1.Pathogenesis, progression and treatment of biliary fibrosis
Jinyu ZHAO ; Yanyan LIN ; Ping YUE ; Jia YAO ; Ningning MI ; Matu LI ; Wenkang FU ; Long GAO ; Azumi SUZUKI ; F Peng WONG ; Kiyohito TANAKA ; Rungsun RERKNIMITR ; H Henrik JUNGER ; T Tan CHEUNG ; Emmanuel MELLOUL ; Nicolas DEMARTINES ; W Joseph LEUNG ; Jinqiu YUAN ; J Hans SCHLITT ; Wenbo MENG
Chinese Journal of Digestive Surgery 2024;23(7):989-1000
Biliary fibrosis (BF) is the result of pathological repair of bile tract injury, characterized by thickening and sclerosis of the bile duct wall and progressive stricture of the lumen, which may ultimately lead to serious adverse outcomes such as biliary obstruction, biliary cirrhosis, liver failure, and hepatobiliary malignancies. Current research describes BF as a pathological feature of certain bile tract diseases, lacking a systematic summary of its etiology, pathophysiology, molecular mechanisms, and treatment. BF is a common but easily neglected disease state in biliary system, which may promote the development and progression of hepatobiliary diseases through abnormal repair mechanism after pathological biliary tract injury. Based on the latest research progress from both domestic and international perspectives, the authors review the concept, clinical manifestation, etiology, pathogenesis, and therapeutic strategies of BF to provide a reference for clinical physicians.
2.Targeting the chromatin structural changes of antitumor immunity
Li NIAN-NIAN ; Lun DENG-XING ; Gong NINGNING ; Meng GANG ; Du XIN-YING ; Wang HE ; Bao XIANGXIANG ; Li XIN-YANG ; Song JI-WU ; Hu KEWEI ; Li LALA ; Li SI-YING ; Liu WENBO ; Zhu WANPING ; Zhang YUNLONG ; Li JIKAI ; Yao TING ; Mou LEMING ; Han XIAOQING ; Hao FURONG ; Hu YONGCHENG ; Liu LIN ; Zhu HONGGUANG ; Wu YUYUN ; Liu BIN
Journal of Pharmaceutical Analysis 2024;14(4):460-482
Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.
3.Effect of honey on bowel preparation before colonoscopy
Jie PAN ; Shaoli GE ; Yao WANG ; Zhonghua LIN ; Yujiao LIN ; Ningning MAO ; Rongrong HAN ; Jianqing SUI
China Journal of Endoscopy 2024;30(9):33-40
Objective To explore the clinical effect of honey in preoperative bowel preparation for colonoscopy in hospitalized patients.Methods 87 patients from April 2022 to July 2022 and underwent preoperative bowel preparation for colonoscopy were selected as the research subjects.Convenience sampling was used to divide them into a control group(n=43)and an observation group(n=44).The control group received a conventional regimen of taking compound polyethylene glycol(PEG)electrolyte powder(Heshuang),while the observation group added 20 mL of honey to the Heshuang solution.Compare the cleanliness of intestine,and palatability of the taste,the incidence of adverse reactions,satisfaction of patients,and the rate of willingness for prepeat bowel preparation between the two groups.Results The intestinal cleanliness of the two groups of patients was equivalent,the difference was not statistically significant(P>0.05).The incidence and severity of nausea,abdominal bloating,hypoglycemia,and anal irritation in the observation group were lower than those in the control group,the differences were statistically significant(P<0.05).The observation group had better taste,patients satisfaction,and the willingness for prepeat bowel preparation compared to the control group,the differences were statistically significant(P<0.05).Conclusion Honey can improve the taste of Heshuang,reduce the severity of oral adverse reactions,increase patient satisfaction,and increase the rate of willingness for prepeat bowel preparation.
