the Bcl-2/Bax signaling pathway to inhibit apoptosis, thereby protecting brain cells from ischemic damage.

ObjectiveTo investigate the association between single and combined exposure to arsenic （As）， mercury （Hg）， and cadmium （Cd） in urine and hearing loss in adults. MethodsA total of 400 adult patients were recruited for the study， comprising 200 participants in the normal hearing group and 200 in the hearing loss group. General demographic information of the study subjects was collected by a self-administered questionnaire， morning urine samples were tested for As， Hg， and Cd concentrations， and hearing status was assessed by Pure Tone Audiometry. A binary Logistic regression model was used to explore the association between the concentrations of the three metals in urine and hearing loss， and a Bayesian kernel-machine regression （BKMR） model was used to further explore the association between the concentrations of the three metal mixtures and hearing loss. ResultsAfter correction for urinary creatinine， As， Hg， and Cd concentrations were higher in the hearing loss group than those in the normal hearing group （P<0.05）. Binary Logistic regression indicated that concentrations of As， Hg， and Cd were positively associated with hearing loss， and the risk of hearing loss was significantly higher in the second quartile of Cd concentration compared to the first quartile （OR=2.000， 95%CI： 1.009-3.964）. BKMR modeling analysis showed that the combined exposure levels of As， Hg， and Cd significantly increased the risk of hearing loss， with Cd being the most important contributor （posterior inclusion probability=0.412）， and that there were potential interactions between As and Cd， and Cd and Hg. ConclusionCombined exposure to As， Hg， and Cd in urine is significantly associated with adult hearing loss， with Cd being the primary contributor in the exposure combination. The interactions between As and Cd， as well as Cd and Hg， may have adverse effects on hearing loss.

Background China has the largest elderly population in the world, and age-related cognitive impairment has become an increasingly important public health issue. Objective To investigate the associations of exposure to selected essential metals (EMs) and non-essential metals (NEMs) with cognitive function among rural older adults and to examine whether EMs modified the association between NEW exposure and cognitive functions. Methods A total of 1045 adults aged 60 years and above were enrolled using baseline survey data from a cohort study. Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine urinary concentrations of five EMs (selenium, cobalt, vanadium, manganese, and boron) and five NEMs (arsenic, chromium, cadmium, lithium, and tin). The Mini-Mental State Examination (MMSE) scale was used to assess cognitive function. Generalized linear models (GLMs) and restricted cubic spline (RCS) models were used to examine the associations of individual EMs and NEMs with MMSE scores. Quantile g-calculation (QGC) and Bayesian kernel machine regression (BKMR) models were used to evaluate the associations of EM and NEM mixtures with MMSE scores. Results The mean age of the participants was (69.72±6.63) years, and 511 participants (48.90%) were male. The mean MMSE score was 21.06±5.79. After adjustment for covariates, GLM analysis showed that cobalt (β=0.575, 95%CI: 0.233, 0.918), selenium (β=0.440, 95%CI: 0.045, 0.836), and vanadium (β=0.633, 95%CI: 0.251, 1.016) were positively associated with MMSE scores, whereas tin (β=−0.379, 95%CI: −0.728, −0.029) was negatively associated with MMSE scores. After categorizing metal concentrations into quartiles and including them in the GLM, cobalt (β_{Q4 vs. Q1}=1.697, 95%CI: 0.806, 2.589) and vanadium (β_{Q4 vs. Q1}=1.598, 95%CI: 0.719, 2.477) remained positively associated with MMSE scores, whereas tin (β_{Q4 vs. Q1}=−0.890, 95%CI: −1.771, −0.008) and lithium (β_{Q4 vs. Q1}=−0.794, 95%CI: −1.689, −0.007) were negatively associated with MMSE scores. RCS model showed linear positive associations of cobalt and vanadium with MMSE scores, a linear negative association of tin with MMSE scores, and an inverted U-shaped association between lithium and MMSE scores. Both QGC and BKMR models indicated that the EMs mixture was positively associated with MMSE scores, with cobalt contributing the most. The NEM mixture showed a negative but nonsignificant association with MMSE scores, with lithium contributing the most. When EMs and NEMs were jointly modeled, no significant association was observed between the overall metal mixture and MMSE scores. Interaction analysis suggested a positive interaction between EMs and NEMs in relation to MMSE scores. Stratified analysis showed that, compared with participants with high cobalt or EMs exposure, those with low cobalt or EMs exposure had a more pronounced and statistically significant negative association between NEMs exposure and MMSE scores. Conclusion The EM mixture is significantly and positively associated with MMSE scores, whereas the NEMs mixture shows a negative but nonsignificant association. EMs and NEMs have a positive interaction on MMSE scores; EMs attenuate the association between NEMs and MMSE scores.

