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 value of digital medical 3D technology versus traditional 2D technology in the diagnosis and treatment of solid abdominal tumors in children. Methods:A total of 80 children with solid abdominal tumors who received surgical treatment guided by digital medical 3D technology at Guigang People's Hospital from January 2018 to January 2022 were included in the observation group. An additional 80 children with solid abdominal tumors who received surgical treatment guided by traditional 2D technology at the same hospital from January 2014 to December 2017 were included in the control group. Clinical efficacy was compared between the two groups.Results:The surgical time, intraoperative blood loss, postoperative exhaust time, postoperative hospital stay in the observation group were (111.8 ± 28.9) minutes, (26.8 ± 25.2) mL, (2.2 ± 1.2) days, (7.5 ± 1.4) days, respectively, which were significantly shorter or less than those in the control group [(193.1 ± 66.0) minutes, (86.2 ± 47.0) mL, (3.7 ± 0.9) days, (12.2 ± 3.5) days, t = 7.00, 6.88, 5.87, 7.53, all P < 0.05]. The complete surgical resection rate in the observation group was significantly higher than that in the control group [92.5% (74/80) vs. 81.3% (65/80), χ2 = 4.44, P < 0.05]. The incidence of complications in the observation group was significantly lower than that in the control group [6.3% (5/80) vs. 16.3% (13/80), χ2 = 4.00, P < 0.05]. Conclusion:The utilization of digital medical 3D technology in the surgical treatment of solid abdominal tumors in children can markedly decrease surgical time, reduce intraoperative blood loss, promote postoperative recovery, achieve a high surgical resection rate, and minimize postoperative complications.

OBJECTIVE To explore the role and mechanism of dental pulp stem cells(DPSCs)in repairing hypoxic injury to rats pulmonary microvascular endothelial cells(PMVECs).METHODS ①PMVECs were treated with cobalt chloride at 0,10,25,50 and 100 μmol·L-1 for 72 h.CCK-8 was used to detect the cell viability,and the protein levels of hypoxia-inducible factor 1α(HIF-1α),zona occludens small-band protein 1(ZO-1),and occludin(OCLN)were detected by Western blotting.②There was a cell control group,model group,and model+DPSCs group,and the levels of reactive oxygen species(ROS)was detected by immunofluorescence staining after at 24 and 48 h of action.The levels of ZO-1 and OCLN proteins were detected by Western blotting.③ A cell control group,model group,model+DPSC group and model+DPSC cell knockdown superoxide dismutase 1(SOD1)group were set up.The mRNA level of SOD1 was detected by real-time fluorescence quantitative PCR 24 and 48 h later,while the protein levels of ZO-1 and OCLN were detected by Western blotting.RESULTS ① Com-pared with the cell control group,72 h of cobalt chloride 100 μmol·L-1 treatment of PMVECs resulted in a cell survival rate above 80%,a significant increase in the level of HIF-1α protein(P<0.05),a signifi-cant decrease in the levels of ZO-1 and OCLN proteins(P<0.01),and establishment of a model of hypoxic injury in PMVECs.② Compared with the cell control group,the ROS level was significantly higher in the model group(P<0.01).Compared with the model group,the ROS level was significantly lower in the model+DPSCs group(P<0.01),while the levels of ZO-1 and OCLN proteins were signifi-cantly higher in the model+DPSCs group(P<0.05).③ Compared with the DPSC group,ZO-1 and OCLN expressions were significantly decreased after knockdown of SOD1 in DPSCs(P<0.05,P<0.01).CONCLUSIONS DPSCs can repair hypoxic injury to PMVECs,and the anti-oxidative stress capacity of DPSCs plays an important role in hypoxic injury repair of PMVECs.

