1.The inhibitory effect of artesunate on hepatocellular carcinoma cells by regulating expression of GADD45A and NACC1
Guan-Tong SHEN ; Jin-Yao DONG ; Jing FENG ; Nan QIN ; Gen-Lai DU ; Fei ZHU ; Ke LIAN ; Xin-Yu LIU ; Qing-Liang LI ; Xun-Wei ZHANG ; Ru-Yi SHI
Chinese Pharmacological Bulletin 2024;40(6):1089-1097
Aim To explore the effect and mechanism of the artesunate(ART)on hepatocellular carcinoma(HCC).Methods The cell lines MHCC-97H and HCC-LM3 were used to be detected.MTT and clone formation were used to determine the cell proliferation;Wound healing was used to detect the cell migration;Transwell was used to test the cell invasion.Flow-cy-tometry was used to detect cell apoptosis and cell cy-cle.RNA-seq and qRT-PCR was used to detect the genes expression.Results The proliferation,migra-tion and invasion of treated cells were obviously inhibi-ted(P<0.01).Moreover,the apoptosis rate in-creased significantly,so did the proportion of G2/M cells.Transcriptomic analysis identified GADD45A as a potential target of ART through RNA-sequencing da-ta,and suggested that ART might induce apoptosis and cell cycle arrest through regulating the expression of GADD45A.In addition,the results of mechanism studies and signaling analysis suggested that GADD45A had interaction with its upstream gene NACC1(nucle-us accumbens associated 1).Moreover,after ART treatment,the expressions of GADD45A and NACC1 were changed significantly.Conclusion ART may be a potential drug to resist HCC by affecting the expres-sion of GADD45A and its upstream gene NACC1,which provides a new drug,a new direction and a new method for the clinical treatment of HCC.
2.Differential Diagnosis of Conventional Ultrasound in Ureteral Polyps and Ureteral Carcinoma via Continuous Observation
Liang MU ; Hao CHEN ; Shuliang NAN ; Li LIU ; Xiangping GUAN ; Qiuyang LI
Chinese Journal of Medical Imaging 2024;32(6):610-615
Purpose To evaluate the differential diagnostic value of conventional ultrasound in the ureteral polyps and ureteral carcinoma via continuous observation.Materials and Methods The conventional ultrasound of patients with ureteral polyps and ureteral carcinoma treated in Shaanxi Provincial People's Hospital were retrospectively analyzed from June 2015 to June 2022.According to the pathological results,all participants were divided into the ureteral polyp group(98 cases)and the ureteral carcinoma group(151 cases).All clinical and ultrasound data were recorded,and the differences of echo,blood flow and peristalsis were compared between the two groups.Results There were significant differences in ureteral peristalsis,color Doppler flow distribution,periureteral tissue thickening,increased echo,and hydronephrosis(χ2=197.50,138.89,26.97,36.13,all P<0.05)between the two groups.Low echo was predominant in both groups[67(68.37)vs.114(75.50)],with no significant difference(χ2=1.52,P>0.05).In the ureteral polyp group,67 cases were found in the upper ureter,89 cases were observed continuously with common peristalsis,and 73 cases with color blood flow were mostly central blood flow,while in the ureteral cancer group,85 cases were found in the middle and lower ureter,148 cases showed almost no peristalsis,and 122 cases with color blood flow were mostly peripheral blood flow.Conclusion There are some differences in clinical features such as the location as well as whether hydronephrosis between ureteral polyps and carcinoma.Peristalsis can provide the differential diagnosis for ureteral polyps and ureteral carcinoma via continuous observation.
