1.Expression and functions of transient receptor potential channels in liver diseases.
Wenhui WANG ; Pengyu LIU ; Yalin ZHANG ; Li YAN ; Michael X ZHU ; Jin WANG ; Ye YU
Acta Pharmaceutica Sinica B 2023;13(2):445-459
Liver diseases constitute a major healthcare burden globally, including acute hepatic injury resulted from acetaminophen overdose, ischemia-reperfusion or hepatotropic viral infection and chronic hepatitis, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). Attainable treatment strategies for most liver diseases remain inadequate, highlighting the importance of substantial pathogenesis. The transient receptor potential (TRP) channels represent a versatile signalling mechanism regulating fundamental physiological processes in the liver. It is not surprising that liver diseases become a newly explored field to enrich our knowledge of TRP channels. Here, we discuss recent findings revealing TRP functions across the fundamental pathological course from early hepatocellular injury caused by various insults, to inflammation, subsequent fibrosis and hepatoma. We also explore expression levels of TRPs in liver tissues of ALD, NAFLD and HCC patients from Gene Expression Omnibus (GEO) or The Cancer Genome Atlas (TCGA) database and survival analysis estimated by Kaplan-Meier Plotter. At last, we address the therapeutical potential and challenges by pharmacologically targeting TRPs to treat liver diseases. The aim is to provide a better understanding of the implications of TRP channels in liver diseases, contributing to the discovery of novel therapeutic targets and efficient drugs.
2.Research progress of palmitoylation in non-alcoholic fatty liver disease and related liver diseases
Yalin ZHANG ; Li YAN ; Fengyu JU ; Wenhui WANG ; Ye YU
Journal of China Pharmaceutical University 2023;54(5):536-543
Non-alcoholic fatty liver disease (NAFLD) has become a major public health hazard threatening human health worldwide.Yet, due to its complex pathogenesis, new drug development is difficult, with still insufficient clinical medication.Palmitoylation is a universal posttranslational modification of proteins catalyzed by palmitoyltransferase, affecting their stability, membrane localization and function.Recent studies have shown that palmitoylation is closely associated with NAFLD.This review summarizes the mechanisms of palmitoylation in NAFLD and analyzes the expression levels of the palmitoyltransferase family in liver tissues of NAFLD patients from GEO database, aiming to provide important clues to explore new mechanisms for NAFLD.
3.Effects of Changtong Recipe on levels of neurotransmitters and inflammatory cytokines in elderly patients with functional constipation
Zhenzhong YE ; Xiao LEI ; Caiqin NIU ; Yalin QUAN ; Zhe ZHANG
International Journal of Traditional Chinese Medicine 2022;44(12):1380-1384
Objective:To explore the effects of Changtong Recipe on levels of intestinal neurotransmitters and inflammatory cytokines in the elderly with functional constipation (FC).Methods:A total of 90 elderly patients with FC meeting the inclusion criteria in the hospital were enrolled between June 2020 and October 2021. According to the principle of random allocation, they were divided into control group (45 cases, treated with oral polyethylene glycol electrolyte powder) and treatment group (45 cases, Changtong Recipe). All were treated for 3 months and followed up for 30 d. Before and after treatment, TCM symptoms were scored. The levels of vasoactive intestinal peptide (VIP) and substance P (SP) were detected by radioimmunoassay. The levels of IL-17A and IL-18 were detected by ELISA. The constipation severity and quality of life were evaluated by clinical constipation scale (CCS) and Patient Assessment of Constipation Quality of Life scale (PAC-QOL). The adverse events during treatment and recurrence during follow-up were recorded. The clinical responsive effect was evaluated.Results:After treatment, there were 44 cases in treatment group and 43 cases in control group included into the statistics. The differences in total response rate between treatment group and control group were statistically significant [97.7% (43/44) vs. 81.4% (35/43); χ2=6.25, P=0.012]. After treatment, scores of TCM symptoms (mental fatigue, shortness of breath and abdominal distension, foreign body sensation in the throat, palpitation, cold extremities) and total score in the treatment group were significantly lower than those in the control group ( t=3.71, 10.25, 2.87, 2.87, 5.68, 26.94, all Ps<0.01), and scores of CCS and PAC-QOL were significantly lower than those in the control group ( t=11.71, 18.84, all Ps<0.001). After treatment, levels of serum VIP [(41.86±1.16) ng/L vs. (35.71±1.97) ng/L, t=17.79] and SP [(42.15±1.90) ng/L vs. (39.53±2.13) ng/L, t=6.06] in treatment group were higher than those in the control group ( P<0.01), while levels of IL-17A [(35.71±5.97 ) pg/L vs. (41.86±5.16) pg/L, t=5.14] and IL-18 [(22.15±3.90) pg/L vs. (26.53±4.13) pg/L, t=5.09] in treatment group were significantly lower than those in the control group ( P<0.01). During treatment, difference in incidence of adverse events between treatment group and control group was not statistically significant [9.1% (4/44) vs. 14.0% (6/43); χ2=0.13, P=0.716]. During the 30d of follow-up, differences in recurrence rate between treatment group and control group were statistically significant [2.3% (1/44) vs. 16.3% (7/43); χ2=5.11, P=0.024]. Conclusion:The Changtong Recipe can improve levels of intestinal neurotransmitters (VIP, SP) and quality of life in elderly patients with FC, reduce levels of inflammatory cytokines (IL-17A, IL-18) and improve clinical curative effect safely.
