This paper aimed to explore the intestinal toxicity of Euphoriae Ebracteolata Radix(EER) before and after being processed with Mongolian medicine Hezi Decoction(HZD) and the toxicity-reducing mechanism of this processing method. The intestinal toxicity in rats treated with unprocessed EER and HZD-processed EER extracts via 95% ethanol was compared. The comparison was based on several indicators, including fecal volume, serum diamine oxidase(DAO) and D-lactate(D-LA) levels, the water content of various intestinal segments and their contents, and inflammatory factor levels in intestinal segments. Tandem mass tag(TMT) quantitative proteomics technology was employed to analyze the key proteins associated with changes in intestinal toxicity between unprocessed EER and HZD-processed EER. The results indicated that compared with the blank group, unprocessed EER significantly increased the fecal volume, serum DAO and D-LA levels, water content of the ileal segment and its contents, as well as the release levels of inflammatory factors, including tumor necrosis factor(TNF-α) and interleukin-1 beta(IL-1β) in the ileal segment of rats(P<0.05), indicating that EER can cause diarrhea, increase intestinal permeability, and induce intestinal inflammation. Compared with those in the unprocessed EER group, all indicators in the HZD-processed EER group were significantly reduced(P<0.05). The TMT quantitative proteomics analysis revealed that a total of 6 487 proteins were identified in the rat ileum tissue. Compared to the blank group, 182 proteins exhibited significant changes in the unprocessed EER group, while 907 proteins in the HZD-processed EER group showed significant changes. The intersection of the differential proteins between the two groups identified 38 common proteins. Among them, the protein levels of intestinal barrier tight junction protein claudin3, squalene monooxidase(Sqle), clusterin, Na~+/H~+ exchange regulatory cofactor NHE-RF3(Pdzk1), and Y+L amino acid transporter 1(Slc7a7) exhibited significant changes before and after processing, and these changes were closely related to intestinal barrier function. Compared with the blank group, the expression of claudin3, Pdzk1, and Slc7a7 in the raw product group was significantly down-regulated(P<0.05),while the expression of Sqle and clusterin was significantly up-regulated(P<0.05).Compared with the raw product group, the expression of claudin3, Pdzk1, and Slc7a7 in the processed product group of HZD was significantly up-regulated(P<0.05), while the expression of Sqle and clusterin was significantly down-regulated(P<0.05). Western blot was used to detect the expression level of claudin 3 in the ileum of rats in each group. The results show that compared to that in the blank group, the expression level of claudin 3 in the unprocessed EER group was significantly reduced(P<0.01); compared to that in the unprocessed EER group, the expression level of claudin 3 in the HZD-processed EER group was significantly increased(P<0.01). This finding aligned with the proteomic outcomes, indicating that claudin 3 protein levels could serve as a crucial indicator for intestinal damage caused by EER. In summary, HZD-processed EER can reduce EER's intestinal toxicity, and the primary mechanism for its alleviation of intestinal barrier damage is the regulation of the intestinal barrier tight junction protein claudin 3 and other intestinal-related proteins.
Animals ; Drugs, Chinese Herbal/adverse effects* ; Proteomics ; Rats ; Male ; Rats, Sprague-Dawley ; Intestines/drug effects* ; Intestinal Mucosa/drug effects* ; Tumor Necrosis Factor-alpha/metabolism*

Objective To explore the effect of methylene blue combined with ropivacaine for sa-phenous nerve block on the postoperative analgesia in patients undergoing total knee arthroplasty.Methods Sixty patients were selected for elective TKA,24 males and 36 females,aged 60-75 years,BMI 18.5-30.0 kg/m2,ASA physical status Ⅱ or Ⅲ.The patients were divided into two groups using randomized nu-merical table method:methylene blue combined with ropivacaine group(group MR)and ropivacaine group(group R),30 patients in each group.Ultrasound-guided saphenous nerve block was performed with 0.10％methylene blue+0.25％ropivacaine composite 20 ml in group MR,and ultrasound-guided saphenous nerve block was performed with 0.25％ropivacaine 20 ml in group R before the combined spinal-epidural anesthe-sia.The VAS pain scores at rest and during activity at 6,12,24,48,and 72 hours postoperatively,the maximum range of motion mobility(ROM)of the knee joint of the affected limb,the quadriceps unarmed manual muscle test(MMT)scores at 24,48,and 72 hours postoperatively,the effective number of analge-sic pump presses,and the time of the first additional time of the remedial analgesic were recorded.The com-plications related to nerve block,such as bleeding,infection,local anesthetic poisoning,nerve injury,and peripheral tissue injury were recorded.Results Compared with group R,the VAS pain score at rest was significantly lower in group MR at 12,24,48,and 72 hours postoperatively(P＜0.05).Compared with group R,the VAS pain scores during activity were significantly lower in the group MR at 48 and 72 hours postoperatively(P＜0.05).Compared with group R,ROM of the knee joint of the affected limb was signif-icantly greater in group MR at 24,48,and 72 hours postoperatively(P＜0.05).The effective number of analgesic pump presses and the rate of remedial analgesia were significantly lower in the group MR compared with group R(P＜0.05).There were no complications related to nerve block during hospital stay in both groups.Conclusion Ultrasound-guided methylene blue combined with ropivacaine for saphenous nerve block can enhance the postoperative analgesic effect,prolong the duration of analgesia,reduce the use of postoperative analgesics,and facilitate the functional exercise of the knee joint in the early postoperative pe-riod.

Objective To investigate the expression of tumor necrosis factor alpha(TNF-α)and its relationship with infiltrating lymphocytes in lichen planus(LP).Methods Tissue specimens were obtained from the lesions of 60 patients with LP and normal skin of 20 human controls.Immunohistochemical SP method was used to detect the expression of TNF-α,and infiltrating lymphocytes were counted in TNF-α-positive tissue sections.Results TNF-α was expressed in 72％ of the LP specimens but in none of the control specimens(P ＜ 0.01).Positive staining for TNF-α was mainly located in the membrane of prickle cells,cytoplasm or membrane of dermal infiltrating lymphocytes.The expression of TNF-α in LP was uncorrelated with age,sex or disease course(all P ＞ 0.05),but was positively correlated with infiltrating lymphocyte number (rs =0.47,P ＜ 0.01).Conclusion TNF-α seems to play a certain role in the pathogenesis of LP.