AIM To observe the effects of Hugan Tablets on high-fat diet induced non-alcoholic fatty liver disease(NAFLD)in a mouse model,and the autophagy,pyroptosis and the PI3K/Akt/mTOR signaling pathway as well.METHODS The C57BL/6 mice were randomly divided into the normal group,the model group,the Hugan Tablets group(0.7 g/kg)and the Yishanfu group(0.23 g/kg),with 10 mice in each group.The NAFLD mouse model was established by 16 weeks feeding of high-fat diet.From the 13th week,the mice started their corresponding dosing of the drug by gavage followed by killing of the mice at the end of 16th week and collection of their serum and liver tissue samples.The mice had their serum ALT,AST,TG,TC,LDL levels,liver TG,TC,NEFA,MDA levels and activities of SOD and GSH-Px detected;their serum levels of IL-1β,IL-6 and TNF-αdetected by ELISA;their hepatic pathological changes observed using HE staining and oil red O staining;and their hepatic protein expressions of ACC,CPT1A,FAS,p-PI3K,p-Akt,p-mTOR,P62,LC3,NLRP3,GSDMD and Caspase1 detected by Western blot.RESULTS Compared with the model group,the Hugan Tablets group displayed decreased body weight and hepatosmatic index level(P＜0.01);decreased levels of serum ALT,AST,TG,TC,LDL,IL-6,IL-1β and TNF-α(P＜0.05,P＜0.01);increased hepatic levels of TG,TC,NEFA and MDA(P＜0.05);decreased activities of SOD and GSH-Px(P＜0.05);improved pathological changes of hepatic lipid deposition and hepatocytic ballooning and decreased NAS score and oil red O staining area(P＜0.01);decreased hepatic protein expressions of ACC1,FAS,NLRP3,Caspase1,GSDMD,P62,p-PI3K,p-Akt and p-mTOR(P＜0.05,P＜0.01);and increased protein expressions of CPT1A and LC3(P＜0.01).CONCLUSION Hugan Tablets can effectively prevent and control the development of high-fat diet induced NAFLD in mice,and the mechanism may be associated with the promotion of autophagy in hepatocytes and the inhibition of pyroptosis via the inhibition of PI3K/Akt/mTOR signaling pathway.

Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.

AIM To observe the effects of Hugan Tablets on high-fat diet induced non-alcoholic fatty liver disease(NAFLD)in a mouse model,and the autophagy,pyroptosis and the PI3K/Akt/mTOR signaling pathway as well.METHODS The C57BL/6 mice were randomly divided into the normal group,the model group,the Hugan Tablets group(0.7 g/kg)and the Yishanfu group(0.23 g/kg),with 10 mice in each group.The NAFLD mouse model was established by 16 weeks feeding of high-fat diet.From the 13th week,the mice started their corresponding dosing of the drug by gavage followed by killing of the mice at the end of 16th week and collection of their serum and liver tissue samples.The mice had their serum ALT,AST,TG,TC,LDL levels,liver TG,TC,NEFA,MDA levels and activities of SOD and GSH-Px detected;their serum levels of IL-1β,IL-6 and TNF-αdetected by ELISA;their hepatic pathological changes observed using HE staining and oil red O staining;and their hepatic protein expressions of ACC,CPT1A,FAS,p-PI3K,p-Akt,p-mTOR,P62,LC3,NLRP3,GSDMD and Caspase1 detected by Western blot.RESULTS Compared with the model group,the Hugan Tablets group displayed decreased body weight and hepatosmatic index level(P＜0.01);decreased levels of serum ALT,AST,TG,TC,LDL,IL-6,IL-1β and TNF-α(P＜0.05,P＜0.01);increased hepatic levels of TG,TC,NEFA and MDA(P＜0.05);decreased activities of SOD and GSH-Px(P＜0.05);improved pathological changes of hepatic lipid deposition and hepatocytic ballooning and decreased NAS score and oil red O staining area(P＜0.01);decreased hepatic protein expressions of ACC1,FAS,NLRP3,Caspase1,GSDMD,P62,p-PI3K,p-Akt and p-mTOR(P＜0.05,P＜0.01);and increased protein expressions of CPT1A and LC3(P＜0.01).CONCLUSION Hugan Tablets can effectively prevent and control the development of high-fat diet induced NAFLD in mice,and the mechanism may be associated with the promotion of autophagy in hepatocytes and the inhibition of pyroptosis via the inhibition of PI3K/Akt/mTOR signaling pathway.

Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.

