Bombesin receptor subtype-3 (BRS3) is an orphan G protein-coupled receptor (GPCR) that plays critical roles in energy homeostasis, glucose metabolism, and insulin secretion. Recent structural studies have elucidated BRS3 signaling mechanisms using synthetic ligands, including BA1 and MK-5046. However, the molecular basis of BRS3 activation by bioactive natural compounds and their derivatives, particularly those derived from traditional Chinese medicine, remains unclear. Here, we present high-resolution cryogenic electron microscopy (cryo-EM) structures of the human BRS3-G_q complex in both unliganded and active states bound by two herb-derived compounds (DSO-5a and oridonin), at resolutions of 2.9, 2.8, and 2.9 Å, respectively. These structures display distinct ligand recognition patterns between DSO-5a and oridonin. Although both compounds bind to the orthosteric pocket, they differentially engage the interaction network of BRS3, as demonstrated by mutagenesis studies assessing calcium mobilization and inositol phosphate 1 (IP1) accumulation. These findings enhance our understanding of BRS3 activation and provide valuable insights into the development of small-molecule BRS3 modulators with therapeutic potential.

OBJECTIVE: To investigate the effects of the combined Yiqi Huoxue Jiedu formula (YHJF) on intestinal microbiota in elderly patients with pulmonary-derived sepsis and identify potential microbial targets. METHODS: A prospective randomized double-blind controlled trial was conducted. Elderly patients with pulmonary infection-induced sepsis admitted to the emergency department of Guangdong Provincial Hospital of Traditional Chinese Medicine (TCM), intensive care unit (ICU) of Fangcun Hospital, and ICU of Daxuecheng Hospital, from November 2020 to October 2021 were enrolled and randomized into two groups. Both groups received conventional Western medicine treatment. The observation group additionally received YHJF (composed of 15 g of Panax ginseng, 9 g of Panax notoginseng, and 3 g of Rheum palmatum, dissolved in 50 mL warm water) orally or via nasogastric tube twice daily for 7 days; while the control group received a placebo. Clinical data and fresh fecal samples were collected before treatment and on days 5-7 of treatment. Intestinal microbiota diversity and structure were analyzed via 16S rDNA sequencing and bioinformatics [α diversity, β diversity, and linear discriminant analysis effect size (LEfSe)]. RESULTS: Fifty-five patients were included (29 in the control group, 26 in the observation group). There were no significantly differences in gender, age, comorbidities, and baseline sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation II (APACHE II), acute gastrointestinal injury (AGI) classification score, and gastrointestinal failure (GIF) score between the two groups. Compared to the control group, the observation group showed significantly lower serum procalcitonin, APACHE II score, and greater reduction in GIF score by day 7. Thirty fecal samples were collected pre-treatment (baseline group), 29 post-treatment from the control group, and 26 from the observation group. Gut microbiota α diversity analysis revealed that Simpson index in the observation group and control group were significantly decreased compared to the baseline group [0.75 (0.53, 0.91), 0.81 (0.32, 0.91) vs. 0.88 (0.87, 0.89), both P < 0.05], but there was no significantly difference between the observation group and the control group. There were no significantly differences in Chao1, Ace, and Shannon indices among three groups. β diversity analysis indicated that distinct microbiota structures among three groups (R² = 0.096, P = 0.026). Species difference analysis showed that, at the phylum level, Firmicutes (53.69%), Actinobacteria (16.23%), Proteobacteria (15.39%), and Bacteroidetes (9.57%) dominated, with no significant intergroup differences. At the genus level, 38 taxa showed significant differences. Compared to the control group, the observation group exhibited increased Erysipelatoclostridium (P = 0.014) and Faecalibacterium (P = 0.013), and decreased Bacteroides (P = 0.009), Bilophila (P = 0.005), Eggerthella (P = 0.002), and Collinsella (P = 0.043). LEfSe analysis highlighted Lactobacillus salivarius, Erysipelatoclostridium, Collinsella, Cloacibacillus, and Bacteroides as key discriminators. CONCLUSION YHJF combined with conventional therapy alters intestinal microbiota structure in patients with elderly pulmonary-derived sepsis, with Bacteroides, Erysipelatoclostridium, and Collinsella identified as potential microbial targets.
Humans ; Gastrointestinal Microbiome/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Double-Blind Method ; Sepsis/drug therapy* ; Aged ; Prospective Studies ; RNA, Ribosomal, 16S/genetics* ; Male ; Female ; Panax notoginseng ; Rheum

