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Obstructive sleep apnea (OSA)-induced endothelial cell (EC) dysfunction contributes to OSA-related cardiovascular sequelae. The mechanistic basis of endothelial impairment by OSA is unclear.The goals of this study were to identify the mechanism of OSA-induced EC dysfunction and explore the potential therapies for OSA-accelerated cardiovascular disease.The experimental methods include data mining, bioinformatics, EC functional analyses, OSA mouse models, and assessment of OSA human subjects.Using mined miRNA-seq data, we found that microRNA 210 (miR-210) conferred the greatest induction by intermittent hypoxia in ECs. Consistently, the serum level of miR-210 was higher in OSA individuals from two independent cohorts. Importantly, miR-210 level was positively correlated with the apnea-hypopnea index. RNA-seq data collected from ECs transfected with miR-210 or treated with OSA serum showed a set of genes commonly altered by miR-210 and OSA serum; which are largely involved in mitochondrion-related pathways. ECs transfected with miR-210 or treated with OSA serum showed reduced oxygen consumption rate, mitochondrial membrane potential and DNA abundance. Mechanistically, intermittent hypoxia induced sterol regulatory element-binding protein 2 (SREBP2) bound to the promoter region of miR-210, which in turn inhibited the iron-sulfur cluster assembly enzyme and led to mitochondrial dysfunction. Moreover, the SREBP2 inhibitor betulin alleviated intermittent hypoxia-increased systolic blood pressure in the OSA mouse model.

Background: Laparoscopic cholecystectomy (LC) is the most common intra-abdominal surgical procedure globally, which frequently leads to substantial postoperative pain. Opioids play a major role in pain management previously. Some studies found that esketamine could reduce pain and opioid consumption. However, the relationship between esketamine and the postoperative quality of recovery and pain is uncertain undergoing LC. Thestudy aimed to evaluate the effects of intraoperative intravenous esketamine infusion on the quality of recovery (QoR) and pain after laparoscopic cholecystectomy (LC). Patients and methods: A total of 152 patients were randomly divided into the control (0.9% saline), 0.2 mg (esketamine bolus 0.2 mg/kg, followed by 0.2 mg/kg/h) and 0.3 mg (esketamine bolus 0.3 mg/kg, followed by 0.3 mg/kg/h) groups. A bolus of 0.9% saline/esketamine was administered before endotracheal intubation, followed by continuous infusion until gallbladder removal. The primary outcomes were 40-item QoR (QoR-40) score on postoperative day 1 (POD-1) and pain (Numerical Rating Scale, NRS) score during rest and coughing at different time points. The secondary outcomes were hemodynamic parameters, propofol and remifentanil consumption, 48-h cumulative consumption of flurbiprofen axetil and tropisetron hydrochloride, postoperative parameters, and adverse events. Results: The global QoR-40 score on POD-1 was lower in the control group than in the 0.2 and 0.3 mg groups. The NRS score during rest and coughing was lower in the 0.2 and 0.3 mg groups than in the control group at alltime points. Hemodynamic parameters were more stable in the esketamine groups. Propofol and remifentanil consumption was higher in the control group than in the esketamine groups. The 48-h cumulative consumption of flurbiprofen axetil and tropisetron hydrochloride was lower in the esketamine groups. The extubation time was longer in the 0.3 mg group than in the control and 0.2 mg groups. The control group had more patients with oxygen saturation (SpO2) Conclusions: Intravenous esketamine infusion improved the QoR on POD-1 after LC. It provided a good analgesic effect, reduced the 48-h cumulative consumption of flurbiprofen axetil and tropisetron hydrochloride, and resulted in stable hemodynamic parameters. However, a higher esketamine dose prolonged the extubation time and increased the incidence of adverse events. Trial registration: This study was approved by the Ethics Committee of Xuzhou Central Hospital (XZXY-LK-20211209-051) and registered at ClinicalTrials.gov (19/12/2021, ChiCTR2100054508). This randomized triple-blind placebo-controlled trial was performed from December 2021 to August 2022. Written informed consent was obtained from all patients. The study was terminated after follow-up completion of the last study participant.

