OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

Bone grafting is a primary method for treating bone defects. Among various graft materials, xenogeneic bone substitutes are widely used in clinical practice due to their abundant sources, convenient processing and storage, and avoidance of secondary surgeries. With the advancement of domestic production and the limitations of imported products, an increasing number of bone filling or grafting substitute materials isentering clinical trials. Relevant experts have drafted this consensus to enhance the management of medical device clinical trials, protect the rights of participants, and ensure the scientific and effective execution of trials. It summarizes clinical experience in aspects, such as design principles, participant inclusion/exclusion criteria, observation periods, efficacy evaluation metrics, safety assessment indicators, and quality control, to provide guidance for professionals in the field.
Humans ; Bone Substitutes/therapeutic use* ; Randomized Controlled Trials as Topic/methods* ; Consensus ; Bone Transplantation ; Research Design

Objective:To construct a prognostic predictive model for patients with moderate to severe traumatic brain injury (msTBI) based on regional cerebral oxygen saturation (rScO 2) and transcranial Doppler ultrasound (TCD) monitoring parameters and validate its effectiveness. Methods:A retrospective cohort study was conducted to analyze the clinical data of 161 patients with msTBI who were treated at Henan Provincial People′s Hospital from January 2021 to December 2022, including 104 males and 57 females, aged 19-76 years [(53.1±12.8)years]. Glasgow coma scale (GCS) score was 3-12 points [(7.0±1.9)points]. Both rScO 2 and TCD monitoring were performed. Based on the results of prognostic evaluation of patients with the modified Rankin scale (mRS) score at 90 days after discharge, the patients were divided into good prognosis group (mRS score≤3 points, n=88) and poor prognosis group (mRS score of 4-6 points, n=73). The following data of the two groups were collected: the general data, clinical data, rScO 2 monitoring parameters and TCD monitoring parameters. Univariate analysis was employed to compare the differences in the relevant prognostic indicators. Multivariate Logistic stepwise regression analysis was conducted to determine the predictors of poor prognostic outcomes in msTBI patients and regression equations were constructed. A nomogram predictive model based on regression equations was drawn with R language. The discriminability of the model was evaluated by drawing the receiver operating characteristic (ROC) curve, to calculate the area under the curve (AUC), sensitivity, specificity, and Jordan index of the model, and measuring the consistency index (C index). Hosmer-Lemeshow (H-L) goodness of fit test was conducted to evaluate the fit of the model, and the calibration curve was used to evaluate the calibration degree of the model. Decision curve analysis (DCA) was employed to evaluate the clinical benefit and applicability of the model. Results:There were significant differences between the two groups in the clinical data (cerebral hernia formation, GCS on admission, acute physiology and chronic health evaluation II (APACHE II) score on admission, Rotterdam CT score on admission, oxygenation index on admission, mean arterial pressure on admission), rScO 2 monitoring parameters (mean rScO 2, maximum rScO 2, rScO 2 variability), TCD monitoring parameters [peak systolic blood flow velocity (Vs), average blood flow velocity (Vm), pulse index (PI)] ( P<0.05 or 0.01). The results of multivariate Logistic stepwise regression analysis showed that cerebral hernia formation ( OR=9.28, 95% CI 3.40, 25.33, P<0.01), Rotterdam CT score on admission ( OR=1.92, 95% CI 1.32, 2.78, P<0.01), rScO 2 variability ( OR=4.66, 95% CI 1.74, 12.43, P<0.01), Vs ( OR=0.66, 95% CI 0.61, 0.75, P<0.01) and PI ( OR=20.07, 95% CI 4.17, 16.50, P<0.01) were predictive factors for poor prognosis in patients with msTBI. The regression equation was constructed with the forementioned 5 variables: Logit [ P/(1- P)]=2.23×"brain hernia formation"+0.65×"Rotterdam CT score on admission"+1.54×"rScO 2 variability"-0.42×"Vs"+3.00×"PI"-6.75. The AUC of prognostic predictive model of msTBI patients was 0.90 (95% CI 0.85, 0.95), with the sensitivity and specificity of 86.3% and 78.4%, Youden index of 0.65 and C index of 0.90. H-L goodness of fit test showed that the calibration degree of the predictive model was accurate ( χ2 =12.58, P>0.05). The average absolute error of the calibration curve was 0.025, showing that the calibration of the model was good. DCA results showed that this model had higher net return rate than the reference model within the probability range of risk threshold (20%-100%), with good clinical application value in evaluating the risk of poor prognosis of msTBI patients. Conclusion:The model constructed based on the combination of rScO 2 and TCD monitoring parameters (rScO 2 variability, Vs and PI) with multiple clinical indicators (cerebral hernia formation and Rotterdam CT score on admission) has good predictive performance for the prognosis of msTBI.

