IL-32 is a multifunctional cytokine with both pro-inflammatory and anti-inflammatory properties.It has been proved that expression of IL-32 increases with progression of gastric mucosal diseases and severity of gastric cancer(GC),thus participating in process of gastric"inflammation-cancer"transformation.However,how IL-32 affects malignant transformation of gastric"inflamma-tion-cancer"and finally leads to adverse outcome of GC invasion and migration is still controversial.In order to better clarify regulatory effect and possible mechanism of abnormal expression of IL-32 on different histopathological stages of gastric"inflammation-cancer"transformation,and to explore new directions and breakthroughs in molecular mechanism of early truncation and treatment of gastric precancerous lesion(GPL),we searched literatures related to IL-32 in six authoritative databases at home and abroad,such as Pubmed,Web of Science and CNKI,in past 30 years.It was found that pathogenicity or protective function of IL-32 in different histo-pathological stages of gastric"inflammation-cancer"transformation depended on its different subtypes,secretory forms,surrounding cytokine environment,disease status and genetic factors.IL-32 may regulate polarization of macrophages through NF-κB,MAPK,COX2,PR3,IDO,NOD,PKCδ,FAK and STAT3,amplify or inhibit chronic inflammatory stimulation of gastric mucosa,and thus participate in process of gastric"inflammation-cancer"transformation.Our new understanding of role of IL-32 in different stages of Cor-rea cascade may contribute to development of cytokine-directed therapy,and therapy aimed at regulating different alternative splicing subtypes of IL-32 and targeting IL-32 signals can be used as a new strategy for medical treatment of GPL and GC in future.

IL-32 is a multifunctional cytokine with both pro-inflammatory and anti-inflammatory properties.It has been proved that expression of IL-32 increases with progression of gastric mucosal diseases and severity of gastric cancer(GC),thus participating in process of gastric"inflammation-cancer"transformation.However,how IL-32 affects malignant transformation of gastric"inflamma-tion-cancer"and finally leads to adverse outcome of GC invasion and migration is still controversial.In order to better clarify regulatory effect and possible mechanism of abnormal expression of IL-32 on different histopathological stages of gastric"inflammation-cancer"transformation,and to explore new directions and breakthroughs in molecular mechanism of early truncation and treatment of gastric precancerous lesion(GPL),we searched literatures related to IL-32 in six authoritative databases at home and abroad,such as Pubmed,Web of Science and CNKI,in past 30 years.It was found that pathogenicity or protective function of IL-32 in different histo-pathological stages of gastric"inflammation-cancer"transformation depended on its different subtypes,secretory forms,surrounding cytokine environment,disease status and genetic factors.IL-32 may regulate polarization of macrophages through NF-κB,MAPK,COX2,PR3,IDO,NOD,PKCδ,FAK and STAT3,amplify or inhibit chronic inflammatory stimulation of gastric mucosa,and thus participate in process of gastric"inflammation-cancer"transformation.Our new understanding of role of IL-32 in different stages of Cor-rea cascade may contribute to development of cytokine-directed therapy,and therapy aimed at regulating different alternative splicing subtypes of IL-32 and targeting IL-32 signals can be used as a new strategy for medical treatment of GPL and GC in future.

