Colorectal cancer(CRC) is a common malignant tumor worldwide. Due to the treatment intolerance and side effects, CRC rank the top among various cancers regarding the incidence and mortality rates. Therefore, exploring new therapies is of great significance for the treatment of CRC. Aerobic glycolysis(AEG) plays an important role in the microenvironment formation, proliferation, metastasis, and recurrence of CRC and other tumor cells. It has been confirmed that intervening in the AEG pathway can effectively curb CRC. The active ingredients and compound prescriptions of traditional Chinese medicine(TCM) can effectively inhibit the proliferation, metastasis, and drug resistance and regulate the apoptosis of tumor cells by modulating AEG-associated transport proteins [eg, glucose transporters(GLUT)], key enzymes [hexokinase(HK) and phosphofructokinase(PFK)], key genes [hypoxia-inducible factor 1(HIF-1) and oncogene(c-Myc)], and signaling pathways(MET/PI3K/Akt/mTOR). Accordingly, they can treat CRC, reduce the recurrence, and improve the prognosis of CRC. Although AEG plays a key role in the development and progression of CRC, the specific mechanisms are not yet fully understood. Therefore, this article delves into the intrinsic connection of the targets and mechanisms of the AEG pathway with CRC from the perspective of tumor cell glycolysis and explores how active ingredients(oxymatrine, kaempferol, and dioscin) and compound prescriptions(Quxie Capsules, Jiedu Sangen Decoction, and Xianlian Jiedu Prescription) of TCM treat CRC by intervening in the AEG pathway. Additionally, this article explores the shortcomings in the current research, aiming to provide reliable targets and a theoretical basis for treating CRC with TCM.
Humans ; Colorectal Neoplasms/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; Glycolysis/drug effects* ; Animals ; Medicine, Chinese Traditional ; Signal Transduction/drug effects*

Prostate cancer(PCa) is a common malignant tumor among elderly men, with high incidence and mortality rates worldwide, posing a serious threat to human health. Traditional treatments face limitations, highlighting the urgent need for novel therapeutic strategies. Recent studies on the regulatory mechanisms of micro ribonucleic acid(microRNA, miRNA) in tumor development has identified miRNA as new targets for PCa diagnosis and treatment. Traditional Chinese medicine(TCM), with its multi-mechanism, multi-target, and multi-pathway regulatory properties, shows promising potential in miRNA-based PCa therapy. This review summarized recent findings on miRNA' roles in PCa and research progress of TCM intervention and found that a variety of miRNA played important regulatory roles in cell differentiation, proliferation, apoptosis, invasion, metastasis, immune microenvironment, and drug resistance, and their potential as biomarkers for PCa diagnosis, prognosis, and therapy, indicating the potential to be a biomarker for the diagnosis, prognosis evaluation, and treatment of PCa. The review concluded that the active components of TCM(terpenoids, flavonoids, alkaloids, and others) and compounds(Yishen Tonglong Decoction, Shenhu Decoction, Zhoushi Qiling Decoction, Fuzheng Yiliu Decoction, and Qilan Formula) could regulate the expression of their downstream target genes by acting on specific miRNA and affect the above biological behaviors of PCa cells, thus playing a role in the treatment of PCa. This review aims to provide a theoretical basis for miRNA as potential biomarkers and therapeutic targets for PCa and suggest new avenues for further development of targeted therapy strategies against miRNA.
Humans ; MicroRNAs/metabolism* ; Prostatic Neoplasms/metabolism* ; Male ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Animals ; Gene Expression Regulation, Neoplastic/drug effects*

