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Abstract To establish a population pharmacokinetic (PopPK) model of posaconazole suspension in Chinese hematopoietic stem cell transplantation (HSCT) patients and to recommend an optimal dosing regimen. A single-center, retrospective, model-based study was conducted in 62 Chinese patients, including 103 with posaconazole plasma concentrations. PopPK analysis using NONMEM software. A one-compartment model of first-order elimination and absorption was in good agreement with the experimental data. Analysis of covariance showed that body weight (WT), creatinine clearance (CCR), and proton pump inhibitor (PPI) had a significant effect on the pharmacokinetics of posaconazole. The dose simulation results show that patients with CCR ≥ 90 mL/min require at least 3 mg/kg TID and 7 mg/kg BID dosing regimens for prevention and treatment, respectively. However, when combined with PPI, at least 5 mg/kg BID and 5 mg/kg TID dosing regimens are required for prevention and treatment, respectively. Regardless of whether it is used in combination with PPI or not, patients with a CCR of 60–90 mL/min can achieve PTA goals by using a 4 mg/kg BID and 4 mg/kg TID regimen for prevention and treatment, respectively. A dosing regimen of 3 mg/kg BID in patients with a CCR of 30–60 mL/min is sufficient to meet the PTA goal of prophylaxis, and the dose needs to be elevated to 4 mg/kg BID for the treatment of fungal infections, and there is no need to change the dose according to the coadministration of PPI. When the patient's CCR is less than 30 mL/min, whether or not combined with PPI, the administration regimen of 2 mg/kg BID and 3 mg/kg BID can meet the PTA goals for prevention and treatment, respectively.

Introduction Acupuncture and related acupoint therapies have been widely used for smoking cessation. Some relevant systematic reviews (SRs) have been published. There is a need to summarize and update the evidence to inform practice and decision-making. Methods Eight databases were searched from their inception to December 2023. SRs, any randomized controlled trials (RCTs) comparing acupuncture therapies with sham acupuncture, pharmacotherapy, behavioral therapy, or no treatment, were included. The primary outcome was the abstinence rate. AMSTAR-2 was employed to assess the quality of SRs. An updated meta-analysis was conducted based on SRs and RCTs. Data were synthesized using risk ratios (RR) with 95% confidence intervals (CIs). The GRADE approach was employed to assess the certainty of the updated evidence. Results Thirteen SRs and 20 RCTs outside of the SRs were identified. The SRs were of low or very low quality by AMSTAR-2. Sixteen (80%) RCTs were at high risk of performance bias. Eight acupuncture and related acupoint therapies were involved. The short-term (≤6 months) abstinence rate outcome was summarized as follows. Most SRs suggested that filiform needle acupuncture or acupressure had a better effect than sham acupuncture, but the findings were inconsistent. The updated meta-analysis also suggested that filiform needle acupuncture was more effective than sham acupuncture (RR=1.44; 95% CI: 1.02–2.02; I 2 = 66%; low certainty; 9 RCTs, n=1358). Filiform needle acupuncture combined with acupressure was comparable to nicotine patches (RR=0.99; 95% CI: 0.74–1.32; low certainty; 6 RCTs, n= 524). Acupressure was superior to counseling (RR=1.46; 95% CI: 1.14–1.87; I 2 =5%; low certainty; 8 RCTs, n=595). No serious adverse events were reported in these SRs or RCTs. Conclusions Low certainty evidence suggests that filiform needle acupuncture and auricular acupressure appear to be safe and effective in achieving short-term smoking cessation. However, long-term follow-up data are needed.

