Simultaneous dislocation of the radial head and distal radio-ulnar joint without fracture in an adult patient: a case report and review of literature.

BACKGROUND: Simultaneous dislocation of the radial head and distal radio-ulnar joint without fracture (Criss-Cross Injury) in an adult patient is rarely reported in previous studies. The pathological changes and injury patterns have not been clearly demonstrated. CASE PRESENTATION: A 26-year-old woman presented with acute pain of the right wrist and elbow after a fall from cycling. Physical examination revealed an unstable elbow and wrist joint. Plain radiographs showed volar dislocation of the radial head and dorsal dislocation of the distal radius without associated fracture, forming a criss-cross appearance of the ulna and radius on the lateral radiograph. MRI images confirmed partial rupture of the proximal interosseous membrane from its dorsal attachment on the radius, as well as partial rupture of the medial collateral ligament. Conservative treatment failed because the radiocapitellar joint and distal radio-ulnar joint could not be simultaneously reduced. Surgical exploration revealed a highly unstable radial head, but the annular ligament was found to be intact. Manual force was applied to reduce the radial head and a percutaneous K-wire was used to stabilize the proximal radioulnar joint with the forearm in full supination. After surgery, the elbow was immobilized in 90° flexion by a long arm cast for 4 weeks. The K-wire was removed at 6 weeks postoperatively. At 18 months postoperatively, the patient had regained a full range of flexion and extension, with normal supination and a slight limitation in pronation. CONCLUSIONS: The proximal IOM, especially the dorsal band, was injured in Criss-Cross injuries, while the central part of the IOM remained intact. This injury pattern distinguished itself from Essex-Lopresti injury, which mainly involves rupture of the central band of the IOM.

Bone marrow lesion on magnetic resonance imaging indicates the last chance for hip osteonecrosis treated with vascularized fibular grafting before collapse.

PURPOSE: Timing of surgery is the most critical prognostic factor for hip osteonecrosis treated with free vascularized fibular grafting (FVFG). Bone marrow lesion (BML) on MRI usually occurs immediately before femoral head collapse. We conducted a retrospective cohort study to evaluate whether the noncollapsed hips with BML can benefit from FVFG. METHODS: Consecutive patients undergoing modified FVFG were identified from our clinical repository between January 2014 and December 2014. Based on whether BML was pre-operatively detected, the four year radiographic and clinical outcomes were compared. RESULTS: In the BML cohort, 22 of 53 hips (42%) showed radiographic signs of osteonecrosis progression, which was significantly higher than that in the control cohort (8 of 49, 16%; P = 0.005). The BML hips showed a significantly lower pre-operative Harris Hip Score (HHS) than those without BML (77.8 vs. 85.5, P = 0.046), whereas no such difference was observed in the final HHS or its post-operative improvement (HHS 90 vs. 94, P = 0.397; HHS improvement 12 vs. 8, P = 0.067). In the subgroup of patients with a pre-operative HHS lower than 80, BML hips were associated with a slightly lower final HHS than hips without BML. Four of 5 (80%) failed hips with BML had a poor pre-operative hip function. CONCLUSION: BML indicates the last chance for a reproducible improvement in the treatment of hip osteonecrosis with FVFG before collapse. However, the concomitant lower pre-operative HHS (< 80) is a poor prognostic factor for BML-positive hips.

Distally based perforator propeller sural flap for foot and ankle reconstruction: a modified flap dissection technique.

