Background and purpose:Gallic acid(GA)induces tumor cells apoptosis and inhibits angiogenesis.Beyond directly attacking tumor cells,another crucial aspect of GA is its ability to modulate and enhance immune system function.For example,it can improve T cell metabolism,alleviate T cell exhaustion,and promote the formation of memory T cell phenotypes.Although several chimeric antigen receptor T(CAR-T)cells products have gained market approval,the technology still faces significant challenges.These limitations include off-target effects,a predisposition to T cell exhaustion and so on.Moreover,similar to exhaustion,cellular senescence is a major hindrance that impairs T cell function.This study aimed to investigate the effects of GA on the anti-tumor function of CAR-T cells both in vitro and in vivo.We further evaluated the impact of GA on CAR-T cells senescence and memory phenotypes,as well as the impact of GA and CAR-T cells on immune cell infiltration within the tumor microenvironment(TME).Methods:Second-generation CAR targeting mouse glypican 3(GPC3)and human epidermal growth factor receptor 2(HER2)were constructed to generate CAR-T cells.CAR-T cells were co-cultured with GA at a concentration of 5 μg/mL,and flow cytometry was used to assess the senescence status and memory phenotype of CAR-T cells and their killing ability against tumor cells at different effector-to-target ratios.Senescence markers included p53,p21,γ-H2AX and senescence-associated β-galactosidase(SA-β-gal),while CCR7 served as the memory phenotype marker.A subcutaneous tumor model was established to explore the effects of GA on the anti-tumor function of CAR-T cells and immune cell infiltration within the TME.Results:We successfully generated human HER2 and murine GPC3 CAR-T cells,achieving a purity of 30%-50%.GA enhanced the in vitro killing ability of CAR-T cells targeting mouse GPC3 and human HER2(P＜0.001)at different E:T ratios,delayed the senescence of mouse GPC3 CAR-T cells(p53,p21,γ-H2AX,P＜0.05;SA-β-gal,P＜0.001;CCR7,P＜0.001).And GA promoted the differentiation of CAR-T cells toward a memory phenotype(P＜0.001).Additionally,GPC3 CAR-T cells inhibited tumor cell growth(P＜0.05),prolonged mouse survival(P＜0.001),and enhanced the infiltration capacity of CAR-cells(P＜0.001)and endogenous immune cells[CD4+T cells,P＜0.05;CD8+T cells,P＜0.01;natural killer(NK)cells,P＜0.01].Conclusion:GA can enhance the cytotoxic activity of CAR-T cells in vitro,and delay the senescence of CAR-T cells.Furthermore,by modulating TME,GA improved immune cell infiltration,thereby augmenting the overall anti-tumor efficacy of CAR-T cells.

OBJECTIVE To establish an in vitro simulated one compartment extravascular adminis-tration model with lanthanum nitrate as the test substance,and explore the differences between this model and the classic in vitro administration model in lanthanum nitrate induced HepG2 cell death.METHODS An in vitro administration device was designed based on compartment model theories which consisted of four functional chambers:the liquid storage chamber,mixing chamber,toxicant exposure chamber,and waste liquid receiving chamber.The four chambers were connected by peristaltic pump hoses.The peristaltic pumps were employed to ensure unidirectional and constant speed trans-mission of liquid between these chambers.According to the preset toxicokinetic parameters such as T1/2a and T1/2,an in vitro simulated one compartment extravascular administration model of lanthanum nitrate was constructed using the device.The content of lanthanum nitrate in the toxicant exposure chamber at different time points was measured using inductively coupled plasma mass spectrometry.The concentration-time curves of lanthanum nitrate were analyzed using PKsolver and GraphPad Prism 8.0 software.The constructed in vitro simulated one compartment extravascular administration model was evaluated by comparing the measured and theoretical values of toxicokinetic parameters.HepG2 cells were treated with lanthanum nitrate in the in vitro simulated one compartment extravascular administration model and classic in vitro administration model,respectively,and cell death was measured using the Hoechst 33342/propidium iodide staining method.RESULTS Within the Cmax range of 3.91-1 000.00 μmol·L-1,the measured concentration-time curves of lanthanum nitrate in the toxicant expo-sure chamber almost conformed with the corresponding calculated theoretical curves(the correlation coefficients were all>0.998 0).The measured values of toxicokinetic parameters,including Ke,T1/2,Ka,T1/2a,Tmax,Cmax,CL and AUC0-∞,were close to the corresponding theoretical values.The fitting coeffi-cients(R2)of the concentration-time curves for each experimental group were all>0.990 0,which was consistent with one compartment model for extravascular administration.In the simulated one compart-ment extravascular administration model,no significant death of HepG2 cells was observed in any lanthanum nitrate dose group.In the classic in vitro administration model,the cell death rate of the 0.500 mmol·L-1 lanthanum nitrate group was higher than that of the solvent control group,but no significant cell death was observed in the 0.119 mmol·L-1 group or 0.243 mmol·L-1 group.When Cmax or Cadministration was 0.500 mmol·L-1,classic in vitro administration induced a higher cell death rate than simulated one compart-ment extravascular administration.However,there was no statistically significant difference in lanthanum nitrate induced HepG2 cell death between the two administration models when the AUC was equal.CONCLUSION The device designed in this study can be used to in vitro simulate one compartment extravascular administration,making in vitro toxicity testing more similar to in vivo scenarios,and providing data for optimizing administration methods of in vitro toxicity testing.There are differences in lanthanum nitrate induced HepG2 cell death between simulated one compartment extravascular administration and classic in vitro administration,indicating that different in vitro exposure modes can affect toxicity.