PURPOSE: To investigate the pathological changes of the synovium in mice with post-traumatic osteoarthritis (PTOA) treated with 4-octyl itaconate (4-OI) and evaluate the therapeutic effects of 4-OI. METHODS: In the phenotypic validation experiment, the mice were randomly divided into 3 groups: wild-type (WT) group, sham group, and destabilization of the medial meniscus (DMM) group. Through MRI, micro-CT, and histological analysis, it was determined that the DMM surgery induced a mouse PTOA model with significant signs of synovitis. At 12 weeks post-DMM surgery, synovial tissues from the DMM group and WT group mice were collected for ribonucleic acid sequencing analysis. In the 4-OI treatment experiment, mice were randomly divided into the sham group, DMM group, DMM + 4-OI (50 mg/kg) group, and DMM + 4-OI (100 mg/kg) group. Von Frey tests and open field tests were conducted at intervals during the 12 weeks following the DMM surgery. After 12 weeks of surgery, the efficacy of 4-OI treatment on PTOA in mice was evaluated using MRI, micro-CT, histological analysis, and quantitative real-time polymerase chain reaction. Finally, we utilized network pharmacology analysis to predict the mechanism of 4-OI in treating PTOA synovitis and conducted preliminary validation. Statistical analysis was performed using one-way ANOVA and the Kruskal-Wallis test. Difference was considered statistically significant at p < 0.05. RESULTS: The DMM surgery effectively induced a PTOA mouse model, which displayed significant symptoms of synovitis. These symptoms included a notable increase in both the number of calcified tissues and osteophytes (p < 0.001), an enlargement of the calcified meniscus and synovial tissue volume (p < 0.001), and thickening of the synovial lining layer attributable to M1 macrophage accumulation (p = 0.035). Additionally, we observed elevated histological scores for synovitis (p < 0.001). Treatment with 4-OI inhibited the thickening of M1 macrophages in the synovial lining layer of PTOA mice (p < 0.001) and reduced fibrosis in the synovial stroma (p = 0.004). Furthermore, it reduced the histological scores of knee synovitis in PTOA mice (p = 0.006) and improved the inflammatory microenvironment associated with synovitis. Consequently, this treatment alleviated pain in PTOA mice (p < 0.001) and reduced spontaneous activity (p = 0.003). Bioinformatics and network pharmacology analyses indicated that 4-OI may exert its therapeutic effects by inhibiting the differentiation of synovial Th17 cells. Specifically, compared to the lipopolysaccharide stimulation group, 4-OI reduced the levels of positive regulatory factors of Th17 cell differentiation (IL-1: p < 0.001, IL-6: p < 0.001), key effector molecules (IL-17A: p < 0.001, IL-17F: p = 0.004), and downstream effector molecules in the IL-17 signaling pathway (CCL2: p < 0.001, MMP13: p < 0.001). CONCLUSION 4-OI is effective in inhibiting synovitis in PTOA, thereby alleviating the associated painful symptoms.
Animals ; Synovitis/etiology* ; Mice ; Osteoarthritis/etiology* ; Disease Models, Animal ; Male ; Succinates/pharmacology* ; Mice, Inbred C57BL ; X-Ray Microtomography

Objective： To investigate the correlation between pathological features at the positive margins and biochemical recurrence after radical prostatectomy for prostate cancer. Methods： From June 2014 to December 2019, a total of 200 patients with organ-confined prostate cancer who underwent radical prostatectomy were included in this study by the method of case matching (1∶1). One hundred patients with positive surgical margin and 100 with negative surgical margin were enrolled in this study. All patients did not receive any adjuvant treatment after surgery with a clinical stage of T2/N0. BCR-free survival was estimated using the Kaplan-Meier method. An optimal cutoff for the PSM length which differentiated risk for BCR was identified by Classification and Regression Tree analysis (CART). Cox proportional hazards regression model was used to assess the association between variables and BCR-free survival. Results： A total of 200 patients were included in this study, and 177 patients with pT2 stage were pathological after operation. The median follow-up time of this group of patients was 32.8 months ranged from 5.6 to 80.5 months. A total of 28 cases of biochemical recurrence were found through PSA follow-up after surgery, including 6 cases (6.0%) in the negative margin group and 22 cases (22.0%) in the positive margin group. The result of Kaplan Meier survival curve analysis showed that the non biochemical recurrence survival time of the negative margin group was longer than that of the positive margin group (log rank χ2=9.336, P=0.003). It was found that the length of positive margin ≥1 mm in the positive margin group was positively correlated with postoperative biochemical recurrence. Multivariate Cox proportional hazards regression was used to identify that the highest Gleason score ≥8 and the length of positive ≥1 mm were independent factors of postoperative biochemical recurrence in both the overall patients and the patients with positive margin. Conclusion：　The patients with highest Gleason score ≥8 and the length of positive ≥1mm are at elevated risk for BCR.
Humans ; Male ; Prostatectomy ; Prostatic Neoplasms/pathology* ; Neoplasm Recurrence, Local ; Margins of Excision ; Prostate-Specific Antigen/blood* ; Proportional Hazards Models ; Middle Aged ; Aged ; Neoplasm Staging ; Kaplan-Meier Estimate