Diaphragm dysfunction (DD) can be classified as mild, resulting in diaphragmatic weakness, or severe, resulting in diaphragmatic paralysis. Various factors such as prolonged mechanical ventilation, surgical trauma, and inflammation can cause diaphragmatic injury, leading to negative outcomes for patients, including extended bed rest and increased risk of pulmonary complications. Therefore, it is crucial to protect and monitor diaphragmatic function. Impaired diaphragmatic function directly impacts ventilation, as the diaphragm is the primary muscle involved in inhalation. Even unilateral DD can cause ventilation abnormalities, which in turn lead to impaired gas exchange, this makes weaning from mechanical ventilation challenging and contributes to a higher incidence of ventilator-induced diaphragm dysfunction and prolonged ICU stays. However, there is insufficient research on DD in non-ICU patients, and DD can occur in all phases of the perioperative period. Furthermore, the current literature lacks standardized ultrasound indicators and diagnostic criteria for assessing diaphragmatic dysfunction. As a result, the full potential of diaphragmatic ultrasound parameters in quickly and accurately assessing diaphragmatic function and guiding diagnostic and therapeutic decisions has not been realized.

Klebsiella pneumoniae is an opportunistic pathogen causing severe infections. The circadian rhythm is the internal rhythm mechanism of an organism and plays an important role in coping with changes in the 24-h circadian rhythm. Disruption of the circadian rhythm can lead to immune, behavioral, mental, and other related disorders. Whether K. pneumoniae can disrupt the circadian rhythm after infection remains unclear. Here, we examined the effects of K. pneumoniae NTUH-K2044 infection on biological rhythm and inflammation in zebrafish using behavioral assays, quantitative real-time reverse transcription PCR, neutrophil and macrophage transgenic fish, and drug treatment. The results showed that K. pneumoniae infection decreased the motor activity of zebrafish and reduced the circadian rhythm amplitude, phase, and period. The expression of core circadian rhythm-associated genes increased under light-dark conditions, whereas they were downregulated under continuous darkness. Analysis of Klebsiella pneumoniae-mediated inflammation using Tg(mpx:EGFP) and Tg(mpeg:EGFP) transgenic zebrafish, expressing fluorescent neutrophils and macrophages, respectively, showed increased induction of inflammatory cells, upregulated expression of inflammatory factor genes, and stronger inflammatory responses under light-dark conditions. These effects were reversed by the anti-inflammatory drug G6PDi-1, and the expression of clock genes following K. pneumoniae treatment was disrupted. We determined the relationship among K. pneumoniae, inflammation, and the circadian rhythm, providing a theoretical reference for studying circadian rhythm disorders caused by inflammation.

Abstract Objective To investigate the changes in amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) values before and after acupuncture in young women with non-menstrual migraine without aura (MWoA) through rest blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI). Methods Patients with non-menstrual MWoA (Group 1, n = 50) and healthy controls (Group 2, n = 50) were recruited. fMRI was performed in Group 1 at 2 time points: before acupuncture (time point 1, TP1); and after the end of all acupuncture sessions (time point 2, TP2), and performed in Group 2 as a one-time scan. Patients in Group 1 were assessed with the Migraine Disability Assessment Questionnaire (MIDAS) and the Short-Form McGill Pain Questionnaire (SF-MPQ) at TP1 and TP2 after fMRI was performed. The ALFF and DC values were compared within Group 1 at two time points and between Group 1 and Group2. The correlation between ALFF and DC values with the statistical differences and the clinical scales scores were analyzed. Results Brain activities increased in the left fusiform gyrus and right angular gyrus, left middle occipital gyrus, and bilateral prefrontal cortex and decreased in left inferior parietal lobule in Group 1, which had different ALFF values compared with Group 2 at TP1. The bilateral fusiform gyrus, bilateral inferior temporal gyrus and right middle temporal gyrus increased and right angular gyrus, right superior marginal gyrus, right inferior parietal lobule, right middle occipital gyrus, right superior frontal gyrus, right middle frontal gyrus, right anterior central gyrus, and right supplementary motor area decreased in activity in Group 1 had different DC values compared with Group 2 at TP1. ALFF and DC values of right inferior temporal gyrus, right fusiform gyrus and right middle temporal gyrus were decreased in Group1 at TP1 compared with TP2. ALFF values in the left middle occipital area were positively correlated with the pain degree at TP1 in Group1 (correlation coefficient r, r = 0.827, r = 0.343; P

