Prognosis of immune checkpoint inhibitor-induced myasthenia gravis: a single center experience and systematic review.

Background: Immune checkpoint inhibitors (ICI)-induced myasthenia gravis (MG) is an uncommon but potentially fatal neurotoxicity. We aim to help physicians familiarize themselves with the clinical characteristics of ICI-induced MG, facilitating early diagnosis and prompt intervention. Methods: We searched the Chinese People's Liberation Army General Hospital medical record system from January 2017 to August 2023 for patients diagnosed with ICI-induced MG. We systematically reviewed the literature until August 2023 to identify all similar patients. We collected clinical information on these patients. Results: 110 patients were identified, 9 from our institution and 101 from case reports. In our institution, Median age was 66 years (range: 49-79 years). 6 were males. The most common was lung cancer (n = 4). All patients had no previous history of MG and received PD-1 or PD-L1 inhibitors. The median time from ICI initiation to first MG symptoms was 4 weeks (range: 2-15 weeks). ICIs were discontinued in all patients. Most patients initially received high-dose corticosteroids, and their symptoms improved. Some patients are discharged with corticosteroids maintenance therapy. In addition, 55 patients (50%) with concomitant myositis and/or myocarditis and MG-induced mortality were more common in the myositis and/or myocarditis group (10.9% vs. 34.5%, p = 0.016). Overlap of myositis with MG (OR = 3.148, p = 0.009) and anti-AChR antibody positivity (OR = 3.364, p = 0.005) were both significantly associated with poor outcomes. Conclusion: Our study reveals the prognosis of ICI-induced MG and suggests that myositis and/or myocarditis are severe comorbidities of ICI-induced MG, emphasizing the importance of early diagnosis and clinical intervention.

Construction and analysis of the immune effect of two different vaccine types based on Vibrio harveyi VgrG.

Vibrio harveyi poses a significant threat to fish and invertebrates in mariculture, resulting in substantial financial repercussions for the aquaculture sector. Valine-glycine repeat protein G (VgrG) is essential for the type VI secretion system's (T6SS) assembly and secretion. VgrG from V. harveyi QT520 was cloned and analyzed in this study. The localization of VgrG was determined by Western blot, which revealed that it was located in the cytoplasm, secreted extracellularly, and attached to the membrane. The effectiveness of two vaccinations against V. harveyi infection-a subunit vaccine (rVgrG) and a DNA vaccine (pCNVgrG) prepared with VgrG was evaluated. The findings indicated that both vaccines provided a degree of protection against V. harveyi challenge. At 4 weeks post-vaccination (p.v.), the rVgrG and pCNVgrG exhibited relative percent survival rates (RPS) of 71.43% and 76.19%, respectively. At 8 weeks p.v., the RPS for rVgrG and pCNVgrG were 68.21% and 72.71%, respectively. While both rVgrG and pCNVgrG elicited serum antibody production, the subunit vaccinated fish demonstrated significantly higher levels of serum anti-VgrG specific antibodies than the DNA vaccine group. The result of qRT-PCR demonstrated that the expression of major histocompatibility complex (MHC) class Iα, tumor necrosis factor-alpha (TNF-α), interferon γ (IFNγ), and cluster of differentiation 4 (CD4) were up-regulated by both rVgrG and pCNVgrG. Fish vaccinated with rVgrG and pCNVgrG exhibited increased activity of acid phosphatase, alkaline phosphatase, superoxide dismutase, and lysozyme. These findings suggest that VgrG from V. harveyi holds potential for application in vaccination.

Pharmacological treatment of Tourette's syndrome: from the past to the future.

Tourette's syndrome (TS) is a neuropsychiatric disease featuring tics and vocal tics, with a prevalence of approximately 1%, including 75% of the total number of male patients. TS seriously disturbs the patients' career, education, and life and brings a serious and unbearable psychological burden to the patients themselves and their families. At present, there are no specific clinical medications recommended for treating TS. Therefore, it is necessary to select the appropriate medication for symptomatic treatment based on the doctor's personal experience and the patient's symptoms, with the main goal of relieving symptoms, thus improving the patient's social skills and psychological problems. Here we conducted a comprehensive search on PubMed to review and organize the history and current status of the development of drug therapy for TS through a timeline format. We also systematically evaluated the effects of each drug for TS treatment to summarize the current problems and new research directions and to provide some ideas for clinical treatment.

