Aprocitentan is a dual endothelin receptor antagonist.Based on the effective evidence of Ⅲ phases of clinical trials,the drug was approved for marketing by the U.S.Food and Drug Administration on March 19,2024 for the treatment of refractory hypertension.At present,multiple clinical studies have confirmed that Aprocitentan has excellent antihypertensive effects and good tolerability.This article reviews the pharmacological effects,preclinical.

Purpose::Cerebral edema (CE) is the main secondary injury following traumatic brain injury (TBI) caused by road traffic accidents (RTAs). It is challenging to be predicted timely. In this study, we aimed to develop a prediction model for CE by identifying its risk factors and comparing the timing of edema occurrence in TBI patients with varying levels of injuries.Methods::This case-control study included 218 patients with TBI caused by RTAs. The cohort was divided into CE and non-CE groups, according to CT results within 7 days. Demographic data, imaging data, and clinical data were collected and analyzed. Quantitative variables that follow normal distribution were presented as mean ± standard deviation, those that do not follow normal distribution were presented as median (Q 1, Q 3). Categorical variables were expressed as percentages. The Chi-square test and logistic regression analysis were used to identify risk factors for CE. Logistic curve fitting was performed to predict the time to secondary CE in TBI patients with different levels of injuries. The efficacy of the model was evaluated using the receiver operator characteristic curve. Results::According to the study, almost half (47.3%) of the patients were found to have CE. The risk factors associated with CE were bilateral frontal lobe contusion, unilateral frontal lobe contusion, cerebral contusion, subarachnoid hemorrhage, and abbreviated injury scale (AIS). The odds ratio values for these factors were 7.27 (95% confidence interval ( CI): 2.08 -25.42, p = 0.002), 2.85 (95% CI: 1.11 -7.31, p = 0.030), 2.62 (95% CI: 1.12 -6.13, p = 0.027), 2.44 (95% CI: 1.25 -4.76, p = 0.009), and 1.5 (95% CI: 1.10 -2.04, p = 0.009), respectively. We also observed that patients with mild/moderate TBI (AIS ≤ 3) had a 50% probability of developing CE 19.7 h after injury (χ 2= 13.82, adjusted R2 = 0.51), while patients with severe TBI (AIS > 3) developed CE after 12.5 h (χ 2= 18.48, adjusted R2 = 0.54). Finally, we conducted a receiver operator characteristic curve analysis of CE time, which showed an area under the curve of 0.744 and 0.672 for severe and mild/moderate TBI, respectively. Conclusion::Our study found that the onset of CE in individuals with TBI resulting from RTAs was correlated with the severity of the injury. Specifically, those with more severe injuries experienced an earlier onset of CE. These findings suggest that there is a critical time window for clinical intervention in cases of CE secondary to TBI.

This study aims to evaluate the methodological and reporting quality of diagnosis and treatment guidelines for hyperuricemia as well as the expert consensuses and promote the understanding and application of the diagnosis and treatment guidelines for hyperuricemia. With "hyperuricemia" "guidelines" "consensus" "recommendations" as the key words in titles, the authors searched for the published clinical guidelines on hyperuricemia in Chinese against CNKI, Wanfang, VIP, Medlive and the official website of the industry association. The retrieval time limit was until May 31, 2021. The appraisal of guidelines for research and evaluation Ⅱ(AGREEⅡ) and the reporting items for practice guidelines in health care(RIGHT) were employed to evaluate the methodological quality and reporting quality of 14 guidelines/consensuses included. The average scores of the guidelines/consensuses were 80.85%(48.61%-98.61%) for the domain of scope and purpose, 34.52%(0-69.44%) for the domain of stakeholder involvement, 35.53%(6.25%-92.19%) for the domain of rigor of development, 55.85%(23.61%-86.11%) for the domain of clarity of presentation, 26.19%(0-76.04%) for the domain of applicability, and 21.42%(0-50.00%) for the domain of editorial independence. Nine guidelines/consensuses were of medium overall quality with grade B recommendation, and five guidelines/consensuses were of poor quality with grade C recommendation. The RIGHT classified the fourteen guidelines/consensuses into one of high reporting quality, three of medium reporting quality, and ten of low reporting quality. The results of this study indicate that the standardization and rigor of the methodological quality and the reporting quality of the clinical guidelines/consensuses for hyperuricemia in China remain to be strengthened.
China ; Consensus ; Humans ; Hyperuricemia/drug therapy* ; Publications ; Reference Standards