Objective:To investigate the characteristics of infectious pathogens in patients with refractory prostatitis,and to detect serum levels of factors related to immune inflammatory response such as macrophage inflammatory protein 1α(MIP-1α),IL-8 and cyclooxygenase-2(COX-2).Methods:A total of 87 patients with refractory chronic prostatitis who were diagnosed and treated in the Outpatient Department of Zhengzhou Ninth People's Hospital and Andrology Outpatient Department of Zhengzhou Central Hospital from October 2018 to June 2020 were selected as observation group,and 87 healthy subjects were selected as control group.Analyzed characteristics of infectious pathogens in patients with refractory prostatitis,compared serum MIP-1α,IL-8,COX-2 levels and the dif-ferent efficacy of the two groups,clinical data of the two groups of patients,serum MIP-1α,IL-8,COX-2 levels before and after treat-ment,and to analyze the correlation of the difference of serum MIP-1α,IL-8,COX-2 and the duration of the disease,the National Institutes of Health-Chronic Prostatitis Symptom Index(NIH-CPSI),maximum urinary flow rate and the relationship between serum MIP-1α,IL-8,COX-2 diffe-rence and the efficacy of patients with refractory prostatitis,and to evaluate the assessment value of serum MIP-1α,IL-8,COX-2 difference on the efficacy of patients with refractory prostatitis.Results:Bacterial infection was present in 87 specimens of prostatic fluid from patients with refractory prostatitis,and 9 patients had concomitant mycoplasma infection.From the prostatic fluid samples of 87 patients with refractory prostatitis,a total of 338 pathogenic bacteria were isolated,including 230 gram-positive bacteria,accounting for 68.05%;108 gram-negative bacteria,accounting for 31.95%;serum MIP-1α,IL-8,COX-2 levels in observation group were higher than that in control group,the difference was statistically significant(P<0.05);the course of disease,NIH-CPSI score,maximum urinary flow rate,levels of MIP-1α,IL-8,COX-2 after treatment,and the difference of MIP-1α,IL-8,COX-2 before and after treatment were compared in patients with different curative effects,and the difference was statistically signifi-cant(P<0.05);the difference between serum MIP-1α,IL-8 and COX-2 in patients with refractory prostatitis before and after treat-ment was positively correlated with disease course and NIH-CPSI score,while negatively correlated with maximum urinary flow rate(P<0.05);the differences of serum MIP-1α,IL-8 and COX-2 before and after treatment were significantly correlated with curative effect of patients with refractory prostatitis(P<0.05);AUC values of serum MIP-1α,IL-8 and COX-2 before and after treatment to evaluate the efficacy of refractory prostatitis patients were 0.856,0.819 and 0.788,respectively,and the combined AUC value was the largest,which was 0.903.Conclusion:Pathogenic bacteria in patients with refractory prostatitis are mainly gram-positive bacteria,and the serum MIP-1α,IL-8 and COX-2 are significantly increased,which are closely related to the evolution of the disease.They can be used to evaluate clinical efficacy,and provide information for subsequent treatment.

