Single image super-resolution with denoising diffusion GANS.

Single image super-resolution (SISR) refers to the reconstruction from the corresponding low-resolution (LR) image input to a high-resolution (HR) image. However, since a single low-resolution image corresponds to multiple high-resolution images, this is an ill-posed problem. In recent years, generative model-based SISR methods have outperformed conventional SISR methods in performance. However, the SISR methods based on GAN, VAE, and Flow have the problems of unstable training, low sampling quality, and expensive computational cost. These models also struggle to achieve the trifecta of diverse, high-quality, and fast sampling. In particular, denoising diffusion probabilistic models have shown impressive variety and high quality of samples, but their expensive sampling cost prevents them from being well applied in the real world. In this paper, we investigate the fundamental reason for the slow sampling speed of the SISR method based on the diffusion model lies in the Gaussian assumption used in the previous diffusion model, which is only applicable for small step sizes. We propose a new Single Image Super-Resolution with Denoising Diffusion GANS (SRDDGAN) to achieve large-step denoising, sample diversity, and training stability. Our approach combines denoising diffusion models with GANs to generate images conditionally, using a multimodal conditional GAN to model each denoising step. SRDDGAN outperforms existing diffusion model-based methods regarding PSNR and perceptual quality metrics, while the added latent variable Z solution explores the diversity of likely HR spatial domain. Notably, the SRDDGAN model infers nearly 11 times faster than diffusion-based SR3, making it a more practical solution for real-world applications.

Laparoscopic resection of a paraganglioma behind the retrohepatic segment of the inferior vena cava: a case report and literature review.

Background: Due to the location of paragangliomas (PGLs) behind the retrohepatic segment of inferior vena cava (IVC), it is difficult to expose and resect the tumor. Case presentation: A tumor measuring 50×45×62cm behind the retrohepatic portion of IVC was found in a 51-year-old female with hypertention and diabetes mellitus. Although the test for catecholamines revealed no signs of disease, the enhanced computed tomography (CT) scan, somatostatin receptor imaging and iodine-131-labeled metaiiodo-benzylguanidine (131I-MIBG) imaging revealed that the tumor was PGL. A three-dimensional printing was performed to visualize the tumor. The laparoscpic surgery for the PGL behind the retrohepatic segment of IVC was performed and the tumor was resected completely without causing any tissues injury. The pathologic diagnosis was PGL and the patient was able to recover well. Conclusions: This case demonstrates that laparoscopic surgery may be helpful in tumor accessibility, and could be used in the appropriate cases to remove PGLs that are located behind the retrohepatic segment of the IVC.

Long-term partial response in a patient with liver metastasis of primary adrenocortical carcinoma with adjuvant mitotane plus transcatheter arterial chemoembolization and microwave ablation: a case report.

Adrenocortical carcinoma (ACC) is a rare, heterogeneous, and aggressive malignancy with a generally poor prognosis. Surgical resection is the optimal treatment plan. After surgery, both mitotane treatment or the etoposide-doxorubicin-cisplatin (EDP) protocol plus mitotane chemotherapy have a certain effect, but there is still an extremely high possibility of recurrence and metastasis. The liver is one of the most common metastatic targets. Therefore, techniques such as transcatheter arterial chemoembolization (TACE) and microwave ablation (MWA) for liver tumors can be attempted in a specific group of patients. We present the case of a 44-year-old female patient with primary ACC, who was diagnosed with liver metastasis 6 years after resection. During mitotane treatment, we performed four courses of TACE and two MWA procedures in accordance with her clinical condition. The patient has maintained the partial response status and has currently returned to normal life to date. This case illustrates the value of the practical application of mitotane plus TACE and MWA treatment.

Drill-and-prechop technique: modification of the drill-and-crack technique for mature cataracts.

BACKGROUND: There are some techniques for disassembly of hard nuclear. It is challenging in hard cataract surgery through microincision. The classic chop or prechop techniques often do not succeed,resulting in incomplete nuclear segmentation. The authors describe a new chop technique for removing hard nucleus cataracts in coaxial microincisional cataract surgery. METHODS: We create a deep hole (drill) in the central nucleus with the phaco tip and divide the nucleus (prechop) with the Nagahara chopper and the modified capsulorhexis forceps inside the hole. The chopper and the modified capsulorhexis forceps are spread apart laterally after they approach at the center of the nucleus, to create a complete fracture across the entire nucleus. Since January 2022, we have completed 27 eyes of 25 patients with hard nucleus cataract using this technique. RESULTS: Complete segmentation of the hard nuclear into two hemispheres was implemented with this drill and prechop technique in all cases. The effective phaco time and ultrasound energy decreased. No intraoperative complication such as iris injury, anterior capsule tears, zonulysis, or posterior capsule rupture with vitreous loss occurred during surgery. CONCLUSIONS: This technique simplifies the previous prechop techniques especially for hard nucleus in microincisional cataract surgery. The technique is efficient, safe and simple.

