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Abstract Introduction Different initial manifestations of peritoneal dialysis-associated peritonitis (PDAP) may depend on the type of pathogenic organism. We investigated the association between the clinical characteristics of PDAP and susceptibility to vancomycin and investigated the possibility of using vancomycin monotherapy alone as an initial treatment regimen for some PDAP patients to avoid unnecessary antibiotic exposure and secondary infection. Methods Patients with culture-positive PDAP were retrospectively analyzed and divided into two groups: peritonitis with only cloudy effluent (PDAP-cloudy) or with cloudy effluent, abdominal pain and/or fever (PDAP-multi). The bacterial culture of PD effluent and antibiotic sensitivity test results were compared between groups. Logistic regression was used to investigate factors predicting susceptibility to vancomycin. Results Of 162 episodes of peritonitis which had a positive bacterial culture of PD fluid, 30 peritonitis were in the PDAP-cloudy group, and 132 peritonitis were in the PDAP-multi group. Thirty (100%) peritonitis in the PDAP-cloudy group had gram-positive bacterial infections, which was significantly greater than that in the PDAP-multi group (51.5%) (P

Artemisia sphaerocephala Krasch. polysaccharide (ASKP) is a novel plant polysaccharide. In this study, an aqueous two-phase system (ATPS) consisting of gelatin (Gel) as the dispersed phase and ASKP 60P (a high-molecular-mass fraction of ASKP) as the continuous phase was constructed based on the thermodynamic incompatibility between 60P and Gel at a specific pH, and Gel/60P ATPS emulsion gels were obtained by introducing Fe3+ into the ATPS in order to induce 60P cross-linking. The results showed that the ATPS, consisting of 0.1%–0.5% Gel and 0.5%–1.5% 60P (m/m), exhibited discrete phase separation. The emulsion gel with 0.6% Gel, 1.5% 60P and 60 mmol/L Fe3+ showed good gel strength and elasticity. This was attributed to the fact that the increase in Gel concentration led to a decrease in the volume proportion of the continuous phase, resulting in exposure of more Fe3+ crosslinking sites, enhancing the interaction between 60P and Fe3+, and improving the mechanical properties of emulsion gels. Therefore, this study proposes a new strategy to improve the properties of ASKP gels, which is favorable for the wide application of ASKP in the food, biological and other fields.

Abstract Objectives To compare color Doppler ultrasound and contrast-enhanced ultrasound (CEUS) in evaluating vascular invasion in pancreatic ductal adenocarcinoma (PDAC). Materials and methods This retrospective study included 210 patients with PDAC who were evaluated by color Doppler ultrasound, CEUS, and contrast-enhanced computed tomography (CECT) at our institution between January 2017 and December 2020. Pathologic results were used as the gold standard in patients who underwent surgical and intraoperative exploration. For nonsurgical patients, CECT results were used as the reference standard. The vessels evaluated included those in the peripancreatic arterial system and venous system. The diagnostic performances of color Doppler ultrasound and CEUS for vascular invasion were compared. Results In 51 patients who underwent surgery and intraoperative exploration, color Doppler ultrasound and CEUS differed only in assessing venous system invasion in patients with PDAC of the pancreatic body and tail, with the former being superior to the latter. In 159 nonsurgical patients, there was no difference between CEUS and color Doppler ultrasound in assessing superior mesenteric arteriovenous invasion. CEUS was superior to color Doppler ultrasound in evaluating the celiac artery and its branches, with an accuracy of up to 97.8% for some vessels. Color Doppler ultrasound was ideal for evaluating the splenic and portal veins. Conclusion CEUS is more suitable for the evaluation of peripancreatic arteries than color Doppler. CEUS combined with color Doppler ultrasound can be used as a potential supplement to CECT and is also expected to be used to evaluate vascular invasion of PDAC after chemotherapy. Critical relevance statement Contrast-enhanced US and color Doppler in the assessment of vascular invasion in pancreatic ductal adenocarcinoma have their respective advantages, through standardized ultrasound processes are expected to improve the efficiency of inspection. Key Points Contrast-enhanced US has unique advantages in assessing pancreatic ductal adenocarcinoma invasion of the celiac artery. Doppler imaging is of high value in assessing venous system invasion. Standardization of ultrasound imaging procedures for pancreatic ductal adenocarcinoma is expected to improve efficiency. Graphical Abstract

