Efficacy and safety of Enhanced Recovery after surgery (ERAS) Protocols for Patients Undergoing Minimally Invasive Transforaminal Lumbar Interbody Fusion Surgery: a Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of enhanced recovery after surgery (ERAS) in minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) for lumbar degenerative disease. METHODS: Electronic databases including PubMed, Embase, the Cochrane Library, Web of Science, Clinical Trials.gov, etc. were searched from inception to October 2023. Randomized controlled trials (RCTs) and cohort studies (CSs) comparing ERAS program with traditional protocol of MIS-TLIF for LDD were included. RESULTS: A total of 11 studies were included for final analysis. The pooled results of RCTs showed that Compared with MIS-TLIF, the ERAS program used in MIS-TLIF could reduce the length of hospital stay, operation time, intraoperative blood loss and incidence of postoperative complications, decrease visual analog scale and oswestry disability index (ODI) score, and improve patient satisfaction (P<0.05). However, the pooled results of CSs revealed no statistical difference in the ODI score, fusion rate, operation time, and incidence of complications between the two groups (P>0.05). CONCLUSIONS: Compared with MIS-TLIF, the ERAS program used in MIS-TLIF could effectively shorten the length of hospital stay, operation time, decrease intraoperative blood loss and incidence of postoperative complications, promote postoperative pain relief, functional recovery, and patient satisfaction. This study confirmed the value of ERAS in MIS-TLIF surgery and provided evidence for the standardization of ERAS in the future. Considering that the pooled results of RCTs and CSs are not completely consistent, more high-quality studies are needed to confirm these conclusions.

Machine learning methods predict recurrence of pN3b gastric cancer after radical resection.

Background: The incidence of stage pN3b gastric cancer (GC) is low, and the clinical prognosis is poor, with a high rate of postoperative recurrence. Machine learning (ML) methods can predict the recurrence of GC after surgery. However, the prognostic significance for pN3b remains unclear. Therefore, we aimed to predict the recurrence of pN3b through ML models. Methods: This retrospective study included 336 patients with pN3b GC who underwent radical surgery. A 3-fold cross-validation was used to partition the participants into training and test cohorts. Linear combinations of new variable features were constructed using principal component analysis (PCA). Various ML algorithms, including random forest, support vector machine (SVM), logistic regression, multilayer perceptron (MLP), extreme gradient boosting (XGBoost), and Gaussian naive Bayes (GNB), were utilized to establish a recurrence prediction model. Model performance was evaluated using the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Python was used for the analysis of ML algorithms. Results: Nine principal components with a cumulative variance interpretation rate of 90.71% were identified. The output results of the test set showed that random forests had the highest AUC (0.927) for predicting overall recurrence with an accuracy rate of 80.5%. Random forests had the highest AUC (0.940) for predicting regional recurrence with an accuracy of 89.7%. For predicting distant recurrence, random forests had the highest AUC (0.896) with an accuracy of 84.3%. For peritoneal recurrence, random forests had the highest AUC (0.923) with an accuracy of 83.3%. Conclusions: ML can personalize the prediction of postoperative recurrence in patients with GC with stage pN3b.

Gene replacement therapy in Bietti crystalline corneoretinal dystrophy: an open-label, single-arm, exploratory trial.

Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2, which results in blindness in the working-age population, and there is currently no available treatment. Here, we report the results of the first-in-human clinical trial (NCT04722107) of gene therapy for Bietti crystalline corneoretinal dystrophy, including 12 participants who were followed up for 180-365 days. This open-label, single-arm exploratory trial aimed to assess the safety and efficacy of a recombinant adeno-associated-virus-serotype-2/8 vector encoding the human CYP4V2 protein (rAAV2/8-hCYP4V2). Participants received a single unilateral subretinal injection of 7.5 × 1010 vector genomes of rAAV2/8-hCYP4V2. Overall, 73 treatment-emergent adverse events were reported, with the majority (98.6%) being of mild or moderate intensity and considered to be procedure- or corticosteroid-related; no treatment-related serious adverse events or local/systemic immune toxicities were observed. Compared with that measured at baseline, 77.8% of the treated eyes showed improvement in best-corrected visual acuity (BCVA) on day 180, with a mean ± standard deviation increase of 9.0 ± 10.8 letters in the 9 eyes analyzed (p = 0.021). By day 365, 80% of the treated eyes showed an increase in BCVA, with a mean increase of 11.0 ± 10.6 letters in the 5 eyes assessed (p = 0.125). Importantly, the patients' improvement observed using multifocal electroretinogram, microperimetry, and Visual Function Questionnaire-25 further supported the beneficial effects of the treatment. We conclude that the favorable safety profile and visual improvements identified in this trial encourage the continued development of rAAV2/8-hCYP4V2 (named ZVS101e).

Targeting epigenetic and post-translational modifications regulating pyroptosis for the treatment of inflammatory diseases.

Inflammatory diseases, including infectious diseases, diabetes-related diseases, arthritis-related diseases, neurological diseases, digestive diseases, and tumor, continue to threaten human health and impose a significant financial burden despite advancements in clinical treatment. Pyroptosis, a pro-inflammatory programmed cell death pathway, plays an important role in the regulation of inflammation. Moderate pyroptosis contributes to the activation of native immunity, whereas excessive pyroptosis is associated with the occurrence and progression of inflammation. Pyroptosis is complicated and tightly controlled by various factors. Accumulating evidence has confirmed that epigenetic modifications and post-translational modifications (PTMs) play vital roles in the regulation of pyroptosis. Epigenetic modifications, which include DNA methylation and histone modifications (such as methylation and acetylation), and post-translational modifications (such as ubiquitination, phosphorylation, and acetylation) precisely manipulate gene expression and protein functions at the transcriptional and post-translational levels, respectively. In this review, we summarize the major pathways of pyroptosis and focus on the regulatory roles and mechanisms of epigenetic and post-translational modifications of pyroptotic components. We also illustrate these within pyroptosis-associated inflammatory diseases. In addition, we discuss the effects of novel therapeutic strategies targeting epigenetic and post-translational modifications on pyroptosis, and provide prospective insight into the regulation of pyroptosis for the treatment of inflammatory diseases.

Inhibition of METTL3 in macrophages provides protection against intestinal inflammation.

Inflammatory bowel disease (IBD) is prevalent, and no satisfactory therapeutic options are available because the mechanisms underlying its development are poorly understood. In this study, we discovered that increased expression of methyltransferase-like 3 (METTL3) in macrophages was correlated with the development of colitis and that depletion of METTL3 in macrophages protected mice against dextran sodium sulfate (DSS)-induced colitis. Mechanistic characterization indicated that METTL3 depletion increased the YTHDF3-mediated expression of phosphoglycolate phosphatase (PGP), which resulted in glucose metabolism reprogramming and the suppression of CD4+ T helper 1 (Th1) cell differentiation. Further analysis revealed that glucose metabolism contributed to the ability of METTL3 depletion to ameliorate colitis symptoms. In addition, we developed two potent small molecule METTL3 inhibitors, namely, F039-0002 and 7460-0250, that strongly ameliorated DSS-induced colitis. Overall, our study suggests that METTL3 plays crucial roles in the progression of colitis and highlights the potential of targeting METTL3 to attenuate intestinal inflammation for the treatment of colitis.

Identification and Verification of Novel Biomarkers Involving Rheumatoid Arthritis with Multimachine Learning Algorithms: An In Silicon and In Vivo Study.

