OBJECTIVE To investigate the effects and potential mechanism of paeoniflorin on oxidative stress of ulcerative colitis （UC） mice based on adenosine monophosphate-activated protein kinase （AMPK）/nuclear factor-erythroid 2-related factor 2 （Nrf2） pathway. METHODS Male BALB/c mice were randomly divided into control group， model group， inhibitor group （AMPK inhibitor Compound C 20 mg/kg）， paeoniflorin low-， medium- and high-dose groups （paeoniflorin 12.5， 25， 50 mg/kg）， high- dose of paeoniflorin+inhibitor group （paeoniflorin 50 mg/kg+Compound C 20 mg/kg）， with 8 mice in each group. Except for the control group， mice in all other groups were given 4% dextran sulfate sodium solution for 5 days to establish the UC model. Subsequently， mice in each drug group were given the corresponding drug solution intragastrically or intraperitoneally， once a day， for 7 consecutive days. The changes in body weight of mice were recorded during the experiment. Twenty-four hours after the last administration， colon length， malondialdehyde （MDA） content， and activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） in colon tissues were measured； histopathological morphology of colon tissues， tight junctions between intestinal epithelial cells， and histopathological scoring were all observed and evaluated； the mRNA expressions of AMPK and Nrf2， as well as the protein expressions of heme oxygenase-1（HO-1）， occludin and claudin-1， were all determined in colon tissue. RESULTS Compared with model group， paeoniflorin groups exhibited recovery from pathological changes such as inflammatory cell infiltration and crypt damage in the colon tissue， as well as improved tight junction damage between intestinal epithelial cells. Additionally， significant increases or upregulations were observed in body weight， colon length， activities of SOD and GSH-Px， phosphorylation level of AMPK， and protein expression of Nrf2， HO-1， occludin， claudin-1， and mRNA expressions of AMPK and Nrf2； concurrently， MDA content and histopathological scores were significantly reduced （P＜ 0.05 or P＜0.01）. In contrast， the inhibitor group showed comparable （P＞0.05） or worse （P＜0.05 or P＜0.01） indicators compared to the model group. Conversely， the addition of AMPK inhibitor could significantly reverse the improvement of high- dose paconiflorin （P＜0.01）. CONCLUSIONS Paeoniflorin can repair intestinal epithelial cell damage in mice， improve tight junctions between epithelial cells， upregulate the expression of related proteins， and promote the expression and secretion of antioxidant-promoting molecules， thereby ameliorating UC； its mechanism may be associated with activating AMPK/Nrf2 antioxidant pathway.

Objective To investigate the effect of diosgenin on the proliferation and apoptosis of breast cancer cells and its potential molecular mechanism. Methods The breast cancer cell line MCF-7 was treated with low, medium, and high doses of diosgenin, and cell proliferation was detected through the MMT method. Flow cytometry was used to detect cell apoptosis. Nuclear-cytoplasmic-protein separation method was applied to detect the subcellular localization of death associated protein (DAXX). qRT-PCR and Western blot were used to detect the expressions of DAXX and c-Jun N-terminal kinase pathway (JNK)-related proteins. Results Diosgenin considerably inhibited the proliferation of MCF-7 cells and promoted cell apoptosis in a concentration-dependent manner. Diosgenin can promote the movement of DAXX from nucleus into the cytoplasm. Diosgenin upregulated the expression of cell surface death receptor (Fas), increased the phosphorylation levels of JNK and mitogen activated protein kinase (p38), and activated the JNK/p38 signaling pathway with concentration dependence. Conclusion Diosgenin inhibits the proliferation and promotes the apoptosis of the breast cancer cell line MCF-7, whose mechanism may be related to the regulation of DAXX subcellular localization and the activation of JNK/p38 signaling pathway.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Objective To introduce a locating device for the entry point of intramedullary nail based on the inertial navigation technology,which utilizes multi-dimensional angle information to assist in rapid and accurate positioning of the ideal direction of femoral anterograde intramedullary nails'entry point,and to verify its clinical value through clinical tests.Methods After matching the locating module with the developing board,which are the two components of the locating device,they were placed on the skin surface of the proximal femur of the affected side.Anteroposterior fluoroscopy was performed.The developing angle corresponding to the ideal direction of entry point was selected based on the X-ray image,and then the yaw angle of the locating module was reset to zero.After resetting,the locating module was combined with the surgical instrument to guide the insertion angle of the guide wire.The ideal direction of entry point was accurately located based on the angle guidance.By setting up an experimental group and a control group for clinical surgical operations,the number of guide wire insertion times,surgical time,fluoroscopy frequency,and intraoperative blood loss with or without the locating device was recorded.Results Compared to the control group,the experimental group showed significant improvement in the number of guide wire insertion times,surgical time,fluoroscopy frequency,and intraoperative blood loss,with a statistically significant difference(P<0.01).Conclusion The locating device can assist doctors in quickly locating the entry point of intramedullary nail,effectively reducing the fluoroscopy frequency and surgical time by improving the success rate of the guide wire insertion with one shot,improving surgical efficiency,and possessing certain clinical value.

