MRI-based endplate bone quality score predicts cage subsidence following oblique lumbar interbody fusion.

BACKGROUND CONTEXT: Cage subsidence is a common complication after lumbar interbody fusion surgery, with low bone mineral density (BMD) being a significant risk factor. ໿Endplate bone quality (EBQ) obtained from clinical MRI scans has been deemed reliable in determining regional BMD. However, the association between EBQ score and cage subsidence following oblique lumbar interbody fusion (OLIF) has not been clearly established. PURPOSE: This study aims to assess the relationship between EBQ score and cage subsidence in patients who underwent single-level OLIF. STUDY DESIGN/SETTING: A retrospective study. PATIENT SAMPLE: The study included adults with degenerative spinal conditions who underwent single-level OLIF at our institution. OUTCOME MEASURES: Cage subsidence, disc height, EBQ score, fusion rate. METHODS: This retrospective study analyzed data from patients who underwent single-level OLIF surgery at our institution between October 2017 and August 2022. Postoperative CT scans were used to measure cage subsidence, while the EBQ score was calculated using preoperative non-contrast T1-weighted MRI. To determine the predictive ability of the EBQ score, receiver operating characteristic (ROC) curve analysis was conducted. Additionally, univariable and multivariable logistic regression analyses were performed. RESULTS: In this study, a total of 88 patients were included and followed up for an average of 15.8 months. It was observed that 32.9% (n=29/88) of the patients experienced cage subsidence. The post-surgery disc height was significantly higher in patients who experienced subsidence compared to those who did not. The mean EBQ scores for patients with non-subsidence and subsidence were 2.31±0.6 and 3.48±1.2, respectively, and this difference was statistically significant. The ROC curve analysis showed that the AUC for the EBQ score was 0.811 (95% CI: 0.717-0.905). The most suitable threshold for the EBQ score was determined to be 2.318 (sensitivity: 93.1%, specificity: 55.9%). Additionally, the multivariate logistic regression analysis revealed a significant association between a higher EBQ score and an increased risk of subsidence (odds ratio [OR]=6.204, 95% CI=2.520-15.272, p<.001). CONCLUSIONS: Our findings indicate that higher preoperative EBQ scores are significantly linked to cage subsidence following single-level OLIF. Preoperative measurement of MRI can serve as a valuable tool in predicting cage subsidence.

A Biomimetic Fibrous Composite Scaffold with Nanotopography-Regulated Mineralization for Bone Defect Repair.

The effective regeneration of large bone defects via bone tissue engineering is challenging due to the difficulty in creating an osteogenic microenvironment. Inspired by the fibrillar architecture of the natural extracellular matrix, we developed a nanoscale bioengineering strategy to produce bone fibril-like composite scaffolds with enhanced osteogenic capability. To activate the surface for biofunctionalization, self-adaptive ridge-like nanolamellae were constructed on poly(ε-caprolactone) (PCL) electrospinning scaffolds via surface-directed epitaxial crystallization. This unique nanotopography with a markedly increased specific surface area offered abundant nucleation sites for Ca2+ recruitment, leading to a 5-fold greater deposition weight of hydroxyapatite than that of the pristine PCL scaffold under stimulated physiological conditions. Bone marrow mesenchymal stem cells (BMSCs) cultured on bone fibril-like scaffolds exhibited enhanced adhesion, proliferation, and osteogenic differentiation in vitro. In a rat calvarial defect model, the bone fibril-like scaffold significantly accelerated bone regeneration, as evidenced by micro-CT, histological histological and immunofluorescence staining. This work provides the way for recapitulating the osteogenic microenvironment in tissue-engineered scaffolds for bone repair.

Health-related Quality of Life (HRQOL) Outcomes of Selective/Nonselective Thoracic Fusion for Lenke 1C Adolescent Idiopathic Scoliosis (AIS) Patients with a Minimum 4-year Follow-up.

