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Background: Derotational distal femoral osteotomy (DDFO) has been used to treat patients with recurrent patellar dislocation (RPD) with increased femoral anteversion. However, no study has reported second-look arthroscopic findings in the patellofemoral joint after DDFO., Purpose: To report clinical and second-look arthroscopic outcomes for DDFO with combined medial patellofemoral ligament reconstruction (MPFL-R) in treating RPD with increased femoral anteversion., Study Design: Case series; Level of evidence, 4., Methods: From 2015 to 2019, 131 consecutive patients (144 knees) with RPD were treated with combined MPFL-R and DDFO. Patients with a femoral anteversion angle >30° and a minimum 2-year clinical follow-up period were included in the study. Three-dimensional computed tomography was performed to evaluate rotational deformities of the lower leg. Radiographic parameters presenting bony abnormalities associated with RPD were measured. Second-look arthroscopic evaluations were available for 86 knees to assess patellar tracking and chondral lesion changes. Moreover, clinical and radiologic outcomes were assessed pre- and postoperatively at a minimum 2 years., Results: A total of 102 knees in 92 patients were included in the present study with a mean clinical follow-up of 4.1 years (range, 2.0-5.6 years). Mean ± SD femoral anteversion changed significantly from 34.7°± 7.5° preoperatively to 11.3°± 0.2° postoperatively ( P < .001), and mean tibial tubercle-trochlear groove distance decreased significantly from 19.6 ± 3.5 mm preoperatively to 17.4 ± 3.2 mm postoperatively ( P < .001). In the majority of knees, at the time of second-look arthroscopic assessment, chondral lesion status remained unchanged at the lateral patellar facet (96%) and trochlear groove (95%); in contrast, chondral damage at the medial patellar facet was aggravated in 9 cases (10%). All functional scores (Tegner, Lysholm, visual analog scale, and Kujala scores) improved significantly at final follow-up. None of the patients experienced redislocation or subluxation after surgery., Conclusion: Chondral lesions in the patellofemoral joint remained unchanged in the majority of cases in second-look arthroscopy after combined MPFL-R and DDFO. Moreover, high-grade trochlear dysplasia and arthroscopic residual patellar maltracking might be associated with cartilaginous deterioration at the medial patellar facet after surgery.

Background: Increased posterior tibial slope (PTS) has been reported to be associated with irreducible anterior tibial subluxation in extension after anatomic anterior cruciate ligament (ACL) reconstruction (ACLR), which raises concerns about the greater risk of graft roof impingement (GRI) although the tibial tunnel is positioned anatomically., Hypothesis: Increased PTS would be associated with greater risk of GRI after anatomic ACLR., Study Design: Case-control study; Level of evidence, 3., Methods: Between January 2016 and December 2017, a total of 418 consecutive patients were diagnosed as having noncontact ACL injuries and underwent primary anatomic ACLR. Among them, 26 patients had ≥1 of the following features during the second-look arthroscopy: fractured/guillotined bundles at the tibial insertion or cyclops lesion. These patients were confirmed to have GRI and were allocated to the study group. They were also matched 1:2 to 52 control participants without GRI. PTS was measured on true lateral whole-leg radiographs. Intra-articular ACL graft signal intensity was evaluated on postoperative magnetic resonance imaging scans (mean, 32.8 months; range, 26-38 months) and divided into 3 grades (I, good; II, moderate; III, poor) based on degree of GRI. Moreover, anterior subluxation of the lateral compartment (ASLC) and medial compartment (ASMC) in extension relative to the femoral condyles were measured on postoperative magnetic resonance imaging scans and compared between the groups. In addition, predictors of GRI were evaluated using multivariate logistic regression analysis and included body mass index, PTS, pivot-shift test, KT-1000 side-to-side difference, and concomitant meniscal tears., Results: PTS in the study group was significantly higher than that in control group (mean ± SD, 13.8°± 1.5° vs 9.5°± 1.8°; P < .05). In the study group (n = 26), patients with grade III (poor) graft signal intensity (n = 9) showed significantly higher PTS than those with grade II (moderate; n = 17) (16.4°± 1.7° vs 12.4°± 1.3°; P < .05). Moreover, the mean postoperative ASLC and ASMC in extension were significantly larger in the study group than the control group (ASLC, 4.1 ± 1.3 vs 0.8 ± 0.4 mm; ASMC, 4.3 ± 1.5 vs 0.9 ± 0.3 mm; P < .05). Furthermore, the abnormal degree of PTS (≥12°) was determined to be an independent risk factor associated with GRI after anatomic ACLR (odds ratio, 9.0 [95% CI, 3.7-30.2]; P < .001), whereas body mass index, grade of pivot-shift test, KT-1000 side-to-side difference, and concomitant meniscal tears were not., Conclusion: Increased PTS (≥12°) was associated with greater risk of GRI after anatomic ACLR. This may provide additional information for counseling patients with greater risk of GRI.