Consequences of Preoperative Oral Carbohydrate Consumption in Septal Deviation Patients Undergoing Endoscopic Septoplasty: A Retrospective Cohort Study.

PURPOSE: Multiple reports have demonstrated the benefits of preoperative oral carbohydrates (CHO) in patients receiving open abdominal, thoracic, and orthopedic surgeries. However, thus far, no reports have investigated the benefits of CHO in patients undergoing nasal endoscopic surgery. Our goal was to evaluate the outcome of preoperative oral of administration of CHO in septal deviation patients, undergoing endoscopic septoplasty, under general anesthesia. DESIGN: A retrospective cohort study from a prospectively collected database. METHODS: Consecutive 400 septal deviation patients, undergoing endoscopic septoplasty, were randomly assigned to receive CHO or plain water (80 CHO cohort vs. 320 control cohort) before general anesthesia. The primary outcome was the risk of acute postoperative hypertension (APH). The secondary outcomes included length of hospital stay (LOS), hospitalization cost, sleep time the day before surgery, fluid infusion volume on surgical day, as well the incidence of postoperative nausea and vomiting (PONV) and aspiration. FINDINGS: Patients in the CHO cohort experienced a lower risk of both diastolic blood pressure (DBP)-based APH (OR, 0.49; 95% CI, 0.25 to 0.96; P = 0.0375) and total APH (OR, 0.49; 95% CI, 0.26 to 0.92; P = 0.0258), lower LOS, lower hospitalization cost, longer sleep time and less fluid infusion volume after adjusting for gender, age, BMI, preoperative blood pressure and pulse. Besides, data showed no significant differences in the incidence of (P = 0.4173) and aspiration (P > 0.99). CONCLUSIONS: Preoperative CHO administration can reduce APH risk in patients undergoing endoscopic septoplasty under general anesthesia. Besides, preoperative CHO administration can improve other clinical outcomes, such as, LOS, hospitalization cost, sleep time, and fluid infusion volume. Moreover, CHO safety was confirmed in our study. In the future, additional investigation is necessary to confirm our results.

The Effects of Cumulative Dose and Polymorphisms in CYP2B6 on the Mitotane Plasma Trough Concentrations in Chinese Patients With Advanced Adrenocortical Carcinoma.

Mitotane is the only drug approved to treat adrenocortical carcinoma (ACC), and a relationship of pharmacokinetic/pharmacodynamic has been characterized. However, limited evidence concerning affecting factors in large interindividual variability of the pharmacokinetics of mitotane is available. To address this question, a retrospective analysis was performed on ACC Chinese patients treated with mitotane for more than 3 months. Mitotane plasma trough concentrations were detected at the steady state, and CYP2B6, CYP3A4, and pregnane X receptor (PXR) polymorphisms were genotyped. After examining homogeneous pharmacologic data, we restricted the analyses to 36 patients that received mitotane for a median (interquartile range, IQR) of 9 months (5.00-22.50) with a median dose of 2 g/day (2.00-2.50). As a result, drug exposure was significantly influenced by the cumulative dose of mitotane, and CYP2B6 516GG and CYP2B6 26570CC were at high risk to be below the therapeutic range of mitotane. No association was found between mitotane concentrations with CYP3A4 or PXR polymorphism. Our data firstly indicated that the cumulative dose of mitotane and polymorphisms of CYP2B6 516 and CYP2B6 26570 might significantly affect mitotane plasma trough concentrations in Chinese ACC patients.

An alternative method for personalized tourniquet pressure in total knee arthroplasty: a prospective randomized and controlled study.