4.Hemodynamic study of patients with early allograft dysfunction after liver transplantation
Mingyang WANG ; Ying TANG ; Weina KONG ; Ningning NIU ; Guoying ZHANG ; Tianchi WANG ; Yao YUAN ; Jing LIU
Chinese Journal of Ultrasonography 2023;32(7):608-613
Objective:To explore the characteristics of postoperative hemodynamic changes in patients with early allograft dysfunction (EAD), and to provide clinical imaging support for the early diagnosis of EAD.Methods:A total of 907 patients who underwent liver transplantation in Tianjin First Central Hospital from December 2012 to June 2021 were retrospectively selected, and they were divided into EAD group (361 cases) and non-EAD group (546 cases) according to EAD diagnostic criteria. The peak systolic velocity(PSV) of the hepatic artery, end-diastolic velocity(EDV) of the hepatic artery, resistance index(RI), S/D(PSV/EDV), diameter of the portal vein(PVD), velocity of the portal vein(PVV), diameter of the middle hepatic vein(MHVD), velocity of the middle hepatic vein(MHVV), the diameter of the right hepatic vein(RHVD), and the velocity of the right hepatic vein (RHVV) were collected from 1 to 7 days after operation (a total of 5 573 ultrasound examination results), and the differences in ultrasound hemodynamic parameters were compared between the two groups. The correlation of S/D<2, PSV<25 cm/s, PVV<15 cm/s, MHVV or RHVV<15 cm/s within 3 days after operation with the occurence of EAO were analyzed by multivariate Logistic regression analysis.Results:①The PSV and EDV of the hepatic artery in the EAD group and the non-EAD group showed a slow upward trend at 1-7 days after operation, while the hepatic artery RI and PVV showed a downward trend, the MHVV and RHVV did not fluctuate significantly. ②The hepatic artery in the EAD group showed low-resistance blood flow in the early postoperative period, and the EDV were significantly higher than that in the non-EAD group on 1 d, 2 d, 3 d and 5 d, RI was significantly lower than that of the non-EAD group (all P<0.05); At 4 d, 6 d and 7 d, there was no significant differences of EDV and RI between the two groups(all P>0.05). The PSV of the EAD group was higher than that of the non-EAD group on 3 d ( P<0.05). Among the parameters of portal vein blood flow, the PVV in the EAD group was significantly higher than that in the non-EAD group on 1 d ( P<0.05), and there was no significant difference of PVD between the two groups at day 1-7. Among the parameters of hepatic venous blood flow, the MHVV and RHVV in the EAD group were significantly lower than those in the non-EAD group (all P<0.05), there was no significant difference between the two groups of MHVD and RHVD at 1-7 days. ③The incidence of grafted hepatic artery S/D<2 within 3 days after operation in EAD group was higher than that in non-EAD group. Binary Logistic regression multivariate analysis showed that the occurrence of grafted hepatic artery S/D<2 within 3 days after operation was significantly correlated with the occurrence of EAD[Exp(B)=1.878, P<0.05]. Conclusions:Patients who develop EAD after liver transplantation show low-resistance blood flow in the hepatic artery during the perioperative period, and the occurrence of hepatic artery S/D<2 within 3 days after operation can early predict the occurrence of EAD.
5.The value of radiomics for individualized prophylactic cranial irradiation in limited-stage small cell lung cancer
Qing HOU ; Lijuan WEI ; Ningning YAO ; Bochen SUN ; Yu LIANG ; Xin CAO ; Yan TAN ; Jianzhong CAO
Chinese Journal of Radiation Oncology 2023;32(1):8-14
Objective:To investigate the predictive value of enhanced CT-based radiomics for brain metastasis (BM) and selective use of prophylactic cranial irradiation (PCI) in limited-stage small cell lung cancer (LS-SCLC).Methods:Clinical data of 97 patients diagnosed with LS-SCLC confirmed by pathological and imaging examination in Shanxi Provincial Cancer Hospital from January 2012 to December 2018 were retrospectively analyzed. The least absolute shrinkage and selection operator (LASSO) Cox and Spearman correlation tests were used to select the radiomics features significantly associated with the incidence of BM and calculate the radiomics score. The calibration curve, the area under the receiver operating characteristic (ROC) curve (AUC), 5-fold cross-validation, decision curve analysis (DCA), and integrated Brier score (IBS) were employed to evaluate the predictive power and clinical benefits of the radiomics score. Kaplan-Meier method and log-rank test were adopted to draw survival curves and assess differences between two groups.Results:A total of 1272 radiomics features were extracted from enhanced CT. After the LASSO Cox regression and Spearman correlation tests, 8 radiomics features associated with the incidence of BM were used to calculate the radiomics score. The AUCs of radiomics scores to predict 1-year and 2-year BM were 0.845 (95% CI=0.746-0.943) and 0.878 (95% CI=0.774-0.983), respectively. The 5-fold cross validation, calibration curve, DCA and IBS also demonstrated that the radiomics model yielded good predictive performance and net clinical benefit. Patients were divided into the high-risk and low-risk cohorts based on the radiomics score. For patients at high risk, the 1-year and 2-year cumulative incidence rates of BM were 0% and 18.2% in the PCI group, and 61.8% and 75.4% in the non-PCI group, respectively ( P<0.001). In the PCI group, the 1-year and 2-year overall survival rates were 92.9% and 78.6%, and 85.3% and 36.8% in the non-PCI group, respectively ( P=0.023). For patients at low risk, the 1-year and 2-year cumulative incidence rates of BM were 0% and 0% in the PCI group, and 10.0% and 20.2% in the non-PCI group, respectively ( P=0.062). In the PCI group, the 1-year and 2-year overall survival rates were 100% and 77.0%, and 96.7% and 79.3% in the non-PCI group, respectively ( P=0.670). Conclusion:The radiomics model based on enhanced CT images yields excellent performance for predicting BM and individualized PCI.
