Kurarinone alleviated Parkinson's disease via stabilization of epoxyeicosatrienoic acids in animal model.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders and is characterized by loss of dopaminergic neurons in the substantia nigra (SN), causing bradykinesia and rest tremors. Although the molecular mechanism of PD is still not fully understood, neuroinflammation has a key role in the damage of dopaminergic neurons. Herein, we found that kurarinone, a unique natural product from Sophora flavescens, alleviated the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced behavioral deficits and dopaminergic neurotoxicity, including the losses of neurotransmitters and tyrosine hydroxylase (TH)-positive cells (SN and striatum [STR]). Furthermore, kurarinone attenuated the MPTP-mediated neuroinflammation via suppressing the activation of microglia involved in the nuclear factor kappa B signaling pathway. The proteomics result of the solvent-induced protein precipitation and thermal proteome profiling suggest that the soluble epoxide hydrolase (sEH) enzyme, which is associated with the neuroinflammation of PD, is a promising target of kurarinone. This is supported by the increase of plasma epoxyeicosatrienoic acids (sEH substrates) and the decrease of dihydroxyeicosatrienoic acids (sEH products), and the results of in vitro inhibition kinetics, surface plasmon resonance, and cocrystallization of kurarinone with sEH revealed that this natural compound is an uncompetitive inhibitor. In addition, sEH knockout (KO) attenuated the progression of PD, and sEH KO plus kurarinone did not further reduce the protection of PD in MPTP-induced PD mice. These findings suggest that kurarinone could be a potential natural candidate for the treatment of PD, possibly through sEH inhibition.

Endovascular thrombectomy versus standard bridging thrombolytic with endovascular thrombectomy within 4·5 h of stroke onset: an open-label, blinded-endpoint, randomised non-inferiority trial.

BACKGROUND: The benefit of combined treatment with intravenous thrombolysis before endovascular thrombectomy in patients with acute ischaemic stroke caused by large vessel occlusion remains unclear. We hypothesised that the clinical outcomes of patients with stroke with large vessel occlusion treated with direct endovascular thrombectomy within 4·5 h would be non-inferior compared with the outcomes of those treated with standard bridging therapy (intravenous thrombolysis before endovascular thrombectomy). METHODS: DIRECT-SAFE was an international, multicentre, prospective, randomised, open-label, blinded-endpoint trial. Adult patients with stroke and large vessel occlusion in the intracranial internal carotid artery, middle cerebral artery (M1 or M2), or basilar artery, confirmed by non-contrast CT and vascular imaging, and who presented within 4·5 h of stroke onset were recruited from 25 acute-care hospitals in Australia, New Zealand, China, and Vietnam. Eligible patients were randomly assigned (1:1) via a web-based, computer-generated randomisation procedure stratified by site of baseline arterial occlusion and by geographic region to direct endovascular thrombectomy or bridging therapy. Patients assigned to bridging therapy received intravenous thrombolytic (alteplase or tenecteplase) as per standard care at each site; endovascular thrombectomy was also per standard of care, using the Trevo device (Stryker Neurovascular, Fremont, CA, USA) as first-line intervention. Personnel assessing outcomes were masked to group allocation; patients and treating physicians were not. The primary efficacy endpoint was functional independence defined as modified Rankin Scale score 0-2 or return to baseline at 90 days, with a non-inferiority margin of -0·1, analysed by intention to treat (including all randomly assigned and consenting patients) and per protocol. The intention-to-treat population was included in the safety analyses. The trial is registered with ClinicalTrials.gov, NCT03494920, and is closed to new participants. FINDINGS: Between June 2, 2018, and July 8, 2021, 295 patients were randomly assigned to direct endovascular thrombectomy (n=148) or bridging therapy (n=147). Functional independence occurred in 80 (55%) of 146 patients in the direct thrombectomy group and 89 (61%) of 147 patients in the bridging therapy group (intention-to-treat risk difference -0·051, two-sided 95% CI -0·160 to 0·059; per-protocol risk difference -0·062, two-sided 95% CI -0·173 to 0·049). Safety outcomes were similar between groups, with symptomatic intracerebral haemorrhage occurring in two (1%) of 146 patients in the direct group and one (1%) of 147 patients in the bridging group (adjusted odds ratio 1·70, 95% CI 0·22-13·04) and death in 22 (15%) of 146 patients in the direct group and 24 (16%) of 147 patients in the bridging group (adjusted odds ratio 0·92, 95% CI 0·46-1·84). INTERPRETATION: We did not show non-inferiority of direct endovascular thrombectomy compared with bridging therapy. The additional information from our study should inform guidelines to recommend bridging therapy as standard treatment. FUNDING: Australian National Health and Medical Research Council and Stryker USA.