Background: Rheumatoid arthritis (RA) remains one of the most prevalent chronic joint diseases. However, due to the heterogeneity among RA patients, there are still no robust diagnostic and therapeutic biomarkers for the diagnosis and treatment of RA. Methods: We retrieved RA-related and pan-cancer information datasets from the Gene Expression Omnibus and The Cancer Genome Atlas databases, respectively. Six gene expression profiles and corresponding clinical information of GSE12021, GSE29746, GSE55235, GSE55457, GSE77298, and GSE89408 were adopted to perform differential expression gene analysis, enrichment, and immune component difference analyses of RA. Four machine learning algorithms, including LASSO, RF, XGBoost, and SVM, were used to identify RA-related biomarkers. Unsupervised cluster analysis was also used to decipher the heterogeneity of RA. A four-signature-based nomogram was constructed and verified to specifically diagnose RA and osteoarthritis (OA) from normal tissues. Consequently, RA-HFLS cell was utilized to investigate the biological role of CRTAM in RA. In addition, comparisons of diagnostic efficacy and biological roles among CRTAM and other classic biomarkers of RA were also performed. Results: Immune and stromal components were highly enriched in RA. Chemokine- and Th cell-related signatures were significantly activated in RA tissues. Four promising and novel biomarkers, including CRTAM, PTTG1IP, ITGB2, and MMP13, were identified and verified, which could be treated as novel treatment and diagnostic targets for RA. Nomograms based on the four signatures might aid in distinguishing and diagnosing RA, which reached a satisfactory performance in both training (AUC = 0.894) and testing (AUC = 0.843) cohorts. Two distinct subtypes of RA patients were identified, which further verified that these four signatures might be involved in the immune infiltration process. Furthermore, knockdown of CRTAM could significantly suppress the proliferation and invasion ability of RA cell line and thus could be treated as a novel therapeutic target. CRTAM owned a great diagnostic performance for RA than previous biomarkers including MMP3, S100A8, S100A9, IL6, COMP, LAG3, and ENTPD1. Mechanically, CRTAM could also be involved in the progression through immune dysfunction, fatty acid metabolism, and genomic instability across several cancer subtypes. Conclusion: CRTAM, PTTG1IP, ITGB2, and MMP13 were highly expressed in RA tissues and might function as pivotal diagnostic and treatment targets by deteriorating the immune dysfunction state. In addition, CRTAM might fuel cancer progression through immune signals, especially among RA patients.

Muti-objective optimization on energy consumption, CO2 emission and production cost for iron and steel industry.

Due to high material density, high energy consumption density and CO2 emission density, it is not only difficult but significant to clarify the relationship between energy consumption, the CO2 emission and the production cost in different conditions. However, the previous researches rarely refer how to balance the energy consumption, the CO2 emission and the production cost after the fluctuation of material, energy and carbon price as well as what will happen to them if production structure changes. Therefore, based on the conservation law of mass and energy, to study iron and steel manufacturing process (ISMP), this paper, taking carbon price into consideration, establishes a muti-optimization model of energy consumption, CO2 emission and cost. After optimization with different objectives, the production cost per tonne of crude steel is reduced by 192.03 CNY (7.71%), the CO2 emission per tonne of crude steel is reduced by 224.22 kg (13.37%), and the energy consumption per tonne of steel is reduced by 51.20 kgce (9.10%). Moreover, based on the optimization results under different objectives, it is ironmaking process (coal ratio and ore ratio) and steelmaking process (amount of scrap steel) that has more impact on three above as well as ore blending and coal blending have a great influence on production cost but little effect on energy consumption and CO2 emission.

Cytoskeletal activation of NHE1 regulates cell volume and DNA methylation.