OBJECTIVE: To investigate the therapeutic effect of Xiangshao Granules (XSG) on post-stroke depression (PSD) and explore the underlying mechanisms. METHODS: Forty-three C57BL/6J mice were divided into 3 groups: sham (n=15), PSD+vehicle (n=14), and PSD+XSG (n=14) groups according to a random number table. The PSD models were constructed using chronic unpredictable mild stress (CUMS) after middle cerebral artery occlusion (MCAO). The sham group only experienced the same surgical operation, but without MACO and CUMS stimulation. The XSG group received XSG (60 mg/kg per day) by gavage for 4 weeks. The mice in the sham and vehicle groups were given the same volume of 0.9% saline at the same time. The body weight and behavior tests including open field test, sucrose preference test, tail suspension test, and elevated plus-maze test, were used to validate the PSD mouse model. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining were used to evaluate the anti-inflammatory effects of XSG. The potential molecular mechanisms were explored and verified through network pharmacology analysis, Nissl staining, Western blot, ELISA, and RT-qPCR, respectively. RESULTS: The body weight and behavior tests showed that MCAO combined with CUMS successfully established the PSD models. XSG alleviated neuronal damage, reduced the expressions of pro-apoptotic proteins Caspase-3 and B-cell lymphoma-2 (BCL-2)-associated X (BAX), and increased the expression of anti-apoptotic protein BCL-2 in PSD mice (P<0.05 or P<0.01). XSG inhibited microglial activation and the expressions of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin (IL)-1 β, and IL-6 via the toll-like receptor 4/nuclear factor kappa-B signaling pathway in PSD mice (P<0.05 or P<0.01). Furthermore, XSG decreased the expression of indoleamine 2,3-dioxygenase1 (IDO1) and increased the concentration of 5-hydroxytryptamine in PSD mice (P<0.05 or P<0.01). CONCLUSION XSG could reverse the anxiety/depressionlike behaviors and reduce the neuronal injury in the hippocampus and prefrontal cortex of PSD mice, which may be a potential therapeutic agent for PSD.
Animals ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism* ; Depression/etiology* ; Drugs, Chinese Herbal/therapeutic use* ; Hippocampus/metabolism* ; Male ; Mice, Inbred C57BL ; Prefrontal Cortex/pathology* ; Microglia/metabolism* ; Stroke/drug therapy* ; Disease Models, Animal ; Mice ; Behavior, Animal/drug effects*

The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

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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 perioperative impact of closure of mesenteric fissure in laparoscopic right hemicolectomy.Methods:The prospective randomized controlled trial was conducted. The clinical data of 320 patients who underwent laparoscopic right hemicolectomy in 11 medical centers, including The First Affiliated Hospital of China Medical University et al, from November 2022 to August 2023 were selected. Based on block randomization, patients were alloca-ted into the mesenteric fissure non-closure group and the mesenteric fissure closure group. Observa-tion indicators: (1) grouping of the enrolled patients; (2) intraoperative conditions; (3) postopera-tive conditions. Measurement data with skewed distribution were represented as M( Q1, Q3) and com-parison between groups was conducted using the Mann-Whitney U test. Count data were represen-ted as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher's exact probability. Comparison of ordinal data was conducted using the rank sum test. Comparison of visual analog scores was analyzed using generalized estimating equations. Results:(1) Grouping of the enrolled patients. A total of 320 patients with colon cancer were screened for eligibility, including 156 males and 164 females, aged 68(59,73)years. All the 320 patients were allocated into the mesenteric fissure non-closure group with 164 cases and the mesenteric fissure closure group with 156 cases. There was no significant difference in the age, body mass index, American Society of Anesthesiologist score, maximum tumor diameter, anastomosis location, anastomosis method, surgical approach, range of lymph node dissection, tumor staging between the two groups ( P>0.05) and there was a significant difference in the sex between them ( P<0.05). (2) Intraoperative conditions. There was no significant difference between the mesenteric fissure closure group and the mesenteric fissure non-closure group in the volume of intraoperative blood loss, operation time, conversion to laparotomy, intraoperative complication ( P>0.05). Three patients in the mesenteric fissure non-closure group were converted to laparotomy. One patient in the mesenteric fissure closure group was converted to laparotomy, and 2 cases with intraoperative complication were mesenteric hematoma. (3) Postoperative conditions. There was no significant difference between the mesenteric fissure non-closure group and the mesenteric fissure closure group in the overall postoperative complications ( χ2=0.28, P>0.05). There was no significant difference in the occurrence of postoperative intestinal obstruction, abdominal distension, ascites, pleural effusion, gastric paralysis, anastomotic bleeding, anastomotic leakage, or surgical wound infection between the two groups ( P>0.05). There was no significant difference between the two groups in the reoperation, postoperative gastric tube replacement. There was no significant differ-ence in time to postoperative first flatus, time to postoperative initial liquid food intake, time to post-operative resumption of bowel movements, duration of postoperative hospital stay, total hospital expenses between the two groups ( Z=-0.01, 0.43, 1.04, -0.54, -0.36, P>0.05). One patient in the mesenteric fissure non-closure group received reoperation. No perioperative internal hernia or death occurred in either group. The visual analog score decreased with time in both groups. There was no significant difference in the visual analog score between the mesenteric fissure closure group and the mesenteric fissure non-closure group [ β=-0.20(-0.53,0.13), P>0.05]. Conclusion:Compared with closure of mesenteric fissure, non-closure of mesenteric fissure during laparoscopic right hemi-colectomy dose not increase perioperative complications or postoperative management risk.

