Pan-KRAS inhibitor disables oncogenic signalling and tumour growth.

KRAS is one of the most commonly mutated proteins in cancer, and efforts to directly inhibit its function have been continuing for decades. The most successful of these has been the development of covalent allele-specific inhibitors that trap KRAS G12C in its inactive conformation and suppress tumour growth in patients1-7. Whether inactive-state selective inhibition can be used to therapeutically target non-G12C KRAS mutants remains under investigation. Here we report the discovery and characterization of a non-covalent inhibitor that binds preferentially and with high affinity to the inactive state of KRAS while sparing NRAS and HRAS. Although limited to only a few amino acids, the evolutionary divergence in the GTPase domain of RAS isoforms was sufficient to impart orthosteric and allosteric constraints for KRAS selectivity. The inhibitor blocked nucleotide exchange to prevent the activation of wild-type KRAS and a broad range of KRAS mutants, including G12A/C/D/F/V/S, G13C/D, V14I, L19F, Q22K, D33E, Q61H, K117N and A146V/T. Inhibition of downstream signalling and proliferation was restricted to cancer cells harbouring mutant KRAS, and drug treatment suppressed KRAS mutant tumour growth in mice, without having a detrimental effect on animal weight. Our study suggests that most KRAS oncoproteins cycle between an active state and an inactive state in cancer cells and are dependent on nucleotide exchange for activation. Pan-KRAS inhibitors, such as the one described here, have broad therapeutic implications and merit clinical investigation in patients with KRAS-driven cancers.

Observation of Diverse Asymmetric Structures in High-Dimensional Einstein-Podolsky-Rosen Steering.

Einstein-Podolsky-Rosen (EPR) steering, a distinctive quantum correlation, reveals a unique and inherent asymmetry. This research delves into the multifaceted asymmetry of EPR steering within high-dimensional quantum systems, exploring both theoretical frameworks and experimental validations. We introduce the concept of genuine high-dimensional one-way steering, wherein a high Schmidt number of bipartite quantum states is demonstrable in one steering direction but not reciprocally. Additionally, we explore two criteria to certify the lower and upper bounds of the Schmidt number within a one-sided device-independent context. These criteria serve as tools for identifying potential asymmetric dimensionality of EPR steering in both directions. By preparing two-qutrit mixed states with high fidelity, we experimentally observe asymmetric structures of EPR steering in the C^{3}⊗C^{3} Hilbert space. Our Letter offers new perspectives to understand the asymmetric EPR steering beyond qubits and has potential applications in asymmetric high-dimensional quantum information tasks.

In vitro and in vivo study of antibacterial and anti-encrustation coating on ureteric stents.

OBJECTIVES: To investigate the ability of propolis-coated ureteric stents to solve complications, especially urinary tract infections (UTIs) and crusting, in patients with long-term indwelling ureteric stents through antimicrobial and anti-calculus activities. MATERIALS AND METHODS: Polyurethane (PU) ureteric stents were immersed in the ethanol extract of propolis (EEP), a well-known antimicrobial honeybee product, and subjected to chemical, hydrophilic, and seismic tests. The antimicrobial activity of the EEP coating was then examined by in vitro investigation. Proteus mirabilis infection was induced in rats within uncoated and EEP-coated groups, and the infection, stone formation, and inflammation were monitored at various time points. RESULTS: The characterisation results showed that the hydrophilicity and stability of the EEP surface improved. In vitro tests revealed that the EEP coating was biocompatible, could eliminate >90% of bacteria biofilms attached to the stent and could maintain bacteriostatic properties for up to 3 months. The in vivo experiment revealed that the EEP-coating significantly reduced the amount of bacteria, stones, and salt deposits on the surface of the ureteric stents and decreased inflammation in the host tissue. CONCLUSIONS: Compared with clinically used PU stents, EEP-coated ureteric stents could better mitigate infections and prevent encrustation. Thus, this study demonstrated that propolis is a promising natural dressing material for ureteric stents.

The key role of major and trace elements in the formation of five common urinary stones.

