Investigation of causal relationships between cortical structure and osteoporosis using two-sample Mendelian randomization.

The mutual interaction between bone characteristics and brain had been reported previously, yet whether the cortical structure has any relevance to osteoporosis is questionable. Therefore, we applied a two-sample bidirectional Mendelian randomization analysis to investigate this relationship. We utilized the bone mineral density measurements of femoral neck (n = 32,735) and lumbar spine (n = 28,498) and data on osteoporosis (7300 cases and 358,014 controls). The global surficial area and thickness and 34 specific functional regions of 51,665 patients were screened by magnetic resonance imaging. For the primary estimate, we utilized the inverse-variance weighted method. The Mendelian randomization-Egger intercept test, MR-PRESSO, Cochran's Q test, and "leave-one-out" sensitivity analysis were conducted to assess heterogeneity and pleiotropy. We observed suggestive associations between decreased thickness in the precentral region (OR = 0.034, P = 0.003) and increased chance of having osteoporosis. The results also revealed suggestive causality of decreased bone mineral density in femoral neck to declined total cortical surface area (ß = 1400.230 mm2, P = 0.003), as well as the vulnerability to osteoporosis and reduced thickness in the Parstriangularis region (ß = -0.006 mm, P = 0.002). Our study supports that the brain and skeleton exhibit bidirectional crosstalk, indicating the presence of a mutual brain-bone interaction.

Deep Learning of Multimodal Ultrasound: Stratifying the Response to Neoadjuvant Chemotherapy in Breast Cancer Before Treatment.

BACKGROUND: Not only should resistance to neoadjuvant chemotherapy (NAC) be considered in patients with breast cancer but also the possibility of achieving a pathologic complete response (PCR) after NAC. Our study aims to develop 2 multimodal ultrasound deep learning (DL) models to noninvasively predict resistance and PCR to NAC before treatment. METHODS: From January 2017 to July 2022, a total of 170 patients with breast cancer were prospectively enrolled. All patients underwent multimodal ultrasound examination (grayscale 2D ultrasound and ultrasound elastography) before NAC. We combined clinicopathological information to develop 2 DL models, DL_Clinical_resistance and DL_Clinical_PCR, for predicting resistance and PCR to NAC, respectively. In addition, these 2 models were combined to stratify the prediction of response to NAC. RESULTS: In the test cohort, DL_Clinical_resistance had an AUC of 0.911 (95%CI, 0.814-0.979) with a sensitivity of 0.905 (95%CI, 0.765-1.000) and an NPV of 0.882 (95%CI, 0.708-1.000). Meanwhile, DL_Clinical_PCR achieved an AUC of 0.880 (95%CI, 0.751-0.973) and sensitivity and NPV of 0.875 (95%CI, 0.688-1.000) and 0.895 (95%CI, 0.739-1.000), respectively. By combining DL_Clinical_resistance and DL_Clinical_PCR, 37.1% of patients with resistance and 25.7% of patients with PCR were successfully identified by the combined model, suggesting that these patients could benefit by an early change of treatment strategy or by implementing an organ preservation strategy after NAC. CONCLUSIONS: The proposed DL_Clinical_resistance and DL_Clinical_PCR models and combined strategy have the potential to predict resistance and PCR to NAC before treatment and allow stratified prediction of NAC response.

Targeted inhibition of the HNF1A/SHH axis by triptolide overcomes paclitaxel resistance in non-small cell lung cancer.

Paclitaxel resistance is associated with a poor prognosis in non-small cell lung cancer (NSCLC) patients, and currently, there is no promising drug for paclitaxel resistance. In this study, we investigated the molecular mechanisms underlying the chemoresistance in human NSCLC-derived cell lines. We constructed paclitaxel-resistant NSCLC cell lines (A549/PR and H460/PR) by long-term exposure to paclitaxel. We found that triptolide, a diterpenoid epoxide isolated from the Chinese medicinal herb Tripterygium wilfordii Hook F, effectively enhanced the sensitivity of paclitaxel-resistant cells to paclitaxel by reducing ABCB1 expression in vivo and in vitro. Through high-throughput sequencing, we identified the SHH-initiated Hedgehog signaling pathway playing an important role in this process. We demonstrated that triptolide directly bound to HNF1A, one of the transcription factors of SHH, and inhibited HNF1A/SHH expression, ensuing in attenuation of Hedgehog signaling. In NSCLC tumor tissue microarrays and cancer network databases, we found a positive correlation between HNF1A and SHH expression. Our results illuminate a novel molecular mechanism through which triptolide targets and inhibits HNF1A, thereby impeding the activation of the Hedgehog signaling pathway and reducing the expression of ABCB1. This study suggests the potential clinical application of triptolide and provides promising prospects in targeting the HNF1A/SHH pathway as a therapeutic strategy for NSCLC patients with paclitaxel resistance. Schematic diagram showing that triptolide overcomes paclitaxel resistance by mediating inhibition of the HNF1A/SHH/ABCB1 axis.