Tourniquet use always carries potential risks, which can range from mild transient functional impairments of thigh pain, skin blisters to severe permanent dysfunction of limb paralysis, nerve injuries or compartment syndrome. The ideal method for minimizing intraoperative tourniquet pressure (TP) for reducing postoperative complications remains controversial. In this prospective, randomized and controlled study, we reinvestigated an estimation formula for TP based on thigh circumferences and systolic blood pressure (SBP) with two traditional methods for TP determination in total knee arthroplasty (TKA): SBP plus 100 mmHg and a fixed value of 300 mmHg. TP values and postoperative thigh pain scores were compared among three groups. The intraoperative TP value of the formula-calculated group was lower than that of the traditional groups (14.7 mmHg, P = 0.3475 and 94.7 mmHg, P < 0.0001, respectively), while no differences of hemostatic effect at the surgical fields and wound complications were detected among groups. The thigh pain scores at the tourniquet site decreased gradually over time and the estimation group had the lowest scores at each timepoint after surgery. Estimation method for TP was easy and rapid, without relying on specific equipment. It could provide a practical low TP and comparable hemostatic effect in TKA using an inflating tourniquet.

A 30-Year, Single-Center Experience of Unilateral Adrenalectomy for Primary Bilateral Macronodular Adrenal Hyperplasia.

OBJECTIVE: The aim was to assess the short- and long-term outcomes of unilateral adrenalectomy (UA) in patients with primary bilateral macronodular adrenal hyperplasia (PBMAH). METHODS: We conducted a retrospective study of 124 patients with PBMAH who underwent UA. RESULTS: One hundred sixteen patients were available for follow-up (median, 28.5 months). Cushingoid features remitted in 43 of 65 patients (70.8%) with overt Cushing syndrome (CS). Hypertension and diabetes mellitus improved in 79 of 96 (82.3%) and 29 of 42 patients (69.0%), respectively. Glucocorticoid insufficiency developed in 7 of 116 patients (6.0%) after the surgery, and it resolved in all the patients during follow-up. The mean 24-hour urinary free cortisol level decreased gradually from 456.02 ± 422.33 mg/24 h at baseline to 84.47 ± 70.06 mg/24 h within 3 months and then increased progressively in some patients. Sixty-four of the 116 patients (55.2%) had biochemical recurrence and 43 patients (67.2%) underwent contralateral adrenalectomy. The median time interval between the second operation and the first UA was 24 months. Patients with overt CS had a larger surgical-side or contralateral adrenal volume than patients without overt CS. Patients with a contralateral adrenal volume of >33.54 mL or with a preoperative urinary free cortisol level of >216.08 mg/24 h were more likely to have recurrence. CONCLUSION: The efficiency of UA is transient for the majority of patients, and the indications should be strictly limited to those with subclinical or milder CS. Patients who undergo successful UA still require close life-time follow-up for the recurrence of hypercortisolism.

Medical image segmentation model based on triple gate MultiLayer perceptron.

To alleviate the social contradiction between limited medical resources and increasing medical needs, the medical image-assisted diagnosis based on deep learning has become the research focus in Wise Information Technology of med. Most of the existing medical segmentation models based on Convolution or Transformer have achieved relatively sound effects. However, the Convolution-based model with a limited receptive field cannot establish long-distance dependencies between features as the Network deepens. The Transformer-based model produces large computation overhead and cannot generalize the bias of local features and perceive the position feature of medical images, which are essential in medical image segmentation. To address those issues, we present Triple Gate MultiLayer Perceptron U-Net (TGMLP U-Net), a medical image segmentation model based on MLP, in which we design the Triple Gate MultiLayer Perceptron (TGMLP), composed of three parts. Firstly, considering encoding the position information of features, we propose the Triple MLP module based on MultiLayer Perceptron in this model. It uses linear projection to encode features from the high, wide, and channel dimensions, enabling the model to capture the long-distance dependence of features along the spatial dimension and the precise position information of features in three dimensions with less computational overhead. Then, we design the Local Priors and Global Perceptron module. The Global Perceptron divides the feature map into different partitions and conducts correlation modelling for each partition to establish the global dependency between partitions. The Local Priors uses multi-scale Convolution with high local feature extraction ability to explore further the relationship of context feature information within the structure. At last, we suggest a Gate-controlled Mechanism to effectively solves the problem that the dependence of position embeddings between Patches and within Patches in medical images cannot be well learned due to the relatively small number of samples in medical images segmentation data. Experimental results indicate that the proposed model outperforms other state-of-the-art models in most evaluation indicators, demonstrating its excellent performance in segmenting medical images.