A 3D-printed analytical device seamlessly integrating sample treatment for electrochemical detection of IAA in Marchantia polymorpha.

Because of the pivotal point of Marchantia polymorpha (M. polymorpha) in plant evolution, its auxin (mainly indole-3-acetic acid, IAA) levels could provide useful evidence for the study of the evolution of IAA. However, M. polymorpha could not be easily pretreated for electrochemical detection because they are at the entry level of land plants. Herein, we designed a three-dimensional (3D)-printed analytical device for seamless integration of sample treatment and electrochemical detection. Specifically, the electrochemical cell could be used as a mortar in which a tiny plant sample could be ground with a 3D-printed pestle, followed by mixing with the buffer solution under vibration for electrochemical detection of IAA with a disposable working electrode at the bottom of the cell. Using our strategy, the limits of quantification could reach 0.05 µmol L-1 after optimization of parameters. We were able to demonstrate that IAA in different tissues of wild-type and mutant M. polymorpha could be successfully differentiated after they were treated with the 3D-printed analytical device. The obtained results were comparable to the samples blended with zirconium beads while the differences of IAA levels in different tissues of M. polymorpha agreed well with previous reports. This study suggested the potential of sample treatment integrated with electrochemical detection for analysis of IAA using the 3D printing techniques and their possible applications in the research of plants and other fields.

Calibrating an unfocused plenoptic camera based on parameters grouping and the light field structure point.

Accurately calibrating an unfocused plenoptic camera is essential to its applications. Rapid progress has been made in this area in the past decades. In this paper, detailed analysis is first performed toward the state-of-the-art projection model. Based on the analysis, parameters in the projection model are divided into two groups. Then, based on the parameter analysis, a new, to the best of our knowledge, form of the projection model, together with a new image feature light field structure point (LF-structure-point), is proposed. The LF-structure-point provides a completely non-redundant representation of the signal structure of the recorded light field raw data and induces a virtual space, "light field structure space," which is related to the real physical space by a 3D-to-3D projective transformation. The extracting algorithm of the LF-structure-point is also presented. Finally, based on the 3D-to-3D projective transformation and parameter grouping, a simple two-step calibration method using the LF-structure-point as the input data is then proposed and achieves satisfactory experimental results.

PNP Nanofluidic Transistor with Actively Tunable Current Response and Ionic Signal Amplification.

Inspired by electronic transistors, electric field gating has been adopted to manipulate ionic currents of smart nanofluidic devices. Here, we report a PNP nanofluidic bipolar junction transistor (nBJT) consisting of one polyaniline (PANI) layer sandwiched between two polyethylene terephthalate (PET) nanoporous membranes. The PNP nBJT exhibits three different responses of currents (quasi-linear, rectification, and sigmoid) due to the counterbalance between surface charge distribution and base voltage applied in the nanofluidic channels; thus, they can be switched by base voltage. Four operating modes (cutoff, active, saturation, and breakdown mode) occur in the collector response currents. Under optimal conditions, the PNP nBJT exhibits an average current gain of up to 95 in 100 mM KCl solution at a low base voltage of 0.2 V. The present nBJT is promising for fabrication of nanofluidic devices with logical-control functions for analysis of single molecules.

Surface Reconstruction of an FeNi Foam Substrate for Efficient Oxygen Evolution.