AIM: To evaluate the effect of symmetrical arc incision correcting corneal astigmatism in femtosecond laser-assisted phacoemulsification (FLACS). METHODS: This study enrolled patients with cataract combined with regular corneal astigmatism of >0.75 D, who underwent FLACS. Symmetrical arc incision was set at 8 mm diameter and 85% depth. The follow-up time was 3-24mo (4.92±3.49mo). Pentacam recorded the corneal astigmatism and higher-order aberration at pre-operation and post-operation. The changes in corneal astigmatism were analyzed by Alpins method. The correlation of astigmatism type, age, corneal horizontal diameter, corneal thickness, arc incision length, and correction index (CI) was analyzed, and the residual corneal astigmatism was compared with the residual whole eye astigmatism. RESULTS: Totally 79 patients (102 eyes) were enrolled, 10 patients had corneal epithelial injury, 1 patient occurred corneal epithelial hyperplasia. The corneal astigmatism was 1.23±0.38 D pre-operation, and decreased to 0.76±0.39 D post-operation (t=10.146, P=0.000). Corneal high-order aberration was 0.17±0.08 μm pre-operation and 0.24±0.11 μm post-operation (t=-5.186, P=0.000). The residual corneal astigmatism and residual whole eye astigmatism were no significant difference (t=-0.347, P=0.729). Using Alpin's method, the following were determined: target-induced astigmatism (TIA) =1.23±0.38 D, surgery-induced astigmatism (SIA) =0.77±0.45 D, difference vector (DV)=0.77±0.39 D, and CI=0.54±0.28. Age, astigmatism size, corneal horizontal diameter, corneal thickness, and arc incision length were not correlated with CI. The CI for against the rule astigmatism (ATR) was better than that for with the rule astigmatism (WTR; P=0.001). CONCLUSION: Femtosecond laser-assisted astigmatic keratotomy has better CI of ATR, but increase higher-order corneal aberration. CI is not ideal, it's not a perfect choice if we pursue ideal correction effect.

Background and objectiveFutile recanalization (FR) is defined as patients with acute ischemic stroke (AIS) due to large vessel occlusion who still exhibits functional dependence although undergoing successful mechanical thrombectomy (MT). We aimed to develop and validate a simple nomogram for predicting the probability of FR after MT treatment in AIS patients.MethodsClinical data of AIS patients in the Jrecan clinical trial in China from March 2018 to June 2019 were collected as the derivation set (n = 162). Meanwhile, clinical data of AIS patients who underwent MT in Baotou Central Hospital and Ningbo No.2 Hospital from 2019 to 2021 were collected as the validation set (n = 170). Multivariate logistic regression analysis was performed for all variables that had p

Abstract Background Sintilimab combined with IBI305 treatment regimen had potential clinical benefits than sorafenib in the first‐line treatment of patients with unresectable hepatic cell carcinoma (HCC). However, whether sintilimab plus IBI305 has economic benefits in China remains unclear. Methods From the perspective of Chinese payers, we used the Markov model to simulate patients with HCC receiving treatment with sintilimab plus IBI305 and sorafenib. The transition probability between health states was estimated using the parametric survival model, and the cumulative medical costs and utility of the two treatment methods were estimated. Considering the incremental cost‐effectiveness ratios (ICERs) as the evaluation index, sensitivity analyses were performed to explore the impact of uncertainty on the results. Results Compared to sorafenib, sintilimab plus IBI305 generated an additional $17552.17 and 0.33 quality‐adjusted life years, resulting in an ICER of $52817.89. The analysis outcomes were most sensitive to the total cost of sintilimab plus IBI305. With a willingness‐to‐pay threshold of $38,334, sintilimab plus IBI305 showed a 1.28% probability of being cost‐effective. The total cost of sintilimab plus IBI305 should be reduced by at least 31.9% to be accepted by Chinese payers. Conclusions Regardless of whether the price of sintilimab plus IBI305 and sorafenib is covered by Medicare, sintilimab plus IBI305 is unlikely to be cost‐effective for first‐line treatment of patients with unresectable HCC.