Fine-Tuned Siamese Network with Modified Enhanced Super-Resolution GAN Plus Based on Low-Quality Chest X-ray Images for COVID-19 Identification.

Coronavirus disease has rapidly spread globally since early January of 2020. With millions of deaths, it is essential for an automated system to be utilized to aid in the clinical diagnosis and reduce time consumption for image analysis. This article presents a generative adversarial network (GAN)-based deep learning application for precisely regaining high-resolution (HR) CXR images from low-resolution (LR) CXR correspondents for COVID-19 identification. Respectively, using the building blocks of GAN, we introduce a modified enhanced super-resolution generative adversarial network plus (MESRGAN+) to implement a connected nonlinear mapping collected from noise-contaminated low-resolution input images to produce deblurred and denoised HR images. As opposed to the latest trends of network complexity and computational costs, we incorporate an enhanced VGG19 fine-tuned twin network with the wavelet pooling strategy in order to extract distinct features for COVID-19 identification. We demonstrate our proposed model on a publicly available dataset of 11,920 samples of chest X-ray images, with 2980 cases of COVID-19 CXR, healthy, viral and bacterial cases. Our proposed model performs efficiently both on the binary and four-class classification. The proposed method achieves accuracy of 98.8%, precision of 98.6%, sensitivity of 97.5%, specificity of 98.9%, an F1 score of 97.8% and ROC AUC of 98.8% for the multi-class task, while, for the binary class, the model achieves accuracy of 99.7%, precision of 98.9%, sensitivity of 98.7%, specificity of 99.3%, an F1 score of 98.2% and ROC AUC of 99.7%. Our method obtains state-of-the-art (SOTA) performance, according to the experimental results, which is helpful for COVID-19 screening. This new conceptual framework is proposed to play an influential role in addressing the issues facing COVID-19 examination and other diseases.

Single-Cell RNA-seq Reveals a Developmental Hierarchy Super-Imposed Over Subclonal Evolution in the Cellular Ecosystem of Prostate Cancer.

Prostate cancer (PCa) is a complex disease. An ongoing accumulation of mutations results in increased genetic diversity, with the tumor acquiring distinct subclones. However, non-genetic intra-tumoral heterogeneity, the cellular differentiation state and the interplay between subclonal evolution and transcriptional heterogeneity are poorly understood. Here, the authors perform single-cell RNA sequencing from 14 untreated PCa patients. They create an extensive cell atlas of the PCa patients and mapped developmental states onto tumor subclonal evolution. They identify distinct subclones across PCa patients and then stratify tumor cells into four transcriptional subtypes, EMT-like (subtype 0), luminal A-like (subtype 1), luminal B/C-like (subtype 2), and basal-like (subtype 3). These subtypes are hierarchically organized into stem cell-like and differentiated status. Strikingly, multiple subclones within a single primary tumor present with distinct combinations of preferential subtypes. In addition, subclones show different communication strengths with other cell types within the tumor ecosystem, which may modulate the distinct transcriptional subtypes of the subclones. Notably, by integrating TCGA data, they discover that both tumor cell transcriptional heterogeneity and cellular ecosystem diversity correlate with features of a poor prognosis. Collectively, their study provides the analysis of subclonal and transcriptional heterogeneity and its implication for patient prognosis.

Multi-Channel Based Image Processing Scheme for Pneumonia Identification.

Pneumonia is a prevalent severe respiratory infection that affects the distal and alveoli airways. Across the globe, it is a serious public health issue that has caused high mortality rate of children below five years old and the aged citizens who must have had previous chronic-related ailment. Pneumonia can be caused by a wide range of microorganisms, including virus, fungus, bacteria, which varies greatly across the globe. The spread of the ailment has gained computer-aided diagnosis (CAD) attention. This paper presents a multi-channel-based image processing scheme to automatically extract features and identify pneumonia from chest X-ray images. The proposed approach intends to address the problem of low quality and identify pneumonia in CXR images. Three channels of CXR images, namely, the Local Binary Pattern (LBP), Contrast Enhanced Canny Edge Detection (CECED), and Contrast Limited Adaptive Histogram Equalization (CLAHE) CXR images are processed by deep neural networks. CXR-related features of LBP images are extracted using shallow CNN, features of the CLAHE CXR images are extracted by pre-trained inception-V3, whereas the features of CECED CXR images are extracted using pre-trained MobileNet-V3. The final feature weights of the three channels are concatenated and softmax classification is utilized to determine the final identification result. The proposed network can accurately classify pneumonia according to the experimental result. The proposed method tested on publicly available dataset reports accuracy of 98.3%, sensitivity of 98.9%, and specificity of 99.2%. Compared with the single models and the state-of-the-art models, our proposed network achieves comparable performance.

