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.

Aim To investigate the effect and mechanism of hydrogen molecule on myocardial injury in severe traumatic brain injury(TBI)rats.Methods Using the fluid percussion injury(FPI)-induced TBI model.72 SD rats were randomly divided into sham group,TBI group and hydrogen molecule-treated group,with 24 rats in each group,and the rats were executed at 48 h after the operation.HE staining was used to observe the myocardial injury and the in-filtration of granulocytes,ELISA was used to detect the level of superoxide dismutase(SOD),Western blot was used to de-tect the expression of inflammation-related factors myeloperoxidase(MPO)and heme oxygenase-1(HO-1)protein,RT-qPCR was used to detect the levels of cardiac troponin T(cTnT),inhibitory factor-1(IF-1),NADH/ubiquinone oxi-doreductase core subunit S7(NDUFS7),nicotinamide adenine dinucleotide phosphate(NADP)and reduced nicotinamide adenine dinucleotide phosphate(NADPH).The changes of post-traumatic echocardiography and the 7-day survival rate and body weight in the rats were observed and recorded.Results Compared with the sham group,rats in the TBI group had significantly higher troponin levels,and the echocardiographic results showed higher left ventricular end-diastolic diameter(LVEDD)and significantly lower left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),and the above pathologic changes were significantly improved after treatment with the hydrogen molecule.Myo-cardial tissue was disorganized with erythrocyte infiltration,and myocardial fibers were infiltrated with granulocytes in the section,which were improved in the hydrogen molecule-treated group.The body weight of the rats decreased dramatically after the operation,and about 5 days later dropped to the lowest level,and then showed a trend of slow recovery.mNSS scores showed that the neurological function of the rats was severely impaired after TBI,and the postoperative myocardial tissues showed an increase in the expression levels of MPO and HO-1 proteins and a decrease in the expression levels of SOD,and the above pathological changes were significantly improved by hydrogen molecule treatment.In the TBI group,the expression levels of NADPH,IF-1 and NDUFS7 were reduced,and the expression levels of the above indicators were significantly increased after hydrogen molecule treatment.Conclusion Hydrogen molecule may be able to increase mitochondrial energy metabolism in cardiomyocytes and reduce myocardial oxidative stress by synergistically enhancing the protein expression of IF-1 and NDUFS7 on the mitochondrial oxidative respiratory chain to increase cardiac function and survival rate in the acute phase of TBI.

Objective:To evaluate the clinical diagnostic significance of altered functional connectivity (FC) within the central executive network (CEN) in patients with mild cognitive impairment (MCI) related to end-stage renal disease (ESRD).Methods:A total of 155 patients with ESRD receiving hemodialysis treatment at the department of nephrology, Changzhou Second People's Hospital, from June 2020 to December 2023, were recruited. According to wether the patient had MCI symptoms, 85 patients were classified in the ESRD with MCI group, while 70 patients were in the ESRD without MCI group. Additionally, 76 healthy volunteers matched for age, sex, and years of education were enrolled in the study. All participants underwent resting-state functional magnetic resonance imaging and were evaluated using the Montreal cognitive assessment. With the dorsolateral prefrontal cortex serving the core of CEN, functional attributes of the CEN were calculated using seed-based FC analysis. Based on these imaging features and clinical data, a LASSO + Logistic regression model was constructed to predict MCI in patients with ESRD, and SPSS 20.0 software was used for analysis.Results:There were significant differences in FC in 10 brain regions, including the inferior temporal gyrus, temporal pole, corpus callosum, ventromedial prefrontal cortex, ventral posterior cingulate cortex, inferior parietal lobule, precuneus, dorsomedial prefrontal cortex, dorsal anterior cingulate cortex, and supplementary motor area, among the three groups (all P<0.001). Post hoc analysis revealed that the zFC values of the ventromedial prefrontal cortex and dorsomedial prefrontal cortex in ESRD with MCI group(0.385±0.219, 0.215±0.247) were significantly higher than those in the ESRD without MCI group (0.278±0.184, 0.121±0.221) and the healthy controls (0.206±0.217, 0.078±0.212) (all P<0.05). In addition to the ventromedial prefrontal cortex and dorsomedial prefrontal cortex, zFC values in all brain regions exhibiting significant differences were markedly reduced in both the ESRD with MCI group (temporal pole (0.157±0.221 vs 0.327±0.191), corpus callosum (0.100±0.184 vs 0.327±0.191), ventral posterior cingulate cortex (0.027±0.199 vs 0.128±0.154), inferior parietal lobule (0.218±0.195 vs 0.387±0.213), precuneus (0.193±0.184 vs 0.358±0.142), supplementary motor area (0.182±0.163 vs 0.231±0.163)) and the ESRD without MCI group (inferior temporal gyrus (0.055±0.125 vs 0.250±0.146), temporal pole (0.048±0.223 vs 0.335±0.195), corpus callosum (0.192±0.161 vs 0.327±0.191), inferior parietal lobule (0.234±0.197 vs 0.387±0.213), dorsal anterior cingulate cortex (0.383±0.242 vs 0.585±0.195), supplementary motor area (0.076±0.162 vs 0.231±0.163)), compared to healthy controls ( P<0.01). The zFC values of 4 brain regions in ESRD with MCI group were significantly higher than those in the ESRD without MCI group (inferior temporal gyrus (0.226±0.205 vs 0.055±0.125), temporal pole (0.157±0.221 vs 0.048±0.223), dorsal anterior cingulate cortex (0.498±0.254 vs 0.383±0.242), supplementary motor area (0.182±0.163 vs 0.076±0.162)) ( P<0.05). The diagnostic model developed from these results demonstrated excellent discrimination(the area under the curve=0.94, the sensitivity=0.89, the specificity=0.86, and the accuracy=0.88). Additionally, it exhibited strong calibration ( R2=0.908) and clinical applicability(patients benefited when the predicted probability exceeded 0.12). Conclusion:The enhancement of FC in CEN and its attenuation with other networks provide relevant evidence for the neuropathological mechanisms underlying MCI in patients with ESRD.The diagnostic model based on FC changes in the CEN, as presented in this study, is valuable for detecting early cognitive impairment in patients with ESRD.

