Genome-wide CRISPR-Cas9 knockout screens identify DNMT1 as a druggable dependency in sonic hedgehog medulloblastoma.

Sonic hedgehog subgroup of medulloblastoma (SHH-MB) is characterized by aberrant activation of the SHH signaling pathway. An inhibition of the positive SHH regulator Smoothened (SMO) has demonstrated promising clinical efficacy. Yet, primary and acquired resistance to SMO inhibitors limit their efficacy. An understanding of underlying molecular mechanisms of resistance to therapy is warranted to bridge this unmet need. Here, we make use of genome-wide CRISPR-Cas9 knockout screens in murine SMB21 and human DAOY cells, in order to unravel genetic dependencies and drug-related genetic interactors that could serve as alternative therapeutic targets for SHH-MB. Our screens reinforce SMB21 cells as a faithful model system for SHH-MB, as opposed to DAOY cells, and identify members of the epigenetic machinery including DNA methyltransferase 1 (DNMT1) as druggable targets in SHH-dependent tumors. We show that Dnmt1 plays a crucial role in normal murine cerebellar development and is required for SHH-MB growth in vivo. Additionally, DNMT1 pharmacological inhibition alone and in combination with SMO inhibition effectively inhibits tumor growth in murine and human SHH-MB cell models and prolongs survival of SHH-MB mouse models by inhibiting SHH signaling output downstream of SMO. In conclusion, our data highlight the potential of inhibiting epigenetic regulators as a novel therapeutic avenue in SMO-inhibitor sensitive as well as resistant SHH-MBs.

CDI-NSTSEG: A clinical diagnosis-inspired effective and efficient framework for non-salient small tumor segmentation.

To accurately segment various clinical lesions from computed tomography(CT) images is a critical task for the diagnosis and treatment of many diseases. However, current segmentation frameworks are tailored to specific diseases, and limited frameworks can detect and segment different types of lesions. Besides, it is another challenging problem for current segmentation frameworks to segment visually inconspicuous and small-scale tumors (such as small intestinal stromal tumors and pancreatic tumors). Our proposed framework, CDI-NSTSEG, efficiently segments small non-salient tumors using multi-scale visual information and non-local target mining. CDI-NSTSEG follows the diagnostic process of clinicians, including preliminary screening, localization, refinement, and segmentation. Specifically, we first explore to extract the unique features at three different scales (1×, 0.5×, and 1.5×) based on the scale space theory. Our proposed scale fusion module (SFM) hierarchically fuses features to obtain a comprehensive representation, similar to preliminary screening in clinical diagnosis. The global localization module (GLM) is designed with a non-local attention mechanism. It captures the long-range semantic dependencies of channels and spatial locations from the fused features. GLM enables us to locate the tumor from a global perspective and output the initial prediction results. Finally, we design the layer focusing module (LFM) to gradually refine the initial results. LFM mainly conducts context exploration based on foreground and background features, focuses on suspicious areas layer-by-layer, and performs element-by-element addition and subtraction to eliminate errors. Our framework achieves state-of-the-art segmentation performance on small intestinal stromal tumor and pancreatic tumor datasets. CDI-NSTSEG outperforms the best comparison segmentation method by 7.38% Dice on small intestinal stromal tumors.

Enhancing degradation of sulfamethoxazole by layered double hydroxide/carbon nanotubes catalyst via synergistic effect of photocatalysis/persulfate activation.