BackgroundThe past decade has witnessed advancements in mechanical thrombectomy (MT) for acute large-vessel occlusions (LVOs). However, only approximately half of the patients with LVO undergoing MT show the best/independent 90-day favorable outcome. This study aimed to develop a nomogram for predicting 90-day poor outcomes in patients with LVO treated with MT.MethodsA total of 187 patients who received MT were retrospectively analyzed. Factors associated with 90-day poor outcomes (defined as mRS of 4–6) were determined by univariate and multivariate logistic regression analyzes. One best-fit nomogram was established to predict the risk of a 90-day poor outcome, and a concordance index was utilized to evaluate the performance of the model. Additionally, 145 patients from a single stroke center were retrospectively recruited as the validation cohort to test the newly established nomogram.ResultsThe overall incidence of 90-day poor outcomes was 45.16%, affecting 84 of 186 patients in the training set. Moreover, five variables, namely, age (odds ratio [OR]: 1.049, 95% CI [1.016–1.083]; p = 0.003), glucose level (OR: 1.163, 95% CI [1.038–1.303]; p = 0.009), baseline National Institute of Health Stroke Scale (NIHSS) score (OR: 1.066, 95% CI [0.995–1.142]; p = 0.069), unsuccessful recanalization (defined as a TICI grade of 0 to 2a) (OR: 3.730, 95% CI [1.688–8.245]; p = 0.001), and early neurological deterioration (END, defined as an increase of ≥4 points between the baseline NIHSS score and the NIHSS score at 24 h after MT) (OR: 3.383, 95% CI [1.411–8.106]; p = 0.006), were included in the nomogram to predict the potential risk of poor outcomes at 90 days following MT in LVO patients, with a C-index of 0.763 (0.693–0.832) in the training set and 0.804 (0.719–0.889) in the validation set.ConclusionThe proposed nomogram provided clinical evidence for the effective control of these risk factors before or during the process of MT surgery in LVO patients.

The viscous resistance caused by the relative motion of plunger and pump barrel is an important factor in the dynamic analysis of the drainage and production mechanism during coalbed methane exploitation. Existing studies mostly focus on deep well (1000–3000 m) large-displacement pump (usually 80–300 m 3 /d), and the interstitial medium is mainly crude oil. Regression fitting is mainly carried out based on empirical formula or experimental simulation method, without considering the characteristics of shallower coalbed gas well (400–800 m) small-displacement pump (

Abstract Objectives To date, the effectiveness of acceptance and commitment therapy (ACT) for acute stroke patients has not been well recognized. The study aimed to discover the effectiveness of group‐based ACT in treating depression for acute stroke patients. Methods We conducted a randomized controlled trial with 140 acute stroke patients with depression. The ACT intervention comprised seven sessions, of 45–60 min over 4 weeks. Data were collected pre‐ and post‐intervention and at 3‐month follow‐up, assessing depression, health‐related quality of life (HRQoL), psychological flexibility, cognitive fusion, sleep quality, and confidence. Results Overall, 99.3% of the included patients were assessed as having mild depression. The ACT intervention significantly reduced depression in acute stroke patients in comparison with the control group post‐intervention and at 3 months (partial η2=.306). Additionally ACT significantly improved HRQoL‐mental component summary, sleep quality, psychological flexibility, cognitive fusion, and confidence compared with control group. Conclusions ACT is effective in treating acute stroke patients with depression, and the efficacy was maintained at 3‐month follow‐up.