Background: Steep posterior tibial slope (PTS; >13°), excessive anterior tibial subluxation (ATS) in extension (>10 mm), and meniscus posterior horn tears (MPHTs) have been identified to be associated with primary anterior cruciate ligament (ACL) reconstruction (ACLR) failure. Recent studies have reported that steep PTS is directly correlated with excessive ATS in extension and concomitant MPHTs, especially for those patients with chronic (>6 months) ACL deficiency. There is increasing biomechanical evidence that slope-reducing tibial osteotomy decreases ATS in extension and protects the ACL graft., Hypothesis: Slope-reducing tibial osteotomy combined with primary ACLR is effective for producing improved knee stability in patients with steep PTS (>13°), excessive ATS in extension (>10 mm), and concomitant chronic MPHTs (>6 months)., Study Design: Case series; Level of evidence, 4., Methods: Between June 2016 and January 2018, 18 patients with ACL injuries who had steep PTS (>13°), excessive ATS in extension (>10 mm), and concomitant chronic MPHTs (>6 months) underwent slope-reducing tibial osteotomy combined with primary ACLR. The PTS and anterior subluxation of the lateral and medial compartment (ASLC and ASMC) in extension before and after the index procedures were regarded as primary clinical outcomes. Moreover, Lysholm score, Tegner activity score, International Knee Documentation Committee (IKDC) objective grade, pivot-shift test, and KT-1000 side-to-side difference were evaluated preoperatively and at the minimum 2-year follow-up visit., Results: The mean PTS was 18.5° (range, 17°-20°) preoperatively and 8.1° (range, 7°-9°) postoperatively ( P < .01). The mean ASLC and ASMC in extension were 12.1 mm and 11.9 mm preoperatively, which reduced to 1.0 mm and 1.5 mm at the last follow-up visit ( P < .05). In addition, all of the following showed significant improvements (pre- vs postoperatively): mean Lysholm score (46.5 vs 89.5; P < .05), mean Tegner activity score (5.7 vs 7.3; P < .05), IKDC objective grading results (18 grade D vs 14 grade A and 4 grade B; P < .05), pivot-shift tests (15 grade 2+ and 3 grade 3+ vs 18 grade 0; P < .01), and KT-1000 side-to-side difference (13.0 mm vs 1.6 mm; P < .01). Moreover, no graft reruptures were found at the final follow-up visit., Conclusion: In this study, slope-reducing tibial osteotomy combined with primary ACLR effectively improved knee stability in patients with steep PTS (>13°), excessive ATS in extension (>10 mm), and concomitant chronic MPHTs (>6 months).