Objective To explore the expression of death domain-associated protein(DAXX)and its subcellular localization in MCF-7 cells,discussing their effect on cellular function of MCF-7 cells.Methods MCF-7 cells were transfected with LV-DAXX-RNAi-GFP plasmid and LV-DAXX-GFP overexpression lentiviral plasmid,DAXX was knocked down and overexpressed.The expression and subcellular localization of DAXX in MCF-7 cells were detected by nuclear-cytoplasm separation methods and immu-nofluorescence,cell apoptosis and cell cycle were detected by flow cytometry,and cell proliferation was detected by MTT method.Results Both of the nuclear-cytoplasm separation methods and immunofluorescence confirmed that DAXX was mainly located in nucleus of MCF-7 cells.The transfection of LV-DAXX-GFP lentiviral plasmid mainly up-regulated the expression of DAXX in the cytoplasm of MCF-7 cells,while the transfection of LV-DAXX-RNAi-GFP lentiviral plasmid mainly down-regulated the expression of DAXX in the nucleus of MCF-7 cells.Flow cytometry confirmed that down-regulated the expression of DAXX located in nucleus could increase the apoptosis rate of MCF-7 cells,decreasing the cell proliferation,and block the cells in S phase,while up-regulated the expression of DAXX in cytoplasm had no significant effect on cell apoptosis,cell cycle and cell proliferation of MCF-7 cells.Conclusion DAXX is mainly located in the nucleus of MCF-7 cells.The expression of DAXX in the nucleus or cytoplasm may have the opposite effect on the cellular function of MCF-7 cells.

OBJECTIVE To determine the prevalence of frontal recess cells variations in patients with frontal sinus associated headache according to the International Frontal Sinus Anatomy Classification(IFAC).METHODS A retrospective study was conducted on the CT scans of sinuses in patients with frontal sinus associated headache.We reviewed 46 patients with frontal sinus-related headache who had clinical symptoms and were relieved after nasal endoscopic surgery.The development of frontal recess cells in the frontal recess drainage area was analyzed,and the variation of middle meatus and sinus involvement were analyzed in the same time.The Anatomical variations and imaging characteristics of frontal recess cells development in patients with frontal sinus associated headache were analyzed.RESULTS A total of 92 sinus CT profiles were analyzed in 46 patients.The most common cells were agger nasi cell(ANC)(100%,92/92),followed by supra bulla cell(SBC)(78.3%,72/92),supra agger cell(SAC)(67.4%,62/92),supra bulla frontal cell(SBFC)(27.2%,25/92),supra agger frontal cell(SAFC)(20.7%,19/92),frontal septal cell(FSC)(8.7%,8/92)and supraorbital ethmoid cell(SOEC)(0%,0/92).In the conventional frontal sinus drainage area,SAFC(P=0.0108),SAC(P=0.0104)and SAFC(P=0.0088)in the IFAC classification were significantly associated with the occurrence of frontal sinus associated headache.At the same time,the middle concha bullosa also showed a significant correlation with the occurrence of frontal sinus associated headache in the lower segment of the frontal recess drainage channel(P=0.0390).CONCLUSION In the frontal recess drainage channel,the abnormal development of SAC,SAFC,SBFC and the middle concha bullosa are significantly correlated with frontal sinus associated headache.