Objective:To construct an evidence-based cluster intervention program for the prevention of enteral nutrition complicated with diarrhea in patients with craniocerebral injury, and to verify its effect, in order to provide the best evidence for reducing the incidence of enteral nutrition complicated with diarrhea in patients with craniocerebral injury and improve the quality of nursing.Methods:By the method of non-synchronous controlled trials, the patients with craniocerebral injury treated by enteral nutrition in the Department of Neurosurgery, Lu'an Hospital of Traditional Chinese Medicine were selected as the research objects by convenient sampling method. Fify-two cases of routine intervention from January 2021 to March 2022 were divided into control group, and 51 cases of evidence-based cluster prevention intervention from April 2022 to February 2024 were divided into observation group. After 14 days of intervention, diarrhea [incidence of diarrhea and defecation traits (watery stool, loose stool), frequency of defecation, time of diarrhea and duration of diarrhea], other complications, nutritional status (serum total protein, serum albumin and hemoglobin), and nursing satisfactory degree were compared between the two groups.Results:Both groups of patients completed the study. There were 33 males and 19 females in the control group, aged (53.96 ± 17.44) years old, and 37 males and 14 females in the observation group, aged (60.05 ± 18.61) years old. The incidence of diarrhea and watery stools in the observation group was 11.76% (6/51) and 7.84% (4/51), respectively, which was lower than the 28.85% (15/52) and 23.08% (12/52) in the control group, and the differences were statistically significant ( χ2=4.63, 4.55, both P<0.05). The frequency of defecation in the observation group was (6.71 ± 1.64) times, which was lower than that in the control group (9.34 ± 2.10) times, and the difference was statistically significant ( t=7.08, P<0.05). The occurrence time of diarrhea in the observation group was (1.97 ± 0.54) d, which was later than that in the control group (1.59 ± 0.42) d, and the difference was statistically significant ( t=3.99, P<0.05). The duration of diarrhea in the observation group was (3.11 ± 0.86) d, which was shorter than that in the control group (5.12 ± 1.74) d, and the difference was statistically significant ( t=7.41, P<0.05). The incidence of other complications in the observation group was 9.80% (5/51), which was lower than the 25.00% (13/52) in the control group, and the difference was statistically significant ( χ2=4.12, P<0.05). After 14 days of intervention, the serum total protein, serum albumin, and hemoglobin levels in the observation group were (60.58 ± 6.37), (41.29 ± 8.24), (120.81 ± 11.72) g/L, respectively, which were higher than those in the control group (57.86 ± 6.15), (37.56 ± 7.64), (111.26 ± 11.25) g/L, and the differences were statistically significant ( t=2.21, 2.38, 4.22, all P<0.05). The patients′ overall satisfaction with nursing care in the observation group was 96.08% (49/51), which was higher than the control group′s 80.77% (42/52), and the difference was statistically significant ( χ2=5.86, P<0.05). Conclusions:The implementation of evidence-based cluster prevention intervention for enteral nutrition patients with craniocerebral injury can reduce the incidence of diarrhea in patients, which is conducive to the recovery of nutritional status, improve nursing satisfaction.