Objective:To summarize the clinical and imaging presentations of the pontine tegmental cap dysplasia (PTCD).Methods:The clinical, high resolution CT(HRCT) and MRI materials of 4 patients with PTCD between August 2007 to December 2024 were retrospectively analyzed. Among these, there were 2 males and 2 females, their ages ranged from 10 months to 16 years.Results:Of 4 PTCD patients, severe or profound severe hearing loss ( n=8 ears), developmental delay, hypotonia and severe facioplegia ( n=3 cases) were found. On HRCT, all of 4 cases were associated with temporal anomalies [including a narrow bony cochlear nerve canal ( n=8 ears), duplicated (each n=4 ears) or narrow ( n=1 ear) internal auditory canal, enlarged vestibular aqueduct ( n=2 ears), enlarged vestibules and dysplastic lateral semicircular canals ( n=3 ears), ossicular deformation( n=2 ears). The stenosis of the labyrinthine segments of the facial nerve canal ( n=3 ears) and facial nerve canal ectopia(n=6 ears)], atrial or ventricular septal defect (each n=1 case), thoracic or lumbar vertebral anomalies and ribs fusion ( n=3 cases). On the brain MRI, the variable flattening of the ventral pons and dysmorphism of the dorsal upper pons cap-like bulging and protruding in the fourth ventricle were shown in all cases, the vermian and cerebellar peduncles hypoplasia gave rise to a molar tooth appearance. The dysplastic ( n=3 ears), aplastic( n=5 ears) cochlear nerves and dysplastic facial nerves ( n=3 ears) were found. Conclusion:The PTCD patients usually present severe hearing loss, developmental delay, hypotonia, and facioplegia. The flattening of the ventral pons and the dorsal upper pons cap-like bulging usually with duplicated internal auditory canal and severe facial and auditory nerves dysplasia are its imaging features.

Objective To explore the correlation between remnant cholesterol level and CI-AKI in elderly patients with ACS and concomitant T2DM following PCI.Methods A retrospective case-control study was conducted on 759 elderly T2DM patients with ACS undergoing PCI in the Affi-liated Hospital of Xuzhou Medical University between January 2020 and December 2023.The pa-tients were randomly allocated into a training group(n=608)and a validation group(n=151)in a ratio of 8∶2.Based on CI-AKI diagnostic criteria,the training group was further stratified into a CI-AKI subgroup(n=95)and a non-CI-AKI subgroup(n=513).Multivariate logistic regression analysis was used to identify the independent risk factors for CI-AKI.Results The remnant cho-lesterol level was significantly higher in the CI-AKI subgroup than the non-CI-AKI subgroup[0.78(0.51,1.07)mmol/L vs 0.57(0.40,0.81)mmol/L,P＜0.01].Red blood cell count,remnant cholesterol,age,uric acid,log-transformed systemic immune-inflammatory(SII)index,and cysta-tin C were identified as independent predictors for CI-AKI in T2DM patients with ACS after PCI(P＜0.01).ROC curve analysis demonstrated that the model combining remnant cholesterol with other independent predictors exhibited superior discriminative performance in both the training group(AUC=0.818,95％CI:0.773-0.863)and validation group(AUC=0.787,95％CI:0.686-0.889)when compared to the models excluding remnant cholesterol(P＜0.01).Conclusion Rem-nant cholesterol is an independent predictor of CI-AKI in elderly patients with ACS and T2DM af-ter PCI.A risk prediction model based on remnant cholesterol and other independent risk factors demonstrates enhanced predictive performance for postoperative CI-AKI in the patients.