4.Guidance of magnetic resonance imaging for target area delineation of postoperative presacral recurrence of rectal cancer
Xianan LI ; Tao LIU ; Chang WANG ; Peng GUO ; Yingjiang YE ; Yalin CHEN ; Jin CHENG
Chinese Journal of Gastrointestinal Surgery 2020;23(12):1170-1176
Objective:Presacral recurrence of rectal cancer have altered the adjacent structures of original pelvic organs due to the previous radical surgery of rectal cancer, and the boundary between recurrent tumor tissues and pelvic internal structures is not clear. Conventional CT examination has poor soft tissue resolution, which makes it difficult to accurately delineate the target area of radiotherapy. This study aimed to explore the guiding role of magnetic resonance imaging (MRI) in delineating the target area of presacral recurrence after radical resection of rectal cancer.Methods:A descriptive case series research method was adopted. From May 2014 to May 2019, the clinical data of 30 patients with presacral recurrence after radical resection of rectal cancer were collected, who were admitted to Peking University People's Hospital, confirmed by pathology or discussed by multidisciplinary team (MDT), with complete MRI, CT and case information. According to the gross tumor volume (GTV) with presacral recurrence outlined in CT and MRI images, including presacral recurrent lesions (GTVT) and metastatic lymph nodes (GTVN), the GTV volume was calculated, and the tumor boundary and diameter were measured. The differences between MRI and CT were compared.Results:The volume of GTVT-CT was larger than that of GTVT-MR in all the 30 patients. The median volume of GTVT-CT was 67.86 (range 5.12-234.10) cm 3, which was significantly larger than 43.02 (range 3.42-142.50) cm 3 of GTVT-MR with statistically significant difference ( Z=-4.288, P<0.001). The mean volume of GTVN outlined by CT and MRI was (0.43±0.11) cm 3 and (0.40±0.10) cm 3 respectively without statistically significant difference ( t=1.550, P=0.132). The mean values of boundary and radial line of the presacral lesions on CT images were all longer than those on MRI images. The vertical diameter of GTVT on CT and MRI images was (6.66±2.92) cm and (5.17±2.40) cm ( t=5.466, P<0.001); the anterior boundary was (3.24±2.51) cm and (2.69±2.48) cm ( t=4.685, P<0.001); the anteroposterior diameter was (4.92±2.02) cm and (4.04±1.57) cm ( t=6.210, P<0.001); the left boundary was (3.05±1.00) cm and (2.64±0.78) cm ( t=2.561, P=0.016); the right boundary was 2.66 (0.00-4.23) cm and 1.82 (-1.10-3.59) cm ( Z=-3.950, P<0.001); the transverse diameter was (5.01±1.78) cm and (3.82±1.29) cm ( t=4.648, P<0.001), respectively, whose differences were all statistically significant. MRI was superior to CT in judging the involvement of anterior organs, such as intestine, prostate, bladder and the posterior sacrum. Fifteen patients received radiotherapy according to the target area guided by MRI and 10 patients obtained clinical symptom relief. Conclusion:Compared with CT, the GTV of postoperative presacral recurrence of rectal cancer outlined in MRI images is smaller, and MRI can determine the boundary between tumor and surrounding normal tissues more precisely, so it can show the invasion range of tumor more accurately and guide the accurate implementation of radiotherapy.