Background: Steep posterior tibial slope (PTS) and excessive anterior tibial translation (ATT) have been identified as important anatomic risk factors for anterior cruciate ligament (ACL) injury, which have raised concerns about clinical outcomes after primary ACL reconstruction (ACLR)., Purpose: To investigate anatomic risk factors of primary ACLR failure and to determine the cutoff values of PTS and ATT for predicting primary ACLR failure., Study Design: Case-control study; Level of evidence, 3., Methods: Between November 2015 and May 2017, a total of 215 consecutive patients with clinically diagnosed noncontact ACL injuries who underwent primary anatomic ACLR were retrospectively analyzed. Among them, 25 patients who showed complete discontinuity of ACL fibers on final follow-up magnetic resonance imaging scans were allocated into the failure group (study group). They were matched 1:2 to 50 control participants who showed clear and continuous ACL fibers on magnetic resonance imaging scans (control group). PTS and ATT were measured on preoperative weightbearing whole leg lateral radiographs and compared between the groups. The cutoff values of PTS and ATT for predicting primary ACLR failure were determined by the receiver operating characteristic curve. Moreover, predictors of primary ACLR failure were assessed by multivariate logistic regression analysis, including sex, age, body mass index, concomitant meniscal tears, degree of pivot-shift test, and KT-1000 arthrometer side-to-side difference, PTS, and ATT., Results: PTS and ATT values in the study group were significantly higher than those in the control group (mean ± SD: PTS, 17.2°± 2.2° vs 14.4°± 2.8°; ATT, 8.3 ± 3.4 mm vs 4.1 ± 3.1 mm; P < .001). The cutoff values of PTS and ATT for predicting primary ACLR failure were 17° (sensitivity, 66.7%; specificity, 90.9%) and 6 mm (sensitivity, 87.5%; specificity, 79.5%), respectively. Additionally, PTS ≥17° (odds ratio, 15.6; 95% CI, 2.7-91.5; P = .002) and ATT ≥6 mm (odds ratio, 9.9; 95% CI, 1.9-51.4; P = .006) were determined to be risk factors of primary ACLR failure, whereas sex, age, body mass index, concomitant meniscal tears, degree of the pivot-shift test, and KT-1000 arthrometer side-to-side difference were not., Conclusion: In this study, PTS ≥17° and ATT ≥6 mm, as measured on weightbearing whole leg radiographs, were identified to be predictive risk factors of primary ACLR failure. This study adds to the existing knowledge about potential surgical indications of simultaneous slope-reducing high tibial osteotomy to mitigate the primary ACLR failure rate.

Background: Anterior tibial subluxation (ATS) in extension after anterior cruciate ligament (ACL) injury highlights an increased anterior position of the tibia relative to the femur. Recent studies demonstrated that subluxation is sometimes irreducible and the normal tibiofemoral relationship is not restored by ACL reconstruction (ACLR), which raises concerns regarding clinical outcomes after ACLR., Hypothesis: Excessive preoperative ATS in extension is associated with inferior knee stability after anatomic ACLR., Study Design: Cohort study; Level of evidence, 3., Methods: From March 2016 to January 2017, a total of 487 consecutive patients with clinically diagnosed noncontact ACL injuries who underwent primary anatomic ACLR were retrospectively analyzed. Of these patients, 430 met the criteria for inclusion in this study. Anterior subluxation of the lateral and medial compartments (ASLC and ASMC) in extension relative to the femoral condyles was measured on preoperative magnetic resonance imaging. Twenty patients (study group) who demonstrated excessive (>10 mm) ASLC and ASMC in extension were matched 1:2 to 40 participants (control group) who showed minimal or no (<3 mm) ASLC and ASMC in extension. The amount of ASLC and ASMC in extension relative to the femoral condyles at 2 years postoperatively was the primary outcome. Moreover, the Lysholm score, IKDC grade (International Knee Documentation Committee), and stability assessments (pivot-shift test and KT-1000 arthrometer