Abstract The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infected a substantial proportion of Chinese population, and understanding the factors underlying the severity of the disease and fatality is valuable for future prevention and clinical treatment. We recruited 64 patients with invasive ventilation for COVID-19 and performed metatranscriptomic sequencing to profile host transcriptomic profiles, plus viral, bacterial, and fungal content, as well as virulence factors and examined their relationships to 28-day mortality were examined. In addition, the bronchoalveolar lavage fluid (BALF) samples from invasive ventilated hospital/community-acquired pneumonia patients (HAP/CAP) sampled in 2019 were included for comparison. Genomic analysis revealed that all Omicron strains belong to BA.5 and BF.7 sub-lineages, with no difference in 28-day mortality between them. Compared to HAP/CAP cohort, invasive ventilated COVID-19 patients have distinct host transcriptomic and microbial signatures in the lower respiratory tract; and in the COVID-19 non-survivors, we found significantly lower gene expressions in pathways related viral processes and positive regulation of protein localization to plasma membrane, higher abundance of opportunistic pathogens including bacterial Alloprevotella, Caulobacter, Escherichia-Shigella, Ralstonia and fungal Aspergillus sydowii and Penicillium rubens. Correlational analysis further revealed significant associations between host immune responses and microbial compositions, besides synergy within viral, bacterial, and fungal pathogens. Our study presents the relationships of lower respiratory tract microbiome and transcriptome in invasive ventilated COVID-19 patients, providing the basis for future clinical treatment and reduction of fatality.

It is still controversial whether glue can be used for mesh fixation in laparoscopic inguinal hernia repair. The aim of this meta-analysis was used to systematically evaluate the effectiveness and safety of glue mesh fixation in laparoscopic tension-free inguinal hernia repair. The PubMed database, EMBASE database and Cochrane Library were searched to collect published randomized controlled trials (RCTs) on laparoscopic tension-free inguinal hernia repair with glue mesh fixation. Sixteen RCTs and 2409 patients with inguinal hernia were included. The meta-analysis showed that compared with the mechanical mesh fixation group(MMFG), the glue mesh fixation group(GMFG) had significantly reduced incidences of chronic pain[relative risk (RR) = 0.40, 95% confidence interval (CI) (0.28,0.57), P

Water-in-water emulsions, which have a very low interfacial tension and a thick interfacial layer, are formed by two thermodynamically incompatible hydrophilic macromolecules in a certain proportion. It has been reported that the system cannot be stabilized by surfactants, but can avoid macroscopic phase separation by gelation of one or two phases. Recently, it has been found that the stability of water-in-water emulsions can be improved by the irreversible adsorption of solid particles at the interface based on the stabilization mechanism of oil-in-water Pickering emulsions. In this review, we summarize recent advances in research on the stabilization of water-in-water emulsions, and focus on the stability of Pickering emulsions stabilized by solid particles and its influential factors, as well as its applications in the food field. It is expected that this review will provide new ideas for food structure design based on the stabilization of water-in-water emulsions.

Yoghurt has high nutritional value and health-promoting functions; however, its quality defects such as whey syneresis and poor coagulation affect the sensory experience of consumers. Researchers commonly use food macromolecules to improve the gel stability and sensory properties of yoghurt by modifying the formation of gel networks or inducing the gelation of milk protein. In this review, we summarize the texture defects of yogurt, the factors influencing them, and the strategies to improve the gel stability of yogurt as well as the underlying mechanism. Also, we discuss future trends. This review will provide important guidance for improving the quality and stability of yoghurt products.

BackgroundInguinal hernia is a common global disease. This study aims to investigate the effectiveness and safety of robot-assisted transabdominal preperitoneal repair (RTAPP) and laparoscopic transabdominal preperitoneal repair (LTAPP) for inguinal hernia.MethodsWe conducted a thorough search in Cochrane Library, Embase, and PubMed for relevant clinical studies. After applying inclusion and exclusion criteria, the quality of selected studies was assessed using the Jadad scale for randomized controlled studies and the Newcastle-Ottawa scale for observational studies. Meta-analysis was performed using RevMan 5.3 software.ResultsA total of ten studies were included, comprising two randomized controlled studies and eight non-randomized controlled studies. Meta-analysis results revealed no statistically significant differences between the RTAPP group and the LTAPP group regarding hospital stay [MD = 0.21 days, 95% CI (-0.09, 0.51), P = 0.17], incidence of seroma [OR = 0.85, 95% CI(0.45, 1.59), P = 0.61], overall complication rate [OR = 1.22, 95% CI(0.68, 2.18), P = 0.51], readmission rate [OR = 1.31, 95% CI(0.23, 7.47), P = 0.76], and recurrence rate [OR = 0.82, 95% CI(0.22, 3.07), P = 0.77]. However, the RTAPP group had longer operation time compared to the LTAPP group [MD = 14.02 minutes, 95% CI (6.65, 21.39), P = 0.0002], and the cost of the RTAPP procedure was higher than that of the LTAPP procedure [MD = $4.17 thousand, 95% CI (2.59, 5.76), PConclusionRTAPP for inguinal hernia is a safe and feasible approach, however, it is associated with increased operation time and treatment costs.