BACKGROUND: Distally based perforator propeller sural flaps that pedicled on an isolated perforator from the peroneal artery or posterior tibial artery are a versatile local reconstructive option for defects of the foot and ankle region. However, flap venous congestion is yet a difficult problem after operation. We hypothesize that containing some adipofascial tissues around the axial perforator can preserve some tiny venous return routes, improve venous drainage, and ultimately enhance flap safety in distally based sural flaps. METHODS: A prospective case series of 12 patients undergoing distally based perforator sural flaps for foot and ankle coverage were included in this study from January 2008 to December 2010. There were 7 posterior tibial artery perforator flaps from the posteromedial sural region and 5 peroneal artery perforator flaps from the posterolateral sural region. After identifying the proper viable perforator during operation as the pivot point, the whole flap was designed in an eccentric propeller shape. The proximal larger blade was a fasciocutaneous flap, whereas the distal smaller blade was a subdermal vascular plexus flap, preserving at least a quarter area of adipofascial tissue intact around the perforator. Postoperatively, flap swelling was classified into a 5-grade assessment scale. Flap survival, complications, and patient functional recovery were evaluated. RESULTS: The proximal fasciocutaneous flap measured 4 × 8 to 6 × 18 cm (mean, 57.8 cm), and the distal subdermal cutaneous flap measured 2 × 2 to 4 × 4 cm (mean, 9.2 cm). The flaps were rotated 160 to 180 degrees. Postoperatively, flap swelling was noted under grade 2 in 9 cases, grade 3 in 2, and grade 4 in 1 with some distal superficial skin necrosis, which occurred in the largest flap in our series. All flaps survived uneventfully. After a mean of 13 months of follow-up, the wounds were cured successfully. All patients recovered walking and shoe wearing function. CONCLUSION: Keeping a quadrant adipofascial tissue around the distal pivot perforator to form a perforator-adipofascial-pedicle can preserve more venous return routes and relieve flap swelling. This technique should be recommended in distally perforator-pedicled propeller flaps because it enhances flap safety yet does not increase the difficulty of 180-degree rotation.

Costal cartilage grafting in the treatment of concurrent osteochondral lesion of the talus in a trimalleolar fracture.

A 49-year-old female sustained a trimalleolar fracture concurrent with 10 years history of symptomatic osteochondral lesions of the talus. We performed a costal cartilage grafting for osteochondral lesions of the talus through the inherent medial malleolar fracture gap, followed by internal fixation of the fracture. During the follow-up, the fracture healed within the expected time, accompanied by favorable functional outcomes and pre-injury pain relief. At 3 years postoperatively, the graft merged with the bone bed of the talus, and progressive endochondral ossification was observed at the graft-bone interface. The case provides us a chance to verify whether the costal cartilage grafting is reliable for the treatment of osteochondral lesions of the talus.

Autologous Costal Cartilage Grafting for a Large Osteochondral Lesion of the Femoral Head: A 1-Year Single-Arm Study with 2 Additional Years of Follow-up.

BACKGROUND: There is currently no ideal treatment for osteochondral lesions of the femoral head (OLFH) in young patients. METHODS: We performed a 1-year single-arm study and 2 additional years of follow-up of patients with a large (defined as >3 cm 2 ) OLFH treated with insertion of autologous costal cartilage graft (ACCG) to restore femoral head congruity after lesion debridement. Twenty patients ≤40 years old who had substantial hip pain and/or dysfunction after nonoperative treatment were enrolled at a single center. The primary outcome was the change in Harris hip score (HHS) from baseline to 12 months postoperatively. Secondary outcomes included the EuroQol visual analogue scale (EQ VAS), hip joint space width, subchondral integrity on computed tomography scanning, repair tissue status evaluated with the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, and evaluation of cartilage biochemistry by delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and T2 mapping. RESULTS: All 20 enrolled patients (31.02 ± 7.19 years old, 8 female and 12 male) completed the initial study and the 2 years of additional follow-up. The HHS improved from 61.89 ± 6.47 at baseline to 89.23 ± 2.62 at 12 months and 94.79 ± 2.72 at 36 months. The EQ VAS increased by 17.00 ± 8.77 at 12 months and by 21.70 ± 7.99 at 36 months (p < 0.001 for both). Complete integration of the ACCG with the bone was observed by 12 months in all 20 patients. The median MOCART score was 85 (interquartile range [IQR], 75 to 95) at 12 months and 75 (IQR, 65 to 85) at the last follow-up (range, 24 to 38 months). The ACCG demonstrated magnetic resonance properties very similar to hyaline cartilage; the median ratio between the relaxation times of the ACCG and recipient cartilage was 0.95 (IQR, 0.90 to 0.99) at 12 months and 0.97 (IQR, 0.92 to 1.00) at the last follow-up. CONCLUSIONS: ACCG is a feasible method for improving hip function and quality of life for at least 3 years in young patients who were unsatisfied with nonoperative treatment of an OLFH. Promising long-term outcomes may be possible because of the good integration between the recipient femoral head and the implanted ACCG. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

[Surgical treatment of flatfoot resulting from calcaneal fractures malunion].