5.Guidance of magnetic resonance imaging for target area delineation of postoperative presacral recurrence of rectal cancer
Xianan LI ; Tao LIU ; Chang WANG ; Peng GUO ; Yingjiang YE ; Yalin CHEN ; Jin CHENG
Chinese Journal of Gastrointestinal Surgery 2020;23(12):1170-1176
Objective:Presacral recurrence of rectal cancer have altered the adjacent structures of original pelvic organs due to the previous radical surgery of rectal cancer, and the boundary between recurrent tumor tissues and pelvic internal structures is not clear. Conventional CT examination has poor soft tissue resolution, which makes it difficult to accurately delineate the target area of radiotherapy. This study aimed to explore the guiding role of magnetic resonance imaging (MRI) in delineating the target area of presacral recurrence after radical resection of rectal cancer.Methods:A descriptive case series research method was adopted. From May 2014 to May 2019, the clinical data of 30 patients with presacral recurrence after radical resection of rectal cancer were collected, who were admitted to Peking University People's Hospital, confirmed by pathology or discussed by multidisciplinary team (MDT), with complete MRI, CT and case information. According to the gross tumor volume (GTV) with presacral recurrence outlined in CT and MRI images, including presacral recurrent lesions (GTVT) and metastatic lymph nodes (GTVN), the GTV volume was calculated, and the tumor boundary and diameter were measured. The differences between MRI and CT were compared.Results:The volume of GTVT-CT was larger than that of GTVT-MR in all the 30 patients. The median volume of GTVT-CT was 67.86 (range 5.12-234.10) cm 3, which was significantly larger than 43.02 (range 3.42-142.50) cm 3 of GTVT-MR with statistically significant difference ( Z=-4.288, P<0.001). The mean volume of GTVN outlined by CT and MRI was (0.43±0.11) cm 3 and (0.40±0.10) cm 3 respectively without statistically significant difference ( t=1.550, P=0.132). The mean values of boundary and radial line of the presacral lesions on CT images were all longer than those on MRI images. The vertical diameter of GTVT on CT and MRI images was (6.66±2.92) cm and (5.17±2.40) cm ( t=5.466, P<0.001); the anterior boundary was (3.24±2.51) cm and (2.69±2.48) cm ( t=4.685, P<0.001); the anteroposterior diameter was (4.92±2.02) cm and (4.04±1.57) cm ( t=6.210, P<0.001); the left boundary was (3.05±1.00) cm and (2.64±0.78) cm ( t=2.561, P=0.016); the right boundary was 2.66 (0.00-4.23) cm and 1.82 (-1.10-3.59) cm ( Z=-3.950, P<0.001); the transverse diameter was (5.01±1.78) cm and (3.82±1.29) cm ( t=4.648, P<0.001), respectively, whose differences were all statistically significant. MRI was superior to CT in judging the involvement of anterior organs, such as intestine, prostate, bladder and the posterior sacrum. Fifteen patients received radiotherapy according to the target area guided by MRI and 10 patients obtained clinical symptom relief. Conclusion:Compared with CT, the GTV of postoperative presacral recurrence of rectal cancer outlined in MRI images is smaller, and MRI can determine the boundary between tumor and surrounding normal tissues more precisely, so it can show the invasion range of tumor more accurately and guide the accurate implementation of radiotherapy.
