1.Targeting cAMP in D1-MSNs in the nucleus accumbens, a new rapid antidepressant strategy.
Yue ZHANG ; Jingwen GAO ; Na LI ; Peng XU ; Shimeng QU ; Jinqian CHENG ; Mingrui WANG ; Xueru LI ; Yaheng SONG ; Fan XIAO ; Xinyu YANG ; Jihong LIU ; Hao HONG ; Ronghao MU ; Xiaotian LI ; Youmei WANG ; Hui XU ; Yuan XIE ; Tianming GAO ; Guangji WANG ; Jiye AA
Acta Pharmaceutica Sinica B 2024;14(2):667-681
Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.
2.Application of CICARE communication model in patient communication in the waiting room for cardiac interventional therapy
Ting YU ; Juan XIAO ; Meili LIU ; Jingwen HU
Chinese Medical Ethics 2024;37(6):738-744
Objective:To explore the application effect of the CICARE communication model in patient communication in the waiting room for cardiac interventional therapy.Methods:The 108 patients in the waiting room for cardiac interventional therapy at a hospital from January 2023 to May 2023 were selected as the study subjects.Among them,55 patients from January to March 2023 were assigned to the control group,and 53 patients from April to May 2023 were assigned to the intervention group.The control group received the traditional communication model for communication and health education,and the intervention group received the CICARE communication model for communication and health education.The intervention effects were compared between the two groups.Results:After implementing the CICARE communication model,the preoperative anxiety level of patients in the intervention group was significantly lower than that in the control group[(12.30±4.30)Vs.(15.41±2.35),P<0.01].The intervention group had a significantly better understanding of surgical objectives and procedures[(4.70±0.54)Vs.(3.66±0.67),P<0.001],preoperative preparation(P<0.001),intra-operative position and communication[(3.89±0.32)Vs.(3.03±0.57),P<0.001],and post-operative precautions[(5.26±0.71)Vs.(4.17±0.71),P<0.001]than the control group.In addition,the number of people in the intervention group who was satisfied with the evaluation of nursing work(χ2=23.923,P<0.001)and the overall satisfaction score were significantly higher than those in the control group[(68.48±6.42)Vs.(45.79±12.56),P<0.001].Conclusion:Patient education based on the CICARE communication model can effectively inprove communication efficiency,improve the body stress response,enhance patient satisfaction with nursing work,and promote a harmonious nurse-patient relationship.
3.Long-term outcome of patients with rectal cancer who achieve complete or near complete clinical responses after neoadjuvant therapy: a multicenter registry study of data from the Chinese Watch and Wait Database
Yiming ZHAO ; Weihu WANG ; Wei ZHANG ; Lin WANG ; Shuai LI ; Jingwen WANG ; Leen LIAO ; Guanyu YU ; Zhen SUN ; Yanli QU ; Yang GONG ; Yun LU ; Tao WU ; Yunfeng LI ; Quan WANG ; Guohua ZHAO ; Yi XIAO ; Peirong DING ; Zhen ZHANG ; Aiwen WU
Chinese Journal of Gastrointestinal Surgery 2024;27(4):372-382
Objective:To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT).Methods:This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups.Results:Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion:Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.
4.Relationship among anxiety,perceived stress and forbearance in college students
Hongyan LIAO ; Jingwen DU ; Rong XIAO
Chinese Mental Health Journal 2024;38(3):277-282
Objective:To explore the relationship of anxiety,perceived stress and forbearance in the college students.Methods:Totally 3 056 college students(1 102 males and 1 954 females)in Guangdong Province were re-cruited and assessed with the Generalized Anxiety Disorder 7-item Scale(GAD-7 score of ≥10 indicates positive anxiety symptoms),Perceived Stress Scale(PSS-10),and Forbearance Scale(FS).SPSS Process model 2 was used to test the moderating effect of different types of forbearance.Results:Totally 486(15.9%)college students had anxiety.The PSS-10 scores were positively correlated with the GAD-7 scores(β=0.63),and FS scores of repres-sive forbearance and active forbearance played a moderating role between the PSS-10 scores and the GAD-7 scores respectively(β=0.05,-0.04).Conclusion:It suggests that anxiety and perceived stress are correlated with for-bearance in college students,and repressive forbearance and active forbearance may moderate the relationship be-tween perceived stress and anxiety.