Dietary Taurine Intake Affects the Growth Performance, Lipid Composition, and Antioxidant Defense of Juvenile Ivory Shell (Babylonia areolata).

In this study, an eight-week feeding trial was performed to investigate the effects of different taurine supplementation levels (0.0% as control, 1.0%, 1.5%, 2.0%, 2.5%, and 3.0%) on the growth performance, lipid composition, and antioxidant ability in juvenile ivory shells Babylonia areolata. The results showed that taurine supplementation significantly improved the specific growth rates (SGRs) and survival rates of ivory shell (except the survival rate in the 3.0% taurine diet group) (p < 0.05). The SGRs showed an increasing and then decreasing tendency with increasing dietary taurine supplementation, and the highest value was observed in the 2.0% taurine diet (2.60%/d). The taurine content in the muscle of ivory shells fed taurine-supplemented diets significantly increased when compared to the control group (p < 0.05). The profiles of C22:2n6 in the muscle of ivory shells fed taurine-supplemented diets were significantly higher than in the control group (p < 0.05), and the highest values were observed in the 2.0% taurine supplementation group. The high-density lipoprotein cholesterol (HDL-C) content in the hepatopancreas showed an increasing and then decreasing tendency with increasing dietary taurine supplementation, while the low-density lipoprotein cholesterol (LDL-C) concentration showed a decreasing tendency. Furthermore, the activities of pepsin and lipase in both the intestine and hepatopancreas significantly increased at moderate taurine supplementation levels compared to the control group (p < 0.05). Accordingly, obvious increases in the histological parameters in the intestine of ivory shells fed taurine-supplemented diets were also found. As for the antioxidant ability, the activities of the total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) showed an increasing and then decreasing tendency with increasing dietary taurine supplementation, and the highest values were observed in the 1.0% and 1.0-2.0% taurine supplementation groups, respectively; the malondialdehyde (MDA) contents significantly decreased with increasing dietary taurine supplementation (p < 0.05). The taurine intake affected the expression of four appetite-related genes in the hepatopancreas, in which orexin and NPY showed an increasing and then decreasing tendency, while leptin and cholecyatoklnin decreased with increasing dietary taurine supplementation. In conclusion, moderate taurine supplementation in an artificial diet (about 1.5-2.0%) could improve the growth performance and antioxidant ability and change the lipid composition of juvenile ivory shells.

Antibacterial Activity and Mechanisms of TroHepc2-22, a Derived Peptide of Hepcidin2 from Golden Pompano (Trachinotus ovatus).

Hepcidin, a cysteine-rich antimicrobial peptide, has a highly conserved gene structure in teleosts, and it plays an essential role in host immune response against various pathogenic bacteria. Nonetheless, few studies on the antibacterial mechanism of hepcidin in golden pompano (Trachinotus ovatus) have been reported. In this study, we synthesized a derived peptide, TroHepc2-22, from the mature peptide of T. ovatus hepcidin2. Our results showed that TroHepc2-22 has superior antibacterial abilities against both Gram-negative (Vibrio harveyi and Edwardsiella piscicida) and Gram-positive (Staphylococcus aureus and Streptococcus agalactiae) bacteria. Based on the results of a bacterial membrane depolarization assay and propidium iodide (PI) staining assay in vitro, TroHepc2-22 displayed antimicrobial activity by inducing the bacterial membrane depolarization and changing the bacterial membrane permeability. Scanning electron microscopy (SEM) visualization illustrated that TroHepc2-22 brought about membrane rupturing and the leakage of the cytoplasm for the bacteria. In addition, TroHepc2-22 was verified to have hydrolytic activity on bacterial genomic DNA in view of the results of the gel retardation assay. In terms of the in vivo assay, the bacterial loads of V. harveyi in the tested immune tissues (liver, spleen, and head kidney) were significantly reduced in T. ovatus, revealing that TroHepc2-22 significantly enhanced the resistance against V. harveyi infection. Furthermore, the expressions of immune-related genes, including tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin 1-ß (IL-1ß), IL-6, Toll-like receptor 1 (TLR1), and myeloid differentiation factor 88 (MyD88) were significantly increased, indicating that TroHepc2-22 might regulate inflammatory cytokines and activate immune-related signaling pathways. To summarize, TroHepc2-22 possesses appreciable antimicrobial activity and plays a vital role in resisting bacterial infection. The observation of our present study unveils the excellent application prospect of hepcidin as a substitute for antibiotics to resist pathogenic microorganisms in teleosts.