Objective:To investigate the application value of a multi-dimensional digital moni-toring platform for perioperative period in gastric cancer patients.Methods:The retrospective cohort study was conducted. The clinical data of 50 patients who underwent laparoscopic radical gastrec-tomy in The Affiliated Hospital of Nanjing University of Chinese Medicine from July 2022 to January 2024 were collected. There were 35 males and 15 females, aged (64±12)years. All patients followed the concept of enhanced recovery after surgery, and the multi-dimensional digital monitoring platform based on wearable monitoring equipment was used to implement perioperative management measures. Observation indicators: (1) results of heart rate variability (HRV) monitoring; (2) results of blood glucose and blood oxygen monitoring; (3) results of exercise and sleep monitoring; (4) results of body composition monitoring. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(IQR). Repeated measurement data were analyzed using the repeated ANOVA. Measurement data with skewed distri-bution were transformed to normal distribution by SPSS transformation function before testing. For comparison between pre- and postoperation, paired sample t test was used for measurement data with normal distribution, and nonparametric Wilcoxon signed rank sum test was used for measure-ment data with skewed distribution. Results:(1) Results of HRV monitoring. From preoperation to the third day after surgery, the standard deviation normal to normal heart beat of 50 patients was changed from(103±26)ms to(101±36)ms, the mean of the standard deviations of normal to normal heart beat calculated per 5 min segment was changed from (45±16)ms to(33±12)ms, the number of pairs of adjacent NN intervals differing by more than 50 ms in the entire recording was changed from 6.02%(4.96%) to 5.79%(4.20%), the low frequency power was changed from 376.78(468.96)ms 2 to 742.79(525.20)ms 2, the high frequency power was changed from 273.61(273.58)ms 2 to 397.48(164.87)ms 2, the ratio of low frequency power to high frequency power was changed from 1.6±0.5 to 1.6±0.6, showing significant differences in above indicators before and after operation ( F=34.43, 26.15, 24.58, 5.51, 6.11, 6.02, P<0.05). (2) Results of blood glucose and blood oxygen monitoring. From preoperation to the third day after surgery, the blood glucose of 50 patients was changed from 6.75(2.05)mmol/L to 6.90(2.63)mmol/L, showng a significant difference before and after operation ( F=45.84, P<0.05). The blood oxygen was changed from 97.00%(5.00%) to 97.50%(3.00%), showing no significant difference before and after operation ( F=2.25, P>0.05). (3) Results of exercise and sleep monitoring. From preoperation to the third day after surgery, the number of steps fo 50 pati-ents was changed from 3 043(1 224) to 1 473(767), sleep duration was changed from(8.2±1.1)hours to(7.3±0.8)hours, sleep score was changed from 80±10 to 78±5,showing significant differences in above indicators before and after operation ( F=716.46, 29.02, 47.32, P<0.05).(4) Results of body composition monitoring. The body weight of 50 patients was changed from (63±8)kg to(61±8)kg before and after operation, body fat rate was changed from 24%±8% to 22%±9%, muscle mass was changed from 43 (12)kg to 41(17)kg, body mass index was changed from (23.0±2.6)kg/m 2 to(22.1±2.5)kg/m 2, showing significant differences in above indicators before and after operation ( t=8.19, 3.00, Z=-2.78, t=7.34, P<0.05), while there was no significant difference in basal metabolic indicators from (1 390±134)kcal to (1 379±139)kcal before and after operation ( t=1.02, P>0.05). Conclusion:The multi-dimensional digital monitoring platform for preoperative period can accurately monitor the perioperative stress level and evaluate the postoperative recovery of gastric cancer patients, which can present the visual results.

Objective To investigate the clinical value of extracellular volume(ECV)based on CT delayed phase in combination with pathologic indicators in predicting early recurrence of gastric mesenchymal tumors after surgery.Methods A retrospective case-control trial was conducted on the imaging,clinical and pathological data of 110 patients with gastric mesenchymal tumors who were surgically resected at the First Affiliated Hospital of Army Medical University from January 2011 to August 2022.They were 60 males and 50 females,at a mean age of 58±10 years.All of them received preoperative multiphase dynamic CT enhancement examination of the abdomen,and ECV value was calculated with the formula:ECV=(1-hematocrit)×(△HU tumor/△HU aorta).According to the postoperative recurrence within 24 months after surgery,they were divided into early recurrence group and non early recurrence group.Statistical indexes:① Consistency analysis.② The factors affecting early recurrence after resection of gastric mesenchymal stromal tumors were analyzed and a prediction model was conducted.Delong test was used to assess the predictive value of the model.Then a nomogram was plotted based on the combines model,and calibration curves were drawn to assess the efficacy of the column charts,and decision curve analysis(DCA)was adopted to assess the value of the model for clinical application.Results ① Consistency analysis.After 2 radiologists outlined the region of interest and obtained ECV value according to the above formula,The intraclass correlation coefficient(ICC)was 0.806.② For the 110 subjected patients,21 cases of them had early recurrence,and 89 one did not.Multivariate analysis showed that ECV value,risk degree,and tumor length were independent influencing factors for predicting early recurrence.Receiver operating characteristic(ROC)curve analysis indicated that the area under the curve(AUC)value of ECV,hazard degree,and tumor length diameter in predicting early recurrence was 0.838(95％CI 0.758～0.918),0.774(95％CI 0.656～0.892),and 0.700(95％CI 0.589～0.810),respectively,and the value of their combined model was 0.899(95％CI 0.811～0.987),which was higher than that of each independent model.The sensitivity and specificity of the combined model was 85.71％and 86.52％,respectively,and the optimal cutoff value was 0.19.Delong test revealed that there was statistical difference between the combined model and the clinical model established by the hazard level(Z=6.548,P＜0.001,95％CI 0.140～0.259).Calibration curve analysis suggested that the combined model had a better fit,and DCA displayed that the combined model had a better net benefit.Conclusion The model established by ECV combined with pathological indicators has good predictive performance and can be used as a more effective predictor of early recurrence of gastric mesenchymal tumors after surgery.

