Gastric cancer is a high-incidence malignancy that poses a serious threat to public health in China, ranking among the top three cancers in both incidence and mortality. The majority of patients are diagnosed at an advanced stage, resulting in limited treatment options and poor prognosis. To address key challenges in gastric cancer diagnosis and treatment, a research team led by Professor Jiafu Ji at Peking University Cancer Hospital has focused on the project "Development and Dissemination of Precision Medicine Approaches in Gastric Cancer Management". Through a series of high-quality multicenter clinical studies, the team established a set of new international standards in perioperative treatment, individua-lized drug selection, intelligent noninvasive diagnostics, and novel immunotherapy strategies. These advances have significantly improved treatment efficacy and reduced surgical trauma, achieving key technological breakthroughs in diagnosis, therapy, and mechanistic understanding, and systematically enhancing outcomes for gastric cancer patients. The project ' s findings had a broad international impact, including hosting China ' s first International Gastric Cancer Congress. Through nationwide dissemination, they have promoted the development of precision diagnosis and treatment of gastric cancer as a discipline, and led the formulation of the National Health Commission's guidelines for gastric cancer diagnosis and treatment. In recognition of its achievements, the project was awarded the First Prize of the 2024 Chinese Medical Science and Technology Award.
Stomach Neoplasms/genetics* ; Humans ; Precision Medicine/methods* ; China ; Immunotherapy/methods*

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Objective To explore the impact of the sialic acid binding lectin-E(Siglec-E)on the inhibitory properties of parthenolide(PTL)against lipopolysaccharide(LPS)-induced M1 polarization of microglia(BV2).Methods ①Single cell sequencing data of Siglece related mouse brain tissue was obtained from Gene Expression Omnibus(GEO)database and divided into the WT group(n=3)and the Siglece-/-group(n=4).The microglia cells were screened,and the enrichment analysis was performed to analyze related differential genes and pathways.BV2 cells were constructed by the shRNA interference technique and were divided into NC-shRNA and Siglece-shRNA to detect the expression level of Siglec-E(Siglece).② NC-shRNA and Siglece-shRNA cells were respectively divided into the Control group,LPS group,PTL group and PTL+LPS group(n=3).The mRNA levels of markers of M1 polarization in microglia,iNOS,IL-1 β and IL-6,were detected by RT-qPCR.Siglecefl/fl and Cx3cr1cre mice were mated to obtain microglia-specific Siglece deletion(Siglecefl/fl×Cx3cr1cre)mice,and LPS-induced neuroinflammation model was established.③ Nine WT and Siglecefl/fl×Cx3cr1cre male mice were assigned to the Control group,LPS group and PTL+LPS group(n=3).RT-qPCR,immunofluorescence assay and Western blotting were used to verify the knock-out effect and polarization-related pathways,and to investigate the mechanism of Siglec-E affecting PTL inhibition of M1 polarization of microglia.Results Compared with the NC-shRNA group,the expression of Siglec-E in the Siglece-shRNA group was significantly decreased(P<0.01),indicating that the Siglec-E knock-down cell model was successfully established.With the stimulation of LPS,mRNA levels ofiNOS,IL-1 β and IL-6 were significantly up-regulated compared with the Control group both in shRNA cells and Siglece-shRNA cells(P<0.01).With the influence of PTL and LPS,the markers of M1 polarization in NC-shRNA cells mentioned before were significantly decreased(P<0.05),while for Siglice-shRNA cells,there were no significant changes in the markers of M1 polarization.PTL inhibited the phosphorylation of JNK and IκB protein(P<0.01)and the nuclear translocation of NF-κB in BV2 cells,down-regulated Siglec-E,and weakened the inhibitory effect.Compared with mice in the WT group,the expression of Siglec-E in microglia of Siglecefl/fl×Cx3cr1cre mice was decreased significantly(P<0.01),and the inhibitory effect of PTL on the phosphorylation of NF-κB in microglia of Siglecefl/fl×Cx3cr1cre mice was also decreased.Conclusion The absence of Siglec-E in microglia attenuates the inhibition of M1 polarization by the MAPK/NF-κB pathway targeted by PTL.