3.Methodological establishment of PTV and PRV margins for MRI guided online adapt-to-position radiotherapy for intracranial tumors
Qiu GUAN ; Nan LIU ; Xin LIAN ; Tingting DONG ; Yunliang SUN ; Hao LIANG ; Wei TIAN ; Lang YU ; Bo YANG ; Jie QIU
Chinese Journal of Radiation Oncology 2024;33(12):1106-1111
Objective:To establish a method for obtaining planning target volume (PTV) and planning risk volume (PRV) margins caused by rotation in the use of adapt-to-position (ATP) modality of magnetic resonance linear accelerator (MRL) for patients with intracranial tumors.Methods:Clinical data of 6 patients with intracranial tumors (150 fractions in total) who received MRI-guided online ATP radiotherapy in Peking Union Medical College Hospital from November 2023 to January 2024 were retrospectively analyzed. The pre-planned CT structure was copied onto each segmented MR image and then the structures were traced back to the CT image according to the three-dimensional registration relationship. The anisotropic distance of the structure based on the original CT structure was calculated to obtain the variation range of the target and the organs at risk. The maximum anisotropic value was taken as the result of the PTV and the relationship between the results and intracranial location of different patients was analyzed. Group comparison was performed by Chi-square test. Two group comparison was conducted by post-hoc Wilcoxon signed-rank test. Results:After the rotation deviation was included, the range of target changes in the six directions of left and right (L/R), anterior and posterior (A/P) and superior and inferior (S/I) of the 6 patients were: (1.24± 0.86) mm/(1.91± 1.07) mm, (2.02± 1.26) mm/(1.66± 1.07) mm, (1.84± 1.84) mm /(2.94±1.93) mm, respectively. The results in the SI direction were significantly different, and the values in the I direction in 2 patients exceeded 4 mm, the margins suitable for all patients were 3.01 mm/2.4 mm(A/P), 1.9 mm/2.93 mm(L/R) and 3.14 mm/4.62 mm(S/I) in different directions, respectively. The L/R direction of the lens and the S/I direction of the optic nerve were significantly changed, and the A/P direction of the brain stem was (3.99± 4.64) mm. Larger values might be required when the target was in the posterior brain (left-down area, right-down area).Conclusions:The rotation deviation, organ movement and intracranial location affect the PTV and the organs at risk PRV in the MRI-guided ATP modality in intracranial tumors patients. The margin generation method based on image fusion can help to quantify the margin value reasonably.
4.Effect of Gegen Qinliantang on SIRT1/FoxO1 Autophagy Pathway in db/db Diabetic Mice
Yuanyuan ZHANG ; Xiangdong ZHU ; Lihui FAN ; Fei SU ; Xiaowen GUAN ; Yanhui ZHAI ; Liren CAO ; Nan ZHOU ; Minfeng HUO ; Jianqing LIANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(14):30-37
ObjectiveTo validate the alleviating effect of Gegen Qinliantang (GGQLT) on insulin resistance in db/db diabetic mice by regulating the silent information regulator 1 (SIRT1)/forkhead transcription factor O1 (FoxO1) autophagy pathway. MethodSeventy-five SPF-grade spontaneous type 2 diabetic db/db mice and 15 control db/m mice were selected and maintained on regular feed for one week before measuring blood glucose. They were randomly divided into six groups, with 15 mice in each group. The groups included a normal group (physiological saline, 0.2 g·kg-1), a metformin group (0.2 g·kg-1), high-, medium-, and low-dose GGQLT groups (31.9, 19.1, 6.9 g·kg-1), and a model group (physiological saline, 0.2 g·kg-1). They were orally treated with corresponding drugs for eight weeks, once daily. Fasting blood glucose (FBG) was measured using a Roche glucometer. Serum levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and total cholesterol (TC) were measured using an automated biochemical analyzer. Fasting serum insulin (INS) levels were determined using enzyme-linked immunosorbent assay (ELISA), and the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Western blot was used to detect the expression of Beclin-1, microtubule-associated protein 1 light chain 3 (LC3), and SIRT1/FoxO1 autophagy pathway-related proteins in liver tissues. Immunohistochemistry was performed to assess the expression of SIRT1, FoxO1, Beclin-1, and LC3B proteins in liver tissues. Transmission electron microscopy was used to observe the formation of autophagosomes in the liver. ResultCompared with the normal group, the model group showed significant increases in FBG, FINS, HOMA-IR, TC, TG, LDL-C, and HDL-C levels (P<0.01), and significant increases in the expression of SIRT1, Beclin-1, LC3, and FoxO1 proteins in liver tissues (P<0.01). Transmission electron microscopy revealed the highest number of autophagosomes in the model group. Compared with the model group, the metformin group and the low-, medium-, and high-dose GGQLT groups showed significant decreases in serum FBG, FINS, HOMA-IR, TC, TG, LDL-C, and HDL-C levels (P<0.05, P<0.01), significant decreases in the expression of SIRT1, Beclin-1, LC3 (P<0.05, P<0.01), and up-regulated FoxO1 protein (P<0.01). Transmission electron microscopy showed a reduction in the degree of autophagy in the treatment groups. Compared with the metformin group, the medium- and high-dose GGQLT groups showed significant decreases in FBG, FINS, and TG levels (P<0.01), significant decreases in the expression of SIRT1, Beclin-1, and LC3 in liver tissues (P<0.05, P<0.01), and reduced FoxO1 protein (P<0.01). The high-dose GGQLT group showed reduced HOMA-IR, TC, LDL-C, and HDL-C levels (P<0.05, P<0.01). Transmission electron microscopy revealed a significant reduction in autophagosomes in the medium- and high-dose GGQLT groups. ConclusionGGQLT can significantly improve glucose and lipid metabolism disorders, alleviate insulin resistance in db/db mice, and prevent and treat type 2 diabetes by activating the SIRT1/FoxO1 autophagy pathway.
