[Study on protective effect of Chaihu Shugan Powder against liver injury in rats with intrahepatic cholestasis by regulating FXR/Nrf2/ARE pathway].

This study aims to investigate the effect of Chaihu Shugan Powder(CHSG) on liver injury in rats with intrahepatic cholestasis by regulating farnesoid X receptor(FXR)/nuclear factor erythroid-2-related factor(Nrf2)/antioxidant response element(ARE) pathway. Eighty-four SD rats were classified into normal group, model group, CHSG-L group(0.5 g·kg~(-1)), CHSG-H group(2.5 g·kg~(-1)), ursodeoxycholic acid group(UDCA group, 100 mg·kg~(-1)), CHSG-H+sh-NC group(2.5 g·kg~(-1) CHSG+subcutaneous injection of sh-NC lentivirus), CHSG-H+sh-FXR group(2.5 g·kg~(-1) CHSG+subcutaneous injection of sh-FXR lentivirus), with 12 rats in each group. Rats were treated with corresponding drugs except for the normal group and the model group, once a day, for 7 days. On 5 th day, rats, except the normal group, were given α-naphthalene isothiocyanate(ANIT) at a dose of 100 mg·kg~(-1), once a day for 3 days to induce intrahepatic cholestasis, and the normal group was given the same amount of normal saline. Rats were anesthetized 1 h after the last administration and the 2 h bile flow was measured. Aeroset chemistry analyzer was employed to detect the levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin(TBIL), and total bile acid(TBA) in rat serum. Based on hematoxylin and eosin(HE) staining, the pathological changes of rat liver tissue were observed. Glutathione peroxidase(GSH-Px), superoxide dismutase(SOD), and malondialdehyde(MDA) in rat liver tissue homogenate were monitored with corresponding kits. Western blot was used to detect the expression of FXR, Nrf2, and heme oxygenase-1(HO-1) proteins in rat liver tissue. Compared with the normal group, the model group showed many spots or concentrated necrotic areas in the liver tissue, infiltration of a large number of inflammatory cells, swelling liver cells with nuclear shrinkage. The 2 h bile flow, levels of GSH-Px and SOD, and relative expression of FXR, Nrf2, and HO-1 proteins were significantly lower, and the levels of ALT, AST, TBIL, TBA and MDA were significantly higher in the model group than in the normal group. Compared with the model group, CHSG-L group, CHSG-H group, and UDCA group demonstrated significant alleviation of pathological damage of the liver tissue, significantly high 2 h bile flow, levels of GSH-Px and SOD, and expression of FXR, Nrf2 and HO-1 proteins, and significantly low levels of ALT, AST, TBIL, TBA and MDA. Compared with the CHSG-H group, the CHSG-H+sh-FXR group had worse liver pathological damage, significantly low levels of 2 h bile flow, levels of GSH-Px and SOD, and expression of FXR, Nrf2, and HO-1 proteins, and significantly high levels of ALT, AST, TBIL, TBA, and MDA. CHSG may protect against liver injury in rats with intrahepatic cholestasis by activating the FXR/Nrf2/ARE pathway.

Posterior cruciate ligament reconstruction with independent internal brace reinforcement: surgical technique and clinical outcomes with a minimum two year follow-up.

PURPOSE: We developed an augmentation technique for PCL reconstruction with independent internal brace reinforcement and evaluated the functional outcome after PCL reconstruction employing autologous hamstrings augmented with an internal brace system for patients with isolated or combined grade 3 posterior instability who were treated with this technique. METHODS: From January 2016 to January 2018, patients with isolated or combined grade 3 PCL tears who underwent single-bundle PCL reconstruction using autologous hamstrings augmented with independent internal braces were studied. The function of the operated knee was evaluated according to the International Knee Documentation Committee (IKDC) score, Lysholm score, and Tegner activity score. The patients were asked the level of returned to their previous sport. Posterior knee laxity was examined with a KT-1000 arthrometer, and data on range of motion (ROM), re-operation, and other complications were collected. RESULTS: A total of 33 consecutive patients who received single-bundle PCL reconstruction using autologous hamstrings augmented with independent internal braces with a minimum two years follow-up were included in this study. Two patients had undergone this procedure during the study period and were not included in this study (one had combined bone fractures, and one patient had previous meniscus surgery). Thirty-one patients were available for final analysis. The mean follow-up was 45.35 ± 10.88 months (range 29-66 months). The average IKDC subjective knee evaluation scores from 51.65 ± 12.35 to 84.52 ± 6.42, the Lysholm score from 53.90 ± 11.86 to 85.68 ± 4.99, and the Tegner score from 2.81 ± 0.79 to 6.71 ± 1.83 (P < 0.05 for all). The mean total posterior side-to-side difference in knee laxity, assessed using a KT-1000 arthrometer, decreased from 12.13 ± 2.66 mm pre-operatively to 1.87 ± 0.56 mm post-operatively at 70° (P < 0.05). Most patients (29/31) had normal or near normal knee ROM post-operatively; two patients revealed a 6-15° loss of knee flexion compared with the contralateral knee. Twenty-nine patients (93.55%) returned to a normal daily exercise level. Twenty-three patients (74.19%) returned to competitive sports with high-level sports (Tegner score of 6 or above; eleven patients (35.48%) reported to be on the same level as well as the Tegner level); six patients (19.35%) returned to recreational sports (Tegner score of 4 or 5). Two patients had Tegner scores of 2 and 3, indicating poor function level. No patient needed PCL revision surgery during the follow-up period. CONCLUSION: Single-bundle PCL reconstruction with internal brace augmentation for PCL injury exhibited satisfactory posterior stability and clinical outcomes in patients with isolated or combined grade 3 PCL injuries at a minimum two year follow-up.