OBJECTIVE: To explore the operative approach and efficacy of flatfoot after calcaneal fractures malunion. METHODS: A total of 116 flatfoot patients after old calcaneal fractures were treated from January 1998 to January 2008. There were 94 males and 22 females with an average age of 33.5 years old (range: 16 - 46). They included unilateral flatfoot after old calcaneal fractures (n = 110) and bilateral flatfoot after old calcaneal fractures (n = 6). The surgical treatments included open reduction, calcaneal osteotomy without subtalar fusion or a reconstruction of calcaneal thalamus and subtalar arthrodesis. RESULTS: A total of 101 patients were followed up for an average of 14 months (range: 12 - 24). No wound healing problem or infection was observed. Solid union was obtained without redislocation in all patients. The mean time of bone union was 12 weeks (range: 10 - 14). The mean time of complete weight loading was 13 weeks (range: 11 - 15 weeks). The height of foot arch increased from 4.2 mm ± 1.7 mm to 14.1 mm ± 4.1 mm (P < 0.05). Calcaneal inclination angle increased from 11.2° ± 2.5° to 19.1° ± 4.4° (P < 0.05). Bohler angle increased from 5.4° ± 3.5° to 25.8° ± 5.2° (P < 0.05). Meary angle recovered from 22.2° ± 4.4° to 5.1° ± 3.2° (P < 0.05). The mean AOFAS Ankle and Hindfoot score increased from 33.4 (range: 27 - 43) to 85.8 (range: 78 - 98). CONCLUSION: As to flatfoot after old calcaneal fractures, surgical treatment has a favorable efficacy. A customized operative approach may achieve a satisfactory outcome.

[Characteristics and surgical treatment of combined calcaneal fractures].

OBJECTIVE: To discuss the characteristics and experience for surgical treatment of combined calcaneal fracture. METHODS: Between February 2004 and September 2007, 17 feet of 13 patients with combined calcaneal fractures underwent surgical operations. Among 17 calcaneal fractures, 8 combined with ipsilateral talus fractures, 5 combined with trimalleolar fractures, 4 combined with Pilon fractures. Firstly, fractures of hinder foot were treatment with open reduction and internal fixation according to the principle. Of all, 15 fractures were treated with screws or titanic plate plus open reduction and internal fixation, the rest 2 fractures were treated with subtalar arthrodesis. Postoperative X-ray assessed the internal fixation and union of fractures. The foot function was evaluated by the Maryland Foot Score. RESULTS: A total of 13 patients were all followed up for 16.0 - 33.0 months (average 26.5 months), superficial infection was found in a patient with open wound 10 d after surgery. All the bone fractures united after surgery from 4 to 6 months. Morphous improvement of the calcaneal were proved by X-ray films and there here was no plates and screws' breakage, loosening. Mild osteoarthritis in Subtalar and ankle joints were found by X-ray after surgery from 9 months to last follow-up. Cystic degeneration and necrosis were found in 5 and 2 cases of talus fractures respectively. According to Maryland Foot Score, excellent was in 3 feet, good in 6 feet, fare in 5 feet and poor in 3 feet, with excellence rate of 52.9%. CONCLUSIONS: Combined calcaneal is a calcaneus-based concomitant ankle and foot fractures after a high-energy injury. Good deal of soft tissue and correct design of operation pre-operatively, restoration of form and power lines of calcaneal, effective bone graft, right place of simple internal fixation or subtalar arthrodesis and good reduction and internal fixation of other fracture in hinder feet intra-operatively and correct function postoperatively are key points to have a relatively satisfied treating effect of combined calcaneal fractures.

[Surgical treatment of malunited or nonunited talus fractures].