BACKGROUND: Urolithiasis has emerged as a global affliction, recognized as one of the most excruciating medical issues. The elemental composition of stones provides crucial information, aiding in understanding the causes, mechanisms, and individual variations in stone formation. By understanding the interactions between elements in various types of stones and exploring the key role of elements in stone formation, insights are provided for the prevention and treatment of urinary stone disease. METHODS: This study collected urinary stone samples from 80 patients in Beijing. The chemical compositions of urinary stones were identified using an infrared spectrometer. The concentrations of major and trace elements in the urinary stones were determined using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES) and Inductively Coupled Plasma Mass Spectrometry (ICP-MS), respectively. The data were processed using correlation analysis and Principal Component Analysis (PCA) methods. RESULTS: Urinary stones are categorized into five types: the calcium oxalate (CO) stone, carbonate apatite (CA) stone, uric acid (UA) stone, mixed CO and CA stone, and mixed CO and UA stone. Ca is the predominant element, with an average content ranging from 2.64 to 27.68% across the five stone groups. Based on geochemical analysis, the high-content elements follow this order: Ca > Mg > Na > K > Zn > Sr. Correlation analysis and PCA suggested significant variations in the interactions between elements for different types of urinary stones. Trace elements with charges and ionic structures similar to Ca may substitute for Ca during the process of stone formation, such as Sr and Pb affecting the Ca in most stone types except mixed stone types. Moreover, the Mg, Zn and Ba can substitute for Ca in the mixed stone types, showing element behavior dependents on the stone types. CONCLUSION: This study primarily reveals distinct elemental features associated with five types of urinary stones. Additionally, the analysis of these elements indicates that substitutions of trace elements with charges and ion structures similar to Ca (such as Sr and Pb) impact most stone types. This suggests a dependence of stone composition on elemental behavior. The findings of this study will enhance our ability to address the challenges posed by urinary stones to global health and improve the precision of interventions for individuals with different stone compositions.

Afterglow/Photothermal Bifunctional Polymeric Nanoparticles for Precise Postbreast-Conserving Surgery Adjuvant Therapy and Early Recurrence Theranostic.

Adjuvant whole-breast radiotherapy is essential for breast cancer patients who adopted breast-conserving surgery (BCS) to reduce the risk of local recurrences, which however suffer from large-area and highly destructive ionizing radiation-induced adverse events. To tackle this issue, an afterglow/photothermal bifunctional polymeric nanoparticle (APPN) is developed that utilizes nonionizing light for precise afterglow imaging-guided post-BCS adjuvant second near-infrared (NIR-II) photothermal therapy. APPN consists of a tumor cell targeting afterglow agent, which is doped with a NIR dye as an afterglow initiator and a NIR-II light-absorbing semiconducting polymer as a photothermal transducer. Such a design realizes precise afterglow imaging-guided NIR-II photothermal ablation of minimal residual breast tumor foci after BCS, thus achieving complete inhibition of local recurrences. Moreover, APPN enables early diagnosis and treatment of local recurrence after BCS. This study thus provides a nonionizing modality for precision post-BCS adjuvant therapy and early recurrence theranostic.

The overexpression of SlBRI1 driven by Atrd29A promoter-transgenic plants improves the chilling stress tolerance of tomato.

MAIN CONCLUSION: Overexpression of SlBRI1 driven by the Atrd29A promoter could increase the cold resistance of tomato plants during chilling stress but did not improve the expression of SlBRI1 and plant growth under normal conditions. Low temperature is the main limiting factor severely affecting tomato plant development, growth, and fruit quality in winter and spring. Brassinosteroids (BRs) and key BR signaling genes positively regulate tomato plant development and response to chilling stress. Brassinosteroid-insensitive 1 (BRI1) is a major BR receptor that initiates BR signaling. Our results showed that overexpression of SlBRI1 driven by the Atrd29A promoter in transgenic plants did not increase the expression of SlBRI1 under normal conditions but rapidly induced the expression of SlBRI1 during chilling stress. The degree of wilting was lower in Atrd29A promoter-transgenic plants than in wild-type (WT) plants after chilling stress. Atrd29A promoter-transgenic plants exhibited low relative electrolyte leakage and reactive oxygen species (ROS) accumulation under chilling stress. Transgenic plants showed higher photosynthetic ability and antioxidant enzyme activity than WT plants under chilling stress. The BR content and expression levels of key genes involved in BR biosynthesis in Atrd29A-promoter transgenic plants were significantly lower than those in WT plants during chilling stress. The abscisic acid (ABA) content and expression levels of key ABA biosynthesis genes in the Atrd29A promoter-transgenic plants were significantly higher than those in the WT plants during chilling stress. In addition, Atrd29A promoter-transgenic plants positively enhanced the expression levels of ICE-CBF-COR cold-responsive pathway genes. Therefore, the overexpression of SlBRI1 driven by the Atrd29A promoter in transgenic plants can be a valuable tool for reducing chilling stress.