Achieving Efficient CO2 Electrolysis to CO by Local Coordination Manipulation of Nickel Single-Atom Catalysts.

Selective electroreduction of CO2 to C1 feed gas provides an attractive avenue to store intermittent renewable energy. However, most of the CO2-to-CO catalysts are designed from the perspective of structural reconstruction, and it is challenging to precisely design a meaningful confining microenvironment for active sites on the support. Herein, we report a local sulfur doping method to precisely tune the electronic structure of an isolated asymmetric nickel-nitrogen-sulfur motif (Ni1-NSC). Our Ni1-NSC catalyst presents >99% faradaic efficiency for CO2-to-CO under a high current density of -320 mA cm-2. In situ attenuated total reflection surface-enhanced infrared absorption spectroscopy and differential electrochemical mass spectrometry indicated that the asymmetric sites show a significantly weaker binding strength of *CO and a lower kinetic overpotential for CO2-to-CO. Further theoretical analysis revealed that the enhanced CO2 reduction reaction performance of Ni1-NSC was mainly due to the effectively decreased intermediate activation energy.

Predicting symptomatic post-hepatectomy liver failure in patients with hepatocellular carcinoma: development and validation of a preoperative nomogram.

OBJECTIVE: To develop and validate a nomogram based on liver stiffness (LS) for predicting symptomatic post-hepatectomy (PHLF) in patients with hepatocellular carcinoma (HCC). METHODS: A total of 266 patients with HCC were enrolled prospectively from three tertiary referral hospitals from August 2018 to April 2021. All patients underwent preoperative laboratory examination to obtain parameters of liver function. Two-dimensional shear wave elastography (2D-SWE) was performed to measure LS. Three-dimensional virtual resection obtained the different volumes including future liver remnant (FLR). A nomogram was developed by using logistic regression and determined by receiver operating characteristic (ROC) curve analysis and calibration curve analysis, which was validated internally and externally. RESULTS: A nomogram was constructed with the following variables: FLR ratio (FLR of total liver volume), LS greater than 9.5 kPa, Child-Pugh grade, and the presence of clinically significant portal hypertension (CSPH). This nomogram enabled differentiation of symptomatic PHLF in the derivation cohort (area under curve [AUC], 0.915), internal fivefold cross-validation (mean AUC, 0.918), internal validation cohort (AUC, 0.876) and external validation cohort (AUC, 0.845). The nomogram also showed good calibration in the derivation, internal validation, and external validation cohorts (Hosmer-Lemeshow goodness-of-fit test, p = 0.641, p = 0.06, and p = 0.127, respectively). Accordingly, the safe limit of the FLR ratio was stratified using the nomogram. CONCLUSION: An elevated level of LS was associated with the occurrence of symptomatic PHLF in HCC. A preoperative nomogram integrating LS, clinical and volumetric features was useful in predicting postoperative outcomes in patients with HCC, which might help surgeons in the management of HCC resection. CLINICAL RELEVANCE STATEMENT: A serial of the safe limit of the future liver remnant was proposed by a preoperative nomogram for hepatocellular carcinoma, which might help surgeons in 'how much remnant is enough in liver resection'. KEY POINTS: • An elevated liver stiffness with the best cutoff value of 9.5 kPa was associated with the occurrence of symptomatic post-hepatectomy liver failure in hepatocellular carcinoma. • A nomogram based on both quality (Child-Pugh grade, liver stiffness, and portal hypertension) and quantity of future liver remnant was developed to predict symptomatic post-hepatectomy liver failure for HCC, which enabled good discrimination and calibration in both derivation and validation cohorts. • The safe limit of future liver remnant volume was stratified using the proposed nomogram, which might help surgeons in the management of HCC resection.