Laparoscopic Hepatectomy for Giant Hepatic Hemangioma Using the Involved Intrahepatic Anatomic Markers Approach.

BACKGROUND: Hepatic hemangioma has been one of the absolute indications of laparoscopic hepatectomy (LH).1 However, the risk of catastrophic intraoperative bleeding and the difficulty to control it make the laparoscopic treatment of giant hepatic hemangioma (GHH) a technical challenge for hepatobiliary surgeons.2 Herein, we presented a video of LH for GHH using the involved intrahepatic anatomic markers approach. METHODS: A 22-year-old female was referred for treatment of an intractable GHH (18 cm), which involved the left hepatic pedicle, left hepatic vein (LHV), and middle hepatic vein (MHV), resulting in the invisibility of the above intrahepatic anatomic markers on CT. The procedure was performed according to the following steps: (1) dissecting and ligating the left hepatic artery (LHA) and left portal vein (LPV) via intrafascial approach, respectively; (2) cutting the accessory LHA; (3) transecting parenchymal along the demarcation line in a caudal-to-cranial direction and exposing the involved caudal middle hepatic vein (MHV); (4) isolating and transecting the involved left hepatic duct; (5) preserving the integrity of involved MHV; (6) isolating and transecting the left hepatic vein (LHV) and splenic vein (SV); (7) mincing and extracting the specimen. This study was approved by the West China Hospital Ethics Committee and was conducted in accordance with the ethical guidelines of the Declaration of Helsinki. All treatments were performed after obtaining written informed consent from the patients. RESULTS: The operative time was 286 min, and blood loss during operation was 160 ml. This procedure ensured the integrity of MHV and maximized the residual functional hepatic volume. The histopathologic examination confirmed the hepatic cavernous hemangioma. The patient had an uneventful postoperative recovery and was discharged on the fifth day after operation. CONCLUSION: LH using the involved intrahepatic anatomic markers approach is feasible and effective for intractable GHH. Its advantages lie in decreasing the risk of disastrous hemorrhage or open conversion rate while maximizing the postoperative functional hepatic reserve.3.

Insulin-like growth factor binding protein 5b of Trachinotus ovatus and its heparin-binding motif play a critical role in host antibacterial immune responses via NF-κB pathway.