A Co3Mn-LDHs and carbon nanotube (Co3Mn-LDHs/CNT) composite catalyst was constructed for permonosulfate (PMS) activation and degrading sulfamethoxazole (SMX) under Vis light irradiation. The introduction of CNTs into Co3Mn-LDHs facilitate the exciton dissociation and carrier migration, and the e- and h+ were readily separated from Co3Mn-LDHs/CNT in the photocatalysis process, which promoted the production rate of reactive oxygen species (ROS), so the Co3Mn-LDHs + Vis + PMS system exhibited better activity with an SMX degradation ratio of 61.25% than those of Co3Mn-LDHs + Vis system (42.30%) and Co3Mn-LDHs + PMS system (48.30%). After 10 cycles, the degradation rate of SMX only decreased by 7.16%, indicating the good reusability of the Co3Mn-LDHs/CNTs catalyst. The results of electron paramagnetic resonance (EPR) analysis and radical quenching experiments demonstrated that that the SO4•- played crucial role for SMX removal in Co3Mn-LDHs/CNTs + Vis + PMS system, and both e- and h+ made an important contribution to activating PMS to produce ROS. Overall, this work provided an excellent catalyst for photo-assisted PMS activation and suggested the activation mechanism for organic pollutant remediation.

Auxiliary management and control channel aided crosstalk online monitoring in multi-core fibers.

As a stochastic perturbation, the inter-core crosstalk (IC-XT) severely distorts the signal in multi-core fibers (MCF), especially for long-haul transmission. How to quickly measure and monitor the IC-XT online for an MCF-based space division multiplexing (SDM) system is of special importance. In this paper, we introduce the technology of auxiliary management and control channel (AMCC) to online monitor the IC-XT of MCF, in which the unique advantage of low-frequency auxiliary management and control signal is fully utilized with the limited influence on high-speed data transmission. Specifically, two orthogonal sequences are chosen as monitoring signals for the signal-channel core and the crosstalk-channel core, respectively, followed by digital signal processing (DSP) for the received signal to evaluate the real-time crosstalk accurately. The experimental verifications of XT online monitoring confirm the effectiveness of our proposed method with very small monitoring error (mostly < 0.5 dB) for both heterodyne XT and homodyne XT in the C and L bands, showing its great potential for future SDM systems.

Photo-electrochemical activation of persulfate for the simultaneous degradation of microplastics and personal care products.

The recent widespread use of microplastics (MPs), especially in pharmaceuticals and personal care products (PPCPs), has caused significant water pollution. This study presents a UV/electrically co-facilitated activated persulfate (PS) system to co-degrade a typical microplastic polyvinyl chloride (PVC) and an organic sunscreen p-aminobenzoic acid (PABA). We investigated the effect of various reaction conditions on the degradation. PVC and PABA degradation was 37% and 99.22%, respectively. Furthermore, we observed alterations in the surface topography and chemical characteristics of PVC throughout degradation. The possible degradation pathways of PVC and PABA were proposed by analyzing the intermediate products and the free radicals generated. This study reveals the co-promoting effect of multiple mechanisms in the activation by ultraviolet light and electricity.

Photocatalytic degradation of p-aminobenzoic acid on N-biomass charcoal etched with Fe-Al-bilayer hydroxide: New insights through spectroscopic investigation.

We investigated the photocatalytic property of etched iron­aluminum layered double hydroxide (LDH) composites using urea-modified biochar (N-BC) carrier to degrade para-aminobenzoic acid (PABA), a refractory organic pollutant. The prepared FeAl-LDH@FeSx-N-BC composite exhibited excellent photocatalytic performance, attributed to the enhanced photogenerated charge-carrier separation by the etched LDH and the improved comparative surface areas by the doped N-BC. The composite photocatalytically degraded 96 % of PABA. The performance was affected by solute concentration, pH and photocatalyst dose. Adding p-benzoquinone and EDTA-2Na significantly decreased the degradation rate, suggesting that superoxide radicals and holes were co-involved in PABA degradation. The excellent PABA removal efficiency was consistent for three consecutive runs. The samples' reactive oxygen species was confirmed, as electron paramagnetic reverberation explained the photodegradation mechanism. Under xenon lamp irradiation, two PABA photocatalytic degradation pathways were proposed using Liquid Chromatograph Mass Spectrometer (LCMS) and density functional theory. As expected, FeAl-LDH@FeSx-N-BC showed excellent photocatalytic performance, expanding a new direction and possibility for future photocatalytic treatment of water pollutants.

Nanoplastics aggravated TDCIPP-induced transgenerational developmental neurotoxicity in zebrafish depending on the involvement of the dopamine signaling pathway.

