Percutaneous Sacroiliac Screw Placement: A Prospective Randomized Comparison of Robot-assisted Navigation Procedures with a Conventional Technique.

BACKGROUND: Sacroiliac (SI) screw fixation is a demanding technique, with a high rate of screw malposition due to the complex pelvic anatomy. TiRobot™ is an orthopedic surgery robot which can be used for SI screw fixation. This study aimed to evaluate the accuracy of robot-assisted placement of SI screws compared with a freehand technique. METHODS: Thirty patients requiring posterior pelvic ring stabilization were randomized to receive freehand or robot-assisted SI screw fixation, between January 2016 and June 2016 at Beijing Jishuitan Hospital. Forty-five screws were placed at levels S1 and S2. In both methods, the primary end point screw position was assessed and classified using postoperative computed tomography. Fisher's exact probability test was used to analyze the screws' positions. Secondary end points, such as duration of trajectory planning, surgical time after reduction of the pelvis, insertion time for guide wire, number of guide wire attempts, and radiation exposure without pelvic reduction, were also assessed. RESULTS: Twenty-three screws were placed in the robot-assisted group and 22 screws in the freehand group; no postoperative complications or revisions were reported. The excellent and good rate of screw placement was 100% in the robot-assisted group and 95% in the freehand group. The P value (0.009) showed the same superiority in screw distribution. The fluoroscopy time after pelvic reduction in the robot-assisted group was significantly shorter than that in the freehand group (median [Q1, Q3]: 6.0 [6.0, 9.0] s vs. median [Q1, Q3]: 36.0 [21.5, 48.0] s; χ2 = 13.590, respectively, P < 0.001); no difference in operation time after reduction of the pelvis was noted (χ2 = 1.990, P = 0.158). Time for guide wire insertion was significantly shorter for the robot-assisted group than that for the freehand group (median [Q1, Q3]: 2.0 [2.0, 2.7] min vs. median [Q1, Q3]: 19.0 [15.5, 45.0] min; χ2 = 20.952, respectively, P < 0.001). The number of guide wire attempts in the robot-assisted group was significantly less than that in the freehand group (median [Q1, Q3]: 1.0 [1.0,1.0] time vs. median [Q1, Q3]: 7.0 [1.0, 9.0] times; χ2 = 15.771, respectively, P < 0.001). The instrumented SI levels did not differ between both groups (from S1 to S2, χ2 = 4.760, P = 0.093). CONCLUSIONS: Accuracy of the robot-assisted technique was superior to that of the freehand technique. Robot-assisted navigation is safe for unstable posterior pelvic ring stabilization, especially in S1, but also in S2. SI screw insertion with robot-assisted navigation is clinically feasible.

Dramatic suppression of colorectal cancer cell growth by the dual mTORC1 and mTORC2 inhibitor AZD-2014.

Colorectal cancer is a major contributor of cancer-related mortality. The mammalian target or rapamycin (mTOR) signaling is frequently hyper-activated in colorectal cancers, promoting cancer progression and chemo-resistance. In the current study, we investigated the anti-colorectal cancer effect of a novel mTOR complex 1 (mTORC1) and mTORC2 dual inhibitor: AZD-2014. In cultured colorectal cancer cell lines, AZD-2014 significantly inhibited cancer cell growth without inducing significant cell apoptosis. AZD-2014 blocked activation of both mTORC1 (S6K and S6 phosphorylation) and mTORC2 (Akt Ser 473 phosphorylation), and activated autophagy in colorectal cancer cells. Meanwhile, autophagy inhibition by 3-methyaldenine (3-MA) and hydroxychloroquine, as well as by siRNA knocking down of Beclin-1 or ATG-7, inhibited AZD-2014-induced cytotoxicity, while the apoptosis inhibitor had no rescue effect. In vivo, AZD-2014 oral administration significantly inhibited the growth of HT-29 cell xenograft in SCID mice, and the mice survival was dramatically improved. At the same time, in xenografted tumors administrated with AZD-2014, the activation of mTORC1 and mTORC2 were largely inhibited, and autophagic markers were significantly increased. Thus, AZD-2014 inhibits colorectal cancer cell growth both in vivo and in vitro. Our results suggest that AZD-2014 may be further investigated for colorectal cancer therapy in clinical trials.

AMP-activated protein kinase (AMPK)/Ulk1-dependent autophagic pathway contributes to C6 ceramide-induced cytotoxic effects in cultured colorectal cancer HT-29 cells.