Objective To investigate the structural characteristics of intestinal flora in children with sepsis and its association with inflammatory response.Methods A prospective cohort study was conducted.The children with sepsis who were admitted from December 2021 to January 2023 were enrolled as the sepsis group,and the children with non-sepsis who were admitted during the same period were enrolled as the non-sepsis group.The two groups were compared in terms of the distribution characteristics of intestinal flora,peripheral white blood cell count(WBC),C reactive protein(CRP),and cytokines,and the correlation of the relative abundance of fecal flora with WBC,CRP,and cytokines was analyzed.Results At the genus level,compared with the non-sepsis group,the sepsis group had significantly lower relative abundance of Akkermansia,Ruminococcus,and Alistipes and significantly higher relative abundance of Enterococcus,Streptococcus,and Staphylococcus(P<0.05).At the phylum level,Proteobacteria was the dominant phylum(37.46%)in the group of children with a score of≤70 from the Pediatric Critical Illness Score(PICS),and Firmicutes was the dominant phylum in the group of children with a score of 71-80 or 81-90 from the PICS(72.20%and 43.88%,respectively).At the genus level,among the 18 specimens,5 had a relative abundance of>50%for a single flora.Compared with the non-sepsis group,the sepsis group had significant higher levels of WBC,CRP,interleukin-6(IL-6),interleukin-10(IL-10),and tumor necrosis factor-α(P<0.05).The Spearman's rank correlation analysis showed that at the genus level,the relative abundance of Ruminococcus,Alistipes,and Parasutterella in the sepsis group was negatively correlated with the levels of WBC,CRP,and IL-6(P<0.05);the relative abundance of Enterococcus was positively correlated with the CRP level(P<0.01);the relative abundance of Streptococcus and Staphylococcus was positively correlated with the levels of CRP and IL-6(P<0.05);the relative abundance of Streptococcus was positively correlated with WBC(P<0.05).Conclusions Intestinal flora disturbance is observed in children with sepsis,and its characteristics vary with the severity of the disease.The structural changes of intestinal flora are correlated with inflammatory response in children with sepsis.

This article aims to analyze the therapeutic effect and probe into the mechanism of Sanhuang Hushen Fangshuai Decoction in treating chronic kidney disease(CKD) based on metabolomics and bioinformatics. The patients with stage 3-4 CKD diagnosed and treated in the Changzhou Hospital of Traditional Chinese Medicine from June 2023 to March 2024 were enrolled in this study. The patients were treated with Sanhuang Hushen Fangshuai Decoction, and the therapeutic effect was evaluated. The serum samples were collected before and after treatment. Ultra-performance liquid chromatography was employed to detect metabolites in the serum, and multivariate statistical analysis was performed. Bioinformatics was employed to screen the active components and targets of the decoction and the potential targets of CKD. The protein-protein interaction(PPI) network of the common targets shared by the decoction and CKD and the drug-component-target network were constructed. The core components and targets were screened according to the correlation degree of the network. The binding between core components and targets was verified by molecular docking. The results showed that Sanhuang Hushen Fangshuai Decoction improved the renal function and reduced proteinuria. Compared with the healthy population, the post-treatment population showed recovery of 54 up-regulated metabolites and 43 down-regulated metabolites. Enrichment analysis results showed that the key pathways included adenosine triphosphate binding cassette(ABC) transport, tryptophan metabolism, and tyrosine metabolism. The results of bioinformatics analysis showed that the core components of Sanhuang Hushen Fangshuai Decoction in treating CKD included kaempferol, β-sitosterol, luteolin, 7-O-methylisolingol, and tanshinone Ⅱ_A. The core targets included TP53, PTGS2, JUN, AKT1, and TNF. Molecular docking results showed that the core components bound well to the target genes. The results of joint pathway analysis suggested that both differential metabolites and key targets were involved in galactose metabolism, nicotinamide metabolism, and other pathways. This study suggests that Sanhuang Hushen Fangshuai Decoction is effective for CKD, and it can regulate multiple abnormal metabolites and participates in multiple metabolic pathways involving amino acids and sugars. The active components such as kaempferol in the decoction may regulate related targets such as TP53 and PTGS2. This study provides a basis for the prevention and treatment of CKD with traditional Chinese medicine.
Drugs, Chinese Herbal/administration & dosage* ; Renal Insufficiency, Chronic/genetics* ; Humans ; Computational Biology ; Male ; Metabolomics ; Protein Interaction Maps/drug effects* ; Middle Aged ; Molecular Docking Simulation ; Female ; Adult ; Aged