Self-Powered Multifunctional Organic Hydrogel Based on Poly(acrylic acid-N-isopropylacrylamide) for Flexible Sensing Devices.

Human-machine interactions, medical monitoring, and flexible robots stimulate interest in hydrogel sensing devices. However, developing hydrogel sensors with multifunctions such as good mechanics, electroconductivity, resistance to solvent volatility as well as freezing, self-adhesion, and independence on external power supply remains a challenge. In the work, a poly(acrylic acid-N-isopropylacrylamide) P(AA-NIPAm) organic hydrogel loading LiCl is prepared by ultraviolet cross-linking in ethylene glycol/H2O. The organic hydrogel exhibits favorable mechanical properties such as an elongation of break at 700% and a breaking strength of 20 KPa, can adhere to various substrates, and resists frost and solvent volatility. Especially, it possesses an excellent conductivity of 8.51 S/m. The organic hydrogel shows wide strain sensitivity based on resistance change, and the gauge factor reaches 5.84 in the range of 300-700%. It has short responsive and recuperative time and is still stable within 1000 rounds. Moreover, the organic hydrogel is also assembled into a self-powered device in which the open-circuit voltage is 0.74 V. The device can transform external stimuli such as stretching or compressing into the output current change, so it detects human motion effectively in real time. The work provides a perspective for electrical sensing engineering.

Therapeutic Drug Monitoring of Perampanel in Children With Refractory Epilepsy: Focus on Influencing Factors on the Free-Perampanel Concentration.

BACKGROUND: This study aimed to assess the effect of perampanel dose, age, sex, and antiseizure medication cotherapy on steady-state free-perampanel concentration in children with refractory epilepsy, as well as the relationship between inflammation and the pharmacokinetics of perampanel. METHODS: This prospective study in China included 87 children with refractory epilepsy treated with adjunctive perampanel therapy. Free and total perampanel concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry. Free-perampanel concentration was compared among patients with various potential influencing factors. RESULTS: A total of 87 pediatric patients (44 female children) aged 2-14 years were enrolled. The mean free-perampanel concentration and free concentration-to-dose (CD) ratio in plasma were 5.7 ± 2.7 ng/mL (16.3 ± 7.7 nmol/L) and 45.3 ± 21.0 (ng/mL)/(mg/kg) [129.6 ± 60.1 (nmol/L)/(mg/kg)], respectively. The protein binding of perampanel in plasma was 97.98%. A linear relationship was observed between perampanel dose and free concentration in plasma, and a positive relationship was found between the total and free-perampanel concentrations. Concomitant use of oxcarbazepine reduced the free CD ratio by 37%. Concomitant use of valproic acid increased the free CD ratio by 52%. Five patients had a plasma high-sensitivity C-reactive protein (Hs-CRP) level of >5.0 mg/L (Hs-CRP positive). The total and free CD ratios of perampanel were increased in patients with inflammation. Two patients with inflammation developed adverse events, which disappeared as the Hs-CRP level returned to normal, and neither required perampanel dose reduction. Age and sex did not influence the free-perampanel concentration. CONCLUSIONS: This study found complex drug interactions between perampanel and other concomitant antiseizure medications, providing valuable information to enable clinicians to apply perampanel in the future reasonably. In addition, it may be important to quantify both the total and free concentrations of perampanel to assess complex pharmacokinetic interactions.

Perampanel and lacosamide monotherapy in pediatric patients with newly diagnosed focal epilepsy: A prospective study evaluating efficacy, tolerability, and behavior.

