Integrating UPLC-Q-Exactive Orbitrap/MS, network pharmacology and experimental validation to reveal the potential mechanism of Tibetan medicine Rhodiola granules in improving myocardial ischemia-reperfusion injury.

ETHNOPHARMACOLOGY RELEVANCE: Rhodiola granules (RG) is a traditional Tibetan medicine prescription that can be used to improve the symptoms of ischemia and hypoxia in cardiovascular and cerebrovascular diseases. However, there is no report on its use to improve myocardial ischemia/reperfusion (I/R) injury, and its potential active ingredients and mechanism against myocardial ischemia/reperfusion (I/R) injury remain unclear. AIM OF THE STUDY: This study aimed to reveal the potential bioactive components and underlying pharmacological mechanisms of RG in improving myocardial I/R injury through a comprehensive strategy. MATERIALS AND METHODS: UPLC-Q-Exactive Orbitrap/MS technology was used to analyze the chemical components of RG, the potential bioactive components and targets were tracked and predicted by the SwissADME and SwissTargetPrediction databases, and the core targets were predicted through the PPI network, as well the functions and pathways were determined by GO and KEGG analysis. In addition, the molecular docking and ligation of the anterior descending coronary artery-induced rat I/R models were experimentally validated. RESULTS: A total of 37 ingredients were detected from RG, including nine flavones, ten flavonoid glycosides, one glycoside, eight organic acids, four amides, two nucleosides, one amino acid, and two other components. Among them, 15 chemical components, such as salidroside, morin, diosmetin, and gallic acid were identified as key active compounds. Ten core targets, including AKT1, VEGF, PTGS2, and STAT3, were discovered through the analysis of the PPI network constructed from 124 common potential targets. These possible targets were involved in the regulation of oxidative stress and HIF-1/VEGF/PI3K-Akt signaling pathways. Furthermore, molecular docking confirmed that the potential bioactive compounds in RG have good potential binding abilities to AKT1, VEGFA, PTGS2, STAT3, and HIF-1α proteins. Then, the animal experiments showed that RG could significantly improve the cardiac function of I/R rats, reduce the size of myocardial infarction, improve the myocardial structure, and reduce the degree of myocardial fibrosis, inflammatory cell infiltration, and myocardial cell apoptosis rate in I/R rats. In addition, we also found that RG could decrease the concentration of AGE, Ox-LDL, MDA, MPO, XOD, SDH, Ca2+, and ROS, and increase the concentration of Trx, TrxR1, SOD, T-AOC, NO, ATP, Na+k+-ATPase, Ca2+-ATPase, and CCO. Moreover, RG could significantly down-regulate the expressions of Bax, Cleaved-caspase3, HIF-1α, and PTGS2, as well up-regulate the expressions of Bcl-2, VEGFA, p-AKT1, and p-STAT3. CONCLUSION: In summary, we revealed for the first time the potential active ingredients and mechanisms of RG for myocardial I/R injury therapy through a comprehensive research strategy. RG may synergistically improve myocardial I/R injury through anti-inflammatory, regulating energy metabolism, and oxidative stress, improving I/R-induced myocardial apoptosis, which may be related to the HIF-1/VEGF/PI3K-Akt signaling pathway. Our study provides new insights into the clinical application of RG and also provides a reference for the development and mechanism research of other Tibetan medicine compound preparations.

An In Vitro Dissolution Determination of Multi-Index Components in Tibetan Medicine Rhodiola Granules.

The composition of the Tibetan medicine Rhodiola granules (RG) is complex, and the overall quality of RG is difficult to determine. Therefore, establishing a method to determine the multi-component in vitro dissolution of RG is of great significance for quality control. This study uses the second paddle method of the fourth general rule 0931 from the Chinese Pharmacopoeia (2020 edition), compliant with apparatus 2 of the United States Pharmacopeia (USP). The dissolution apparatus was set to a rotation speed of 100 rpm with ultrapure water as the dissolution medium. A sample volume of 1 mL was collected at each timepoint. Furthermore, the cumulative dissolution of gallic acid, salidroside, and ethyl gallic acid in RG at different time points was determined by high-performance liquid chromatography (HPLC). Finally, the dissolution curves were drawn, and the curves were fitted to the GompertzMod, the Gompertz, the Logistic, and the Weibull equations. The results showed that the cumulative dissolution of gallic acid in RG was over 80% at 1 min, the cumulative dissolution of salidroside and ethyl gallic acid was over 65% at 5 min, and the cumulative dissolution of each index component decreased after 30 min. The curve fitting demonstrated that the GompertzMod equation was the best-fitting model for each index component of RG. In conclusion, the dissolution test method described in this protocol is simple, accurate, and reliable. It can characterize the dissolution behavior of the index components in RG in vitro, which provides a methodological reference for quality control of RG and quality evaluation of other ethnic compounds.

