Search

ObjectiveTo determine the diagnostic accuracy of serological tests for coronavirus disease-2019 (COVID-19).MethodsPubMed, Embase and the Cochrane Library were searched from January 1 2020 to September 2 2022. We included studies that measured the sensitivity, specificity or both qualities of a COVID-19 serological test and a reference standard of a viral culture or reverse transcriptase polymerase chain reaction (RT–PCR). The risk of bias was assessed by using quality assessment of diagnostic accuracy studies 2 (QUADAS-2). The primary outcomes included overall sensitivity and specificity, as stratified by the methods of serological testing [enzyme-linked immunosorbent assays (ELISAs), lateral flow immunoassays (LFIAs) or chemiluminescent immunoassays (CLIAs)] and immunoglobulin classes (IgG, IgM, or both). Secondary outcomes were stratum-specific sensitivity and specificity within the subgroups, as defined by study or participant characteristics, which included the time from the onset of symptoms, testing via commercial kits or an in-house assay, antigen target, clinical setting, serological kit as the index test and the type of specimen for the RT–PCR reference test.ResultsEight thousand seven hundred and eighty-five references were identified and 169 studies included. Overall, we judged the risk of bias to be high in 47.9 % (81/169) of the studies, and a low risk of applicability concerns was found in 100% (169/169) of the studies. For each method of testing, the pooled sensitivity of the ELISAs ranged from 81 to 82%, with sensitivities ranging from 69 to 70% for the LFIAs and 77% to 79% for the CLIAs. Among the evaluated tests, IgG (80–81%)-based tests exhibited better sensitivities than IgM-based tests (66–68%). IgG/IgM-based CLIA had the highest sensitivity [87% (86–88%)]. All of the tests displayed high specificity (97–98%). Heterogeneity was observed in all of the analyses. The detection of nucleocapsid protein (77–80%) as the antigen target was found to offer higher sensitivity results than surface protein detection (66–68%). Sensitivity was higher in the in-house assays (78–79%) than in the commercial kits (47–48%).ConclusionAmong the evaluated tests, ELISA and CLIA tests performed better in terms of sensitivity than did the LFIA. IgG-based tests had higher sensitivity than IgM-based tests, and combined IgG/IgM test-based CLIA tests had the best overall diagnostic test accuracy. The type of sample, serological kit and timing of use of the specific tests were associated with the diagnostic accuracy. Due to the limitations of the serological tests, other techniques should be quickly approved to provide guidance for the correct diagnosis of COVID-19.

Background: Drug-eluting beads bronchial arterial chemoembolization (DEB-BACE) has been used in the treatment of locally advanced lung cancer and has the potential to improve outcomes and reduce recurrence. However, DEB-BACE shows a poor therapeutic effect in advanced lung cancer after failure of multiple therapies. This study assessed the effect of DEB-BACE in the treatment of progressive lung cancer with refractory obstructive atelectasis.Methods: Progressive advanced lung cancer patients with refractory obstructive atelectasis were voluntarily enrolled in this study after failure of multiple conventional therapies. Baseline information, DEB-BACE treatment process, and changes in clinical symptoms were recorded. The primary endpoints were the objective response rate (ORR) and improvement rate of dyspnea. The secondary endpoints were time-to-progression (TTP), overall survival (OS), and rate of pulmonary re-expansion. Treatment-related adverse events and serious adverse events were analyzed to assess the safety of DEB-BACE. The Cox regression model was performed to analyze the possible factors impacting prognosis of DEB-BACE.Results: DEB-BACE was successfully performed with CalliSpheres beads loaded with vinorelbine in the 20 enrolled patients. ORR and disease control rate were 80% and 85%, respectively, at the first follow-up (43.4 ± 15.26 days). The improvement rate of dyspnea was 85% and 80% at 1 week and 1 month (p < 0.0001, p < 0.0001), respectively. TTP was 41.25 ± 14.43 days and 89.55 ± 61.7 days before and after DEB-BACE, respectively; DEB-BACE delayed the progression of advanced lung cancer (p < 0.0001). OS was 238.03 ± 33.74 days (95% confidence interval: 171.9–304.16). The rate of pulmonary re-expansion was 80% at the first follow-up. The reasons for poor prognosis were tumor necrosis, longer disease duration, and pulmonary atelectasis duration (p = 0.012, p = 0.038, p = 0.029). Massive hemoptysis was observed in two cases, and one patient died of asphyxia caused by hemoptysis. Moderate hemoptysis occurred in one case. All three adverse events were considered as the result of the tumor cavity after DEB-BACE.Conclusion: DEB-BACE loaded with vinorelbine is a feasible option for progressive advanced lung cancer with obstructive atelectasis after failure of other treatments.