PURPOSE: Perampanel (PER) and lacosamide (LCM) are the new third-generation anti-seizure medications (ASMs) that were approved for the monotherapy of focal epilepsy in children over four years of age in China, in 2021. Very few studies have analyzed the application of PER monotherapy among pediatric patients aged ≥four years, and no study compared the efficacy and tolerability of PER monotherapy with LCM monotherapy in pediatric patients with focal epilepsy. The present study aimed to investigate the efficacy, tolerability, and effect on behavior and emotion of PER and LCM as monotherapy in pediatric patients with newly diagnosed focal epilepsy, which is beneficial for clinicians to have more choices to treat pediatric patients with focal epilepsy. METHODS: This was a prospective, single-center, observational study that involved pediatric patients (disease onset age ≥four years) with newly diagnosed focal epilepsy treated with PER or LCM as primary monotherapy. Outcomes included retention, being responders, and seizure-free rates after 3, 6, and 12 months. Adverse events (AEs) were noticed throughout the follow-up period. Behavioral outcomes were evaluated with Achenbach Child Behavior Checklist (CBCL/4-16) at baseline and after three and six months. RESULTS: Using randomization, 60 patients receiving PER (31 females, 29 males, median age: 7.79 [5.34, 10.16] years, median dose: 3.0 [2.0, 4.0] mg/day) and 60 patients receiving LCM (25 females, 35 males, median age: 7.72 [5.91, 10.72] years, median dose: 150.0 [100.0, 200.0] mg/day) were enrolled in the study. At the 12-month follow-up, the retention rates in the PER and LCM groups, both were 90.4%, and the responder rates were 65.4% and 71.2%, while seizure-free rates were 57.7% and 67.3%, respectively. There were no significant differences in the retention, responder and seizure-free rates between the two groups (P > 0.05). There were no significant differences in the responder rates between patients with BECTS, abnormal brain magnetic resonance imaging (MRI), or types of seizure in the two groups (P > 0.05). In the PER group, 28.8% (15/52) of patients experienced AEs, of which the most frequently reported were irritability (n = 7; 13.5%), dizziness (n = 5; 9.6%), somnolence (n = 3; 5.8%), ataxia (n = 1; 1.9%), headache (n = 1; 1.9%), and rash (n = 1; 1.9%). In the LCM group, 15.4% (8/52) of the patients had AEs, including headache (n = 4; 7.5%), dizziness (n = 4; 7.5%), nausea (n = 2; 3.8%), somnolence (n = 2; 3.8%), irritability (n = 1; 1.9%), stomach ache (n = 1; 1.9%), and vomiting (n = 1; 1.9%). The incidence of irritability was significantly higher in the PER group than in the LCM group (13.5% vs. 1.9%, P = 0.031), which occurred mainly within eight weeks after drug administration. Patients with irritability were not dangerous to surrounding people by the assessment of parental observation in the life. And the symptoms were relieved spontaneously within a few months. The outcomes of total scores, internalizing scores, and externalizing scores of the CBCL did not show statistically significant differences in the PER and LCM groups between baseline and three and six months. Characteristics of behavior and emotion did not have substantial changes in patients treated with PER and LCM monotherapy. CONCLUSIONS: The present study documented similar good effectiveness and good tolerance of PER and LCM as monotherapy in pediatric patients with newly diagnosed focal epilepsy and showed no behavioral or emotional impact, as assessed by the CBCL. Though the incidence of irritability with PER monotherapy may be higher than that with LCM monotherapy soon after medication initiation, this side effect appears to resolve spontaneously within a few months. At present, this study was the first research about PER and LCM monotherapy in pediatric patients with newly diagnosed focal epilepsy evaluating efficacy, tolerability, and behavior in China.

Ultrasound-Guided Capsular Thyroid Injection Therapy With Dexamethasone and Lidocaine Mixture for Subacute Thyroiditis: A Single-Center Study.