Space radiation is the most important environmental harmful factor in long-term manned spaceflight and deep space exploration, and it may produce deterministic and stochastic effects on tissues and organs. In-depth research into the biological effects, mechanisms, and protective measures of space radiation is essential and serves as an important foundation for exploring radiation biology and promoting major manned space projects. Firstly, this review introduces the spatiotemporal distribution characteristics of space radiation during low-earth orbit flights, manned lunar landings, and deep space exploration missions, as well as the health risks and challenges it posed to astronauts. Then, it discusses medical requirements and exposure limits, risk assessment, and protection technologies included in the space radiation protection system established internationally and over 30 years of Chinese manned spaceflight departments. Finally, it outlines the subsequent work and prospects for further research.

Objective To explore the mediating effects of self-disclosure and rumination on stigma and self-image in patients with head and neck cancer after surgery,so as to provide a reference for targeted intervention.Methods A total of 390 postoperative patients with head and neck cancer who were hospitalized in a Class Ⅲ Grade A general hospital in Shandong Province were selected by quota sampling method according to disease type.The general information questionnaire,shame and stigma scale in head and neck cancer distress disclosure index,ruminative responses scale and body image scale were used to investigate.Results A total of 360 patients with head and neck cancer after surgery completed the survey.The scores of stigma,self-image,rumination and self-disclosure were(37.9±11.0),(13.9±5.6),(56.5±12.4)and(28.9±7.3),respectively.There was a negative correlation between stigma and self-disclosure in patients with head and neck cancer after surgery(r=-0.386,P<0.001),and a positive correlation with self-image and rumination(r=0.455,0.565,all P<0.001).Self-disclosure and rumination had parallel mediating effects on stigma and self-image in patients with head and neck cancer after surgery,and the mediating effect accounted for 38.82％of the total effect.Conclusion The degree of self-image of postoperative patients with head and neck cancer not only directly affects the level of stigma,but also indirectly affects stigma through the mediating effect of self-disclosure and rumination.In clinical work,measures can be taken to improve the level of self-image and self-disclosure ability of patients,reduce the level of rumination and reduce the stigma of patients.

ObjectiveTo explore the therapeutic effect of Xuebijing injection （XBJ） on severe acute pancreatitis induced acute lung injury （SAP-ALI） by regulating formyl peptide receptors （FPRs）/nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） inflammatory pathway. MethodsSixty rats were randomly divided into a sham group， a SAP-ALI model group， low-， medium-， and high-dose XBJ groups （4， 8， and 12 mL·kg^-1）， and a positive drug （BOC2， 0.2 mg·kg^-1） group. For the sham group， the pancreas of rats was only gently flipped after laparotomy， and then the abdomen was closed， while for the remaining five groups， SAP-ALI rat models were established by retrograde injection of 5% sodium taurocholate （Na-Tc） via the biliopancreatic duct. XBJ and BOC2 were administered via intraperitoneal injection once daily for 3 d prior to modeling and 0.5 h after modeling. Blood was collected from the abdominal aorta 6 h after the completion of modeling， and the expression of interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） in plasma was measured by enzyme-linked immunosorbent assay （ELISA）. The amount of ascites was measured， and the dry-wet weight ratios of pancreatic and lung tissue were determined. Pancreatic and lung tissue was taken for hematoxylin-eosin （HE） staining to observe pathological changes and then scored. The protein expression levels of FPR1， FPR2， and NLRP3 in lung tissue were detected by the immunohistochemical method. Western blot was used to detect the expression of FPR1， FPR2， and NLRP3 in lung tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of FPR1， FPR2， and NLRP3 in lung tissue. ResultsCompared with the sham group， the SAP-ALI model group showed significantly decreased dry-wet weight ratio of lung tissue （P<0.01）， serious pathological changes of lung tissue， a significantly increased pathological score （P<0.01）， and significantly increased protein and mRNA expression levels of FPR1， FPR2， and NLRP3 in lung tissue （P<0.01）. After BOC2 intervention， the above detection indicators were significantly reversed （P<0.01）. After treatment with XBJ， the groups of different XBJ doses achieved results consistent with BOC2 intervention. ConclusionXBJ can effectively improve the inflammatory response of the lungs in SAP-ALI rats and reduce damage. The mechanism may be related to inhibiting the expression of FPRs and NLRP3 in lung tissue， which thereby reduces IL-1β and simultaneously antagonize the release of inflammatory factors IL-6 and TNF-α.