Objective:To explore the effect of the non-suicidal self-injury (NSSI) management plan for hospitalized adolescents with mood disorders based on hazard analysis and critical control point (HACCP) theory.Methods:From February to July 2023, convenience sampling was used to select 76 adolescents with mood disorders and NSSI from two closed full care wards of the Affiliated Brain Hospital of Nanjing Medical University as the research subject. Adolescents were randomly divided into a control group and an experimental group. The control group received the routine diagnosis, treatment, nursing, and risk management plan, while the experimental group implemented the management plan based on the HACCP theory. This study compared the incidence of NSSI, Adolescent Non-suicidal Self-injury Assessment Questionnaire (ANSSIQ), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), and Accompanying Family Member Satisfaction Questionnaire scores before and after intervention between two groups of adolescents.Results:The control group included 35 patients, while the experimental group included 32 patients. After intervention, the anxiety and depression scores of the experimental group patients were lower than those of the control group, and the difference was statistically significant ( P<0.05). The incidence of NSSI in the experimental group was lower than that in the control group with a statistical difference ( P<0.05). The satisfaction of accompanying family members in the experimental group was better than that in the control group, and the difference was statistically significant ( P<0.05) . Conclusions:The management plan based on the HACCP theory is beneficial for reducing the occurrence of NSSI in hospitalized adolescents with mood disorders, improving their negative emotions, enhancing the satisfaction of accompanying family members, and ensuring the safety of the ward.

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

Objective:To investigate the effect of different concentrations of human adipose-derived mesenchymal stromal cells (hADMSCs) derived exosome-mimetic nanovesicles (NVs)and exosomes (EXOs) on the biological function of human umbilical vein endothelial cells (HUVECs) .Methods:(1) Through hydrodynamic liposuction, adipose tissue was obtained from the thighs of 10 women (aged 18-65 years) in Fujian Medical University Union Hospital from June 2019 to August 2020. The hADMSCs were isolated by enzymatic hydrolysis, cultured to passage 4 and induced into adipocytes and osteocytes. The surface protein markers were identified by flow cytometry. (2) hADMSCs-NVs and hADMSCs-EXOs were prepared and observed under an electron microscope. Their surface protein markers were analyzed with particle size analyzer, particle size was analyzed with nanoparticle tracker. Protein quantitative analysis and nanoparticle tracking were used to detect the total protein and particle number of NVs and EXOs produced by 1×10 6 hADMSCs. (3) The control group (DMEM basic medium), 40, 60, 80 μg/ml NVs groups and 20, 40, 60 μg/ml EXOs groups were set to compare the proliferation, migration and angiogenesis of HUVECs through CCK-8 proliferation test, cell scratch test and angiogenesis test respectively. Graphpad Prism 7.0 was used for statistical analysis, and the measurement data were expressed as Mean±SD. Repeated measurement analysis of variance was applied to the comparison between multiple groups, and Tukey test was applied to pairwise comparison. P<0.05 represented statistical significance. Results:(1) The fourth generation of hADMSCs were slender spindle-shaped cells under optical microscope. After 21 days of adipogenesis induction, the transparent lipid droplets inside the cells were stained red by oil red O staining. After 14 days of osteogenesis induction, a large proportion of brown black staining area was observed by alkaline phosphatase calcium cobalt staining. The surface protein markers CD90 and CD29 of hADMSCs were positive. (2) Under transmission electron microscope, the structures of hADMSCs-NVs and EXOs were similar, both were discoid vesicles. The expression levels of CD9, CD81 and IgG were similar between NVS and EXOs. The particle sizes of NVs and EXOs were about the same, which were (72.0 ± 21.51) nm and (81.27±22.37) nm. The total protein content of