Plastics pose a hazard to the environment. Although plastics have toxicity, microplastics (MPs) and nanoplastics (NPs) are capable of interacting with the rest pollutants in the environment, so they serve as the carriers and interact with organic pollutants to modulate their toxicity, thus resulting in unpredictable ecological risks. PS-NPs and TDCIPP were used expose from 2 h post-fertilization (hpf) to 150 days post-fertilization (dpf) to determine the bioaccumulation of tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and its potential effects on neurodevelopment in F1 zebrafish (Danio rerio) offspring under the action of polystyrene nano plastics (PS-NPs). The exposure groups were assigned to TDCIPP (0, 0.4, 2 or 10 µg/L) alone group and the PS-NPs (100 µg/L) and TDCIPP co-exposed group. F1 embryos were collected and grown in clean water to 5 dpf post-fertilization. PS-NPs facilitated the bioaccumulation of TDCIPP in the gut, gill, head，gonad and liver of zebrafish in a sex-dependent manner and promoted the transfer of TDCIPP to their offspring, thus contributing to PS-NPs aggravated the inhibition of offspring development and neurobehavior of TDCIPP-induced. In comparison with TDCIPP exposure alone, the combination could notably down-regulate the levels of the dopamine neurotransmitter, whereas the levels of serotonin or acetylcholine were not notably different. This result was achieved probably because PS-NPs interfered with the TDCIPP neurotoxic response of zebrafish F1 offspring not through the serotonin or acetylcholine neurotransmitter pathway. The increased transfer of TDCIPP to the offspring under the action of PS-NPs increased TDCIPP-induced transgenerational developmental neurotoxicity, which was proven by a further up-regulation/down-regulation the key gene and protein expression related to dopamine synthesis, transport, and metabolism in F1 larvae, in contrast to TDCIPP exposure alone. The above findings suggested that dopaminergic signaling involvement could be conducive to the transgenerational neurodevelopmental toxicity of F1 larval upon parental early co-exposure to PS-NPs and TDCIPP.

Effect of cadmium on polystyrene transport in parsley roots planted in a split-root system and assessment of the combined toxic effects.

Micro and nanoplastics (MPs/NPs) coupled with heavy metals are prevalent in both aquatic and terrestrial ecosystems. Their ecological toxicity and combined adverse effects have obtained significant concern. Past studies primarily focused on how MPs/NPs influence the behavior of heavy metals. Yet, the possible effects of heavy metals on MP/NP transport and toxicity within co-contaminated systems are still not well-understood. In this study, we conducted split-root experiments to explore the transport and toxicity of polystyrene (PS) particles of varying sizes in parsley seedlings, both with and without the addition of cadmium (Cd). Both the PS-NPs (100 nm) and PS-MPs (300 nm) traveled from the PS-spiked roots (Roots-1) to the non-PS-spiked roots (Roots-2), with or without Cd, possibly because of phloem transport. Furthermore, the presence of Cd reduced the accumulation and movement of PS-NP/MP in the roots, likely due to the increased positive charge (Cd2+) on the PS surface. PS-NPs/MPs in both Roots-1 and Roots-2 were observed using transmission electron microscopy (TEM). When Cd was added to either Roots-1 (PS + Cd|H) or Roots-2 (PS|Cd), there was a minor reduction in the chlorophyll a and carotenoids content in leaves with PS|H. The adverse impacts of MPs|H on both indicators were influenced by the MP concentration. However, chlorophyll b significantly increased in the PS|H, PS + Cd|H, and PS|Cd treatments. Consequently, the chlorophyll a/b ratio declined, indicating inhibition of photosynthesis. The dehydrogenase content showed a minor change in Roots-1 and Roots-2 without Cd stress, whereas it significantly decreased on the Cd-spiked side and subsequently inhibited root growth. In contrast, the marked rise in glutathione (GSH) levels within Cd-spiked roots suggested, based on Gaussian analysis, that GSH and Cd chelation were instrumental in mitigating Cd toxicity. When Cd was introduced to both Roots-1 and Roots-2 simultaneously (PS + Cd|Cd), the aforementioned index showed a notable decline.