5.Significance of infiltration of M1 tumor-associated macrophages in hepatocellular carcinoma
Feng XIAO ; Tonglin XU ; Lin ZHU ; Jingwen XIAO ; Tianqi WU ; Chunyan GU
China Oncology 2024;34(8):726-733
Background and purpose:Tumor-associated macrophages(TAM)as the main stromal cells in the tumor microenvironment play an important role in tumor progression.This study aimed to explore the clinical significance of M1 type TAM infiltration in hepatocellular carcinoma(HCC).Methods:We collected tissue paraffin samples from 320 HCC patients who underwent surgery at the Affiliated Nantong Hospital Three of Nantong University from January 2012 to December 2020.Immunohistochemical methods were used to detect the distribution of CD86 labeled M1 type TAM in HCC tissues,and positive cell density was calculated.Groups were established according to cell density,high-density group had cells with greater than average density(29 cells/mm2),and low-density group had cells with less than or equal to average density.The correlation and prognostic significance of M1 TAM density with clinicopathologic features and tumor infiltrating CD8+T lymphocytes of HCC were analyzed.Using immunohistochemistry to detect the expression of programmed death ligand-1(PD-L1),the cases were divided into four groups based on the cell density of CD86 and PD-L1.In the CD86+high-density group,PD-L1 high-density(CD86highPD-L1high)and PD-L1 low-density(CD86highPD-L1low)groups were included.In the CD86+low-density group,the PD-L1 high-density(CD86lowPD-L1high)and PD-L1 low-density(CD86lowPD-L1low)groups were included.We analyzed the prognostic significance of CD86+M1 type TAM density combined with PD-L1 expression.This study was approved by the Ethics Committee of Affiliated Nantong Hospital Three of Nantong University(ethics number:EK2022005).Results:CD86+M1 type TAM was mainly distributed in the tumor stroma.Its high-density rate was 44.7%(143/320).The density of CD86+M1 type TAM was positively correlated with tumor infiltrating CD8+T lymphocyte density(P<0.001)and negatively correlated with hepatitis B virus surface antigen(HBsAg)positivity(P=0.003),and had no significant correlation with clinical and pathological features such as patient age,gender,cirrhosis,tumor size,histological grading and microvascular invasion.The CD86+M1 type TAM high-density group had better overall survival(OS)and disease-free survival(DFS)than the low-density group,and the differences were statistically significant(all P<0.001).Multivariate Cox proportional hazards regression model analysis showed that low-density CD86+M1 type TAM was an independent risk factor for evaluating OS and DFS(OS:HR=1.468,P=0.022;DFS:HR=2.233,P<0.001).The CD86highPD-L1high group had poor OS and DFS than the CD86highPD-L1low group,and the differences were statistically significant(both P<0.05).The CD86lowPD-L1high group had poor OS and DFS than the CD86lowPD-L1low group.The difference in OS between the two groups was statistically significant(P<0.05),while the difference in DFS was not statistically significant.Conclusion:The presence of high-density CD86+M1 type TAM in HCC tissue suggests a good prognosis and is an independent prognostic factor.Expression of PD-L1 in HCC tissue suggests increased invasiveness and poorer prognosis.
6.Long-term outcome of patients with rectal cancer who achieve complete or near complete clinical responses after neoadjuvant therapy: a multicenter registry study of data from the Chinese Watch and Wait Database
Yiming ZHAO ; Weihu WANG ; Wei ZHANG ; Lin WANG ; Shuai LI ; Jingwen WANG ; Leen LIAO ; Guanyu YU ; Zhen SUN ; Yanli QU ; Yang GONG ; Yun LU ; Tao WU ; Yunfeng LI ; Quan WANG ; Guohua ZHAO ; Yi XIAO ; Peirong DING ; Zhen ZHANG ; Aiwen WU
Chinese Journal of Gastrointestinal Surgery 2024;27(4):372-382
Objective:To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT).Methods:This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups.Results:Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion:Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.
