The development of atherosclerosis （AS） is closely associated with endothelial dysfunction and mitochondrial metabolic abnormalities. These alterations are fundamentally characterized by metabolic reprogramming， in which the tricarboxylic acid （TCA） cycle serves as a central regulatory hub. Disruption of the homeostasis of TCA cycle intermediates， including succinate， α -ketoglutarate， and itaconate， contributes to AS progression through multiple mechanisms， such as the modulation of oxidative stress， inflammation， and glucose and lipid metabolic networks. Owing to their multi-target and multi-pathway regulatory properties， bioactive compounds derived from traditional Chinese medicine （TCM） have demonstrated unique advantages in correcting metabolic dysregulation. Flavonoids， glycosides， and other bioactive constituents of TCM can target key enzymes and metabolites involved in the TCA cycle， thereby restoring aberrant metabolic reprogramming， alleviating endothelial injury induced by oxidative stress， inflammation， and glucose and lipid metabolic disorders， ultimately improving metabolic homeostasis and attenuating the progression of AS.

The development of atherosclerosis （AS） is closely associated with endothelial dysfunction and mitochondrial metabolic abnormalities. These alterations are fundamentally characterized by metabolic reprogramming， in which the tricarboxylic acid （TCA） cycle serves as a central regulatory hub. Disruption of the homeostasis of TCA cycle intermediates， including succinate， α -ketoglutarate， and itaconate， contributes to AS progression through multiple mechanisms， such as the modulation of oxidative stress， inflammation， and glucose and lipid metabolic networks. Owing to their multi-target and multi-pathway regulatory properties， bioactive compounds derived from traditional Chinese medicine （TCM） have demonstrated unique advantages in correcting metabolic dysregulation. Flavonoids， glycosides， and other bioactive constituents of TCM can target key enzymes and metabolites involved in the TCA cycle， thereby restoring aberrant metabolic reprogramming， alleviating endothelial injury induced by oxidative stress， inflammation， and glucose and lipid metabolic disorders， ultimately improving metabolic homeostasis and attenuating the progression of AS.

Objective To evaluate the reliability and validity of the Chinese version of the hyperacusis scale and estimate its applicability in the Chinese population.Methods The patients admitted to the Department of Oto-laryngology of Xijing Hospital from June 2017 to December 2017 were surveyed.A total of 300 questionnaires were sent out and 293 valid questionnaires were collected with effective response rate of 97.67％.All participants comple-ted a basic information survey,pure tone audiometry and fill in the Chinese version of the hyperacusis scale.The re-liability and validity of this scale were evaluated.Results Among the 293 respondents,243(82.93％)were compli-cated with tinnitus.A total of 181 cases(61.77％)were subjectively diagnosed with hyperacusis through question-naire survey.According to the scale evaluation,174 cases(59.39％)were diagnosed with hyperacusis,and the Kappa value of conformity test of the two methods was 0.81(P＜0.001).Reliability analysis indicated a Cronbach'sα coefficient of 0.93 for the entire scale.Each dimension had a Cronbach's α coefficient＞0.60.The split-half relia-bility coefficient for the entire scale was 0.86,and for each dimension,it was＞0.60.Exploratory factor analysis of validity suggested that 25 items could be grouped under 4 factors,such as functional part,social part,emotional part and harmonic sensitivity part.These factors had eigenvalues greater than 1,accounting for 59.42％of the total variance.Post-rotation,the 25 items were distributed across the 4 components,with each item having a factor load-ing＞0.40.Confirmatory factor analysis of validity showed model fit parameters as:x2/df=1.98,GFI=0.91,AGFI=0.83,CFI=0.92,TLI=0.89,RMSEA=0.08.Each item had a standardized factor loading＞0.40.Con-clusion The Chinese version of the hyperacusis scale demonstrated strong reliability and validity,making it suitable for use among the Chinese population.