ObjectiveTo explore the mediating effect of personality traits between job stress and mental symptoms among firefighters. Methods A total of 974 firefighters in Shandong Province were selected as the research subjects using convenience sampling method. The Job Stress Scale, Brief Version of Chinese Big Five Personality Inventory and Symptom Checklist 90 were used to investigate their job stress, personality traits and mental symptoms. Results Job stress was found at a relatively high level in 39.7% of the firefighters, and 19.2% of the firefighters had high level of neurotic personality trait tendency. The positive detection rate of mental symptoms was 9.9% among firefighters. The score of job stress of the firefighters had a positive correlation with neuroticism and the score of mental symptoms (all P<0.01). The score of job stress and mental symptoms of the firefighters had a negative correlation with the personality traits score of extraversion, openness, agreeableness, and conscientiousness (all P<0.05). Neuroticism played a partially positive mediating effect between job stress and mental symptoms, and its mediating effect accounted for 39.6% of the total effect. Extraversion, agreeableness and conscientiousness played a partially negative mediating effect between work stress and mental symptoms, and the mediating effect accounted for 12.0%, 17.8% and 8.4% of the total effect respectively. There was no mediating effect of openness between job stress and mental symptoms. Conclusion Neurotic personality trait may enhance the negative effects of work stress on firefighters' mental health.

At present,precise radiotherapy has been widely used through the development with many years,but the existing technique still is limited by the limitation of tolerance dose of normal tissues,which cannot achieve the optimal goal of treating tumor.Flash radiotherapy(Flash-RT)is one kind of radiotherapy technique that uses the beam with ultra-high dose rate(UHDR)to conduct irradiation,which can furthest treat tumors while significantly reduce radiation injury of normal tissues.But until now,the biological mechanism,key physical parameters and triggering mechanism of Flash-RT are still unclear,and its principle and clinical translational application are still in the stage of research.This review clarified the technological advance and clinical translational application of Flash-RT research through summarized the relevant research of Flash-RT.