Analysis of hemorrhage upon ultrasound-guided percutaneous renal biopsy in China: a retrospective study.

PURPOSE: Ultrasound-guided percutaneous renal biopsy (PRB) has been considered as a golden standard for CKD diagnosis and is employed to identify potential therapeutic targets since 1950s. Post-biopsy hemorrhage is the most common complication, while severe bleeding complication might cause nephrectomy or death. Therefore, how to reduce the occurrence of complications while ensuring the success of PRB is always a clinical research topic. METHODS: This study retrospectively collected and established a renal biopsy database of each patient who underwent ultrasound-guided PRB at a tertiary teaching hospital from September 2017 to December 2020 through the Health Information System. All the data were statistically processed by SPSS software. RESULTS: A total of 1146 patients underwent PRB for various reasons. The overall rate of post-biopsy hemorrhage was 37.70% (432/1146). Of those bleedings, minor bleeding after PRB was found in 337 (29.41%), middle bleeding 84 (7.33%), major bleeding 11 (0.96%). Besides that, there were 96 patients (8.38%) reported their discomfort symptoms. There was no death. Females were at significantly increased risk of hemorrhagic complication than males (OR = 2.017, CI = 1.531-2.658). While the risk for hemorrhagic complication significantly decreased as BMI and platelet before renal biopsy increased (OR = 0.956, CI = 0.924-0.989; OR = 0.998, CI = 0.996-1.000). As the APTT time prolonged, the risk for hemorrhagic complication significantly increased (OR = 1.072, CI = 1.023-1.123). Those patients whose albumin were higher, also had higher risk for hemorrhagic complication than other patients (OR = 1.020, CI = 1.000-1.041). Specifically, postoperative urination within 4 h increased the risk for hemorrhagic complication (OR = 1.741, CI = 1.176-2.576). CONCLUSION: Our analysis finds that the incidence of post-biopsy bleeding complication is 37.70%, and its risk is associated with female, lower BMI, lower platelet before renal biopsy, prolonged APTT, higher albumin, and postoperative urination within 4 h. The findings highlighted the importance of perioperative management for renal biopsy, including adequate risk assessment, tailored careful observation after PRB. And medical staff should pay more attention to fluid management after ultrasound-guided PRB.

Development of a multiple convolutional neural network-facilitated diagnostic screening program for immunofluorescence images of IgA nephropathy and idiopathic membranous nephropathy.

Background: Immunoglobulin A nephropathy (IgAN) and idiopathic membranous nephropathy (IMN) are the most common glomerular diseases. Immunofluorescence (IF) tests of renal tissues are crucial for the diagnosis. We developed a multiple convolutional neural network (CNN)-facilitated diagnostic program to assist the IF diagnosis of IgAN and IMN. Methods: The diagnostic program consisted of four parts: a CNN trained as a glomeruli detection module, an IF intensity comparator, dual-CNN (D-CNN) trained as a deposition appearance and location classifier and a post-processing module. A total of 1573 glomerular IF images from 1009 patients with glomerular diseases were used for the training and validation of the diagnostic program. A total of 1610 images of 426 patients from different hospitals were used as test datasets. The performance of the diagnostic program was compared with nephropathologists. Results: In >90% of the tested images, the glomerulus location module achieved an intersection over union >0.8. The accuracy of the D-CNN in recognizing irregular granular mesangial deposition and fine granular deposition along the glomerular basement membrane was 96.1% and 93.3%, respectively. As for the diagnostic program, the accuracy, sensitivity and specificity of diagnosing suspected IgAN were 97.6%, 94.4% and 96.0%, respectively. The accuracy, sensitivity and specificity of diagnosing suspected IMN were 91.7%, 88.9% and 95.8%, respectively. The corresponding areas under the curve (AUCs) were 0.983 and 0.935. When tested with images from the outside hospital, the diagnostic program showed stable performance. The AUCs for diagnosing suspected IgAN and IMN were 0.972 and 0.948, respectively. Compared with inexperienced nephropathologists, the program showed better performance. Conclusion: The proposed diagnostic program could assist the IF diagnosis of IgAN and IMN.