NVs produced by 1×10 6 hADMSCs was (140.7±5.1) μg, about 100 times that of EXOs, which was (1.3±0.3) μg. The number of NVs [(644.5 ± 17.1)×10 8/ml] particles was about 90 times that of EXOs [(7.1±0.1)×10 8/ml]. (3) In CCK-8 proliferation assay, at 12, 24 and 48 hours after culture, the growth trend of HUVECs in the groups were generally consistent, and the difference in absorbance value was statistically significant ( P<0.01); at 48 hours after culture, the absorbance values of 60 μg/ml NVs and 40 μg/ml EXOs were higher than those in the control group (all P<0.01), but there was no significant difference between the two experimental groups ( P>0.05). At 8 and 24 hours after cell scratch assay, the changes of scratch width in each group were different, and the difference was statistically significant ( P<0.01); at 24 hours after scratch, the change of scratch width in 60 μg/ml NVs and 40 μg/ml EXOs groups were greater than that in the control group (all P<0.01), but there was no significant difference between the two experimental groups ( P>0.05). In the angiogenesis assay, the number of branch points and the length of blood vessels in each group were different, and the difference was statistically significant ( P<0.01). The number of capillary branches formed by HUVECs in 60 μg/ml NVs and 40 μg/ml EXOs groups were higher than that in the control group (all P<0.01), but there was no significant difference between the two experimental groups (all P>0.05). The capillary length of 60 μg/ml NVs and 40 μg/ml EXOs groups were longer than that of the control group ( all P<0.01), but there was no significant difference between the two experimental groups ( P>0.05). Conclusions:The shape and size of NVs were similar to EXOs, while the total protein content of NVs was about 100 times that of EXOs. The effects of hADMSCs-NVs and EXOs on the biological functions of HUVECs are similar and the optimum concentrations of NVs and EXOs are 60 μg/ml and 40 μg/ml, respectively.

Objective:To investigate the effect of different concentrations of human adipose-derived mesenchymal stromal cells (hADMSCs) derived exosome-mimetic nanovesicles (NVs)and exosomes (EXOs) on the biological function of human umbilical vein endothelial cells (HUVECs) .Methods:(1) Through hydrodynamic liposuction, adipose tissue was obtained from the thighs of 10 women (aged 18-65 years) in Fujian Medical University Union Hospital from June 2019 to August 2020. The hADMSCs were isolated by enzymatic hydrolysis, cultured to passage 4 and induced into adipocytes and osteocytes. The surface protein markers were identified by flow cytometry. (2) hADMSCs-NVs and hADMSCs-EXOs were prepared and observed under an electron microscope. Their surface protein markers were analyzed with particle size analyzer, particle size was analyzed with nanoparticle tracker. Protein quantitative analysis and nanoparticle tracking were used to detect the total protein and particle number of NVs and EXOs produced by 1×10 6 hADMSCs. (3) The control group (DMEM basic medium), 40, 60, 80 μg/ml NVs groups and 20, 40, 60 μg/ml EXOs groups were set to compare the proliferation, migration and angiogenesis of HUVECs through CCK-8 proliferation test, cell scratch test and angiogenesis test respectively. Graphpad Prism 7.0 was used for statistical analysis, and the measurement data were expressed as Mean±SD. Repeated measurement analysis of variance was applied to the comparison between multiple groups, and Tukey test was applied to pairwise comparison. P<0.05 represented statistical significance. Results:(1) The fourth generation of hADMSCs were slender spindle-shaped cells under optical microscope. After 21 days of adipogenesis induction, the transparent lipid droplets inside the cells were stained red by oil red O staining. After 14 days of osteogenesis induction, a large proportion of brown black staining area was observed by alkaline phosphatase calcium cobalt staining. The surface protein markers CD90 and CD29 of hADMSCs were positive. (2) Under transmission electron microscope, the structures of hADMSCs-NVs and EXOs were similar, both were discoid vesicles. The expression levels of CD9, CD81 and IgG were similar between NVS and EXOs. The particle sizes of NVs and EXOs were about the same, which were (72.0 ± 21.51) nm and (81.27±22.37) nm. The total protein content of NVs produced by 1×10 6 hADMSCs was (140.7±5.1) μg, about 100 times that of EXOs, which was (1.3±0.3) μg. The number of NVs [(644.5 ± 17.1)×10 8/ml] particles was about 90 times that of EXOs [(7.1±0.1)×10 8/ml]. (3) In CCK-8 proliferation assay, at 12, 24 and 48 hours after culture, the growth trend of HUVECs in the groups were generally consistent, and the difference in absorbance value was statistically significant ( P<0.01); at 48 hours after culture, the absorbance values of 60 μg/ml NVs and 40 μg/ml EXOs were higher than those in the control group (all P<0.01), but there was no significant difference between the two experimental groups ( P>0.05). At 8 and 24 hours after cell scratch assay, the changes of scratch width in each group were different, and the difference was statistically significant ( P<0.01); at 24 hours after scratch, the change of scratch width in 60 μg/ml NVs and 40 μg/ml EXOs groups were greater than that in the control group (all P<0.01), but there was no significant difference between the two experimental groups ( P>0.05). In the angiogenesis assay, the number of branch points and the length of blood vessels in each group were different, and the difference was statistically significant ( P<0.01). The number of capillary branches formed by HUVECs in 60 μg/ml NVs and 40 μg/ml EXOs groups were higher than that in the control group (all P<0.01), but there was no significant difference between the two experimental groups (all P>0.05). The capillary length of 60 μg/ml NVs and 40 μg/ml EXOs groups were longer than that of the control group ( all P<0.01), but there was no significant difference between the two experimental groups ( P>0.05). Conclusions:The shape and size of NVs were similar to EXOs, while the total protein content of NVs was about 100 times that of EXOs. The effects of hADMSCs-NVs and EXOs on the biological functions of HUVECs are similar and the optimum concentrations of NVs and EXOs are 60 μg/ml and 40 μg/ml, respectively.

Objective:To evaluate the efficacy of remimazolam for induction and maintenance of general anesthesia in patients undergoing abdominal surgery.Methods:A total of 100 patients of both sexes, aged 18-64 yr, with body mass index of 18-30 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, undergoing elective abdominal surgery with general anesthesia requiring tracheal intubation, were enrolled in this study and divided into 2 groups ( n=50 each) using a random number table method: remimazolam group (group R) and propofol group (group P). Anesthesia was induced by intravenously infusing propofol 1.0-2.5 mg/kg in group P and remimazolam 0.15-0.35 mg/kg in group R. Sufentanil 0.4-0.5 μg/kg and rocuronium 0.6 mg/kg were intravenously injected in group R and group P. Anesthesia was maintained by intravenously injecting remimazolam 0.3-1.0 mg·kg -1·h -1 in group R and propofol 4-12 mg·kg -1·h -1 in group P. Remifentanil 8-15 μg·kg -1·h -1 was intravenously injected in group R and group P. Narcrotrend index (NI) was maintained at 37-64 (D 0-D 2). The success of sedation, time for loss of consciousness, time of disappearance of eyelash reflex, time when NI dropped to D 0, incidence of tidal volume, respiratory rate and apnea after the patients lost consciousness, duration of stay in post-anesthesia care unit, the fluctuation range of mean arterial pressure at 1, 3 and 5 min of induction, and the development of intraoperative and postoperative adverse events. Results:The success rate of sedation in group R and group P was 100%.Compared with group P, time for loss of consciousness, time of disappearance of eyelash reflex and time when NI dropped to D 0 were significantly prolonged, tidal volume and respiratory rate were increased, the incidence of apnea after the patients lost consciousness was decreased, awakening time was shortened, the incidence of intraoperative sinus bradycardia, injection pain and dream was decreased, fluctuation range of blood pressure at 1, 3 and 5 min of induction was decreased in group R ( P<0.05). Conclusion:Remimazolam can be safely and effectively used for induction and maintenance of general anesthesia in patients undergoing abdominal surgery, and its induction dose is 0.15-0.35 mg/kg, and maintenance dose is 0.3-1.0 mg·kg -1·h -1.