Objective: This study aimed to compare the resistance rates of Blattella germanica to beta-cypermethrin nanoemulsion and conventional emulsion and establish reference values via biochemical detection for conventional emulsion. Methods: We conducted experiments using subcultured Blattella germanica and applied the micro-drop method for treatment. Subsequently, the activity of metabolic enzymes was measured using spectrophotometry. Profile analysis was employed to study the resistance rates of beta-cypermethrin nanoemulsion and beta-cypermethrin emulsion. Results: The regression equation for the relationship between generation and resistance factor in Blattella germanica treated with beta-cypermethrin nanoemulsion was as follows: y1 = 0.091x1 + 0.991, with an r-value of 0.990 (F = 95.184, p = 0.01 < 0.05). Similarly, the regression equation for Blattella germanica treated with emulsion was y2 = 0.376x2 + 1.051, with an r-value of 0.993 (F = 141.094, p = 0.007 < 0.05). The comparison of slopes between these two regression equations yielded an F-value of 8.61, indicating a significant difference (p = 0.001 < 0.05). Conclusion: Our findings suggest that the resistance factor in Blattella germanica treated with beta-cypermethrin nanoemulsion differs from that treated with beta-cypermethrin emulsion. Specifically, the resistance factor of beta-cypermethrin nanoemulsion increased at a slower rate compared to beta-cypermethrin emulsion.

(1) Background: Hydroponic forage plays an increasingly important role in animal breeding during winter and spring in arid and cold regions due to its rich nutrient and good palatability. In the present study, the profiles of growth, physiological indexes, nutritional value and in vitro degradation of hydroponic forage cultivated with different salt concentration were evaluated. (2) Methods: The compound salt was extracted from soil surrounding the Tarim River Basin, and five compound salt solution treatment groups (three replicates each) with concentrations of 0%, 0.4%, 0.8%, 1.2% and 1.6% were prepared. Winter wheat seeds were selected as hydroponic forage for germination experiments, and the germination, physiological indicators, nutritional value and in vitro fermentation degradation rate were analyzed. (3) Results: The results showed that the germination and growth of hydroponic herbage were significantly (p < 0.05) inhibited by compound salt concentration higher than 0.8% from the third day. Compared with the 0% concentration group, the chlorophyll content in the 0.4% concentration group was significantly increased (p < 0.05), and contents of chlorophyll a, chlorophyll b and total chlorophyll were 729.71 mg·g−1, 223.19 mg·g−1 and 952.9 mg·g−1, respectively. The total chlorophyll content in the 0.8% and 1.2% concentration groups were significantly lower than those in the 0% and 0.4% concentration groups (p < 0.05), and in the 1.6% concentration group, the content undetected. With the increase in compound salt concentration, the contents of soluble sugar and proline were significantly increased (p < 0.05). The nutrient compositions were significantly increased (p < 0.05) under the 0.4% and 0.8% concentration groups, in which the content of crude protein in 0.4% concentration group was 15.23%. The results of gas production and fermentation parameters suggested that the 0.8% concentration group could enhance rumen fermentation characteristics. (4) Conclusions: In summary, 0.8% as the upper limit concentration and 0% to 0.4% as the optimal concentration range of compound salt can be considered for cultivating hydroponic forage wheat.

The advent of additive manufacturing (AM) in Australian small and medium-sized enterprises offers the direct benefits of time-saving and labour cost-effectiveness for Australian manufacturing to be highly competitive in global markets. Australian local businesses can tailor their products to a diverse range of customers with a quicker lead time on the sophisticated design and development of products under good quality control in the whole advanced manufacturing process. This review outlines typical AM techniques used in Australian manufacturing, which consist of vat polymerisation (VP), environmentally friendly AM, and multi-material AM. In particular, a practical case study was also highlighted in the Australian jewellery industry to demonstrate how manufacturing style is integrated into their manufacturing processes for the purpose of reducing lead time and cost. Finally, major obstacles encountered in AM and future prospects were also addressed to be well positioned as a key player in the revolutionised Industry 4.0.