Lung volume reduction loop uses bronchoscopic lung volume reduction(BLVR) technology to compress and collapse the necrotic emphysema tissue and exhaust the internal gas to achieve the purpose of lung volume reduction to treat emphysema. After the lung volume reduction loop is implanted into the human body, the compressed part of the lung tissue tends to expand with breathing, which makes the lung volume reduction loop expand into a linear trend periodically. Fatigue resistance is one of the most important performance indexes of the lung volume reduction loop. In the paper, Z-direction vibration fatigue machine was used to simulate the changes of human respiratory cycle movement to test the fatigue performance of lung volume reduction loop, which can provide some reference for the test method of in vitro fatigue performance of lung volume reduction related products in the future.
Bronchoscopy/methods* ; Emphysema/surgery* ; Humans ; Lung ; Pneumonectomy/methods* ; Pulmonary Emphysema/surgery* ; Treatment Outcome

Obesity is increasingly prevalent globally, searching for therapeutic agents acting on adipose tissue is of great importance. Equisetin (EQST), a meroterpenoid isolated from a marine sponge-derived fungus, has been reported to display antibacterial and antiviral activities. Here, we revealed that EQST displayed anti-obesity effects acting on adipose tissue through inhibiting adipogenesis in vitro and attenuating HFD-induced obesity in mice, doing so without affecting food intake, blood pressure or heart rate. We demonstrated that EQST inhibited the enzyme activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), a therapeutic target of obesity in adipose tissue. Anti-obesity properties of EQST were all offset by applying excessive 11β-HSD1's substrates and 11β-HSD1 inhibition through knockdown in vitro or 11β-HSD1 knockout in vivo. In the 11β-HSD1 bypass model constructed by adding excess 11β-HSD1 products, EQST's anti-obesity effects disappeared. Furthermore, EQST directly bond to 11β-HSD1 protein and presented remarkable better intensity on 11β-HSD1 inhibition and better efficacy on anti-obesity than known 11β-HSD1 inhibitor. Therefore, EQST can be developed into anti-obesity candidate compound, and this study may provide more clues for developing higher effective 11β-HSD1 inhibitors.

BACKGROUND: Although congenital hypothyroidism (CH) has been widely studied in Western countries, CH incidence at different administrative levels in China during the past decade remains unknown. This study aimed to update the incidence and revealed the spatial pattern of CH incidence in the mainland of China, which could be helpful in the planning and implementation of preventative measures. METHODS: The data used in our study were derived from 245 newborns screening centers that cover 30 provinces of the Chinese Newborn Screening Information System. Spatial auto-correlation was analyzed by Global Moran I and Getis-Ord Gi statistics at the provincial level. Kriging interpolation methods were applied to estimate a further detailed spatial distribution of CH incidence at city level throughout the mainland of China, and Kulldorff space scanning statistical methods were used to identify the spatial clusters of CH cases at the city level. RESULTS: A total of 91,921,334 neonates were screened from 2013 to 2018 and 42,861 cases of primary CH were identified, yielding an incidence of 4.66 per 10,000 newborns screened (95% confidence interval [CI]: 4.62-4.71). Neonates in central (risk ratio [RR] = 0.84, 95% CI: 0.82-0.85) and western districts (RR = 0.71, 95% CI: 0.69-0.73) had lower probability of CH cases compared with the eastern region. The CH incidence indicated a moderate positive global spatial autocorrelation (Global Moran I value = 0.394, P  < 0.05), and the CH cases were significantly clustered in spatial distribution. A most likely city-cluster (log-likelihood ratio [LLR] = 588.82, RR = 2.36, P  < 0.01) and 25 secondary city-clusters of high incidence were scanned. The incidence of each province and each city in the mainland of China was estimated by kriging interpolation, revealing the most affected province and city to be Zhejiang Province and Hangzhou city, respectively. CONCLUSION This study offers an insight into the space clustering of CH incidence at provincial and city scales. Future work on environmental factors need to focus on the effects of CH occurrence.
China/epidemiology* ; Cluster Analysis ; Congenital Hypothyroidism/epidemiology* ; Humans ; Incidence ; Infant, Newborn ; Retrospective Studies ; Spatial Analysis