The regulation of mammalian cell volume is crucial for maintaining key cellular processes. Cells can rapidly respond to osmotic and hydrostatic pressure imbalances during environmental challenges, generating fluxes of water and ions that alter volume within minutes. While the role of ion pump and leak in cell volume regulation has been well-established, the role of the actomyosin cytoskeleton and its substantial interplay with ion transporters are still unclear. In this work, we discover a system of cell volume regulation controlled by cytoskeletal activation of ion transporters. Under hypotonic shock, NIH-3T3 and MCF-10A display a 20% secondary volume increase (SVI) following the initial regulatory volume decrease. We show that SVI is initiated by Ca 2+ influx through stretch activated channel Piezo1 and subsequent actomyosin remodeling. Rather than contracting cells, actomyosin triggers cell swelling by activating Na + -H + exchanger 1 (NHE1) through their co-binding partner ezrin. Cytoskeletal activation of NHE1 can be similarly triggered by mechanical stretch and attenuated by soft substrates. This mechanism is absent in certain cancer cell lines such as HT1080 and MDA-MB-231, where volume regulation is dominated by intrinsic response of ion transporters. Moreover, cytoskeletal activation of NHE1 during SVI induces nuclear deformation, leading to DNA demethylation and a significant, immediate transcriptomic response in 3T3 cells, a phenomenon that is absent in HT1080 cells. Overall, our findings reveal the central role of Ca 2+ and actomyosin-mediated mechanosensation in the regulation of ion transport, cell volume, DNA methylation, and transcriptomics.

Roles of protein post-translational modifications in glucose and lipid metabolism: mechanisms and perspectives.

The metabolism of glucose and lipids is essential for energy production in the body, and dysregulation of the metabolic pathways of these molecules is implicated in various acute and chronic diseases, such as type 2 diabetes, Alzheimer's disease, atherosclerosis (AS), obesity, tumor, and sepsis. Post-translational modifications (PTMs) of proteins, which involve the addition or removal of covalent functional groups, play a crucial role in regulating protein structure, localization function, and activity. Common PTMs include phosphorylation, acetylation, ubiquitination, methylation, and glycosylation. Emerging evidence indicates that PTMs are significant in modulating glucose and lipid metabolism by modifying key enzymes or proteins. In this review, we summarize the current understanding of the role and regulatory mechanisms of PTMs in glucose and lipid metabolism, with a focus on their involvement in disease progression associated with aberrant metabolism. Furthermore, we discuss the future prospects of PTMs, highlighting their potential for gaining deeper insights into glucose and lipid metabolism and related diseases.

Kcnma1 is involved in mitochondrial homeostasis in diabetes-related skeletal muscle atrophy.

Uncontrolled diabetes causes a catabolic state with multi-organic complications, of which impairment on skeletal muscle contributes to the damaged mobility. Kcnma1 gene encodes the pore-forming α-subunit of Ca2+ - and voltage-gated K+ channels of large conductance (BK channels), and loss-of-function mutations in Kcnma1 are in regards to impaired myogenesis. Herein, we observed a time-course reduction of Kcnma1 expression in the tibialis anterior muscles of leptin receptor-deficient (db/db) diabetic mice. To investigate the role of Kcnma1 in diabetic muscle atrophy, muscle-specific knockdown of Kcnma1 was achieved by mice receiving intravenous injection of adeno-associated virus-9 (AAV9)-encoding shRNA against Kcnma1 under the muscle creatine kinase (MCK) promoter. Impairment on muscle mass and myogenesis were observed in m/m mice with AAV9-shKcnma1 intervention, while this impairment was more obvious in diabetic db/db mice. Simultaneously, damaged mitochondrial dynamics and biogenesis showed much severer in db/db mice with AAV9-shKcnma1 intervention. RNA sequencing revealed the large transcriptomic changes resulted by Kcnma1 knockdown, and changes in mitochondrial homeostasis-related genes were validated. Besides, the artificial alteration of Kcnma1 in mouse C2C12 myoblasts was achieved with an adenovirus vector. Consistent results were demonstrated by Kcnma1 knockdown in palmitate-treated cells, whereas opposite results were exhibited by Kcnma1 overexpression. Collectively, we document Kcnma1 as a potential keeper of mitochondrial homeostasis, and the loss of Kcnma1 is a critical event in priming skeletal muscle loss in diabetes.

Effective immobilization of Cd(II) in soil by biotic zero-valent iron and coexisting sulfate.