Objective:To compare the effects of intensive and standard blood pressure control on the outcomes of patients with acute ischemic stroke in the anterior circulation who have successfully recanalized after endovascular therapy (EVT).Methods:A multicenter, open-label, blinded-endpoint, randomized controlled design was used. Patients with anterior circulation stroke received EVT and successfully recanalized in Nanjing First Hospital, Nanjing Medical University and several branch hospitals from July 2020 to October 2022 were prospectively included. They were randomly divided into the intensive blood pressure control group (target systolic blood pressure [SBP] 100-120 mmHg) or the standard blood pressure control group (target SBP 121-140 mmHg). The blood pressure of both groups needs to achieve the target within 1 h and maintain for 72 h. The primary outcome endpoint was outcome at 90 d, and the good outcome was defined as a score of 0-2 on the modified Rankin Scale. Secondary outcome endpoints included early neurological improvement, symptomatic intracranial hemorrhage (sICH) within 24 h, and death and serious adverse events within 90 d.Results:A total of 120 patients were included, including 63 in the intensive blood pressure control group and 57 in the standard blood pressure control group. There was no statistically significant difference in baseline characteristics between the two groups. The SBP at 72 h after procedure was 122.7±8.1 mmHg in the intensive blood pressure control group and 130.2±7.4 mmHg in the standard blood pressure control group, respectively. There were no significantly differences in the good outcome rate (54.0% vs. 54.4%; χ2=0.002, P=0.963), the early neurological improvement rate (45.2% vs. 34.5%; χ2=1.367, P=0.242), the incidence of sICH (6.3% vs. 3.5%; P=0.682), mortality (7.9% vs. 14.0%; χ2=1.152, P=0.283) and the incidence of serious adverse events (12.7% vs. 15.8%; χ2=0.235, P=0.628) at 90 d between the intensive blood pressure control group and the standard blood pressure control group. Conclusion:In patients with anterior circulation stroke and successful revascularization of EVT, early intensive blood pressure control don’t improve clinical outcomes and reduce the incidence of sICH.

Purpose: C5α receptor 1 (C5ΑR1) is associated with the development of various human cancers. However, whether it is involved in the development of hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC) is poorly understood. We explored the expression, biological role, and associated mechanisms of C5AR1 in HBV-related hepatoma cells. Materials and Methods: The expression of C5ΑR1 mediated by HBV and HBV core protein (HBc) was detected in hepatoma cells. The function of nuclear factor кB (NF-κB) pathway in HBc-induced C5AR1 expression was assessed. The roles of C5ΑR1 in the activation of intracellular signal pathways, the upregulation of inflammatory cytokines, and the growth and migration of hepatoma cells mediated by HBc, were investigated. The effect of C5α in the development of HCC mediated by C5AR1 was also measured. Results: C5ΑR1 expression was increased in HBV-positive hepatoma cells. Dependent on HBc, HBV enhanced the expression of C5ΑR1 at the mRNA and protein levels. Besides, HBc could promote C5ΑR1 expression via the NF-κB pathway. Based on the C5ΑR1, HBc facilitated the activation of JNK and ERK pathways and the expression and secretion of interleukin-6 in hepatoma cells. Furthermore, C5ΑR1 was responsible for enhancing the growth and migration of hepatoma cells mediated by HBc. Except these, C5α could promote the malignant development of HBc-positive HCC via C5AR1. Conclusion We provide new insight into the mechanisms of hepatocarcinogenesis mediated by HBc. C5ΑR1 has a significant role in the functional abnormality of hepatoma cells mediated by HBc, and might be utilized as a potential therapeutic target for HBV-related HCC.