Dihydrofolate reductase (DHFR), a housekeeping enzyme in primary metabolism, has been extensively studied as a model of acid-base catalysis and a clinic drug target. Herein, we investigated the enzymology of a DHFR-like protein SacH in safracin (SAC) biosynthesis, which reductively inactivates hemiaminal pharmacophore-containing biosynthetic intermediates and antibiotics for self-resistance. Furthermore, based on the crystal structure of SacH−NADPH−SAC-A ternary complexes and mutagenesis, we proposed a catalytic mechanism that is distinct from the previously characterized short-chain dehydrogenases/reductases-mediated inactivation of hemiaminal pharmacophore. These findings expand the functions of DHFR family proteins, reveal that the common reaction can be catalyzed by distinct family of enzymes, and imply the possibility for the discovery of novel antibiotics with hemiaminal pharmacophore.

Abstract Objective The KEYNOTE‐590 trial showed that individuals with advanced esophageal cancer who received Pembrolizumab in combination with chemotherapy as a first‐line regimen achieved a significant extension of survival. However, this treatment option increases the financial burden on patients and the economic benefits remain to be further evaluated. Methods A Markov model was used to simulate 10‐year survival of patients with esophageal cancer from the perspective of United States (US) Medicare payers. We evaluated the economics of Pembrolizumab plus chemotherapy in the PD‐L1 positive score (CPS ≥10) and any PD‐L1 expression groups, respectively. We estimated total costs, quality‐adjusted life years (QALYs), and calculated incremental cost effectiveness ratios (ICERs). Sensitivity analyses were conducted to explore the impact of uncertainties on the results. Subgroup analysis was also performed. Results The analysis results showed that the ICER for pembrolizumab plus chemotherapy versus chemotherapy alone was $293,513.17/QALYs in the any PD‐L1 expression group. This exceeded the threshold of willingness to pay ($150,000/QALYs). ICERs were most sensitive to the cost of pembrolizumab and the ICERs exceeded $150,000/QALYs in all subgroups. Conclusions Evidence suggests that first‐line pembrolizumab in combination with chemotherapy is not a cost‐effective option for advanced esophageal cancer in the US, regardless of PD‐L1 expression status.

The fungal genus Nigrospora is known to be a plant pathogen, endophyte, and saprobe, and it is usually isolated from various substrates like soil and air. During the surveys of soil fungi in Hebei Province of China, two isolates of Nigrospora were obtained. A multi-locus phylogeny of combined loci of the 5.8S nuclear ribosomal gene with the two flanking transcribed spacers (ITS), part of the translation elongation factor 1-alpha (tef1), and the beta-tubulin (tub2) loci, in conjunction with morphological characters were used to identify the newly collected isolates. Nigrospora humicola sp. Nov. is described and proposed herein, which differs from its phylogenetically close species N. chinensis and N. globosa by the sequences of ITS, tef1, and tub2.

Chronic kidney disease (CKD) causes irreversible damage to kidney structure and function. Arising from various etiologies, risk factors for CKD include hypertension and diabetes. With a progressively increasing global prevalence, CKD is an important public health problem worldwide. Medical imaging has become an important diagnostic tool for CKD through the non-invasive identification of macroscopic renal structural abnormalities. Artificial intelligence (AI)-assisted medical imaging techniques aid clinicians in the analysis of characteristics that cannot be easily discriminated by the naked eye, providing valuable information for the identification and management of CKD. Recent studies have demonstrated the effectiveness of AI-assisted medical image analysis as a clinical support tool using radiomics- and deep learning-based AI algorithms for improving the early detection, pathological assessment, and prognostic evaluation of various forms of CKD, including autosomal dominant polycystic kidney disease. Herein, we provide an overview of the potential roles of AI-assisted medical image analysis for the diagnosis and management of CKD.