Objective:To investigate the regulation of transcription factor CCCTC binding factor (CTCF) on the expression of B-cell lymphoma 2 ( Bcl-2) gene in pterygium and its molecular mechanism. Methods:Pterygium tissue samples from 22 primary pterygium patients who underwent pterygium excision combined with autologous limbal stem cell transplantation in The First Hospital of Changsha from June 2017 to February 2019 were collected during the operation as pterygium group.Normal conjunctival tissue from 20 patients with ocular trauma due to conjunctiva rupture, eyeball rupture or eyeball perforation in the same period were collected during the repair of ocular trauma as control group.Real-time PCR and Western blot were used to detect the expression levels of CTCF and Bcl-2 in the two groups.The DNA methylation level of the Bcl-2 promoter in the samples of the two groups was detected by bisulfite sequencing PCR (BSP). Pterygium fibroblasts were isolated and cultured.Fibroblasts were identified by immunohistochemistry using vimentin antibody.The cultured pterygium fibroblasts were divided into a CTCF interference group transfected with CTCF interference plasmid, and a control group transfected with control plasmid.The expression levels of CTCF and Bcl-2 in pterygium fibroblasts in CTCF interference and control groups were detected by real-time PCR and Western blot.The cell vitality was detected with cell counting kit-8 at 12, 24, and 48 hours after transfection.The DNA methylation level of the Bcl-2 promoter in the cells of the CTCF interference and control groups after transfection was determined by BSP.Differences of the indexes among groups were analyzed.Correlation between Bcl-2 mRNA and Bcl-2 gene promoter methylation level of CTCF protein in pterygium tissue was analyzed by Pearson linear correlation analysis.This study protocol was approved by the Ethics Committee of The First Hospital of Changsha (No.KL-2017021). Written informed consent was obtained from the patients from whom the specimens were collected.Results:The relative expression levels of CTCF mRNA and protein in pterygium group were 7.23±3.34 and 0.92±0.21, respectively, which were significantly higher than 1.10±0.44 and 0.28±0.07 in normal conjunctiva group ( t=-8.136, -13.025; both at P<0.01). The relative expression levels of Bcl-2 mRNA and protein in pterygium group were 10.27±4.64 and 0.95±0.27, which were higher than 1.10±0.41 and 0.32±0.14 in normal conjunctiva group, showing statistically significant differences ( t=-8.789, -10.782; both at P<0.01). The CTCF protein expression was significantly positively correlated with the Bcl-2 mRNA expression in pterygium group ( r=0.746, P<0.01). The DNA methylation level of the Bcl-2 promoter in pterygium group was 0.65±0.09, which was lower than 0.83±0.06 in normal conjunctiva group, with a statistically significant difference ( t=7.408, P<0.01). The DNA methylation level was significantly negatively correlated with the Bcl-2 mRNA expression in pterygium group ( r=-0.635, P<0.01). After the interference of CTCF expression in pterygium fibroblasts, the relative expression levels of CTCF and Bcl-2 mRNA in CTCF interference group were 0.37±0.03 and 0.53±0.06, which were significantly lower than 1.02±0.06 and 0.99±0.07 in control group ( t=20.035, 9.029; both at P<0.01). The relative expression levels of CTCF and Bcl-2 proteins in CTCF interference group were 0.23±0.06 and 0.56±0.07, which were lower than 0.52±0.05 and 0.92±0.12 in control group, showing statistically significant differences ( t=6.914, 4.719; both at P<0.01). The cell viability of pterygium fibroblasts in CTCF interference group was 0.10±0.01, 0.17±0.01, 0.38±0.04 at 12, 24, and 48 hours after interference, respectively, which were lower than 0.12±0.01, 0.29±0.01 and 0.85±0.06 in control group, and the differences were statistically significant ( t=3.718, 18.350, 15.621; all at P<0.01). The DNA methylation level of Bcl-2 promoter in CTCF interference group was 0.75±0.04, which was significantly higher than 0.61±0.03 in control group ( t=-4.472, P<0.05). Conclusions:CTCF is excessively expressed in pterygium, which may mediate the overexpression of Bcl-2 through down-regulating DNA methylation level.