Background: Nasogastric tube inserted before laparoscopic cholecystectomy is a preoperative common preparation, which is an invasive procedure and exacerbates the patient’s anxiety level. This prospective, observational, cohort study aimed to explore the effects of preoperative anxiety level in patients with nasogastric tube inserted on the postoperative quality of recovery and pain undergoing laparoscopic cholecystectomy, and analyze the correlation between preoperative anxiety level and the postoperative quality of recovery. Method: Patients with STAI-S＞40 were excluded the day before surgery. After entering the operating room, patients were assessed anxiety level using the Anxiety - Visual Analog Scale. The quality of recovery was assessed using 15 - items quality of recovery on postoperative day 1 and 2. The pain was evaluated with the Numerical Rating Scale. 17 cases were excluded, and a total of 80 patients were enrolled in this study.Results: Compared with the group N, Anxiety Visual Analog Scale scores were higher in the group Y (with nasogastric tube inserted) after entering the operating room (P < 0.001), 15 - items quality of recovery scores on postoperative day 1 in the group Y was lower than group N (without nasogastric tube inserted) (P < 0.001). Pain intensity was higher in group Y at 2, 4, 8, 12, 24 and 48h after surgery than in Group N (P < 0.050). Anxiety Visual Analog Scale scores were significantly and negatively correlated with the 15- items quality of recovery scores (r = -0.91, P < 0.001). Compared with group N, group Y had longer time to get out of bed and postoperative first flatus time (P < 0.001). The AIS scores were higher on the night after surgery in group Y than in group (P < 0.001). Conclusion: In summary, nasogastric tube inserted increases preoperative anxiety level, which is associated with lower postoperative quality of recovery and higher pain intensity after surgery, and affects the patient's emergence time and postoperative sleep quality. We can implement intervention measures according to patients' conditions to relieve patients' preoperative anxiety level, improve the postoperative quality of recovery, improve patients' satisfaction and speed up recovery.Trial registration: This prospective, observational, cohort study selected patients who underwent laparoscopic cholecystectomy at Xuzhou Central Hospital from April 2022 to June 2022. The study was approved by the Ethics Committee of Xuzhou Central Hospital (XZXY-LK-20220318-024) and registered on Clinicaltrials.gov (10/04/2022, ChiCTR2200058548).

Ischemic cardiovascular disease (ICVD) has high incidence and high mortality worldwide. The studies of its risk factors were mostly concentrated on an individual level, and there are scarce studies on the two levels of risk factors which include individual and regional levels.The data were obtained from a community-based study in 4 cities and 6 counties of Henan, China. Risk factors were initially screened by one-way analysis of variance or chi-square test. Then, they were re-analyzed using a two-level logistic regression model to construct a personal disease risk prediction model.A two-level ICVD risk prediction model comprised 11 variables: age, body mass index (BMI), family history of hypertension, marital status, salt intake, smoking, moderate recreational physical activities, alcohol intake, and education at the individual level. Among the unalterable risk factors, for each additional unit of age and family history of hypertension, the risk of ICVD increased by 1.08 and 1.07 units [β95% confidence interval (95%CI): 0.99-1.16, 0.97-1.17, both p 0.0001], respectively. Among the modifiable risk factors, the ICVD risk increases by 0.67, 0.27, and 0.28 units for each additional unit of BMI, marital status, and education (β95%CI: 0.60-0.74, p 0.0001; β95%CI: 0.14-0.40, p = 0.0012, 0.18-0.37, p = 0.0001).The two-level ICVD risk model can predict that the risk of one person for ICVD will be lower if one is younger, thinner, and well-educated without a family history of hypertension. Overall, the two-level ICVD risk prediction model gets a better fitting effect than the single-level model.

Cementum regeneration is considered the gold standard for the treatment of periodontitis. As one of the most important primary proinflammatory cytokines, interleukin 1β (IL1β) plays an essential role during the early stage of periodontitis and its amounts simultaneously increase dramatically during this stage. Though promising, the differentiation of cementoblasts upon IL1β-induced inflammation of the microenvironment and the relative interaction mechanism are still unknown. Here, we found that IL1β inhibited cementoblast differentiation and microRNA-325-3p (miR-325-3p) was increased during IL1β-stimulated cementoblasts. Bioinformatics analysis and luciferase reporter assay demonstrated miR-325-3p targeted runt-related transcription factor 2 directly. Transfection of miR-325-3p suppressed cementoblast differentiation in vitro and the formation of cementum-like tissues in vivo. The inhibitor of miR-325-3p could mitigate the above effects induced by IL1β. Accordingly, our finding suggests a critical role of miR-325-3p in linking inflammation to impaired cementum regeneration and provides a potential possibility for applying miR-325-3p inhibitors in the treatment of periodontitis-related bone loss.