OBJECTIVE: Both the selective thoracic fusion (STF) and nonselective thoracic fusion (NSTF) are treatments for Lenke 1C adolescent idiopathic scoliosis (AIS). To date, the impacts of the two surgical strategies on patients' long-term quality of life remain unclear. Therefore, the purpose of this study was to explore the long-term effects of STF/NSTF on the quality of life in Lenke 1C AIS patients through a 4-10-year follow-up. METHODS: From January 2011 to April 2018, according to the inclusion and exclusion criteria, a retrospective single-center study of 75 surgical patients with Lenke 1C curves was performed (n = 75). They all underwent posterior fusion, and patients were divided into the selective thoracic fusion (STF) group (n = 42) and the nonselective thoracic fusion (NSTF) group (n = 33) based on their surgical approach. All participants received the survey of the visual analogue scale (VAS), SRS30, SF12, and Oswestry disability index (ODI) scales. Patients' gender, age, body mass index (BMI), surgical approach (STF/NSTF), surgical segments (UIV and LIV), follow-up time, complications, preoperative, postoperative, and last follow-up Cobb angles, and health-related quality of life (HRQOL) outcomes were collected, and analyzed through the Shapiro-Wilks test, Wilcoxon rank-sum test, t-test, and χ2 test. RESULTS: The mean follow-up of the entire cohort was 73 ± 5.6 months. The lumbar Cobb angle in the STF group improved from 31.8 ± 6.5° to 11.5 ± 5.1° after the operation and 10.3 ± 6.9° at the last follow-up. The postoperative correction rate of the lumbar curve was 63.8%, which increased to 67.7% at the last follow-up. In the NSTF group, the lumbar Cobb angle improved from 34.3 ± 11.3° to 4.3 ± 3.7° after the operation, and was 5.1 ± 3.1° at the last follow-up. The postoperative correction rate of the lumbar curve was 87.4%, and 85.1% at the last follow-up. At the last follow-up, the STF group had higher overall HRQOL scores than the NSTF group, and there were statistically differences between the different groups (STF/NSTF) in SRS-30-Mental health (p = 0.03), SRS-30-Satisfaction with management (p = 0.02), SRS-30-Pain (p = 0.03), ODI (p = 0.01), SF-12 PCS (p = 0.03), VAS back pain (p = 0.005) and VAS leg pain (p = 0.001). No statistically differences were found in SF12 MCS, SRS-30-Self-image/Appearance and SRS-30 Function/activity. CONCLUSION: After 4-10 years of follow-up, we found that the STF group achieved satisfactory correction results, and compared with the NSTF group, their overall HRQOL scores were higher, especially in terms of pain and satisfaction, where the STF group shows a significant advantage.

Corydalis tomentella Franch. Exerts anti-inflammatory and analgesic effects by regulating the calcium signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Corydalis tomentella Franch. is a perennial cespitose plant commonly used to treat stomachaches as a folk medicine. The C. tomentella total alkaloids have good protective effects against acute liver injury and potential anti-hepatoma and anti-Alzheimer's disease activities. AIM OF THE STUDY: To establish an effective purification process for total alkaloids from C. tomentella and investigate the mechanism of their anti-inflammatory effects. MATERIALS AND METHODS: Corydalis tomentella were purified using macroporous resin. Then the crude and purified C. tomentella extracts (cCTE and pCTE) were qualitatively analyzed using UPLC-Triple-TOF-MS/MS. The cCTE and pCTE were used to investigate and compare their anti-inflammatory effects on lipopolysaccharide (LPS)-induced RAW264.7 cells. Doses at 100, 200 and 400 mg/kg/d of pCTE were used to study their anti-inflammatory and analgesic activities in mice with xylene-induced ear swelling and acetic acid-induced writhing tests. Content of nitric oxide (NO), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) were determined both in RAW264.7 cells and mice. Network pharmacology was used to predict the anti-inflammatory mechanism of C. tomentella, and the key enzymes were validated using qPCR and Western Blot analysis. Concentration of intracellular Ca2+ was detected using flow cytometric analysis. RESULTS: The C. tomentella total alkaloid purity increased from 6.29% to 47.34% under optimal purification conditions. A total of 54 alkaloids were identified from CTE. Both cCTE and pCTE could suppress the LPS-induced production of NO, IL-6, IL-1ß, and TNF-α in RAW264.7 cells. The pCTE exhibited a more potent anti-inflammatory effect; it also inhibited pain induced by xylene and acetic acid in mice. The calcium signaling pathway is associated with the anti-inflammatory and analgesic activities of C. tomentella. The mRNA expression of nitric oxide synthase (NOS) 2, NOS3 and calmodulin1 (CALM1) was regulated by C. tomentella through the reduction of inflammation-induced Ca2+ influx, and it also exhibited a more pronounced effect than the positive control (L-NG-nitro arginine methyl ester). CONCLUSIONS: Purified C. tomentella extract shows anti-inflammatory effect both in vitro and in vivo. It exerts anti-inflammatory and analgesic effects through the calcium signaling pathway by down-regulating NOS2 and CALM1 expression and up-regulating NOS3 expression in LPS-induced RAW264.7 cells, and decreasing intracellular Ca2+ concentration.