Caffeic acid phenethyl ester suppresses intestinal FXR signaling and ameliorates nonalcoholic fatty liver disease by inhibiting bacterial bile salt hydrolase activity.

Propolis is commonly used in traditional Chinese medicine. Studies have demonstrated the therapeutic effects of propolis extracts and its major bioactive compound caffeic acid phenethyl ester (CAPE) on obesity and diabetes. Herein, CAPE was found to have pharmacological activity against nonalcoholic fatty liver disease (NAFLD) in diet-induced obese mice. CAPE, previously reported as an inhibitor of bacterial bile salt hydrolase (BSH), inhibited BSH enzymatic activity in the gut microbiota when administered to mice. Upon BSH inhibition by CAPE, levels of tauro-ß-muricholic acid were increased in the intestine and selectively suppressed intestinal farnesoid X receptor (FXR) signaling. This resulted in lowering of the ceramides in the intestine that resulted from increased diet-induced obesity. Elevated intestinal ceramides are transported to the liver where they promoted fat production. Lowering FXR signaling was also accompanied by increased GLP-1 secretion. In support of this pathway, the therapeutic effects of CAPE on NAFLD were absent in intestinal FXR-deficient mice, and supplementation of mice with C16-ceramide significantly exacerbated hepatic steatosis. Treatment of mice with an antibiotic cocktail to deplete BSH-producing bacteria also abrogated the therapeutic activity of CAPE against NAFLD. These findings demonstrate that CAPE ameliorates obesity-related steatosis at least partly through the gut microbiota-bile acid-FXR pathway via inhibiting bacterial BSH activity and suggests that propolis enriched with CAPE might serve as a promising therapeutic agent for the treatment of NAFLD.

Role of Preoperational Imaging Traits for Guiding Treatment in Single ≤ 5 cm Hepatocellular Carcinoma.

BACKGROUND: Imaging traits including nonsmooth tumor margins, internal arteries, peritumoral enhancement, and absence of hypodense halos can reflect tumor aggressiveness preoperatively and may affect treatment selection. This study aimed to explore the role of these four imaging traits in treatment selection between surgical resection (SR) and radiofrequency ablation (RFA) for patients with single ≤ 5 cm hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Three hundred eight-one patients with single ≤ 5 cm HCC who underwent SR (n = 202) or RFA (n = 179) in the First Affiliated Hospital of Sun Yat-sen University from April 2010 to December 2019 were retrospectively enrolled. The efficacy of SR and RFA in patients with the imaging traits that significantly influenced recurrence-free survival (RFS) or overall survival (OS) was compared and analyzed. RESULTS: Multivariable Cox regression analysis identified that having internal arteries (P = 0.001) was an independent influencing factor for RFS, while internal arteries (P = 0.005) and peritumoral enhancement (P = 0.001) were independent influencing factors for OS. In patients with internal arteries, subgroup analysis based on tumor size demonstrated that both RFS and OS of SR were superior to those of RFA in patients with 3-5 cm HCC (RFS, P = 0.023; OS, P = 0.015). In patients with peritumoral enhancement, both RFS and OS of SR were superior to those of RFA (RFS, P = 0.019; OS, P = 0.042). CONCLUSION: SR may be associated with improved survival compared with RFA in patients with single 3-5 cm HCC having internal arteries and patients with single ≤ 5 cm HCC having peritumoral enhancement.

Liver Stiffness Measured by Two-Dimensional Shear Wave Elastography for Predicting Symptomatic Post-hepatectomy Liver Failure in Patients with Hepatocellular Carcinoma.