Designing earth-abundant electrocatalysts that are highly active, low-cost, and stable for the oxygen evolution reaction (OER) is crucial for electrochemical water splitting. However, in conventional electrode fabrication strategies, NiFe layered double hydroxide (NiFe LDH) catalysts are usually coated onto substrates as external components, which suffers from poor conductivity, easily detaches from the substrate, and hinders their long-term utilization. Herein, the surface-reconstruction strategy is used to synthesize in situ autologous NiFe LDH to increase the surficial active sites numbers. The FeNi foam (FNF) serves as both the metal source and substrate, and the obtained NiFe LDH nanosheets (NSs) are firmly anchored in the monolithic FNF. What needs to be emphasized is that the strategy does not involve any high-temperature or high-pressure processes, apart from a cost-effective etching and a specified drying treatment. The nanostructure of NiFe LDH and the synergistic effect between Fe and Ni simultaneously lead to an enhanced catalytic effect for the OER. Remarkably, the sr-FNF46 requires only an ultralow overpotential of 283 mV to achieve a current density of 100 mA cm-2 for the OER in 1 M KOH electrolyte, and exhibits excellent stability. Thus, the obtained electrode holds promise for electrocatalytic applications. Finally, the formation mechanism of NiFe LDH NSs due to surface reconstruction is investigated and discussed in detail.

Diagnostic Performance of Dynamic Susceptibility Contrast-Enhanced Perfusion-Weighted Imaging in Differentiating Recurrence From Radiation Injury in Postoperative Glioma: A Meta-analysis.

PURPOSE: It is important to differentiate between radiation injury (RI) and tumor recurrence (TR) in patients with glioma after surgery and radiotherapy. Our objective was to evaluate the use of dynamic susceptibility contrast-enhanced perfusion-weighted imaging to distinguish between TR and RI in patients with glioma. METHODS: Relevant studies published until October 2021 were identified in the PubMed, Embase, and Cochrane Library databases. Stata v12.0 and RevMan 5.3 were used for meta-analysis. RESULTS: In total, the meta-analysis incorporated 13 retrospective studies that included 513 patients with 522 lesions. Among the 522 lesions, 329 lesions were TRs and 193 lesions were RIs. The pooled relative cerebral blood volume value was significantly greater in the TR group ( P < 0.00001) with significant heterogeneity ( I2 = 88%). The pooled sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were 83% (95 confidence interval [CI], 77%-88%), 85% (95 CI, 77%-91%), 5.60 (95 CI, 3.61-8.70), and 0.20 (95% CI, 0.14-0.27), respectively. The heterogeneity of sensitivity ( I2 = 33.18%), specificity ( I2 = 24.01%), PLR ( I2 = 0.00%), and NLR ( I2 = 6.68%) is not significant. The area under the receiver operating characteristic curve was 0.91 (95% CI, 0.88-0.93). The 3.0 T magnetic resonance imaging, high-grade glioma, and Europe/America patient subgroups showed PLR greater than 5 and NLR less than 0.2. There was no significant indication of publication bias in the analysis ( P = 0.496). CONCLUSIONS: It is concluded that dynamic susceptibility contrast-enhanced perfusion-weighted imaging is effective for the diagnostic differentiation between TR and RI in patients with glioma.

[Anti-osteoarthritis components and mechanism of Fufang Duzhong Jiangu Granules].