Objective:To investigate respiratory virus infection in children with septic shock in pediatric care units (PICU) in China and its influence on clinical outcomes.Methods:The clinical data of children with septic shock in children′s PICU from January 2018 to December 2019 in 10 Chinese hospitals were retrospectively collected. They were divided into the pre-COVID-19 and post-COVID-19 groups according to the onset of disease, and the characteristics and composition of respiratory virus in the 2 groups were compared. Matching age, malignant underlying diseases, bacteria, fungi and other viruses, a new database was generated using 1∶1 propensity score matching method. The children were divided into the respiratory virus group and non-respiratory virus group according to the presence or absence of respiratory virus infection; their clinical characteristics, diagnosis, and treatment were compared by t-test, rank sum test and Chi-square test. The correlation between respiratory virus infection and the clinical outcomes was analyzed by logistic regression. Results:A total of 1 247 children with septic shock were included in the study, of them 748 were male; the age was 37 (11, 105) months. In the pre-and post-COVID-19 groups, there were 530 and 717 cases of septic shock, respectively; the positive rate of respiratory virus was 14.9% (79 cases) and 9.8% (70 cases); the seasonal distribution of septic shock was 28.9% (153/530) and 25.9% (185/717) in autumn, and 30.3% (161/530) and 28.3% (203/717) in winter, respectively, and the corresponding positive rates of respiratory viruses were 19.6% (30/153) and 15.7% (29/185) in autumn, and 21.1% (34/161) and 15.3% (31/203) in winter, respectively. The positive rates of influenza virus and adenovirus in the post-COVID-19 group were lower than those in the pre-COVID-19 group (2.1% (15/717) vs. 7.5% (40/530), and 0.7% (5/717) vs. 3.2% (17/530), χ2=21.51 and 11.08, respectively; all P<0.05). Rhinovirus virus were higher than those in the pre-Covid-19 group (1.7% (12/717) vs. 0.2% (1/530), χ2=6.51, P=0.011). After propensity score matching, there were 147 cases in both the respiratory virus group and the non-respiratory virus group. Rate of respiratory failure, acute respiratory distress, rate of disseminated coagulation dysfunction, and immunoglobulin usage of the respiratory virus group were higher than those of non-respiratory virus group (77.6% (114/147) vs. 59.2% (87/147), 17.7% (26/147) vs. 4.1% (6/147), 15.6% (25/147) vs. 4.1% (7/147), and 35.4% (52/147) vs. 21.4% (32/147); χ2=11.07, 14.02, 11.06 and 6.67, all P<0.05); and PICU hospitalization of the former was longer than that of the later (7 (3, 16) vs. 3 (1, 7)d, Z=5.01, P<0.001). Univariate logistic regression analysis showed that the presence of respiratory viral infection was associated with respiratory failure, disseminated coagulation dysfunction, the use of mechanical ventilation, and the use of immunoglobulin and anti-respiratory viral drugs ( OR=2.42, 0.22, 0.25, 0.56 and 1.12, all P<0.05). Conclusions:The composition of respiratory virus infection in children with septic shock is different between pre and post-COVID-19. Respiratory viral infection is associated with organ dysfunction in children with septic shock. Decreasing respiratory viral infection through respiratory protection may improve the clinical outcome of these children.