OBJECTIVES: To evaluate the ability of liver stiffness (LS) measured by two-dimensional shear wave elastography (2D SWE) to predict symptomatic post-hepatectomy liver failure (SPHLF) in patients with hepatocellular carcinoma (HCC). METHODS: A total of 119 patients who underwent hepatectomy for HCC between August 2018 and July 2019 were enrolled. Preoperative assessments for LS and other clinicopathological tests were performed in all patients. Univariate and multivariate analyses were conducted for the risk factors of SPHLF. Further subgroup analysis was performed according to multivariate analysis results. RESULTS: SPHLF occurred in 38 patients (31.9%). The best cutoff value of LS for predicting SPHLF was 9.5 kPa. Multivariate analysis identified LS ≥ 9.5 kPa, greater Child-Turcotte-Pugh (CTP) grade, and major hepatectomy as independent predictors of SPHLF. Based on the extent of hepatectomy, CTP grade could stratify the risk of SPHLF in the minor hepatectomy group (12.2% vs. 100.0%, p = 0.001), whereas LS was superior in predicting SPHLF in the major hepatectomy group (18.9% vs. 72.4%, p < 0.001). In patients with CTP grade A, LS could further stratify the risks of SPHLF in both the minor and major hepatectomy groups (3.7% vs. 22.7%, p = 0.043; 17.6% vs. 70.4%, p < 0.001, respectively). CONCLUSIONS: LS measured using 2D SWE could predict SPHLF using the best cutoff value of 9.5 kPa. CTP grade was a stronger indicator of SPHLF in minor hepatectomy, whereas LS was more effective in selecting candidates for major hepatectomy. LS could further stratify the risk of SPHLF in CTP grade A patients, regardless of the extent of hepatectomy.

Potential impact of a novel pathway for suspected myocardial infarction utilising a new high-sensitivity cardiac troponin I assay.

BACKGROUND: High-sensitivity cardiac troponin I (hs-cTnI) assays promise high diagnostic accuracy for myocardial infarction (MI). In an ED where conventional cTnI was in use, we evaluated an assessment pathway using the new Access hsTnI assay. METHODS: This retrospective analysis recruited ED patients with suspected MI between June and September 2019. All patients received routine care with a conventional cTnI assay (AccuTnI +3: limit of detection (LoD) 10 ng/L, 99th centile upper reference limit (URL) 40 ng/L, abnormal elevation cut-point 80 ng/L). Arrival, then 90-minute or 360-minute cTnI levels for low and non-low risk patients, respectively (ED Assessment of Chest pain score) guided diagnosis and disposition which was at treating physician discretion. The same patients had arrival and 90-minute or 180-minute samples drawn for hs-cTnI levels (Access hsTnI: LoD 2 ng/L, 99th centile URL 10 ng/L (females) and 20 ng/L (males); abnormal elevation above the URL and delta >30%). Treating physicians were blinded to the hs-cTnI results. Using the hs-cTnI values, investigators retrospectively assigned likely diagnosis, disposition and likelihood of a 30-day major adverse cardiac event (MACE). Admission was recommended for significantly rising hs-cTnI elevations. The primary objective was to demonstrate an acceptable unexpected 30-day post-discharge MACE rate of <1%. cTnI elevation rates, diagnostic outcomes and ED disposition were also compared between pathways. RESULTS: For the 935 patients, unexpected 30-day post-discharge MACE rates were 0/935 (0%, 95% CI 0% to 0.4%) with the conventional or novel pathway. For the high-sensitivity and conventional assays, respectively, abnormal elevation rates were 29% (95% CI 26% to 32%) and 19% (95% CI 17% to 22%), for MI were 9% (95% CI 8% to 11%) and 8% (95% CI 6% to 10%), and for hospital admission were 42% (95% CI 39% to 45%) and 43% (95% CI 40% to 47%). CONCLUSION: The novel pathway using the Access hsTnI assay has an acceptably low 30-day MACE rate.

[Effects of Nardostachys jatamansi on gut microbiota of rats with Parkinson's disease].