Introduction: Insulin-like growth factor binding protein 5 (IGFBP5) exerts an essential biological role in many processes, including apoptosis, cellular differentiation, growth, and immune responses. However, compared to mammalians, our knowledge of IGFBP5 in teleosts remains limited. Methods: In this study, TroIGFBP5b, an IGFBP5 homologue from golden pompano (Trachinotus ovatus) was identified. Quantitative real-time PCR (qRT-PCR) was used to check its mRNA expression level in healthy condition and after stimulation. In vivo overexpression and RNAi knockdown method were performed to evaluate the antibacterial profile. We constructed a mutant in which HBM was deleted to better understand the mechanism of its role in antibacterial immunity. Subcellular localization and nuclear translocation were verified by immunoblotting. Further, proliferation of head kidney lymphocytes (HKLs) and phagocytic activity of head kidney macrophages (HKMs) were detected through CCK-8 assay and flow cytometry. Immunofluorescence microscopy assay (IFA) and dual luciferase reporter (DLR) assay were used to evaluate the activity in nuclear factor-κB (NF-κß) pathway. Results: The TroIGFBP5b mRNA expression level was upregulated after bacterial stimulation. In vivo, TroIGFBP5b overexpression significantly improved the antibacterial immunity of fish. In contrast, TroIGFBP5b knockdown significantly decreased this ability. Subcellular localization results showed that TroIGFBP5b and TroIGFBP5b-δHBM were both present in the cytoplasm of GPS cells. After stimulation, TroIGFBP5b-δHBM lost the ability to transfer from the cytoplasm to the nucleus. In addition, rTroIGFBP5b promoted the proliferation of HKLs and phagocytosis of HKMs, whereas rTroIGFBP5b-δHBM, suppressed these facilitation effects. Moreover, the in vivo antibacterial ability of TroIGFBP5b was suppressed and the effects of promoting expression of proinflammatory cytokines in immune tissues were nearly lost after HBM deletion. Furthermore, TroIGFBP5b induced NF-κß promoter activity and promoted nuclear translocation of p65, while these effects were inhibited when the HBM was deleted. Discussion: Taken together, our results suggest that TroIGFBP5b plays an important role in golden pompano antibacterial immunity and activation of the NF-κß signalling pathway, providing the first evidence that the HBM of TroIGFBP5b plays a critical role in these processes in teleosts.

Molecular characterization and functional analysis of tartrate-resistant acid phosphatase (ACP5) gene in red drum (Sciaenops ocellatus).

Tartrate-resistant acid phosphatase (ACP5) plays an important biological function in immune defense and is highly expressed in activated macrophages, osteoclasts and dendritic cells. In teleost, the functionality of ACP5 remains to be revealed. In this study, we cloned and identified SoACP5 from red drum (Sciaenops ocellatus) and analyzed its function in vivo and in vitro. The open reading frame of SoACP5 is 1002 bp in length, encoding 333 amino acids. SoACP5 shares high sequence identities (96.70%-49.25%) with ACP5 of other species. The SoACP5 mRNA was widely distributed in collected tissues of healthy red drum, and with the maximum in gills. The expression of SoACP5 increased significantly in vivo following challenge with Edwardsiella tarda. Moreover, the recombinant SoACP5 protein (rSoACP5) was purified with his-tag band resin columns, and confirmed to have phosphatase activity which was optimal at pH 5 and 55 °C. Various metal ions (K+, Zn2+, Mn2+, Mg2+, Ca2+, Cu2+, Fe2+ and Fe3+) have different effects on phosphatase activity. rSoACP5 induced the cellular proliferation of peripheral blood leukocytes. The over-expression and knockdown of SoACP5 in vivo had a significant effect on bacterial proliferation. Furthermore, both of the antibacterial activity and phosphatase activity were decreased when the reducedSoACP5 was oxidized by H2O2. In summary, the present study indicated that SoACP5 is likely involved in host defense against bacterial infection in S. ocellatus.

Cromileptes altivelis microRNA Transcriptome Analysis upon Nervous Necrosis Virus (NNV) Infection and the Effect of cal-miR-155 on Cells Apoptosis and Virus Replication.

MicroRNAs (miRNAs) could regulate various biological processes. Nervous necrosis virus (NNV) is one of the primary germs of the Humpback grouper (Cromileptes altivelis), a commercial fish of great importance for Asian aquaculture. However, there is limited available information on the host-virus interactions of C. altivelis. miRNAs have been shown to play key roles in the host response to infection by a variety of pathogens. To better understand the regulatory mechanism of miRNAs, we constructed miRNA transcriptomes and identified immune-related miRNAs of C. altivelis spleen in response to NNV infection. Reads from the three libraries were mapped onto the Danio rerio reference genome. As a result, a total of 942 mature miRNAs were determined, with 266 known miRNAs and 676 novel miRNAs. Among them, thirty-two differentially expressed miRNAs (DEmiRs) were identified compared to the PBS control. These DEmiRs were targeted on 895 genes, respectively, by using miRanda v3.3a. Then, 14 DEmiRs were validated by qRT-PCR and showed consistency with those obtained from high-throughput sequencing. In order to study the relationship between viral infection and host miRNA, a cell line from C. altivelis brain (CAB) was used to examine the expressions of five known DEmiRs (miR-132-3p, miR-194a, miR-155, miR-203b-5p, and miR-146) during NNV infection. The results showed that one miRNA, cal-miRNA-155, displayed significantly increased expression in response to the virus infection. Subsequently, it was proved that overexpression of cal-miR-155 enhanced cell apoptosis with or without NNV infection and inhibited virus replication in CAB cells. Oppositely, the cal-miRNA-155 inhibitor markedly suppressed apoptosis in CAB cells. The results of the apoptosis-related genes mRNA expression also showed the regulation of cal-miR-155 on the apoptosis process in CAB cells. These findings verify that miR-155 might exert a function as a pro-apoptotic factor in reply to NNV stimulation in CAB cells and help us further study the molecular mechanisms of the pathogenesis of NNV in C. altivelis.

