Inflammatory bowel disease (IBD), which mainly includes ulcerative colitis (UC) and Crohn's disease (CD), is a group of chronic bowel diseases that are characterized by abdominal pain, diarrhea, and ...bloody stools. IBD is strongly associated with depression, and its patients have a higher incidence of depression than the general population. Depression also adversely affects the quality of life and disease prognosis of patients with IBD. The tryptophan-kynurenine metabolic pathway degrades more than 90% of tryptophan (TRP) throughout the body, with indoleamine 2,3-dioxygenase (IDO), the key metabolic enzyme, being activated in the inflammatory environment. A series of metabolites of the pathway are neurologically active, among which kynerunic acid (KYNA) and quinolinic acid (QUIN) are molecules of great interest in recent studies on the mechanisms of inflammation-induced depression. In this review, the relationship between depression in IBD and the tryptophan-kynurenine metabolic pathway is overviewed in the light of recent publications.
Pelvic radiograph (PXR) is essential for detecting proximal femur and pelvis injuries in trauma patients, which is also the key component for trauma survey. None of the currently available algorithms ...can accurately detect all kinds of trauma-related radiographic findings on PXRs. Here, we show a universal algorithm can detect most types of trauma-related radiographic findings on PXRs. We develop a multiscale deep learning algorithm called PelviXNet trained with 5204 PXRs with weakly supervised point annotation. PelviXNet yields an area under the receiver operating characteristic curve (AUROC) of 0.973 (95% CI, 0.960-0.983) and an area under the precision-recall curve (AUPRC) of 0.963 (95% CI, 0.948-0.974) in the clinical population test set of 1888 PXRs. The accuracy, sensitivity, and specificity at the cutoff value are 0.924 (95% CI, 0.912-0.936), 0.908 (95% CI, 0.885-0.908), and 0.932 (95% CI, 0.919-0.946), respectively. PelviXNet demonstrates comparable performance with radiologists and orthopedics in detecting pelvic and hip fractures.
We investigate the integer Hall conductivity and longitudinal conductivity of silicene under the magnetic field, electric field, and exchange field in this paper. We focus not only on the case of ...low-temperature and
δ
-function impurities (i.e., independent of the scattering momentum), which only exist the intra-Landau level transition, but also on the case of inter-Landau level transition which also with the non-elastic scattering. The resulting longitudinal conductivity is very different from the intra-Landau level one at low-temperature. The expressions of the Hall conductivity, longitudinal conductivity, valley contributed Hall conductivity, and the spin or valley Hall conductivity are deduced in this paper. We also compute the dynamical polarization under the magnetic field which is an important quantity related to many exciting and novel properties of the two-dimension materials, including the screened Coulomb scattering due to the charged impurities. The polarization function here is also related to the Landau level index under the magnetic field, and shows a step-like feature rather than the logarithmically divergent as which appears in the zero-magnetic field case, and it is also naturally related to the conductivity in silicene. The generalized Laguerre polynomial is used in both the longitudinal conductivity and dynamical polarization function under magnetic field. Our results are also valid for the silicene-like materials like the genmanene, MoS
2
.
Graphical abstract
This work proposes a simple but robust 4‐node 24‐DOF facet shell element for static analysis of small‐scale thin shell structures. To accommodate the size effects, the modified couple stress theory ...is employed as the theoretical basis. The element is constructed via two main innovations. First, the trial functions that can a priori satisfy related governing differential equations are adopted as the basic functions for formulating the element interpolations. Second, the generalized conforming theory and the penalty function method are employed to meet the C1 continuity requirement in weak sense for ensuring the computation convergence property. Several benchmarks of shells with different geometries are tested to assess the new facet shell element's capability. The numerical results reveal that the element can effectively simulate the size‐dependent mechanical behaviors of small‐scale thin shells, exhibiting satisfactory numerical accuracy and low susceptibility to mesh distortion. Moreover, as the shell element uses only six degrees of freedom per node, it can be incorporated into the commonly available finite element programs very readily.