OBJECTIVES: Subacute thyroiditis (SAT) is a self-limiting, inflammatory thyroid disease possibly caused by viral infection. In recent years, the incidence of SAT is increasing, especially during the pandemic of the COVID-19. This study aimed to evaluate the efficacy, safety, and recovery time of capsular thyroid injection therapy under ultrasound guidance for SAT. METHODS: A total of 73 patients with SAT were divided into two groups. Patients in group A (n = 48) received an ultrasound-guided capsular injection consisting of dexamethasone (DEX) and lidocaine in the thyroid lesion area, while patients in group B (n = 25) received oral prednisolone (PSL). The two groups were compared for pain relief and treatment duration, the recovery time of thyroid function, recurrence rates, hypothyroidism incidence, and drug-related side effects. RESULTS: The follow-up time was 1 year. In group A, the duration of pain relief, treatment, and recovery time of thyroid function were significantly shorter than that in group B (P < .05), and no statistically significant differences in recurrence rate or incidence of hypothyroidism were observed (P > .05). Weight gain was significantly higher in group A at the end of treatment (P < .001). CONCLUSIONS: Compared with oral PSL treatment, ultrasound-guided local injection of DEX and lidocaine into the capsular thyroid is a safe and effective procedure that can significantly reduce the treatment time of SAT.

Present-Day Tectonic Stress Evolution in Southern Yunnan Based on Focal Mechanisms.

Tectonic extrusion bypassing the eastern Himalayan syntaxis results in a significant increase in regional stress instability and the associated frequent occurrence of earthquakes in southern Yunnan, China. However, the stress field, and the relationship between the focal mechanism of earthquakes and stress evolution in southern Yunnan, remain enigmatic. In this paper, using a modified grid point test method, we calculated the focal mechanism of ML ≥ 2.5 earthquakes in southern Yunnan (22-25° N, 100-104° E) from January 2009 to June 2023. Utilizing the solutions of historical earthquake focal mechanisms, we obtained the present-day regional tectonic stress field in southern Yunnan via inversion. The results indicate complex and diverse seismic focal mechanisms, and the main types of earthquakes are strike-slip events, followed by normal fault and reverse fault events. The orientations of the maximum and minimum principal stress axes rotate in a clockwise direction from northeast to southwest. The internal stress orientation distribution of the rhombic Sichuan-Yunnan block in the study area is consistent, and the block boundary zone is the site where stress deflection occurs, and the regional tectonic stress field is influenced by the interaction among different blocks. The distribution of R-value in the Lamping-Simao block gradually increases from north to south, indicating that the compressive stress required for material transport becomes relatively small. Combined with the geological and tectonic background of the study area, our results suggest that the speed of block movement gradually decreases from north to south; the distribution of R-value in the South China block is significantly smaller than that of the interior of the Sichuan-Yunnan rhombus, and the proportion of compressive stresses is larger, indicating a stronger extrusion in this region, which may be related to the fact that the Sichuan-Yunnan rhombus is strongly resisted by the South China block in the east.

Strontium isotope ratios in kidney stones reveal the environmental implications for humans in Beijing, China.

Kidney stones are a common disease that threatens human health on a global scale and are closely related to the contemporary environment. The strontium isotope ratio (87Sr/86Sr) has been widely used to trace the migration of ancient humans through bones and teeth, which recorded their bioavailable Sr from the environment. However, no 87Sr/86Sr data for kidney stones have been reported. Therefore, this study explored the Sr content of kidney stones and reported their 87Sr/86Sr data for the first time to reflect the environmental implications for humans; 66 calcium oxalate kidney stones collected in Beijing were measured for calcium (Ca), magnesium (Mg) and strontium (Sr) content to explore Sr distribution behavior in kidney stones, and 17 samples were tested for strontium isotopes. Ca and Mg had a joint effect on the Sr content of kidney stones, with magnesium having a stronger effect, whereas 87Sr/86Sr values were unaffected by these elements. The 87Sr/86Sr values of kidney stones ranged from 0.709662 to 0.710990, within the range of environmental soil and water in Beijing. Drinking water and surface soils (representing food sources) mainly contributed to the bioavailable Sr of kidney stones, while sea spray and dust storm did not. This study is the first to report 87Sr/86Sr values for kidney stones. Evidence of Sr isotope ratios in kidney stones reveals environmental implications for humans and bioavailable Sr sources, demonstrating a great potential of Sr isotope ratios at the intersection of life and environmental sciences.