Objective To explore the effect of M2 polarization of macrophages on intestinal metaplasia(IM)of gastric mucosa and its therapeutic target,so as to provide new ideas and directions for the prevention and treatment of IM with traditional Chinese medicine.Methods The data sets related to IM and macrophage M2 polarization were downloaded from the public database,and the correlation between IM and macrophage M2 polarization was further expounded by immune infiltration analysis,gene correlation analysis,functional enrichment analysis,protein interaction network and experimental verification.Finally,the obtained hub genes were mapped with Coremine Medical platform to predict the effective traditional Chinese medicine and treatment of IM.Results Immunoinfiltration and immunofluorescence analysis showed that the expression of macrophage M2 polarization markers CD68+CD163+(P=0.0394)and CD68+CD206+(P=0.002)in IM group was significantly higher than that in normal group,and the infiltration level of M2 macrophages in IM group was significantly higher than that in normal group(P＜0.05).IM related marker genes(CDX1,MUC2,TFF3)were positively correlated with macrophage M2 polarization markers(CD209,ARG1,MSR1,STAT3,IL32,SELENOP)(P＜0.05).Functional enrichment analysis showed that the differential genes co-expressed by IM and macrophage M2 polarization were closely related to molecular biological functions such as carboxylic acid transmembrane transporter activity and organic acid transmembrane transporter activity.Finally,7 pivotal differential genes co-expressed by IM and macrophage M2 were screened,which were TRAF1,TNFRSF12A,BIRC3,TNFRSF11A,CTSV,SLC29A1 and CDA,respectively.According to the prediction of traditional Chinese medicine,23 kinds of traditional Chinese medicine for IM were predicted,which could be classified into 14 categories according to their efficacy,among which heat-clearing antidote appeared most frequently,followed by drugs for tonifying qi and painkillers for promoting blood circulation drugs.Conclusion Macrophage M2 polarization may be involved in the pathogenesis and development of IM through exocrine pathway.IM and seven hub genes co-expressed by macrophage M2 polarization(TRAF1,TNFRSF12A,BIRC3,TNFRSF11A,CTSV,SLC29A1 and CDA)and IM specific molecules CDX1,MUC2 and TFF3 may be associated with each other and participate in the progression of IM.The therapeutic method of Jianpi Huayu Jiedu is the core treatment of IM in traditional Chinese medicine.Starting from the M2 polarization of macrophages,it is expected to become a new direction and breakthrough in clinical prevention and treatment of IM.

