OBJECTIVE: To observe postoperative analgesia and preemptive analgesia of Tramadol hydrochloride sustained release tablets for nasal endoscopic operation. METHOD: A total of 188 patients undergoing nasal endoscopic operation were randomized into the experimental group and control group, with 94 patients in each group. Each patient in experimental group was gaved on Tramadol hydrochloride sustained release tablets at 12h, 24h, 48h, postoperation and before the cleaning up procession respectively, the control group was not administered. VAS scores were observed at 12, 24, and 48 hours after operation. The discomfort reaction during postoperation and cleaning up procession such as insomnia, impatien, nervous, frightening, syncope and shock were also observed and recorded. RESULT: Visuala analogue scale scores of the experimental groups after 12, 24 hours and 48h were significantly lower than the control group. The discomfort reaction appear more frequently in control group. CONCLUSION Tramadol hydrochloride sustained release tablets effectively relieves postoperative pain of nasal endoscopic operation. It can also decrease the discomfort reaction during postoperation and cleaning up procession and facilitate recovering of patients.
Adolescent ; Adult ; Analgesics, Opioid ; administration & dosage ; therapeutic use ; Delayed-Action Preparations ; Endoscopy ; methods ; Female ; Humans ; Male ; Middle Aged ; Nasal Surgical Procedures ; methods ; Pain Measurement ; Pain, Postoperative ; drug therapy ; Postoperative Period ; Tramadol ; administration & dosage ; therapeutic use ; Young Adult

Thymic stromal lymphopoietin (TSLP) is a type I interleukin 2 family cytokine composed of four short-chain α-helix bundles and has homology with interleukin-7. TSLP plays an important role in many allergic diseases or autoimmune diseases, such as asthma, atopic dermatitis, eosinophilic esophagitis, and inflammatory bowel disease, and promotes the development of these diseases. At present, there are some reports on TSLP in liver diseases, and some studies showed that it can promote the development and progression of liver diseases, while others showed that it plays a protective role in liver diseases. This article reviews the molecular composition and biological features of TSLP and the role of TSLP in benign liver diseases and liver tumors and elaborates on the research advances in TSLP in liver diseases.

ObjectiveTo investigate the role and mechanism of thymic stromal lymphopoietin （TSLP） in a mouse model of acetaminophen （APAP）-induced acute liver injury. MethodsA total of 16 wild-type （WT） male C57BL/6J mice were randomly divided into control group and APAP group， with 8 mice in each group， and the mice in the APAP group were given intraperitoneal injection of APAP solution at a dose of 400 mg/kg to establish an animal model， while those in the control group were given injection of an equal volume of normal saline， with samples collected after 6 hours. An automatic chemical analyzer was used to measure the serum levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST）； quantitative real-time PCR was used to measure the mRNA expression levels of the inflammatory factors tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in liver tissue； the kit was used to measure the content of glutathione （GSH） in liver tissue homogenate； quantitative real-time PCR and Western blot were used to measure the transcriptional level and protein expression level of TSLP. Furthermore， 22 WT male C57BL/6J mice were randomly divided into control group with 8 mice， APAP group with 8 mice， and APAP+recombination TSLP （rTSLP） group with 6 mice； the mice in the APAP+rTSLP group were given intraperitoneal injection of rTSLP solution， while those in the control group and the APAP group were given injection of the solvent PBS； after 30 minutes， the mice in the APAP+rTSLP group and the APAP group were given injection of APAP solution， while those in the control group were given injection of an equal volume of normal saline. The serum levels of ALT and AST were measured； HE staining was used to observe the pathological changes of the liver； kits were used to measure the levels of the oxidative stress indices malondialdehyde （MDA） and superoxide dismutase （SOD） in liver tissue homogenate； Western blot was used to measure the expression levels of the autophagy-related proteins LC3‍Ⅰ/Ⅱ， Beclin1， and P62 and the molecules such as nuclear factor erythroid 2-related factor 2 （Nrf2）， protein kinase B （Akt）， phosphorylated Akt （p-Akt）， mammalian target of rapamycin （mTOR）， and phosphorylated mTOR （p-mTOR）. In addition， 16 WT male C57BL/6J mice and 16 TSLP receptor-silenced （TSLPR^-/-） mice were divided into WT mouse control group， WT mouse APAP group， TSLPR^-/- mouse control group， and TSLPR^-/- mouse APAP group， with 8 mice in each group； the mice in the WT mouse APAP group and the TSLPR^-/- mouse APAP group were used for modeling by intraperitoneal injection of APAP solution at a dose of 400 mg/kg， and those in the WT mouse control group and the TSLPR^-/- mouse control group were given injection of an equal volume of normal saline. The serum levels of ALT and AST and the content of MDA in liver tissue were measured for these four groups， and Western blot was used to measure the protein expression levels of LC3Ⅰ/Ⅱ， Akt， and p-Akt. The independent-samples t test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsAfter the mouse model of APAP-induced acute liver injury was established successfully， there were significant increases in the mRNA and protein expression levels of TSLP compared with the control group （both P<0.01）. In the study of rTSLP， compared with the control group， the APAP group had significant increases in ALT and AST （both P<0.001） and radial necrosis along the central vein observed by HE staining of liver tissue， as well as significant reductions in the protein expression levels of the oxidative stress indices SOD and Nrf2 and a significant increase in the level of MDA （all P<0.01）； compared with the APAP group， the APAP+rTSLP group had significant reductions in ALT and AST， a significant reduction in necrotic area of liver tissue， significant increases in the protein expression levels of SOD and Nrf2， and a significant reduction in MDA （all P<0.05）； there were significant differences in the protein expression levels of LC3Ⅰ/Ⅱ， Beclin1， P62， p-Akt， and p-mTOR between the APAP+rTSLP group and the control group （all P<0.01）. In the study of TSLPR^-/- mice， compared with the WT mice after modeling， the TSLPR^-/- mice had significant increases in the levels of ALT， AST， and MDA and significant reductions in the expression levels of LC3Ⅰ/Ⅱ and p-Akt （all P<0.05）. ConclusionTSLP can increase autophagy， reduce oxidative stress， and thus improve acute liver injury induced by APAP overdose， possibly by activating the PI3K/Akt signaling pathway and inhibiting mTOR.

Acetaminophen (APAP) is the most common antipyretic, analgesic and anti-inflammatory drug, but its overdose often leads to acute liver injury, even acute liver failure, and death in some severe cases. At present, there is still a lack of specific treatments. The c-Jun N-terminal kinase (JNK) signal pathway is one of the potential therapeutic targets identified in recent years in overdose APAP-induced acute liver injury. This article reviews the JNK signaling pathway of APAP in liver metabolism, the activation of JNK signaling pathway and the amplification of oxidative stress, other pathways or cellular processes related to JNK signaling pathway, and the possible challenges of drugs targeting JNK, so as to provide direction and feasibility analysis for further research and clinical application of JNK signaling pathway targets in APAP hepatotoxicity, and to provide reference for searching for other targets.
Animals ; Mice ; Acetaminophen/adverse effects* ; Chemical and Drug Induced Liver Injury ; Chemical and Drug Induced Liver Injury, Chronic/metabolism* ; JNK Mitogen-Activated Protein Kinases/metabolism* ; Liver ; Mice, Inbred C57BL ; Signal Transduction