In this work, zero-valent iron (ZVI) combined with anaerobic bacteria was used in the remediation of Cd(II)-polluted soil under the mediation of sulfate (SO42-). Owing to hydrogen-autotrophic sulfate reduction, serious corrosion occurred on sulfate-mediated biotic ZVI in terms of solid phase characterization as massive corrosive products (e.g., goethite, magnetite and green rust) were formed, which were crucial in the immobilization of Cd(II). Thus, this integrated system achieved a 4.9-fold increase in aqueous Cd(II) removal and converted more than 53% of easily available Cd(II)-fractions (acid-extractable and reducible) to stable forms (oxidizable and residual) based on the sequential extraction results as compared to the sulfate-mediated ZVI system. Increasing SO42- concentration and ZVI dosage both demonstrated positive correlation to Cd(II) immobilization, which further reflected that hydrogenotrophic desulfuration acted an essential role in improving Cd(II) immobilization. It indicated that hydrogenotrophic desulfuration could accelerate iron corrosion and promote reactive mineral formation through biomineralization, as well as generate cadmium sulfide precipitates (CdS) to achieve excellent immobilization performance for Cd(II). Besides, this reaction was favorable under neutral pH condition. Our results highlighted the promoted effect of hydrogen-autotrophic desulfuration on ZVI corrosion to immobilize Cd(II) and offered a practicable technique in Cd(II)-polluted soil remediation.

Betaine supplementation alleviates dextran sulfate sodium-induced colitis via regulating the inflammatory response, enhancing the intestinal barrier, and altering gut microbiota.

Inflammatory bowel disease (IBD) is a multifaceted and recurrent immune disorder that occurs in the gastrointestinal tract. Betaine is a natural compound that exerts beneficial anti-inflammatory effects. However, the role of betaine in protecting IBD is still unclear. Therefore, the aim of our study was to investigate the anti-inflammatory effect of betaine in dextran sulfate sodium (DSS)-induced colitis. The results showed that betaine greatly increased the body weight and decreased the disease activity index score of DSS-treated mice. Furthermore, betaine effectively downregulated the protein levels of pro-inflammatory cytokines (IL-1ß, IL-6, and TNFα) and upregulated tight junction proteins (occludin and ZO-1) in the mice. Additionally, betaine exposure remarkably restricted the DSS-induced phosphorylation of IκB and NF-κB p65 in mice. Similarly, betaine pretreatment improved the inflammatory response and intestinal barrier of Caco-2 cells. Betaine altered the gut microbiota composition, markedly decreasing the relative abundance of Firmicutes and Proteobacteria and considerably increasing the relative abundance of Bacteroidota and Campylobacterota in DSS-induced mice. In conclusion, betaine could attenuate colitis via regulating the inflammatory response, enhancing the intestinal barrier, and altering gut microbiota and is conducive to developing new drugs for treating human diseases.

Characteristics, Treatments, and Survival of Uveal Melanoma: A Comparison between Chinese and American Cohorts.

Uveal melanoma (UM) is the most common intraocular malignant carcinoma. This study aimed to compare the clinical features, treatment modalities, and prognosis of UM patients in China with those in America over a 15-year period. In the study, 4088 American patients with primary UM from the Surveillance, Epidemiology, and End Results (SEER) database and 1508 Chinese patients from Tongren-ophthalmology Research Association of Clinical Evaluation (TRACE) were included. Univariable and multivariable analyses were performed to determine prognostic factors and propensity score matching (PSM) and sensitivity analyses were applied to adjust for confounders and identify independent prognostic factors. Chinese patients were diagnosed at a younger age (mean ± SD, 47.3 ± 12.5 years vs. 59.7 ± 14.8 years) and tumors at diagnosis were larger (diameter: 12.0 ± 3.54 mm vs. 11.3 ± 8.27 mm; thickness: 7.13 ± 3.28 mm vs. 4.91 ± 3.01 mm). Chinese patients were more likely to undergo brachytherapy than American patients. Chinese patients had better overall survival than American patients while no significant differences exhibited after adjusting for age through PSM. In conclusion, compared with American patients, Chinese patients had younger onset age, larger tumors at diagnosis and better prognosis, mainly because of their younger age.