Identification of Diabetic Retinopathy Using Weighted Fusion Deep Learning Based on Dual-Channel Fundus Scans.

It is a well-known fact that diabetic retinopathy (DR) is one of the most common causes of visual impairment between the ages of 25 and 74 around the globe. Diabetes is caused by persistently high blood glucose levels, which leads to blood vessel aggravations and vision loss. Early diagnosis can minimise the risk of proliferated diabetic retinopathy, which is the advanced level of this disease, and having higher risk of severe impairment. Therefore, it becomes important to classify DR stages. To this effect, this paper presents a weighted fusion deep learning network (WFDLN) to automatically extract features and classify DR stages from fundus scans. The proposed framework aims to treat the issue of low quality and identify retinopathy symptoms in fundus images. Two channels of fundus images, namely, the contrast-limited adaptive histogram equalization (CLAHE) fundus images and the contrast-enhanced canny edge detection (CECED) fundus images are processed by WFDLN. Fundus-related features of CLAHE images are extracted by fine-tuned Inception V3, whereas the features of CECED fundus images are extracted using fine-tuned VGG-16. Both channels' outputs are merged in a weighted approach, and softmax classification is used to determine the final recognition result. Experimental results show that the proposed network can identify the DR stages with high accuracy. The proposed method tested on the Messidor dataset reports an accuracy level of 98.5%, sensitivity of 98.9%, and specificity of 98.0%, whereas on the Kaggle dataset, the proposed model reports an accuracy level of 98.0%, sensitivity of 98.7%, and specificity of 97.8%. Compared with other models, our proposed network achieves comparable performance.

COVID-19 Identification from Low-Quality Computed Tomography Using a Modified Enhanced Super-Resolution Generative Adversarial Network Plus and Siamese Capsule Network.

Computed Tomography has become a vital screening method for the detection of coronavirus 2019 (COVID-19). With the high mortality rate and overload for domain experts, radiologists, and clinicians, there is a need for the application of a computerized diagnostic technique. To this effect, we have taken into consideration improving the performance of COVID-19 identification by tackling the issue of low quality and resolution of computed tomography images by introducing our method. We have reported about a technique named the modified enhanced super resolution generative adversarial network for a better high resolution of computed tomography images. Furthermore, in contrast to the fashion of increasing network depth and complexity to beef up imaging performance, we incorporated a Siamese capsule network that extracts distinct features for COVID-19 identification.The qualitative and quantitative results establish that the proposed model is effective, accurate, and robust for COVID-19 screening. We demonstrate the proposed model for COVID-19 identification on a publicly available dataset COVID-CT, which contains 349 COVID-19 and 463 non-COVID-19 computed tomography images. The proposed method achieves an accuracy of 97.92%, sensitivity of 98.85%, specificity of 97.21%, AUC of 98.03%, precision of 98.44%, and F1 score of 97.52%. Our approach obtained state-of-the-art performance, according to experimental results, which is helpful for COVID-19 screening. This new conceptual framework is proposed to play an influential task in the issue facing COVID-19 and related ailments, with the availability of few datasets.

Ras inhibitor farnesylthiosalicylic acid conjugated with IR783 dye exhibits improved tumor-targeting and altered anti-breast cancer mechanisms in mice.

Ras has long been viewed as a promising target for cancer therapy. Farnesylthiosalicylic acid (FTS), as the only Ras inhibitor has ever entered phase II clinical trials, has yielded disappointing results due to its strong hydrophobicity, poor tumor-targeting capacity, and low therapeutic efficiency. Thus, enhancing hydrophilicity and tumor-targeting capacity of FTS for improving its therapeutic efficacy is of great significance. In this study we conjugated FTS with a cancer-targeting small molecule dye IR783 and characterized the anticancer properties of the conjugate FTS-IR783. We showed that IR783 conjugation greatly improved the hydrophilicity, tumor-targeting and therapeutic potential of FTS. After a single oral administration in Balb/c mice, the relative bioavailability of FTS-IR783 was increased by 90.7% compared with FTS. We demonstrated that organic anion transporting polypeptide (OATP) and endocytosis synergistically drove the uptake of the FTS-IR783 conjugate in breast cancer MDA-MB-231 cells, resulting in superior tumor-targeting ability of the conjugate both in vitro and in vivo. We further revealed that FTS-IR783 conjugate could bind with and directly activate AMPK rather than affecting Ras, and subsequently regulate the TSC2/mTOR signaling pathway, thus achieving 2-10-fold increased anti-cancer therapeutic efficacy against 6 human breast cancer cell lines compared to FTS both in vivo and in vitro. Overall, our data highlights a promising approach for the modification of the anti-tumor drug FTS using IR783 and makes it possible to return FTS back to the clinic with a better efficacy.

