ObjectiveTo investigate the role of Ras-GTPase-activating protein SH3 domain-binding protein 2 （G3BP2） in regulating the activation， proliferation， and migration of hepatic stellate cells （HSCs）. MethodsThe mouse HSCs （JS-1 cell line） were treated with 5 μg/L transforming growth factor-beta 1（TGF-β1） for 24 hours to establish an HSC activation and proliferation model. A G3BP2 knockdown system was constructed using siRNA interference technology. The experiment was divided into four groups： Control， TGF-β1 treatment， TGF-β1+si-NC， and TGF-β1+ G3BP2-siRNA. The expression levels of key fibrosis indicators， including type I collagen （Collagen I）， α-smooth muscle actin （α-SMA）， and G3BP2， were detected by Western blot and RT-qPCR. Cell proliferation activity was assessed using the CCK-8 proliferation assay kit and EdU fluorescence labeling technology. Cell migration ability was analyzed by scratch wound healing assay and Transwell migration assay. The formation level of stress granules was quantified by immunofluorescence microscopy to investigate the effects of G3BP2 on stress granule formation in activated HSCs. ResultsStimulation with TGF-β1 upregulated the expression of G3BP2 in JS-1 cells （RT-qPCR： P0.000 1； Western blot： P0.000 1）， while a downward trend in its expression was observed in the G3BP2‑silenced group （RT-qPCR： P0.01； Western blot： P0.000 1）. Compared with the control group， the TGF-β1 group exhibited increased protein expression levels of α-SMA and Collagen I （RT-qPCR： both P0.01； Western blot： P0.01 and P0.05， respectively）， concomitant with an increased number of stress granules and enhanced cell proliferation and migration capacity （all P0.001）. The experimental results demonstrated that G3BP2 knockout effectively reversed the aforementioned phenotypes， with the G3BP2-silenced group showing reduced expression of fibrotic markers （all P0.01）， decreased stress granule formation （P0.01）， and reduced cell proliferation and migration capacity （all P0.05）， compared to the negative control group. ConclusionG3BP2 enhances the activation， proliferation， and migration of HSCs by promoting the formation of stress granules， thereby accelerating the pathological progression of liver fibrosis. This suggests that stress granules may serve as important regulators in controlling the activation， proliferation， and migration of HSCs.

Objective To propose a novel method based on three-dimensional depthwise separable convolution network(3D DSN)for the separation of PET images with dual tracers of 18F-FDG and 18F-FAPI.Methods A total of 120 pairs of 18F-FDG and 18F-FAPI PET images of the same patient scanned separately at different time points were collected,and the dual-tracer PET image was generated through simulation.After the image registration of PET images of two tracers for ensuring spatial position matching,the registered PET images were forward-projected to generate sinogram data,and the sinogram data of two tracers were accumulated to obtain mixed sinogram data.Subsequently,the dual-tracer PET image was reconstructed using maximum likelihood expectation maximization and input into a 3D DSN based network for image separation,thereby obtaining PET images of two single tracers.Results Compared with 3D CNN method,the proposed method increased the structure similarity index measure(SSIM)of the separated 18F-FDG images to the real 18F-FDG images by 0.87%,increased the peak signal-to-noise ratio(PSNR)by 11.8%,and reduced the normalized root mean square error(NRMSE)by 52%.The SSIM of the separated 18F-FAPI images to the real 18F-FAPI images increased by 1.1%,PSNR increased by 17.0%,and NRMSE decreased by 51%.Conclusion The proposed method can be effectively applied to simultaneous PET imaging with dual PET tracers,reducing the number of scans and costs in time and money,and providing clinical doctors more accurate and abundant diagnostic information.