Colorectal cancer is the second leading cause of cancer-related deaths. Drug resistance and/or off-target toxicity against normal cells limit the effectiveness of current chemotherapies for the treatment of colorectal cancer. In the current study, we studied the potential cytotoxic effects of short-chain and cell-permeable C6 ceramide in cultured colorectal cancer HT-29 cells and focused on the underlying mechanisms. We observed that C6 ceramide-induced HT-29 cell death and growth inhibition in a dose- and time-dependent manner. However, no significant apoptosis was observed in C6 ceramide-treated HT-29 cells. Our data support that autophagy contributed to C6 ceramide-induced cytotoxic effects, as autophagy inhibitors, 3-methyladenine (3-MA) and hydroxychloroquine, inhibited C6 ceramide's effect; however, autophagy activators, everolimus (RAD001) and temsirolimus, mimicked C6 ceramide effects and induced HT-29 cell death. Further, we indentified that AMP-activated protein kinase (AMPK)/Ulk1 signaling was required for autophagy induction by C6 ceramide, and AMPK silencing by a specific short hairpin RNA suppressed C6 ceramide-induced autophagy and cytotoxic effects. Reversely, forced activation of AMPK by its activator AICAR or by genetic manipulation caused autophagic death in HT-29 cells, which was inhibited by 3-MA. Our results suggest that autophagy, but not apoptosis, is a major contributor for C6 ceramide-induced cytotoxic effects in HT-29 cells, and activation of AMPK/Ulk1 is required for the process.

5,7-Dimethoxy-isobenzofuran-1(3H)-one.

The asymmetric unit of the title compound, C(10)H(10)O(4), which has been isolated from rhizoma Polygonum Cuspidatum, a Chinese folk medicine, contains two crystallographically independent mol-ecules. The mol-ecules are essentially planar, with a maximum deviation of 0.061 (2) Šfrom the best planes. The crystal packing is stabilized by weak inter-molecular C-H⋯O hydrogen-bonding inter-actions, with a stacking direction of the mol-ecules parallel to [101].

[Accurate traction of long bone fracture with full-length planning module of orthopedic robot system: experiments in vitro and in vivo].

OBJECTIVE: To evaluate the precision in location and clinical flexibility of the newly designed full-length planning module of orthopedic robot system in treatment of fractures of long bone. METHODS: Nine plastic tibia models were selected for the image mosaicing. The full length of each tibia model was measured on the constructed panorama and compared with the real model length to record the length deviation and conduct the precision analysis. Fracture of tibia and fibula with shortening and angulation deformity was caused on a cadaver specimen with two lower limbs. Full-length planning was carried out on the entire tibial panorama with the fracture. After the reduction distance was determined quantitatively, automatic close traction procedure was carried out with the tibial reduction frame to analyze the precision and effectiveness of this module. At the same time, the relative length variation between the two bone fragments was monitored utilizing video camera to ensure the safety of the reduction operation. Image mosaicing, surgical planning, and bone traction were performed on a clinical case of tibial fracture to validate the clinical feasibility of the module. RESULTS: An entire tibial panorama could be constructed from 7 - 10 C-arm images collected during the operation. 1.5 min was needed for image collection. The average mosaicing and planning time was 3 min. The mosaicing error was less than 1.5 mm. The average time for the traction frame installation and traction operation was 4 min. Traction resulted in accurate reposition of the fracture ends meeting the requirement of surgery in both the cadaver specimen and the clinical case. CONCLUSION: The newly designed full-length planning module of orthopedic robot system is easy to use and provides effective and accurate traction result in long bone fracture therapy. This module can not only achieve the minimally invasive surgery, but also dramatically decrease the radiation damage to the medical staff.

[Intra-operative stereotactic accuracy of computer-assisted robot orthopaedic trauma surgery planning system].

OBJECTIVE: To investigate the feasibility and accuracy of the software computer-assisted robot orthopaedic trauma surgery planning system (CAOTS). METHODS: The software CAOTS was developed and used on 85 cases of stereotactic operation, 24 model bones, 21 cadaveric extremity bones, and 40 patients. 307 groups of directional targets in these cases were randomly sampled. The distribution of error sources for evaluating system performance was embodied using Monte-Carlo method in order to derive the theoretic guarantees for further optimizing and enhancing the system performance, then the software SPSS 2.0 was used to analyze the errors. RESULTS: The statistical area of deviation number was 0.0408 +/- 0.4578 mm, corresponding to the result by Monte-Carlo method. Punching succeeded at the first run for all 307 cases without wrong locking and other clinical complications. CONCLUSION: Accurate and reliable, CAOTS improves the intra-operative navigation techniques and facilitates the orthopedists to perform operation.