A Small Intestinal Stromal Tumor Detection Method Based on an Attention Balance Feature Pyramid.

Small intestinal stromal tumor (SIST) is a common gastrointestinal tumor. Currently, SIST diagnosis relies on clinical radiologists reviewing CT images from medical imaging sensors. However, this method is inefficient and greatly affected by subjective factors. The automatic detection method for stromal tumors based on computer vision technology can better solve these problems. However, in CT images, SIST have different shapes and sizes, blurred edge texture, and little difference from surrounding normal tissues, which to a large extent challenges the use of computer vision technology for the automatic detection of stromal tumors. Furthermore, there are the following issues in the research on the detection and recognition of SIST. After analyzing mainstream target detection models on SIST data, it was discovered that there is an imbalance in the features at different levels during the feature fusion stage of the network model. Therefore, this paper proposes an algorithm, based on the attention balance feature pyramid (ABFP), for detecting SIST with unbalanced feature fusion in the target detection model. By combining weighted multi-level feature maps from the backbone network, the algorithm creates a balanced semantic feature map. Spatial attention and channel attention modules are then introduced to enhance this map. In the feature fusion stage, the algorithm scales the enhanced balanced semantic feature map to the size of each level feature map and enhances the original feature information with the original feature map, effectively addressing the imbalance between deep and shallow features. Consequently, the SIST detection model's detection performance is significantly improved, and the method is highly versatile. Experimental results show that the ABFP method can enhance traditional target detection methods, and is compatible with various models and feature fusion strategies.

Y-mediated optimization of 3DG-PbO2 anode for electrochemical degradation of PFOS.

In our previous study, the three-dimensional graphene-modified PbO2 (3DG-PbO2) anode was prepared for the effective degradation of perfluorooctanesulfonat (PFOS) by the electrochemical oxidation process. However, the mineralization efficiency of PFOS at the 3DG-PbO2 anode still needs to be further improved due to the recalcitrance of PFOS. Thus, in this study, the yttrium (Y) was doped into the 3DG-PbO2 film to further improve the electrochemical activity of the PbO2 anode. To optimize the doping amount of Y, three Y and 3DG codoped PbO2 anodes were fabricated with different Y3+ concentrations of 5, 15, and 30 mM in the electroplating solution, which were named Y/3DG-PbO2-5, Y/3DG-PbO2-15 and Y/3DG-PbO2-30, respectively. The results of morphological, structural, and electrochemical characterization revealed that doping Y into the 3DG-PbO2 anode further refined the ß-PbO2 crystals, increased the oxygen evolution overpotential and active sites, and reduced the electron transfer resistance, resulting in a superior electrocatalytic activity. Among all the prepared anodes, the Y/3DG-PbO2-15 anode exhibited the best activity for electrochemical oxidation of PFOS. After 120 min of electrolysis, the TOC removal efficiency was 80.89% with Y/3DG-PbO2-15 anode, greatly higher than 69.13% with 3DG-PbO2 anode. In addition, the effect of operating parameters on PFOS removal was analyzed by response surface, and the obtained optimum values of current density, initial PFOS concentration, pH, and Na2SO4 concentration were 50 mA/cm2, 12.21 mg/L, 5.39, and 0.01 M, respectively. Under the optimal conditions, the PFOS removal efficiency reached up to 97.16% after 40 min of electrolysis. The results of the present study confirmed that the Y/3DG-PbO2 was a promising anode for electrocatalytic oxidation of persistent organic pollutants.

Malignancy-associated membranous nephropathy: focus on diagnosis and treatment.