side-to-side difference) were evaluated preoperatively and at the last follow-up visit., Results: The preoperative mean ASLC and ASMC in extension of the study group were both significantly larger than those of the control group (study group vs control group: ASLC, 13.5 mm vs 1.2 mm; ASMC, 12.4 mm vs 1.0 mm; P < .05). Moreover, patients in the study group showed significantly larger posterior tibial slope than the patients in the control group (17.8°± 2.5° vs 9.5°± 1.5°; P < .05). At the final follow-up visit, the mean ASLC and ASMC of the study group were 8.1 mm and 7.3 mm, which were significantly larger than those of the control group (ASLC, 0.9 mm; ASMC, 0.7 mm; P < .05). In addition, the study group showed inferior knee stability when compared with the control group in terms of both the pivot-shift test (study group vs control group: 2 grade 2, 10 grade 1, and 8 grade 0 vs 1 grade 1 and 39 grade 0; P < .05) and the KT-1000 arthrometer side-to-side difference (study group vs control group: 4.4 ± 1.2 mm vs 1.5 ± 0.6 mm; P < .05). Furthermore, the study group showed significantly lower mean Lysholm score (study group vs control group: 80.3 ± 6.3 vs 93.3 ± 4.3, P < .05) and IKDC grading results (study group vs control group: 3 grade C, 16 grade B, and 1 grade A vs 3 grade B and 37 grade A; P < .05) as compared with the control group., Conclusion: In this short-term study, the excessive (>10 mm) preoperative ATS in extension after ACL injury was associated with inferior knee stability after anatomic ACLR.

Background: The lateral meniscus posterior root (LMPR) lesion further decreases dynamic knee stability after anterior cruciate ligament (ACL) injury owing to the loss of the "wedge effect" maintained by the posterior horn of the lateral meniscus. However, the effect of LMPR lesions on the static tibiofemoral relationship in extension after ACL injuries is not determined., Purpose: To (1) determine the effect of LMPR lesions on anterior tibial subluxation of the lateral compartment (ATSLC) in extension in patients with ACL injuries and to (2) identify the LMPR-related factors associated with excessive ATSLC in extension., Study Design: Cohort study; Level of evidence, 3., Methods: Between January 2015 and December 2017, 405 consecutive patients with diagnosed ACL injuries who underwent primary ACL reconstructions were retrospectively reviewed. Among them, 45 patients with combined ACL injuries and LMPR lesions (ACL+LMPR group) and 51 patients with isolated ACL injuries (ACL group) were identified. Values of ATSLC in extension were measured on preoperative supine magnetic resonance imaging and classified into high grade (≥6 mm) and low grade (<6 mm). The mean ATSLC in extension and the proportion of patients with high-grade ATSLC in extension were compared between the groups by univariate analysis. In the ACL+LMPR group, predictors of high-grade ATSLC in extension-including age, sex, body mass index, affected side, cause of injury, period from injury (<12 or ≥12 weeks), LMPR lesion pattern (radial tear or root avulsion), and meniscofemoral ligament integrity (intact or impaired)-were assessed by univariate analysis and multivariate logistic regression analysis., Results: The mean ATSLC in extension in the ACL+LMPR group was significantly greater than that in the ACL group (5.6 mm vs 3.1 mm; P = .001). The proportion of patients with high-grade ATSLC in extension in the ACL+LMPR group was also significantly larger than that in the ACL group (44.4% vs 15.7%; P = .002). In addition, the root avulsion (instead of radial tear) (odds ratio, 28.750; 95% CI, 2.344-352.549; P = .009) and the period from injury ≥12 weeks (odds ratio, 17.095; 95% CI, 1.207-242.101; P = .036) were determined to be the 2 independent predictors of high-grade ATSLC in extension. However, age, sex, body mass index, affected side, cause of injury, and meniscofemoral ligament integrity were not., Conclusion: After ACL injuries, concomitant LMPR lesion further increased ATSLC in extension. Chronic LMPR avulsion was associated with high-grade ATSLC in extension.