Backgrounds: The Qing-Fei-Pai-Du Decoction (QFPDD) was reported to ameliorate the inflammatory coagulopathy and thrombocytopenia in COVID-19 patients. This work investigated the effects of QFPDD in endotoxaemia rats and then further studied its influence on platelet production using cultured megakaryocytes. Methods: The coagulation indexes and platelet aggregation reactivity of LPS-induced endotoxemia rats with or without QFPDD treatment were analyzed. The platelet parameters, the expression of thrombopoietin (TPO) in the liver and the kidney, number of the megakaryocytes in bone marrow smear of rats were checked. The maturation and platelet production of human megakaryoblastic MEG-01 cells treated with QFPDD or isochlorogenic acid A (ISA), an active component of QFPDD, were observed. Results: QFPDD improved the coagulation indexes of LPS-induced endotoxaemia rats and decreased the hyper-reactivity of platelets. QFPDD ameliorated LPS-induced decrease in platelet number, partially alleviated increase in liver TPO expression and exhibited no influence on increase in the number of bone marrow megakaryocytes. QFPDD promoted maturation and production of platelet-like particles of MEG-01 megakaryocytes. The effects of QFPDD on MEG-01 megakaryocytes might be related to activation of AKT pathway and up-regulation of related transcription factors. ISA also could induce the maturation of MEG-01 cells. Conclusions: QFPDD effectively ameliorated coagulopathy and thrombocytopenia in rats under inflammatory state. The mechanisms of QFPDD in ameliorating thrombocytopenia might be based on both decreasing effects on platelet depletion in coagulation and inducing effects on maturation and platelet production of megakaryocytes. ISA might be one of the components which contribute to the effects of QFPDD on megakaryocytes.

Abstract Friend leukemia integration 1 (FLI1) is an ETS transcription factor family member. Here, we identified cg11017065 as the most hyper‐methylated cytosine and guanine (CpG) in colorectal cancer (CRC), which belongs to the FLI1 gene. Moreover, integrated bioinformatics prediction and analysis of our cohort showed that FLI1 expression was downregulated and DNA methylation was elevated in CRC. Bioinformatics prediction also indicated that patients overexpressing FLI1 had higher survival rates than those with low FLI1 expression. CRC cells with ectopic expression of FLI1 had reduced invasion, migration, cloning ability and increased apoptosis. Furthermore, DNA‐methyltransferase 3b (DNMT3b) was found to be significantly overexpressed in CRC, and low DNMT3b expression predicted a prolonged survival. DNMT3b bound to the FLI1 promoter. Inhibition of DNMT3b increased FLI1 expression and inhibited the malignant phenotype of CRC cells. Inhibition of FLI1 reversed the phenotypic modulation by DNMT3b depletion in vitro and in vivo. In conclusion, our data indicate that DNMT3b potentiates CRC cell proliferation, migration, and invasion through downregulating FLI1.

In this paper, an improved multicomponent lattice Boltzmann model is employed to investigate the impact of the gas properties, specifically the gas adiabatic index, on the thermodynamic effects of cavitation bubble collapse. The study focuses on analyzing the temperature evolution in the flow field and the resulting thermal effects on the surrounding wall. The accuracy of the developed model is verified through comparisons with analytical solutions of the Rayleigh-Plesset equation and the validation of the adiabatic law. Then, a thermodynamic model of cavitation bubble composed of two-mixed gases collapsing near a wall is established to explore the influence of the gas adiabatic index γ on the temperature behavior. Key findings include the observation that the γ affects the temperature of the first collapse significantly, while its influence on the second collapse is minimal. Additionally, the presence of low-temperature regions near the bubble surface during collapse impacts both bubble and wall temperatures. The study also demonstrates that the γ affects maximum and minimum wall temperatures. The results have implications for selecting specific non-condensable gas properties within cavitation bubbles for targeted cooling or heating purposes, including potential applications in electronic component cooling and environmental refrigeration.