Computer-assisted auto-frame navigation system for distal locking of tibial intramedullary nails: a preliminary report on clinical application.

OBJECTIVE: To evaluate the clinical feasibility and effect of the computer-assisted auto-frame navigation system for distal locking of tibial intramedullary nails. METHODS: The hardware components of the system included a PC computer with a monitor, auto mechanical stereotactical localization cubic frame, foot holder and localization operative apparatus. Special navigation software can be used for registration of X-ray fluoroscopic images and real-time controlling navigation of tools. Twenty-one cases of close tibial and fibular fractures were treated with closed intramedullary nailing, 6 of which involved in middle third, 12 in middle and lower third, 3 in lower third. C-arm alignment and registration time, fluoroscopic time and drilling time involved in the locking procedure were recorded. The size of unreamed or reamed tibial nails ranged from 8/300-11/330. RESULTS: All distal holes except 1 were locked successfully. In 9 of 41 locked holes (21.95%), the drill bit touched the canal of locking hole without damage of the nail and clinical consequences. The fluoroscopy time per pair of screws was 2.23+/-0.31 s. CONCLUSIONS: The computer-assisted auto-frame navigation system for distal locking is well designed, easy to operate and do not need additional instruments during the procedure. The developed system enables the physician to precisely navigate surgical instruments throughout the anatomy using just a few computer-calibrated radiographic images. The total time of X-ray exposure per procedure can be significantly reduced.

Saponins from Polygala japonica and their effects on a forced swimming test in mice.

Five new triterpenoid saponins, polygalasaponins E (1), F (2), G (3), H (4), and J (5), along with eight known ones (6-13), were isolated from the aerial parts of Polygala japonica. Their structures were established by chemical and spectroscopic means. Forced swimming tests on mice showed that saponins 1 and 4 significantly reduce the immobility status by 58.1% and 51.3% at a dosage of 100 mg/kg administrated orally once daily for 5 days, respectively.

Two new iridoids from Patrinia scabra.

From the roots of Patrinia scabra two new iridoids, 3-methylbutyric acid 7-hydroxy-7-hydroxymethyl-4-(3-methyl-butyryloxymethyl)-6-oxo-1,6,7,7a-tetrahydrocyclopenta[c]pyran-1-yl ester (1) and 6-hydroxy-7-methylhexahydrocyclopenta[c]pyran-3-one (2) have been isolated. Their structures were determined by means of NMR spectra and X-ray crystallographic analysis.

[Design and experimental study of computer-assisted orthopaedic system for distal locking of intramedullary nails].

OBJECTIVE: To test the safety and accuracy of the computer-assisted orthopaedic system for distal locking of intramedullary nails and apply it to internal fixation with intramedullary nails in the lower limb. METHODS: According to the theory of mechanical arms stereotactic localization in computer-assisted orthopaedic surgery (CAOS), we design a CAOS system for distal locking of intramedullary nails. The system comprised 2 independent modules: computer-assisted imaging and registration workstation; mechanical stereotactic framework. Ten plastic tibia models, 20 plastic femur models (Synbone AG, Malans, Switzerland) and 6 human cadaver lower limbs were randomly divided into 2 groups undergoing internal fixation with intramedullary nails (Orthofix, Germany). The first group (CAOS group with 5 plastic tibia models, 10 plastic femur models, 6 human cadaver tibia, 6 human cadaver femur; each nail had 2 holes, and 2 distal locking screws were inserted in each bone, which gave a total number of 54 holes) used a computer-assisted orthopaedic system, the second group (CONTROL GROUP is the same as CAOS group) used Orthofix mechanical targeting device for distal locking. Comparison between 2 groups was made in radiation exposure time, operating time, percentage of correctly placed screws. RESULTS: CAOS group: operating time was (4.44 +/- 2.99) min; radiation exposure time was (1.16 +/- 0.38) min; correctly placed screws rate was (100 +/- 0)%. CONTROL GROUP: operating time was (10.42 +/- 4.18) min; radiation exposure time was (4.71 +/- 3.86) min; correctly placed screws rate was (94.44 +/- 0.36)%. Operating time and radiation exposure time in CAOS group were significantly shorter than those in control group (P < 0.05), no differences were found between 2 groups in relation to the percentage of correctly placed screws. CONCLUSIONS: By using CAOS system for distal locking of intramedullary nails, the locking holes can be drilled accurately and safely. Radiation exposure significantly reduced.