BACKGROUND: The clinicopathological features of malignancy-associated membranous nephropathy have been described previously, but information about diagnosis and treatment remains limited. METHODS: Patients with malignancy-associated membranous nephropathy in a tertiary hospital in China between June 2012 and October 2021 were retrospectively reviewed. RESULTS: Forty-two patients with malignancy-associated membranous nephropathy were identified. Compared to patients with idiopathic membranous nephropathy, patients with malignancy-associated membranous nephropathy were older and less frequently showed glomerular phospholipase A2 receptor staining (37.9% vs 85.0%) and IgG4 predominant deposition (66.7% vs 95.0%). At diagnosis of membranous nephropathy, the malignancy was unknown in 67% (28/42) of patients and was detected only by tumor screening. Among the 19 patients with concurrent diagnosis of cancer and biopsy-proven membranous nephropathy, 15 received anticancer treatment alone initially. Six of the 10 patients who attained cancer remission achieved remission of membranous nephropathy, while none of the 5 patients without remission of cancer did, suggesting a causal relationship between the two diseases. Some patients with persistent or relapsing membranous nephropathy following cancer remission achieved remission of membranous nephropathy after immunosuppressive therapy. Over a median follow-up of 24 months, 25% (10/40) of patients died, mainly due to neoplasia. CONCLUSIONS: Tumor screening is important in patients with membranous nephropathy, especially in elderly patients and patients with negative phospholipase A2 receptor or non-IgG4 predominant deposition. Remission of membranous nephropathy can be observed following remission of cancer in some cases. Immunosuppressive therapy may be considered if membranous nephropathy does not remit after remission of cancer.

A novel 3-dimensional graphene-based cobalt-manganese bimetallic layered double hydroxide:Formation mechanism and performance in photo-assisted permonosulfate-activated degradation of sulfamethoxazole in aqueous solution.

Sulfamethoxazole (SMX) is a common antibiotic used mainly for bacterial treatment. In this study, a novel three-dimensional cobalt-manganese bimetallic layered double hydroxide graphene hydrogel (CoMn-LDHs/rGO) has been prepared for photo-assisted permonosulfate (PMS)-activated degradation of SMX in water. Compared with the CoMn-LDHs/rGO + PMS and CoMn-LDHs/rGO + Vis systems, the degradation effect of CoMn-LDHs/rGO + PMS + Vis system is the best, and the degradation effect of CoMn-LDHs/rGO system could reach more than 98% under the optimal conditions. After 10 cycles, the catalytic degradation performance of CoMn-LDHs/rGO system remained good, while effectively preventing the leaching of metal ions. Based on the synergistic effect of photocatalysis and PMS oxidation, electron spin resonance spectroscopy and quenching experiments showed that three active substances (•OH, •SO4- and O2•-) were involved in the degradation of SMX. Density functional theory and liquid chromatography-mass spectrometry (LC-MS) results further proposed the SMX degradation transformation calculation. As expected, the study of the reaction mechanism of 3D CoMn-LDHs/rGO assisted PMS activation under visible light provides an efficient and rapid method for the sustainable degradation of pollutants in water system.

Low crosstalk trapezoid-index thirteen-core single-mode fiber for multi-channel and high-density applications.

Multi-core fiber based on space division multiplexing technology provides a practical solution to achieve multi-channel and high-capacity signal transmission. However, long-distance and error-free transmission remains challenging due to the presence of inter-core crosstalk within the multi-core fiber. Here, we propose and prepare a novel trapezoid-index thirteen-core single-mode fiber to solve the problems that MCF has large inter-core crosstalk and the transmission capacity of single-mode fiber approaches the upper limit. The optical properties of thirteen-core single-mode fiber are measured and characterized by experimental setups. The inter-core crosstalk of the thirteen-core single-mode fiber is less than -62.50 dB/km at 1550 nm. At the same time, each core can transmit signals at a data rate of 10 Gb/s and achieve error-free signal transmission. The prepared optical fiber with a trapezoid-index core provides a new and feasible solution for reducing inter-core crosstalk, which can be loaded into current communication systems and applied in large data centers.

On the performance stability of MCF-based SDM system affected by inter-core crosstalk fluctuation.