Osteoarthritis is a common disease characterized by degenerative lesions of articular cartilage in the elderly.Fufang Duzhong Jiangu Granulues(FDJG), a classical prescription for the treatment of osteoarthritis, has the effects of nourishing liver and kidney, nourishing blood and sinew, and dredging collaterals and relieving pain.In this study, molecular simulation technology was combined with molecular biology methods to explore and verify the potential pharmacodynamic substances and molecular mechanism of FDJG in the treatment of osteoarthritis.Arachidonic acid(AA) metabolic pathway is a typical anti-inflammatory pathway, and secretory phospholipase A2 group ⅡA(sPLA2-ⅡA), 5-lipoxygenase(5-LOX), cyclooxygenase-2(COX-2), and leukotriene A4 hydrolase(LTA4 H) are the key targets of the pathway.Therefore, in this study, based on the pharmacophores and molecular docking models of the four key targets in AA pathway, a total of 1 522 chemical components in 12 medicinals of FDJG were virtually screened, followed by weighted analysis of the screening results in combination with the proportions of the medicinals in the prescription.The results showed that mainly 73 components in the preparation could act on the above four targets, suggesting they might be the potential anti-osteoarthritis components of FDJG.Considering the predicted effectiveness, availability, and compatibility of the medicinals, coniferyl ferulate, olivil, and baicalin were selected for further verification.Specifically, lipopolysaccharide(LPS)-induced RAW264.7 inflammatory cell model was used to verify the anti-inflammatory activity of the three components.The results showed that the three can effectively inhibit the release of NO, supporting the above selection.In addition, targets 5-LOX, COX-2, and LTA4 H had high activity, which suggested that they may be the key anti-osteoarthritis targets of FDJG.The comprehensive activity values of Eucommiae Cortex, Achyranthis Bidentatae Radix, Ginseng Radix et Rhizoma, Lycii Fructus, and Astragali Radix were much higher than that of other medicinals in the prescription, indicating that they may be the main effective medicinals in FDJG acting on the AA pathway.In this study, the potential anti-osteoarthritis components of FDJG were obtained.Moreover, it was clarified that the anti-osteoarthritis mechanism of FDJG was to act on LOX and COX pathway in AA metabolic pathway, which provided a reference for the study of pharmacodynamic substances and molecular mechanism of FDJG.

[Quality assessment of different forms of Cervi Cornu Pantotrichum based on content of free amino acids].

In this study, we analyzed the composition and content of 25 free amino acids in 32 batches of different forms of Cervi Cornu Pantotrichum(CCP; one-branched, two-branched, and three-branched) from 15 producing areas. The clustering analysis and orthogonal partial least squares discriminant analysis(OPLS-DA) were performed based on the content of 25 free amino acids. Potential differential metabolites were identified based on VIP value. The results showed that there were 25 free amino acids in CCP, and the average content of essential, non-essential, and total amino acids was 6.13, 32.99, and 39.12 mg·g~(-1), respectively. The clustering analysis and OPLS-DA demonstrated that 25 free amino acids had different content among the three forms of CCP, of which two-branched CCP samples were separately gathered into a group. Five differential components, including glutamic acid, tryptophan, ornithine, γ-aminobutyric acid, and hydroxylysine, were screened out as potential quality markers for the identification of different forms of CCP. This study provides a theoretical basis for the quality evaluation, processing, and utilization of different forms of CCP.

[Detection of chondroitin sulfate in Cervi Cornu Pantotrichum and Cervi Cornu of different specifications and its application in quality evaluation].

The present study comprehensively compared the content of chondroitin sulfate in Cervi Cornu Pantotrichum(CCP) and Cervi Cornu(CC) of different specifications and explored the feasibility of chondroitin sulfate as an indicator to distinguish between CCP and CC. Twenty-two batches of CCP of different specifications(two-branched velvet antler and three-branched velvet antler) from 15 habitats, CC from 6 habitats, and 60 batches of CCP slices prepared from different parts(wax slices, powder slices, gauze slices, and bone slices) were collected. High-performance liquid chromatography(HPLC) was used to determine chondroitin sulfate content in CCP and CC of different specifications. Cluster analysis was used to classify CCP slices of different specifications. The results showed that CCP contained abundant chondroitin sulfate. The average content of chondroitin sulfate was 2.35 mg·g~(-1) in two-branched velvet antler and 1.79 mg·g~(-1) in three-branched velvet antler, significantly higher than 0.11 mg·g~(-1) in CC. Chondroitin sulfate content in wax slices, powder slices, gauze slices, and bone slices were 7.81, 8.39, 1.33, and 0.54 mg·g~(-1), respectively. Cluster analysis showed that gauze slices and bone slices could be clustered into one category and distinguished from wax slices and powder slices. CCP slices prepared from different parts could be separated well through chondroitin sulfate content. Based on the five principles of Q-marker selection, chondroitin sulfate can be used as a potential Q-marker for the identification of CCP and CC, as well as a potential quality indicator for CCP slices of different specifications(wax slices, powder slices, gauze slices, and bone slices). This research provides data support for CCP quality evaluation.