When the historical data of the early phase trial and the interim data of the Phase III trial are available, we should use them to give a more accurate prediction in both futility and efficacy analysis. The predictive power is an important measure of the practical utility of a proposed trial, and it is better than the classical statistical power in giving a good indication of the probability that the trial will demonstrate a positive or statistically significant outcome. In addition to the four predictive powers with historical and interim data available in the literature and summarized in Table 1, we discover and calculate another four predictive powers also summarized in Table 1, for one-sided hypotheses. Moreover, we calculate eight predictive powers summarized in Table 2, for the reversed hypotheses. The combination of the two tables gives us a complete picture of the predictive powers with historical and interim data for futility and efficacy analysis. Furthermore, the eight predictive powers with historical and interim data are utilized to guide the futility analysis in the tamoxifen example. Finally, extensive simulations have been conducted to investigate the sensitivity analysis of priors, sample sizes, interim result and interim time on different predictive powers.

Abstract Background Analyzing disease–disease relationships plays an important role for understanding etiology, disease classification, and drug repositioning. However, as cardiovascular diseases with causative links, the molecular relationship among stable angina pectoris (SAP), ischemic cardiomyopathy (ICM) and chronic heart failure (CHF) is not clear. Methods In this study, by integrating the multi-database data, we constructed paired disease progression modules (PDPMs) to identified relationship among SAP, ICM and CHF based on module reconstruction pairs (MRPs) of K-value calculation (a Euclidean distance optimization by integrating module topology parameters and their weights) methods. Finally, enrichment analysis, literature validation and structural variation (SV) were performed to verify the relationship between the three diseases in PDPMs. Results Total 16 PDPMs were found with K > 0.3777 among SAP, ICM and CHF, in which 6 pairs in SAP–ICM, 5 pairs for both ICM–CHF and SAP–CHF. SAP–ICM was the most closely related by having the smallest average K-value (K = 0.3899) while the maximum is SAP–CHF (K = 0.4006). According to the function of the validation gene, inflammatory response were through each stage of SAP–ICM–CHF, while SAP–ICM was uniquely involved in fibrosis, and genes were related in affecting the upstream of PI3K–Akt signaling pathway. 4 of the 11 genes (FLT1, KDR, ANGPT2 and PGF) in SAP–ICM–CHF related to angiogenesis in HIF-1 signaling pathway. Furthermore, we identified 62.96% SVs were protein deletion in SAP–ICM–CHF, and 53.85% SVs were defined as protein replication in SAP–ICM, while ICM–CHF genes were mainly affected by protein deletion. Conclusion The PDPMs analysis approach combined with genomic structural variation provides a new avenue for determining target associations contributing to disease progression and reveals that inflammation and angiogenesis may be important links among SAP, ICM and CHF progression.

Eight Gram-negative, aerobic, motile with paired polar flagella and rod-shaped bacteria were isolated from six tobacco fields in Yunnan, PR China. 16S rRNA gene sequence analysis revealed that all the strains belonged to the genus Ralstonia. Among them, strain 22TCCZM03-6 had an identical 16S rRNA sequence to that of R. wenshanensis 56D2T, and the other strains were closely related to R. pickettii DSM 6297T (98.34–99.86%), R. wenshanensis 56D2T (98.70–99.64%), and R. insidiosa CCUG 46789T (97.34–98.56%). Genome sequencing yielded sizes ranging from 5.17 to 5.72 Mb, with overall G + C contents of 63.3–64.1%. Pairwise genome comparisons showed that strain 22TCCZM03-6 shared average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values above the species cut-off with R. wenshanensis 56D2T, suggesting that strain 22TCCZM03-6 is a special strain of the R. wenshanensis. Five strains, including 21MJYT02-10T, 21LDWP02-16, 22TCJT01-1, 22TCCZM01-4, and 22TCJT01-2, had ANI values >95% and dDDH values >70% when compared with each other. These five strains had ANI values of 73.32–94.17% and dDDH of 22.0–55.20% with the type strains of the genus Ralstonia individually, supporting these five strains as a novel species in the genus Ralstonia. In addition, strains 21YRMH01-3T and 21MJYT02-11T represent two independent species. They both had ANI and dDDH values below the thresholds for species delineation when compared with the type species of the genus Ralstonia. In strains 21YRMH01-3T and 21MJYT02-10T, the main fatty acids were summed features 3, 8, and C16:0; however, strain 21MJYT02-11T contained C16:0, cyclo-C17:0, and summed features 3 as major fatty acids. The main polar lipids, including diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylethanolamine, were identified from strains 21YRMH01-3T, 21MJYT02-10T, and 21MJYT02-11T. The ubiquinones Q-7 and Q-8 were also detected in these strains, with Q-8 being the predominant quinone. Based on the above data, we propose that the eight strains represent one known species and three novel species in the genus Ralstonia, for which the names Ralstonia chuxiongensis sp. nov., Ralstonia mojiangensis sp. nov., and Ralstonia soli sp. nov. are proposed. The type strains are 21YRMH01-3T (=GDMCC 1.3534T = JCM 35818T), 21MJYT02-10T (=GDMCC 1.3531T = JCM 35816T), and 21MJYT02-11T (=GDMCC 1.3532T = JCM 35817T), respectively.