Objective:To investigate the spatial and temporal distribution characteristics of brucellosis in Heilongjiang Province, Jilin Province and Inner Mongolia Autonomous Region (hereafter referred to as the Hei-Ji-Meng province and region), and study the influencing factors of brucellosis incidence.Methods:Using a retrospective analysis method, the data of brucellosis incidence in 22 prefecture-level cities in the Hei-Ji-Meng province and region from 2014 to 2018, as well as the data of natural environmental factors (precipitation, temperature, relative humidity, solar radiation, wind speed, vegetation index) and social environmental factors (livestock breeding, livestock and poultry meat production, cultivated land area) were collected and integrated. The spatial autocorrelation model and spatial Dubin model were used to analyze the spatial and temporal distribution rule of brucellosis and the impact of environmental factors on the incidence of brucellosis in prefecture-level cities.Results:From 2014 to 2018, the incidence of brucellosis in the Hei-Ji-Meng province and region was 18.77/100 000, among which the incidence in Inner Mongolia Autonomous Region was 33.45/100 000, followed by Heilongjiang Province (13.67/100 000) and Jilin Province (6.57/100 000). Among all prefecture-level cities, the brucellosis incidence was relatively higher in Hinggan League of Inner Mongolia Autonomous Region (69.10/100 000). Except 2016, the brucellosis incidence in other years had a positive spatial correlation (global Moran's I > 0, P < 0.05). The high-high concentration aggregation pattern was mainly concentrated in Ulanqab City, Xilingol League, Chifeng City, Tongliao City, Hinggan League, Hohhot City, and Hulunbuir City of Inner Mongolia Autonomous Region. Among the environmental factors related to brucellosis, cultivated land area and sheep breeding density had a positive effect on brucellosis incidence in the local area, with the effect intensity of 0.39 and 0.32, respectively ( P < 0.001). The average humidity from April to July had a negative effect on the brucellosis incidence in the local area, with the effect intensity of - 0.22 ( P = 0.023). The indirect effect of the number of pigs slaughtered on the brucellosis incidence in adjacent areas was the most significant, and the effect intensity was 2.15 ( P < 0.001). Conclusions:Among the Hei-Ji-Meng province and region, the annual average incidence rate of brucellosis in Inner Mongolia Autonomous Region is relatively higher, and the high-high concentration areas are mainly concentrated in this region. Among the environmental factors, the cultivated land area, sheep breeding density, the average humidity from April to July and the number of pigs slaughtered have an impact on brucellosis incidence.