BackgroundChatGPT, a dialogue-based artificial intelligence language model, has shown promise in assisting clinical workflows and patient-clinician communication. However, there is a lack of feasibility assessments regarding its use for perioperative patient education in thoracic surgery. ObjectiveThis study aimed to assess the appropriateness and comprehensiveness of using ChatGPT for perioperative patient education in thoracic surgery in both English and Chinese contexts. MethodsThis pilot study was conducted in February 2023. A total of 37 questions focused on perioperative patient education in thoracic surgery were created based on guidelines and clinical experience. Two sets of inquiries were made to ChatGPT for each question, one in English and the other in Chinese. The responses generated by ChatGPT were evaluated separately by experienced thoracic surgical clinicians for appropriateness and comprehensiveness based on a hypothetical draft response to a patient’s question on the electronic information platform. For a response to be qualified, it required at least 80% of reviewers to deem it appropriate and 50% to deem it comprehensive. Statistical analyses were performed using the unpaired chi-square test or Fisher exact test, with a significance level set at P

Abstract Background Heterotaxy syndrome (HTX) is caused by aberrant left–right patterning early in embryonic development, which results in abnormal positioning and morphology of the thoracic and abdominal organs. Currently, genetic testing discerns the underlying genetic cause in less than 20% of sporadic HTX cases, indicating that genetic pathogenesis remains poorly understood. In this study, we aim to garner a deeper understanding of the genetic factors of this disease by documenting the effect of different matrix metalloproteinase 21 (MMP21) variants on disease occurrence and pathogenesis. Methods Eighty-one HTX patients with complex congenital heart defects and 89 healthy children were enrolled, and we investigated the pathogenetic variants related to patients with HTX by exome sequencing. Zebrafish splice-blocking Morpholino oligo-mediated transient suppression assays were performed to confirm the potential pathogenicity of missense variants found in these patients with HTX. Results Three MMP21 heterozygous non-synonymous variants (c.731G > A (p.G244E), c.829C > T (p.L277F), and c.1459A > G (p.K487E)) were identified in three unrelated Chinese Han patients with HTX and complex congenital heart defects. Sanger sequencing confirmed that all variants were de novo. Cell transfection assay showed that none of the variants affect mRNA and protein expression levels of MMP21. Knockdown expression of mmp21 by splice-blocking Morpholino oligo in zebrafish embryos revealed a heart looping disorder, and mutant human MMP21 mRNA (c.731G > A, c.1459A > G, heterozygous mRNA (wild-type&c.731G > A), as well as heterozygous mRNA (wild-type& c.1459A > G) could not effectively rescue the heart looping defects. A patient with the MMP21 p.G244E variant was identified with other potential HTX-causing missense mutations, whereas the patient with the MMP21 p.K487E variant had no genetic mutations in other causative genes related to HTX. Conclusion Our study highlights the role of the disruptive heterozygous MMP21 variant (p.K487E) in the etiology of HTX with complex cardiac malformations and expands the current mutation spectrum of MMP21 in HTX.

Background As one of the most common stroke sequelae, poststroke cognitive impairment significantly impacts 17.6%–83% of survivors, affecting their rehabilitation, daily living and quality of life. Improving cognitive abilities among patients in stroke recovery is therefore critical and urgent. Transcutaneous auricular vagus nerve stimulation (TAVNS) is a non-invasive, safe, cost-effective treatment with great potential for improving the cognitive function of poststroke patients. This clinical research will evaluate the effectiveness, and help elucidate the possible underlying mechanisms, of TAVNS for improving poststroke cognitive function.Methods and analysis A single-centre, parallel-group, allocation concealment, assessor-blinded randomised controlled clinical trial. We will allocate 88 recruited participants to the TAVNS or sham group for an intervention that will run for 8 weeks, 5 days per week with twice daily sessions lasting 30 min each. Blood tests will be performed and questionnaires issued at baseline and 8-week and 12 week follow-ups. Primary outcomes will be changes in cognitive function scores. Secondary outcomes will be changes in activities of daily living, quality of life and serum oxidative stress indicators.Ethics and dissemination The Ethics Committee of the First Affiliated Hospital of Hunan University of Chinese Medicine has approved the protocol (No. HN-LL-YJSLW-2022200). Findings will be published in peer-reviewed academic journals and presented at scientific conferences.Trial registration number ChiCTR2200057808.

The coefficient problem is an essential topic in the theory of univalent functions theory. In the present paper, we consider a new subclass SQ of analytic functions with f′(z) subordinated to 1/(1−z)2 in the open unit disk. This class was introduced and studied by Răducanu. Our main aim is to give the sharp upper bounds of the second Hankel determinant H2,3f and the third Hankel determinant H3,1f for f∈SQ. This may help to understand more properties of functions in this class and inspire further investigations on higher Hankel determinants for this or other popular sub-classes of univalent functions.