Purpose: C5α receptor 1 (C5ΑR1) is associated with the development of various human cancers. However, whether it is involved in the development of hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC) is poorly understood. We explored the expression, biological role, and associated mechanisms of C5AR1 in HBV-related hepatoma cells. Materials and Methods: The expression of C5ΑR1 mediated by HBV and HBV core protein (HBc) was detected in hepatoma cells. The function of nuclear factor кB (NF-κB) pathway in HBc-induced C5AR1 expression was assessed. The roles of C5ΑR1 in the activation of intracellular signal pathways, the upregulation of inflammatory cytokines, and the growth and migration of hepatoma cells mediated by HBc, were investigated. The effect of C5α in the development of HCC mediated by C5AR1 was also measured. Results: C5ΑR1 expression was increased in HBV-positive hepatoma cells. Dependent on HBc, HBV enhanced the expression of C5ΑR1 at the mRNA and protein levels. Besides, HBc could promote C5ΑR1 expression via the NF-κB pathway. Based on the C5ΑR1, HBc facilitated the activation of JNK and ERK pathways and the expression and secretion of interleukin-6 in hepatoma cells. Furthermore, C5ΑR1 was responsible for enhancing the growth and migration of hepatoma cells mediated by HBc. Except these, C5α could promote the malignant development of HBc-positive HCC via C5AR1. Conclusion We provide new insight into the mechanisms of hepatocarcinogenesis mediated by HBc. C5ΑR1 has a significant role in the functional abnormality of hepatoma cells mediated by HBc, and might be utilized as a potential therapeutic target for HBV-related HCC.

Objective:To investigate the predictive value of serum hypersensitive C-reactive protein (hs-CRP) for stroke-associated pneumonia (SAP) in patients with acute ischemic stroke (AIS) who received intravenous thrombolysis.Methods:From May 2015 to April 2017, the clinical data of the patients with AIS treated with intravenous thrombolysis in Nanjing First Hospital were collected retrospectively. Multivariate logistic regression analysis was used to determine the independent risk factors for SAP in patients with AIS after intravenous thrombolysis. Receiver operating characteristic (ROC) curve and nomogram-based methods were used to analyze the predictive value of hs-CRP for SAP. Results:A total of 243 patients with AIS who received intravenous thrombolysis were included, and 63 (34.6%) of them had SAP. There were significant differences in age ( P=0.006), leukocyte count ( P=0.044), fasting blood glucose level ( P=0.003), serum hs-CRP level ( P=0.001), hs-CRP classification ( P=0.001) and dysphagia rate ( P=0.035) between the SAP group and non-SAP group. Multivariate logistic regression analysis showed that after adjusting for the confounding factors, taking the first quartile of serum hs-CRP level as a reference, the third quantile (odds ratio [ OR] 18.790, 95% confidence interval [ CI] 4.771-74.007; P=0.001) and the fourth quantile ( OR 54.054, 95% CI 12.248-324.088; P=0.001) of hs-CRP were the independent predictors of SAP. The area under the ROC curve of the baseline serum hs-CRP level for predicting SAP was 0.805 (95% CI 0.742-0.868; P<0.001). When the optimal cut-off value of hs-CRP was 5.54 mg/L, the sensitivity and specificity of predicting SAP were 76.11% and 76.19%, respectively. The analysis of nomogram also showed that hs-CRP was an independent predictor of SAP (consistency index 0.862, 95% CI 0.738-0.986; P<0.001). Conclusions:The increased serum hs-CRP was an independent predictor of SAP in patients with AIS receiving intravenous thrombolysis, and had a higher predictive value.