Objective To investigate the predictive value of serum low-density lipoprotein cholesterol(LDL-C)and high-sensitive C-reactive protein(hs-CRP)in combination with carotid ultrasound parameters for assessing the risk of coronary heart disease(CHD)in patients with suspected cases.Methods A total of 260 patients who underwent coronary angiography(CAG)in the Department of Cardiology at Wujin Affiliated Hospital of Nanjing University of Traditional Chinese Medicine from August 2022 to August 2024 due to suspected CHD were enrolled in this study.Based on CAG results,patients were categorized into a non-CHD group(n=110)and a CHD group(n=150).General clinical characteristics,serum LDL-C,hs-CRP levels,and carotid ultrasound arameters-including carotid intima-media thickness(CIMT)and Crouse score of carotid artery plaque-were compared between the two groups.Spearman correlation analysis and multivariate logistic regression analysis were conducted to evaluate the associations among these parameters.The predictive value of individual and combined markers for suspected CHD was assessed by using receiver operating characteristic(ROC)curve analysis.Results(1)The coronary heart disease(CHD)group had higher age,smoking,fasting plasma glucose(FPG),and blood pressure compared to the non-CHD group(P>0.05).No significant difference was observed in the gender ratio,alcohol consumption rates,and body mass index(BMI),between the two groups(P>0.05).(2)Total cholesterol(TC),LDL-C,hs-CRP levels,and carotid ultrasound parameters were significantly higher in the CHD group than those in the non-CHD group(P<0.05).(3)Spearman correlation analysis and multivariate logistic regression analysis revealed that serum LDL-C,hs-CRP,and carotid ultrasound parameters were significantly correlated with coronary heart disease(P<0.05).(4)ROC curve analysis demonstrated that the combined assessment of serum LDL-C,hs-CRP,and carotid ultrasound parameters achieved the highest area under the curve(AUC),sensitivity,and specificity,with statistically significant differences compared to individual markers(P<0.05).Conclusions Serum LDL-C,hs-CRP,and carotid ultrasound parameters individually have predictive value for coronary heart disease,while their combined assessment offers superior predictive accuracy.The enhanced diagnostic performance of the combined valuation provides valuable guidance for the diagnosis and management of patients with suspected coro-nary heart disease.

Objective To clarify the anti-fibrotic effect of hypericin on preventing renal fibrosis.To explore if hypericin can improve renal tubulointerstitial fibrosis by inhibiting the Yes-associated protein(YAP).Methods Thirty-six male mice were randomly allocated into 6 groups(n=6 per group):sham group,sham+hypericin(120 mg/kg)group,UUO model group,hyperi-cin(30,60,120 mg/kg)treatment groups.Except for the sham group,renal interstitial fibrosis was induced in all other groups via unilateral ureteral obstruction(UUO).Mice in the hypericin treatment group received corresponding doses of hypericin sus-pension via oral gavage,while sham group and UUO model group were administered equivalent volumes of normal saline through the same route for 14 consecutive days.Additionally,an in vitro model was established using NRK-52E cells treated with TGF-β1(10 ng/mL).To evaluate the anti-fibrotic effects of hypericin,protein expression levels of α-SMA,fibronectin,col-lagen Ⅰ and collagen Ⅲ were assessed in both the UUO mouse kidney tissues and TGF-β1-stimulated NRK-52E cells using Western blotting.Blood urea nitrogen(BUN)and creatinine(Cr)levels in mice were measured to assess the renal protective effects of hypericin.Histological changes and collagen deposition in the kidneys were observed using hematoxylin-eosin and Masson staining.The expression levels of YAP and its downstream target gene CTGF were also determined using Western blot-ting.The specific mechanism of hypericin in improving renal interstitial fibrosis was further explored using the YAP inhibitor verteporfin.Results The protein expression levels of α-SMA,FN,collagen Ⅰ,and collagen Ⅲ in renal tissues of UUO mice and TGF-β1-induced NRK-52E cells were markedly reversed by hypericin(all P＜0.01).The levels of Cr and BUN in UUO mice se-rum were effectively reduced(both P＜0.01),and renal histopathological alterations and interstitial collagen deposition were markedly ameliorated.Potent inhibitory effects on YAP and CTGF protein expression were observed both in vivo and in vitro(both P＜0.01),exhibiting similar effects to verteporfin.Both treatments dramatically reduced TGF-β1-induced fibrosis in NRK-52E cells.Conclusion Hypericin can inhibit renal tubulointerstitial fibrosis by inhibiting YAP.

