Objective To investigate the effects of internal and external biliary drainage on liver regeneration of the obstructive jaundice rats after partial hepatectomy.Methods The rat models of obstructive jaundice with 70％ liver resection were successfully constructed.All the 120 rats were randomly divided into the control group:rats received middle and left hepatic lobectomy; internal drainage group:a drainage tube was placed between the dilated bile duct and the duodenum; external drainage group:a drainage tube was placed in the dilated bile duct.There were 40 rats in each group.Rats in the internal and external drainage groups received middle and left hepatic lobectomy at postoperative day 7.The blood and hepatic tissues were collected at postoperative day 0,1,2,4,12,24,48,72 hours after operation,and the rate of liver regeneration and mitotic index were determined.The expression of proliferating cell nuclear antigen (PCNA) and signal transducer and activator of transcription 3 (STAT3) in the hepatic tissues were detected by immunohistochemistry,and the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were detected by ELISA,and the mRNA expressions of TNF-α and IL-6 were detected by RT-PCR.All data were analyzed using the one way analysis of variance or SNK test.Results Within 72 hours after partial hepatectomy,the rate of liver regeneration of the internal drainage group was 94.86％± 12.72％,which was significant higher than 62.39％±8.01％ of the external drainage group and 45.77％ ± 5.41％ of the control group (F =33.62,P ＜ 0.05).The mitotoic index and PCNA levels of the 3 groups had obvious increase at postoperative hour 12,and the mitotoic index and PCNA levels of the external drainage group reached peak at postoperative hour 24,which were 24.47％ ± 4.01％ and 88.1％ ± 9.2％,respectively,the mitotoic index and PCNA levels of the control group and the external drainage group reached peak at postoperative hour 48,which were 15.80％ ± 1.08％,58.3％ ± 5.8％ and 18.40％ ± 1.12％,70.2％ ± 6.9％,respectively.The mitotoic index and PCNA levels of the internal drainage group were significantly higher than those of the control group and the external drainage group (P ＜ 0.05).The expression of STAT3 expression of the internal drainage group reached peak at postoperative hour 4,which was 42.6％ ± 3.6％ ;the expression of STAT3 expression of the control group and the external drainage group reached peak at postoperative hour 12,which were 22.9％ ± 2.0％ and 29.2％± 3.7％.The peak level of STAT3 of the internal drainage group was significantly higher than those of the control group and the external drainage group (P ＜0.05).The levels of TNF-α and IL-6 of the internal drainage group reached peak at postoperative hour 12,which were (227 ±23)U/L and (256 ± 32)U/L; the levels of TNF-α and IL-6 of the control group and the external drainage group reached peak at postoperative hour 24,which were (309 ± 41) U/L and (388 ± 40) U/L,(287 ± 30)U/L and (346± 33)U/L,respectively.The levels of TNF-α and IL-6 of the internal drainage group at postoperative hour 0,1,2,4,12,24,48,72 were significantly lower than those of the control group and the external drainage group (P ＜ 0.05).The expressions of TNF-α mRNA of the control group,internal drainage group and external drainage group reached peak at postoperative hour 4,which were 0.92 ±0.14,0.39 ±0.05,0.80 ±0.15,respectively.The expressions of IL-6 mRNA reached peak at postoperative hour 12,which were 0.79 ± 0.07,0.38 ± 0.06,0.63 ±0.10,respectively.The expressions of TNF-α mRNA and IL-6 mRNA of the internal drainage group at postoperative hour 0,1,2,4,12,24,48,72 were significantly lower than those of the control group and the external drainage group (P ＜ 0.05).Conclusions Both internal and external drainage can improve liver regeneration of obstructive jaundice rats following partial hepatectomy,while the effect of internal drainage is superior.Internal biliary drainage has influence on the expression of STAT3 by decreasing the levels of TNF-α and IL-6,and help to improve liver regeneration of obstructive jaundice rats following partial hepatectomy.

Lymphocyte-activation gene 3(LAG-3)is an inhibitory immune checkpoint receptor that negatively regulates the function of T cells to prevent over-activation of the immune system from damaging human body.In the existence of tumors and chronic infections,persistent antigenic stimulation induces upregulation of LAG-3 expression in effector T cells,leading to T cell exhaustion and tumor immune escape.Targeting LAG-3 drugs can reactivate the anti-tumor function of T cells by specifically blocking the signaling pathway of LAG-3,and have shown promising efficacy in a variety of solid tumors,hematologic tumors and autoimmune diseases.In this paper,we summarize the current research progress on the structure,ligand and regulatory function of LAG-3,review the current status of clinical trials of LAG-3-targeted drugs,and further discuss the clinical application strategy and development direction of LAG-3-targeted drugs,with a view to providing reference for further in-depth research on LAG-3.