6.Construction and application of the public health practice teaching model of "internal-external interactions"
Qiujuan LI ; Xiance SUN ; Xiaoxia SHI ; Jun CAO ; Ningning WANG ; Rui LI ; Xiaofeng YAO
Chinese Journal of Medical Education Research 2023;22(6):838-842
Practice teaching is an important link in the training of public health talents in colleges and universities. At present, there are still some problems in the education of public health and preventive medicine in the colleges and universities in China, such as attaching greater importance to theory than to practice and weak training of practical skills among students. In view of this situation, a public health practice teaching model of "internal-external interactions" has been constructed in Dalian Medical University with focuses on the following aspects: ①experiments in the university are optimized based on social needs; ②the practice base outside the university is expanded based on the teaching in the university; ③"internal-external interactions" are adopted to enhance practice training and improve post competence. The teaching practice shows that the implementation of the teaching model of "internal-external interactions" can help to improve practice teaching ability, promote the improvement in the training quality of public health talents, and meet the social demand for application-oriented professionals.
7.Value of derived neutrophil-to-lymphocyte ratio in predicting prognosis of extensive-stage small cell lung cancer patients treated with the first-line atezolizumab immunotherapy and chemotherapy
Jinfeng GUO ; Qing HOU ; Ningning YAO ; Bochen SUN ; Yu LIANG ; Xin CAO ; Jianzhong CAO
Cancer Research and Clinic 2023;35(9):658-663
Objective:To investigate the value of derived neutrophil-to-lymphocyte ratio (dNLR) in predicting the prognosis of extensive-stage small cell lung cancer (ES-SCLC) patients treated with the first-line atezolizumab immunotherapy and chemotherapy.Methods:From the Project Data Sphere platform, the clinical data and laboratory test data of 53 ES-SCLC patients who received the first-line atezolizumab immunotherapy and chemotherapy in the global multicenter phase Ⅱ prospective study NCT03041311 from February 2017 to February 2022 were collected. The Contal-O'Quigley method was used to calculate the optimal cut-off value of baseline dNLR for determining the overall survival (OS) of patients. The dNLR higher than or equal to the optimal cut-off value was defined as high dNLR, and less than the optimal cut-off value was defined as low dNLR. According to optimal cut-off value, the dNLR levels at baseline and after 4 cycles of chemotherapy were determined, and dynamic dNLR grouping was performed (low risk: low dNLR at baseline and after 4 cycles of chemotherapy; intermediate risk: high dNLR at baseline or after 4 cycles of chemotherapy; high risk: high dNLR at baseline and after 4 cycles of chemotherapy). The differences in clinicopathological features between the baseline high dNLR group and low dNLR group were analyzed. Kaplan-Meier method was used to draw the OS and progression-free survival (PFS) curves, and log-rank test was used to compare the differences between the two groups. Univariate Cox proportional hazards model was used to analyze the influencing factors of OS and PFS. The time-dependent receiver operating characteristic (ROC) curve was used to evaluate the predictive value of baseline dNLR grouping and dynamic dNLR grouping for 1-year OS rate in ES-SCLC patients receiving the first-line atezolizumab immunotherapy and chemotherapy.Results:Among the 53 patients, 34 (64.20%) were male and 19 (35.80%) were female; 27 (50.90%) were < 65 years old and 26 (49.10%) were ≥65 years old. The optimal cut-off value of baseline dNLR for determining the OS was 1.79. There were 17 cases in low dNLR group and 36 cases in high dNLR group at baseline. The proportion of patients with elevated serum lactate dehydrogenase (LDH) in the baseline high dNLR group was higher than that in the baseline low dNLR group [58.33% (21/36) vs. 17.65% (3/17), χ2 = 7.72, P = 0.005]. The 1-year OS rates of the baseline high and low dNLR groups were 44.0% and 81.9%, and the 1-year PFS rates were 2.5% and 17.6%. The differences in OS and PFS between the two groups were statistically significant (both P < 0.05). There were 38 patients with complete dynamic dNLR data, including 9 cases of low-risk, 19 cases of medium-risk and 10 cases of high-risk, and the 1-year OS rates of the three groups were 90.0%, 67.5% and 33.3%, the difference in OS between the three groups was statistically significant ( P = 0.011). Univariate Cox regression analysis showed that baseline dNLR (low dNLR vs. high dNLR) was the influencing factor for OS of patients ( HR = 0.163, 95% CI 0.057-0.469, P = 0.001) and PFS ( HR = 0.505, 95% CI 0.268-0.952, P = 0.035). Time-dependent ROC curve analysis showed that the area under the curve (AUC) of baseline dNLR grouping and dynamic dNLR grouping for predicting 1-year OS rate of ES-SCLC patients receiving the first-line atezolizumab combined with chemotherapy was 0.674 (95% CI 0.575-0.887) and 0.731 (95% CI 0.529-0.765). Conclusions:Baseline and dynamic dNLR grouping may be effective markers for predicting the prognosis of ES-SCLC patients receiving the first-line atezolizumab immunotherapy and chemotherapy.