Drug therapy is a common method to cure diseases and relieve symptoms.The value of patient-reported outcome(PRO)in evaluating the effect of drug therapy has been increasingly paid attention.The PRO scale is a standardized questionnaire,which can scientifically evaluate the experiences and subjective effects of drug use from a patient-centered perspective,and help patients and clinicians make more reasonable medication decisions.By reviewing and sorting out relevant global literature,this paper found that the content of the PRO scales relevant to drug therapy focused on five fields:"medication satisfaction""medication adherence""drug treatment burden""medication-related quality of life"and"adverse drug reactions".This paper described the basic information,measurement characteristics and application of common scales in recent years respectively,and summarized and analyzed the problems and enlightenment of scale development,aiming to provide theoretical reference for the selection,application and development of PRO scales.

Objective To investigate the impacts of tanshinone ⅡA(Tan ⅡA)on lipopolysaccharide(LPS)induced proliferation and apoptosis of dental pulp stem cells by regulating the fatty acid synthase(Fas)/fatty acid synthase ligand(FasL)signaling pathway.Methods Identification of human pulp stem cells(hDPSCs)isolated from the third molar of 18～20 years old patients requiring orthodontics.Lps-induced hDPSCs were treated with low,medium and high doses of Tan ⅡA,and then human recombinant FasL protein(rh FasL)was used to intervene the LPS-induced hDPSCs after high dose Tan ⅡA.Proliferation and apoptosis of hDPSCs,levels of tumor necrosis factor-α(TNF-α)and interleukin(IL)-6 in hDPSCs supernatant,proliferating cell nuclear antigen(PCNA),Cleaved aspartate-specific cysteine proteinase-3(Cleaved Caspase-3),Fas,FasL protein expression were detected.Results hDPSCs were successfully isolated.In a dose-dependent manner,Tan ⅡA promoted LPS-induced proliferation,inhibited apoptosis,up-regulated PCNA protein expression,and inhibited TNF-α,IL-6 level,Cleaved Caspase-3,Fas,and FasL protein expression.The effect of rh FasL on LPS-induced dental pulp stem cells was opposite to the above indexes(P<0.05).rh FasL attenuates the effect of high-dose Tan ⅡA on pro-liferation and apoptosis of LPS-induced dental pulp stem cells.Conclusion Tan ⅡA may promote LPS induced hDPSCs proliferation and inhibit apoptosis by inhibiting the Fas/FasL signaling pathway.

In order to optimize the clinical service experience and provide efficient, convenient and high-quality logistics services, a multi-campus hospital has taken a series of measures, including establishing a logistics one-stop service center, building a logistics operation and maintenance management platform based on mobile Internet, normalizing quality control circle activities, building logistics command and dispatch center and business data center, and establishing performance evaluation system of logistics service personnel, etc., to provide homogeneous logistics service. The practice of multi-campus logistics management based on one-stop service mode can improve the level of logistics service, improve the clinical experience of logistics service, improve the satisfaction and sense of belonging of logistics staff, and play an important role in improving the rapid response ability of the hospital.