Cathepsin C (CTSC) contributes to the antibacterial immunity in golden pompano (Trachinotus ovatus).

Cathepsins, as a class of protein hydrolases, are widely found in the lysosomes of many tissues and play an essential role in various physiological activities. Cathepsin C (CTSC), a lysosomal cysteine protease, is an essential component of the lysosomal hydrolase family. In this study, we identified a CTSC from Trachinotus ovatus (TroCTSC) and analyzed its function. TroCTSC contained an ORF of 1368 bp and encoded 455 amino acids, which included three conserved catalytically active sites (Cys251, His397, and Asn419). It shares high homology (69.47%-90.77%) with the other known CTSC sequences of teleosts, which was most closely related to Seriola dumerili. TroCTSC was most abundant in the muscle, liver, and head kidney. After Vibrio harveyi infection, the expression levels of TroCTSC in liver, spleen, and head kidney were significantly up-regulated. TroCTSC was found in the cytoplasm with some of which were co-located with the lysosome. After V. harveyi stimulation, TroCTSC was translocated to nucleus in golden pompano snout (GPS) cells. In vitro, results revealed that the optimal hydrolase activity of the recombinant protein, rTroCTSC, was at 40 °C and pH 5.5. The activity of rTroCTSC was promoted by Zn2+ and Ca2+ but inhibited by Fe2+ and Cu2+. However, three mutant proteins, rTroCTSC-C251A, rTroCTSC-H397A, rTroCTSC-N419A, were dramatically reduced the proteolytic activity. Furthermore, in vivo results showed that overexpression of TroCTSC could significantly enhance body's ability to resist V. harveyi and promote the expression of proinflammatory cytokines, including interleukin 1-beta (IL-1ß), IL-6, IL-8, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α). In contrast, the interference of TroCTSC expression induced a significant increase in the number of bacteria after V. harveyi infection. Our results suggested that TroCTSC was an essential effector of the innate immune system and played a pivotal role in antibacterial immunity.

Wunderlich syndrome secondary to severe acute pancreatitis.

A 35-year-old male was diagnosed with severe acute pancreatitis (SAP). CT showed inflammation changes of the pancreas and peripancreatic tissue, known as pseudocyst formation. The patient subsequently heard a clicking noise in his abdomen, followed by left low back pain and abdominal distension with palpitation and hemodynamic instability. Blood tests showed a high white blood cell count (38.2 x 109/L) and low hemoglobin level (55 g/L). CT revealed a massive subcapsular hematoma of the left kidney that filled the left abdominal cavity.

Citation analysis on the research frontiers and evolution of enhanced recovery after surgery.

AIMS: To evaluate the research frontiers and evolution laws in the field of enhanced recovery after surgery (ERAS) and to predict the next direction of development. BACKGROUND: In recent years, the clinical applications of ERAS have been widely recognized by the medical community. Nursing work is present throughout the entire process, and nurses not only play a role in multidisciplinary coordination but also maintain independent professional characteristics. METHODS: The citation analysis method was used to analyse the research documents in the Web of Science database over the last 10 years. RESULTS: The number of documents in the field published from 2011 to 2020 increased annually. The application in colorectal surgery was the most important research frontier. From 2016 to 2020, the research frontiers were diversified. The application in colorectal surgery remains the most important research frontier, and perioperative nursing will play an important role in the future. CONCLUSIONS: This study used citation analysis to analyse the research frontiers and evolution of ERAS in the last 10 years. IMPLICATIONS FOR NURSING MANAGEMENT: This research will help nursing managers to carry out research and clinical promotion plans in the ERAS field and guide the transformation of scientific research achievements into nursing practice.