Objective To evaluate the protective effect of dental pulp stem cells(DPSCs)against high-altitude pulmonary edema(HAPE)and explore the mechanism.Methods Twenty-one Sprague-Dawley rats were randomly divided into the normal control group(Control),high altitude pulmonary edema group(HAPE)and DPSC prevention group(DPSC).Three days and one day before the hypobaric and hypoxia environment was simulated,DPSCs were administrated via the tail vein in the DPSC group,and phosphate buffered saline(PBS)of the same volume was injected in the control group and HAPE group.After that,rats in the HAPE group and DPSC group were placed in a simulated hypobaric and hypoxic cabin to simulate the environment at an altitude of 6000 m before an HAPE model was established.The rats were sacrificed 3 days later,and the histopathological changes of lung tissue were observed via hematoxylin-eosine(HE)staining.The dry/wet weight of lung tissues was recorded.The concentrations of total protein in lung homogenate were detected using the BCA method.The expression of aquaporin 1(APQ-1)in lung tissue was detected by real-time reverse transcription polymerase chain reaction(RT-PCR)and Western blotting.Colorimetry and enzyme linked immunosorbent assay(ELISA)were used to detect the concentrations of plasma vasoactive substances.The expression of inflammatory factors in serum and lung tissue was detected by ELISA and RT-PCR respectively.Results After three days of treatment in a simulated hypobaric and hypoxic environment,the lung tissue of the HAPE group showed infiltration of inflammatory cells,alveolar wall thickening,alveolar septum thickening and increases of exudation.DPSC prevention could significantly reduce the histopathological damage to the lung.Lung water content(LWC)and total protein content of lung homogenate were significantly increased in the HAPE group but obviously reduced in the DPSC prevention group,and the difference between the two groups was statistically significant(P＜0.01).The protein and mRNA expression levels of AQP-1 in lung tissue of the HAPE group were significantly decreased,but prevention via DPSCs could enhance the expression of AQP-1 in lung tissue.In the HAPE group,the concentrations of nitrous oxide(NO)and prostacyclin(PGI2)in plasma were significantly decreased,but prevention via DPSCs could significantly increase the expression of plasma vasoactive substances.The expressions of inflammatory factors interleukin-1 α(IL-1α)and tumor necrosis factor-α(TNF-α)in serum and lung tissue of the HAPE group increased significantly,but decreased in the DPSC prevention group.Conclusion DPSCs can help prevent high-altitude pulmonary edema in rats by promoting the expression of aquaporin,increasing the content of vasodilators in plasma and reducing the expression of inflammatory factors in serum and lung tissue.

OBJECTIVE To observe whether mitochondria can be transferred from mesenchymal stem cells(MSCs)to irradiated cells by establishing a mitochondrial fluorescent reporting system.METHODS The lentiviral vector pSIN-EF1α-COX8A-DsRed2(named COX8A-DsRed2)that might guide the expres-sion of red fluorescence protein in the membrane of mitochondria was constructed.A lentivirus(named Lv-COX8A-DsRed2)was prepared in 293T cell line.Dental pulp stem cells(DPSCs)(named DPSC-COX8A-DsRed2)was infected with Lv-COX8A-DsRed2.The intracellular expression of the red fluores-cence protein in DPSC was observed under fluorescence microcopy.The mitochondrial localization of the expressed red fluorescent probe in DPSC-COX8A-DsRed2 was confirmed according to TOMM20 immunostaining and MitoTracker Green staining results,which could specifically label mitochondria.The IEC-6 cells that received 10 Gy X-ray radiation were used as an injured cell model.The co-culture system was established by supplementing DPSC-COX8A-DsRed2 into the culture plate with the irradi-ated IEC-6 labelled by CFSE for 24 h.RESULTS The imaging results of fluorescent microcopy obser-vation showed that DPSC-COX8A-DsRed2 expressed the mitochondrial fluorescent reporting system,which was co-located with TOMM20 protein and Mito Tracker Green.The imaging results of confocal fluorescence microcopy showed that the mitochondria with red fluorescent protein were transferred from DPSC-COX8A-DsRed2 to the irradiated IEC-6 cells,suggesting that the established mitochondrial fluorescent reporting system could indicate mitochondrial transfer from donor cells to injured ones.CONCLUSION DPSC-COX8A-DsRed2 stably expressing the mitochondrial fluorescent reporting system is established,which can be used to track mitochondrial transfer.

Objective To compare the effect of hip artificial replacement and DHS internal fixation for the treatment of intertrochanteric fracture, and investigate the difference of the two method. Methods Eighty-six pa- tients with intertrochanterie fracture patients were treated with hip arthroplasty, and dynamic hip screw. The pa- tients were followed up for 6 months, and compared the operation rime, blood loss, postoperative complications, sur- vival rate, postoperative hip function score and lose situation. Results There was no significant difference in opera- tion time,blood loss,postoperative complications,in local symptoms hip varus deformation occured in the DHS inter- hal fixation because lag screw cut-our and the collapse of the medial cortex, hip and thigh pain oecured in artificial re- placement,hip function score dropped 9.5 % in DHS and 9.2% in artificial replacement. Conclusion For elderly patients, eomminuted fracture and osteoporosis, and other types of unstable intertrochanteric fracture patients, the primary purpose of surgery is to provide to patients more activities of the early conditions,so hip arthroplasty can be used to the treatment of intertrochanteric fracture,as a reasonable replacement surgery.

Objective To analyze the effect of clavicular hook plate(CHP) in treating distal clavicular fracture and acromioclavicular joint dislocation. Methods Eighteen patients with distal clavicular fracture(NeerⅡ) and acromioclavicular joint disclocation(Tossy Ⅲ) were treated by CHP. Results Sixteen patients were observed after operation,according to Lazzcano curative effect standard, fifteen cases were excellent, take 93.75 percent,1 case was good, with 6.25 percent, the excellent and good rates were 100.00 percent. The phenomenon such as the steel plate fracture,loose,escape hook and acromioclavicular joint re-dislocation were not happened. Conclusion CHP is an effective,scientific and convenience way for distal clavicular fracture and acromioclavicular joint dislocation,it worth being promoted.