Background: The disease burden of comorbidity is growing steadily in many developing countries, affecting residents' physical and mental health. General Practitioners are considered as the suitable service providers for the prevention and control of comorbidity. However, the current knowledge on the clinical and epidemiological characteristics of comorbidity among inpatients in the general practice departments of hospital is limited, which hinders the precise promotion of the service capacity and quality of GPs. Objective: The current study aimed to analyze the clinical prevalence of comorbidities in central China and to provide evidence-based policy recommendations for quality improvement in general medical services. Methods: The study was conducted at the general practice departments of all 27 tertiary grade-A hospitals of Henan Province, China. 3 registered GPs of each hospital were selected by random, and all direct admissions of the 81 GPs from December 2016 to November 2020 were followed up. The clinical epidemiological characteristics and influencing factors of comorbidity were evaluated using descriptive statistical analysis and logistic regression models. Results: Comorbidity was present in 93.1 percent of the 2385 direct admitted patients, with a male-to-female ratio of 1: 1. Comorbidity was significantly more prevalent in patients aged 45-59 years (OR=3.018, 95% CI=1.945-4.683), 60-74 years (OR=4.349, 95% CI=2.574-7.349), ≥75 years (OR=7.804, 95% CI=3.665-16.616), and those with body mass index (BMI) ≥28 kg/m2 (OR=3.770, 95% CI =1.453-9.785). The circulatory system is the most commonly involved human body system in comorbidity, accounting for 79% of all cases. The endocrine, nutritional, and metabolic systems, as well as the digestive and respiratory systems, were all significantly affected, with prevalence rates of 62 percent, 48 percent, and 37 percent, respectively. Conclusion: Comorbidity is common among the inpatients attending the provincial tertiary grade-A hospitals. Since old age and obesity are independent risk factors for comorbidity, healthy lifestyle interventions should be strengthened, as should the implementation of the patient-centered prevention and control model. Meanwhile, quality improvement priorities should be given to improving GPs' clinical diagnosis and treatment of the circulatory system, endocrine system, metabolic system, digestive system, and respiratory system.

Gout is a multifaceted inflammatory disease involving vascular impairments induced by hyperuricemia. Experiments using human umbilical vein endothelial cells treated with uric acid (UA), monosodium urate (MSU), or serum from gout patients showed increased expression of pro-inflammatory genes (ie, VCAM1, ICAM1, CYR61, CCNA1, and E2F1) with attendant increase in monocyte adhesion. Mechanistically, UA- or MSU-induced SREBP2 expression and its transcriptional activity. RNA sequencing analysis and real-time PCR showed the induction of YAP signaling and pro-inflammatory pathways in HUVECs transfected with adenovirus-SREBP2. The SREBP2 knockdown by siRNA partially abolished UA- or MSU-induced YAP activity, pro-inflammatory gene expression, and monocytes adhesion. Vascular intima from transgenic mice overexpressing SREBP2 in endothelium or mice with hyperuricemia exhibited activated YAP signaling and increased expression of pro-inflammatory genes. Betulin, an SREBP pharmacological inhibitor, attenuated the UA-, MSU-, or gout serum-induced endothelial cell inflammation and dysfunction. In the human study, endothelial cell function, assessed by EndoPAT, was negatively correlated with serum UA level among gouty patients and healthy controls. Collectively, UA or MSU causes endothelial dysfunction via SREBP2 transactivation of YAP. Betulin inhibition of SREBP2 may restrain gout-induced endothelial dysfunction.

Background: Obstructive Sleep Apnea (OSA) is a highly prevalent condition that is associated with several comorbidities including cardiovascular disease (CVD). Recent studies have revealed mixed results as to whether standard OSA therapy reverses CVD in adult patients. Thus, many advocate for earlier recognition of OSA induced CVD, as early as childhood, to prompt treatment antecedent to the onset of irreversible CVD. Here we investigated if the serum level of miR-92a, a known biomarker for CVD, can be used to identify patients with OSA in both children and adults. Methods: Consecutive snoring patients undergoing polysomnography were recruited for determination of circulating miR-92a, in addition to inflammatory and metabolic profiles. We assessed whether circulating miR-92a was associated with OSA severity. Results: Using two separate cohorts of adults (n=57) and children (n=13), we report a significant increase in the serum level of miR-92a in patients with severe OSA (p=0.021) and further demonstrate a significant correlation (Spearman rank correlation 0.308, p=0.010) with serum miR-92a levels and the apnea hypopnea index (AHI), a primary measure of OSA severity. Stepwise regression analysis revealed that serum miR-92a levels were independently associated with AHI (ß=0.332, p=0.003), age (ß=0.394, p=0.002) and LDL cholesterol levels (ß=0.368, p=0.004). Conclusion: Our study is the first to establish that miR-92a is a useful biomarker for OSA severity in both children and adults. Given the canonical role of miR-92a on endothelial dysfunction, miR-92a may be useful to identify early onset CVD in OSA patients or stratify patient CVD risk to identify those that may benefit from earlier OSA treatment.

The Distributed Electric Propulsion(DEP) UAV has the advantages of high efficiency, low noise, low emission and high control redundancy. Especially, it is more difficult about dynamic modeling and attitude controller design due to its Propulsion Airframe Integration(PAI) for DEP UAV with vectorable power section and the V/STOL capability. In this paper, aerodynamic data of different state points in the clean configuration of DEP UAV is caculated, and the nonlinear aerodynamic model is established by cubic spline interpolation method. Then, the wind tunnel data of the power section are analyzed, and the model for PAI is established. Finally, Linear Active Disturbance Rejection Control(LADRC) controller combined fal-function is designed for attitude control of nonlinear model of clean configuration aircraft, and PAI is added as controller disturbance in full speed envelope flight simulation. Taking pitch angle control as an example, compared with PID algorithm and LADRC, the modified LADRC method in this paper is not only more robust to PAI effects, but also better to the dynamic response of the system, which lays a foundation for S/VTOL of DEP UAV.