Expanding bile leaks after blunt liver trauma require more aggressive treatment than contained bile leaks. In this retrospective study approved by institution review board, we analyzed if ...non-invasive contrast-enhanced magnetic resonance cholangiography (CEMRC) using hepatocyte-specific contrast agent (gadoxetic acid disodium) could detect and characterize traumatic bile leaks. Between March 2012 and December 2014, written informed consents from 22 included patients (17 men, 5 women) with a median age of 24.5 years (IQR 21.8, 36.0 years) were obtained. Biliary tree visualization and bile leak detection on CEMRC acquired at 10, 20, 30, 90 minutes time points were independently graded by three radiologists on a 5-point Likert scale. Intraclass Correlation (ICC) was computed as estimates of interrater reliability. Accuracy was measured by area under receiver operating characteristic curves (AUROC). Biliary tree visualization was the best on CEMRC at 90 minutes (score 4.30) with excellent inter-rater reliability (ICC = 0.930). Of 22 CEMRC, 15 had bile leak (8 expanding, 7 contained). The largest AUROC of bile leak detection by three radiologists were 0.824, 0.914, 0.929 respectively on CEMRC at 90 minutes with ICC of 0.816. In conclusion, bile leaks of blunt liver trauma can be accurately detected and characterized on CEMRC.
Background
The incidence of biliary events (BE) following percutaneous cholecystostomy (PC) in acute cholecystitis (AC) patients is high. Therefore, definitive laparoscopic cholecystectomy (LC) is ...recommended. We aimed to investigate the optimal timing of LC following PC with regard to the clinical course and pathological findings.
Methods
All 744 AC patients with PC were included. The incidence and median number of BE were investigated with the concept of competing risks. The 344 patients with interval LC were divided into two groups based on the pathological findings of resected gallbladders: the acute/acute‐and‐chronic group (AANC group) (n = 221) and the chronic group (n = 123). A comparative analysis of the demographic data and perioperative outcomes was performed.
Results
Among the 744 AC patients with PC, 142 patients experienced recurrent BE. The cumulative incidence of BE was 26.6%, and the median time to recurrence was 67.5 days. The PC‐to‐LC days of the chronic group were longer than those of the AANC group (73.51 vs 63.00, P < .001). The multivariate analysis indicated that the operation time was longer in the AANC group than in the chronic group (P = .040).
Conclusion
In terms of the clinical course and sequential pathological changes in the gallbladder, a 9‐ to 10‐week interval after PC is the optimal timing for LC.
Highlight
Hung and colleagues performed a retrospective study to determine the optimal timing of laparoscopic cholecystectomy following percutaneous cholecystostomy placement for acute cholecystitis. Based on the sequential pathological changes to the gallbladder and the risk of recurrent biliary events, 9‐10 weeks after percutaneous cholecystostomy was considered the optimal timing.
Bufo gargarizans (Cantor, 1842) (BGC), a traditional medicinal animal distributed in many provinces of China, is well known for the pharmaceutical value of Chansu and Chanpi. As traditional Chinese ...medicines (TCMs), Chansu and Chanpi, with their broad-spectrum of therapeutic applications, have long been applied to detoxification, anti-inflammation, analgesia, etc.
We critically analyzed the current evidence for the traditional uses, chemical profiles, pharmacological activity, toxicity and quality control of BGC (Bufonidae family) to provide a scientific basis for future in-depth studies and perspectives for the discovery of potential drug candidates.
All of the available information on active constituents and TCMs derived from BGC was obtained using the keywords “Bufo gargarizans”, “Chansu”, “Chanpi”, “Huachansu”, or “Cinobufacini” through different electronic databases, including PubMed, Web of Science, Chinese National Knowledge Infrastructure (CNKI), the Wanfang Database, and Pharmacopoeia of China. In addition, Chinese medicine books from different times were used to elucidate the traditional uses of BGC. Electronic databases, including the “IUCN Red List of Threatened Species”, “American Museum of Natural History” and “AmphibiaWeb Species Lists”, were used to validate the scientific name of BGC.
To date, about 118 bufadienolide monomers and 11 indole alkaloids have been identified from BGC in total. The extracts and isolated compounds exhibit a wide range of in vitro and in vivo pharmacological effects. The literature search demonstrated that the ethnomedicinal uses of BGC, such as detoxification, anti-inflammation and the ability to reduce swelling and pain associated with infections, are correlated with its modern pharmacological activities, including antitumor, immunomodulation and attenuation of cancer-derived pain. Bufadienolides and indole alkaloids have been regarded as the main active substances in BGC, among which bufadienolides have significant antitumor activity. Furthermore, the cardiotoxicity of bufadienolides was discussed, and the main molecular mechanism involves in the inhibition of Na+/K+-ATPase. Besides, with the development of modern analytical techniques, the quality control methods of BGC-derived TCMs are being improved constantly.