Single-cell transcriptome analysis identifies a unique tumor cell type producing multiple hormones in ectopic ACTH and CRH secreting pheochromocytoma.

Ectopic Cushing's syndrome due to ectopic ACTH&CRH-secreting by pheochromocytoma is extremely rare and can be fatal if not properly diagnosed. It remains unclear whether a unique cell type is responsible for multiple hormones secreting. In this work, we performed single-cell RNA sequencing to three different anatomic tumor tissues and one peritumoral tissue based on a rare case with ectopic ACTH&CRH-secreting pheochromocytoma. And in addition to that, three adrenal tumor specimens from common pheochromocytoma and adrenocortical adenomas were also involved in the comparison of tumor cellular heterogeneity. A total of 16 cell types in the tumor microenvironment were identified by unbiased cell clustering of single-cell transcriptomic profiles from all specimens. Notably, we identified a novel multi-functionally chromaffin-like cell type with high expression of both POMC (the precursor of ACTH) and CRH, called ACTH+&CRH + pheochromocyte. We hypothesized that the molecular mechanism of the rare case harbor Cushing's syndrome is due to the identified novel tumor cell type, that is, the secretion of ACTH had a direct effect on the adrenal gland to produce cortisol, while the secretion of CRH can indirectly stimulate the secretion of ACTH from the anterior pituitary. Besides, a new potential marker (GAL) co-expressed with ACTH and CRH might be involved in the regulation of ACTH secretion. The immunohistochemistry results confirmed its multi-functionally chromaffin-like properties with positive staining for CRH, POMC, ACTH, GAL, TH, and CgA. Our findings also proved to some extent the heterogeneity of endothelial and immune microenvironment in different adrenal tumor subtypes.

HSPA13 facilitates NF-κB-mediated transcription and attenuates cell death responses in TNFα signaling.

RIP1 has emerged as a master regulator in TNFα signaling that controls two distinct cellular fates: cell survival versus programmed cell death. Because the default response of most cells to TNFα is NF-κB­mediated inflammation and survival, a specific mechanism must exist to control the divergence of signaling outcome. Here, we identify HSPA13 as a transcription-independent checkpoint to modulate the role of RIP1 in TNFα signaling. Through specific binding to TNFR1 and RIP1, HSPA13 enhances TNFα-induced recruitment of RIP1 to TNFR1, and consequently promotes downstream NF-κB transcriptional responses. Meanwhile, HSPA13 attenuates the participation of RIP1 in cytosolic complex II and prevents cells from programmed death. Loss of HSPA13 shifts the transition of RIP1 from complex I to complex II and promotes both apoptosis and necroptosis. Thus, our study provides compelling evidence for the cellular protective function of HSPA13 in fine-tuning TNFα responses.

Comparison of analgesic activities of aconitine in different mice pain models.

Aconitine (AC) is the primary bioactive and secondary metabolite alkaloidin of Aconitum species which is accounted for more than 60% of the total diester-diterpenoid alkaloids in Aconite. To evaluate the analgesic effects of AC, 4 different pain models including hot plate assay, acetic acid writhing assay, formalin and CFA induced pain models were adopted in this study. In hot plate experiment, AC treatment at concentration of 0.3 mg/kg and 0.9 mg/kg improved the pain thresholds of mice similar to the positive drug aspirin at the concentration of 200 mg/kg (17.12% and 20.27% VS 19.21%). In acetic acid writhing experiment, AC significantly reduced the number of mice writhing events caused by acetic acid, and the inhibition rates were 68% and 76%. These results demonstrated that AC treatment revealed significant analgesic effects in both acute thermal stimulus pain model and chemically-induced visceral pain model. The biphasic nociceptive responses induced by formalin were significantly inhibited after AC treatment for 1h or 2h. The inhibition rates were 33.23% and 20.25% of AC treatment for 1h at 0.3 mg/kg and 0.9 mg/kg in phase I. In phase II, the inhibition rates of AC and aspirin were 36.08%, 32.48% and 48.82% respectively, which means AC showed similar analgesic effect to non-steroidal anti-inflammatory compounds. In the chronic CFA-induced nociception model, AC treatment also improved mice pain threshold to 131.33% at 0.3 mg/kg, which was similar to aspirin group (152.03%). Above all, our results verified that AC had obviously analgesic effects in different mice pain models.