AIM:This study aimed to confirm the glycolytic inhibitory activity of 3-bromopyruvic acid(3BP)and to assess whether this inhibition could ameliorate hypoxia-induced pulmonary hypertension in rats.METHODS:PAH model rats were generated from normal SD rats via exposure to normal pressure and hypoxia.Intervention groups I and II(6 rats per group)were then intraperitoneally injected with 3BP(15 mg/kg),and the normal and hypoxia groups(6 rats per group)were given the same amount of normal saline for a total of 21 d.The average pulmonary artery pressure of the rats in each group was measured via right heart catheterisation,and hilar tissue measurements.The right ventricle(RV),left ventricle,and interventricular septum(LV+S)were weighed,and the ratio of RV/(LV+S)was calculated as an index of right ventricular hypertrophy.Right lower lung tissues were fixed in 4%paraformaldehyde-PBS buffer,sec-tioned in conventional paraffin(5 μm thick),stained with HE and Masson,photographed under a microscope.Then the thickness ratio of the tunica media and the area ratio of collagen fibres were calculated.The expression of pyruvate kinase isozyme type M2(PKM2),nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),and pyruvate de-hydrogenase(PDH)proteins in the hilar tissues of each group were detected by western blot,whereas interleukin-1β(IL-1β)and IL-18 contents were detected using ELISA,and lactic acid content was detected using a lactic acid kit.RE-SULTS:The results showed that 3-brpa effectively inhibited glycolysis and significantly improved hypoxia-induced pulmo-nary hypertension in rats.Compared with the hypoxia group,in intervention group II,PKM2 expression was decreased(P<0.05),PDH expression increased significantly(P<0.01),and NLRP3 expression was decreased(P<0.05).The IL-18 and IL-1β contents decreased(P<0.05 or P<0.01,respectively).Pulmonary hemodynamic indexes showed that the pro-portion of the right ventricle and the mean pressure of the pulmonary artery decreased(P<0.05 or P<0.01,respectively).The HE and Masson staining results showed that the thickness ratio of the tunica media and the area ratio of collagen fibres decreased significantly(P<0.01).Lactic acid content was significantly decreased(P<0.01).CONCLUSION:This study showed that 3BP can inhibit glycolysis and alleviate hypoxia-induced pulmonary hypertension in rats.

Objective:To evaluate the incidence and risk factors of pneumonia in patients with thoracic cancer treated with immunotherapy combined with radiotherapy (RT).Methods:The clinic data of 265 patients with thoracic cancer who received RT and at least 2 cycles of immunotherapy at Renmin Hospital of Wuhan University between January 2020 and January 2024 were retrospectively analyzed. Patients were divided into 2 groups according to treatment sequence: 100 patients with sequential immunotherapy after RT, 165 patients with RT after immunotherapy, including sequential RT after immunotherapy (119 cases) and concurrent RT with immunotherapy (46 cases). The occurrence and grading of treatment-related pneumonia were determined by clinical symptoms, signs, and chest CT findings. The relationship between interval time window of different treatment methods and pneumonia was analyzed by Pearson correlation analysis. χ2 test was used for univariate analysis of risk factors, and logistic regression for multivariate analysis. Results:In the sequential immunotherapy after RT group, the incidence of pneumonia was 12.0% (12/100), with grade ≥2 pneumonia in 4.0% (4/100). The interval time between RT and immunotherapy, has a strong negative correlation with pneumonia incidence and grade ≥2 pneumonia incidence ( r=-0.88, -0.79; both P<0.001). When immunotherapy was initiated ≥7 weeks after RT, the incidence of pneumonia significantly decreased to 5% ( P=0.020), with no grade ≥2 cases. In the immunotherapy followed by sequential / concurrent RT cohort, the incidence of pneumonia was significantly higher in the concurrent subgroup compared with the sequential subgroup [65% (30/46) vs. 44.5% (53/119), P=0.027], and the comparison of the incidence of grade ≥2 pneumonia was the same [33% (15/46) vs. 14.3% (17/119), P=0.014]. The interval time window of RT after immunotherapy was strongly negatively correlated with the incidence of pneumonia and grade ≥2 pneumonia ( r=-0.77, -0.83; both P<0.001). When RT was initiated ≥4 weeks after immunotherapy, the incidence of pneumonia significantly decreased ( P<0.001). Pneumonia incidence differed significantly across RT target sites (intrapulmonary vs. extrapulmonary), total dose (<60 Gy vs. ≥ 60 Gy), and fractionation regimen (conventional vs. hypofractionation) ( P < 0.001, = 0.008, = 0.031), but was not associated with age, gender, smoking history, type of immune checkpoint inhibitor (anti-programmed death-1 vs. anti-programmed death ligand-1), or the number of prior immunotherapy cycles (all P > 0.05). Multivariate analysis identified RT within the lung and interval time of RT after immunotherapy ≤ 4 weeks as independent risk factors for the incidence of pneumonia (both P < 0.001). Conclusions:The interval window between RT and immunotherapy is a critical determinant of pneumonia incidence. Delaying immunotherapy for more than 7 weeks after RT, or delaying RT for more than 4 weeks after immunotherapy, can significantly reduce the risk of radiation-related pneumonia.