7.Feasibility Study on Guiding Antihypertensive Treatment Based on Hemodynamic Phenotypes
Wenqi XIAO ; Huixian HUANG ; Ping HAN ; Liping SONG ; Jingwen YANG ; Lin ZHOU ; Ningling SUN
Chinese Circulation Journal 2024;39(7):710-715
Objectives:To explore the feasibility of using hemodynamic phenotypes to guide antihypertensive treatment medication. Methods:This study prospectively included 100 hypertensive patients who received outpatient treatment at Haidian Hospital in Beijing from January 2021 to December 2021.Evaluation of blood pressure was conducted using laboratory and home blood pressure measurements,impedance cardiogram(ICG)detection was performed.Following hemodynamic phenotypes and therapeutic phenotypes were established:hyperkinetic phenotype(increased heart rate)using β-blockers,large artery phenotype(increased large artery resistance index)using calcium antagonists,peripheral vascular phenotype(increased peripheral vascular resistance index)using renin angiotensin system inhibitors,and high-volume phenotype(increased blood volume saturation)using diuretics.Patients were randomly divided into ICG group(n=50,medication treatment based on hemodynamic characteristics)and control group(n=50,treatment based on hypertension guidelines and clinical experience).Patients were followed up for 8 weeks and the blood pressure reduction amplitude and compliance rate were compare between the two groups. Results:There was no statistically significant difference in baseline data such as sex,age,height,weight,and hemodynamic parameters between the two groups(all P>0.05).There was no statistically significant difference in the types of baseline medication between the two groups(P>0.05).After medication adjustment,the types of medication increased,but the difference between the two groups was still not statistically significant(P>0.05).Clinic blood pressure:After 8 weeks,decreases in systolic([8.38±27.78]mmHg,1 mmHg=0.133 kPa)and diastolic([3.94±18.15]mmHg)blood pressure were greater in the ICG group as compared to the control group(both P<0.05).The blood pressure compliance rate(<140/90 mmHg)was higher in the ICG group than that in the control group(66.0%vs.42.0%,P<0.05).Family blood pressure:after 8 weeks,the reduction in systolic([8.22±21.31]mmHg,P<0.01)and diastolic([4.76±13.88]mmHg,P<0.05)blood pressure was greater in the ICG group compared to the control group.The blood pressure compliance rate(<135/85 mmHg)was higher in the ICG group than that in the control group(70.0%vs.48.0%,P<0.05).Changes in corresponding hemodynamic parameters before and after two different antihypertensive drugs:the heart rate,arterial resistance index,peripheral vascular resistance index,and blood volume saturation of the ICG group all significantly decreased compared to baseline(all P<0.05).The control group showed a significant decrease in peripheral vascular resistance index compared to baseline(P<0.05),while there was no statistically significant difference in heart rate,large artery resistance index,and blood volume saturation compared to baseline(all P>0.05). Conclusions:By using impedance cardiogram to assess hemodynamic phenotypes and accurately guide the selection of antihypertensive drugs based on hemodynamic phenotypes,it is possible to more effectively lower blood pressure and improve blood pressure compliance.