In order to investigate the effect of salidroside on inhibiting liver fibrosis and its relationship with CXC chemokine ligand 16(CXCL16) in vivo and in vitro, totally 45 C57 BL/6 J male mice were randomly divided into normal group, model group and salidroside group, with 15 mice in each group. The mice in model group and salidroside group were injected intraperitoneally with 15% carbontetrachloride(CCl_4) olive oil solution to establish liver fibrosis model, and the mice in normal group were injected intraperitoneally with the same dose of olive oil. Salidroside group was given with 100 mg·kg~(-1 )salidroside by gavage, while the normal group and model group received the same amount of double distilled water by gavage. All mice were sacrificed after 5 weeks of intragastric administration. The pathological changes of mouse liver were observed by hematoxylin-eosin(HE) staining, and the degree of liver fibrosis was observed by sirius red staining. The protein expressions of collagen Ⅰ(ColⅠ), α-smooth muscle actin(α-SMA), fibronectin(FN), CXCL16, phosphorylated Akt(p-Akt), Akt in liver tissues were detected by Western blot. Hepatic stellate cell line JS 1 was cultured in vitro and divided into control group, model group(100 μg·L~(-1) CXCL16) and salidroside group(100 μg·L~(-1) CXCL16+1×10~(-5) mol·L~(-1) salidroside). Cell migration was detected by cell scratch, the mRNA expressions of ColⅠ and α-SMA were detected by RT-PCR, and the protein expressions of p-Akt and Akt were detected by Western blot. As compared with the normal group, the protein expressions of ColⅠ, α-SMA, FN, CXCL16, and p-Akt in the model group were significantly increased, and salidroside could reduce the expression of these indicators(P<0.05 or P<0.01). In vitro, CXCL16 could promote the migration of JS 1, increase the mRNA expressions of ColⅠ and α-SMA in JS 1, and enhance Akt phosphorylation in JS 1(P<0.05 or P<0.01). As compared with the model group, salidroside could inhibit the migration of JS 1 induced by CXCL16(P<0.05), and reduce the high expression of ColⅠ and α-SMA mRNA and the phosphorylation of Akt in JS 1 induced by CXCL16(P<0.05). In conclusion, salidroside might attenuate CCl_4-induced liver fibrosis in mice by inhibiting the migration, activation and Akt phosphorylation of hepatic stellate cells induced by CXCL16.
Animals ; Carbon Tetrachloride ; Chemokine CXCL16 ; Glucosides ; Hepatic Stellate Cells ; Liver/pathology* ; Liver Cirrhosis/genetics* ; Male ; Mice ; Phenols

In 2006, the Hepatology Committee of Chinese Association of Integrative Medicine issued the "Guidelines for the Prevention and Treatment of Liver Fibrosis with Integrated Traditional Chinese and Western Medicine." In recent years, the fields of Chinese medicine, Western medicine, and integrative medicine have made rapid advances in basic and clinical research into chronic liver disease, and accumulated new evidence for the prevention and treatment of hepatic fibrosis. Therefore, in order to meet clinical needs, liver disease experts of integrated traditional Chinese and Western medicine were united to revise the previous guidelines in order to help physicians make correct and reasonable decisions in the diagnosis and treatment of hepatic fibrosis.

OBJECTIVETo investigate the relationship between early peak body temperature and neutropenia duration and its potential mechanism.

METHODSA total of 111 patients with CR1 phase acute leukemia (AL) with neutropenia infection were enrolled in this study. The relationship between early peak body temperature and neutropenia duration was analyzed retrospectively, and the IL-6 serum level in patients with different peak of body temperature was detected, and the single cell culture system in vitro was established, the incorparation rate of EdU in vivo was detected, and the effect of IL-6 on mouse hematopoietic stem cells /progenitor cells was analyzed.

RESULTSOut of 111 patients with nentropenia, the body temperature <38 °C and the neutropenia duration 9.5±3.69 d were observed in 44 patients, while the body temperature >38 °C and neutropenia duration 7.33±4.20 d were observed in 69 patients, the differences between 2 groups was statistically signficant (P<0.05). The EdU test showed that the number of EdU hematopoietic stem cells and progenitor cells increased. The IL-6 level was different in patients with different peaks of initial bady temperature (P<0.05). The results of amimal experiment showed that the IL-6 could promote the proliferation of hematopoietic stem cells/ progenitor cells in vitro and in vivo.

CONCLUSIONFor patients with neutropenic infection when initial body temperature peak is <38 °C, the probability of neutropenia duration prolonging after chamotherapy increases, which may relate with promotive effect of pro-inflammatory cytokins on prliferation of hematopoietic stem cells/progenitor cells.