Neurovascular coupling is the function of regulating blood flow of the central nervous system at the level of neurovascular units. The central nervous system diseases related to neurovascular coupling mainly include cerebrovascular diseases such as chronic cerebral ischemia and neurodegenerative diseases such as Alzheimer's disease,Parkinson's disease and Lewy body dementia. The main mechanism of neurovascular coupling dysfunction leading to the above diseases is cerebrovascular dysfunction or loss,which leads to serious damage to neuronal ischemia and affects its function. Therefore,this paper reviews the research status of neurovascular coupling and its related central nervous system diseases,in order to guide the follow-up research. The purpose of this paper is to provide a basis for the prevention,relief and treatment of central nervous system diseases related to neurovascular coupling through the mechanism of neurovascular coupling.

Humans ; Aortic Valve/surgery* ; Aortic Valve Stenosis/surgery* ; Calcinosis/surgery* ; Transcatheter Aortic Valve Replacement ; Heart Valve Prosthesis

Humans ; Aortic Valve/surgery* ; Aortic Valve Stenosis/surgery* ; Calcinosis/surgery* ; Transcatheter Aortic Valve Replacement ; Heart Valve Prosthesis

Objective:To observe the clinical value of intracranial pressure (ICP) monitoring combined with target temperature management (TTM) in patients with acute anterior circulation ischemic stroke after mechanical thrombectomy.Methods:A prospective analysis was performed. Ninety-two patients with acute anterior circulation ischemic stroke who received mechanical thrombectomy from March 2019 to June 2022 in Department of Neurosurgery, He'nan Provincial People's Hospital were enrolled. Within 1-5 d of mechanical thrombectomy, these patients were randomly divided into observation group ( n=46) and control group ( n=46). The patients in observation group received comprehensive management for neurological critical illness through multimodal monitoring such as ICP real-time monitoring combined with TTM (controlling the core temperature at 33℃-35℃), while patients in control group received simple ICP real-time monitoring. ICP monitoring for both groups lasted for 5-7 d, and routine symptomatic support treatment was given. Stepwise treatment was adopted based on real-time changes of ICP. The differences in clinical data, ICP at different times, incidence of adverse events, length of hospital stay, mortality rate, and prognoses were compared between the 2 groups. Results:On the 2 nd, 3 rd, 4 th, and 5 th d of monitoring, the observation group had significantly decreased ICP compared with the control group ( P<0.05). Both observation group and control group had significantly increased ICP on the 2 nd, 3 rd, 4 th, and 5 th d of monitoring compared with that on the 1 st d of monitoring ( P<0.05). Compared with the control group, the observation group had statistically higher incidences of shivers and electrolyte disorders, and statistically lower incidences of unstable blood pressure, cerebral heart syndrome, septic shock, and cerebral hernia during hospitalization ( P<0.05). Compared with the control group, the observation group had significantly shortened hospital stay, and statistically lower modified Rankin scale (mRS) scores, higher Glasgow outcome scale-extended (GOS-E) scores, higher good prognosis rate, and lower mortality rate 6 months after mechanical thrombectomy ( P<0.05). Compared with the control group, the observation group had statistically lower incidences of postoperative cerebral hemorrhage conversion and recurrent cerebral infarction ( P<0.05). Kaplan-Meier survival analysis showed that the survival rate in the observation group was significantly higher than that in the control group ( P<0.05). Conclusion:ICP monitoring combined with TTM can reduce early complications, shorten hospital stay, reduce mortality, and improve long-term prognosis in patients with acute anterior circulation ischemic stroke after mechanical thrombectomy.