8.Effects of early enteral nutrition intervention on systemic inflammation and intestinal injury through NF-κB pathway in rats with acute pancreatitis
Di JIN ; Jingwen QUAN ; Mengliu JIANG ; Min MURONG ; Weifen LIANG ; Guizhen XIAO
Chinese Journal of Endocrine Surgery 2023;17(3):261-267
Objective:To investigate the effects of early enteral nutrition intervention on systemic inflammation and intestinal injury in rats with acute pancreatitis and its mechanism.Method:Rat acute pancreatitis model was established. The rats were divided into sham surgery groups, model group, 12 h nutrition support group, 24 h nutrition support group, 48 h nutrition support group, and 48 h nutrition support group +PMA group according to the random number chart method, with 10 rats in each group. After laparotomy, the rats in sham operation group were closed after gently turning the pancreas. The sham operation group and model group were injected with the same amount of physiological salt. Nutritional support group for 12 h, nutritional support group for 24 h and nutritional support group for 48 h were given enteral nutrition support for 12, 24 and 48 h, respectively. Nutritional support group for 48 h +PMA group, intraperitoneal injection of 5 mg/kg NF-κB signaling pathway activator PMA was given after modeling, and nutritional support was given for 48 h. The contents of lipase, amylase and creatinine in serum of each group were detected by automatic biochemical analyzer. The serum levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) and D-lactic acid were detected by enzyme-linked immunosorbent assay (ELISA). The content of diamine oxidase (DAO) was detected by colorimetry. Hematoxylin-eosin (HE) staining was used to detect the pathological changes of intestinal mucosa. Western blot was used to detect the expression of NF-κB pathway-related proteins in pancreatic tissue of rats in each group.Results:(1) Lipase, amylase and creatinine in sham operation group, model group, 12 h nutrition support group, 24 h nutrition support group and 48 h nutrition support group were (4.37±0.61) vs (12.021±1.00) vs (8.77±0.62) vs (6.88±0.63) vs (5.20±0.41) U/ml, (1674.03±172.24) vs (4356.30±229.38) vs (3676.11±382.43) vs (2990.06±251.93) vs (1919.75±179.40) U/L, (32.12±3.37) vs (91.73±9.76) vs (72.38±6.83) vs (53.72±5.98) vs (41.82±4.00) U/L. Compared with sham operation group, the contents of serum lipase, amylase and creatinine in model group were significantly increased. Compared with model group, the contents of lipase, amylase and creatinine were significantly decreased after 12, 24 and 48 h of nutritional support, and were time-dependent ( P<0.05). (2) The levels of IL-6, IL-1β, TNF-α and IL-10 were (40.26±3.93) vs (123.34±13.19) pg/ml in sham operation group, model group, 12 h nutritional support group, 24 h nutritional support group and 48 h nutritional support group, respectively vs (108.97±12.70) vs (77.36±6.75) vs (49.18±4.97) pg/ml, (77.53±9.95) vs (316.36±23.76) vs (254.79±13.96) vs (177.92±17.20) vs (119.19±13.17) pg/ml, (62.94±5.39) vs (353.16±28.03) vs (275.87±22.11) vs (198.78±24.33) vs (94.60±9.41) pg/ml, (41.21±4.29) vs (6.92±1.01) vs (10.76±0.66) vs (21.24±1.64) vs (35.33±1.69) pg/ml. Compared with sham operation group, the contents of serum inflammatory cytokines IL-6, IL-1β and TNF-α in model group were significantly increased, while the content of IL-10 was significantly decreased. Compared with model group, the contents of IL-6, IL-1β and TNF-α were significantly decreased after 12, 24 and 48 h of nutritional support, while the contents of IL-10 were significantly increased in a time-dependent manner ( P<0.05). (3) The intestinal histopathological scores, DAO and D-lactic acid of sham operation group, model group, 12 h nutritional support group, 24 h nutritional support group and 48 h nutritional support group were (0.00±0.00) vs (4.20±0.60) vs (3.00±0.45) points, respectively vs (1.90±0.54) vs (1.30±0.64) points, (4.92±0.42) vs (14.95±1.20) vs (11.87±1.13) vs (9.02±0.53) vs (6.30±0.59) U/L, (2.39±0.22) vs (6.92±0.46) vs (5.21±0.28) vs (3.64±0.39) vs (2.95±0.15) nmol/ml. Compared with sham operation group, intestinal histopathological