Objective: To investigate the molecular mechanism of Syk in phagocytosis induced by CD36 antibodies. Methods: In vitro, two CD36 monoclonal antibodies, GZ1 (IgG2a) and GZ4 (IgG1), at different concentrations were co-incubated with platelets from CD36-positive blood donors, and the affinity of the antibodies for platelets was assessed using flow cytometry. CD36 positive platelets from donors were labeled with Red-SE. The GZ1 and GZ4 antibodies were added together with dye-labeled platelets to peripheral blood from blood donors for phagocytosis experiments. The expression of the Spleen Tyrosine Kinase (Syk), P-Syk, P38 MAPK and P-P38 were detected using Western blot(WB). In the in vitro phagocytosis inhibition assay, Fcγ receptor (FcγR) antibodies or Syk inhibitor (R406) were pre-incubated with monocytes prior to performing the phagocytosis experiment. In vivo experiments were performed using female C57BL/6J mice. R406 was administered via intraperitoneal injection, followed by tail vein infusion of GZ1 or GZ4 antibodies. Additionally, a treatment group was set up in which the antibodies were infused first, followed by administration of R406. Changes in platelet counts were analyzed using a blood routine analyzer, and antibody binding to platelets was detected by flow cytometry. Results: GZ1 had higher affinity for CD36positive platelets than GZ4. The phagocytosis rate induced by GZ1 was significantly higher than that of GZ4 [(42.12±2.25)% vs (16.25±6.45)%, P<0.001]. Moreover, GZ1-mediated platelet phagocytosis mainly depends on FcγRⅠ of monocytes, while GZ4-mediated platelet phagocytosis mainly relies on FcγRⅡ of monocytes. WB results showed that the GZ1 group significantly upregulated the expression of Syk and phosphorylated Syk (P-Syk), and induced phosphorylation of the downstream P38 MAPK signaling pathway. Pretreatment of monocytes with R406 inhibited the phagocytosis of antibodyopsonized platelets by monocytes. After injecting GZ1 or GZ4 antibodies into C57BL/6 female mice through the tail vein, GZ1 mAbs had a stronger binding rate to the platelets compared with GZ4 mAbs, leading to a significant decrease in platelet count. After pre-injecting R406 into mice, the platelet count reduction in both the GZ1 and GZ4 groups was alleviated, and the binding rate of antibodies to platelets was also significantly reduced. However, administration of R406 after antibody injection failed to prevent the decrease in platelet counts in mice. Conclusion: This study indicates that Syk plays an important role in the phagocytosis of anti-CD36 opsonized platelets by monocytes/macrophages and is closely associated with the activation of the P38 MAPK signaling pathway.

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.

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.

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.

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.

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.

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.

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.

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.

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.