Abstract Background Valgus deformity of the knee remains a complaint after total hip arthroplasty (THA) among some patients with Crowe type IV hip dysplasia. We aimed to identify the knee alignment in these patients before and after surgery, and to explore the factors contributing to postoperative knee valgus alignment. Materials and methods We retrospectively reviewed a series of Crowe type IV patients who received THA between February 2010 and May 2019 in our hospital. The patients’ medical data were collected from the hospital information system. On both preoperative and postoperative full limb length standing radiographs, the following parameters were measured: hip–knee–ankle angle (HKA), mechanical lateral distal femoral angle (mLDFA), medial proximal tibial angle, anatomical tibiofemoral angle, anatomical lateral distal femoral angle, femoral neck-shaft angle, pelvic obliquity, limb length, height and lateral distance of hip center, and femoral offset. Univariate and multivariate binary logistic regression were used to identify the factors influencing postoperative knee valgus alignment. Results A total of 64 Crowe type IV patients (87 hips) were included in the study. Overall, HKA improved from 176.54 ± 3.52° preoperatively to 179.45 ± 4.31° at the last follow-up. Those hips were subdivided into non-valgus group (≥ 177.0°, n = 65) and valgus group (

Objective To develop and evaluate a psychosocial adaptation (PSA) questionnaire of women with breast cancer treated with adjuvant endocrine therapy (AET).Design Cross-sectional study.Setting Conducted study in a tertiary care centre in China from March to June 2021.Participants Women with breast cancer who have received AET.Methods Item development and extraction were based on literature, qualitative interviews (n=16) and assessment of content validity. 300 participants were recruited to perform item analysis, internal consistency reliability and exploratory factor analysis by cross-sectional studies. Finally, test–retest, criterion validity and confirmatory factor analysis of the questionnaire were performed with 96 respondents.Results An initial questionnaire was devised. The exploratory factor analysis demonstrated four factors: emotional response (six items), self-worth (five items), physical impacts (three items) and social communication (two items). The cumulative contribution of the factors was 65.057%. Cronbach’s alpha coefficient of the questionnaire was 0.876. The correlation coefficient between the questionnaire and General Self-Efficacy Scale was 0.565 (p

BackgroundPost-stroke shoulder pain (PSSP) is characterized by shoulder pain on the hemiplegic side, which can limit physical activity in patients with stroke. Acupuncture combined with rehabilitation training (AR) has been widely used in PSSP, but the evidence of its effectiveness is still unclear.ObjectiveThe study aimed to evaluate the effect and safety of AR vs. rehabilitation training (RT) alone on PSSP.MethodsWe searched PubMed, the Cochrane Library, the Chinese Biological Medicine Database (CBM), the Chinese Scientific Journal Database (VIP), China National Knowledge Infrastructure (CNKI), and the WAN FANG database for relevant studies from their inception to February 2022. Only randomized controlled trials (RCTs) comparing the effect of AR with RT alone on PSSP were considered. The primary outcome was shoulder pain. Secondary outcomes included upper limb motor function, activities of daily living (ADL), shoulder range of motion (ROM), and adverse events (AEs). Subgroup analysis and sensitivity analysis were also conducted. Quality assessment was implemented based on Cochrane risk of bias (ROB) criteria, which consist of seven items. When more than four items in a study were judged as low ROB, the overall quality of this study was considered low risk.ResultsA total of 40 studies were included in the qualitative analysis, and 35 (87.5%) studies with 2,554 patients were included in the meta-analysis. Of the 40 studies, 14 (35.0%) were of moderate-to-high quality. The meta-analysis results showed that AR is better than RT alone in reducing shoulder pain (MD −1.32, 95% CI −1.58 to −1.07), improving upper limb motor function (MD 6.81, 95% CI 4.95–8.67), ADL (MD 11.17, 95% CI 9.44–12.91), and shoulder ROM (internal rotation: MD 10.48, 95% CI 8.14–12.83; backward extension: MD 7.82, 95% CI 6.00–9.64; anteflexion: MD 12.88, 95% CI 5.47–20.29; external rotation: MD 11.40, 95% CI 6.17–16.64; abduction: MD 16.96, 95% CI 8.61–25.31) without obvious AEs.ConclusionAR may be better than RT alone for the improvement of shoulder pain, upper limb motor function, ADL, and shoulder ROM, without obvious AEs in patients with PSSP. However, considering the clinical and statistical heterogeneity, our findings need to be interpreted with caution. More rigorous RCTs in this area should be conducted in the future.Systematic review registration[www.crd.york.ac.uk], identifier [CRD42022326763].

BackgroundPatients with MMT often face difficulties such as sleep disturbance, headaches, and difficulty in complete abstinence from drugs. Research has shown that acupuncture can mitigate side effects while attenuating methadone dependence. It also has a synergistic and attenuated effect on methadone maintenance treatment (MMT). Exploring the predictors of the efficacy of acupuncture intervention in MMT might help clinicians and patients promote acupuncture-assisted participation in MMT, and improve clinical treatment strategies for MMT.ObjectiveTo describe the effect of potential predictors on MMT after acupuncture intervention by building a decision-tree model of data from A Clinical Study of Acupuncture-assisted MMT.Design, setting, and participantsIn this randomized controlled trial, 135 patients with MMT underwent acupuncture at the Substance Dependence Department of Guangzhou Huiai Hospital in Guangzhou, Guangdong Province, China.InterventionA total of 135 patients were 1:1 randomly assigned to either an acupuncture plus routine care group (acupuncture plus methadone) or a routine group (methadone only) for 6 weeks, and followed up for 10 weeks. Sex, age, education level, route of previous opioid use, years of opioid use, and MMT time were recorded before the trial.Outcome measurements and statistical analysisAll analyses were based on the intention-to-treat (ITT) population. The two decision tree models used the change of methadone dosage and the VAS score for opioid desire as response variables, respectively, and the evaluation criteria were positive effect (decreased by ≥20%) and no effect (decreased by