Objective To evaluate the protective effect and mechanism of mild hypothermia on swine kidney after cardiopulmonary resuscitation, and whether changes in body temperature during mild hypothermia weaken the protective effect of mild hypothermia. Methods 18 swines were randomly divided into constant mild hypothermia group (CMH), variable mild hypothermia group (VMH) and control group (CON), with 6 swines in each group. Cardiac arrest model was successfully made. Then ECPR and temperature management was adopted. The target body temperature was 34℃ in the CMH group, and 37℃ in the control group, while the target body temperature of the VMH group fluctuated from 33 to 35 ℃ every two hours. After 24h, the animals were slowly reheated and then sacrificed. The kidneys were taken for real-time quantitative PCR, immunohistochemistry and histopathological examination. Results The expression levels of Bax, GRP78 and CHOP in the CMH group were lower than those in the CON group. Moreover, the expression of GRP78 in the CMH group were lower than those in the VMH group. The expression of Bcl-2 in the CMH group were higher than those in the VMH group and the CON group, and the expression of Bcl-2 in the VMH group were higher than those in the CON group (all P < 0.05). The positive expression of Bax was the most significant in the CON group and the least in the CMH group. The positive expression of Bcl-2 was the most significant in the CMH group and the least in the CON group. The nuclear membrane of porcine kidney cells shrank, nucleoli shrank and mitochondria swelled obviously in the CON group. The morphological injury changes were mild in the CMH group compared with the VMH group, while the CON group showed the severest change. Conclusion Mild hypothermia could attenuate the renal tubular cells apoptosis after cardiopulmonary resuscitation by inhibiting endoplasmic reticulum stress pathway, thus playing a protective role to the kidney. While aAbnormal temperature fluctuation during mild hypothermia maintenance may weaken the protection of kidney by mild hypothermia.

Objective To evaluate the effect of alprostadil on the microcirculation and mortality after the fluid resuscitation in patients with septic shock.Methods The patients who met the criteria of septic shock admitted to our hospital from March 2015 to September 2016 were selected as the subjects.After the shock resuscitation reached the standard,they were randomly divided into control group and alprostadil group.Control group was given a standard treatment.On the basis of standard treatment,alprostadil group was given alprostadil 10μg/d plus tube.The heart rate,mean arterial pressure (MAP),central venous pressure (CVP),lactic acid (Lac) and urine volume were recorded at 0,1,3 and 7 days.The microcirculation index under the tongue including small vessel density (TvDs),perfused small microvessel density (PvDs),small vessel perfusion ratio (PPVs),microvascular flow index (MFI) and heterogeneity index (HI) were recorded at 0,6,24 and 72h.The patients' hospitalization time in ICU,total hospitalization time and mortality rate of follow-up 28 days were recorded.Results Forty-eight patients were enrolled in this study,of which 23 were in control group and 25 in alprostadil group.The heart rate and MAP had no significant changes in alprostadil group,but the CVP decreased significantly compared with control group (P＜0.05) at 1,3,7 days after the treatment,and urine volume increased at 3 and 7 days in the alprostadil group (P＜0.05);but TvDs did not increase at 6 and 24h in the two groups,while PvDs,PPVs,MFI,HI increased at 6,24 and 72h in the two groups,with a higher value at 24 and 72h than the 6h.The 72-h indexes were significantly higher in alprostadil group than in control group (P＜0.05).The mechanical ventilation (MV) was significantly lower in alprostadil group than in control group (P＜0.05);ICU hospitalization time and total hospitalization time was significantly shorter in alprostadil group than in control group (P＜0.05).The hospital mortality and 28-day mortality were lower in alprostadil group than in control group (P＜0.05).Conclusions Alprostadil could significantly improve the microcirculation and urine volume in the patients after resuscitation for septic shock,with little effect on systemic circulation,effectively improve the prognosis of patients,and shortening the mechanical ventilation time,ICU stay time and total hospitalization time,thus reducing the mortality rate.