Under the guidance of the traditional Chinese medicine(TCM) theory of "Zangfu-organs of spleen and stomach" and the modern theory of "microbiota-gut-brain axis", this study explored the effects of Nardostachys jatamansi on the gut microbiota of rats with Parkinson's disease(PD). The 40 SD rats were randomly divided into the control group, PD model group, levodopa group, and Nardostachys jatamansi ethanol extract group. The PD model was established by subcutaneous injection of rotenone in the neck and back area. After 14 days of intragastric administration, the PD rats' behaviors were analyzed through open field test, inclined plane test, and pole test. After the behavioral tests, the striatum, colon, and colon contents of rats in each group were collected. Western blot was employed to detect the protein expression of tyrosine hydroxylase(TH) and α-synuclein(α-syn) in striatum and that of α-syn in colon. Enzyme linked immunosorbent assay(ELISA) was used to detect the levels of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), and nuclear factor-kappa B(NF-κB) in striatum and colon. High-throughput sequencing of 16 S rRNA gene was conducted to detect the differences in microbial diversity, abundance, differential phyla, and dominant bacteria of rats between groups. The results indicated that Nar. ethanol extract could relieve dyskinesia, reverse the increased levels of α-syn, TNF-α, IL-1ß, and NF-κB in striatum, and improve the protein expression of TH in striatum of PD rats. The α diversity analysis indicated a significant decrease in diversity and abundance of gut microbiota in the PD model. The results of linear discriminant analysis effect size(LEfSe) of dominant bacteria indicated that Nardostachys jatamansi ethanol extract increased the relative abundance of Clotridiaceae, Lachnospiraceae, and Anaerostipes, and reversed the increased relative abundance of Proteobacteria, Gammaproteobacteria, Enterobacteriaceae, and Escherichia-Shigella in PD model group to exhibit the neuroprotective effect. In summary, the results indicated that Nar. ethanol extract exert the therapeutic effect on PD rats. Specifically, the extract may regulate gut microbiota, decrease the levels of proinflammatory cytokines, and reduce the protein aggregation of α-syn in the colon and striatum to alleviate intestinal inflammation and neuroinflammation. This study provides a basis for combining the theory of "Zangfu-organs of spleen and stomach" with the theory of "microbiota-gut-brain axis" to treat PD.

High-intensity focused ultrasound treatment as an alternative regimen for myxofibrosarcoma.

Myxofibrosarcoma is a common soft-tissue sarcoma in elderly patients, characterized by an infiltrative growth pattern and a high risk for persistent local recurrence. A 35-years-old woman was diagnosed with myxofibrosarcoma on the right upper arm and the tumor is surgically resected. The tumor relapsed 7 months later. Then the patient received five cycles of low power cumulative high-intensity focused ultrasound (HIFU) treatments, which completely ablated the tumor without complications. Now the patient is disease free with a high quality of life more than 30 months. This case indicates HIFU ablation might be a novel, promising therapy for recurrent myxofibrosarcoma.

MicroRNA-138 and SIRT1 form a mutual negative feedback loop to regulate mammalian axon regeneration.

Regulated gene expression determines the intrinsic ability of neurons to extend axons, and loss of such ability is the major reason for the failed axon regeneration in the mature mammalian CNS. MicroRNAs and histone modifications are key epigenetic regulators of gene expression, but their roles in mammalian axon regeneration are not well explored. Here we report microRNA-138 (miR-138) as a novel suppressor of axon regeneration and show that SIRT1, the NAD-dependent histone deacetylase, is the functional target of miR-138. Importantly, we provide the first evidence that miR-138 and SIRT1 regulate mammalian axon regeneration in vivo. Moreover, we found that SIRT1 also acts as a transcriptional repressor to suppress the expression of miR-138 in adult sensory neurons in response to peripheral nerve injury. Therefore, miR-138 and SIRT1 form a mutual negative feedback regulatory loop, which provides a novel mechanism for controlling intrinsic axon regeneration ability.

[Spectrum-effect relationship of hemostatic effects of Notoginseng Radix et Rhizoma with different commodity specifications].