The inter-core crosstalk (IC-XT) of multi-core fiber (MCF) limits the capacity of space division multiplexing system (SDM) fundamentally. We develop a closed-form expression of the magnitude of IC-XT for various types of signals, which can well explain the mechanism of different fluctuation behaviors of the real-time short-term average crosstalk (STAXT) and bit error ratio (BER) for the optical signals with and without strong optical carrier. The experimental verifications with the real-time measurement of the BER and outage probability in a 7 × 10-Gb/s SDM system agree well with the proposed theory and confirm that the unmodulated optical carrier plays a substantial role in fluctuation of BER. The range of fluctuation can be reduced by 3 orders of magnitude for the optical signal without optical carrier. We also investigate the effect of IC-XT in a long-haul transmission system based on a recirculating 7-core fiber loop and develop a frequency-domain IC-XT measurement technique. Longer transmission distance is shown to have a narrower BER fluctuation range, since IC-XT is no longer the only dominant factor on transmission performance.

Utility of video-assisted method for identifying and preserving the external branch of the superior laryngeal nerve during thyroidectomy.

Background: The EBSLN is vulnerable to damage during thyroidectomy, results in voice related complications, negatively affect patient quality of life, routine identification of the EBSLN prior to surgical manipulation is necessary for a complication-free thyroidectomy. We aimed to validate a video-assisted procedure for identifying and preserving the external branch of the superior laryngeal nerve (EBSLN) during thyroidectomy and analyze the EBSLN Cernea classification and the localization of the nerve entry point (NEP) from the insertion of the sternothyroid muscle. Methods: A prospective descriptive study was performed; 134 patients, who scheduled for lobectomy with an intraglandular tumor max diameter ≤ 4 cm and without extrathyroidal extension, were randomly divided into the video-assisted surgery (VAS) and conventional open surgery (COS) groups. We used the video-assisted surgical procedure for visually identifying the EBSLN directly, and compared the differences in the visual identification rate and total identification rate of the two groups. We also measured the localization of the NEP using the insertion of the sternothyroid muscle as a reference. Results: There was no statistically significant difference in clinical characteristics between the two groups. The visual identification rate and total identification rate were significantly higher in the VAS group than the COS group (91.04% vs. 77.61%, 100% vs. 89.6%). The EBSLN injury rate was 0 in both groups. The mean vertical distance (VD) of the NEP from the sternal thyroid insertion was 1.18 mm (SD 1.12 mm, range, 0-5 mm), with approximately 88.97% of the results occurring within the 0-2 mm range. The mean horizontal distance (HD) was 9.33 mm (SD 5.03 mm, range, 0-30 mm), with over 92.13% of the results occurring within the 5-15 mm range. Conclusion: Both the visual and total identification rates of the EBSLN were significantly higher in the VAS group. This method provided a good visual exposure rate of the EBSLN, aiding in identifying and protecting the EBSLN during thyroidectomy.

Antimalarial activity and sensitization of chrysosplenetin against artemisinin-resistant genotype Plasmodium berghei K173 potentially via dual-mechanism of maintaining host P-glycoprotein homeostasis mediated by NF-κB p52 or PXR/CAR signaling pathways and regulating heme/haemozoin metabolism.

This study investigated antimalarial efficacy and sensitization of chrysosplenetin against artemisinin-resistant Plasmodium berghei K173 and potential molecular mechanism. Our data indicated a risk of artemisinin resistance because a higher parasitaemia% and lower inhibition% under artemisinin treatment against resistant parasites than those in the sensitive groups were observed. Two non-antimalarial components, verapamil and chrysosplentin, being P-gp inhibitors, possessed a strong efficacy against resistant parasites but it was not the case for Bcrp inhibitor novobiocin. Artemisinin-chrysosplenetin combination improved artemisinin susceptibility of resistant P. berghei. Artemisinin activated intestinal P-gp and Abcb1/Abcg2 expressions and suppressed Bcrp whereas chrysosplenetin reversed them. Resistant parasite infection led to a decreased haemozoin in organs or an increased heme in peripheral bloods compared with the sensitives; however, that in Abcb1-deficient knockout (KO)-resistant mice reversely got increased or decreased versus wild type (WT)-resistant animals. Chrysosplenetin as well as rifampin (nuclear receptor agonist) increased the transcription levels of PXR/CAR while showed a versatile regulation on hepatic and enternal PXR/CAR in WT- or KO-sensitive or -resistant parasites. Oppositely, hepatic and enteric NF-κB p52 mRNA decreased conformably in WT but increased in KO-resistant mice. NF-κB pathway potentially involved in the mechanism of chrysosplenetin on inhibiting P-gp expressions while PXR/CAR play a more complicated role in this mechanism.