Background: COVID-19 epidemic has become a significant public health crisis affecting global health. We aimed further to clarify the clinical and medical expense characteristics of COVID-19. Methods: In this retrospective, single-center study, we included all cured cases with confirmed COVID-19 in Henan Provincial People's Hospital from Jan 23 to Mar 10, 2020. Cases were analyzed for demographic, epidemiological, clinical, and radiological features and medical expense data. Findings: The average age of the 54 successfully treated patients with COVID-19 was 53.2 years old (SD 19.0), including 27 men and 27 women. Off this, 31 (57.4%) patients had chronic diseases. Patients commonly had clinical manifestations of fever (45 [83.3%] patients), cough (29[54.7%] patients), expectoration (28 [51.9%] patients), fatigue (24[44.4%] patients) and diarrhea (8[14.8%] patients) on admission. There was a 10-day interval from the onset of signs and symptoms to hospital admission. About 80% of them got recovery after a two-week treatment. During the treatment, 43(78.2%) patients had at least one comorbid illness, and 11(20.4%) had more than five comorbid illnesses. The mean interval from the onset of signs and symptoms to hospital discharge was 20.5 (IQR 16-29) days. The median total medical expense of the treated patient, in general, was 2579.6 (IQR 1366.1-4837.6) U.S. dollars. Still, the median medical expense was 8904.1 (IQR 6660.1- 27143.8) U.S. dollars in patients with more than five comorbid conditions during the treatment. Interpretation: There is a 3-week interval from the onset of signs and symptoms to cure, and most hospitalized patients get recovery within two weeks. Although COVID-19 can result in fatal respiratory diseases and even death. The total medical expense of cases with more than five comorbid conditions during the treatment is higher. Quite a few COVID cases with other serious diseases are likely to account for most of the total medical expenses. Funding Statement: This study was funded by National Natural Science Foundation of China (number 71603132), and the Central Government Guides the Development of Local Science and Technology Special Fund of China (number Z135050009017). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The study was approved by the Henan Provincial People's Hospital Ethics Committee

The aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) in the vascular wall are crucial pathological events involved in cardiovascular impairments including hypertension, heart failure, and atherosclerosis. At the molecular level, the mammalian target of rapamycin (mTOR)-ribosomal protein S6 kinase beta-1 (p70S6K) signaling pathway is essential to potentiate VSMC proliferation and migration. Although angiotensin II receptor type 1 ­(AT1-R) antagonists such as valsartan and telmisartan have a significant cardiovascular protective effect, the molecular basis of this class of drugs in VSMC proliferation and migration remains elusive. By using cultured VSMCs, adenosine monophosphate-activated protein kinase (AMPK) α2 knockout mice, and hypertensive rat models, this study investigated whether AT1-R antagonists can inhibit the mTOR-p70S6K signaling pathway in VSMCs and the vascular wall. Valsartan activated AMPK, which in turn suppressed reactive oxygen species production and consequently attenuated VSMC proliferation and migration. In vivo, a clinical dose of telmisartan significantly inhibited the mTOR-p70S6K signaling pathway in the vascular wall of wild-type but not AMPKα2–/– mice. Furthermore, spontaneously hypertensive rats had significantly elevated phosphorylation of mTOR and p70S6K in the aorta compared to Wistar-Kyoto rats, which were reduced by telmisartan administration. These data suggest that AT1-R antagonists inhibit VSMC proliferation and migration via their regulation of AMPK, mTOR, and p70S6K, which contribute to the cardioprotective effects of these drugs.

Goji berries (Lycium fruits) are usually found in Asia, particularly in northwest regions of China. Traditionally, dried goji berries are cooked before they are consumed. They are commonly used in Chinese soups and as herbal tea. Moreover, goji berries are used for the production of tincture, wine, and juice. Goji berries are high antioxidant potential fruits which alleviate oxidative stress to confer many health protective benefits such as preventing free radicals from damaging DNA, lipids, and proteins. Therefore, the aim of the review was to focus on the bioactive compounds and pharmacological properties of goji berries including their molecular mechanisms of action. The health benefits of goji berries include enhancing hemopoiesis, antiradiation, antiaging, anticancer, improvement of immunity, and antioxidation. There is a better protection through synergistic and additive effects in fruits and herbal products from a complex mixture of phytochemicals when compared to one single phytochemical.