Association between physical activity and online sexual objectification experience: The mediating role of body-image depression.

Objective: With the popularization and development of online media technology, more and more women are paying attention to their body image and physical behavior. The purpose of this study was to investigate the effect of online sexual objectification experience on the physical activity of female college students and verify the mediating role of body-image depression between them. Methods: A cross-sectional convenient sample of 882 female college students from four universities in Hubei Province completed an online survey, and the Online Sexual Objectification Experience Scale (OSOES), the Body-Image Depression Questionnaire, and the Physical Activity Rating Scale (PARS) were used to collect the data. The mediating effect of the association between online sexual objectification experience and physical activity, was examined using the process procedure in SPSS and the bootstrap method. Results: Online sexual objectification experience was significantly positively correlated with physical activity (r = 0.420, p < 0.01). Body-image depression was significantly negatively correlated with online sexual objectification experience and physical activity (r = -0.484, p < 0.01; r = -0.569, p < 0.01). Online sexual objectification experience can affect physical activity directly (ß = 6.49, p < 0.001, effect value 44.97%) and also indirectly through body-image depression (ß = 7.95, p < 0.001, effect value 55.03%); there were significant differences between major and education-level categories in body-image depression and physical activity. Conclusion: Both online sexual objectification experience and body-image depression can promote physical activity among female college students, and body-image depression has a mediating effect between online sexual objectification experience and physical activity.

Ly-6D of Japanese flounder (Paralichthys olivaceus) functions as a complement regulator and promotes host clearance of pathogen.

The Lymphocyte antigen-6 (Ly-6) superfamily has been considered to play an important role in the innate immunity of mammals. The functions of Ly-6 proteins are diverse since their low sequence homology. Currently, the function of Ly-6D, a member of Ly-6 family proteins, is completely unknown in teleost. In the present study, we identified and characterized a Ly-6D homologue (named PoLy-6D) from the teleost fish Paralichthys olivaceus and examined its immune function. PoLy-6D possesses a hydrophobic signal peptide, a LU domain including a conserved "LXCXXC" motif in N-terminus and a "CCXXXXCN" motif in C-terminus. Under normal physiological condition, PoLy-6D expression distributes in all the examined tissues, the highest three tissues are successively spleen, head kidney, and blood. When infected by extracellular and intracellular bacterial pathogens and viral pathogen, PoLy-6D expression was induced and the patterns vary with different types of microbial pathogens infection and different immune tissues. In vitro experiment showed recombinant PoLy-6D (rPoLy-6D) inhibited the lysis of rabbit red blood cells by serum and selectively improved bacterial survival in serum. After serum were treated by antibody of rPoLy-6D, bacteriostatic effect of serum was obviously enhanced. These results indicate the importance of PoLy-6D as a complement regulator. rPoLy-6D possessed the binding activity to multiple bacteria but did not exhibit antimicrobial activities. The interaction between rPoLy-6D and bacteria suggests that PoLy-6D is involved in host clearance of pathogens probably by serving as a receptor for pathogens. Overexpression of PoLy-6D in vivo promoted the host defense against invading E. piscicida. These findings add new insights into the regulation mechanism of the complement system in teleost and emphasize the importance of Ly-6D products for the control of pathogen infection.

Demystifying the Dark Web Opioid Trade: Content Analysis on Anonymous Market Listings and Forum Posts.