A Novel Technique for Autograft Preparation Using Patient-Specific Instrumentation (PSI) Assistance in Total Hip Arthroplasty in Developmental Dysplasia of Hip (DDH).

Due to the change in the structure of the proximal femur and acetabulum in patients with developmental dysplasia of the hip, total hip arthroplasty (THA) was difficult to perform for surgeons. To elevate the acetabular coverage rate, we developed a technique in the use of a patient-specific instrumentation (PSI) graft in patients with developmental dysplasia of hip (DDH) undergoing surgery. This study aims to evaluate the peri-operative outcomes of THA with PSI graft in patients with DDH. This study recruited 6 patients suffering from Crowe I DDH with secondary Grade IV osteoarthritis. All the patients underwent THA with PSI graft performed by a well-experienced surgeon. Perioperative outcomes included surgical procedures, blood loss during operation, the volume of blood transfusion, length of hospitalization, complications, and the mean difference in hemoglobin levels before and after surgery. All the outcomes analyzed were assessed by mean and standard deviation. The average duration of the surgical procedure was found to be 221.17 min, with an SD of 19.65 min. The mean blood loss during the operation was 733.33 mL, with an SD of 355.90 mL. The mean length of hospital stay was calculated to be 6 days, with an SD of 0.89 days. Furthermore, the mean difference between the pre- and postoperative hemoglobin levels was 2.15, with an SD of 0.99. A total of three patients received 2 units of leukocyte-poor red blood cells (LPR) as an accepted blood transfusion. There were no reported complications observed during the admission and one month after the operation. This study reported the peri-operative outcomes in the patients with DDH who underwent THA with PSI graft. We found that THA with PSI graft would provide a safe procedure without significant complications. We assumed that the PSI graft in THA may increase the coverage rate of the acetabulum, which may increase the graft union rates. Further cohort studies and randomized controlled trials were needed to confirm our findings.

The Influence of Screw Positioning on Cage Subsidence in Patients with Oblique Lumbar Interbody Fusion Combined with Anterolateral Fixation.

OBJECTIVES: Cage subsidence (CS) has been reported to be one of the most common complications following oblique lumbar interbody fusion (OLIF). To reduce the incidence of CS and improve intervertebral fusion rates, anterolateral fixation (AF) has been gradually proposed. However, the incidence of CS in patients with oblique lumbar interbody fusion combined with anterolateral fixation (OLIF-AF) is still controversial. Additionally, there is a lack of consensus regarding the optimal placement of screws for OLIF-AF, and the impact of screw placement on the incidence of CS has yet to be thoroughly investigated and validated. The objective of this investigation was to examine the correlation between screw placements and CS and to establish an optimized approach for implantation in OLIF-AF. METHODS: A retrospective cohort study was undertaken. From October 2017 to December 2020, a total of 103 patients who received L4/5 OLIF-AF for lumbar spinal stenosis or spondylolisthesis or degenerative instability in our department were followed up for more than 12 months. Demographic and radiographic data of these patients were collected. Additionally, screw placement related parameters, including trajectory and position, were measured by anterior-posterior X-ray and axial CT. Analysis was done by chi-square, independent t-test, univariable and multivariable binary logistic regression to explore the correlation between screw placements and CS. Finally, the receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive ability of screw placement-related parameters. RESULTS: A total of 103 patients were included, and CS was found in 28 (27.18%) patients. Univariable analysis was firstly performed for each parameter. Next, variables with p-value of <0.05, including bone mineral density (BMD), concave morphology, and screw placement-related parameters were included in the multivariate logistic regression analysis. Significant predictor factors for subsidence were coronal plane angle (CPA) (OR 0.580 ± 0.208, 95% CI 1.187-2.684), implantation point (IP) (L4) (OR 5.732 ± 2.737, 95% CI 1.445-12.166), and IP (L5) (OR 7.160 ± 3.480, 95% CI 1.405-28.683). Furthermore, ROC curves showed that the predictive accuracy of CS was 88.1% for CPA, 77.6% for IP (L4) and 80.9% for IP (L5). CONCLUSIONS: We demonstrate that the trajectory of vertebral screws, including angle and position, was closely related to CS. Inserting screws parallel to each other and as close to the endplate as possible while keeping the cage inside the range of the superior and inferior screws are an optimal implantation strategy for OLIF-AF.