6.Effect of structured lipid emulsion on acute phase protein and acute inflammatory reaction in gastrointestinal cancer patients after operation
Qingquan LYV ; Jian SUN ; Yalin YE ; Hanjun MA
Clinical Medicine of China 2014;30(3):304-307
Objective To explore the influence of structured lipid emulsion on acute phase protein and acute inflammatory reaction in gastrointestinal cancer patients after operation.Methods Eighty postoperative patients with gastrointestinal caner from July 2010 to February 2012 were randomly divided into observation group and control group,and 40 cases for each group.Patients in observation group were given structured lipid emulsion,while in control group were given physic mixture of medium-chain/long-chain triglycerides group.Meanwhile patients in both groups were received isonitrogenous and isocaloric parenteral nutrition for 6 days after operation.The general conditions after operation were recorded.Acute phase protein and acute inflammatory reaction were measured before operation,the 1 st day and 7th day after operation.Results After 6 days parenteral nutrition,the vital sign data,blood routine indices,liver and renal function,blood fat were back to normal values in two groups.There was no significant difference in the incidence of postoperative infection complication and hospitalization duration between observation group and control group (12.5% (5/40) vs.25.0% (10/40) ; (12.9 ± 0.7) d vs.(13.1 ± 0.9) d; P > 0.05).The serum levels of Albumin (ALB),Prealbumin(PAB) and Transferrin(TRF) on the 1st day after operation in two groups were significantly lower than those before operation,while the serum levels of C reactive protein (CRP) and fibrinogen (Fib) were significantly higher,then gradually recovering.The serum levels of ALB,PAB,TRF,CRP,Fib on the 7th day after operation in observation group were (37.11 ± 3.30) g/L,(0.25 ± 0.08) g/L,(2.35 ± 0.49) g/L,(21.84±16.76) mg/L,(3.95 ± 1.23) g/L,significant different from those on the 1st day before nutrition therapy ((31.52±2.92) g/L,(0.15 ±0.02) g/L,(1.90 ±0.54) g/L,(83.80 ±47.13) mg/L,(4.35 ±0.98) g/L) and control group ((34.50 ±2.71) g/L,(0.18 ±0.05) g/L,(2.00 ±0.52) g/L,(41.36 ±23.49) mg/L,(4.76 ± 2.35) g/L; P < 0.05).The serum levels of interleukin (IL)-1,IL-2,IL-6,tumor necrosis factor (TNF)-α decreased on the 1st day after operation of two groups,then gradually increasing.The serum levels of IL-2,IL-6 on the 7th day after operation in observation group were (987 ±203) ng/L) and (277 ± 107) ng/L,significant different from those on the 1st day before nutrition therapy ((890 ± 197) ng/L and (355 ± 107) ng/L;P <0.05),and lower than those in control group ((1 347 ± 195) ng/L,(752 ± 187) ng/L; P <0.05).The serum levels of TNF-α on the 7th day after operation in observation group was (197 ±98) ng/L,which was as same as that on the 1 st day before nutrition therapy ((167 ± 79) ng/L,P > 0.05) and lower than this in control group((342 ± 106) ng/L;P <0.05).Conclusion Structured lipid emulsion can effectively improve the synthesis of acute phase protein in gastrointestinal cancer patients after operation,regulate the inflammatory cell factors producing and releasing,which is benefit to smoothly through stress reaction period.
7.Screening the best ratio of artesunate and ursolic acid for lipid-lowering
Yalin YE ; Yuliang WANG ; Zejian WANG ; Ming YIN ; Hailiang XIN ; Lei ZHANG
Journal of Pharmaceutical Practice 2014;(3):195-198
Objective To observe the effect of different doses unilateral and compound of artesunate and ursolic acid on lipid metabolism in rats′model, find out the best ratio of artesunate and ursolic acid .Methods Lipid metabolism disorders model was in-duced by feeding high fat diet in rat .The best ratio was screened through comparing the lipid level of rats ofdifferent groups .Results The results showed that Artesunate ( high dose ) +Ursolicacid ( high dose ) significantly reduced TG , CHO and LDL-C, increased HDL-C and H/L.Lipid-lowering effect was superior the positive drug fenofibrate , but also superior to the same dose of artesunate and ursolic acid alone.No significant effect of each test sample on the rat liver function was observed (P>0.05).Conclusion Artesunate and ursolic acid ratio of 1:1 had the best lipid-lowering effect, and the recommended dose was (50+50) mg/kg.