Objective:To investigate the effect of exercise both before and after myocardial infarction (MI) on microvessel density in the left ventricle, and on the mRNA and protein expression of vascular endothelial growth factor (VEGF) and its receptors.Methods:Ninety-six male Sprague-Dawley rats were randomly divided into a sedentary sham operation group (Sed-Sh), a pre-MI exercise sham operation group (PreE-Sh), a sedentary MI group (Sed-MI), a pre-MI exercise group (PreE-MI), a post-MI exercise group (PostE-MI) and a combined exercise group (ComE-MI). The rats of the exercise groups underwent 60min of treadmill training daily five times a week for five weeks, while those of the Sed-Sh and Sed-MI groups remained sedentary. Then all of the rats underwent either an operation to induce an acute MI (Sed-MI, PreE-MI, PostE-MI and ComE-MI groups) or a sham MI operation (Sed-Sh and PreE-Sh groups). Four weeks after the operation, the exercise groups underwent five days adaptive training, followed by 8 weeks of 60min of treadmill training daily, five times a week. All of the rats were then sacrificed. The microvessel densities in the infarcted and uninfarcted volumes were detected using Factor VIII-related antigen staining, while the mRNA expressions of VEGF and its receptors were examined using a real-time polymerase chain reaction. The protein expressions of VEGF and its receptors were measured using western blotting.Results:Compared with Sed-MI group, the average microvessel densities of the PostE-MI and ComE-MI groups had increased significantly, with the average density of the PostE-MI group significantly higher than that of the PreE-MI group, but significantly lower than the ComE-MI group′s average. Compared with the Sed-MI group, the average mRNA expression of VEGF and its receptors in the PostE-MI and ComE-MI groups was significantly higher, without significant differences between the two groups.Conclusions:Pre-MI exercise does not significantly improve left ventricular function or microvessel density, while post-MI exercise does, as it can upregulate the expression of VEGF and its receptors to activate VEGF signaling. The increase in microvessel density may benefit left ventricular remodeling and cardiac function.

Objective: To explore peptidomic changes of peptides in saliva and gingival crevicular fluid (GCF) before and after treatment of gingivitis. Methods: From January 2017 to September 2017, seventeen participants at the age of 24-62 (6 males and 11 females) at Department of Preventive Dentistry, Peking University School and Hospital of Stomatology with gingivitis were recruited in the present study. Their clinical parameters were measured and recorded. Saliva and GCF samples were collected from each of the participants at the baseline and 7 days after ultrasonic supragingival scaling, respectively. Matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) was employed to detect the changes of peptidomic profiles, while ano-liquid chromatography-electrospray ionization-tandem mass spectrometry (nano-LC/ESI-MS/MS) was performed to identify the possible proteins from which the peptides might derive. Results: Initially, four peptide peaks [mass-to-charge ratio (m/z) values: 1 030.6, 1 043.4, 1 053.4 and 1 064.6] were screened out exhibiting a decreasing trend after treatment (P<0.05). Besides, five peptide peaks from gingival crevicular fluid (P<0.05) exhibited differential expression, among which 1 055.5 and 1 168.3 demonstrating a decrease after treatment, while 3 363.7, 3 480.9 and 3 489.5 increased overtime. Certain positive correlations were detected between some peptides and clinical parameters. Principle component analysis using the above mentioned peptide peaks showed a distinct distribution before and after treatment and peptides from GCF showed a slightly better capacity to discriminate patients before and after treatment. The peptides with m/z values of 1 055.5 in GCF and 1 064.6 in saliva were identified to be segments of serum albumin and complement C3, respectively. Conclusions Several differentially expressed peptides were detected in saliva and GCF by MALDI-TOF MS, exhibiting the potentiality to act as biomarkers in gingivitis patients.