Objective To explore the effect of M2 polarization of macrophages on intestinal metaplasia(IM)of gastric mucosa and its therapeutic target,so as to provide new ideas and directions for the prevention and treatment of IM with traditional Chinese medicine.Methods The data sets related to IM and macrophage M2 polarization were downloaded from the public database,and the correlation between IM and macrophage M2 polarization was further expounded by immune infiltration analysis,gene correlation analysis,functional enrichment analysis,protein interaction network and experimental verification.Finally,the obtained hub genes were mapped with Coremine Medical platform to predict the effective traditional Chinese medicine and treatment of IM.Results Immunoinfiltration and immunofluorescence analysis showed that the expression of macrophage M2 polarization markers CD68+CD163+(P=0.0394)and CD68+CD206+(P=0.002)in IM group was significantly higher than that in normal group,and the infiltration level of M2 macrophages in IM group was significantly higher than that in normal group(P＜0.05).IM related marker genes(CDX1,MUC2,TFF3)were positively correlated with macrophage M2 polarization markers(CD209,ARG1,MSR1,STAT3,IL32,SELENOP)(P＜0.05).Functional enrichment analysis showed that the differential genes co-expressed by IM and macrophage M2 polarization were closely related to molecular biological functions such as carboxylic acid transmembrane transporter activity and organic acid transmembrane transporter activity.Finally,7 pivotal differential genes co-expressed by IM and macrophage M2 were screened,which were TRAF1,TNFRSF12A,BIRC3,TNFRSF11A,CTSV,SLC29A1 and CDA,respectively.According to the prediction of traditional Chinese medicine,23 kinds of traditional Chinese medicine for IM were predicted,which could be classified into 14 categories according to their efficacy,among which heat-clearing antidote appeared most frequently,followed by drugs for tonifying qi and painkillers for promoting blood circulation drugs.Conclusion Macrophage M2 polarization may be involved in the pathogenesis and development of IM through exocrine pathway.IM and seven hub genes co-expressed by macrophage M2 polarization(TRAF1,TNFRSF12A,BIRC3,TNFRSF11A,CTSV,SLC29A1 and CDA)and IM specific molecules CDX1,MUC2 and TFF3 may be associated with each other and participate in the progression of IM.The therapeutic method of Jianpi Huayu Jiedu is the core treatment of IM in traditional Chinese medicine.Starting from the M2 polarization of macrophages,it is expected to become a new direction and breakthrough in clinical prevention and treatment of IM.

Objective:To investigate the Chinese anesthesiologist′s proficiency, training experience and needs of flexible bronchoscope-guided awake flexible bronchoscopy intubation (AFBI) using a questionnaire method.Methods:The cluster sampling was used, and self-designed questionnaires that addressed 54 questions in 5 categories were distributed through WeChat and online platforms. The survey took one month, and the answers were automatically recorded by the WeChat server.Results:A total of 1 250 anesthesiologists participated in the survey in 30 provinces of China, 9 of them were not anesthesiologists, and 1 241 (99.28%) questionnaires were validated. In the valid questionnaires, 52.70% (654) of the anesthesiologists were from tertiary hospitals, and 74.78% (928) of the anesthesiologists were attending physicians or above, only 7.57% (94) of the anesthesiologists had sufficient confidence in AFBI. Twenty-five point two two percent (313) of the anesthesiologists preferred fiberoptic intubation as the first tool when dealing with the anticipated difficult airway. Forty-eight point one one percent (597) of the anesthesiologists had implemented AFBI. Among them, 80.74% (482) had experienced unsuccessful AFBI practices. Eight hundred and ninety-four anesthesiologists had received AFBI training, and the most common AFBI training strategy was theoretical lectures. In addition, the degree of satisfaction regarding the theoretical lectures quality, technical training, clinical practice relativity and non-technical skills training was 21.47% (192), 14.32% (128), 12.3% (110) and 17.90% (160), respectively. The degree of satisfaction with all the 4 training elements mentioned above was 7.27% (65).Conclusions:The awareness and practice of Chinese anesthesiologists in terms of clinical application of AFBI to treat difficult airways need to be strengthened at present, and the lack of high-quality AFBI training may be the key.