8.Normal reference range of ultrasound hemodynamics in adult liver transplantation from big data and the analysis of the influencing factors: a single-center retrospective study
Ningning NIU ; Ying TANG ; Mingyang WANG ; Yao YUAN ; Huimin YU ; Guoying ZHANG
Chinese Journal of Ultrasonography 2022;31(10):865-871
Objective:To obtain the normal reference range of ultrasound hemodynamic parameters after liver transplantation through big data query and statistical analysis, and to analyze its influencing factors.Methods:The clinical liver transplantation Ultrasound Image Database Software V1.0 developed by Tianjin First Center Hospital was used to query adult patients after liver transplantation from December 2012 to June 2021. The ultrasonic hemodynamic parameters including the diameter of portal vein (PVD), the flow velocity of portal vein (PVV), the peak flow velocity of hepatic artery (S), the end diastolic flow velocity of hepatic artery (D), the S/D of hepatic artery, the resistance index of hepatic artery (RI), the diameter of middle hepatic vein (MHVD), the flow velocity of middle hepatic vein (MHVV), the diameter of right hepatic vein (RHVD), the flow velocity of right hepatic vein (RHVV), in the first day (1D), the seventh day (7D), the first month (1M), the sixth month (6M), the first year (1Y), the fifth year (5Y) and the tenth year (10Y) after operation were analyzed statistically, and the 95% reference value range of each parameter was obtained.Results:A total of 1 740 patients with 12 242 monitoring results after adult liver transplantation were included, and the longest follow-up time was 22 years. There was no significant change in PVD. PVV decreased slightly from postoperative 1D to long-term follow-up. The S and D of hepatic artery were the highest in group 7D after liver transplantation, and then decreased gradually with the extension of postoperative time. Hepatic artery S/D was the lowest in group 7D after operation, with the extension of monitoring time after liver transplantation, it showed an upward trend, but fluctuated. Hepatic artery RI was the highest in postoperative 1D group, and fluctuated with the extension of monitoring time after liver transplantation. There was no significant change in MHVD and RHVD.MHVV and RHVV were the highest in group 7D after liver transplantation, with the extension of postoperative monitoring time, they showed a decreasing trend and fluctuated. The normal range of each parameter was estimated according to the range of 95% medical reference value. The influencing factors of blood flow monitoring of transplanted liver were analyzed, including the various factors in perioperative period, the surgery, the primary disease before operation, the source of donor, the postoperative infection, rejection, drug damage, individual differences and so on.Conclusions:This study obtains the trend of each parameter with the extension of follow-up time and the reference value range of each parameter after liver transplantation, which is of great clinical significance for early detection and diagnosis of postoperative vascular complications. However, the blood flow after adult liver transplantation is affected by many factors. In clinical monitoring, it is necessary to make judgment combined with the individual state of patients and conduct dynamic follow-up.