5.Predictive value of ALBI combined with in severe acute pancreatitis
Xueqi LI ; Nan LIANG ; Lan GUAN ; Zhaoxing TIAN
Chinese Journal of Emergency Medicine 2023;32(10):1340-1345
Objective:To analyze the predictive value of serological measures within 24 hours of admission in acute pancreatitis patients against patients with severe acute pancreatitis(SAP), because the severity of acute pancreatitis was characterized by a timely assessment and prediction by emergency department physicians upon visit.Methods:A total of 119 acute pancreatitis patients admitted in Emergency Department in Beijing Jishuitan Hospital, Capital Medical University from January 2022 to December 2022 were retrospectively collected. According to the revised Atlanta classification, patients were characterized by mild acute pancreatitis group (77 cases), moderately severe acute pancreatitis group (27 cases), and SAP group (15 cases). Basic characteristics, early disease severity scores and early serological indexes of the three groups were compared, independent risk factors of serological indexes affecting the occurrence of SAP were analyzed, and receiver operator characteristic curve was drawn, evaluate the predictive value of related serological indexes for SAP.Results:There were no significant differences in the basic characteristics of the three groups including of gender, age, BMI, type of pancreatitis and complications ( P>0.05), but there were significant differences in early BISPA, Ranson, APACHEⅡ and Panc3 scores among the three groups ( P<0.05).Albumin-bilirubin score ( OR=3.653, 95% CI 1.665-8.012, P=0.001), blood urea nitrogen ( OR=1.117, 95% CI 1.039-1.202, P=0.003) were independent risk factors for SAP. The areas under ROC curve predicted by albumin-bilirubin score, blood urea nitrogen and albumin-bilirubin score combined with blood urea nitrogen were 0.762, 0.776 and 0.857, respectively, which showed no statistical difference compared with earlier Ranson, BISAP and APACHE Ⅱ scoring systems, respectively ( P>0.05). Conclusions:Early albumin-bilirubin score and blood urea nitrogen indexes of acute pancreatitis patients have good predictive value for SAP. Albumin-bilirubin score combined with blood urea nitrogen can improve the predictive value of SAP, and the predictive effect is as good as early Ranson, BISAP and APACHEⅡ scoring systems.