ABSTRACT This study aimed to investigate the antibacterial mechanism of cefiderocol (CFDC) using data-independent acquisition quantitative proteomics combined with cellular and molecular biological assays. Numerous differentially expressed proteins related to the production of NADH, reduced cofactor flavin adenine dinucleotide (FADH2), NADPH and reactive oxygen species (ROS), iron-sulfur cluster binding, and iron ion homeostasis were found to be upregulated by CFDC. Furthermore, parallel reaction monitoring analysis validated these results. Meanwhile, we confirmed that the levels of NADH, ROS, H2O2, and iron ions were induced by CFDC, and the sensitivity of Escherichia coli to CFDC was inhibited by the antioxidant vitamin C, N-acetyl-l-cysteine, and deferoxamine. Moreover, deferoxamine also suppressed the H2O2 stress induced by CFDC. In addition, knockout of the NADH-quinone oxidoreductase genes (nuoA, nuoC, nuoE, nuoF, nuoG, nuoJ, nuoL, nuoM) in the respiratory chain attenuated the sensitivity of E. coli to CFDC far beyond the effects of cefepime and ceftazidime; in particular, the E. coli BW25113 ΔnuoJ strain produced 60-fold increases in MIC to CFDC compared to that of the wild-type E. coli BW25113 strain. The present study revealed that CFDC exerts its antibacterial effects by inducing ROS stress by elevating the levels of NADH and iron ions in E. coli. IMPORTANCE CFDC was the first FDA-approved siderophore cephalosporin antibiotic in 2019 and is known for its Trojan horse tactics and broad antimicrobial activity against Gram-negative bacteria. However, its antibacterial mechanism is not fully understood, and whether it has an impact on in vivo iron ion homeostasis remains unknown. To comprehensively reveal the antibacterial mechanisms of CFDC, data-independent acquisition quantitative proteomics combined with cellular and molecular biological assays were performed in this study. The findings will further facilitate our understanding of the antibacterial mechanism of CFDC and may provide a theoretical foundation for controlling CFDC resistance in the future.

Foxtail and broomcorn millets are the most important crops in northern China since the early Neolithic. However, little evidence is available on how people managed these two crops in the past, especially in prehistory. Previous research on major C3 crops in western Eurasia demonstrated the potential of stable carbon and nitrogen isotope analysis of charred archaeobotanical remains to reveal the management of water and manure, respectively. Here, we evaluate the feasibility of a similar approach to C4 millets. Foxtail and broomcorn millet plants grown in pots in a greenhouse under different manuring and watering regimes were analysed to test the effects of management on stable carbon and nitrogen isotope values of grains. Stable nitrogen isotope values of both millets increased as manuring level increased, ranging from 1.7 ‰ to 5.8 ‰ in different conditions; hence, it appears a feasible tool to identify manuring practices, in agreement with results from recent field studies. However, the two millets exhibit opposing trends in stable carbon isotope values as watering level increased. The shift in stable carbon isotope values of millets is also smaller than that observed in wheat grown in the same experimental environment, making it difficult to identify millet water status archaeologically. In addition, we charred millet grains at different temperatures and for varying durations to replicate macro-botanical remains recovered archaeologically, and to evaluate the offsets in carbon and nitrogen isotope values induced by charring. We found that the stable nitrogen isotope values of foxtail millet and broomcorn millet can shift up to 1–2 ‰ when charred, while the stable carbon isotope values change less than 0.3 ‰. Overall, we demonstrate that stable nitrogen isotope values of charred foxtail and broomcorn millet seeds could provide insight into past field management practices, and both carbon and nitrogen isotope values can together inform palaeodietary reconstruction.