Background: Static anterior tibial subluxation of the lateral compartment after an anterior cruciate ligament (ACL) injury highlights an increased anterior position of the tibia relative to the femur. However, the precise cause of this phenomenon is not entirely clear. Recently, an increased posterior tibial slope (PTS) has been identified as an independent risk factor for noncontact ACL injuries., Hypothesis: An increased PTS is associated with an increased anterior position of the lateral compartment of the tibia relative to the femur after acute ACL injuries., Study Design: Case-control study; Level of evidence, 3., Methods: From March 2016 to March 2017, a total of 154 patients with clinically diagnosed noncontact ACL injuries who underwent primary ACL reconstruction were retrospectively analyzed. Static anterior subluxation of the lateral compartment relative to the lateral femoral condyle was measured on preoperative magnetic resonance imaging. Among them, 23 patients (study group) who demonstrated ≥6-mm anterior subluxation of the lateral compartment were matched in a 1:1 fashion to 23 control participants (control group), who showed <6-mm anterior subluxation of the lateral compartment. The PTS was measured on routinely available preoperative weightbearing lateral knee radiographs. Predictors of increased (≥6 mm) static anterior subluxation of the lateral compartment, including body mass index (BMI), PTS, injuries to the anterolateral ligament (ALL), and concomitant lateral meniscal lesions, were assessed by multivariable conditional logistic regression analysis., Results: The mean PTS in the study group was 15.4°, which was significantly larger than that in the control group (8.8°) ( P < .001). In addition, an abnormal degree of PTS (≥10.0°) was determined to be an independent risk factor (odds ratio, 8.0 [95% CI, 2.7-29.2]; P < .001) associated with ≥6-mm anterior subluxation of the lateral compartment after acute ACL injuries. However, BMI, presence of concomitant lateral meniscal lesions, and presence of ALL ruptures were not., Conclusion: An increased PTS was identified to be an independent anatomic risk factor of increased (≥6 mm) anterior subluxation of the lateral compartment in acute noncontact ACL injuries. For patients with obviously increased anterior tibial subluxation of the lateral compartment after ACL injuries, the PTS should be measured.

Background: A special type of meniscal lesion involving the peripheral attachment of the posterior horn of the medial meniscus (PHMM), termed a "ramp lesion," is commonly associated with an anterior cruciate ligament (ACL) injury. However, its treatment is still controversial. Recently, stable ramp lesions treated with abrasion and trephination alone have been shown to have good clinical outcomes after ACL reconstruction., Hypothesis: Stable ramp lesions treated with abrasion and trephination alone during ACL reconstruction will result in similar clinical outcomes compared with those treated with surgical repair., Study Design: Randomized controlled trial; Level of evidence, 2., Methods: A prospective randomized controlled study was performed in 91 consecutive patients who had complete ACL injuries and concomitant stable ramp lesions of the medial meniscus. All patients were randomly allocated to 1 of 2 groups based on whether the stable ramp lesions were surgically repaired (study group; n = 50) or only abraded and trephined (control group; n = 41) during ACL reconstruction. All surgical procedures were performed by a single surgeon who was blinded to the functional assessment findings of the patients. The Lysholm score, subjective International Knee Documentation Committee (IKDC) score, and stability assessments (pivot-shift test, Lachman test, KT-1000 arthrometer side-to-side difference, and KT-1000 arthrometer differences of <3, 3-5, and >5 mm) were evaluated preoperatively and at the last follow-up. Moreover, magnetic resonance imaging (MRI) was used to evaluate the healing status of the ramp lesions., Results: All consecutive patients who were screened for eligibility from August 2008 to April 2012 were enrolled and observed clinically. There were 40 patients in the study group and 33 patients in the control group who were observed for at least 2 years. At the final follow-up, there were no significant differences between the study group and the control group in terms of the mean Lysholm score (88.7 ± 4.8 vs 90.4 ± 5.8, respectively; P = .528), mean subjective IKDC score (83.6 ± 3.7 vs 82.2 ± 4.5, respectively; P = .594), pivot-shift test results ( P = .658), Lachman test results ( P = .525), KT-1000 arthrometer side-to-side difference (1.6 ± 1.2 vs 1.5 ± 1.1, respectively; P = .853), or KT-1000 arthrometer grading ( P = .738). Overall, for both groups (n = 73), 67 patients showed completely healed (38 study, 29 control), 3 showed partially healed (1 study, 2 control), and 3 showed nonhealed (1 study, 2 control) signals on follow-up MRI when evaluating the healing status of the ramp lesions. There was no significant difference regarding the healing status of the ramp lesions between the 2 groups ( P = .543)., Conclusion: This prospective randomized controlled trial showed that, in terms of subjective scores, knee stability, and meniscal healing status, concomitant stable ramp lesions of the medial meniscus treated with abrasion and trephination alone during ACL reconstruction resulted in similar clinical outcomes compared with those treated with surgical repair.