Discovery of Novel 3,11-Bispeptide Ester Arenobufagin Derivatives with Potential in Vivo Antitumor Activity and Reduced Cardiotoxicity.

Arenobufagin, one of the bufadienolides isolated from traditional Chinese medicine Chan'su, exhibits potent antitumor activity. However, serious toxicity and small therapeutic window limits its drug development. In the present study, to our knowledge, novel 3,11-bispeptide ester arenobufagin derivatives have been firstly designed and synthesized on the base of our previous discovery of active 3-monopeptide ester derivative. The in vitro antiproliferative activity evaluation revealed that the moiety at C3 and C11 hydroxy had an important influence on cytotoxic activity and selectivity. Compound ZM350 notably inhibited tumor growth by 58.8 % at a dose 10 mg/kg in an A549 nude mice xenograft model. Therefore, compound ZM350 also presented a concentration-dependent apoptosis induction and low inhibitory effect against both hERG potassium channel and Cav1.2 calcium channel. Our study suggests that novel 3,11-bispeptide ester derivatives will be a potential benefit to further antitumor agent development of arenobufagin.

Featuring few essential Raman spectroscopic signatures between heterogeneous cells.

Here we demonstrate it is instructive to quantify cell Raman spectroscopy by sparse regularization. To be able to extract the specific spectral differences in a heterogeneous cell system with great spectroscopic similarities derived from many common biomolecular components, the maximum information entropy probability was proposed and exemplified by identifying normal lymphocytes from leukemia cells. The essential spectroscopic features were observed to locate at three Raman peaks whose spectral signatures were commensurate. The applicability of the extracted features was acknowledged by that the predicted identification accuracy of up to 93% was still achieved when only two peaks were loaded into decision tree model, which may provide the possibility of a clinically rapid hematological malignancy detection.

Correlation and Difference Between Raman Spectral Characteristic and Feature Evaluation for Leukocytes and Tumor Cells.

Tumor detection supported by Raman spectroscopy is becoming increasingly popular, yet the relevance of spectral variation and feature selection retains unclear. Here we determined the correlation and difference between spectral characteristic and feature evaluation for leukocytes and tumor cells. Some peaks were found to show noticeable spectral differences, and their intensity distributions were investigated, finding using log-normal distribution to describe Raman intensity pattern may be more appropriate. Further the importance of all Raman features was calculated, where some other peak features occupied the top status. By surveying the intensity variation and feature evaluation for those peaks, we concluded the peak with the highest importance does not correspond to the peak location with the most noticeable intensity difference in spectra. Moreover, the peak intensity ratio of I1517/I719 associated with protein to nucleic acid level presented the maximum separation, thus, it can be recognized as a special indicator to develop an alternative cancer detection. It is inspiring to introduce advanced statistical models into bio-spectroscopic fields but those intrinsic spectral variations rather than classification performance should be valued. Our explorations can provide possibilities to reveal the essences within tumor carcinogenesis based on Raman spectroscopy, further overwhelming the obstacles during the translation into clinical applications.

Gastrodia remodels intestinal microflora to suppress inflammation in mice with early atherosclerosis.

Atherosclsis is a critical actuator causing cardiac-cerebral vascular disease with a complicated pathogeneon, refered to the disorders of intestinal flora and persistent inflammation. Gastrodin (4-(hydroxymethyl) phenyl-ß-D- Glucopyranoside) is the most abundant glucoside extracted from the Gastrodiaelata, which is a traditional Chinese herbal medicine for cardiac-cerebral vascular disease, yet its mechanisms remain little known. In the present study, the gastrodia extract and gastrodin attenuate the lipid deposition and foam cells on the inner membrane of the inner membrane of the thoracic aorta in the early atherosclerosis mice. Blood lipid detection tips that TC and LDL-C were reduced in peripheral blood after treatment with the gastrodia extract and gastrodin. Furthermore, unordered gut microbes are remodeled in terms of bacterial diversity and abundance at family and genus level. Also, the intestinal mucosa damage and permeability were reversed, accompaniedwith the reducing of inflammatory cytokines. Our findings revealed that the functions of gastrodia extract and gastrodin in cardiac-cerebral vascular disease involved to rescued gut microbes and anti-inflammation may be the mechanismof remission lipid accumulation.