Frailty as a predictor of mortality among patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: A large number of studies have explored the association between frailty and mortality among COVID-19 patients, with inconsistent results. The aim of this meta-analysis was to synthesize the evidence on this issue. METHODS: Three databases, PubMed, Embase, and Cochrane Library, from inception to 20th January 2021 were searched for relevant literature. The Newcastle-Ottawa Scale (NOS) was used to assess quality bias, and STATA was employed to pool the effect size by a random effects model. Additionally, potential publication bias and sensitivity analyses were performed. RESULTS: Fifteen studies were included, with a total of 23,944 COVID-19 patients, for quantitative analysis. Overall, the pooled prevalence of frailty was 51% (95% CI: 44-59%). Patients with frailty who were infected with COVID-19 had an increased risk of mortality compared to those without frailty, and the pooled hazard ratio (HR) and odds ratio (OR) were 1.99 (95% CI: 1.66-2.38) and 2.48 (95% CI: 1.78-3.46), respectively. In addition, subgroup analysis based on population showed that the pooled ORs for hospitalized patients in eight studies and nursing home residents in two studies were 2.62 (95% CI: 1.68-4.07) and 2.09 (95% CI: 1.40-3.11), respectively. Subgroup analysis using the frailty assessment tool indicated that this association still existed when using the clinical frailty scale (CFS) (assessed in 6 studies, pooled OR = 2.88, 95% CI: 1.52-5.45; assessed in 5 studies, pooled HR = 1.99, 95% CI: 1.66-2.38) and other frailty tools (assessed in 4 studies, pooled OR = 1.98, 95% CI: 1.81-2.16). In addition, these significant positive associations still existed in the subgroup analysis based on study design and geographic region. CONCLUSION: Our study indicates that frailty is an independent predictor of mortality among patients with COVID-19. Thus, frailty could be a prognostic factor for clinicians to stratify high-risk groups and remind doctors and nurses to perform early screening and corresponding interventions urgently needed to reduce mortality rates in patients infected by SARS-CoV-2.

Horseshoe kidney with PLA2R-positive membranous nephropathy.

BACKGROUND: Horseshoe kidney (HSK) is a common congenital defect of the urinary system. The most common complications are urinary tract infection, urinary stones, and hydronephrosis. HSK can be combined with glomerular diseases, but the diagnosis rate of renal biopsy is low due to structural abnormalities. There are only a few reports on HSK with glomerular disease. Here, we have reported a case of PLA2R-positive membranous nephropathy occurring in a patient with HSK. CASE PRESENTATION: After admission to the hospital due to oedema of both the lower extremities, the patient was diagnosed with nephrotic syndrome due to abnormal 24-h urine protein (7540 mg) and blood albumin (25 g/L) levels. Abdominal ultrasonography revealed HSK. The patient's brother had a history of end-stage renal disease due to nephrotic syndrome. Therefore, the patient was diagnosed with PLA2R-positive stage II membranous nephropathy through renal biopsy under abdominal ultrasonography guidance. He was administered adequate prednisone and cyclophosphamide, and after 6 months of treatment, urinary protein excretion levels significantly decreased. CONCLUSION: The risk and difficulty of renal biopsy in patients with HSK are increased due to structural abnormalities; however, renal biopsy can be accomplished through precise positioning with abdominal ultrasonography. In the literature, 20 cases of HSK with glomerular disease have been reported thus far. Because of the small number of cases, estimating the incidence rate of glomerular diseases in HSK is impossible, and the correlation between HSK and renal pathology cannot be stated. Further studies should be conducted and cases should be accumulated to elucidate this phenomenon.

Alisma genus: Phytochemical constituents, biosynthesis, and biological activities.