9.Value of pretreatment albumin in prognostic assessment of extranodal nasal type NK/T cell lymphoma
Yu LIANG ; Hongwei LI ; Qing HOU ; Xin CAO ; Ningning YAO ; Bochen SUN ; Jianzhong CAO
Cancer Research and Clinic 2022;34(4):281-286
Objective:To explore the prognostic value of pretreatment albumin in extranodal nasal type NK/T cell lymphoma (ENKTL).Methods:The clinical data of 184 ENKTL patients in Shanxi Province Cancer Hospital from January 2002 to December 2018 were retrospectively analyzed. The Contal-O'Quigley change point method was used to determine the optimal cut-off value of albumin for predicting the prognosis of patients. The propensity score matching (PSM) was used to minimize selection biases. The Kaplan-Meier method was used for survival analysis, and Cox proportional hazards model was used to determine the factors affecting survival. The time-dependent receiver operating characteristic curve, Akaike information criterion and integrated Brier score were used to evaluate the efficacy of international prognostic index (IPI), Korean prognostic index (KPI) and prognostic index of NK cell lymphoma (PINK) models incorporating albumin for predicting the prognosis of patients.Results:The optimal cut-off value of pretreatment albumin for predicting the prognosis of ENKTL patients was 37.5 g/L. The 3-year and 5-year overall survival (OS) rates in >37.5 g/L group (126 cases) were 66.2% and 60.3%, and the progression-free survival (PFS) rates were 58.8% and 49.6%; the 3-year and 5-year OS rates in ≤37.5 g/L group (58 cases) were 35.0% and 32.4%, and the PFS rates were 32.5% and 30.0%. The OS and PFS in > 37.5 g/L group were better than those in ≤37.5 g/L group (both P<0.001). After PSM, the OS and PFS in >37.5 g/L group were still better than those in ≤37.5 g/L group (both P = 0.002). Multivariate analysis showed that albumin was an independent influencing factor for OS ( RR = 0.419, 95% CI 0.266-0.660, P < 0.001) and PFS ( RR = 0.493, 95% CI 0.322-0.755, P < 0.001). After PSM, albumin was still an independent influencing factor for OS ( RR = 0.305, 95% CI 0.156-0.598, P = 0.001) and PFS ( RR = 0.341, 95% CI 0.185-0.627, P = 0.001). The prognostic prediction performance of the IPI, KPI and PINK models incorporating albumin were all improved. Conclusions:Pretreatment albumin is an important prognostic indicator for ENKTL.
10.Efficacy analysis of hypofractionated intensity-modulated radiation therapy combined with hormonal therapy for pelvic lymph node metastatic prostate cancer
Lihong YAO ; Yueping LIU ; Yexiong LI ; Shulian WANG ; Jing JIN ; Hui FANG ; Yongwen SONG ; Yu TANG ; Yuan TANG ; Yong YANG ; Shunan QI ; Bo CHEN ; Ningning LU ; Zihao YU
Chinese Journal of Radiation Oncology 2021;30(1):42-46
Objective:To investigate the efficacy and prognosis of hypofractionated intensity-modulated radiation therapy combined with hormonal therapy in the treatment of pelvic lymph node metastatic prostate cancer.Methods:Clinical data of 42 IV A prostate cancer patients who received hypofractionated intensity-modulated radiation therapy combined with hormonal therapy in Cancer Hospital of Chinese Academy of Medical Sciences between 2006 and 2018 were retrospectively analyzed. The total irradiation doses to the prostate and seminal vesicles were 67.5 Gy/25f, 2.7 Gy/f. The prophylactic irradiation doses to the pelvic lymph nodes were 45-50 Gy with a daily fraction dose of 1.8-2.0 Gy. Thirty-three patients with residual lymph nodes were boosted to 60.0-67.5 Gy for the residual area, 2.4-2.7 Gy/f. Androgen deprivation therapy included surgical castration or luteinizing hormone-releasing hormone agonists combined with antiandrogens. Survival rate was calculated using Kaplan- Meier method. The differences between two groups were analyzed by log-rank test. Prognostic factors were identified by univariate and multivariate analyses. Results:The median follow-up was 65.5 months (range, 5 to 150 months). The 5-year and 10-year failure-free survival (FFS) rates in the whole group were 67% and 45%, respectively. No clinical recurrence was observed in the irradiation field. The 5-year and 10-year prostate cancer-specific survival/overall survival (PCSS/OS) rates were 85% and 60%, respectively. Gleason score (≥8 and<8) and duration of hormonal therapy impacted the FFS (both P<0.05). The duration of hormonal therapy was an independent prognostic factor for PCSS/OS ( P=0.003). Conclusions:Hypofractionated intensity-modulated radiotherapy combined with hormonal therapy yields optimistic clinical efficacy in the treatment of pelvic lymph node metastatic prostate cancer. Gleason score (≥8 and <8) and duration of hormonal therapy are critical prognostic factors.

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