Objective:To study the efficiency and biosafety of Electrochemical advanced oxidation processes(EAOP)in dental bleaching,and conduct preliminary application.Methods:Indigo carmine and coffee were used as the indicator to assess the effi-cacy of EAOP.High resistance meter was used to measure the resistance of the tooth to verify the safety of the working voltage.Twenty wisdom teeth after tooth extraction were collected,dyed and bleached in vitro to verify the bleaching efficiency.Subsequent-ly,the bleached teeth were examined by scanning electron microscopy,hardness testing,and bacterial adhesion experiments to as-sess surface damage.To determine its cytotoxicity,cells were co-cultured with electrolyte.Initial samples of bleaching tray was prepared,and its durability were verified.Results:The EAOP could bleach indigo carmine within 10 min and coffee within 90 min at an operating voltage of 8 V.The resistance at the groove of the tooth socket was(3.4±1.2)MΩ,and the theoretical calculated current was less than 3 μA.The efficiency of EAOP tooth bleaching was slightly lower than that of traditional office bleaching and higher than that of home bleaching.Compared with the traditional bleaching method,scanning electron microscopy showed that EAOP had less demineralization effect on tooth surface.The tooth hardness before and after bleaching had no statistical difference(P=0.912).The bacterial adhesion test after tooth bleaching showed that EAOP method could reduce about 60％bacterial adhe-sion(P＜0.001).The cytotoxicity test showed that EAOP electrolyte had no obvious toxic effect.The durability test shows that the bleached denture still has good bleaching effect after 20 h of use.Conclusion:Compared with the traditional bleaching method,EAOP bleaching had excellent tooth bleaching effect,little effect on tooth damage,high safety,and the related bleaching devices had good durability.

Objective:To evaluate the incidence and risk factors of pneumonia in patients with thoracic cancer treated with immunotherapy combined with radiotherapy (RT).Methods:The clinic data of 265 patients with thoracic cancer who received RT and at least 2 cycles of immunotherapy at Renmin Hospital of Wuhan University between January 2020 and January 2024 were retrospectively analyzed. Patients were divided into 2 groups according to treatment sequence: 100 patients with sequential immunotherapy after RT, 165 patients with RT after immunotherapy, including sequential RT after immunotherapy (119 cases) and concurrent RT with immunotherapy (46 cases). The occurrence and grading of treatment-related pneumonia were determined by clinical symptoms, signs, and chest CT findings. The relationship between interval time window of different treatment methods and pneumonia was analyzed by Pearson correlation analysis. χ2 test was used for univariate analysis of risk factors, and logistic regression for multivariate analysis. Results:In the sequential immunotherapy after RT group, the incidence of pneumonia was 12.0% (12/100), with grade ≥2 pneumonia in 4.0% (4/100). The interval time between RT and immunotherapy, has a strong negative correlation with pneumonia incidence and grade ≥2 pneumonia incidence ( r=-0.88, -0.79; both P<0.001). When immunotherapy was initiated ≥7 weeks after RT, the incidence of pneumonia significantly decreased to 5% ( P=0.020), with no grade ≥2 cases. In the immunotherapy followed by sequential / concurrent RT cohort, the incidence of pneumonia was significantly higher in the concurrent subgroup compared with the sequential subgroup [65% (30/46) vs. 44.5% (53/119), P=0.027], and the comparison of the incidence of grade ≥2 pneumonia was the same [33% (15/46) vs. 14.3% (17/119), P=0.014]. The interval time window of RT after immunotherapy was strongly negatively correlated with the incidence of pneumonia and grade ≥2 pneumonia ( r=-0.77, -0.83; both P<0.001). When RT was initiated ≥4 weeks after immunotherapy, the incidence of pneumonia significantly decreased ( P<0.001). Pneumonia incidence differed significantly across RT target sites (intrapulmonary vs. extrapulmonary), total dose (<60 Gy vs. ≥ 60 Gy), and fractionation regimen (conventional vs. hypofractionation) ( P < 0.001, = 0.008, = 0.031), but was not associated with age, gender, smoking history, type of immune checkpoint inhibitor (anti-programmed death-1 vs. anti-programmed death ligand-1), or the number of prior immunotherapy cycles (all P > 0.05). Multivariate analysis identified RT within the lung and interval time of RT after immunotherapy ≤ 4 weeks as independent risk factors for the incidence of pneumonia (both P < 0.001). Conclusions:The interval window between RT and immunotherapy is a critical determinant of pneumonia incidence. Delaying immunotherapy for more than 7 weeks after RT, or delaying RT for more than 4 weeks after immunotherapy, can significantly reduce the risk of radiation-related pneumonia.