[Effect of High-Concentration Uric Acid on Nitric Oxide].

Uric acid (UA) is the final product of purine metabolism in human body,and its metabolic disorder will induce hyperuricemia (HUA).The occurrence and development of HUA are associated with a variety of pathological mechanisms such as oxidative stress injury,activation of inflammatory cytokines,and activation of renin-angiotensin-aldosterone system.These mechanisms directly or indirectly affect the bioavailability of endogenous nitric oxide (NO).The decrease in NO bioavailability is common in the diseases with high concentration of UA as an independent risk factor.In this review,we summarize the mechanisms by which high concentrations of UA affect the endogenous NO bioavailability,with a focus on the mechanisms of high-concentration UA in decreasing the synthesis and/or increasing the consumption of NO.This review aims to provide references for alleviating the multisystem symptoms and improving the prognosis of HUA,and lay a theoretical foundation for in-depth study of the correlations between HUA and other metabolic diseases.

Retrieving High-Dimensional Quantum Steering from a Noisy Environment with N Measurement Settings.

One of the most often implied benefits of high-dimensional (HD) quantum systems is to lead to stronger forms of correlations, featuring increased robustness to noise. Here, we experimentally demonstrate the n-setting linear HD quantum steering criterion. We verify the large violation of the steering inequalities without full-state tomography. The lower bound of the violation is 2.24±0.01 in 11 dimensions, exceeding the bound (V<2) of two-setting criteria. Hence, a higher strength of steering has been revealed. Moreover, we demonstrate the method for enhancing the noise robustness without increasing dimension, alternatively, by increasing measurement settings. Using the entanglement in 11 dimensions, we experimentally retrieve steering nonlocality with 63.4±1.4% isotropic noise fraction, surpassing the 50% limitation of two-setting criteria. Our Letter offers the potential for practical one-sided device-independent quantum information processing that tolerates the noisy environment, lossy detection, and transcends the present transmission distance limitation.

Current synthetic chemistry towards cyclic antimicrobial peptides.

Antimicrobial peptides (AMPs) have great potentials for developing novel antibiotics against multi-drug resistant (MDR) bacteria. However, the clinical application of AMPs is limited due to their poor protease stability and high hemolytic toxicity. Various strategies have been widely explored to improve the pharmacological properties of natural or artificial antimicrobial peptides, including D- or non-natural amino acid residue replacement, backbone modification, cyclization, PEGlytion, and lipidation. Among others, peptide cyclization, which has been widely applied to enhance the biostability and target selectivity of bioactive peptide, is a very appealing and promising strategy for developing novel antibiotics based on AMPs. Herein, we summarize the current strategies for synthesizing cyclic antimicrobial peptides and the resulting influence of peptide cyclization on the biological activities.

Potentially toxic elements in cascade dams-influenced river originated from Tibetan Plateau.

Rivers originated from Tibetan Plateau are of great significance due to their environmental sensibility and fragility. However, the pollution of suspended particulate matter (SPM) in these rivers is rarely reported, in particular, the potentially toxic elements (PTEs) contamination. To clarify the status, sources, behavior, and risks of PTEs in SPM, a full investigation was conducted in dams-influenced Lancangjiang River basin. The findings revealed that the PTEs content (mg kg-1) ranked Mn (766) > V (151.7) > Zn (131.0) > Cr (94.6) > Ni (44.2) > Pb (36.7) > Cu (29.4) > Co (14.6) > Sb (2.6) > Mo (1.6) > Tl (0.78) > Cd (0.48). The multi-index assessment suggested that Sb and Cd were moderately severe to severe enriched PTEs with the enrichment factor values of 10.0 and 8.8 and the geo-accumulation index values of 2.2 and 2.0, respectively, while the rest of PTEs were minor/no enrichment. In contrast, Cr and Ni were major toxic elements in SPM which contributed 25 ± 10%, 24 ± 8% to the total toxic risk index. The high partition coefficients (e.g., 6.1 for Cr) were observed in most PTEs and resulted in the 96.3% of Cr, 85.2% of Zn, 83.6% of Pb, 77.8% of Ni, and 63.2% of Cu transportation in the SPM form. Natural inputs (e.g., soil erosion) are the main source (53.6%∼61.9%) of V, Cr, Mn, Co, Ni, and Tl, while fuel burning contributed 40.9% of Zn, 32.5% of Pb, and 37.3% of Cd. Moreover, 51.2% of Sb was attributed to industrial waste source, while porphyry copper/molybdenum deposits related milltailings were the co-source of Mo (54.4%) and Cu (34.8%). Overall, the PTEs geochemistry of SPM showed the potential in tracing regional environmental change.