The genus Alisma contains 11 species distributed worldwide, of which at least two species (A. orientale [Sam.] Juzep. and A. plantago-aquatica Linn.) have been used as common herbal medicines. Secondary metabolites obtained from the genus Alisma are considered to be the material basis for the various biological functions and medicinal applications. In this review, we mainly focused on the recent investigations of secondary metabolites from plants of the genus Alisma and their biological activities, with the highlighting on the diversity of the chemical structures, the biosynthesis of interesting secondary metabolites, the biological activities, and the relationships between structures and bioactivities.

Effect of different treatments on recurrent aphthous stomatitis: laser versus medication.

Recurrent aphthous stomatitis (RAS) is a common disease with ulcers in oral cavity which may trigger chewing, speaking, and swallowing difficulties to patients. Treatment of RAS is primarily aimed at pain relief and the promotion of wound healing. However, few agents have been found to have definite effect in the management of RAS and most of the medicinal products may cause adverse reactions or other disadvantages, which makes their clinical usage questionable. The purpose of this randomized controlled clinical trial (RCT) was to assess the clinical effect of diode laser and traditional medication treatment on RAS. In this study, 56 patients were randomly assigned to two groups (n = 28). Laser group was treated using diode laser (810 nm, 1.0 W, CW, irradiation time 20 s for 3 applications) once daily for continuous 3 days. Medication group was treated with triamcinolone acetonide 0.1% three times a day until the lesion was healed. Spontaneous and functional pain level on the third day of treatment was significantly less in the laser group. Significant difference was observed with respect to healing time; however, the order of difference is small albeit of statistical significance. Diode laser with the chosen parameters had better effects on pain relief and no distinct advantage on wound healing comparing with medication. Trial registration number: ChiCTR2000030298; date of registration: 26 February 2020 (retrospectively registered).

Advances of Artificial Intelligence Application in Medical Imaging of Ovarian Cancers.

Ovarian cancer is one of the three most common gynecological cancers in the world, and is regarded as a priority in terms of women's cancer. In the past few years, many researchers have attempted to develop and apply artificial intelligence (AI) techniques to multiple clinical scenarios of ovarian cancer, especially in the field of medical imaging. AI-assisted imaging studies have involved computer tomography (CT), ultrasonography (US), and magnetic resonance imaging (MRI). In this review, we perform a literature search on the published studies that using AI techniques in the medical care of ovarian cancer, and bring up the advances in terms of four clinical aspects, including medical diagnosis, pathological classification, targeted biopsy guidance, and prognosis prediction. Meanwhile, current status and existing issues of the researches on AI application in ovarian cancer are discussed.

External and Internal Validation of a Computer Assisted Diagnostic Model for Detecting Multi-Organ Mass Lesions in CT images.

Objective We developed a universal lesion detector (ULDor) which showed good performance in in-lab experiments. The study aims to evaluate the performance and its ability to generalize in clinical setting via both external and internal validation. Methods The ULDor system consists of a convolutional neural network (CNN) trained on around 80K lesion annotations from about 12K CT studies in the DeepLesion dataset and 5 other public organ-specific datasets. During the validation process, the test sets include two parts: the external validation dataset which was comprised of 164 sets of non-contrasted chest and upper abdomen CT scans from a comprehensive hospital, and the internal validation dataset which was comprised of 187 sets of low-dose helical CT scans from the National Lung Screening Trial (NLST). We ran the model on the two test sets to output lesion detection. Three board-certified radiologists read the CT scans and verified the detection results of ULDor. We used positive predictive value (PPV) and sensitivity to evaluate the performance of the model in detecting space-occupying lesions at all extra-pulmonary organs visualized on CT images, including liver, kidney, pancreas, adrenal, spleen, esophagus, thyroid, lymph nodes, body wall, thoracic spine, etc. Results In the external validation, the lesion-level PPV and sensitivity of the model were 57.9% and 67.0%, respectively. On average, the model detected 2.1 findings per set, and among them, 0.9 were false positives. ULDor worked well for detecting liver lesions, with a PPV of 78.9% and a sensitivity of 92.7%, followed by kidney, with a PPV of 70.0% and a sensitivity of 58.3%. In internal validation with NLST test set, ULDor obtained a PPV of 75.3% and a sensitivity of 52.0% despite the relatively high noise level of soft tissue on images. Conclusions The performance tests of ULDor with the external real-world data have shown its high effectiveness in multiple-purposed detection for lesions in certain organs. With further optimisation and iterative upgrades, ULDor may be well suited for extensive application to external data.