Objective:To evaluate the clinical and radiographic efficacy of micro crestal flap-alveolar ridge preservation following extraction of mandibular molars with severe periodontitis compared with natu-ral healing,and to preliminarily propose the surgical indication.Methods:A retrospective analysis was conducted on clinical data from patients with mandibular molars with severe periodontitis either receiving micro crestal flap-alveolar ridge preservation(MCF-ARP group)or undergoing natural healing in depart-ment of periodontology,Peking University School and Hospital of Stomatology from September 2013 to June 2021.Cone-beam computed tomography scannings performed before/immediately after extraction(as baseline)and repeated before implantation(after the extraction socket healing)were used to measure the ridge width,height and volumetric changes of the sockets,and the proportion of guided bone regeneration(GBR)during implant therapy were compared between the two groups.Results:Between baseline and healing,significant differences in changes of MCF-ARP group[(8.34±2.81)mm]and natural healing group[(3.82±3.58)mm]in the distances from mandibular canal to center of the tooth socket were recorded(P＜0.001).The ridge width at 1 mm below the most coronal aspect of the crest increased by(3.50±4.88)mm in the MCF-ARP group but decreased by(0.16±5.70)mm in the natural healing group,respectively(P=0.019).After healing,the MCF-ARP group showed the dis-tances from mandibular canal to center of the tooth socket＞8 mm in all the cases,with 97.1％excee-ding 10 mm.Natural healing group displayed 23.1％of the cases with center bone height＜8 mm and 61.5％exceeding 10 mm.Volume changes at the buccal and lingual aspect as well as the total socket were significantly greater in the MCF-ARP group compared with natural healing group(P＜0.001).At the time of implantation,GBR was performed in 5 out of 68 subjects(8.3％)in the MCF-ARP group,whereas 8 out of 26 subjects(30.8％)in the natural healing group required GBR,reflecting significant difference(P=0.003).Conclusion:In the sites of mandibular molars with severe periodontitis,when the distances from mandibular canal to center of the tooth socket was not enough(less than 7 mm),clini-cians could consider performing the micro crestal flap-alveolar ridge preservation to achieve augmentation for alveolar ridge and reduce the proportion of guided bone regeneration during implant therapy to reduce the difficulty and risk of injuries during implant therapy.

Objective:To explore the method for selecting characteristic prices of Chinese patent medicines based on informa-tion entropy theory.It involves analyzing the connotative differences among various price indicators and utilizing information entropy metrics to validate the scientific rigor of characteristic price selection so as to optimize the pricing model for Chinese patent medi-cines and improve the accuracy of price evaluation.Methods:A correlation analysis and information entropy calculation are con-ducted on the median price of the smallest preparation unit,average daily cost,and average course cost of TCM.It compares the information diversity and uncertainty of different pricing indicators.Results:The average daily cost exhibits the highest information diversity and uncertainty among all the pricing indicators examined.Conclusion:It is recommended that the average daily cost be used as the dependent variable for characteristic prices in TCM pricing research.This choice plays an important role in optimizing TCM pricing models and enhancing the accuracy of price evaluation.

Objective:To establish a scientific,systematic,and objective indicator system for the characteristic price variables of Traditional Chinese Patent Medicines(TCPM),providing a reference framework for the pricing mechanism of TCPM.Methods:The brainstorming method was initially used to screen related variable indicators.The Nominal Group Technique(NGT)and Delphi methods were applied to gather expert opinions,and SPSS 28.0 was employed for data statistical analysis.It led to the development of a TCPM characteristic price variable indicator system consisting of 6 dimensions,14 characteristic variables and 26 measurement indicators.Results:The authority coefficient of the experts exceeded 0.7,indicating the representativeness of the results.Expert opinions were generally concentrated.Based on the collected opinions and statistical analysis,the scope of selected TCPM characteristic price variables was preliminarily established.Conclusion:The TCPM characteristic price variable indicator system was initially developed.However,due to the complexity of the pricing mechanism and divergent expert opinions,further qualitative and quantitative research methods,along with a dynamic adjustment mechanism,are needed to verify and refine the system.

The National Essential Medicines System could protect public health and ensure access to essential medications.Although the current selection methods for China's National Essential Medicines Lists(NEMLs)are becoming more scientific and standardized,there are still problems such as much emphasis on expert experience and the lack of transparency of decision-making basis.To address these issues,it proposes an evidence-based decision-making pathway for NEMLs selection guided by clinical value.This approach ensures a strong integration of evidence and decision-making,offering valuable insights for improving the adjustment procedures and selection criteria of the NEMLs in China.