Multiscale Pore Structure Characteristics and Crack Propagation Behavior of Coal Samples from High Gas Seam.

Investigation on the pore-fracture features and crack propagation behavior of coal is necessary to prevent coal mine disasters. The pore structure features of coal samples taken from high gas seam were obtained by mercury injection porosimetry (MIP) and gas adsorption methods. The process of deformation and failure for coal samples under three-point bending conditions were obtained. The results demonstrate that the adsorption pores with diameter less than 100 nm are the most developed and their surfaces are the roughest (the average surface fractal dimension Ds is 2.933). The surface of micro-cracks is smoother (Ds is 2.481), which is conducive to gas seepage. It may be the explanation for that 14-3# coal seam is a high gas seam, while there was almost no gas outburst accident so far. At the initial stage of crack propagation, the main crack on the coal sample expanded along the direction of the natural cracks. In the process of crack propagation, the surface fractal dimension of the main crack increased, suggesting that the bending degree of the main crack enhanced. The brittle characteristics of coal samples can be reflected by the ratio of the dissipated energy to the accumulated energy.

Intrinsically unidirectional chemically fuelled rotary molecular motors.

Biological systems mainly utilize chemical energy to fuel autonomous molecular motors, enabling the system to be driven out of equilibrium1. Taking inspiration from rotary motors such as the bacterial flagellar motor2 and adenosine triphosphate synthase3, and building on the success of light-powered unidirectional rotary molecular motors4-6, scientists have pursued the design of synthetic molecular motors solely driven by chemical energy7-13. However, designing artificial rotary molecular motors operating autonomously using a chemical fuel and simultaneously featuring the intrinsic structural design elements to allow full 360° unidirectional rotary motion like adenosine triphosphate synthase remains challenging. Here we show that a homochiral biaryl Motor-3, with three distinct stereochemical elements, is a rotary motor that undergoes repetitive and unidirectional 360° rotation of the two aryl groups around a single-bond axle driven by a chemical fuel. It undergoes sequential ester cyclization, helix inversion and ring opening, and up to 99% unidirectionality is realized over the autonomous rotary cycle. The molecular rotary motor can be operated in two modes: synchronized motion with pulses of a chemical fuel and acid-base oscillations; and autonomous motion in the presence of a chemical fuel under slightly basic aqueous conditions. This rotary motor design with intrinsic control over the direction of rotation, simple chemical fuelling for autonomous motion and near-perfect unidirectionality illustrates the potential for future generations of multicomponent machines to perform mechanical functions.

Amine-functionalized magnetic biochars derived from invasive plants Alternanthera philoxeroides for enhanced efficient removal of Cr(VI): performance, kinetics and mechanism studies.

In this study, novel magnetic biochars derived from Alternanthera philoxeroides and modified by different amines (hexanediamine, melamine, and L-glutathione) were successfully prepared by hydrothermal carbonization and employed as an efficient adsorbent for Cr(VI). When pH = 2.0, T = 25 °C, c0 = 100 mg/L, and the dosage of biochars is 0.05 g, the maximum adsorption capacity of Cr(VI) by pristine biochar (BAP) was 42.47 mg/g and modified biochars (MFBAP, MEBAP, LBAP) was 80.58, 62.26, and 55.66 mg/g, respectively. It was found that hexanediamine and melamine could enhance the SBET of biochars, while L-glutathione could reduce its SBET, which could be supported by BET measurement and SEM images. Adsorption kinetics and isotherm studies showed that the Cr(VI) adsorption process of MFBAP followed Elovich kinetic model and Langmuir isotherm, respectively, which means that it was mainly a chemical adsorption process. The characterization results proved that -NH2 derived from amines plays a significant role in removing Cr(VI), which is mainly degraded by complexation reaction, electrostatic interaction, and reduction. In sum, the biochar modified by amines has excellent Cr(VI) adsorption performance, highly enhanced SBET, and excellent recyclability, which is a promising candidate for solving the problem of invasive plants and wastewater treatment.