Objective To explore the correlation between fasting blood glucose (FBG) and hepatocarcinogenesis.Methods The retrospective cohort study was conducted.The data of 94 264 participants who participated health examination at the Kailuan General Hospital of North China University of Science and Technology,Kailuan Linxi Hospital,Kailuan Zhaogezhuang Hospital,Kailuan Tangjiazhuang Hospital,Kailuan Fan'gezhuang Hospital,Kailuan Jinggezhuang Hospital,Kailuan Lyujiatuo Hospital,Kailuan Linnancang Hospital,Kailuan Qianjiaying Hospital,Kailuan Majiagou Hospital and Kailuan Branch Hospital from July 2006 to December 2015 were collected.There were 75 134 males and 19 130 females,aged (51:±:12)years,with a range of 18-98 years.All the subjects were allocated into 3 groups according to tertiles of FBG,including 31 083 with FBG ＜ 4.82 mmol/L in the T1 group,31 594 with 4.82 mmol/L≤ FBG ＜5.49 mmol/L in the T2 group and 31 587 with FBG ≥5.49 mmol/L in the T3 group.All participants received the same-order health examinations by the fixed team of doctors in 2006,2008,2010,2012 and 2014 at the same place.Epidemiological investigation,anthropometric parameters and biochemical indicators were collected.Observation indicators:(1) comparisons of clinical characteristics among the 3 groups;(2) follow-up and incidence of liver cancer;(3) situations of non-liver cancer death;(4) risk factors analysis affecting new-onset liver cancer;(5) comparisons of the prognostic value of FBG on liver cancer model;(6) effects of FBG on new-onset liver cancer using competing risk model.Follow-up using physical examination was performed to detect new-onset liver cancer and survival up to December 31,2015.The start time of follow-up was the first health examination in 2016 and the terminal event was new-onset liver cancer,loss of follow-up and death.Measurement data with normal distribution were expressed as Mean±SD,and comparisons among groups were analyzed using the one-way ANOVA.Measurement data with skewed distribution were described as M (range),and comparisons among groups were analyzed using the Kruskal-Wallis rank sum test.Count data were described as absolute number and percentage,and comparisons among groups were analyzed using the chi-square test.The cumulative incidence and mortality of new-onset liver cancer were calculated and incidence curve was drawn by the Kaplan-Meier method,and comparisons of incidences among groups were done by the Log-rank test.The incidence of liver cancer in patients with different levels of FBG was calculated by person-year incidence (incidence density).The hazard ratio (HR) and 95％ confidence interval (CI) of different levels of FBG (classification variable and continuous variable) on new-onset liver cancer were estimated by the COX proportional hazards regression models.Restrictive cubic spline regression was used to calculate the dose-response relation between the continuous FBG and the risks of new-onset liver cancer.The fitting degree of FBG on new-onset liver cancer model was calculated by the likelihood ratio test and akaike information criterion (AIC).The predictive power of different models was calculated using the C-statistics.The net effects of FBG on incidence of liver cancer were analyzed using cause-specific hazard function (CS) and sub-distribution hazard function (SD).Results (1) Comparisons of clinical characteristics among the 3 groups:gender (male),age,systolic pressure,diastolic pressure,waistline,body mass index (BMI),total cholesterol (TC),alanine aminotransferase (ALT),triglyceride (TG),cases with drinking,smoking,physical exercise,positive HBsAg and fatty liver were 23 567,(51±13)years,(128±21)mmHg (1 mmHg=0.133 kPa),(82±12)mmHg,(86± 10) cm,(24±3) kg/m2,(4.8± 1.2) mmol/L,17.12 U/L (range,12.21-24.01 U/L),1.18 mmol/L (range,0.82-1.75 mmol/L),5 080,9 423,4 779,724,7 591 in the T1 group,24 870,(50±12)years,(129±:20)mmHg,(83±12)mmHg,(86±10)cm,(25±3)kg/m2,(4.9±l.1) mmol/L,18.31 U/L (range,13.01-24.31 U/L),1.23 mmol/L (range,0.88-1.83 mmol/L),5 448,9 397,4 570,619,9 009 in the T2 group and 26 697,(53±11)years,(135±22)mmHg,(86±12)mmHg,(89±10)cm,(26±3)kg/m2,(5.1± 1.2) mmol/L,19.00 U/L (range,13.79-26.61 U/L),1.44 mmol/L (range,1.00-2.21 mmol/L),6 354,10 292,5 369,608,13 397 in the T3 group,showing statistically significant differences among groups (x2 =761.68,F=417.84,1 010.71,747.64,702.73,1 075.06,703.83,x2=447.44,2 109.38,165.97,66.69,78.90,15.50,2 576.95,P＜0.05).(2) Follow-up and incidence of liver cancer:all 94 264 participants were followed up for 817 475 person-year,with a total person-year incidence of 3.71/10 000 person-year,1.13/10 000 person-year in the female participants and 4.37/10 000 person-year in the male participants.The incidence density of liver cancer was 2.84/10 000 person-year,3.64/10 000 person-year,4.64/10 000 person-year in the T1,T2,T3 groups,respectively.The cumulative incidence was 2.76‰,3.90‰,4.90‰ in the T1,T2,T3 groups,respectively,showing statistically significant differences among groups (x2=11.95,P ＜ 0.05),showing no statistically significant difference between T1 and T2 groups (x2 =2.73,P＞0.05),showing statistically significant differences between T1 and T3 groups,between T2 and T3 groups (x2=11.56,4.10,P＜0.05).(3) Situations of non-liver cancer death:during the follow-up,6 880 of 94 264 participants had of non-liver cancer related death,with a non-liver cancer death intensity of 84.16/10 000 person-year.The non-liver cancer death intensity was 79.19/10 000 person-year,68.17/10 000 person-year,105.32/10 000 person-year in the T1,T2,T3 groups.The accumulative mortality was 78.90‰,67.80‰,104.40‰ in the T1,T2,T3 groups,respectively,showing a statistically significant difference among groups (x2 =1 231.46,P ＜ 0.05),showing statistically significant differences between T1 and T2 groups,between T1 and T3 groups (x2 =5.29,4.36,P＜0.05),showing no statistically significant difference between T2 and T3 groups (x2 =0.09,P＞ 0.05).(4) Risk factors analysis affecting new-onset liver cancer.Results of COX proportional hazards regression model analysis showed that continuous FBG was a related factor affecting new-onset liver cancer after adjustment of gender,age,BMI,ALT,drinking,smoking,physical exercise,positive HBsAg,fatty liver,liver cirrhosis,malignant tumor in immediate family (HR =1.06,95％ CI:1.01-1.12,P＜0.05).After ln transformation of FBG,ln FBG was a related factor affecting new-onset liver cancer (HR=1.81,95％ CI:1.21-2.70,P＜0.05).Results of restrictive cubic spline regression showed that continous FBG and ln FBG were nonlinear correlated with incidence of liver cancer (RCS_ S1_x2 =7.21,4.36,P＜0.05).After adding FBG as classification variable in the COX model,risk of new-onset liver cancer in the T2 and T3 groups was increased compared with the T1 group (HR=1.45,1.67,95％ CI:1.07-1.95,1.25-2.22,P ＜ 0.05).(5) Comparisons of the prognostic value of FBG on liver cancer model:multivariate model was constructed after adding risk factors of gender,age,BMI,ALT,drinking,smoking,physical exercise,positive HBsAg,fatty liver,liver cirrhosis,malignant tumor in immediate family,and C-value,-2Log L and AIC were 0.79,6 313.30 and 6 345.30 for the multivariate model.Then FBG variable was added into the multivariate model,and the C-value,-2Log L and AIC of the multivariate model + FBG model were 0.80,6 300.48 and 6 336.48,respectively,showing statistically significant differences compared with the T1 group (x2 =12.82,P＜0.05).(6) Effects of FBG on new-onset liver cancer using competing risk model.Results of competing risk model showed that the risk of new-onset liver cancer in the T2 group was not affected compared with the T 1 group (HR =1.42,95％CI:0.98-1.97,P＞0.05) and risk of new-onset liver cancer in the T3 group was increased compared with the T1 group with the SD model (HR=1.63,95％ CI:1.16-2.26,P＜0.05),after adjustment of gender,age,BMI,ALT,drinking,smoking,physical exercise,positive HBsAg,fatty liver,liver cirrhosis,malignant tumor in immediate family.In the CS model,the risk of new-onset liver cancer in the T2 group was not affected compared with the T1 group (HR=1.43,95％ CI:0.99-1.97,P＞0.05) and risk of new-onset liver cancer in the T3 group was increased compared with the T1 group (HR=1.65,95％ CI:1.18-2.23,P＜ 0.05).Conclusions The elevated FBG is an independent risk factor for the incidence of liver cancer.After considering the competitive risk of death,the risk effect of high-level FBG on the liver cancer still exists.