A nomogram prediction model for early death in patients with persistent pulmonary hypertension of the newborn.

Background: Persistent pulmonary hypertension of the newborn (PPHN) is a major lethal disorder in neonates that leads to an extremely high mortality rate. Thus, the early identification of adverse outcomes in PPHN is critical for clinical practice. This research attempted to develop a nomogram prediction system for assessing the mortality of newborns with PPHN. Methods: Two hundred and three newborns with PPHN diagnosed from January 2015 to March 2022 were involved in the study. The clinical features of these newborns and pregnancy details were compared between newborns in the survival and lethal groups. Univariable and multivariate analyses were established in sequence to demonstrate the essential risk factors. The nomogram prediction model was built. Results: A total of 203 newborns were included in the analysis. 136 (67.0%) newborns represented the hospital survival group. Plasma pH value (OR = 0.606, p = 0.000, 95% CI 0.45715-0.80315), septicemia (OR = 3.544, p = 0.000, 95% CI 1.85160-6.78300), and abnormal pregnancy history (OR = 3.331, p = 0.008, 95% CI 1.37550-8.06680) were identified as independent risk factors for neonatal death in newborns associated with PPHN. Finally, the nomogram predictive model was established based on multivariate analysis results, indicating the efficacies of prediction and calibration. Conclusion: This study generated an applicable risk score formula using the plasma pH value, septicemia, and abnormal pregnancy history to recognize neonatal death in newborns with PPHN, presenting a sufficient predictive value and calibration.

Cephalometric craniofacial features of patients with Sagliker syndrome: a primary analysis of our experience.

BACKGROUND: Sagliker syndrome (SS) is characterized by a severe uglifying facial appearance resulting from untreated or inadequately treated secondary hyperparathyroidism (SHPT). To date, the craniofacial morphology of patients with SS has yet to be analyzed. The present research sought to cephalometrically evaluate the craniofacial features of patients with SS and to perform an in-depth analysis of their serum biochemical parameters, with the aim of furthering the theoretical basis for the early diagnosis and prevention of SS. METHODS: A retrospective chart review of 9 patients who fulfilled the diagnostic criteria for SS were included in this study, and their serum biochemical parameters were collected. After subjecting standard lateral cephalometric radiographic images to correction for distortions caused by magnification followed by digitization, we conducted a cephalometric analysis. Student's two-tailed t tests or Mann-Whitney U tests were used to analyze the data. Thirty-three patients with patients with SHPT alone were also included as controls. RESULTS: The lower anterior facial height (ANS-ME) and total anterior facial height (N-Me) measurements of patients with SS were significantly increased compared to those of the controls. The angles between the Frankfort horizontal, palatal, and occlusal planes and the mandibular plane, were greater in the SS group than in the control group, as was the gonial angle. Patients with SS also exhibited a significantly larger maxillary protrusion angle and relative position of the maxilla to the mandible. Most patients with SS had class II malocclusion, whereas most of the controls exhibited normal occlusion. Soft tissue largely followed the same pattern as craniofacial changes. Our investigation also showed that among patients with SHPT, female sex, longer duration of dialysis, and higher serum levels of alkaline phosphatase and intact parathyroid hormone were associated with development to SS. CONCLUSIONS: Patients with SS show facial and biochemical differences compared to patients with SHPT. Female sex, long dialysis duration, and high serum levels of intact parathyroid hormone and alkaline phosphatase may be potential risk factors for SS.

Efficacy of Acupuncture at the Sphenopalatine Ganglion in the Treatment of Persistent Allergic Rhinitis.