A retrospective comparative study of postoperative sagittal balance in isthmic L5-S1 spondylolisthesis using single segment or two-segment pedicle screw fixation.

OBJECTIVE: To compare the radiographic parameters and clinical outcomes of isthmic L5-S1 spondylolisthesis with single segment or two-segment pedicle screw fixation. METHODS: Between January 2018 and January 2019, a total of 76 patients with isthmic L5-S1 spondylolisthesis were included in this study. All patients were treated with varying numbers of pedicle screw fixation with single-segment fusion during posterior lumbar interbody fusion (PLIF). Patients were divided into two groups, based on the number of pedicle screws placed during fixation, namely, 4 screws (4S) group and 6 screws (6S) group. Subsequently, the sagittal balance parameters were measured, which included slippage degree (SD), lumbar lordosis (LL), segmental lordosis (SL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), and sagittal vertical axis (SVA). Clinical functional outcomes were assessed using the visual analog scale (VAS) for back pain and the oswestry disability index (ODI) scores. RESULTS: The 4S group comprised of 10 males and 27 females, with a median age of 55.2 ± 10.8 years old and a mean follow-up of 16.95 ± 4.16 months. The 6S group comprised of 14 males and 25 females, with a median age of 58.1 ± 7.5 years old and a median follow-up of 17.33 ± 3.81 months. No significant differences were evident in all preoperative parameters between both groups. In contrast, the postoperative LL, SL, PT, SS, and SD values increased significantly, compared to the preoperative values in both groups (all P < 0.05). At the last follow-up, the 6S group exhibited better correction in LL, SL, and PT, relative to the 4S group (all P < 0.05). A significant SD difference was observed between both groups at all points post surgery (P < 0.05). The postoperative slip correction rate was significantly larger in the 6S group, compared to the 4S group (P < 0.05). The postoperative VAS and ODI scores of both groups improved significantly, when compared to the preoperative scores (both P < 0.05). However, there were no significant differences in the ODI and VAS scores between the two groups at all time points. CONCLUSIONS: The clinical outcomes of both approaches appeared to be satisfactory. In terms of short-term outcomes, the 6S group exhibited better spinal sagittal restoration and stability than the 4S group.

Comparing quality of life between patients undergoing trans-areola endoscopic thyroid surgery and trans-oral endoscopic thyroid surgery.

BACKGROUND: Compared with conventional open surgery, endoscopic thyroidectomy via the oral vestibular approach (ETVOA) and endoscopic thyroidectomy via the areola approach (ETAA) avoided scarring of the skin, which may help patients achieve a better quality of life (QOL). However, the benefit of the QOL from this technique has not been adequately investigated, therefore this study compared the QOL outcomes between ETVOA and ETAA. METHODS: 131 patients were enrolled in this study. ETAA surgery and ETVOA surgery were performed in 74 patients and 57 patients, respectively. These patients were followed up at 2 weeks, 4 weeks, and 8 weeks, and their QOL was evaluated using a thyroid surgery-specific questionnaire and a short-form health survey (SF-36). RESULTS: There were no differences in clinical characteristics such as gender, age, body mass index (BMI), and tumor size between the two groups. The volume of intraoperative blood loss, cost of hospitalization, and complications between the two procedures showed no differences. Compared with ETAA, ETVOA has a longer operation time, no drainage, and shorter hospital stay. In the QOL questionnaire, several parameters in ETVOA were better. The satisfaction scores of patients undergoing ETVOA were higher. In addition, the cosmetic satisfaction in patients who received ETOVA was significantly better than that of patients who underwent ETAA. The degree of neck movement disorder in patients with ETVOA was milder. Patients who received ETVOA had higher score on the SF-36. CONCLUSIONS: The trans-oral endoscopic approach can acquire better cosmetic results and achieved high-level QOL.