Objective To investigate the safety and effectiveness of rescue stenting after failure of mechanical thrombectomy in patients with acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). Methods From December 2015 to December 2017, patients with AIS caused by LVO and treated with Solitaire AB stent thrombectomy in the Fifth Central Hospital of Tianjin were enrolled retrospectively. CT scans were performed within 24 h after surgery. Symptomatic intracraninal hemorrhage (sICH) was defined as CT confirmed intracranial hemorrhage and the National Institutes of Health Stroke Scale score increased ≥4. Clinical outcomes were assessed using the modified Rankin Scale at 90 d after onset, and 0 to 2 was defined as good outcome. According to whether to receive rescue stenting or not, the patients were divided into 2 groups. The clinical outcomes and incidence of sICH were compared between the 2 groups. Results A total of 39 patients were enrolled. Among them, 29 (74. 3％) were successfully recanalized by mechanical thrombectomy and 10 (25. 6％) performed stenting after failure of mechanical thrombectomy. Four (40. 0％) in the stenting group and 11 (37. 9％) the non-stenting group had good outcomes respectively at 90 d. There was no significant difference (P = 1. 000). Two patients (20. 0％) and 1 patient (3. 4％) developed sICH within 24 h after operation in the stenting group and the non-stenting group respectively. There was also no significant difference (P = 0. 156). Conclusions Rescue stenting can be used as a safe and effective remedy for patients with failure of mechanical thrombectomy.