New triterpenoid saponins from bulbs of Bolbostemma paniculatum.

Nine new triterpenoid saponins were isolated from the bulbs of Bolbostemma paniculatum (Maxim.) Franquet (Cucurbitaceae): 7beta,18,20,26-tetrahydroxy-(20S)-dammar-24 E-en-3-O-alpha-L-(3-acetyl)arabinopyranosyl-(1-->2)-beta-D-glucopyranoside, 7beta,18,20,26-tetrahydroxy-(20S)-dammar-24E-en-3-O-alpha-L-(4-acetyl)arabinopyranosyl-(1-->2)-beta-D-glucopyranoside, 7beta,18,20,26-tetrahydroxy-(20S)-dammar-24E-en-3-O-alpha-L-arabinopyranosyl-(1-->2)-beta-D-(6-acetyl)glucopyranoside, 7beta,20,26-trihydroxy-(20S)-dammar-24E-en-3-O-alpha-L-arabinopyranosyl-(1-->2)-beta-D-glucopyranoside, 7beta,20,26-trihydroxy-(20S)-dammar-24E-en-3-O-alpha-L-(3-acetyl)arabinopyranosyl-(1-->2)-beta-D-glucopyranoside, 7beta,20,26-trihydroxy-(20S)-dammar-24E-en-3-O-alpha-L-(4-acetyl)arabinopyranosyl-(1-->2)-beta-D-glucopyranoside, 7beta,20,26-trihydroxy-8-formyl-(20S)-dammar-24E-en-3-O-alpha-L-(3-acetyl)arabinopyranosyl-(1-->2)-beta-D-glucopyranoside, 7beta,20,26-trihydroxy-8-formyl-(20S)-dammar-24E-en-3- O-alpha-L-(4-acetyl)arabinopyranosyl-(1-->2)-beta-D-glucopyranoside and 6'-O-palmitoyltubeimoside I. In addition, four known triterpenoid saponins: tubeimoside I, tubeimoside II, tubeimoside III and tubeimoside IV were isolated. The structures of the above compounds were elucidated based on spectroscopic studies, and the configuration of C-20 of tubeimoside IV was revised as S rather than R as reported in previous literature. The compounds were tested for their antiviral activity

[Studies on chemical constituents in bulbs of Bolbostemma paniculatum].

OBJECTIVE: To investigate the chemical constituents of the bulbs of Bolbostemma panicultum. METHOD: The compounds were isolated by column chromatography on silica gel, C18, Sephadex LH-20 separately and their structures were elucidated by chemical and spectroscopic technologies. RESULT: Eight compounds were isolated and identified as maltol(I), emodin(II), cucurbitacin B(III), cucurbitacin E(IV), stigmasta-7, 22, 25-triene-3-ol(V), stigmasta-7, 22, 25-triene-3-nonadecanoic acid ester(VI), stigmasta-7, 22, 25-triene-3-O-beta-D-glucopyranoside(VII), stigmasta-7, 22, 25-triene-3-O-beta-D-(6'-palmitoyl) glucopyranoside(VIII). CONCLUSION: I-VIII were obtained from this plant for the first time; VI and VIII are new compounds.

[Studies on the lignans from Patrinia scabra].

AIM: To study the lignans from Patrinia scabra Bunge. METHODS: The constituents were separated and purified by column chromatography with silical gel, RP-silical gel and Sephadex LH-20. Their structures were identified on the basis of spectral data (IR, MS, 1HNMR, 13CNMR, HMQC and HMBC). RESULTS AND CONCLUSION: A new lignan was obtained and its structure was elucidated as 4-[1-ethoxyl-1-(4-hydroxy-3-methoxy)benzyl]methyl- 2-(4-hydroxy-3-methoxy)benzyl-3-hydroxymethyl-tetrahydro-furan (2), along with three known lignans, lariciresinol (1), isolariciresinol (3) and nortracheloside (4).

Pyrrole alkaloids from Bolbostemma paniculatum.

Three pyrrole alkaloids were isolated from Bolbostemma paniculatum. Their structures were elucidated as 4-(2-formyl-5-methoxymethylpyrrol-1-yl)butyric acid methyl ester (1), 2-(2-formyl-5-methoxymethylpyrrol-1-yl)-3-phenylpropionic acid methyl ester (2) and alpha-methyl pyrrole ketone (3) by spectroscopic techniques. Among them, 1 and 2 are new compounds.