The aim of this paper was to observe the function of bone marrow mesenchymal stem cell (BMSC) transplantation in process of liver injury induced by carbon tetrachloride (CCl₄) and the intervention effect of Yiguanjian (YGJ), a compound of Chinese herbal medicine. Wistar rats were randomly divided into five groups: normal group, model group, cell transplantation (CT) group, YGJ group and cell transplantation plus Yiguanjian (CTY) group. Liver injury was induced through subcutaneous injection with CCl₄ at a dose of 3 mL·kg⁻¹ body weight for 4 weeks, twice a week. They were injected for a total of 9 times. After the first injection with CCl₄, rats in the CT group and CTY group were injected with the third-generation BMSCs at dose 1×10⁶ (suspended in 1 mL saline solution) via tail vein. Rats in the YGJ and CTY groups were also intragastrically administered with Yiguanjian once a day. Rat serum ALT and AST activities were increased significantly on the second day after injection with CCl₄, while BMSC transplantation and Yiguanjian decreased their activities. After 4 weeks of injection with CCl₄, serum ALT, AST and -GT activities, and serum TNF- and IL-6 expressions were increased, while TBIL were decreased in model rats compared with normal rats. Meanwhile, liver cells edema, plasmatic loose, and numerous lipid droplets were observed in rats of the model group. BMSC transplantation aggravated liver injury compared with model rats, which was manifested by decreasing SOD activity, increased MDA, TG, TNF- and IL-6 levels, and aggravated necrosis level of hepatocytes, fusion of lipid droplets, and collagen deposition in liver tissue. Yiguanjian decreased liver injury induced by CCl₄ alone and CCl₄ plus BMSC transplantation. SRY gene hybridization method was used to detect the positive SRY expressions in heart, liver, spleen, lung and kidney, especially in liver, while Yiguangjian decreased liver SRY expression. Wnt and -catenin showed high expressions in rats of normal group, which were decreased significantly in rats of models group, while Yiguanjian increased their expressions. In conclusion, BMSC transplantation could exacerbate liver injury, while Yiguanjian could protect liver injury induced by CCl₄ and BMSC transplantation, which was related to decreasing the homing of BMSCs to liver and up-regulating Wnt/-catenin signaling pathway.
Animals ; Bone Marrow ; Carbon Tetrachloride ; Chemical and Drug Induced Liver Injury ; therapy ; Drugs, Chinese Herbal ; pharmacology ; Liver ; Liver Cirrhosis, Experimental ; therapy ; Mesenchymal Stem Cell Transplantation ; Rats ; Rats, Wistar ; Wnt Signaling Pathway

OBJECTIVE: To explore the effects of aquaporin 4( APQ4) in rat toxic brain edema induced by subacute 1,2-dichloroethane( 1,2-DCE) exposure. METHODS: Thirty-two specific pathogen free healthy adult female SD rats were randomly divided into control( 8 rats),low-dose( 12 rats) and high-dose( 12 rats) groups. The treatment groups were exposed to 1,2-DCE( low-dose: 600 mg / m3; high-dose: 1 800 mg/m3,nose-only) and the control group was exposed to fresh air by dynamic inhalation for 8 hours per day for consecutive 7 days. After exposure,histopathologic changes were examined in the cerebral cortex. Real-time polymerase chain reaction was used to detect the mRNA relative expression of matrix metalloproteinase 2( MMP2),Na-K-Cl cotransporter-1( NKCC1) and AQP4. The Western blotting was used to detect the expression of AQP4 protein in the cerebral cortex. RESULTS: The pathological results showed that the cerebral cortex tissues were loose around the peripheral vessels and the vessels tissue space appeared widen in low-dose exposure group. The pathological change was more serious in high-dose group than low-dose group,with obvious loosen vessels and vacuole. Compared with those of the control group and the low-dose group,the relative expression level of MMP2 mRNA in the high-dose group increased significantly[( 1. 07 ± 0. 41) vs( 1. 56 ± 0. 55),( 1. 21 ± 0. 59) vs( 1. 56 ± 0. 55),P <0. 05],while the the relative expression level of AQP4 mRNA in the high-dose group significantly decreased [( 1. 03 ±0. 25) vs( 0. 81 ± 0. 12),( 1. 00 ± 0. 20) vs( 0. 81 ± 0. 12),P < 0. 05]. The relative expression levels of NKCC1 mRNA in all groups showed no statistical difference [( 1. 03 ± 0. 31) vs( 1. 14 ± 0. 43) vs( 1. 36 ± 0. 50),P > 0. 05]. The relative expression level of AQP4 protein in the high-dose group was lower than that of the control group [( 0. 80 ± 0. 25) vs( 1. 19 ± 0. 42),P < 0. 05]. CONCLUSION: The brain edema induced by subacute inhalation of 1,2-DCE is of mixed types with vasogenic edema as its main symptom. Its pathogenesis is related to the changes of AQP4 expression.

To observe the effect of calycosin on the proliferation and activation of primary hepatic stellate cells (HSCs) in rats, and prove calycosin shows the effects through peroxisome proliferator-activated receptor γ(PPARγ) and farnesoid X receptor (FXR). The results indicated that calycosin could inhibit HSC proliferation and expressions of activation marker smooth muscle actin-α and type I collagen. With the increase in HSC activation time, FXR expression reduced, but with no notable impact from calycosin. Calycosin could up-regulate PPARγ expression and its nuclear transition in a concentration-dependent manner. Its prohibitory effect on HSC activation could be blocked by PPARγ antagonist. In conclusion, calycosin could inhibit HSC activation and proliferation, which may be related with the up-regulation of PPARγ signal pathway.
Animals ; Cell Proliferation ; drug effects ; Cells, Cultured ; Drugs, Chinese Herbal ; pharmacology ; Hepatic Stellate Cells ; cytology ; drug effects ; metabolism ; Isoflavones ; pharmacology ; Male ; PPAR gamma ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Cytoplasmic and Nuclear ; genetics ; metabolism ; Up-Regulation ; drug effects