Background: Pyroptosis is a recently identified mode of programmed inflammatory cell death that has remarkable implications for cancer development. lncRNAs can be involved in cellular regulation through various pathways and play a critical role in gastric cancer (GC). However, pyroptosis -related lncRNAs (PRlncRNAs) have been rarely studied in GC.Methods: Pyroptosis-related gene were abstracted from the literature and GSEA Molecular Signatures data resource. PRlncRNAs were obtained using co-expression analysis. LASSO Cox regression assessment was employed to build a risk model. Kaplan-Meier (KM), univariate along with multivariate Cox regression analysis were adopted to verify the predictive efficiency of the risk model in terms of prognosis. qRT-PCR was adopted to validate the expression of PRlncRNAs in GC tissues. In addition, immune cell infiltration assessment and ESTIMATE score evaluation were adopted for assessing the relationship of the risk model with the tumor immune microenvironment (TME). Finally, immune checkpoint gene association analysis and chemotherapy drug sensitivity analysis were implemented to assess the worthiness of our risk model in immunotherapy and chemotherapy of GC.Results: We identified 3 key PRlncRNAs (PVT1, CYMP-AS1 and AC017076.1) and testified the difference of their expression levels in GC tumor tissues and neighboring non-malignant tissues (p < 0.05). PRlncRNAs risk model was able to successfully estimate the prognosis of GC patients, and lower rate of survival was seen in the high-GC risk group relative to the low-GC risk group (p < 0.001). Other digestive system tumors such as pancreatic cancer further validated our risk model. There was a dramatic difference in TMB level between high-GC and low-GC risk groups (p < 0.001). Immune cell infiltration analysis and ESTIMATE score evaluation demonstrated that the risk model can be adopted as an indicator of TME status. Besides, the expressions of immunodetection site genes in different risk groups were remarkably different (CTLA-4 (r = −0.14, p = 0.010), VISTA (r = 0.15, p = 0.005), and B7-H3 (r = 0.14, p = 0.009)). PRlncRNAs risk model was able to effectively establish a connection with the sensitivity of chemotherapeutic agents.Conclusion: The 3 PRlncRNAs identified in this study could be utilized to predict disease outcome in GC patients. It may also be a potential therapeutic target in GC therapy, including immunotherapy and chemotherapy.

Van der Waals magnetic materials (vdWs) have allowed for the exploration of the two dimensional limit of magnetism, however, most vdWs are only magnetic at low temperature. Herein, the authors overcome this limitation, observing room temperature magnetic ordering in Cobalt doped graphene-like Zinc-Oxide.

Food safety risk prediction is crucial for timely hazard detection and effective control. This study proposes a novel risk prediction method for food safety called TabNet-GRA, which combines a specialized deep learning architecture for tabular data (TabNet) with a grey relational analysis (GRA) to predict food safety risk. Initially, this study employed a GRA to derive comprehensive risk values from fused detection data. Subsequently, a food safety risk prediction model was constructed based on TabNet, and training was performed using the detection data as inputs and the comprehensive risk values calculated via the GRA as the expected outputs. Comparative experiments with six typical models demonstrated the superior fitting ability of the TabNet-based prediction model. Moreover, a food safety risk prediction and visualization system (FSRvis system) was designed and implemented based on TabNet-GRA to facilitate risk prediction and visual analysis. A case study in which our method was applied to a dataset of cooked meat products from a Chinese province further validated the effectiveness of the TabNet-GRA method and the FSRvis system. The method can be applied to targeted risk assessment, hazard identification, and early warning systems to strengthen decision making and safeguard public health by proactively addressing food safety risks.

Thermoplastic polyurethane (TPU) belongs to a polyurethane family that possesses an elongation much higher than 300%, despite having low mechanical strength, which can be overcome by incorporating clay-based halloysite nanotubes (HNTs) as additives to manufacture TPU/HNT nanocomposites. This paper focuses on the co-influence of HNT content and 3D printing parameters on the mechanical properties of 3D printed TPU/HNT nanocomposites in terms of tensile properties, hardness, and abrasion resistance via fused deposition modelling (FDM). The optimum factor-level combination for different responses was determined with the aid of robust statistical Taguchi design of experiments (DoEs). Material characterisation was also carried out to evaluate the surface morphology, nanofiller dispersion, chemical structure, thermal stability, and phase behaviour corresponding to the DoE results obtained. It is evidently shown that HNT level and infill density play a significant role in impacting mechanical properties of 3D-printed TPU/HNT nanocomposites.

Abstract The tumor microenvironment plays an important role in tumor progression. Hyaluronic acid (HA), an important component of the extracellular matrix in the tumor microenvironment, abnormally accumulates in a variety of tumors. However, the role of abnormal HA accumulation in glioma remains unclear. The present study indicated that HA, hyaluronic acid synthase 3 (HAS3), and a receptor of HA named CD44 were expressed at high levels in human glioma tissues and negatively correlated with the prognosis of patients with glioma. Silencing HAS3 expression or blocking CD44 inhibited glioma cell proliferation in vitro and in vivo. The underlying mechanism was attributed to the inhibition of autophagy flux and maintaining glioma cell cycle arrest in G1 phase. More importantly, 4-methylumbelliferone (4-MU), a small competitive inhibitor of Uridine diphosphate (UDP) with the ability to penetrate the blood-brain barrier (BBB), also inhibited glioma cell proliferation in vitro and in vivo. Thus, approaches that interfere with HA metabolism by altering the expression of HAS3 and CD44 and the administration of 4-MU potentially represent effective strategies for glioma treatment.