ObjectiveTo explore the mechanism of Huanglian Jiedutang in inhibiting the pyroptosis mediated by NOD-like receptor protein 3 （NLRP3） inflammasomes and alleviating the acute liver injury （ALI） induced by lipopolysaccharide （LPS） in the mouse model of sepsis. MethodFifty-four male C57BL/6 mice were randomized into blank， model， low- （3.08 g·kg^-1）， medium- （6.15 g·kg^-1）， and high-dose （12.30 g·kg^-1） Huanglian Jiedutang， and positive control （dexamethasone） groups （n=9）. The mice were administrated with Huanglian Jiedutang at different doses by gavage for 7 days， and then LPS （15 mg·kg^-1） was injected intraperitoneally for the modeling of sepsis. In the positive control group， dexamethasone （0.05 g·kg^-1） was injected intraperitoneally 1.5 h after modeling， and the mouse sepsis score （MSS） was recorded 12 h after modeling. The mice were sacrificed for the collection of blood and liver tissue samples. The levels of alanine transaminase （ALT） and aspartate transaminase （AST） were measured by a biochemical analyzer. The levels of tumor necrosis factor （TNF）-α， interleukin （IL）-6， IL-1β， and IL-18 in the serum were measured by enzyme-linked immunosorbent assay kits. Hematoxylin-eosin staining was used to observe the pathological changes in the liver tissue. The content of NLRP3 was observed by the immunofluorescence assay. The expression of apoptosis-associated speck-like protein containing CARD （ASC） was detected by immunohistochemistry. The protein levels of NLRP3， ASC， Caspase-1， and gasdermin D （GSDMD） in the liver tissue were determined by Western blot. Real-time quantitative polymerase chain reaction（Real-time PCR） was employed to determine the mRNA levels of GSDMD， Caspase-1， IL-1β， and IL-18. ResultCompared with the blank group， the model group showed elevated levels of ALT and AST （P<0.01） and risen levels of inflammatory cytokines in the serum （P<0.01）. In addition， the modeling resulted in edema and necrosis in the liver， and up-regulated the protein levels of GSDMD， NLRP3， ASC， and Caspase-1 （P<0.01） and the mRNA levels of GSDMD， Caspase-1， IL-1β， and IL-18 （P<0.01）. Compared with the model group， the drug intervention groups showed reduced content of inflammatory cytokines （P<0.01）， alleviated pathological damage in the liver tissue， and down-regulated protein levels of GSDMD， NLRP3， ASC， and Caspase-1 （P<0.05，P<0.01） and mRNA levels of GSDMD， Caspase-1， IL-1β， and IL-18 （P<0.05，P<0.01） in the liver tissue. ConclusionHuanglian Jiedutang can inhibit pyroptosis and reduce inflammation by inhibiting the activation of NLRP3 inflammasomes， thus demonstrating a therapeutic effect on acute liver injury in the mouse model of sepsis induced by LPS.

Objective:To evaluate the effect of gastrogin on AMP-activated protein kinase (AMPK)/transient receptor potential anchor protein 1 (TRPA1) signaling pathway in rats with neuropathic pain.Methods:Thirty-six SPF-grade healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-230 g, were divided into 3 groups ( n=12 each) using a random number table method: sham operation+ normal saline group (SHAM group), neuropathic pain+ normal saline group (NP group), and neuropathic pain+ gastrogin group (GAS group). Neuropathic pain was induced by chronic constrictive injury to sciatic nerve under 2% isoflurane anaesthesia. The sciatic nerve was only exposed but not ligated in SHAM group. Gastrogin 100 mg/kg was intraperitoneally injected for 14 consecutive days after developing the model in GAS group, while the equal volume of normal saline was given instead in SHAM and NP groups. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before developing the model (T 0) and 1, 3, 5, 7, 10 and 14 days after developing the model (T 1-6). The rats were anesthetized and sacrificed following the measurement of pain thresholds at T 4 and T 6. The lumbar segment (L 4-6) of the spinal cord was removed for determination of TRPA1 mRNA expression (by quantitative real-time polymerase chain reaction), expression of TRPA1, AMPK and p-AMPK (by Western blot), expression of TRPA1 (by immunofluorescence staining) and expression of tumor necrosis-alpha(TNF-α), interleukin-1beta(IL-1β) and c-fos (by immunohistochemistry). Results:Compared with SHAM group, MWT and TWL were significantly decreased at T 1-6, the expression of TRPA1 mRNA, TRPA1, TNF-α, IL-1β and c-fos was up-regulated, the expression of p-AMPK was down-regulated ( P<0.05), and no significant change was found in AMPK expression in NP group ( P>0.05). Compared with NP group, MWT at T 3-6 and TWL at T 2-6 were significantly increased, the expression of TRPA1 mRNA, TRPA1, TNF-α, IL-1β and c-fos was down-regulated, and p-AMPK expression was up-regulated ( P<0.05), and no significant change was found in AMPK expression in GAS group ( P>0.05). Conclusions:The mechanism by which gastrogin reduces neuropathic pain may be related to modulating the expression of the AMPK/TRPA1 signaling pathway in rats.