Vancomycin lavage for the incidence of acute surgical site infection following primary total hip arthroplasty and total knee arthroplasty.

BACKGROUND: Surgical site infection is a rare but serious complication associated with total joint arthroplasty (TJA). There are limited data on the effectiveness of intrawound irrigation with vancomycin solution (1000 mg/L; 2 L) before wound closure for preventing acute surgical site infection following primary total hip arthroplasty (THA) and total knee arthroplasty (TKA). AIM: To investigate the effectiveness of prophylactic intraoperative application of vancomycin (1000 mg/L; 2 L) solution vs. plain irrigation in reducing the incidence of acute surgical site infection following primary THA and TKA. METHODS: A retrospective review of 2725 consecutive patients undergoing THA or TKA from January 2012-December 2019 was performed. These patients received either intrawound irrigation with normal saline before wound closure between January 2012 and December 2015 (group 1, 1018 patients; 453 undergoing THA and 565 undergoing TKA) or intrawound irrigation with vancomycin solution (1000 mg/L) before wound closure between January 2016 and December 2019 (group 2, 1175 patients; 512 undergoing THA and 663 undergoing TKA). The outcomes were the incidences of postoperative surgical site infection and wound healing complications within 3 mo of primary TJA. RESULTS: There were no significant demographic differences between the 2 groups. There was a significantly higher incidence of acute infection at the surgical site in patients who received intrawound irrigation with normal saline before wound closure than in those who received intrawound irrigation with vancomycin solution (1000 mg/L; 2 L) before wound closure (overall incidence of infection: group 1, 2.46% vs group 2, 0.09%, P < 0.001). There was no significant difference in the incidence of wound healing complications between the two groups. CONCLUSION: Prophylactic irrigation with vancomycin solution (1000 mg/L; 2 L) significantly decreases the incidence of acute surgical site infection after primary TJA. This strategy is a safe, efficacious, and inexpensive method for reducing the incidence of acute surgical site infection after TJA.

Biomechanical evaluation of a novel transtibial posterior cruciate ligament reconstruction using high-strength sutures in a porcine bone model.

BACKGROUND: Multiple techniques are commonly used for posterior cruciate ligament (PCL) reconstruction. However, the optimum method regarding the fixation of PCL reconstruction after PCL tears remains debatable. The purpose of this study was to compare the biomechanical properties among three different tibial fixation procedures for transtibial single-bundle PCL reconstruction. METHODS: Thirty-six porcine tibias and porcine extensor tendons were randomized into three fixation study groups: the interference screw fixation (IS) group, the transtibial tubercle fixation (TTF) group, and TTF + IS group (n = 12 in each group). The structural properties of the three fixation groups were tested under cyclic loading and load-to-failure. The slippage after the cyclic loading test and the stiffness and ultimate failure load after load-to-failure testing were recorded. RESULTS: After 1000 cycles of cyclic testing, no significant difference was observed in graft slippage among the three groups. For load-to-failure testing, the TTF + IS group showed a higher ultimate failure load than the TTF group and the IS group (876.34 ±â€Š58.78 N vs. 660.92 ±â€Š77.74 N [P < 0.001] vs. 556.49 ±â€Š65.33 N [P < 0.001]). The stiffness in the TTF group was significantly lower than that in the IS group and the TTF + IS group (92.77 ±â€Š20.16 N/mm in the TTF group vs. 120.27 ±â€Š15.66 N/m in the IS group [P = 0.001] and 131.79 ±â€Š17.95 N/mm in the TTF + IS group [P < 0.001]). No significant difference in the mean stiffness was found between the IS group and the TTF + IS group (P = 0.127). CONCLUSIONS: In this biomechanical study, supplementary fixation with transtibial tubercle sutures increased the ultimate failure load during load-to-failure testing for PCL reconstruction.

The molecular mechanism and effect of cannabinoid-2 receptor agonist on the blood-spinal cord barrier permeability induced by ischemia-reperfusion injury.

Previous studies have shown that modulation of the receptor-mediated endocannabinoid system during ischemia injury can induce potent neuroprotective effects. However, little is known about whether cannabinoid-2 (CB2) receptor agonist would produce a protective effect on blood-spinal cord barrier (BSCB) during ischemia. Using an in vivo transient spinal cord ischemia model in rats, JWH-015 (1mg/kg, i.p.), a CB2 receptor selective agonist, or vehicles were injected 20 min before ischemia. The effects of JWH-015 on BSCB permeability, the major structural protein for the formation of caveolae, caveolin-1 (cav-1), tight junction (TJ) protein Occludin and zona occludens protein-1 (ZO-1) were examined at day 1, day 3 and day 7 of reperfusion after transient spinal cord ischemia in rats. Here we demonstrated that JWH-015 significantly down-regulated the expression of cav-1, up-regulated the expression of TJ proteins, and then decreased the permeability of BSCB compared with control group. In addition, using an in vitro BBB model, oxygen glucose deprivation (OGD) was applied to simulate spinal cord ischemia in vitro in Human brain microvascular endothelial cells (HBMECs). JWH-015 greatly increased the transepithelial electrical resistance (TEER) and changed the distribution of ZO-1 and Occludin. Moreover, JWH-015 induced the expression of p-PKB and p-FoxO1 protein and decreased the expression of cav-1, which were greatly reversed by ROS inhibitor or PI3K inhibitor. Taken together, all of these results suggested that JWH-015 might regulate the BSCB permeability and this effect could be related to paracellular and transcellular pathway. And pharmacological CB2R ligands offer a new strategy for BSCB protection during ischemic injury.