Background: A special type of meniscal lesion involving the peripheral attachment of the posterior horn of the medial meniscus (PHMM), termed ramp lesion, is commonly associated with anterior cruciate ligament (ACL) injury. However, no study has investigated its anatomic risk factors. Recently, increased meniscal slope has been identified as an independent anatomic risk factor for noncontact ACL injury., Hypothesis: Increased medial meniscal slope (MMS) as measured on magnetic resonance imaging (MRI) will correlate with greater risk of concomitant ramp lesion in noncontact ACL injury., Study Design: Case-control study; Level of evidence, 3., Methods: From January 2011 to December 2013, a total of 1012 consecutive patients were diagnosed as having noncontact ACL injuries and underwent primary ACL reconstructions. Among them, 160 patients were arthroscopically verified to have concomitant ramp lesions. Study exclusion criteria included partial ACL rupture, multiligamentous injury, associated medial/lateral meniscal lesions other than ramp lesion, skeletal immaturity, general joint laxity, severe malalignment of the lower extremity, history of knee surgery, lack of available preoperative MRI, and history of trauma to the proximal tibia. This left 53 patients in the study group (ACL + ramp group), who were matched in a 1:1 fashion to 53 control participants (isolated ACL group) who were arthroscopically verified to have isolated complete ACL injury during the same study period. Patients were matched by age, sex, and time from injury to surgery (TFI). Patients from the matched control group were selected by applying the same exclusion criteria as mentioned above. The MMS and medial posterior tibial slope (MPTS) were measured on the preoperative MRI in a blinded fashion. Predictors of ramp lesion, including MMS, MPTS, body mass index, pivot-shift test grade, and KT-1000 arthrometer side-to-side difference, were assessed by multivariable conditional logistic regression analysis., Results: The mean MMS in the study group was 3.5°, which was significantly larger than that in the control group (2.0°; P < .001). In addition, increased MMS was significantly (odds ratio [OR], 5.180; 95% CI, 1.814-32.957; P < .001) associated with concomitant ramp lesion in noncontact ACL injury, especially for those with a TFI of ≥6 months (OR, 13.819; 95% CI, 2.251-49.585; P < .001). However, no significant association was identified between MPTS and concomitant ramp lesion., Conclusion: Increased MMS was identified to be an independent anatomic risk factor of concomitant ramp lesions in noncontact ACL injuries, particularly for those with a TFI ≥6 months. This may provide additional information for counseling patients who have increased MMS on the greater risk of secondary PHMM lesions if their ACL-deficient knee joints are not well stabilized initially., (© 2016 The Author(s).)