6.The practical value of conventional ultrasound combined with contrast-enhanced ultrasound in the diagnosis of urothelial carcinoma of the renal pelvis in elderly patients
Liang MU ; Jiaojiao XU ; Shuliang NAN ; Jiancheng ZHOU ; Wanli DUAN ; Hao CHEN ; Xiangping GUAN ; Li LIU
Chinese Journal of Geriatrics 2023;42(11):1314-1319
Objective:To assess the combination of conventional ultrasound with contrast-enhanced ultrasound(CEUS)in the diagnosis of urothelial carcinoma(UC)of the renal pelvis in elderly patients.Methods:Sixty-seven elderly patients with a histopathologic diagnosis of UC of the renal pelvis and surgically treated at our hospital between April 2015 and March 2023 were retrospectively analyzed.Characteristics of regular preoperative 2D ultrasound, color Doppler flow imaging(CDFI)and CEUS were examined.Results:Of 67 patients, 49(73.13%)were found to have localized lesions in the renal pelvis and renal calyces.Lesions in 53 patients(79.10%)could be clearly identified by conventional ultrasound, with 46(86.79%)being isoechoic or hypoechoic, and 7(13.21%)being hyperechoic.Analysis of tumor blood flow by CDFI found 22 cases(41.51%)with avascular lesions, 21(39.62%)with hypovascular lesions and 10(18.87%)with hypervascular lesions.The average value of the resistance index(RI)was 0.64.Enhancement was seen in 62 lesions(92.54%)by CEUS after injection of SonoVue.Compared with the cortex of the ipsilateral kidney, a slow enhancement pattern was observed in 46(74.19%), 14(22.58%)showed simultaneous enhancement, and 2(3.23%)showed fast enhancement.At peak enhancement, 43 lesions(69.35%)had hypo-enhancement, 10(16.13%)had iso-enhancement, and 9(14.52%)had hyper-enhancement, compared with the cortex.Concerning the homogeneity of enhancement, 16(25.81%)displayed heterogeneous enhancement, with tumor necrosis or hemorrhage, and 46(74.19%)had homogeneous enhancement.When the contrast agent washout rate was assessed, a fast washout pattern was observed in 53(85.48%), synchronous washout in 6(9.68%), and slow washout in 3(4.84%).Conclusions:UC of the renal pelvis mostly shows isoechoic and hypoechoic lesions on conventional ultrasound, avascular or hypo-vascular lesions on CDFI, and slow-in, fast-out and hypo-enhancement on CEUS, compared with the cortex.Conventional ultrasound combined with CEUS can help improve the diagnostic accuracy of UC of the renal pelvis.
7.Risk factors of systemic allergic reactions caused by subcutaneous allergen immunotherapy.
Li Sha LI ; Kai GUAN ; Jia YIN ; Liang Lu WANG ; Yu Xiang ZHI ; Jin Lü SUN ; Hong LI ; Li Ping WEN ; Rui TANG ; Jian Qing GU ; Zi Xi WANG ; Le CUI ; Ying Yang XU ; Sai Nan BIAN
Chinese Journal of Preventive Medicine 2023;57(12):1972-1977
Objective: To investigate the incidence and risk factors of systemic allergic reactions induced by subcutaneous immunotherapy (SCIT) in patients undergoing SCIT injections in Peking Union Medical College Hospital (PUMCH). Methods: This is a single center retrospective cohort study. Using the outpatient information system of PUMCH, the demographic information and injection-related reaction data of patients undergoing SCIT injection in Allergy Department of PUMCH from December 2018 to December 2022 were retrospectively analyzed to count the incidence and risk factors of systemic allergic reactions caused by SCIT. Mann-Whitney nonparametric test or chi-square test was used for single-factor analysis, and multiple logistic regression was used for multiple-factor analysis. Results: A total of 2 897 patients received 18 070 SCIT injections in Allergy Department during the four years, and 40 systemic allergic reactions occurred, with the overall incidence rate of 0.22%. The incidence of systemic allergic reaction was 0.37% when using imported dust mite preparation and 0.15% when using domestic multi-component allergen preparation. The risk factors significantly related with SCIT-induced systemic allergic reactions in patients using imported dust mite preparation were age less than 18 years old (OR=3.186,95%CI: 1.255-8.085), highest injection concentration (OR value could not be calculated because all patients with systemic reactions were injected with highest concentration), and large local reaction in previous injection (OR=22.264,95%CI: 8.205-60.411). The risk factors for SCIT-induced systemic allergic reactions in patients using domestic allergen preparation were 5 or more types of allergens (OR=3.455,95%CI: 1.147-10.402), highest injection concentration (OR=3.794,95%CI: 1.226-11.740) and large local reaction in previous injection (OR=63.577,95%CI: 22.248-181.683). However, SCIT injection in pollen allergic patients during the pollen season did not show a correlation with systemic allergic reaction. Conclusion: The incidence of SCIT-induced systemic allergic reactions was low in the Chinese patient population of this study. Patients with one or more risk factors, such as multiple allergen injection, highest injection concentration, large local reaction in previous injection, should be given high attention and vigilance against systemic allergic reactions.