8.Effect of structured lipid emulsion on inflammatory cell factors and immunologic function in gastrointestinal cancer patients after operation
Qingquan Lü ; Jian SUN ; Yalin YE ; Hanjun MA
Chinese Journal of Postgraduates of Medicine 2012;35(27):1-4
Objective To explore the influence of structured lipid emulsion on inflammatory cell factors and immunologic function in gastrointestinal cancer patients after operation.Methods From July 2010 to February 2012,80 postoperative patients with gastrointestinal cancer were randomly divided into 2 groups with 40 cases each by stratified sampling method:structured lipid emulsion group (observation group),physical mixture of medium-chain/long-chain triglycerides group (control group).Both groups received isonitrogenous and isocaloric parenteral nutrition for 6 days after operation.The general conditions after operation were compared between two groups.Inflammatory cell factors and immunologic function were measured before operation,the 1st day and 7th day after operation.Results After 6 days parenteral nutrition,the vital sign data,blood routine,liver and renal function,blood fat etc was normal in two groups.There was no significant difference in the incidence of postoperative infection complication and hospitalization duration between observation group and control group [12.5%(5/40) vs.25.0%(10/40),[( 12.9 ± 0.7 d) vs.(13.1 ±0.9) d] (P >0.05).The serum levels of interleukin (IL)-1,IL-2,IL-6,tumor necrosis factor (TNF)-α on the 1st day after operation in two groups decreased,then gradually increasing.The serum levels of IL-2,IL-6,TNF- α on the 7th day after operation in observation group[(987 ± 203),(277 ± 107),( 197 ± 98) ng/L] were lower than those in control group [(1347 ± 195),(752 ± 187),(342 ± 106) ng/L](P<0.05 ).The serum levels of IgG,IgA,IgM,CD3+,CD4+ and CD8+ on the 1st day after operation in two groups decreased,then gradually increasing.The serum levels of IgG,CD3+,CD4+ were higher in observation group [( 14.2 ± 1.8 ) g/L,0.746 ± 0.111,0.580 ± 0.067] than those in control group [( 12.1 ± 2.8) g/L,0.606 ±0.101,0.404 ± 0.072] (P <0.05).Conclusion Structured lipid emulsion can reduce immunological suppression and inflammation in gastrointestinal cancer patients after operation,regulate the inflammatory cell factors producing and releasing,improve the immunologic function.
9.Supernatant of Toxoplasma gondii culture inhibits the proliferation of human lung cancer cell line A549
Pu GE ; Chunli LI ; Yalin RAN ; Bin YE
Basic & Clinical Medicine 2010;30(2):185-188
Objective To investigate whether there is an inhibition of the human lung cancer cell line A549 induced by the culture supernatant of Toxoplasma gondii in vitro and the mechanism of the inhibition. Methods A549 cells 5 x 10~4mL~(-1) were cultured and harvested. The cells were treated for different hours with different concentrations of Toxoplasma gondii culture supernatant (the concentrations of tachyzoites were 4×10~7mL~(-1), 8 × 10~7mL~(-1), 16 ×10~7mL~(-1) respectively). Growth inhibition rate was measured with the MTT method; Cell cycle was checked with flow cytometer. Western blot was used to detect the level of cyclinBl and cdc2 of cells. Results The culture supernatants of Toxoplasma gondii inhibited proliferation of A549 cells in a time-dose dependent manner. Cell cycle was significantly stopped at G_2/M phase by the culture supernatants with FCM technology. The culture supernatant of Toxoplasma gondii reduced the expressions of gene cyclinBl and cdc2 of A549 cells. Conclusion The culture supernatant of Toxoplasma gondii may inhibit A549 cell and arrest the cell cycle of A549 cells mainly by regulating the expression of gene cyclinBl and cdc2.
10.Application of reserved jejunal feeding tube during postoperative chemotherapy of gastric cancer
Hanjun MA ; Sanrong LI ; Hansheng JIN ; Jian SUN ; Xianlin SHU ; Yalin YE ; Qingquan LV ; Qi WEI
Chinese Journal of Postgraduates of Medicine 2008;31(20):30-32
Objective To evaluate the effects of reserved jejunal feeding tube during postoperative chemotherapy of gastric cancer. Methods Forty-two patients with gastric cancer underwent radical gastrectomy and going to adjuvant chemotherapy,conventional placed jejunal feeding tube. All of the patients weredivided into group A and group B randomly by pathological staging and tumor site, group A reserved jejunal feeding tube and received enteral nutrition through the tube during chemotherapy, and group B non-reservedjejunal feeding tube and been given daily diet,compared nutrition and immune indicators of two groups beforeand after chemotherapy ,compared the rate of vomiting,and observed complications long-term reserved jejunal feeding tube. Results In post-chemotherapy,nutrition and immune indicators of group A were betterthan those of group B, the difference was statistically significant (P<0.05) ,the rate of vomiting in group Awas significantly lower than that of in group B (X2= 9.75, P<0.01 ), no serious complieations occurred forlong-term reserved jejunal feeding tube. Conclusions Reserved jejunal feeding tube and received enteralnutrition through the tube during postoperative chemotherapy of gastric cancer can significantly improve the nutritional and immune status. It is safe and reliable, worth promoting.

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