The Attitude towards Preventive Measures and Knowledge of COVID-19 Inpatients with Severe Mental Illness in Economically Underdeveloped Areas of China.

Patients with severe mental illnesses (SMI) were at high risk of infection during Coronavirus Diseases 2019 (COVID-19) pandemic. This study examined hospitalized SMI patients' attitude and knowledge towards the COVID-19 infection. A cross-sectional survey was conducted in five psychiatric hospitals located in Gansu province, the most economically underdeveloped area in China. Patients' attitude towards preventive measures and knowledge of COVID-19 were measured by a self-report questionnaire. A total of 925 hospitalized patients with SMI were recruited. Of them, 84.8% (95%CI: 82.4%-87.1%) had positive attitudes towards preventive measures of the COVID-19 outbreak. Being married (OR: 1.55, 95%CI: 1.05-2.30) and a higher educational level (OR: 1.63, 95%CI: 1.12-2.38) were independently associated with positive attitudes towards COVID-19 preventive measures, whereas higher educational level was associated with better knowledge of the COVID-19 outbreak (ß: 0.231, P < 0.001). Patients mainly received COVID-19 relevant knowledge from public media (58.9%), followed by their clinicians (33.2%). Most hospitalized SMI patients in economically underdeveloped areas in China showed positive attitudes towards COVID-19 preventive measures. However, public health education on COVID-19 relevant knowledge by mental health professionals was inadequate to reduce the risk of transmission and infection.

Clinical Characteristics and Mutation Analyses of Ovarian Sertoli-Leydig Cell Tumors.

BACKGROUND: There are limited studies on Sertoli-Leydig cell tumors (SLCTs) and no data in the population of Chinese patients with SLCTs from the genetic level. In addition, previous studies on SLCTs have focused exclusively on mutations in the DICER1 gene and no data exists on the genetic landscape of SLCTs. METHODS: Patients with moderately or poorly differentiated SLCTs who underwent surgical resection between January 2012 and October 2018 in our institution were recruited. Whole exome sequencing was performed on formalin-fixed, paraffin-embedded tumor tissue and peripheral blood or normal tissue samples. RESULTS: Seventeen patients were recruited with 19 tumor samples. The rate of tumor-associated germline mutations was 6 of 17 (35.3%), and that of DICER1 germline mutations was 4 of 17 (23.5%). Regarding clinical relapse, patients with germline tumor-associated mutations had significantly poorer prognosis than those without (p = .007), and those with germline DICER1 mutations were relatively more likely to exhibit clinical relapse, although not to a significant degree (p = .069). Regarding somatic mutations, firstly, the subclone evolution analysis demonstrated that the two tumors on the contralateral ovary were primary tumors, respectively. Secondly, somatic mutations were most commonly found in CDC27 (10/19, 52.6%), DICER1 (4/19, 21.1%), and MUC22 (4/19, 21.1%). And the analysis of cancer cell fractions showed that DICER1 mutations were correlated with tumorigenesis of SLCTs. The rates of germline and somatic DICER1 mutations were higher in patients who were younger than 18 years than those in older patients (p = .022 and p = .001, respectively). CONCLUSION: Our study indicates that genetic testing may have important clinical significance for patients with SLCTs, particularly for younger patients. IMPLICATIONS FOR PRACTICE: Bilateral ovarian Sertoli-Leydig cell tumors were verified to be primary tumors from the genetic perspective. The rates of germline and somatic DICER1 mutations were 4 of 17 (23.5%) and 4 of 19 (21.1%), respectively. The rates of germline and somatic DICER1 mutations were higher in patients who were younger than 18 years than those in older patients (p = .022 and p = .001, respectively).