Colitis-associated colorectal cancer (CAC) is a specific type of colorectal cancer (CRC) with high mortality and morbidity, the chronic inflammation in the intestinal mucosal is the characteristic of CAC. Chang Qing formula (CQF) is a Chinese herbal formula used clinically for the treatment of CAC with remarkable clinical efficacy, but its mechanism remains unclear. In the present work, Combined network pharmacology and transcriptomics were used to analyze the potential active ingredients and elucidate molecular mechanism of CQF in treating CAC. Firstly, the constituents migrating to blood of CQF were analyzed and identified by UPLC-Q-TOF-MS/MS, and core genes and pathways were screened by network pharmacology analysis. Encyclopedia of Genes and Genomes (KEGG) analysis showed that the IL-17 signaling pathway involved in CAC may be closely associated with the potential mechanismof action of CQF. Subsequently, the results from animal studies indicated that CQF profoundly reduced tumor numbers and tumor size in AOM/DSS mice. The RNA-seq data was analysed utilizing Ingenuity Pathway Analysis (IPA), and the results supported the idea that CQF exerts a tumour-suppressive effect via the IL-17 signalling pathway. Further studies demonstrated that CQF significantly reduced IL-17A levels, which in turn inhibited NF-κB/IL-6/STAT3 signaling cascade, suppressed MMP9 expression and promoted tumor cell apoptosis. In conclusion, the current study demonstrated that CQF remarkably improved inflammatory tumor microenvironment, and hindered the transformation of inflammation into cancer. These findings may help to design future strategies for the treatment of CAC.

The Wuji pill, also called Wuji Wan (WJW), is an effective traditional medicine for the clinical treatment of irritable bowel syndrome (IBS). It is principally composed of Rhizoma Coptidis, Fructus Evodiae Rutaecarpae, and Radix Paeoniae Alba. There have been no reports on the pharmacokinetics of WJW on IBS. Because it is more meaningful to study pharmacokinetics in relation to specific pathological conditions, our study investigated the pharmacokinetic differences of five representative components (berberine, palmatine, evodiamine, rutaecarpine, and paeoniflorin) in normal rats and chronic visceral hypersensitivity IBS (CVH-IBS) model rats after single dose and multiple doses of WJW using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Transmission electron microscopy, immunohistochemistry, and immunofluorescence were used to explore mechanisms behind the pharmacokinetic differences in terms of tight junction proteins (Occludin and ZO-1), myosin light chain kinase (MLCK), and transporters including P-glycoprotein (P-gp), multidrug resistance associated protein 1 (MRP1), and multidrug resistance associated protein 2 (MRP2) in rat colons. After a single dose, for all components except rutaecarpine, significant differences were observed between normal and model groups. Compared with normal group, T1/2 and AUC0-t of berberine and palmatine in model group increased significantly (562.5 ± 237.2 vs. 1,384.9 ± 712.4 min, 733.8 ± 67.4 vs. 1,532.4 ± 612.7 min; 5,443.0 ± 1,405.8 vs. 9,930.8 ± 2,304.5 min·ng/ml, 2,365.5 ± 410.6 vs. 3,527.0 ± 717.8 min·ng/ml), while Cl/F decreased (840.7 ± 250.8 vs. 397.3 ± 142.7 L/h/kg, 427.7 ± 89.4 vs. 288.9 ± 114.4 L/h/kg). Cmax and AUC0-t of evodiamine in model group increased significantly (1.4 ± 0.6 vs. 2.4 ± 0.7 ng/ml; 573 ± 45.3 vs. 733.9 ± 160.2 min·ng/ml), while T1/2, Tmax, Cl/F, and Vd/F had no significant difference. Tmax and AUC0-t of paeoniflorin in model group increased significantly (21.0 ± 8.2 vs. 80.0 ± 45.8 min; 15,428.9 ± 5,063.6 vs. 33,140.6 ± 5,613.9 min·ng/ml), while Cl/F decreased (110.5 ± 48.1 vs. 43.3 ± 9.5 L/h/kg). However, after multiple doses, all five components showed significant differences between normal and model groups. Moreover, these differences were related to tight junction damage and the differential expression of transporters in the colon, suggesting that dose adjustment might be required during administration of WJW in the clinical treatment of IBS.