Objective To investigate the role of silencing regulatory protein 1(Sirt1)in the regulation of Vibrio vulnificus sepsis-induced macrophage apoptosis and the molecular mechanisms.Methods Mouse RAW264.7 macrophages which stably overexpressed Sirt1 were constructed and screened by genistein G418.CCK-8 analysis was used to detect the proliferation of cells in the control group and Sirt1-Flag group.The changes of expression levels of apoptosis-associated protein poly ADP-ribose polymerase(PARP),cleaved-PARP,caspase3,cleaved-caspase3 and acetylated p53 in different treatment groups were detected via Western blotting.A Vibrio vulnificus sepsis model in mice was established,and the expression levels of apoptosis-associated protein cleaved-caspase3 in the lung,spleen and liver of mice of different treatment groups were detected by immunohistochemistry.Results Overexpression of Sirt1 reduced VVC-induced RAW264.7 cell damage.Overexpression of Sirt1 as well as RSV pretreatment lowered the expression of apoptosis-associated protein cleaved-PARP,cleaved-caspase3 and acetylated p53 in VVC-stimulated RAW264.7 cells and mouse peritoneal macrophages.In the mouse model of Vibrio vulnificus sepsis,therapeutic administration of RSV reduced the expression of apoptosis-associated protein marker cleaved-caspase3 in lung,spleen and liver tissues.Conclusion Sirt1 can inhibit p53 acetylation and reduces apoptosis in mouse macrophages,which helps protect against Vibrio vulnificus sepsis.

Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection is a new respiratory infectious disease.Patients with chronic kidney disease are at high risk of SARS-CoV-2 infection.Once they develop SARS-CoV-2 infection,the rate of progression to severe illness or even death is much higher than that of the general population.Nirmatrelvir/ritonavir significantly reduce the risk of severe illness and death in patients infected with SARS-CoV-2.In this paper,the dosing regimen and drug interaction of nirmatrelvir/ritonavir in patients with different stages of chronic kidney disease complicated with SARS-CoV-2 infection were reviewed to provide a reference for clinical rational medication for patients with chronic kidney disease.

ObjectiveTo explore the syndrome elements and evolving patterns of patients with hepatitis B virus-related acute on chronic liver failure （HBV-ACLF） at different stages. MethodsClinical information of 1,058 hospitalized HBV-ACLF patients， including 618 in the early stage， 355 in the middle stage， and 85 in the late stage， were collected from 18 clinical centers across 12 regions nationwide from January 1， 2012 to February 28， 2015. The “Hepatitis B-related Chronic and Acute Liver Failure Chinese Medicine Clinical Questionnaire” were designed to investigate the basic information of the patients， like the four diagnostic information （including symptoms， tongue， pulse） of traditional Chinese medicine （TCM）， and to count the frequency of the appearance of the four diagnostic information. Factor analysis and cluster analysis were employed to determine and statistically analyze the syndrome elements and patterns of HBV-ACLF patients at different stages. ResultsThere were 76 four diagnostic information from 1058 HBV-ACLF patients， and 53 four diagnostic information with a frequency of occurrence ≥ 5% were used as factor analysis entries， including 36 symptom information， 12 tongue information， and 5 pulse information. Four types of TCM patterns were identified in HBV-ACLF， which were liver-gallbladder damp-heat pattern， qi deficiency and blood stasis pattern， liver-kidney yin deficiency pattern， and spleen-kidney yang-deficiency pattern. In the early stage， heat （39.4%， 359/912） and dampness （27.5%， 251/912） were most common， and the pattern of the disease was dominated by liver-gallbladder damp-heat pattern （74.6%， 461/618）； in the middle stage， dampness （30.2%， 187/619） and blood stasis （20.7%， 128/619） were most common， and the patterns of the disease were dominated by liver-gallbladder damp-heat pattern （53.2%， 189/355）， and qi deficiency and blood stasis pattern （27.6%， 98/355）； and in the late stage， the pattern of the disease was dominated by qi deficiency （26.3%， 40/152） and yin deficiency （20.4%， 31/152）， and the patterns were dominated by qi deficiency and blood stasis pattern （36.5%， 31/85）， and liver-gallbladder damp-heat pattern （25.9%， 22/85）. ConclusionThere are significant differences in the distribution of syndrome elements and patterns at different stages of HBV-ACLF， presenting an overall trend of evolving patterns as "from excess to deficiency， transforming from excess to deficiency"， which is damp-heat → blood stasis → qi-blood yin-yang deficiency.