Potential effect of tropical fruits Phyllanthus emblica L. for the prevention and management of type 2 diabetic complications: a systematic review of recent advances.

Phyllanthus emblica is a fruit widely consumed in subtropical areas, which is rich in polyphenols and other nutrients. There are increasing evidences that as a daily and nutritious fruit, it may have a positive role in controlling diabetic complications. According to the new study, its mechanisms include enhancing the functioning of insulin, reducing insulin resistance, activating the insulin-signaling pathway, protecting ß-cells, scavenging free radicals, alleviating inflammatory reactions, and reducing the accumulation of advanced glycation end products. Owing to its few side effects, and low price, it should be easily accepted by patients and has potential for preventing diabetes. Taken together, Phyllanthus emblica may be an ideal fruit for controlling diabetic complications. This review highlights the latest findings of the role of Phyllanthus emblica in anti-diabetes and its complications, especially clarifies the molecular mechanism of the chemical components related to this effect, and prospects some existing problems and future research directions.

Discovery of 3-peptide substituted arenobufagin derivatives as potent antitumor agents with low cardiotoxicity.

Active natural productscan be valuable lead compounds and numerous drugs derived from natural products have successfully entered the clinic. Arenobufagin, one of the important active components of toad venom, indicates significant antitumor activities with limited preclinical development for its strong cardiotoxicity. Ten 3-monopeptide substituted arenobufagin derivatives have been designed and synthesized. Antitumor activity and cardiotoxicity assays lead to the discovery of compound ZM226 as a potent antitumor agent with low cardiotoxicity. These findings suggest optimization of arenobufagin on position 3 maybe an efficacious strategy for the development of antitumor drug candidates derived from arenobufagin.

Concentrated stress effects of contoured and non-contoured high Tibial osteotomy plates: A finite-element study.

BACKGROUND: The TomoFix plate has been extensively used in high tibial osteotomy surgery to stabilize the distracted tibial bones. However, distal pain related to plate irritation was considered one of the most relevant complications for this fixation device. This study aimed to correlate reports of distal pain with the profiles of the distracted tibia and initial plate and plate contour. METHODS: This study used the finite-element method to investigate the profile-, distraction-, and contour-induced effects on stress distribution of the distal tibia-plate contact. The associations of two tibia profiles (normal and concave), distraction angles, and two plate profiles (contoured and non-contoured) were discussed in this study. The areas and stresses of the distal tibia-plate contact were chosen as comparison indices. FINDINGS: Before weight-bearing, the non-contoured plates of the normal and concave tibia profiles consistently showed less contact area at the distal tibia-plate region. Consequently, the physiological loads make the non-contoured plate subject to more concentrated bone stresses and thus may induce more pain at the distal tibia-plate region than a contoured plate. When the distraction angle decreases, the tibia-plate gap increases. Prior to fixation, the tibia-plate gap can be evaluated by the profiles of the distracted tibia and non-contoured plate by use of anteroposterior radiograph and computer-aided simulation. INTERPRETATION: In the situations of a lower distraction angle or a large tibia-plate gap, the use of a plate bender or a lag screw is recommended in order to contour the plate for reducing the concentrated stress at the distal tibia-plate region.

Metabolites from Bufo gargarizans (Cantor, 1842): A review of traditional uses, pharmacological activity, toxicity and quality control.