Objective:To investigate the knowledge, attitudes, and practices (KAP) of pulse oximetry among pediatric healthcare providers in China and analyze the factor influencing the KAP.Methods:A self-developed questionnaire was used for an online research on the KAP of 11 849 pediatric healthcare providers from 31 provinces, autonomous regions, and municipalities of China from March 11 to 14, 2022.The factors influencing the KAP of pulse oximetry among pediatric healthcare providers were examined by Logistic regression. Results:The scores of KAP, of pulse oximetry were 5.57±0.96, 11.24±1.25 and 11.19±4.54, respectively.The corresponding scoring rates were 69.61%, 74.95%, and 55.99%, respectively. Logistic regression results showed that the gender and working years of pediatric healthcare providers, the region they were located, and whether their medical institution was equipped with pulse oximeters were the main factors affecting the knowledge score (all P<0.05). Main factors influencing the attitude score of pediatric healthcare providers included their knowledge score, gender, educational background, working years, region, medical institution level, and whether the medical institution was equipped with pulse oximeters (all P<0.05). For the practice score, the main influencing factors were the knowledge score, gender, age, and whether the medi-cal institution was equipped with pulse oximeters (all P<0.05). Conclusions:Chinese pediatric healthcare providers need to further improve their knowledge about and attitudes towards pulse oximetry.Pulse oximeters are evidently under-used.It is urgent to formulate policies or guidelines, strengthen education and training, improve knowledge and attitudes, equip more institutions with pulse oximeters, and popularize their application in medical institutions.

Objective To investigate the clinical efficacy and safety of preoperative hypofractionated and conventionally-fractionated chemoradiotherapy for thoracic esophageal cancer. Methods A total of 86 patients with thoracic esophageal cancer receiving chemoradiotherpy in Sichuan Cancer Hospital between 2002 and 2011 were enrolled and randomized into the preoperative hypofractionated chemoradiotherapy group ( group A, n=41, 30 Gy in 10 fractions for 2 weeks ) and conventionally-fractionated chemoradiotherapy group ( group B, n=45, 40 Gy in 20 fractions for 4 weeks ) . Surgery was performed at 2-6 weeks after chemoradiotherapy. The probability of patients' survival was estimated by Kaplan-Meier method and analyzed by log-rank test. Results In groups A and B, the pathological downstaging rates were 68％ and 56％( P=0. 270) , the R0 resection rates were 95％ and 89％( P=0. 437) and the pCR rates of 32％ and 24％( P=0. 480).The 1-,3-and 5-year overall survival (OS) rates were 78％ and 69％,44％ and 44％,29％ and 33％(P=0. 114,0. 223,0. 289), and the progression-free survival (PFS) rates were 71％ and 62％,39％ and 38％,24％ and 29％(P=0. 211,0. 689,0. 331), respectively. The incidence rate of chemoradiothery-and surgery-related adverse events did not differ between two groups (P=0. 089-0. 872).The average length of hospital stay, radiotherapy cost and preoperative treatment costs in group A were significantly less compared with those in group B (P=0. 000,0. 000,0. 000). Conclusions Both preoperative hypofractionated and conventionally-fractionated chemoradiotherapy can be used as the regimen of preoperative chemoradiotherapy in patients with resectable thoracic esophageal carcinoma. Compared with conventionally-fractionated chemoradiotherapy, preoperative hypofractionated chemoradiotherapy has shorter treatment cycle, shorter length of hospital stay and lower radiotherapy cost, which is more easily accepted by patients.

Objective To evaluate the efficacy and safety of consolidation chemotherapy after thoracic radical concurrent chemoradiotherapy for patients with oligometastatic non?small cell lung cancer ( NSCLC) . Methods Sixty?six NSCLC patients with more than five metastases from 2008 to 2013 were enrolled, and image?guided radiotherapy with conventionally fractionated or hypofractionated doses were performed for these patients. Platinum?based doublets chemotherapy was applied for both concurrent chemoradiotherapy and consolidation chemotherapy. Short?term outcome, adverse reactions, and survival rate were assessed for the patients after treatment. Results Sixty?four patients completed the treatment. The median biologically equivalent dose for planning target volume of thoracic primary tumor lesions was 72 Gy, with a median number of chemotherapy cycles of 4. The objective response rate for thoracic lesions was 70%. The follow?up rate was 97%. The 1?, 2?, and 3?year overall survival ( OS) rates were 72%, 53%, and 31%, respectively, with a median OS time of 25 months;the 1?, 2?, and 3?year progression?free survival ( PFS) rates were 56%, 26%, and 7%, respectively, with a median PFS time of 14 months. The incidence of grade 2?3 acute radiation pneumonitis and radiation esophagitis was 1% and 17%, respectively, and the incidence of grade 3?4 decreases in leukocytes, hemoglobin, and platelet count was 39%, 11%, and 16%, respectively. Conclusions Radical radiotherapy combined with concurrent and consolidation chemotherapy for oligometastatic NSCLC can achieve good short?term outcome and long?term survival, with tolerable adverse effects.