Humans
;
Allergens
;
Asian People
;
Desensitization, Immunologic/adverse effects*
;
Hypersensitivity/epidemiology*
;
Retrospective Studies
8.Risk factors of systemic allergic reactions caused by subcutaneous allergen immunotherapy.
Li Sha LI ; Kai GUAN ; Jia YIN ; Liang Lu WANG ; Yu Xiang ZHI ; Jin Lü SUN ; Hong LI ; Li Ping WEN ; Rui TANG ; Jian Qing GU ; Zi Xi WANG ; Le CUI ; Ying Yang XU ; Sai Nan BIAN
Chinese Journal of Preventive Medicine 2023;57(12):1972-1977
Objective: To investigate the incidence and risk factors of systemic allergic reactions induced by subcutaneous immunotherapy (SCIT) in patients undergoing SCIT injections in Peking Union Medical College Hospital (PUMCH). Methods: This is a single center retrospective cohort study. Using the outpatient information system of PUMCH, the demographic information and injection-related reaction data of patients undergoing SCIT injection in Allergy Department of PUMCH from December 2018 to December 2022 were retrospectively analyzed to count the incidence and risk factors of systemic allergic reactions caused by SCIT. Mann-Whitney nonparametric test or chi-square test was used for single-factor analysis, and multiple logistic regression was used for multiple-factor analysis. Results: A total of 2 897 patients received 18 070 SCIT injections in Allergy Department during the four years, and 40 systemic allergic reactions occurred, with the overall incidence rate of 0.22%. The incidence of systemic allergic reaction was 0.37% when using imported dust mite preparation and 0.15% when using domestic multi-component allergen preparation. The risk factors significantly related with SCIT-induced systemic allergic reactions in patients using imported dust mite preparation were age less than 18 years old (OR=3.186,95%CI: 1.255-8.085), highest injection concentration (OR value could not be calculated because all patients with systemic reactions were injected with highest concentration), and large local reaction in previous injection (OR=22.264,95%CI: 8.205-60.411). The risk factors for SCIT-induced systemic allergic reactions in patients using domestic allergen preparation were 5 or more types of allergens (OR=3.455,95%CI: 1.147-10.402), highest injection concentration (OR=3.794,95%CI: 1.226-11.740) and large local reaction in previous injection (OR=63.577,95%CI: 22.248-181.683). However, SCIT injection in pollen allergic patients during the pollen season did not show a correlation with systemic allergic reaction. Conclusion: The incidence of SCIT-induced systemic allergic reactions was low in the Chinese patient population of this study. Patients with one or more risk factors, such as multiple allergen injection, highest injection concentration, large local reaction in previous injection, should be given high attention and vigilance against systemic allergic reactions.
Humans
;
Allergens
;
Asian People
;
Desensitization, Immunologic/adverse effects*
;
Hypersensitivity/epidemiology*
;
Retrospective Studies
9.Near-infrared targeted probe designed for intraoperative imaging of prostatic neurovascular bundles.
Zhan Yi ZHANG ; Fan ZHANG ; Ye YAN ; Cai Guang CAO ; Chang Jian LI ; Shao Hui DENG ; Yue Hao SUN ; Tian Liang HUANG ; Yun He GUAN ; Nan LI ; Min LU ; Zhen Hua HU ; Shu Dong ZHANG
Journal of Peking University(Health Sciences) 2023;55(5):843-850
OBJECTIVE:
To investigate the imaging effect of a near-infrared fluorescent targeted probe ICG-NP41 on the neurovascular bundles (NVB) around the prostate in rats.
METHODS:
A near-infrared fluorescent targeted probe ICG-NP41 was synthesized. An animal model for NVB imaging was established using Sprague-Dawley rats (250-400 g). Experiments were conducted using a custom-built near-infrared windowⅡ(NIR-Ⅱ) small animal in vivo imaging system, and images collected were processed using ImageJ and Origin. The fluorescence signal data were statistically analyzed using GraphPad Prism. The signal-to-background ratio (SBR) for NVB was quantitatively calculated to explore the effective dosage and imaging time points. Finally, paraffin pathology sections and HE staining were performed on the imaging structures.