Objective To provide a route map regarding systematic reviews (SRs) of acupuncture therapies that will meet two goals: (1) to identify areas in which more or better evidence is required and (2) to identify acupuncture applications that, although proven effective, remain underused in practice, and thus warrant more effective knowledge dissemination.Eligibility criteria We included SRs that conducted meta-analyses (MAs) of randomised controlled trials (RCTs) for this overview.Information sources We searched for SRs without language restrictions from January 2015 to November 2020 in four Chinese electronic databases and Epistemonikos database. And we also searched for newly published RCTs that were eligible for selected best SRs in PubMed, Medline, Cochrane Central Register of Controlled Trials, Embase and four Chinese electronic databases from its lasted search dates to November 2020.Synthesis of results We reanalysed the selected MAs if new primary studies were added. We used random-effect model to calculate the overall effect.Results Our search identified 120 SRs published in the last 5 years addressing acupuncture therapies across 12 therapeutic areas and 77 diseases and conditions. The SRs included 205 outcomes and involved 138 995 participants from 1402 RCTs. We constructed 77 evidence matrices, including 120 SRs and their included RCTs in the Epistemonikos database. Seventy-seven SRs represented the effect estimate of acupuncture therapies. Finally, we system summarised the areas of possible underutilisation of acupuncture therapies (high or moderate certainty evidence of large or moderate effects), and the areas of warranting additional investigation of acupuncture therapies (low or very low certainty evidence of moderate or large effects).Conclusion The evidence maps and overview of SRs on acupuncture therapies identified both therapies with substantial benefits that may require more assertive evidence dissemination and promising acupuncture therapies that require further investigation.

Background: Jaranol has shown a wide range of pharmacological activities; however, no study has yet examined in vivo toxicity. The study aimed to investigate the oral acute and sub-acute toxicity of jaranol in mice.Methods: The acute toxicity was determined by a single oral dose of jaranol (2000 mg/kg). Therein animal behaviour and mortality rate were observed for 14 days. The jaranol (50, 100 and 200 mg/kg BW·d−1) was given by gavage for 28 days daily in the sub-acute study. The mouse body weight (BW), organ weight, food, water intake, biochemical, haematological parameters, and histopathology were studied in acute and sub-acute toxicity.Results: During the acute toxicity test, a single oral dose (2000 mg/kg) jaranol did not cause significant alteration in majority of the hematological indices. However, jaranol decreased the level of serum alanine aminotransferase and aspartate aminotransferase. Those results showed that the oral lethal dose 50 (LD50) of jaranol was higher than 2000 mg/kg BW, regardless of sex. In repeated daily oral doses (50, 100 and 200 mg/kg BW·d−1), no mortality was recorded in the various experimental groups. The jaranol reduced body weight gain (200 mg/kg BW·d−1), the relative spleen weight (all doses) and serum alanine aminotransferase activity (200 mg/kg BW·d−1). On the other hand, jaranol significantly elevated red blood cell count (100 and 200 mg/kg BW·d−1) and serum creatinine levels (200 mg/kg BW·d−1). Histological study revealed that spleen bleeding was identified in 200 mg/kg jaranol-treated mice.Conclusion: Jaranol was relatively safe in Kunming Mice when repetitively administered orally in small doses for a prolonged period of time. We recommend more chronic toxicity studies and clinical trials on jaranol to ensure that its use is free of potential toxicity to humans.

Abstract. Rationale:. Prompt diagnosis of nontuberculous Mycobacterial (NTM) vertebral osteomyelitis is challenging, yet necessary to prevent serious morbidity and mortality. Here, we report 3 cases of vertebral osteomyelitis caused by NTM with imaging findings. Patient concerns:. Case 1, a 58-year-old male patient, was admitted to our hospital because of the presence of a pulmonary mass for 6 months with cough and chest pain. Case 2, a 50-year-old male patient, had fever and cough for 3 years and was diagnosed with tuberculosis. Antituberculosis treatment was ineffective, accompanied by lymph node enlargement and osteosclerotic changes involving vertebral bodies. Case 3, a 66-year-old female patient, was admitted to our hospital with a mass on the top of her head for 1 month, which ruptured in the last 2 weeks. Diagnoses:. Case 1: Sputum culture revealed Mycobacterium (M.) avium. Case 2: The final culture results of the lymph node biopsy samples were M. intracellulare. Case 3: Culture results of the sputum and pus from the abscess were M. gordon. We found sclerosing lesions in the spine in all 3 NTM patients, which were easily misdiagnosed as metastatic tumors. In 2 cases, there was bone destruction in the ilium with limbic sclerosis, and there were abscesses near the ilium and in front of the sacrum in 1 case. Interventions:. Case 1 was transferred to other specialist hospital. Case 3 received surgical treatment for cranial lesions and abscess drainage. Case 2 and case 3 received targeted treatment for nontuberculous mycobacteria in our hospital. Outcome:. The condition of case 1 was unknown. Recovery of case 2 was uneventful because of prolonged illness; however, inflammation gradually improved overall. Case 3 had no recurrence following surgical treatment. Lessons:. In our 3 cases of NTM vertebral osteomyelitis, bone lesions were often misdiagnosed as bony metastases because of the presence of multiple sclerotic lesions. Diagnoses were challenging and delayed. It is important to consider osteomyelitis by NTM when disseminated osteosclerosis with or without osteolytic bone lesions is present in conjunction with continuous inflammatory symptoms and signs. Moreover, an open biopsy of the lesion should be performed for a definitive diagnosis.