Objective To investigate the effect of the fixation of CVC catheter via the 3M elastic cloth adhesive tape. Methods As for the control group, 60 patients with double cavity CVC catheterwereselected from January to June, 2013. They used the 3M Tegaderm TM transparent film regularly to fix the CVC catheter. As for the experimental group,62 patients with double cavity CVC catheter were selected from July to December, 2013. They were treated with the 3M Tegaderm TM transparent film to fix the CVC catheter, and then used the 3M elastic cloth adhesive tape to fix the uncovered tube of the CVC catheter. The rates of catheter displacement, catheter occlusion, transparent film hemming, transparent film renewal were compared. Results The rates of catheter displacement, catheter occlusion, transparent film hemming, transparent film renewal were 6%, 6%, 8%, 8% of theexperimental group, which were significantly lower than 42%, 33%, 52%, 42% of the control group (χ2 =20. 87, 13. 94, 27. 87, 18. 57, respectively;P<0. 01). Conclusions The fixation method of experimental group is superior to the control group, and it has better effect on fixation of the CVC catheter, which has a great clinical significance.

Objective To compare the treatment effects of Qingyi Huoxue decoction and infliximab on acute necrosis pancreatitis ( ANP) complicated with MODS in a rat model. Methods 4.5% sodium taurocholate was injected into the pancreatic duct to induce the ANP complicated with MODS model. The ANP rats were randomly divided into 3 groups, ANP group (ANP), Qingyi Huoxue decoction treatment group ( QG) , infliximab treatment group (IG). Rats in infliximab group received infliximab injection at a dose of 8 mg/kg body weight via tail vein 6 h after the ANP induction. The ANP and QG received normal saline and Qingyi Huoxue decoction (20 ml/kg) via gastric lavage 4 h before and 3 h, 9 h after ANP induction. After 24 h, all rats were sacrificed, the serum levels of amylase, total bilirubin, Cr, TNF-α, diamine oxidase ( DAO) , intra-abdominal pressure (IAP) and the rate of carbon propelling rate in ileum were measured. The pancreas samples were collected for pathological examination. The pathological score of pancreas was calculated. Results The pathological scores in ANP, QG, IG were 13.8 ±0.8, 6.1 ±0.4, 3.9 ±0.6, and the difference was statistically significant (P <0.05). The serum levels of amylase, total bilirubin, Cr, TNF-α were significantly decreased. In ANP, QG, IG the serum levels of DAO were (186.3 ± 10.2 ) , ( 134.6 ± 14.3 ) , ( 149.1 ± 16.3) U/L; the carbon propelling rates in ileum were (53 ±0.1)% , (89 ±0.1)% , (61 ±0.1)% ; the IAPs were (11.8 ±1.5), (4.1±0.8), (5.8 ±1.2) mmHg(1 mmHg=0.133 kPa). The DAO and IAP in AG, IG were significantly decreased when compared with that in ANP group, but the carbon propelling rates in ileum was significantly higher than that in ANP group, and the difference was statistically significant ( P < 0.05). In addition, the carbon propelling rates in ileum in QG were higher than that in IG, and IAP and DAO levels were lower than that in IG, and the difference was statistically significant (P <0.05). Conclusions The Qingyi Huoxue decoction and infliximab were significantly effective in the treatment of ANP rats complicated with MODS. But the effects of Qinyi Huoxue decoction on promoting gastrointestinal motility, reducing the IAP and improving the intestinal barrier function were better than those of the infliximab.

OBJECTIVETo investigate the biomechanical effect of anterior screw fixation on the type II fractured odontoid process.

METHODSTwenty fresh human C1-C2 vertebrae specimens were harvested and randomly divided into three groups. The angle of type II fracture line was 0 degree in group I (n=6), 17 degrees in group II (n=8) and 25 degrees in group III (n=6). The fractures were treated by anterior screw fixation. Insertion torque,maximal axial pullout force and stiffness of the bone-screw were tested.

RESULTSThere was no significant difference of screw insertion torque and the pull-out strength between each group. The displacement of the odontoid fragment had an association to the angle of the fracture line,the displacement of the small angle was significantly higher than that of the large one (P < 0.5). No significant difference of structure stiffness of the bone-screw was found between each group.

CONCLUSIONAnterior screw fixation is feasible for type II odontoid fracture with certain fracture line extends from anteroinferior to posterosuperior.

Biomechanical Phenomena ; Bone Screws ; Cervical Vertebrae ; injuries ; Fracture Fixation, Internal ; methods ; Humans ; Spinal Fractures ; physiopathology ; surgery

Independent component analysis (ICA) is a novel method developed in recent years for Blind Source Separation. In this paper, the phonocardiogram (PCG) was separated into three components by applying ICA. The basic principle of ICA was introduced in this paper. A fast and robust fixed-point algorithm for ICA was used to analyze PCG signals in this study. The experiments showed that ICA could separate the components of heart sounds from PCG signals successfully.
Algorithms ; Heart Sounds ; Humans ; Phonocardiography ; methods ; Principal Component Analysis ; Signal Processing, Computer-Assisted