ETHNOPHARMACOLOGICAL RELEVANCE: Bufo gargarizans (Cantor, 1842) (BGC), a traditional medicinal animal distributed in many provinces of China, is well known for the pharmaceutical value of Chansu and Chanpi. As traditional Chinese medicines (TCMs), Chansu and Chanpi, with their broad-spectrum of therapeutic applications, have long been applied to detoxification, anti-inflammation, analgesia, etc. OVERARCHING OBJECTIVE: We critically analyzed the current evidence for the traditional uses, chemical profiles, pharmacological activity, toxicity and quality control of BGC (Bufonidae family) to provide a scientific basis for future in-depth studies and perspectives for the discovery of potential drug candidates. METHODOLOGY: All of the available information on active constituents and TCMs derived from BGC was obtained using the keywords "Bufo gargarizans", "Chansu", "Chanpi", "Huachansu", or "Cinobufacini" through different electronic databases, including PubMed, Web of Science, Chinese National Knowledge Infrastructure (CNKI), the Wanfang Database, and Pharmacopoeia of China. In addition, Chinese medicine books from different times were used to elucidate the traditional uses of BGC. Electronic databases, including the "IUCN Red List of Threatened Species", "American Museum of Natural History" and "AmphibiaWeb Species Lists", were used to validate the scientific name of BGC. RESULTS: To date, about 118 bufadienolide monomers and 11 indole alkaloids have been identified from BGC in total. The extracts and isolated compounds exhibit a wide range of in vitro and in vivo pharmacological effects. The literature search demonstrated that the ethnomedicinal uses of BGC, such as detoxification, anti-inflammation and the ability to reduce swelling and pain associated with infections, are correlated with its modern pharmacological activities, including antitumor, immunomodulation and attenuation of cancer-derived pain. Bufadienolides and indole alkaloids have been regarded as the main active substances in BGC, among which bufadienolides have significant antitumor activity. Furthermore, the cardiotoxicity of bufadienolides was discussed, and the main molecular mechanism involves in the inhibition of Na+/K+-ATPase. Besides, with the development of modern analytical techniques, the quality control methods of BGC-derived TCMs are being improved constantly. CONCLUSIONS: An increasing number of reports suggest that BGC can be regarded as an excellent source for exploring the potential antitumor constituents. However, the future antitumor research of BGC needs to follow the standard pharmacology guidelines, so as to provide comprehensive pharmacological information and aid the reproducibility of the data. Besides, to ensure the efficacy and safety of BGC-derived TCMs, it is vital to construct a comprehensive quality evaluation model on the basis of clarifying pharmacodynamic-related and toxicity-related compositions.

A Potential Anti-Tumor Herb Bred in a Tropical Fruit: Insight into the Chemical Components and Pharmacological Effects of Momordicae Semen.

Gac fruit (Momordica cochinchinensis Spreng) is a popular tropical fruit in southeast Asia. What is amazing is that its seeds (Momordicae Semen) and arils are traditional herbs with anti-tumor activity, and have protected human health for more than 1000 years. In recent years, its anti-tumor activity has received extensive attention and research. This manuscript summarized the chemical composition of saponins, fatty acids, volatile constituents, proteins, peptides, and other components from Momordicae Semen (MSE). The effect and mechanism of MSE and its extract on breast cancer, gastric cancer, lung cancer, esophagus cancer, melanomas, and human cervical epithelial carcinoma were discussed. In addition, its antioxidant, anti-inflammatory, and other pharmacological effects were also analyzed. We hope that this review will provide new ideas for the treatment of cancer and other diseases, and become a reference for the further research into complementary and alternative medicine.

Seeing the Unseen of the Combination of Two Natural Resins, Frankincense and Myrrh: Changes in Chemical Constituents and Pharmacological Activities.

For the treatment of diseases, especially chronic diseases, traditional natural drugs have more effective therapeutic advantages because of their multi-target and multi-channel characteristics. Among many traditional natural medicines, resins frankincense and myrrh have been proven to be effective in the treatment of inflammation and cancer. In the West, frankincense and myrrh have been used as incense in religious and cultural ceremonies since ancient times; in traditional Chinese and Ayurvedic medicine, they are used mainly for the treatment of chronic diseases. The main chemical constituents of frankincense and myrrh are terpenoids and essential oils. Their common pharmacological effects are anti-inflammatory and anticancer. More interestingly, in traditional Chinese medicine, frankincense and myrrh have been combined as drug pairs in the same prescription for thousands of years, and their combination has a better therapeutic effect on diseases than a single drug. After the combination of frankincense and myrrh forms a blend, a series of changes take place in their chemical composition, such as the increase or decrease of the main active ingredients, the disappearance of native chemical components, and the emergence of new chemical components. At the same time, the pharmacological effects of the combination seem magically powerful, such as synergistic anti-inflammation, synergistic anticancer, synergistic analgesic, synergistic antibacterial, synergistic blood-activation, and so on. In this review, we summarize the latest research on the main chemical constituents and pharmacological activities of these two natural resins, along with chemical and pharmacological studies on the combination of the two.