BackgroundPedigree data (family history) are indispensable for genetics studies and the assessment of individuals' disease susceptibility. With the popularity of genetics testing, the collection of pedigree data is becoming more common. However, it can be time-consuming, laborious, and tedious for clinicians to investigate all pedigree data for each patient. A self-service robot could inquire about patients' family history in place of professional clinicians or genetic counselors. ObjectiveThe aim of this study was to develop a mobile-based and self-service tool to collect and visualize pedigree data, not only for professionals but also for those who know little about genetics. MethodsThere are 4 main aspects in the iPed construction, including interface building, data processing, data storage, and data visualization. The user interface was built using HTML, JavaScript libraries, and Cascading Style Sheets (version 3; Daniel Eden). Processing of the submitted data is carried out by PHP programming language. MySQL is used to document and manage the pedigree data. PHP calls the R script to accomplish the visualization. ResultsiPed is freely available to all users through the iPed website. No software is required to be installed, no pedigree files need to be prepared, and no knowledge of genetics or programs is required. The users can easily complete their pedigree data collection and visualization on their own and through a dialogue with iPed. Meanwhile, iPed provides a database that stores all users’ information. Therefore, when the users need to construct new pedigree trees for other genetic traits or modify the pedigree trees that have already been created, unnecessary duplication of operations can be avoided. ConclusionsiPed is a mobile-based and self-service tool that could be used by both professionals and nonprofessionals at any time and from any place. It reduces the amount of time required to collect, manage, and visualize pedigree data.

Abstract Background The four major RNA adenosine modifications, i.e., m6A, m1A, alternative polyadenylation, and adenosine-to-inosine RNA editing, are mediated mostly by the “writer” enzymes and constitute critical mechanisms of epigenetic regulation in immune response and tumorigenesis. However, the cross-talk and potential roles of these “writers” in the tumor microenvironment (TME), drug sensitivity, and immunotherapy remain unknown. Methods We systematically characterized mRNA expression and genetic alterations of 26 RNA modification “writers” in colorectal cancer (CRC), and evaluated their expression pattern in 1697 CRC samples from 8 datasets. We used an unsupervised clustering method to assign the samples into two patterns of expression of RNA modification “writers”. Subsequently, we constructed the RNA modification “writer” Score (WM_Score) model based on differentially expressed genes (DEGs) responsible for the RNA modification patterns to quantify the RNA modification-related subtypes of individual tumors. Furthermore, we performed association analysis for WM_Score and characteristics of TME, consensus molecular subtypes (CMSs), clinical features, transcriptional and post-transcriptional regulation, drug response, and the efficacy of immunotherapy. Results We demonstrated that multi-layer alterations of RNA modification “writer” are associated with patient survival and TME cell-infiltrating characteristics. We identified two distinct RNA modification patterns, characterized by a high and a low WM_Score. The WM_Score-high group was associated with worse patient overall survival and with the infiltration of inhibitory immune cells, such as M2 macrophages, EMT activation, and metastasis, while the WM_Score-low group was associated with a survival advantage, apoptosis, and cell cycle signaling pathways. WM_Score correlated highly with the regulation of transcription and post-transcriptional events contributing to the development of CRC. In response to anti-cancer drugs, WM_Score highly negatively correlated (drug sensitive) with drugs which targeted oncogenic related pathways, such as MAPK, EGFR, and mTOR signaling pathways, positively correlated (drug resistance) with drugs which targeted in apoptosis and cell cycle. Importantly, the WM_Score was associated with the therapeutic efficacy of PD-L1 blockade, suggesting that the development of potential drugs targeting these “writers” to aid the clinical benefits of immunotherapy. Conclusions Our study is the first to provide a comprehensive analysis of four RNA modifications in CRC. We revealed the potential function of these writers in TME, transcriptional and post-transcriptional events, and identified their therapeutic liability in targeted therapy and immunotherapy. This work highlights the cross-talk and potential clinical utility of RNA modification “writers” in cancer therapy.