scores, DAO and D-lactic acid levels were significantly increased in model group. Compared with model group, intestinal histopathological scores, DAO and D-lactic acid levels were significantly decreased after 12, 24 and 48 h of nutritional support ( P<0.05). (4) The protein expressions of NF-κB p65 and p-IκBα were (0.23±0.03) vs (0.94±0.10) vs (0.75±0.06) vs (0.62±0.06) in sham operation group, model group, 12 h nutrition support group, 24 h nutrition support group and 48 h nutrition support group, respectively. vs (0.41±0.06), (1.06±0.12) vs (0.25±0.04) vs (0.47±0.03) vs (0.62±0.08) vs (0.85±0.08). Compared with sham operation group, NF-κB p65 protein level in model group was significantly increased, while p-IκBα protein level was significantly decreased. Compared with model group, the NF-κB p65 protein level was significantly decreased after 12, 24 and 48 h of nutritional support, while the P-iκBα protein was significantly increased ( P<0.05). (5) NF-κB p65, p-IκBα, IκBα, IL-6, IL-1β, TNF-α, IL-10, lipase, amylase and creatinine were (0.41±0.06) vs (0.82±0.06) in the 48 h group and the 48 h +PMA group, respectively. (0.85±0.08) vs (0.37±0.02), (1.05±0.11) vs (1.10±0.14), (49.18±4.97) vs (105.68±10.69) pg/ml, (119.19±13.17) vs (247.16±23.41) pg/ml, (94.60±9.41) vs (328.24±30.86) pg/ml, (5.20±0.41) vs (10.33±1.01) U/ml, (1919.75±179.40) vs (4023.40±334.56) U/L, (5.20±0.41) vs (10.33±1.01) U/ml, (41.82±4.00) U/L vs (81.33±7.96) U/L. Compared with the 48 h group, the expression level of NF-κB p65 protein, IL-6, IL-1β, TNF-α, lipase, amylase and creatinine in the 48 h +PMA group were significantly increased, while the expression level of P-iκBα protein and the content of IL-10 were significantly decreased ( P<0.05) . Conclusion:Early nutritional intervention can inhibit inflammatory response, reduce intestinal injury and control the development of acute pancreatitis by regulating NF-κB signaling pathway.
9.Clinical significance of infiltration of M2 tumor-associated macrophage in hepatocellular carcinoma
Feng XIAO ; Jingwen XIAO ; Haiyan ZHANG ; Chunyan GU
Chinese Journal of Digestion 2023;43(5):327-332
Objective:To investigate the distribution of M2 tumor-associated macrophage (TAM) in hepatocellular carcinoma (HCC) and their correlation with clinicopathological features, and the significance of programmed death-ligand 1 (PD-L1) expression.Methods:From January 1, 2012 to December 31, 2020, a total of 320 HCC patients who underwent surgical resection at the Third People′s Hospital of Nantong were included. The distribution of CD163 labeled and PD-L1 CD163 double-labeled M2 TAM in HCC tissues was detected by immunohistochemistry, and the cell density was calculated. The cell density> the average cell density (112/mm 2) was judged as high-density, the cell density≤ the average cell density was judged as low-density. The correlation between CD163 positive and PD-L1 CD163 double positive M2 TAM density and the clinical pathological characteristics of HCC and its impact on prognosis were analyzed. Chi-square test was used to analyze the correlation between M2 TAM expression and the clinical pathological characteristics of HCC. Kaplan-Meier method was used to draw survival curves, and log-rank test was used for inter group comparison. Univariate and multivariate Cox proportional hazards regression analysis was used to indentify the relevant factors affecting the prognosis of HCC. Results:TAM were mainly distributed in the tumor edge stroma and tumor sinusoids, CD163 positive M2 TAM were the main macrophage subtype. PD-L1 expression was observed in CD163 positive M2 TAM in HCC tissues, and PD-L1 positive M2 TAM were mainly distributed in the tumor edge stroma. The rate of high-density CD163 positive M2 TAM in HCC tissues was 44.4% (142/320). High-density CD163 positive M2 TAM was correlated with histological grade, TNM stage, and PD-L1 expression on tumor infiltrating immune cells in HCC tissues ( χ2=4.65, 6.72 and 42.19, P=0.031, =0.011 and <0.001). High-density PD-L1 and CD163 double positive M2 TAM in HCC tissues was correlated with microvascular invasion and TNM stage ( χ2=11.96 and 8.74, P=0.001 and 0.004). The median