Angioplasty With Stent Implantation for Portal Venous Stenosis Caused by Abdominal Tuberculosis: A Case Report and Literature Review.

Abdominal tuberculosis is one of common forms of extra-pulmonary tuberculosis. However, portal vein involvement leading to portal venous stenosis and portal hypertension is a rare complication in abdominal tuberculosis. Because of the non-specific presentations and insensitive response to anti-tuberculosis therapy of the lesions involving portal vein, it continues to be both a diagnostic and treatment challenge. We have reported a 22-year-old woman presented with massive ascites and pleural effusion, which was proved to be TB infection by pleural biopsy. After standard anti-tuberculosis therapy, her systemic symptoms completely resolved while ascites worsened with serum-ascites albumin gradient >11 g/L. Contrast-enhanced computed tomography and portal venography showed severe main portal vein stenosis from compression by multiple calcified hilar lymph nodes. Finally, the patient was diagnosed with portal venous stenosis due to lymphadenopathy after abdominal tuberculosis infection. Portal venous angioplasty by balloon dilation with stent implantation was performed and continued anti-tuberculosis therapy were administrated after discharge. The ascites resolved promptly with no recurrence occurred during the six-month follow-up. Refractory ascites due to portal venous stenosis is an uncommon vascular complication of abdominal tuberculosis. Portal venous angioplasty with stent placement could be a safe and effective treatment for irreversible vascular lesions after anti-tuberculosis therapy.

Design of a self-centring drill bit for orthopaedic surgery: A systematic comparison of the drilling performance.

Bone drilling is an indispensable and demanding operation among many orthopaedic operations. A dedicated drill bit that can achieve low-trauma and self-centring drilling is in urgent need. In this study, a three-step orthopaedic low-traumatic drill bit design was proposed. In order to evaluate the drilling performance of the proposed drill, comprehensive comparison tests were carried out with various commercial medical drills in terms of skiving force, thrust force, temperature rise, and surface quality. The experimental results show that the proposed three-step drill design with the optimal point angle, a small chisel edge, transition arc and web thinning can obtain lower and more stable thrust force, slighter bending force, smaller temperature rise, and higher hole quality compared with the commercial drill bits. The proposed drill shows satisfactory drilling performance and has great application potential in clinical surgery.

Simultaneous separation and determination of four active ingredients in Picria fel-terrae Lour. and its preparations by micellar electrokinetic chromatography.

INTRODUCTION: Picfeltarraenins IA, IB and IV and acteoside are the four bioactive ingredients of Picria fel-terrae Lour. Their pharmacological effects include central inhibitory, cardiovascular, anti-inflammatory, anti-pyretic, analgesic, anti-bacterial, antioxidative and anti-tumor effects. OBJECTIVE: We aimed to develop an efficient micellar electrokinetic chromatography (MEKC) method modified with mixed organic solvents for the simultaneous separation and determination of the four components in Picriae Herba and its formulations. METHODS: Method optimization was carried out by investigating influences of significant factors on the separation, and this method was successfully applied for the determination of the four components in Picriae Herba and its formulations. RESULTS: The optimal running buffer was composed of 20 mM sodium tetraborate, 40 mM sodium cholate, 10% (v/v) methanol and 10% (v/v) isopropanol (pH 9.76). The separation voltage was 18 kV, the temperature was 25°C and the detection wavelength was 266 nm. Under the optimal separation conditions, the baseline separation of four components was achieved in less than 14 min. The correlation coefficients of the calibration curves were 0.9984-0.9995 for the analytes. The intraday and interday precision ranged from 1.5% to 2.5% and from 1.4% to 5.0%, respectively. Recoveries of analytes varied from 96.6% to 104.1%. CONCLUSION: The method was proved suitable for the determination of four components in Picriae Herba and its formulations. Good performance was obtained under optimal conditions, and the method provides an effective tool for the quality control of Picriae Herba and its formulations.