A novel method based on similarity and triangulation for predicting the toxicities of various binary mixtures.

There is currently no generally accepted model to predict the hormesis of mixtures. In order to accurately predict the hormesis of a mixture, we developed a method based on similarity and triangulation, which we named SimTri in this paper. SimTri takes the mixture as scatter points in space, which is constructed by the concentration axes of various components in the mixture system. To test the predictive capability of SimTri, the toxicities of three different types of binary mixtures (no hormetic compound, one hormetic compound, and two hormetic compounds) on Vibrio qinghaiensis sp.-Q67 were determined at 0.25 h and 12 h. For each mixture system, the toxicities of five mixture rays, which were designed by direct equipartition ray design, were used for the internal validation (leave-one-out cross-validation, LOOCV). The toxicities of two mixture rays, which were designed by fixed-ratio ray design on the basis of the NOEC and EC70 ratios, were used for the external validation. The results of LOOCV and external validation indicated that the accuracy of SimTri was greater than 90%, which means that SimTri can accurately predict the toxicity of three different types of binary mixtures and may provide a new way to predict the toxicity of mixtures.

Technique for endoscopic thyroidectomy with selective lateral neck dissection via a chest-breast approach.

BACKGROUND: Endoscopic thyroidectomy has been widely accepted because it can effectively avoid neck scarring. However, there are seldom reports concerning completely endoscopic lateral neck dissection approaches. In this study, we introduced a technique for performing endoscopic thyroidectomy with lateral neck dissection via a chest-breast approach. METHODS: We retrospectively reviewed 18 patients who underwent endoscopic total thyroidectomy along with levels II, III, IV, and VI dissection. All major outcomes, such as cosmetic effect, operative time and complications, etc., were analyzed. In addition, another 20 patients who underwent traditional open surgery (open group) were enrolled in the study to conduct a contrasting analysis between patients treated with the endoscopic technique (endoscopic group) and open group patients, in terms of demographic data and main operative outcomes, to evaluate the feasibility of this technique. RESULTS: All 18 endoscopic surgery cases were successfully performed, and no patient was converted to the open procedure intra-operatively. There were no significant differences between the two groups regarding age (P = 0.209), Body Mass Index (P = 0.479), sex (P = 0.218), drainage time (P = 0.153), operation time (P = 0.065), intra-operative blood loss (P = 0.139), post-operative pain (P = 0.114), and number of dissected lateral lymph nodes (II: P = 0.201; III + IV: P = 0.107). The mean total and lateral lymph nodes dissection (LLND) time in the endoscopic group were longer than those of the open group (P = 0.002; 235 ± 35 vs. 182 ± 20 min, P = 0.000; 125 ± 21 vs. 80 ± 14 min, P = 0.000). The primary lesion diameter of the endoscopic group was smaller than that of the open group (1.7 ± 0.8 vs. 2.9 ± 1.3 cm, P = 0.002). The scores for cosmetic satisfaction in the endoscopic group were higher than those in the open group (8.3 ± 0.7 vs. 4.4 ± 0.9, P = 0.000). Among the complications, there was no significant difference between the two approaches in transient vocal cord paresis (1/18 vs. 0/20, P = 0.474), transient hypoparathyroidism (4/18 vs. 4/20, P = 1.000), post-operative lymphatic leakage (1/18 vs. 3/20, P = 0.606), and intra-operative large blood vessel injury (2/18 vs. 0/20, P = 0.218). There was no incidence of uncontrolled bleeding, mental nerve injury, permanent hypoparathyroidism, permanent recurrent laryngeal nerve (RLN) injury, skin bruise on the neck, asphyxia/dyspnea or other complications like tracheal injury, esophageal injury, etc., nor was there any death or recurrence in either of the two groups during the short follow-up period. CONCLUSION: It is feasible to perform LLND (levels II, III, IV, and VI) with endoscopic thyroidectomy via a chest-breast approach. In particular, this technique avoids a large scar on the patient's neck and has well operative outcomes compared with open surgery. Accordingly, this technique may offer one more option for selective patients.