Histone lysine crotonylation (KCR), a novel epigenetic modification, is important in regulating a broad spectrum of biological processes and various diseases. However, whether KCR is involved in neuropathic pain remains to be elucidated. We found KCR occurs in macrophages, sensory neurons, and satellite glial cells of trigeminal ganglia (TG), neurons, astrocytes, and microglia of the medulla oblongata. KCR in TG was detected mainly in small and medium sensory neurons, to a lesser extent in large neurons. Peripheral nerve injury elevated KCR levels in macrophages in the trigeminal and dorsal root ganglia and microglia in the medulla oblongata but reduced KCR levels in sensory neurons. Inhibition of histone crotonyltransferases (p300) by intra-TG or intrathecal administration of C646 significantly alleviated partial infraorbital nerve transection (pIONT)- or spinal nerve ligation (SNL)-induced mechanical allodynia and thermal hyperalgesia. Intra-TG or intrathecal administration of Crotonyl coenzyme A trilithium salt to upregulate KCR dose-dependently induced mechanical allodynia and thermal hyperalgesia in mice. Mechanismly, inhibition of p300 alleviated pIONT-induced macrophage activation and reduced the expression of pain-related inflammatory cytokines Tnfα, Il1β and chemokines Ccl2 and Cxcl10. Correspondingly, exogenous crotonyl-CoA induced macrophage activation and the expression of Tnfα, Il1β, Il6, Ccl2 and Ccl7 in TG, which C646 can repress. These findings suggest that histone crotonylation might be functionally involved in neuropathic pain and neuroinflammation regulation.

Torsades de Pointes (TdP) occurred in a 68-year-old female with epidermal growth factor receptor (EGFR) mutant lung cancer administered osimertinib, the third-generation EGFR tyrosine kinase inhibitor (TKI). Electrocardiogram (ECG) recorded at Tdp showed QT prolongation (QTc = 515 ms), to which a Traditional Chinese Medicine (TCM) named “Litsea Cubeba” may have contributed. After discontinuation of osimertinib and Litsea Cubeba, magnesium supplementation, potassium supplementation, lidocaine infusion, and the pacemaker frequency adjustment, Tdp terminated. However, QT prolongation sustained at discharge (QTc = 528 ms), partly because of the emergency use of amiodarone. Osimertinib may prolong the QT interval leading to TdP, especially when multiple risk factors to lengthen QT interval are incidentally overlapped. Thus, regular monitoring of ECG and appropriate management of concomitant drugs are highly recommended.

Objective To establish an effective CRISPR-Cas9 system targeting at mouse Krt14 that may simulate the pathogenic site mutation of human KRT14. Methods Databases such as OMIM, ExAC and ClinVar were retrieved to identify the strong pathogenic sites of human KRT14, the causative gene of human epidermolysis bullosa simplex. Then, the human and mouse KRT14 protein sequence alignment analysis was carried out to identify the strong pathogenic sites on the mouse genome. Based on the gene targeting principle of the CRISPR-Cas9 system, 4 sgRNAs targeting the mouse Krt14 and 4 expression plasmids were constructed. Then, the sgRNA expression plasmids and Cas9 expression plasmid were co-transfected into mouse NIH 3T3 cells simultaneously. PCR product sequencing, TA clone sequencing of the positive cells screened by drugs were performed to verify the target efficiency of the 4 sgRNAs. Results The p.Arg125 site of human KRT14 protein was identified to be a strong pathogenic site, which corresponded to the p.Arg131 site of mouse KRT14 protein. According to the DNA sequence of the mouse p.Arg131 site, 4 sgRNA expression plasmids targeting at this site was successfully constructed. Sequencing of PCR amplification products of the target site from drug screen positive cells showed that 4 sites were all mutated. The results of TA cloning sequencing showed that the mutation efficiency of the four sites was 70%, 90%, 65% and 100% respectively. Conclusions The above results indicates that efficient CRISPR-Cas9 system targeting at the mouse Krt14 based on the highly pathogenic sites of the human KRT14 has successfully constructed. This result lays a foundation for the in-depth study of Krt14 function and for the establishment of Krt14 gene editing mouse model in order to explore the mechanism and treatment strategy of disease.

Human pancreatic lipase (hPL) is a crucial digestive enzyme responsible for the digestion of dietary lipids in humans, and inhibition of hPL is effective in reducing triglyceride intake, thereby preventing and treating obesity. In this study, a series of fatty acids with different carbon chain lengths were constructed to the fluorophore resorufin based on the substrate preference of hPL. Among them, RLE was found to have the best combination of stability, specificity, sensitivity and reactivity towards hPL. Under physiological conditions, RLE can be rapidly hydrolyzed by hPL and released to resorufin, which triggered approximately 100-fold fluorescence enhancement at 590 nm. RLE was successfully applied for sensing and imaging of endogenous PL in living systems with low cytotoxicity and high imaging resolution. Moreover, a visual high-throughput screening platform was established using RLE, and the inhibitory effects of hundreds of drugs and natural products toward hPL were evaluated. Collectively, this study reports a novel and highly specific enzyme-activatable fluorogenic substrate for hPL that could serve as a powerful tool for monitoring hPL activity in complex biological systems and showcases the potential to explore physiological functions and rapid screening of inhibitors.