BACKGROUND: Opioid use disorder presents a public health issue afflicting millions across the globe. There is a pressing need to understand the opioid supply chain to gain new insights into the mitigation of opioid use and effectively combat the opioid crisis. The role of anonymous online marketplaces and forums that resemble eBay or Amazon, where anyone can post, browse, and purchase opioid commodities, has become increasingly important in opioid trading. Therefore, a greater understanding of anonymous markets and forums may enable public health officials and other stakeholders to comprehend the scope of the crisis. However, to the best of our knowledge, no large-scale study, which may cross multiple anonymous marketplaces and is cross-sectional, has been conducted to profile the opioid supply chain and unveil characteristics of opioid suppliers, commodities, and transactions. OBJECTIVE: We aimed to profile the opioid supply chain in anonymous markets and forums via a large-scale, longitudinal measurement study on anonymous market listings and posts. Toward this, we propose a series of techniques to collect data; identify opioid jargon terms used in the anonymous marketplaces and forums; and profile the opioid commodities, suppliers, and transactions. METHODS: We first conducted a whole-site crawl of anonymous online marketplaces and forums to solicit data. We then developed a suite of opioid domain-specific text mining techniques (eg, opioid jargon detection and opioid trading information retrieval) to recognize information relevant to opioid trading activities (eg, commodities, price, shipping information, and suppliers). Subsequently, we conducted a comprehensive, large-scale, longitudinal study to demystify opioid trading activities in anonymous markets and forums. RESULTS: A total of 248,359 listings from 10 anonymous online marketplaces and 1,138,961 traces (ie, threads of posts) from 6 underground forums were collected. Among them, we identified 28,106 opioid product listings and 13,508 opioid-related promotional and review forum traces from 5147 unique opioid suppliers' IDs and 2778 unique opioid buyers' IDs. Our study characterized opioid suppliers (eg, activeness and cross-market activities), commodities (eg, popular items and their evolution), and transactions (eg, origins and shipping destination) in anonymous marketplaces and forums, which enabled a greater understanding of the underground trading activities involved in international opioid supply and demand. CONCLUSIONS: The results provide insight into opioid trading in the anonymous markets and forums and may prove an effective mitigation data point for illuminating the opioid supply chain.

Pharmacokinetics and Metabolism Research of Shenkang Injection in Rats Based on UHPLC-MS/MS and UHPLC-Q-Orbitrap HRMS.

PURPOSE: Shenkang injection, a traditional Chinese herbal prescription, had been widely used in renal disease due to its perfect curative effect. In this research, a novel, sensitive, accurate and rapid liquid chromatography-tandem mass spectrometric method was developed to simultaneously detect the seven active ingredients in rat plasma of Shenkang injection and investigate its pharmacokinetic behaviors with metabolism profiling meanwhile. METHODS: For accurate pharmacokinetic quantitation, a WATERS ACQUITY UPLC® BEH C18 column was used to perform a separation and acetonitrile-water (0.1% formic acid) was selected as mobile phase for gradient elution with a flow rate of 0.20 mL/min. A heated electrospray ionization with selective reaction monitoring mode was used to monitor the precursor-product ion transitions for all the analytes and IS. RESULTS: They all showed good linearity over a wide concentration range (r>0.996 3) and the lower limit of quantification (LLOQ) was 0.1-1.0 ng/mL for analytes. The validation parameters were all within the acceptable limits. Furthermore, for metabolism profiling study, metabolites of the seven ingredients were identified from the rat plasma based on the accurate mass and fragment ions. The metabolic pathways mainly focus on reduction, dehydration and conjugation. CONCLUSION: This study provided an overview of disposition of Shenkang injection, which is highly instructive for better understanding the effectiveness and toxicity of this drug.

Gap-matching algorithm with the impCEEMDAN in scanning white-light interference microscopy.

Coherence scanning interferometry (CSI) is a common optical measurement method for measuring three-dimensional surface profiles. However, batwings and ghost steps are common obstacles in CSI. In this paper, we proposed a gap-matching algorithm with the improved complete ensemble empirical mode decomposition with adaptive noise (impCEEMDAN) to solve the above two obstacles without any priori knowledge of the surface geometry from the tested sample. A micro-component with 500 nm and 1200 nm step heights and a 10 µm standard step of were used as test samples to evaluate the accuracy of the proposed method. Simulations and experimental results show that this approach can effectively suppress the batwings effect and eliminate the ghost steps. Experiments also confirm that the approach has good accuracy and repeatability.