Objective To investigate the predictive value of serum low-density lipoprotein cholesterol(LDL-C)and high-sensitive C-reactive protein(hs-CRP)in combination with carotid ultrasound parameters for assessing the risk of coronary heart disease(CHD)in patients with suspected cases.Methods A total of 260 patients who underwent coronary angiography(CAG)in the Department of Cardiology at Wujin Affiliated Hospital of Nanjing University of Traditional Chinese Medicine from August 2022 to August 2024 due to suspected CHD were enrolled in this study.Based on CAG results,patients were categorized into a non-CHD group(n=110)and a CHD group(n=150).General clinical characteristics,serum LDL-C,hs-CRP levels,and carotid ultrasound arameters-including carotid intima-media thickness(CIMT)and Crouse score of carotid artery plaque-were compared between the two groups.Spearman correlation analysis and multivariate logistic regression analysis were conducted to evaluate the associations among these parameters.The predictive value of individual and combined markers for suspected CHD was assessed by using receiver operating characteristic(ROC)curve analysis.Results(1)The coronary heart disease(CHD)group had higher age,smoking,fasting plasma glucose(FPG),and blood pressure compared to the non-CHD group(P>0.05).No significant difference was observed in the gender ratio,alcohol consumption rates,and body mass index(BMI),between the two groups(P>0.05).(2)Total cholesterol(TC),LDL-C,hs-CRP levels,and carotid ultrasound parameters were significantly higher in the CHD group than those in the non-CHD group(P<0.05).(3)Spearman correlation analysis and multivariate logistic regression analysis revealed that serum LDL-C,hs-CRP,and carotid ultrasound parameters were significantly correlated with coronary heart disease(P<0.05).(4)ROC curve analysis demonstrated that the combined assessment of serum LDL-C,hs-CRP,and carotid ultrasound parameters achieved the highest area under the curve(AUC),sensitivity,and specificity,with statistically significant differences compared to individual markers(P<0.05).Conclusions Serum LDL-C,hs-CRP,and carotid ultrasound parameters individually have predictive value for coronary heart disease,while their combined assessment offers superior predictive accuracy.The enhanced diagnostic performance of the combined valuation provides valuable guidance for the diagnosis and management of patients with suspected coro-nary heart disease.

Objective To clarify the anti-fibrotic effect of hypericin on preventing renal fibrosis.To explore if hypericin can improve renal tubulointerstitial fibrosis by inhibiting the Yes-associated protein(YAP).Methods Thirty-six male mice were randomly allocated into 6 groups(n=6 per group):sham group,sham+hypericin(120 mg/kg)group,UUO model group,hyperi-cin(30,60,120 mg/kg)treatment groups.Except for the sham group,renal interstitial fibrosis was induced in all other groups via unilateral ureteral obstruction(UUO).Mice in the hypericin treatment group received corresponding doses of hypericin sus-pension via oral gavage,while sham group and UUO model group were administered equivalent volumes of normal saline through the same route for 14 consecutive days.Additionally,an in vitro model was established using NRK-52E cells treated with TGF-β1(10 ng/mL).To evaluate the anti-fibrotic effects of hypericin,protein expression levels of α-SMA,fibronectin,col-lagen Ⅰ and collagen Ⅲ were assessed in both the UUO mouse kidney tissues and TGF-β1-stimulated NRK-52E cells using Western blotting.Blood urea nitrogen(BUN)and creatinine(Cr)levels in mice were measured to assess the renal protective effects of hypericin.Histological changes and collagen deposition in the kidneys were observed using hematoxylin-eosin and Masson staining.The expression levels of YAP and its downstream target gene CTGF were also determined using Western blot-ting.The specific mechanism of hypericin in improving renal interstitial fibrosis was further explored using the YAP inhibitor verteporfin.Results The protein expression levels of α-SMA,FN,collagen Ⅰ,and collagen Ⅲ in renal tissues of UUO mice and TGF-β1-induced NRK-52E cells were markedly reversed by hypericin(all P＜0.01).The levels of Cr and BUN in UUO mice se-rum were effectively reduced(both P＜0.01),and renal histopathological alterations and interstitial collagen deposition were markedly ameliorated.Potent inhibitory effects on YAP and CTGF protein expression were observed both in vivo and in vitro(both P＜0.01),exhibiting similar effects to verteporfin.Both treatments dramatically reduced TGF-β1-induced fibrosis in NRK-52E cells.Conclusion Hypericin can inhibit renal tubulointerstitial fibrosis by inhibiting YAP.