Abstract Background China is the second highest pulmonary tuberculosis (PTB) burden country worldwide. However, retreatment of PTB has often developed resistance to at least one of the four first-line anti-TB drugs. The cure rate (approximately 50.0–73.3%) and management of retreatment of PTB in China needs to be improved. Qinbudan decoction has been widely used to treat PTB in China since the 1960s. Previously clinical studies have shown that the Qinbudan tablet (QBDT) promoted sputum-culture negative conversion and lesion absorption. However, powerful evidence from a randomized controlled clinical trial is lacking. Therefore, the aim of this study was to compare the efficacy and safety of QBDT as an adjunct therapy for retreatment of PTB. Methods We conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial in China. People diagnosed with PTB were enrolled who received previous anti-TB treatment from April 2011 to March 2013. The treatment group received an anti-TB regimen and QBDT, and the control group was administered an anti-TB regimen plus placebo. Anti-TB treatment options included isoniazid, rifampicin, pyrazinamide, ethambutol, streptomycin for 2 months (2HRZES), followed by isoniazid, rifampicin, ethambutol for 6 months (6HRE), daily for 8 months. Primary outcome was sputum-culture conversion using the MGIT 960 liquid medium method. Secondary outcomes included lung lesion absorption and cavity closure. Adverse events and reactions were observed after treatment. A structured questionnaire was used to record demographic information and clinical symptoms of all subjects. Data analysis was performed by SPSS 25.0 software in the full analysis set (FAS) population. Results One hundred eighty-one cases of retreatment PTB were randomly divided into two groups: the placebo group (88 cases) and the QBDT group (93 cases). A total of 166 patients completed the trial and 15 patients lost to follow-up. The culture conversion rate of the QBDT group and placebo group did not show a noticeable improvement by using the covariate sites to correct the rate differences (79.6% vs 69.3%; rate difference = 0.10, 95% confidence interval (CI): - 0.02–0.23; F = 2.48, P = 0.12) after treatment. A significant 16.6% increase in lesion absorption was observed in the QBDT group when compared with the placebo group (67.7% vs 51.1%; rate difference = 0.17, 95% CI: 0.02–0.31; χ 2 = 5.56, P = 0.02). The intervention and placebo group did not differ in terms of cavity closure (25.5% vs 21.1%; rate difference = 0.04, 95% CI: - 0.21–0.12; χ 2 = 0.27, P = 0.60). Two patients who received chemotherapy and combined QBDT reported pruritus/nausea and vomiting. Conclusions No significant improvement in culture conversion was observed for retreatment PTB with traditional Chinese medicine plus standard anti-TB regimen. However, QBDT as an adjunct therapy significantly promoted lesion absorption, thereby reducing lung injury due to Mycobacterium tuberculosis infection. Trial registration This trial is registered at ClinicalTrials.gov, NCT02313610 .

Context Panax ginseng C. A. Meyer (Araliaceae) root and leaf have always been considered in the traditional theory as hot and cold properties, respectively. Objective To clarify the hot and cold properties of ginseng root and leaf from a thermodynamic viewpoint. Materials and methods Thirty ICR male mice were randomly assigned to control (water), ginseng root group (GRP) and ginseng leaf group (GLP) with a concentration of 0.075 g/mL; the volume was 0.1 mL/10 g (body mass) per day by intragastric administration for 20 days. Ultra-Performance Liquid Chromatography (UPLC) was used to determine quality control through seven ginsenosides contained in ginseng root and leaf. Rest metabolic rate (RMR) and energy expenditure were monitored every 9 days by TSE System. At the 20th day, serum T3 or T4, liver or brown adipose tissue (BAT) mitochondrial respiration were investigated. Results The quality control of GRP and GLP were within requirements of 2015 China Pharmacopoeia. The RMR (mLO2/h) in GLP (47.95 ± 4.20) was significantly lower than control (52.10 ± 4.79) and GRP (55.35 ± 4.48). Mitochondrial protein concentration and respiration were significantly increased in GRP (BAT, 79.12 ± 2 .08 mg/g, 239.89 ± 10.24 nmol O2/min/g tissue; Liver, 201.02 ± 10.89, 202.44 ± 3.24) and decreased in GLP (BAT, 53.42 ± 3.48, 153.49 ± 5.58; Liver, 138.69 ± 5.69, 104.50 ± 6.25) compared with control. Conclusions The hot and cold properties of ginseng root and leaf are correlated with thermogenic capacity and mitochondrial function of BAT and liver, which deserve to further research.