Objective: The aim of this research was to explore the hypothesis that acupuncture at the sphenopalatine ganglion (SPG), a new a new method of acupuncture, would be more efficacious and safe than traditional acupuncture in the treatment of persistent allergic rhinitis (PAR). Materials and Methods: For this study, 120 patients with PAR were randomly assigned to SPG acupuncture, traditional acupuncture (Yingxiang [LI 20], Hegu [LI 4], and Yintang [Ex-HN 3]), or drug treatment (budesonide nasal spray). Efficacy was assessed by using single symptoms, including sneezing, rhinorrhea, nasal obstruction and nasal itch, a total nasal symptoms score (TNSS), and a Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) before treatment, the day treatment ended, and 4-, 8-, 12-weeks later, respectively. Results: Four weeks after treatment ended, the effectiveness rate in the SPG-acupuncture group was superior to that of the traditional-acupuncture group (P = 0.033) but was still lower than that of the drug-treatment group (P = 0.039), with mean effectiveness rates of 69.70%, 44.44%, and 71.43%, respectively. However, these rates gradually decreased in each group during weeks 8 through 16. Moreover, statistically significant improvements in TNSS', and reductions in nasal congestion and sneezing symptoms were observed in the SPG-acupuncture group, compared with those in the traditional-acupuncture group as early as the day treatment ended and this continued throughout the observation period (P < 0.05). However, the improvement did not continue for sneezing, during weeks 8 through weeks 12 after treatment ended. The RQLQ of the SPG-acupuncture group was lower than that of the traditional-acupuncture group at week 12; however, there were no differences at weeks 8 and 16. Conclusions: The data generated by this study confirmed that acupuncture at the SPG alleviated the symptoms of PAR rapidly and safely, especially nasal obstruction, and improved the patients' life quality. These results were worthy of clinical promotion.

Experimental demonstration of wave-front coded imaging with a very low response of the modulation transfer function at the Nyquist frequency.

Wave-front coding (WFC) is a well-known technique that can be used to extend the depth of field (DOF) of incoherent imaging systems. The phase masks make the optical transfer function drop significantly, and digital restoration must be used to obtain a clear image with a largely extended DOF. According to the existing literature, in order to obtain satisfactory restoration results, the optical modulation transfer function (MTF) at the Nyquist frequency is required to be bigger than 0.1, which has already become a popularly accepted design constraint. However, according to our experimental research reported in this paper, this requirement is overly strict. By assembling one already fabricated WFC lens and another camera having physically higher resolution, the MTF of the newly assembled WFC system used in the experimentation has quite a low response at its Nyquist frequency. The experimental results demonstrate that when the optical MTF value at the Nyquist frequency reaches the minimum value of about 0.05, visually satisfactory restoration results can still be obtained as long as the MTF is optimized to be highly insensitive to defocus and the corresponding SNR of the coded intermediate images goes beyond 20 dB at the same time. The experimental results indicate that the overly strict constraint could be alleviated while designing a WFC system.

Postsurgical Evaluation of Secondary Nephrogenic Hyperparathyroidism.

Parathyroidectomy is useful for the treatment of secondary hyperparathyroidism (SHPT) caused by chronic renal failure. The following three types of parathyroidectomy can be performed: subtotal parathyroidectomy, total parathyroidectomy and total parathyroidectomy plus autologous transplantation (tPTX+AT). Each of the three types of surgery has advantages and disadvantages. The present study retrospectively analyzed the efficacy of tPTX+AT for the treatment of SHPT over 1 year. Thirty-seven patients who were diagnosed with secondary nephrogenic hyperparathyroidism and treated with tPTX+AT were selected between September 2014 and October 2016 and followed up for 1 year. Their average age was 66.5±46.0 years, and the average time of dialysis was 48.1±8.2 months. The patients' conditions, including the levels of intact parathyroid hormone (iPTH) and bone metabolism, were compared preoperatively and 1 and 7 days and 1, 3, 6 and 12 months after surgery. In addition, the postoperative complications, pathological data, SHPT recurrence and prognosis were examined. The results showed that the postoperative level of ostalgia and cutaneous pruritus significantly decreased in the patients. An inspection of the parathyroid tissues during the operation confirmed the presence of parathyroid gland hyperplasia with no carcinoma detected. Three patients with hoarseness recovered within 1 month, and 1 patient with unilateral recurrent laryngeal nerve injury improved after 6 months of voice training. Compared to the preoperative condition, the postoperative serum iPTH, serum calcium and serum phosphate levels were significantly decreased (P<0.001), and these differences remained significant 12 months after surgery. Compared to the preoperative condition, the alkaline phosphatase (ALP) concentration was decreased on postoperative day 1 (P<0.05), but no differences were observed on day 7 or at 1 month (P>0.05). The ALP levels continuously decreased at 3, 6 and 12 months (P<0.01). In conclusion, tPTX+AT significantly improves the quality of life and serum biomarker levels of these patients. The convenient surgical removal of the hyperplastic parathyroid gland for postoperative recurrence supports tPTX+AT as the recommended treatment for relevant patients.