RESULTS:
Except for rats in the control group (n=2), right-sided NVB of the rats injected with ICG-NP41 (n=2 per group) were all observed in NIR-Ⅱ fluorescence mode 2 h and 4 h after administration. At 2 h and 4 h, average SBR of cavernous nerve in 2 mg/kg group in fluorescence mode was 1.651±0.142 and 1.619±0.110, respectively, both higher than that in white light mode (1.111±0.036), with no significant difference (P>0.05); average SBR of 4 mg/kg group in fluorescence mode were 1.168±0.066 and 1.219±0.118, respectively, both higher than that in white light mode (1.081±0.040), with no significant difference (P>0.05). At 2 h and 4 h, the average SBR of 2 mg/kg and 4 mg/kg groups in fluorescence mode were higher than that of the control group (SBR=1), the average SBR of the 2 mg/kg group was higher than that of the 4 mg/kg group, and all the above with no significant difference (P>0.05). The average diameter of the nerve measured by full width at half maxima method was about (178±15) μm. HE staining of paraffin sections showed the right major pelvic ganglion.
CONCLUSION
The near-infrared fluorescent targeted probe ICG-NP41 can be used for real-time imaging of the NVB around the prostate in rats, providing a potential feasible solution for localizing NVB in real time during nerve-sparing radical prostatectomy.
Male
;
Rats
;
Animals
;
Prostate/diagnostic imaging*
;
Paraffin
;
Indocyanine Green
;
Rats, Sprague-Dawley
;
Fluorescent Dyes
10.The Use of Lipoprotein-Associated Phospholipase A2 in a Chinese Population to Predict Cardiovascular Events.
Hui XI ; Guan Liang CHENG ; Fei Fei HU ; Song Nan LI ; Xuan DENG ; Yong ZHOU
Biomedical and Environmental Sciences 2022;35(3):206-214
Objective:
To explore associations between lipoprotein-associated phospholipase A2 (Lp-PLA2) and the risk of cardiovascular events in a Chinese population, with a long-term follow-up.
Methods:
A random sample of 2,031 participants (73.6% males, mean age = 60.4 years) was derived from the Asymptomatic Polyvascular Abnormalities Community study (APAC) from 2010 to 2011. Serum Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay (ELISA). The composite endpoint was a combination of first-ever stroke, myocardial infarction (MI) or all-cause death. Lp-PLA2 associations with outcomes were assessed using Cox models.
Results:
The median Lp-PLA2 level was 141.0 ng/mL. Over a median follow-up of 9.1 years, we identified 389 events (19.2%), including 137 stroke incidents, 43 MIs, and 244 all-cause deaths. Using multivariate Cox regression, when compared with the lowest Lp-PLA2 quartile, the hazard ratios with 95% confidence intervals for developing composite endpoints, stroke, major adverse cardiovascular events, and all-cause death were 1.77 (1.24-2.54), 1.92 (1.03-3.60), 1.69 (1.003-2.84), and 1.94 (1.18-3.18) in the highest quartile, respectively. Composite endpoints in 145 (28.6%) patients occurred in the highest quartile where Lp-PLA2 (159.0 ng/mL) was much lower than the American Association of Clinical Endocrinologists recommended cut-off point, 200 ng/mL.
Conclusion
Higher Lp-PLA2 levels were associated with an increased risk of cardiovascular event/death in a middle-aged Chinese population. The Lp-PLA2 cut-off point may be lower in the Chinese population when predicting cardiovascular events.
1-Alkyl-2-acetylglycerophosphocholine Esterase/blood*
;
Asians
;
Cardiovascular Diseases/diagnosis*
;
China/epidemiology*
;
Female
;
Humans
;
Longitudinal Studies
;
Male
;
Middle Aged
;
Mortality
;
Myocardial Infarction/blood*
;
Predictive Value of Tests
;
Risk Factors
;
Stroke/blood*

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