Objective To compare the outcomes of Solitaire AB stent mechanical thrombectomy for the treatment of large-artery atherosclerotic stroke (LAA) and cardioembolic stroke (CES).Methods Acute ischemic stroke patients treated with Solitaire stent retriever device were enrolled retrospectively. They were divided into either a LAA group or a CES group according to the etiology. The outcomes in both groups were compared. Multivariate logistic regression analysis was used to determine the independent risk factors for poor outcome (defined as the modified Rankin Scale score > 2) at 90 d after onset. Results A total of 39 patients were enrolled in the study. There were 18 patients in the LAA group (49. 2％), 6 (33. 3％) had good outcome at 90 days; there were 21 patients (50. 8％) in the CES group, 9 (42. 9％) had good outcome at 90 days. There was no significant difference in the the good outcome rate at 90 days in both groups (P = 0. 223). Multivariate logistic regression analysis showed that only age was independently associated with poor outcome (odds ratio 1. 107, 95％ confidence interval 1. 016-1. 206; P = 0. 047), and stroke etiology subtype was not independently associated with poor outcome (odds ratio 0. 671, 95％ confidence interval 0. 078- 5. 743; P = 0. 716). Conclusions There was no significant difference in the clinical outcome between the patents with LAA and CES who received mechanical thrombectomy with Solitaire AB stent.

Objective: To isolate and identify exosomes from human serum, explore the feasibility of exosomal CEA for the diagnosis of colorectal cancer. Methods: Retrospective study.64 cases with colorectal cancer patients(41 cases with normal CEA results and 23cases with high CEA results), 20 cases with benign colorectal diseases patients and 40 cases with healthy people of department of physical examination from October 2015 to December 2016 in Tongji Hospital of Tongji University. Exosomes were isolated from these serum using ExoQuick, and then identified by using transmission electron microscopy, and Western Blot for morphology and molecular phenotype.The serum level of CEA and exosomal CEA was measureed by enzyme linked immunosorbent assay (ELISA). The diagnostic efficacy of serum Exosomal CEA concentration in the colorectal cancer by using U test and the subject work characteristic curve (ROC). Results: Exosomes in human serum was successfully extracted with ExoQuick kit.Exosomal CEA concentration in 64 cases with colorectal cancer patients (1 056.36-28 637.78)pg/ml was significantly higher than in cases with benign colorectal diseases patients (394.61-2 437.83)pg/ml and healthy controls(610.89-2 076.70)pg/ml(U=124.000, U=119.000, P<0.01). Exosomal CEA concentration in 41 colorectal cancer patients with normal serum CEA concentration(1 056.36-5 832.07)pg/ml was significantly higher than in benign colorectal diseases patients and healthy controls(U=113.000, U=119.000; P<0.01). ROC analysis of exosomal CEA yielded an AUC(area under the ROC curve)of 0.954(95% CI=0.919-0.988), which was higher than the serum CEA.The area under the ROC curve of serum Exosomal CEA concentration for colorectal cancer diagnosis is 0.954(95% CI=0.919-0.988), which is superior to the serum CEA concentration[0.636 (95% CI=0.531-0.742)]. Conclusions Isolation and detection of serum Exosomal CEA concentrations have a good diagnostic efficacy in colorectal cancer. It′s possible to be a marker for early diagnosis of colorectal cancer.(Chin J Lab Med, 2018, 41: 503-508)