Metformin is currently a strong candidate anti-tumor agent in multiple cancers. However, its anti-tumor effectiveness varies among different cancers or subpopulations, potentially due to tumor heterogeneity. It thus remains unclear which hepatocellular carcinoma (HCC) patient subpopulation(s) can benefit from metformin treatment. Here, through a genome-wide CRISPR-Cas9-based knockout screen, we find that DOCK1 levels determine the anti-tumor effects of metformin and that DOCK1 is a synthetic lethal target of metformin in HCC. Mechanistically, metformin promotes DOCK1 phosphorylation, which activates RAC1 to facilitate cell survival, leading to metformin resistance. The DOCK1-selective inhibitor, TBOPP, potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids, and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models. Notably, metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression. This study shows that metformin effectiveness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for metformin-resistant HCC patients.
Animals ; Antineoplastic Agents/therapeutic use* ; Carcinoma, Hepatocellular/metabolism* ; Cell Line, Tumor ; Clustered Regularly Interspaced Short Palindromic Repeats ; Genome ; Humans ; Liver Neoplasms/metabolism* ; Metformin/therapeutic use* ; Mice ; Phosphorylation ; Synthetic Lethal Mutations ; Transcription Factors/metabolism* ; rac GTP-Binding Proteins/metabolism*

AIM To study the effects of No.1 Weiyan Decoction (Codonopsis Radix,Paeoniae Radix alba,Taraxaci Herba,etc.) on hypoxia and hypoxic tolerance in gastric mucosal epithelial cells in rats with precancerous lesion of gastric cancer (PLGC).METHODS Forty rats were randomly divided into normal,model,Vitacoenzyme Tablets and No.1 Weiyan Decoction groups.Except for the normal group,the rats in the other groups were given with N-methyl-N'-nitro-N-nitrosoguanidine and Little Chengqi Decoction to establish a PLGC rat model.Ten weeks after the administration,the gastric mucosal epithelial microvascular ultrastructure was observed,the expressions of Hif1a mRNA,HIF-1 α protein and VEGF protein in gastric mucosal epithelium were detected.RESULTS Compared with the normal group,the number of microvasculatures in gastric mucosal epithelium was decreased;lumen was severely stenosed or expansive;inner wall was not smooth and had adhesion;vascular endothelial cells were swollen;the expression of Hif1α mRNA showed an increasing trend;the expressions of HIF-1α protein and VEGF protein were anomalous in the model group.Compared with the model group,the gastric mucosal vascular lesion of PLGC rats was improved,and the expressions of Hif1a mRNA,HIF-1α protein and VEGF protein were significantly decreased in the No.1 Weiyan Decoction group.CONCLUSION No.1 Weiyan Decoction can improve hypoxia and hypoxia tolerance,and induce angiogenesis in gastric mucosal epithelium in PLGC rats.

BACKGROUND:The prevalence of osteoporosis is high in the patients undergoing total hip arthroplasty. Osteoporosis is associated with the survival of prostheses. Both canal flare index and bone mineral density are aged-related.
OBJECTIVE:To study the cxorrelation between canal flare index of the proximal femur and bone mineral density of femoral neck, and to pay more attention to osteoporosis.
METHODS:A retrospective study of the correlation between canal flare index of the proximal femur on pelvic radiograph and bone mineral density of femoral neck was made in 57 patients undergoing total hip arthroplasty.
RESULTS AND CONCLUSION:The canal flare index were ranged 1.8-4.8 (3.1±0.7) in 57 patients. There were 23 patients in canal flare index<3 (chimney-type medul ary cavity), 33 in canal flare index between 3 and 4.7 (normal-type medul ary cavity), and one in canal flare index>4.7 (funnel-type medul ary cavity). The age had an impact on the type of medul ary cavity. The prevalence of chimney-type medul ary cavity were significantly higher in>60 years old group than≤60 years old group, and bone mineral density of femoral neck in the group of canal flare index≥3 was significantly higher than the group of canal flare index<3. The bone mineral density of femoral neck was gradual y reduced with age, and were significantly higher in≤60 years old group than in>60 years old group [(0.751±0.235) g/cm2, (0.590±0.092) g/cm2, P=0.000]. As bone mineral density reduced, canal flare index was also decreased. Experimental findings indicate that, the bone mineral density of femoral neck is significantly correlated with canal flare index.