OBJECTIVETo investigate the prevalence and possible factors influencing metabolic syndrome in people from Guizhou Province and to explore the predictive value of the fat-to-muscle ratio in diagnosing metabolic syndrome.

METHODSA multistage stratified sampling method was used in this cross-sectional study of 20-80 years old Han and Bouyei populations from Guizhou Province, southwestern China, from October-December 2012. The study included 4,553 cases of metabolic syndrome, that was defined according to 2005 International Diabetes Federation criteria. The receiver operating characteristic curve was used for determining the sensitivity, specificity, and predictive ability of the fat-to-muscle ratio for the diagnosis of metabolic syndrome.

RESULTSThe age-standardized prevalence of metabolic syndrome was 11.38% (men: 9.76%; women: 12.72%) for Han and 4.78% (men: 4.43%; women: 5.30%) for Bouyei populations. In Guizhou Province, the cut-off value for the men fat-to-muscle ratio was 0.34, the area under the curve was 0.95, and the sensitivity and specificity were 0.94 and 0.85, respectively. The cut-off value for the women fat-to-muscle ratio was 0.55, the area under the curve was 0.91, and the sensitivity and specificity were 0.93 and 0.79, respectively.

CONCLUSIONThe fat-to-muscle ratio is highly predictive of metabolic syndrome in Guizhou Province, and a useful reference indicator.

Adipose Tissue ; physiology ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; Body Composition ; genetics ; physiology ; China ; epidemiology ; Genetic Predisposition to Disease ; Humans ; Metabolic Syndrome ; epidemiology ; genetics ; Middle Aged ; Muscle, Skeletal ; physiology ; Young Adult

Background and purpose:Recently, a large number of researches have shown that cruciferous plants have the chemopreventive effect on tumor. Mechanisms of antitumorigenesis were investigated on antioxidation, antimutation, immunity and inducing apoptosis, and so on. Mustard seeds (MS) are the seeds belong to the cruciferous plants. This study aimed to investigate antioxidation and immune deviation of MS on colorectal tumor in rats induced by 1, 2-dimethylhydrazine (DMH). Methods:A total of 48 male Wistar rats were randomly divided into four groups:DMH alone, DMH+5%MS, DMH+7.5%MS, and the untreated control group(Saline). Colorectal tumorigenesis was induced by intraperitoneal injecting 30 mg/kg DMH once a week for 20 weeks. At the end of 32 weeks, the rats were sacrificed, then colorectal tumor incidence was observed and histological type was determined by HE staining. A colorimetric assay was used to detect levels of the lipid peroxidation product malondialdehyde (MDA) and the activity of antioxidant enzymes in the serum of all rats. The levels of Th1 and Th2 cytokines were detected with Luminex200. Results: No tumorous lesion was found in the untreated control group. However, the total tumor incidence in DMH+5%MS group and DMH+7.5%MS group was signiifcantly decreased 33.3%and 58.3%respectively, compared with the DMH group’s (100%, P<0.05). As DMH induced colorectal tumorigenesis, MDA and Th2 cytokines in the serum were signiifcantly higher in the DMH group than those in the untreated control group (P<0.05), but the activities of antioxidant enzymes were signiifcantly lower (P<0.05). While the MS treatment, compared with the DMH group, signiifcantly suppressed the MDA level but enhanced the activities of antioxidant enzymes and levels of Th1 cytokines (P<0.05). Conclusion: MS significantly decrease prevalence rates of DMH-induced colorectal tumor in rats. The mechanism may be related with the antioxidation and immune balance deviation.