Objective: To evaluate the efficacy and safety of low dose sublingual nifedipine dripping pills (5 mg) in treating moderate and severe hypertension in comparison with normal dose (10 mg) of sublingual nifedipine dripping pills. Methods: This study was designed as a randomized, double-blind, positive drug parallel controlled, multi-center, non-inferiority clinical trial. Patients with moderate and severe hypertension were enrolled by 14 clinical trial centers, randomly divided into the trial group (sublingual 5 mg nifedipine dripping pills) and the control group (sublingual 10 mg nifedipine dripping pills). The changes in blood pressure were monitored continuously within 2 hours after the initial administration, repeated the dose in 20 minutes interval after the initial administration for up to additional 3 doses (maximum 4 doses) if the antihypertensive efficacy was not satisfactory. The efficacy of antihypertensive therapy between the two groups was evaluated by repeated administration rates and blood pressure changes at 60 minutes post the initial administration, and the safety of treatment was evaluated by recording adverse event rate of the two groups. Results: The anti-hypertensive effective rates at 60 minutes after sublingual administration were 83.5% (202/242) and 86.7% (208/240) respectively between the trial group and control group (χ²=1.307, P=0.253) . On the aspect of antihypertensive effectiveness at 60 minutes after single dose of sublingual administration, the anti-hypertension effective rates of the trial group and the control group were 85.6% (154/180) and 87.2% (164/188) respectively (χ²=0.221, P=0.639). Prevalence of the repeated administration was also similar between the two groups (25.6%(62/242) in the trial group and 21.7% (52/240) in the control group, χ²=1.043, P=0.307). On the safety aspect, there was no adverse events/reactions in the trial group, but there were 15 cases of adverse events/reactions occurred in control group (6.25%, χ²=15.611, P<0.001). Conclusions In the treatment of moderate to severe hypertension, the antihypertensive efficacy of low dose nifedipine dripping pills is similar to that of conventional dosage, and the safety profile of low dose nifedipine dripping pills is better than that of the conventional dose.

Objective To investigate the effect and safety of intravenous thrombolytic therapy in the endovascular treatment of acute anterior circulation vascular occlusive stroke.Methods The clinical data of 226 patients with acute anterior circulation vascular occlusive stroke who underwent endovascular treatment in Nanjing First Hospital,Nanjing Medical University from May 2015 to May 2018 were retrospectively collected.According to whether or not intravenous thrombolysis was performed,the patients were classified into simple thrombectomy group (n=112) and bridging treatment group (n=114).The modified Thrombolysis in Cerebral Infarction Score (mTICI) was used to evaluate the vascular opening effect,and the blood vessel recanalization time,mTICI,the symptomatic intracranial hemorrhage rate,and the modified Rankin Scale (mRS) score at 90 days after surgery were evaluated.Results There were no statistically significant differences in gender,age,past history and National Institute of Health Stroke Scale score between the two groups (P＞0.05).There was no statistically significant difference in door-to-recanalization time between the two groups (P＞0.05).Excluding the patients with post-wake stroke and unexplained onset time,the simple thrombectomy group (n=63) and the bridging treatment group (n=1 11) showed statistically significant differences in onset-to-door time ((235.04± 182.64) min vs (102.48±60.51) min,t=7.01,P＜0.01)and onset-to-recanalization time ((405.31 ± 148.89) min vs (337.31 ± 117.65) min,t=3.32,P=0.01).The difference in number of thrombectomy between the simple thrombolysis group (2.55± 1.52) and the bridging treatment group (2.11± 1.48) was statistically significant (t=2.246,P=0.026).The total reperfusion (mTICI 2b/3) rate was 89.8％ (203/226),88.4％ (99/112) in the simple thrombectomy group and 91.2％ (104/114) in the bridging treatment group,with no statistically significant difference between the two groups (P＞0.05).The differences in symptomatic intracranial hemorrhage rate (8.93％ (10/112) vs 11.4％ (13/114)),mortality rate (12.5％ (12/112) vs 16.7％ (19/114)) and 90-day good functional outcome (mRS score 0-2;54.5％ (61/112) vs 55.8％ (63/114)) between the two groups were not statistically significant (P＞0.05).Conclusions In patients with acute anterior circulation vascular occlusive stroke undergoing endovascular treatment,intravenous thrombolysis can reduce the number of thrombectomy,not increase the door-to-recanalization time,the risk of symptomatic intracranial hemorrhage and mortality,and has similar good functional outcome as the simple thrombeetomy group.Therefore,intravenous thrombolysis is safe and effective for endovascular treatment of acute anterior circulation large vessel occlusive stroke.