Clinical Experience Using a 3D-Printed Patient-Specific Instrument for Medial Opening Wedge High Tibial Osteotomy.

PURPOSE: High tibial osteotomy (HTO) has been adopted as an effective surgery for medial degeneration of the osteoarthritis (OA) knee. However, satisfactory outcomes necessitate the precise creation and distraction of osteotomized wedges and the use of intraoperative X-ray images to continually monitor the wedge-related manipulation. Thus HTO is highly technique-demanding and has a high radiation exposure. We report a patient-specific instrument (PSI) guide for the precise creation and distraction of HTO wedge. METHODS: This study first parameterized five HTO procedures to serve as a design rationale for an innovative PSI guide. Preoperative X-ray and computed tomography- (CT-) scanning images were used to design and fabricate PSI guides for clinical use. The weight-bearing line (WBL) of the ten patients was shifted to the Fujisawa's point and instrumented using the TomoFix system. The radiological results of the PSI-guided HTO surgery were evaluated by the WBL percentage and tibial slope. RESULTS: All patients consistently showed an increased range of motion and a decrease in pain and discomfort at about three-month follow-up. This study demonstrates the satisfactory accuracy of the WBL adjustment and tibial slope maintenance after HTO with PSI guide. For all patients, the average pre- and postoperative WBL are, respectively, 14.2% and 60.2%, while the tibial slopes are 9.9 and 10.1 degrees. The standard deviations are 2.78 and 0.36, respectively, in postoperative WBL and tibial slope. The relative errors of the pre- and postoperative WBL percentage and tibial slope averaged 4.9% and 4.1%, respectively. CONCLUSION: Instead of using navigator systems, this study integrated 2D and 3D preoperative planning to create a PSI guide that could most likely render the outcomes close to the planning. The PSI guide is a precise procedure that is time-saving, radiation-reducing, and relatively easy to use. Precise osteotomy and good short-term results were achieved with the PSI guide.

Combination of Cinobufacini and Doxorubicin Increases Apoptosis of Hepatocellular Carcinoma Cells through the Fas- and Mitochondria-Mediated Pathways.

Cinobufacini, a traditional Chinese medicine, has been used widely for cancer treatment, such as hepatocellular carcinoma (HCC), sarcoma, and leukemia. Previous studies done by our lab indicated that cinobufacini could suppress HCC cells through mitochondria-mediated and Fas-mediated apoptotic pathways. Here, we use a combination of cinobufacini and doxorubicin to inhibit the growth of HCC cells. The combination group induced more significant apoptosis by affecting proteins and RNA of apoptosis-related elements, such as Bcl-2, Bax, Bid, and cytochrome c. Furthermore, cinobufacini, as a mixture of a number of components, had stronger apoptosis-inducing activity than particular individual components or a simple mixture of a few components. Overall, these results suggested that the combination of cinobufacini and doxorubicin may provide a new strategy for inhibiting the proliferation of HCC cells.

Direct Intracochlear Acoustic Stimulation Using a PZT Microactuator.

Combined electric and acoustic stimulation has proven to be an effective strategy to improve hearing in some cochlear implant users. We describe an acoustic microactuator to directly deliver stimuli to the perilymph in the scala tympani. The 800 µm by 800 µm actuator has a silicon diaphragm driven by a piezoelectric thin film (e.g., lead-zirconium-titanium oxide or PZT). This device could also be used as a component of a bimodal acoustic-electric electrode array. In the current study, we established a guinea pig model to test the actuator for its ability to deliver auditory signals to the cochlea in vivo. The actuator was placed through the round window of the cochlea. Auditory brainstem response (ABR) thresholds, peak latencies, and amplitude growth were calculated for an ear canal speaker versus the intracochlear actuator for tone burst stimuli at 4, 8, 16, and 24 kHz. An ABR was obtained after removal of the probe to assess loss of hearing related to the procedure. In some animals, the temporal bone was harvested for histologic analysis of cochlear damage. We show that the device is capable of stimulating ABRs in vivo with latencies and growth functions comparable to stimulation in the ear canal. Further experiments will be necessary to evaluate the efficiency and safety of this modality in long-term auditory stimulation and its ability to be integrated with conventional cochlear implant arrays.