The Tuchengzi Formation is widely distributed in western Liaoning Province with a clear top and bottom. It is the focal area for the delineation of the terrestrial Jurassic–Cretaceous boundary in China. Based on continuous core samples taken from well YD1, detailed lithostratigraphic sequences and zircon uranium–lead (U-Pb) dating WERE used to investigate the Tuchengzi Formation. The zircon U-Pb ages of the tuff samples taken from the First and Third Members of the Tuchengzi Formation ranged from 153.8 to 137.16 Ma, indicating that they were formed in the late Middle Jurassic–Early Cretaceous. Dating results from the bottom of the Second Member of the Tuchengzi Formation indicate that the sedimentary time of the stratum is no later than 145.7 ± 2.1 Ma. We concluded that the Jurassic–Cretaceous boundary of the Jinyang Basin in western Liaoning province may be located at the interface at a depth of 464 m in well YD1. This conclusion is consistent with the Jurassic–Cretaceous boundary that has been presumed by other researchers based on paleontological assemblage features found in recent years, and can provide useful geological marker beds for the future study of the terrestrial Jurassic–Cretaceous boundary. In addition, the authors also systematically sorted the potential development areas and layers of the terrestrial Jurassic–Cretaceous boundary line, which may also provide useful geological marker beds for the future study of the terrestrial Jurassic–Cretaceous boundary.

AIM: To study the clinical effect of silica gel drainage tube combined with lomefloxacin hydrochloride eye ophthalmic gel in the treatment of lacrimal duct obstruction.METHODS: Totally 86 cases(138 eyes)of lacrimal duct embolism treated in our hospital from February to December 2015 were divided into 43 cases(68 eyes)as control group and 43 cases(70 eyes)of the observation group according to whether they were treated with lomefloxacin hydrochloride eye ophthalmic gel. Patients in the control group were treated with silica gel drainage, while the observation group was treated with lomefloxacin hydrochloride eye ophthalmic gel on the basis of the control group. The total effective rate, serum hypersensitivity C-reactive protein(h-CRP)level, complications and recurrence rate were observed and compared between the two groups. RESULTS: The total effective rate in the patients with obstructive nasolacrimal duct, common lacrimal duct obstruction, and lacrimal duct obstruction in observation group were 95.2%, 100.0%, 96.7%, higher than those in control group(PP>0.05). The serum levels of h-CRP in patients in the observation group at 3d and 7d after operation respectively were 2.40±0.84g/mL, 1.94±0.84g/mL, lower than those of control group at the same time(PPPCONCLUSION: The combination of silica gel drainage tube and lomefloxacin hydrochloride eye ophthalmic gel in the treatment of obstruction of lacrimal duct has good clinical efficacy, low inflammatory reaction, low complication rate and low recurrence rate.

Inhibition of β-lactamases presents a promising strategy to restore the β-lactams antibacterial activity to resistant bacteria. In this work, we found that aromatic carboxyl substituted 2-triazolylthioacetamides 1a−j inhibited VIM-2, exhibiting an IC50 value in the range of 20.6−58.6 μM. The structure-activity relationship study revealed that replacing the aliphatic carboxylic acid with aromatic carboxyl improved the inhibitory activity of 2-triazolylthioacetamides against VIM-2. 1a−j (16 mg/mL) restored the antibacterial activity of cefazolin against E. coli cell expressing VIM-2, resulting in a 4−8-fold reduction in MICs. The isothermal titration calorimetry (ITC) characterization suggested that the primary binding 2-triazolylthioacetamide (1b, 1c, or 1h) to VIM-2 was a combination of entropy and enthalpy contributions. Further, the crystal structure of VIM-2 in complex with 1b was obtained by co-crystallization with a hanging-drop vapour-diffusion method. The crystal structure analysis revealed that 1b bound to two Zn(II) ions of the enzyme active sites, formed H-bound with Asn233 and structure water molecule, and interacted with the hydrophobic pocket of enzyme activity center utilizing hydrophobic moieties; especially for the phenyl of aromatic carboxyl which formed π-π stacking with active residue His263. These studies confirmed that aromatic carboxyl substituted 2-triazolylthioacetamides are the potent VIM-2 inhibitors scaffold and provided help to further optimize 2-triazolylthioacetamides as VIM-2 even or broad-spectrum MβLs inhibitors.