Inula japonica ameliorated bleomycin-induced pulmonary fibrosis via inhibiting soluble epoxide hydrolase.

Pulmonary fibrosis is a progressive, irreversible, and fatal fibrotic lung disease with a high mortality and morbidity, and commonly nonresponsive to conventional therapy. Inula japonica Thunb. is a traditional Chinese medicine, known as "Xuan Fu Hua" in Chinese, and has been widely applied to relieve cough and dyspnea and eliminate retained phlegm with a long history. In this study, we aimed to evaluate the anti-fibrosis effect and action mechanism of I. japonica extract (IJE) for the treatment of bleomycin (BLM)-induced pulmonary fibrosis in mice. IJE treatment significantly restored BLM-induced alterations in body weight loss and lung function decline, decreased the collagen deposition induced by BLM in lung tissues, and inhibited fibrotic and inflammatory factors, such as α-SMA, TGF-ß1, TNF-α, IL-6, COX-2, NF-κB, and GSK3ß, in a dose-dependent manner. We found that IJE could enhance the concentration of 8,9-epoxyeicosatrienoic acid (8,9-EET) and decrease concentrations of 8,9-dihydroxyeicosatrienoic acid (8,9-DHET), 11,12-DHET, and 14,15-DHET in BLM-induced mice. Meanwhile, IJE suppressed protein and mRNA expression levels of soluble epoxide hydrolase (sEH), and significantly displayed the inhibition of sEH activity with an IC50 value of 0.98 µg/mL. Our results indicated that IJE exerted remarkable anti-fibrosis effect on BLM-induced pulmonary fibrosis in mice via inhibiting sEH activity, resulting in the regulation of GSK3ß signaling pathway. Our findings revealed the underlying action mechanism of I. japonica, and suggested that I. japonica could be regarded as a candidate resource for the treatment of pulmonary fibrosis.

Clinicopathological characteristics and prognosis analysis of ovarian metastases in colorectal cancer: a single-center experience.

PURPOSE: This study aimed to improve the management of ovarian metastases (OM) in colorectal cancer (CRC) by evaluating the clinicopathological characteristics, therapeutic strategies, and prognostic factors associated with OM originating from CRC. METHODS: Medical records of patients who were histopathologically diagnosed with OM of CRC origin were reviewed from January 2011 to December 2018 in our medical center. Data related to clinicopathological characteristics, therapeutic strategies, and survival time were recorded and analyzed. Survival and prognosis analyses were carried out to identify variables significantly associated with the outcomes. RESULTS: Forty-six patients were included in the study with a median follow-up of 14 months. Premenopausal (< 50 years) and colon cancer patients were more likely to develop OM. Synchronous OM was found in 34 patients and elevated carbohydrate antigen 125 value could be seen in 67.4% of patients. Bilateral ovarian involvement (27/46, 58.8%) and combined extra-ovarian metastases (32/46, 69.6%) were common in included patients. Complete cytoreduction surgery (R0 resection) was finally achieved in 19 of included patients and 41 patients received postoperative chemotherapy. However, the overall prognosis remains poor, with a median survival time of only 12 months. In univariate analysis, histological types (P = 0.002), peritoneal metastasis (P < 0.0001), the extent of metastatic lesions (P = 0.0001), and completeness of cytoreduction surgery (P < 0.0001) were found to be closely related to prognosis. Finally, completeness of cytoreduction surgery was considered to be the independent determinant of patients' outcome (HR 0.186, 95% CI 0.047-0.727, P = 0.016) by multivariate analysis. CONCLUSIONS: In multitudinous factors, complete cytoreduction surgery (R0 resection) may provide survival benefits in patients with OM of CRC origin. Thus, it is reasonable to recommend aggressive surgery with curative intent even if extra-ovarian metastases are present. Furthermore, postoperative chemotherapy may exert a positive effect on the treatment, but needs to be confirmed by large-scale trials with more participants in the future.