Objective To explore the mediating effects of self-disclosure and rumination on stigma and self-image in patients with head and neck cancer after surgery,so as to provide a reference for targeted intervention.Methods A total of 390 postoperative patients with head and neck cancer who were hospitalized in a Class Ⅲ Grade A general hospital in Shandong Province were selected by quota sampling method according to disease type.The general information questionnaire,shame and stigma scale in head and neck cancer distress disclosure index,ruminative responses scale and body image scale were used to investigate.Results A total of 360 patients with head and neck cancer after surgery completed the survey.The scores of stigma,self-image,rumination and self-disclosure were(37.9±11.0),(13.9±5.6),(56.5±12.4)and(28.9±7.3),respectively.There was a negative correlation between stigma and self-disclosure in patients with head and neck cancer after surgery(r=-0.386,P<0.001),and a positive correlation with self-image and rumination(r=0.455,0.565,all P<0.001).Self-disclosure and rumination had parallel mediating effects on stigma and self-image in patients with head and neck cancer after surgery,and the mediating effect accounted for 38.82％of the total effect.Conclusion The degree of self-image of postoperative patients with head and neck cancer not only directly affects the level of stigma,but also indirectly affects stigma through the mediating effect of self-disclosure and rumination.In clinical work,measures can be taken to improve the level of self-image and self-disclosure ability of patients,reduce the level of rumination and reduce the stigma of patients.

To summarize the diagnosis and management of a highly sensitized renal transplant recipient who developed Legionella pneumophila infection during the perioperative period. A 48-year-old male recipient presented early after transplantation with both acute allograft rejection and pulmonary infection. The acute rejection episode was successfully reversed with appropriate treatment, whereas the pulmonary infection continued to progress. Initial microbiological tests were negative, and empirical antimicrobial therapy was ineffective. Legionella pneumophila was subsequently detected by metagenomic next-generation sequencing of bronchoalveolar lavage fluid obtained via bronchoscopy. Following combined therapy with moxifloxacin and tigecycline, along with withdrawal of immunosuppressive agents, the pulmonary lesions completely resolved.

Objective:To explore the clinical efficacy of the posterior to anterior malleolar extended lateral approach (PAMELA) in the treatment of quadrimalleolar fractures.Methods:A retrospective study was conducted to analyze the clinical data of 12 patients with quadrimalleolar fracture who had been admitted to Foot and Ankle Surgery Department, Henan Luoyang Orthopaedic & Traumatological Hospital from June 2022 to June 2023. There were 5 males and 7 females, with an age of (37.3±12.2) years and a duration from injury to surgery of (8.8±3.5) d. Open reduction and internal fixation of displaced Chaput tubercle fractures, lateral and posterior malleolar fractures were conducted through the PAMELA for all patients. The incision exposure, operation time, intraoperative bleeding, and incision healing were noted. Postoperatively, the fracture reduction was evaluated using the Burwell-Charnley criteria. The clinical efficacy was evaluated at the final follow-up using the ankle-hindfoot score of American Orthopaedic Foot & Ankle Society (AOFAS), visual analogue scale (VAS), and range of motion (ROM) of the ankle joint.Results:Good exposure of the Chaput tubercle, anterolateral tibiotalar joint, and lateral and posterior malleoli was achieved during surgery in all patients. The follow-up time for the 12 patients was (14.3±1.8) months, the operation time (152.5±26.0) minutes, and the intraoperative bleeding (137.5±44.1) mL. All incisions healed at the first stage postoperatively without any complications. According to the Burwell-Charnley criteria, anatomic reduction was achieved in all patients. CT scans showed good reduction of the distal tibiofibular syndesmosis. At the final follow-up, their AOFAS score was (94.1±8.3) points, VAS 0 (0, 1) point, and ankle joint ROM 17.5°±9.0° for dorsiflexion and 35.2°±9.6° for plantarflexion.Conclusions:In the treatment of quadrimalleolar fractures, because the PAMELA can lead to good exposure of the anterolateral ankle joint, distal tibiofibular syndesmosis, and lateral and posterior malleolar fractures, it results in a high rate of anatomic reduction of the fractures, safe incisions and limited soft tissue complications. Therefore, it is a safe, simple, and effective surgical approach.