This article aims to establish the fingerprints, determine the hemostatic pharmacodynamic indicators, and explore the spectrum-effect relationship of Notoginseng Radix et Rhizoma in 12 different specifications. Firstly, HPLC and liquid chromatography-mass spectrometry(LC-MS) were employed to establish the fingerprints of Notoginseng Radix et Rhizoma. The rat plasma recalcification experiment and the rat gastric bleeding experiment were conducted to determine the pharmacodynamic indicators, including plasma recalcification time(PRT), thrombin time(TT), prothrombin time(PT), and activated partial thromboplastin time(APTT). Afterwards, the partial least squares method was employed to explore the spectrum-effect relationship of Notoginseng Radix et Rhizoma in different specifications. Twenty-six common peaks were detected in the HPLC fingerprints of different specifications of Notoginseng Radix et Rhizoma, and 11 out of the 26 common peaks represented saponins. The content of dencichine was determined by LC-MS. The rat experiments showed that the pharmacodynamic indicators were significantly different among different specifications of Notoginseng Radix et Rhizoma. The spectrum-effect relationship was explored between 27 common components and pharmacodynamic indicators. Among them, 16 components had positive effects on the pharmacodynamic indicators of Notoginseng Radix et Rhizoma, and 11 exerted negative effects. This study provides a basis for the precision medication and quality control of Notoginseng Radix et Rhizoma.

Algibacter marinivivus sp. nov., isolated from the surface of a marine red alga.

A Gram-stain-negative, non-flagellated bacterium, designated ZY111T, was isolated from the surface of a marine red alga, which was collected from the coast in Weihai, Shandong Province, PR China. Strain ZY111T exhibited growth at 4-37 °C (optimum, 25-28 °C) in the presence of 0-8.0 % (w/v) NaCl (optimum, 2.0-4.0% NaCl) and at pH 6.5-9.5 (optimum, pH 7.0-8.0). The 16S rRNA gene sequence analysis revealed that strain ZY111T belonged to the genus Algibacter, with Algibacter amylolyticus DSM 29199T as its closest relative (97.7 % similarity). The averagenucleotide identity value of strain ZY111T with A. amylolyticus DSM 29199T was 79.03 %. The digitalDNA-DNA hybridization value of strain ZY111T with A. amylolyticus DSM 29199T was 22.40 %. The dominant fatty acids were iso-C15 : 0, iso-C15 : 1 G, iso-C15 : 0 3-OH and iso-C17 : 0 3-OH. The sole respiratory quinone was determined to be menaquinone-6. The polar lipid profile of strain ZY111T consisted of phosphatidylethanolamine, two unidentified aminolipids and three unidentified lipids. The G+C content was 31.9 mol%. The phenotypic, chemotaxonomic and phylogenetic data clearly showed that strain ZY111T represents a novel species of the genus Algibacter, for which the name Algibacter marinivivus sp. nov. is proposed. The type strain is ZY111T (=KCTC 62373T=MCCC 1H00295T).

Marinobacter vulgaris sp. nov., a moderately halophilic bacterium isolated from a marine solar saltern.

A facultatively anaerobic, Gram-stain-negative and non-gliding bacterium, designated F01T, was isolated from marine solar saltern in Weihai, PR China. Cells of F01T were 0.2-0.4 µm wide and 1.4-4.1 µm long, weakly catalase-positive and oxidase-negative. Growth of F01T was determined to occur at 4-40 °C (optimum, 33-37 °C), pH 6.5-8.5 (optimum, 7.0-8.0), and with 0.5-18.0 % (w/v) NaCl (optimum, 3.0-6.0 %). The 16S rRNA gene sequence analysis indicated that F01T represented a member of the genus Marinobacter within the family Alteromonadaceae. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the isolate was most closely related to Marinobacter algicola DSM 16394T, with a sequence similarity of 97.5 %. The DNA G+C content of the isolate was 57.6 mol%. The major respiratory quinone of F01T was ubiquinone-9 (Q-9) and the major fatty acids were anteiso-C15 : 0, C16 : 0 and C18 : 1ω9c. The major polar lipids were phosphoaminolipid, phosphatidylglycerol and phosphatidylethanolamine. On the basis of the results of the phylogenetic analysis and phenotypic properties, it is concluded that F01T can be considered to represent a novel species in the genus Marinobacter, for which the name Marinobacter vulgaris sp. nov. is proposed. The type strain is F01T (=MCCC 1H00290T=KCTC 52700T).

Lesion outline and thermal field distribution of ablative in vitro experiments in myocardia: comparison of radiofrequency and laser ablation.