OBJECTIVE: To explore the operative methods of malunited or nonunited talus fractures. METHODS: Twenty-two patients of malunions or nonunions after displaced talar fractures were treated from January 2000 to January 2008. There were 17 males and 5 females with an average age of 34 years (ranged from 15 to 52 years). According to classification of posttraumatic talar deformities (Zwipp 2003), there were 10 cases of type I (malunion and/or joint displacement), 8 cases of type II (nonunion with joint displacement), 4 cases of type III (type I/II with partial AVN). The surgical treatments included open reduction, osteotomy, correction and internal fixation with plate, screw or K-wire, or the ankle, subtalar arthrodesis. RESULTS: Seventeen patients were followed up for 14 months in average (ranged from 12 to 24 months). No wound healing problems or infections were observed. Solid union was obtained without redislocation in all patients. The mean time of bone union was 14 weeks (ranged from 12 to 18 weeks). The mean time of completely weight loading was 14 weeks (ranged from 12 to 18 weeks). The mean AOFAS ankle and hindfoot score increased from 35.4 (ranged from 28.0 to 41.0) to 86.6 (ranged from 78.0 to 98.0). CONCLUSIONS: As to posttraumatic talar deformities, surgical treatment can lead to a favorable outcome. According to concrete status of malunions or nonunions after displaced talar fractures, suitable surgical treatment should be applied to obtain satisfactory outcome.

A circular RNA derived from DAB1 promotes cell proliferation and osteogenic differentiation of BMSCs via RBPJ/DAB1 axis.

Osteogenesis (OS) is a type of differentiation that is of great importance for bone homeostasis. Increasing studies suggest circular RNAs (circRNAs) as pivotal regulators in OS. This study proposed to investigate mechanism mediated by circRNAs in OS. Based on GEO data and qRT-PCR assay, we found that circ-DAB1 (has_circ_0113689) was significantly up-regulated during osteogenic differentiation in human BMSCs. Overexpressing circ-DAB1 proliferation and osteogenic differentiation of BMSCs, whereas silencing circ-DAB1 elicited opposite functions. Subsequently, recombination signal-binding protein for immunoglobulin kappa J region (RBPJ), an important transcription factor in NOTCH pathway, was found to interact with DAB1 promoter while not to combine with circ-DAB1. Interestingly, circ-DAB1 overexpression could result in the increasing binding between RBPJ and DAB adaptor protein 1 (DAB1) promoter. Overexpressing circ-DAB1 upregulated RBPJ in BMSCs to induce DAB1 level. Further, we uncovered that circ-DAB1 upregulated RBPJ through sequestering miR-1270 and miR-944. Restoration experiments demonstrated that knocking down either RBPJ or DAB1 partially recovered BMSC proliferation and osteogenic differentiation that was suppressed by circ-DAB1 overexpression. Conclusively, circ-DAB1 promotes cell proliferation and osteogenic differentiation of BMSCs via NOTCH/RBPJ pathway.

The Delayed-Onset Mechanical Pain Behavior Induced by Infant Peripheral Nerve Injury Is Accompanied by Sympathetic Sprouting in the Dorsal Root Ganglion.

BACKGROUND: Sympathetic sprouting in the dorsal root ganglion (DRG) following nerve injuries had been proved to induce adult neuropathic pain. However, it is unclear whether the abnormal sprouting occurs in infant nerve injury. METHODS: L5 spinal nerve ligation (SNL) or sham surgery was performed on adult rats and 10-day-old pups, and mechanical thresholds and heat hyperalgesia were analyzed on 3, 7, 14, 28, and 56 postoperative days. Tyrosine hydroxylase-labeled sympathetic fibers were observed at each time point, and 2 neurotrophin receptors (p75NTR and TrkA) were identified to explore the mechanisms of sympathetic sprouting. RESULTS: Adult rats rapidly developed mechanical and heat hyperalgesia from postoperative day 3, with concurrent sympathetic sprouting in DRG. In contrast, the pup rats did not show a significantly lower mechanical threshold until postoperative day 28, at which time the sympathetic sprouting became evident in the DRG. No heat hyperalgesia was presented in pup rats at any time point. There was a late expression of glial p75NTR in DRG of pups from postoperative day 28, which was parallel to the occurrence of sympathetic sprouting. The expression of TrkA did not show such a postoperative syncing change. CONCLUSION: The delayed-onset mechanical allodynia in the infant nerve lesion was accompanied with parallel sympathetic sprouting in DRG. The late parallel expression of glial p75NTR injury may play an essential role in this process, which provides novel insight into the treatment of delayed adolescent neuropathic pain.

Distally based sural fasciomyocutaneous flap: anatomic study and modified technique for complicated wounds of the lower third leg and weight bearing heel.