A model for predicting degree of malignancy in patients with intraductal papillary mucinous neoplasm.

Background/Objectives: There is no predictive model available to address early stage malignant intraductal papillary mucinous neoplasm (IPMN) including high grade dysplasia (HGD) and pT1a (invasive component≤0.5 cm). The aim of this study was to establish an objective and sufficient model to predict the degree of malignancy in patients with IPMN, which can be easily applied in daily practice and adopted for any type of lesion. Methods: A retrospective cohort study of 309 patients who underwent surgical resection for IPMN was performed. Members of the cohort were randomly allocated to the training or testing set. A detection tree model and random forest model were used for a 3-class classification to distinguish low grade dysplasia (LGD), HGD/pT1a IPMN, and invasive intraductal papillary mucinous cancer (I-IPMC) beyond pT1a. Results: Of the 309 patients, 54 (17.4%) had early stage malignancy (19 HGD, 35 pT1a), 49 (15.9%) had I-IPMC beyond pT1a, and 206 (66.7%) had LGD IPMN. We proposed a 3-class classification model using a random forest algorithm, and the model had an accuracy of 99.5% with the training set, and displayed an accuracy of 96.0% with the testing set. We used SHAP for interpretation of the model and showed the top five factors (mural nodule size, main pancreatic duct diameter, CA19-9 levels, lesion edge and common bile duct dilation) were most likely to influence the 3-class classification results in terms of interpretation of the random forest model. Conclusions: This predictive model will help assess an individual's risk for different stages of IPMN malignancy and may help identify patients with IPMN who require surgery.

Combining Serum Procalcitonin Level, Thromboelastography, and Platelet Count to Predict Short-term Development of Septic Shock in Intensive Care Unit.

OBJECTIVE: Despite the recent advances in diagnosis and treatment, sepsis continues to lead to high morbidity and mortality. Early diagnosis and prompt treatment are essential to save lives. However, most biomarkers can only help to diagnose sepsis, but cannot predict the development of septic shock in high-risk patients. The present study determined whether the combined measurement of procalcitonin (PCT), thromboelastography (TEG) and platelet (PLT) count can predict the development of septic shock. METHODS: A retrospective study was conducted on 175 septic patients who were admitted to the intensive care unit between January 2017 and February 2021. These patients were divided into two groups: 73 patients who developed septic shock were assigned to the septic shock group, while the remaining 102 patients were assigned to the sepsis group. Then, the demographic, clinical and laboratory data were recorded, and the predictive values of PCT, TEG and PLT count for the development of septic shock were analyzed. RESULTS: Compared to the sepsis group, the septic shock group had statistically lower PLT count and TEG measurements in the R value, K value, α angle, maximum amplitude, and coagulation index, but had longer prothrombin time (DT), longer activated partial thromboplastin time (APTT), and higher PCT levels. Furthermore, the Sequential Organ Failure Assessment (SOFA) score was higher in the septic shock group. The multivariate logistic regression analysis revealed that PCT, TEG and PLT count were associated with the development of septic shock. The area under the curve analysis revealed that the combined measurement of PCT, TEG and PLT count can be used to predict the development of septic shock with higher accuracy, when compared to individual measurements. CONCLUSION: The combined measurement of PCT, TEG and PLT count is a novel approach to predict the development of septic shock in high-risk patients.