OBJECTIVES: To explore the lesion outline and thermal field distribution of radiofrequency ablation (RFA) and laser ablation (LA) in myocardial ablation in vitro. MATERIALS AND METHODS: Twenty-four fresh porcine hearts were ablated with RFA or LA in vitro. The radiofrequency electrode or laser fiber and two parallel thermocouple probes were inserted into the myocardium under ultrasound guidance. The output power for RFA was 20 W/s and for LA was 5 W/s, and the total thermal energies were 1200 J, 2400 J, 3600 J, and 4800 J. The range of ablation lesions was measured, and temperature data were recorded simultaneously. RESULTS: All coagulation zones were ellipsoidal with clear boundaries. The center of LA was carbonized more obviously than that of RFA. With the accumulation of thermal energy and the extended time, all the ablation lesions induced by both RFA and LA were enlarged. By comparing the increase in thermal energy between the two groups, both the short-axis diameter and the volume change showed significant differences between the 1200 J and 3600 J groups and between the 2400 J and 4800 J groups (all P < 0.05). Both the short-axis diameter and the volume of the coagulation necrosis zone formed by LA were always larger than those of RFA at the same accumulated thermal energy. The temperatures of the two thermocouple probes increased with each energy increment. At the same accumulated energy, the temperature of LA was much higher than that of RFA at the same point. The initial temperature increase at 0.5 cm of LA was rapid. The temperature reached 43 °C and the accumulated energy reached 1200 J after approximately 4 min. After that the temperature increased at a slower rate to 70  C. For the RFA at the point of 0.5 cm, the initial temperature increased rapidly to 30 °C with the same accumulated energy of 1200 J after only 1 min. In the range of 4800 J of accumulated thermal energy, only the temperature of LA at the point of 0.5 cm exceeded 60 °C when the energy reached approximately 3000 J. CONCLUSIONS: Both RFA and LA were shown to be reliable methods for myocardial ablation. The lesion outline and thermal field distribution of RFA and LA should be considered when performing thermal ablation in the intramyocardial septum during hypertrophic obstructive cardiomyopathy.

Serum markers in the differential diagnosis of Waldenstrom macroglobulinemia and other IgM monoclonal gammopathies.

BACKGROUND: IgM monoclonal gammopathy can be present in a broad spectrum of diseases. We evaluated the value of serum markers in the differential diagnosis of Waldenstrom macroglobulinemia (WM) and other types of IgM monoclonal gammopathies. METHODS: We included patients who were first admitted to hospital and identified as having IgM monoclonal gammopathy by serum immunofixation electrophoresis (sIFE). We evaluated basic clinical features, sIFE, diagnosis, and serum markers. Furthermore, we applied the receiver operating characteristic (ROC) curve to analyze the differential diagnosis value of serum markers for WM. Finally, we used logistic regression and ROC curve to analyze the differential diagnosis value of multimarker combinations to identify WM. RESULTS: IgM monoclonal gammopathy was most frequently found in patients with Waldenstrom macroglobulinemia, followed by monoclonal gammopathy of undetermined significance (MGUS), B-cell non-Hodgkin Lymphoma (B-NHL), and multiple myeloma (MM). Serum markers showed significant differences among the four diseases. The diagnostic markers LDH, IgM, IgG, IgA, and serum light chain К had higher diagnostic efficiency. Among these markers, serum IgM provided the highest diagnostic efficiency. Additionally, the combined use of all five serum markers provided the most effective diagnosis. CONCLUSIONS: The five serum markers, LDH, IgM, IgG, IgA, and К, each yielded a specific efficacy in differential diagnosis of WM. The single marker with the highest diagnostic efficiency was the serum IgM level. However, a combination of multiple serum markers was better than the use of a single marker in diagnosing WM. The combined use of all five serum markers provided the most effective diagnosis, with an AUC of .952 and sensitivity and specificity of 87.8% and 86.9%, respectively.

Predictive value of dynamic change of haemoglobin levels during therapy on treatment outcomes in patients with Enneking stage IIB extremity osteosarcoma.