The reconstruction of the distal third leg and weight-bearing heel, especially when complicated with infection and/or dead space, remains a challenge in reconstructive surgery. The distally based sural neurofasciomyocutaneous flap has been proved a valuable tool in repair of the soft tissue defects of those areas. In this report, we present the results of the anatomical study on vascular communication between the suprafascial sural neurovascular axis and the deep gastrocnemius muscle and a modified technique in clinical applications for reconstruction of the soft tissue defects in the distal lower leg and heel. Six lower limbs of fresh cadavers were injected with red gelatin and dissected. A constant vascular connection with average four musculo-fasciocutaneous perforators with diameter 0.2-0.5 mm was identified in the overlapping area between the suprafascial sural neurovascular axis and the deep gastrocnemius muscle. Based on these findings, a modified distally based sural neurofasciomyocutaneous flap including the distal gastrocnemius muscle component was designed and used for repairs of the soft tissue defects in the distal lower limb and plantar heel pad in six patients. The blood supplies of flaps comprised either the peroneal perforator and adipofascial pedicle or the peroneal perforator only. The average size of the fasciocutaneous flap was 51 cm(2), and the muscle component 17.7 cm(2). All flaps survived uneventfully. Our results suggest that this technical modification could provide wider range for applications of the distally based sural neurofasciomyocutaneous flap in repair of the soft tissue defects of the lower extremity and heel.

Treatment of isolated posterior coronal fracture of the lateral tibial plateau through posterolateral approach for direct exposure and buttress plate fixation.

PURPOSE: To present a case series of patients with isolated posterior coronal fractures of lateral tibial plateau treated by direct exposure and buttress plate fixation through posterolateral approach. METHODS: Between May 2007 and April of 2008, eight middle aged patients were identified that had isolated posterior coronal fractures of the lateral tibial plateau. All eight patients underwent direct fracture exposure, reduction under visualization, and buttress plate fixation through posterolateral approach. RESULTS: There were 1 case of split, two cases of pure depression and five cases of split-depression fractures. Four were associated fibular head split fractures without common peroneal nerve injuries. Five patients were injured from a simple fall on riding electrical bicycle while the knee was relaxed in 90 degrees position The articular displacement (8 cases) measured in CT scan was 10.5 mm in average (range 8-15 mm). The cortical split length (from the articular rim to the distal tip, 6 cases) was 2.8 cm in average (range 2.4-3.5 cm). The articular reduction was perfect in seven (absolutely no step-off) and imperfect in 1(<2 mm step-off) as measured by X-ray. With a mean follow-up of 10 months (6 cases > 12 months), the average range of motion arc was 119 degrees , four patients have flexion lag 10 degrees -20 degrees . The average SMFA dysfunction score was 15.8, and average HSS score was 98. All eight patients stated they were highly satisfied. CONCLUSIONS: Direct posterolateral approach by dividing lateral border of soleus muscle, provides excellent fracture reduction under visualization and internal buttress plate fixation for posterior coronal fracture of the lateral tibial plateau. Good functional results and recovery can be expected.

Plate fixation for Letenneur type I Hoffa fracture: a biomechanical study.

BACKGROUND: A coronal fracture of the posterior femoral condyle, also known as a Hoffa fracture, is an unusual injury, and there are only a handful of case reports or series exploring it. The optimal fixation method of these intraarticular fractures remains controversial; improper or unstable fixation usually lead to an unsatisfactory prognosis. The use of posterior-anterior or reversed lag screw fixation is still a popular method. Additional buttress plating is also recommended for fixation of these difficult fractures. The purpose of this study was to compare the mechanical strength of four different fixation patterns for this uncommon fracture. MATERIAL AND METHODS: Sixteen sawbone simulated models of Letenneur type I Hoffa fractures were created with one of four fixation patterns: two screws implanted in the anterior-posterior (AP) direction or posterior-anterior (PA) direction; one screw in the PA direction with a plate implanted in the posterior position of the distal femoral condyle or with a plate in the lateral position. Biomechanical testing was performed to determine the post-fixation axial stiffness, the maximum load to failure and the fragment vertical displacement for each of the four constructs. RESULTS: The plate fixation patterns whether implanted in the posterior or lateral position were shown to provide higher overall axial stiffness and load to failure, and less vertical displacement than the other two patterns of pure screw fixation. Among these constructs, the lateral plate fixation was found to provide the highest stiffness and load to failure and the least displacement for the posterior condylar fragments, followed by the posterior plate fixation. The lowest overall stiffness and load to failure and the largest vertical displacement were found in the construct with the AP direction placed screws. CONCLUSION: It was concluded that the lateral position implanted plate is biomechanically the strongest fixation method for Letenneur type I Hoffa fractures. However, this plate fixation is not recommended for all cases. The choice of internal fixation pattern depends on the surgeons.