By simulating the sound field of a round piston transducer with the Kirchhoff integral theorem and analyzing the shape of ultrasound beams and propagation characteristics in a metal container wall, this study presents a model for calculating the echo sound pressure by using the Kirchhoff paraxial approximation theory, based on which and according to different ultrasonic impedance between gas and liquid media, a method for detecting the liquid level from outside of sealed containers is proposed. Then, the proposed method is evaluated through two groups of experiments. In the first group, three kinds of liquid media with different ultrasonic impedance are used as detected objects; the echo sound pressure is calculated by using the proposed model under conditions of four sets of different wall thicknesses. The changing characteristics of the echo sound pressure in the entire detection process are analyzed, and the effects of different ultrasonic impedance of liquids on the echo sound pressure are compared. In the second group, taking water as an example, two transducers with different radii are selected to measure the liquid level under four sets of wall thickness. Combining with sound field characteristics, the influence of different size transducers on the pressure calculation and detection resolution are discussed and analyzed. Finally, the experimental results indicate that measurement uncertainly is better than ±5 mm, which meets the industrial inspection requirements.

The proposed method for measuring the liquid level focuses on the ultrasonic impedance and echo energy inside a metal wall, to which the sensor is attached directly, not on ultrasonic waves that penetrate the gas–liquid medium of a container. Firstly, by analyzing the sound field distribution characteristics of the sensor in a metal wall, this paper proposes the concept of an "energy circle" and discusses how to calculate echo energy under three different states in detail. Meanwhile, an ultrasonic transmitting and receiving circuit is designed to convert the echo energy inside the energy circle into its equivalent electric power. Secondly, in order to find the two critical states of the energy circle in the process of liquid level detection, a program is designed to help with calculating two critical positions automatically. Finally, the proposed method is evaluated through a series of experiments, and the experimental results indicate that the proposed method is effective and accurate in calibration of the liquid level outside a sealed metal container.

All-trans retinoic acid (ATRA) is a revolutionary agent for acute promyelocytic leukemia (APL) treatment via differentiation induction. However, ATRA treatment also increases cytokine, chemokine, and adhesive molecule (mainly ICAM-1) expression, which can cause clinical complications, including a severe situation known as differentiation syndrome (DS) which can cause death. Therefore, it is of clinical significance to find a strategy to specifically blunt inflammatory effects while preserving differentiation. Here we report that the natural compound, celastrol, could effectively block lung infiltrations in DS animal models created by loading ATRA-induced APL cell line NB4. In ATRA-treated NB4 cells, celastrol could potently inhibit ICAM-1 elevation and partially reduce TNF-α and IL-1β secretion, though treatment showed no effects on IL-8 and MCP-1 levels. Celastrol's effect on ICAM-1 in ATRA-treated NB4 was related to reducing MEK1/ERK1 activation. Strikingly and encouragingly, celastrol showed no obvious effects on ATRA-induced NB4 differentiation, as determined by morphology, enzymes, and surface markers. Our results show that celastrol is a promising and unique agent for managing the side effects of ATRA application on APL, and suggest that hyper-inflammatory ability is accompanied by, but not necessary for, APL differentiation. Thus we offered an encouraging novel strategy to further improve differentiation therapy.

Abstract Background Conotruncal heart defects (CTDs) are present in 75-85% of patients suffering from the 22q11.2 deletion syndrome. To date, no consistent phenotype has been consistently correlated with the 22q11.2 deletions. Genetic studies have implicated TBX1 as a critical gene in the pathogenesis of the syndrome. The aim of study was to determine the incidence of the 22q11.2 deletion in Chinese patients with CTDs and the possible mechanism for pathogenesis of CTDs. Methods We enrolled 212 patients with CTDs and 139 unrelated healthy controls. Both karyotypic analysis and multiplex ligation-dependent probe amplification were performed for all CTDs patients. Fluorescence in situ hybridization was performed for the patients with genetic deletions and their relatives. The TBX1 gene was sequenced for all patients and healthy controls. The χ2 and Fisher's exact test were used in the statistical analysis. Results Thirteen of the 212 patients with CTDs (6.13%) were found to have the 22q11.2 deletion syndrome. Of the 13 cases, 11 presented with a hemizygous interstitial microdeletion from CLTCL1 to LZTR1; one presented with a regional deletion from CLTCL1 to DRCR8; and one presented with a regional deletion from CDC45L to LZTR1. There were eight sequence variants in the haploid TBX1 genes of the del22q11 CTDs patients. The frequency of one single nucleotide polymorphism (SNP) in the del22q11 patients was different from that of the non-del patients (P < 0.05), and the frequencies of two other SNPs were different between the non-del CTDs patients and controls (P < 0.05). Conclusions CTDs, especially pulmonary atresia with ventricular septal defect and tetralogy of Fallot, are the most common disorders associated with the 22q11.2 deletion syndrome. Those patients with both CTDs and 22q11.2 deletion generally have a typical or atypical deletion region within the TBX1 gene. Our results indicate that TBX1 genetic variants may be associated with CTDs.