Background: Recent literature has demonstrated that involvement in pivoting sports at the time of injury, increased posterior-inferior tibial slope (PITS), anterolateral capsular ligament (ALCL) disruptions, and combined lateral meniscal lesions all contribute to a higher grade of pivot shift after acute anterior cruciate ligament (ACL) injuries., Purpose: To identify risk factors associated with grade 3 pivot shift after acute ACL injuries., Study Design: Case-control study; Level of evidence, 3., Methods: A database of patients undergoing primary ACL reconstruction from 2009 to 2015 after acute ACL injuries was retrospectively reviewed. A total of 30 patients (30 knees) with grade 3 pivot shift were identified as the study group. Moreover, 30 patients (30 knees) with grade 1 and 30 patients (30 knees) with grade 2 pivot shift were randomly chosen as the 2 control groups. All pivot-shift tests were performed with the patients under anesthesia. Predictors of grade 3 pivot shift that were explored included patient age, sex, time from injury to surgery, pivoting sports involvement at the time of injury, lateral PITS, medial PITS, ALCL disruptions, preoperative KT-1000 arthrometer side-to-side difference, and combined lateral or medial meniscal lesions. Comparisons were performed between the study group and the 2 control groups. Univariable and multivariable logistic regressions were used to identify independent risk factors that were associated with grade 3 pivot shift., Results: Univariable and multivariable logistic regressions between the study group and the 2 control groups showed that pivoting sports involvement at the time of injury (odds ratio1 [OR1; grade 3 vs grade 1 pivot shift with grade 1 = reference], 11.88; 95% CI, 1.94-149.91; OR2 [grade 3 vs grade 2 pivot shift with grade 2 = reference], 3.41; 95% CI, 1.92-22.60), abnormal degree of lateral PITS (OR1, 14.41; 95% CI, 1.69-174.78; OR2, 6.41; 95% CI, 1.48-47.70), ALCL disruptions (OR1, 8.28; 95% CI, 1.71-117.14; OR2, 4.96; 95% CI, 1.07-28.75), and combined lateral meniscal lesions (OR1, 27.56; 95% CI, 5.48-240.52; OR2, 5.83; 95% CI, 1.21-38.56) were independent risk factors of grade 3 pivot shift after acute ACL injuries., Conclusion: For acute ACL injuries, the best set of predictors of grade 3 pivot shift were pivoting sports involvement at the time of injury, abnormal lateral PITS, ALCL disruptions, and combined lateral meniscal lesions. These results may provide additional information for counseling patients on residual laxity and risks for graft rerupture after ACL reconstruction., (© 2015 The Author(s).)

Six dammarane-type saponins were extracted from steamed Panax notoginseng. Their chemical structures were identified spectroscopically as ginsenosides Rh1 (1), Rg1 (2), 20 (S)-Rg3 (3), 20 (R)-Rg3 (4), Rb3 (5), and Rb1 (6). Compounds (0.1-10 μM) were tested for inhibition of tumor necrosis factor-α (TNF)-induced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) luciferase reporter activity using a human kidney 293T cell-based assay. Ginsenoside Rb3 (5) showed the most significant activity with an IC50 of 8.2 μM. This compound also inhibited the induction of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) messenger Ribonucleic acid (mRNA) in a dose-dependent manner after HepG2 cells had been treated with TNF-α (10 ng/mL).

Hepatitis B virus (HBV) is the third most common disease after venereal diseases and chickenpox. HBV currently infects 2 billion people in the world, of which 350 million are chronic carriers. At least 1 million chronically infected individuals die each year due to HBV-related diseases, especially cirrhosis and liver cancer. The greatest concern about the diffusion of this virus is in endemic regions in central and southern Africa, South-East Asia and South America, where neonatal exposure results in high mortality rates. Anti-HBV therapy has made important progresses in the last decade, with two approved drugs and a number of other potent agents in the pharmaceutical industry pipeline. Nevertheless, resistance and viral rebound are still major issues in devising a winning strategy, and there is a continuous need of developing new active compounds, as well as therapeutic protocols based on combination therapy and a prophylactic approach. This review will summarize the latest advances in anti-HBV therapy, with particular regard to the latest clinical data on the most significant anti-HBV agents. Issues such as viral resistance and combination therapy will be highlighted.