Hydroxycinnamoylmalated flavone C-glycosides from Lemna japonica.

Three previously undescribed flavone C-glycosides (1-3), along with seven known ones (4-10), were isolated and characterized from the smallest flowering aquatic plant, Lemna japonica. On the basis of spectroscopic analysis and alkaline hydrolysis, compounds 1-3 were identified to be luteolin 6-C-(2″-O-trans-caffeoyl-d-malate)-ß-glucoside (1), apigenin 6-C-(2″-O-trans-caffeoyl-d-malate)-ß-glucoside (2), and luteolin 6-C-(2″-O-trans-coumaroyl-d-malate)-ß-glucoside (3). Compounds 1-3 are characteristic of a trans-coumaroyl-d-malate or trans-caffeoyl-d-malate linked to C-2″ of the glucose, which was reported for the first time. Compounds 1-3 exhibited weak cytotoxicity against HepG-2, SW-620, and A-549 cell lines, with IC50 values between 42.5 and 19.2µg/ml, and moderate antioxidant activity. Meanwhile compound 3 displayed moderate nematocidal activity with an EC50 value of 1.56mg/ml.

BN-coated Ca(1-x)Sr(x)S:Eu solid-solution nanowires with tunable red light emission.

We report on the controlled growth of novel BN-coated Ca(1-x)Sr(x)S:Eu nanowires via a solid-liquid-solid process. The Ca(1-x)Sr(x)S solid solution forms as one-dimensional nanowires and has been coated with homogeneous protective BN nanolayers. The structure and luminescence properties of this new nanocomposite have been systematically investigated. High-spatial-resolution cathodoluminescence investigations reveal that effective red color tuning has been achieved by tailoring the composition of the Ca(1-x)Sr(x)S nanowires. Moreover, codoping of Ce(3+) and Eu(2+) in the CaS nanowire can induce energy transfer in the matrix and make it possible to obtain enhanced orange color in the nanowires. The BN-coated Ca(1-x)Sr(x)S:Eu solid-solution nanowires are envisaged to be valuable red-emitting nanophosphors and useful in advanced nanodevices and white LEDs.

Porous boron nitride with a high surface area: hydrogen storage and water treatment.

We report on the synthesis of high-quality microporous/mesoporous BN material via a facile two-step approach. An extremely high surface area of 1687 m(2) g(-1) and a large pore volume of 0.99 cm(3) g(-1) have been observed in the synthesized BN porous whiskers. The formation of the porous structure was attributed to the group elimination of organic species in a BN precursor, melamine diborate molecular crystal. This elimination method maintained the ordered pore structure and numerous structural defects. The features including high surface area, pore volume and structural defects make the BN whiskers highly suitable for hydrogen storage and wastewater treatment applications. We demonstrate excellent hydrogen uptake capacity of the BN whiskers with high weight adsorption up to 5.6% at room temperature and at the relatively low pressure of 3 MPa. Furthermore, the BN whiskers also exhibit excellent adsorption capacity of methyl orange and copper ions, with the maximum removal capacity of 298.3 and 373 mg g(-1) at 298 K, respectively.

[Systematic reviews on efficacy and safety of beclomethasone nasal spray in the treatment of chronic adenoid hypertrophy in children].

OBJECTIVE: To systematically review the efficacy and safety of beclomethasone nasal spray in the treatment of chronic adenoid hypertrophy in children. METHODS: We computerized searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (issue1, 009), MEDLINE (1950 to August 2008), EMbase (1984 to August 2008), CNKI (1994 to September 2008), and VIP (1989 to August 2008), WANFANG DATA, Annual Review-s and Elsevier Science. Also the reference lists of all papers were identified for further trials. All searches were initially performed in May 2007 and updated in April 2009.Randomized controlled trials (RCT) and quasi-RCTs were identified and analyzed according to the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: Three RCT were included. Meta-analysis was not performed due to heterogeneity and the data were summarized in a narrative format. The trials showed that higher doses of beclomethasone (336 microg/d, 400 microg/d) might improve the nasal obstruction symptoms and reduce adenoid size in children with adenoid hypertrophy. CONCLUSIONS: Higher and subsequently half doses of beclomethasone (336 microg/d, 400 microg/d) can improve the nasal obstruction symptoms in children with adenoid hypertrophy.The improvement appears to be associated with a reduction of adenoid size. Because of a lack of the RCT, further studies are required to support the use of beclomethasone as a first-line approach for these children.