[Study on thermal decomposition of HMX energetic materials by in-situ FTIR spectroscopy].

In-situ FTIR spectroscopy is a rising and dynamic technique. This technique, which combines the advantages of investigation in-situ and accurate structure analysis by FTIR spectsoscopy, can detect the chemical change of materials in different temperature with real time and obtain the relationship between micromechanism of materials and temperature. In the present paper, thermal decomposition of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) heated with 5 degrees C x min(-1) was investigated by in-situ FTIR spectroscopy. The results demonstrate that C-N bond cleavage and N-N bond cleavage of HMX occur at 205 degrees C. With increasing temperature, the rupture rate of C-N bond is faster than that of N-N bond, which verifies that the cleavage of C-N bond is the dominant rupture form. The augment in tension of HMX cyclic confirms that intramolecular cyclization occurs in breakage of HMX. Eight kinds of gaseous products such as CO2, N2O, CO, NO, HCHO, HONO, NO2 and HCN were determined. According to the structure change in condensed state and gaseous products, the decomposition mechanism was deduced that HCHO, N2O, HONO and HCN were released due to the cleavage of C-N bond, and NO2 was released due to the cleavage of N-N bond.

A Comparison of Surgical Invasions for Spinal Nerve Ligation with or without Paraspinal Muscle Removal in a Rat Neuropathic Pain Model.

L5 spinal nerve ligation (SNL) in rats is one of the most popular models for studying neuropathic pain because of its high reproducibility. During the surgery, a part of the L5 paraspinal muscle is usually removed, which produces extra trauma and may potentially affect the physiological processes involved in neuropathic pain. To reduce the surgical trauma, the paraspinal muscle retraction was developed for exposure of the spinal nerve. The current study was aimed at comparing the surgical invasions between the L5 SNL models with paraspinal muscle removal or retraction. The results showed that both methods induced similar neuropathic pain behavior. However, the paraspinal muscle retraction group exhibited an average of 2.7 mg less blood loss than the muscle removal group. This group also showed a significantly lower increase in serum myoglobin and creatine phosphokinase levels on postoperative days 1 and 2, as well as a lower increase in interleukin-1ß and interleukin-6 levels on postoperative day 1. The paraspinal muscle maintained normal morphological features following paraspinal muscle retraction. Our results indicate that the SNL rat model with paraspinal muscle retraction is a reliable physiological model that is reproducible, readily available, and less invasive than the model with muscle removal.

Dihydromethysticin kavalactone induces apoptosis in osteosarcoma cells through modulation of PI3K/Akt pathway, disruption of mitochondrial membrane potential and inducing cell cycle arrest.

The objective of the present study was to evaluate the tumor and apoptotic effects of dihydromethysticin kavalactone against human osteosarcoma (MG-63) cells. Antiproliferative activity was measured with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis induction by dihydromethysticin was demonstrated by fluorescence microscopy, quantitative videomicroscopy and Annexin V-FITC apoptosis detection kit. Mitochondrial membrane potential disruption was demonstrated by rhodamine-123 dye using flow cytometry. We also evaluated the effect of dihydromethysticin on PI3K/Akt pathway with an immunoblotting analysis. The results showed that the compound induced dose-dependent as well as time-dependent antiproliferative effects against MG-63 cell growth. Cell death and apoptotic body formation was noticed followed dihydromethysticin treatment at various doses. The percentage of apoptotic cells (early apoptosis+late apoptosis) increased from 6.63% in untreated control to 23.92%, 23.81% and 93.9% in 25 µM, 75 µM and 100 µ Mdihydromethysticin-treated cells respectively. Flow cytometric analysis showed dihydromethysticin induced an increase in G0/G1 cells (apoptotic cells). Furthermore, we observed mitochondrial transmembrane depolarization along with decreased phosphorylation levels for PI3K, AKT (Ser 473), AKT (Thr 308), GSK-3ß, and BAD. These reductions were associated with down regulation of AKT and upregulation of both GSK-3ß and BAD.