BACKGROUND: We aimed to investigate the roles of hemoglobin (Hb) concentrations and dynamic change during treatment on outcomes of patients with extremity osteosarcoma. METHODS: We retrospectively analysed 133 patients with Enneking stage IIB extremity osteosarcoma who underwent standard treatments, including univariate and multivariate analyses of patient charateritics, Hb concentrations and changes during pretreatment, neoadjuvant, adjuvant chemotherapy, and decreased Hb levels (ΔHb) to assess their prognostic value in 5-year overall survival (OS) and lung metastasis-free survival (LMFS). RESULTS: Five-year OS or LMFS were similar between patients who were anaemic and non-anaemic during pretreatment, neoadjuvant or adjuvant chemotherapy. Patients with continuously decreasing Hb had lower 5-year OS (52.3%) than those without continuous Hb decrease (68.5%, P = 0.04). Patients with ΔHb > 7.6 g/L had lower 5-year OS (57.5%) than those with ΔHb ≤7.6 g/L (75.8%, P = 0.04). However, continuous Hb decrease had no prognostic effect on 5-year LMFS. Subgroup analyses showed that patients who were anaemic during pretreatment, neoadjuvant, or adjuvant chemotherapy with ΔHb ≤7.6 g/L had better outcomes than those with ΔHb > 7.6 g/L (P < 0.05, for both). CONCLUSION: Dynamic Hb decrease and ΔHb > 7.6 predicted poor5-year OS in patients with Enneking stage IIB extremity osteosarcoma. Attempts to correct anaemia and their effects on outcomes for osteosarcoma patients should be investigated in future trials.

HCBP6 Is Involved in the Development of Hepatic Steatosis Induced by High-Fat Diet and CCL4 in Rats.

INTRODUCTION AND AIM: Hepatitis C virus core-binding protein 6 (HCBP6) was previously found to be an hepatitis C virus corebinding protein, its biological function remains unclear. Our research aims to investigate the role of HCBP6 in the development of hepatic steatosis induced by high-fat diet and carbon tetrachloride (CCL4) in rats. MATERIAL AND METHODS: Eighteen Wistar rats were randomly allocated into 3 groups: control group, model group 1, and model group 2. The control group was treated with a standard diet for 5 weeks. Model groups were treated with high-fat diet and CCL4 injection twice a week for 3 weeks in Group 1 and 5 weeks in Group 2, respectively. After the intervention, hepatic steatosis was observed by histological staining with hematoxylin and eosin (H&E) and Oil Red O staining. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total colesterol (TC), and triglycerides (TGs) were measured. The TG content in liver homogenates was evaluated. Expressions of HCBP6 and SREBP-1c were determined by immunofluorescence, quantitative real-time PCR, and Western blot analysis. RESULTS: Hepatic steatosis was successfully induced in model groups. ALT, AST, TC, and TGs elevated in model groups compared with those in control group (P < 0.05). Hepatic steatosis induced by high-fat diet and CCL4 resulted in low expression of HCBP6 and high expression of SREBP-1c in the liver of rats (P < 0.05). CONCLUSION: HCBP6 is involved in the development of high-fat diet- and CCL4-induced hepatic steatosis and related negatively with SREBP-1c.

A new modified neuroendoscope technology to remove severe intraventricular haematoma.

BACKGROUND: Minimally invasive endoscopic haematoma evacuation is widely used in the treatment of intraventricular haemorrhage. However, its technique still has room for improvement. A new modified neuroendoscope technology (MNT) was used in this study and we explored its safety and efficacy in the treatment of severe acute intraventricular haemorrhage by comparing it with extraventricular drainage plus urokinase thrombolytic (EVD + UT) therapy. METHODS: The following parameters were compared between the MNT group and the control group: incision design, operation time, ICU monitoring time, ventricular drainage tube (VDT) placement time, post-operative drainage tube obstruction (PDTO) rate, post-operative complications rate, 6-month mortality and Glasgow Outcome Scale (GOS). RESULTS: A total of 85 patients were enrolled. The ICU monitoring times, VDT placement times, PDTO rate were shorter in the MNT group. Multivariable logistic regression identified that good medium-term outcome (GOS scores 4-5) was significantly associated with MNT applied (OR 1.017, 95% CI 1.005-1.029, p = 0.008), age under 65 years (OR 4.223, 95% CI, 1.322-17.109, p = 0.034) and pre-operation GCS scores more than 10 (OR 3.427, 95% CI 1.048-11.205, p = 0.040). CONCLUSION: MNT surgery for severe intraventricular haematoma evacuation is a safe and efficient new surgical option. This technique is minimally invasive and may be helpful to provide good outcomes for selected patients.