Sum of High-Risk Gene Mutation (SHGM): A Novel Attempt to Assist Differential Diagnosis for Adrenocortical Carcinoma with Benign Adenoma, Based on Detection of Mutations of Nine Target Genes.

There has been no research on applying gene detection to differential diagnosis of adrenocortical carcinoma (ACC). We attempted to explore a novel auxiliary method for differential diagnosis between ACC with benign adrenocortical adenoma (ACA), based on mutations of target genes in tissues. Nine genes were chosen as target genes, including TP53, CTNNB1, ARMC5, PRKAR1A, ZNRF3, RB1, APC, MEN1, and RPL22. Exons sequencing of target genes were performed in 98 cases of tissue samples by FastTarget technology, including 41 ACC tissues, 32 ACA tissues, and 25 normal adrenal gland tissues. Significant mutations were detected and identified, and the clinical information was collected, for further comparative analysis and application to assist differential diagnosis of ACC. We identified 132 significant gene mutations and 227 significant mutation sites in 37 ACC tissues, much more than ACA and normal adrenal gland tissues. Mutation rates of 6 genes in ACC tissues were obviously higher than ACA tissues, including ZNRF3, ARMC5, TP53, APC, RB1, and PRKAR1A, regarded as high-risk genes. The sum of mutated high-risk genes detected in each sample was denominated sum of high-risk gene mutation (SHGM), and the rates of SHGM > 0 and SHGM > 1 in ACC tissues were 73.0% and 62.2%, respectively, both obviously higher than those in ACA tissues, with significant statistic differences. Especially for 8 cases of ACC with diameter < 5 cm, SHGM > 0 and SHGM > 1 were found in 6 samples (75%) and 4 samples (50%), respectively. However, no relevance was found between SHGM and clinical characteristics of ACC. We identified 6 high-risk genes in ACC tissues, with significantly higher mutation rates than ACA or normal adrenal gland tissues. The sum of mutated high-risk genes detected in ACC tissues was denominated SHGM, which was potential to assist the differential diagnosis of ACC with ACA, especially for the small-size ACC.

Ideal intraarticular application dose of tranexamic acid in primary total knee arthroplasty: a prospective, randomized and controlled study.

BACKGROUND: Combined use of tranexamic acid (TXA) via intravenous (IV) and intraarticular (IA) routes is more effective in reducing blood loss than any single route in primary total knee arthroplasty (TKA), but the optimal dose of topical administration remains controversial. The aim of this study was to evaluate the efficacy and safety of different combined administration strategies and to determine an ideal IA application dose of TXA. METHODS: A total of 180 patients who underwent primary TKA were randomized to four groups (groups A/B/C/D) with the same single IV dose of 1 g TXA preoperatively and four different IA doses after wound closure: group A (0 g), group B (1 g), group C (2 g), and group D (4 g). The primary outcome measures included wound blood drainage, hemoglobin (Hb) concentration, and blood transfusion. The secondary outcome measures included wound complications, deep vein thrombosis (DVT) and symptomatic pulmonary embolism (PE). RESULTS: A total of 165 patients finished at least 3 months of follow-up visits. The amount of 48-hour blood drainage and calculated total blood loss in four groups decreased with the increased dose of TXA injected via IA route, and no difference was observed between groups C and D (P=0.6237 and P=0.9923, respectively). Hb was significantly higher in groups C and D than in groups A and B at postoperative day 1, 3 and 7, respectively (P<0.0001). Hb in group A was significantly lower than that in groups C and D at 1 month after surgery, whereas no intergroup difference was found in other groups. No intergroup difference was observed regarding DVT, PE or wound complications. CONCLUSIONS: The topical injection of 2 g TXA may have reached the "ceiling effect" of local use. A preoperative IV dose of 1 g TXA combined with an IA dose of 2 g TXA could be an optimal combination regimen.