An increasing number of reports suggest that BGC can be regarded as an excellent source for exploring the potential antitumor constituents. However, the future antitumor research of BGC needs to follow the standard pharmacology guidelines, so as to provide comprehensive pharmacological information and aid the reproducibility of the data. Besides, to ensure the efficacy and safety of BGC-derived TCMs, it is vital to construct a comprehensive quality evaluation model on the basis of clarifying pharmacodynamic-related and toxicity-related compositions.
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Biomolecules that respond to different external stimuli enable the remote control of genetically modified cells. We report herein a sonogenetic approach that can manipulate target cell activities by ...focused ultrasound stimulation. This system requires an ultrasound-responsive protein derived from an engineered auditory-sensing protein prestin. Heterologous expression of mouse prestin containing two parallel amino acid substitutions, N7T and N308S, that frequently exist in prestins from echolocating species endowed transfected mammalian cells with the ability to sense ultrasound. An ultrasound pulse of low frequency and low pressure efficiently evoked cellular calcium responses after transfecting with prestin(N7T, N308S). Moreover, pulsed ultrasound can also noninvasively stimulate target neurons expressing prestin(N7T, N308S) in deep regions of mouse brains. Our study delineates how an engineered auditory-sensing protein can cause mammalian cells to sense ultrasound stimulation. Moreover, our sonogenetic tools will serve as new strategies for noninvasive therapy in deep tissues.
Opinion statement
Inflammatory myofibroblastic tumor (IMT), characterized by intermediate malignancy and a propensity for recurrence, has presented a formidable clinical challenge in diagnosis and ...treatment. Its pathological characteristics may resemble other neoplasms or reactive lesions, and the treatment was limited, taking chemotherapies as the only option for those inoperable. However, discovering anaplastic lymphoma kinase (ALK) protein expression in approximately 50% of IMT cases has shed light on a new diagnostic approach and application of targeted therapies. With the previous success of combating ALK
+
non-small-cell lung cancers with ALK tyrosine kinase inhibitors (TKIs), crizotinib, a first-generation ALK-TKI, was officially approved by the U.S. Food and Drug Administration in 2020, to treat unresectable ALK
+
IMT. After the approval of crizotinib, other ALK-TKIs, such as ceritinib, alectinib, brigatinib, and lorlatinib, have proven their efficacy on ALK
+
IMT with sporadic case reports. The sequential treatments of targeted therapies in may provide the insight into the choice of ALK-TKIs in different lines of treatment for unresectable ALK
+
IMT.
ObjectivesThis study aimed to investigate the availability, price, and affordability of nationally negotiated innovative anticancer medicines in China.DesignRetrospective observational study based on ...data from a nationwide medical database.Data sources/settingQuarterly data about the use of innovative anticancer medicines from 2020 to 2022 were collected from the Chinese Medicine Economic Information Network. This study covered 895 public general hospitals in 30 provincial administrative regions in China. Of the total hospitals, 299 (33.41%) were secondary and 596 (66.59%) were tertiary.Main outcome measuresThe adjusted WHO and Health Action International methodology was used to calculate the availability and affordability of 33 nationally negotiated innovative anticancer medicines in the investigated hospitals. Price is expressed as the defined daily dose cost.ResultsOn average, the total availability of 33 innovative anticancer medicines increased annually from 2020 to 2022. The median availability of all investigated medicines in tertiary hospitals from 2020 to 2022 was 24.04%, 33.60% and 37.61%, respectively, while the indicators in secondary hospitals were 4.90%, 12.54% and 16.48%, respectively. The adjusted prices of the medicines newly put in Medicare (in March 2021) decreased noticeably, with the decline rate ranging from 39.98% to 82.45% in 2021 compared with those in 2020. Most generic brands were priced much lower than the originator brands. The affordability of anticancer medicines has improved year by year from 2020 to 2022. In comparison, rural residents had lower affordability than urban residents.ConclusionsThe overall accessibility of 33 nationally negotiated innovative anticancer medicines improved from 2020 to 2022. However, the overall availability of most anticancer medicines in China remained at a low level (less than 50%). Further efforts should be made to sufficiently and equally benefit patients with cancer.
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