disease-free survival (DFS) time and overall survival (OS) time of patients with high-density CD163 positive M2 TAM were 21 and 36 months, respectively, which were lower than those of patients with low-density CD163 positive M2 TAM (50 and 103 months, respectively); the median DFS time and OS time of patients with high-density PD-L1 CD163 double-positive M2 TAM were 12 and 15 months, respectively, which were lower than those of patients with low-density PD-L1 CD163 double-positive M2 TAM (28 and 45 months, respectively), and the differences were statistically significant (all log-rank tests, all P<0.001). The results of multivariate Cox proportional hazards regression analysis showed that high-density CD163 positive M2 TAM, microvascular invasion and high TNM stage were independent risk factors for evaluating DFS and OS of patients with HCC (DFS time: HR=2.408 (95% confidence interval (95% CI) 1.778 to 3.261), 2.603 (95% CI 1.860 to 3.641), 4.032 (95% CI 2.833 to 5.747), all P<0.001. OS time: HR=2.007 (95% CI 1.457 to 2.764), 4.144 (95% CI 2.881 to 5.960), 4.292 (95% CI 2.915 to 6.329), all P<0.001). Conclusions:High-density of CD163 positive M2 TAM in HCC tissues indicates high malignancy and poor prognosis, and it is an independent prognostic risk factor. The expression of PD-L1 in M2 TAM suggests stronger tumor aggressiveness and worse prognosis in HCC.
10.Application of Self-assembled Nano-strategies of Traditional Chinese Medicine in Tumor Therapy: A Review
Ju HUANG ; Yu ZHU ; Hang XIAO ; Songtao LI ; Jingwen LIU ; Qiao ZHENG ; Xiangrui MENG ; Jianyuan TANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(24):185-193
Chinese medicine self-assembly nano-strategies(CSAN) is to utilize the self-assembly property of Chinese medicine components, so that the Chinese medicine components can self-assemble to form structurally stable nano-preparations through non-covalent interactions. The formation of Chinese medicine self-assembly nano-preparations is often a synergistic result of a variety of non-covalent interactions, and many Chinese medicine monomers are susceptible to self-assembly due to their structural characteristics, and the phenomenon of self-assembly of Chinese medicine is also common in the decoction of single or compound Chinese medicine, which has attracted the attention of researchers. It is found that CSAN can improve the solubility and bioavailability of active components in Chinese medicine, which is of positive significance for the development and application of insoluble components of Chinese medicine. The self-assembly phenomenon of Chinese medicine decoction is closely related to the therapeutic efficacy, and the study of self-assembly phenomenon of Chinese medicine will bring a new perspective for the explanation of the mechanism of Chinese medicine decoction. At the same time, traditional Chinese medicine(TCM) has unique advantages in the field of anti-tumor. The application of CSAN in the field of oncology can not only exert the anti-tumor effect of the active components of Chinese medicine directly, but also act as a natural nano-carrier to carry chemotherapy drugs for combination chemotherapy, improve the targeting of drugs, enhance the anti-tumor efficacy, and reduce the side effects of chemotherapy, which has excellent anti-tumor potential. The preparation method of Chinese medicine self-assembly nano-preparations is simple, low cost, and has better safety than traditional nano-preparations, which is conducive to the promotion of the clinical transformation of nano-preparations, and also helps to provide new strategies and perspectives for promoting the modernization of TCM. Therefore, based on a large number of researches in this field in recent years, this paper reviewed the formation mechanism, different assembly forms, formation conditions and stability of Chinese medicine self-assembly nano-preparations by searching databases such as China national knowledge infrastructure(CNKI), PubMed, WanFang data and VIP, and summarized the application of CSAN in different tumor therapies, providing a reference for further research on CSAN.

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