Cellular residues after lipid extraction are the primary waste by-products of microbial polyunsaturated fatty acid production. To mitigate the discharge of cellular residues and reduce the cost of DHA and ARA production, this study examined the utilization of enzymatically hydrolyzed Aurantiochytrium cellular residues (ACRs) and Mortierella alpina cellular residues (MCRs) as nitrogen sources. Results demonstrated that ACRs and MCRs could partially substitute yeast extract (YE) without adverse effects on DHA and ARA fermentation. Moreover, the implementation of a new fermentation medium incorporating ACRs, MCRs, and YE as mixed nitrogen sources resulted in DHA and ARA yields of 17.78 and 5.77 g/L, respectively. These values represented increases of 10.37% and 9.28% compared to traditional cultural methods, while simultaneously reducing the usage of YE by 80% and 60%, respectively. Therefore, the strategy of recycling waste cellular residues presents a novel approach for reducing the costs and environmental impact associated with microbial fermentations.

Abstract Polycystic ovary syndrome (PCOS) is an endocrine disease associated with reproduction. The Cuscuta-Salvia formula has been widely used to treat for PCOS in clinic. However, its chemical and pharmacological properties remain unclear. We identified the active components and related targets of Cuscuta-Salvia using UHPLC-ESI-Q-TOF-MS and TCMSP database. Disease targets were obtained from the DisGeNET and GeneCards databases. Subsequently, common targets between Cuscuta-Salvia and PCOS were identified using a Venn diagram. PPI network was established. Core genes were selected using a Cytoscape software plugin. GO and KEGG enrichment analyses were performed for common targets using the “pathview” package in R. Several core targets were verified using molecular and Immunological methods. By combining UHPLC-ESI-Q-TOF-MS with a network pharmacology study, 14 active components and a total of 80 common targets were obtained. Ten core genes were regulated by Cuscuta-Salvia in PCOS, including IL6, AKT1, VEGFA, TP53, TNF, MAPK1, JUN, EGF, CASP3, and EGFR. GO results showed that cellular response to drugs, response to oxygen levels, response lipopolysaccharides, and response to molecule of bacterial origin in BP category; membrane, transcription regulator complex, nuclear chromatin, postsynaptic membrane, and vesicle lumen in CC category; DNA-binding transcription factor binding, RNA polymerase II-specific DNA-binding transcription factor binding, DNA-binding transcription activator activity, RNA polymerase II-specific, DNA-binding transcription activator activity, and cytokine receptor binding in MF terms. The KEGG enrichment pathway was mainly involved in the PI3K − Akt, MAPK, TNF, IL-17 signalling pathways, and in cellular senescence. Furthermore, the results of the experimental study showed that Cuscuta-Salvia ameliorated the pathological changes in the ovaries, liver and adipose tissue. And it improved the expressions of the genes or proteins. Our results demonstrate that Cuscuta-Salvia may provide a novel pharmacological basis in an experimental model of PCOS by regulating gene expression. This study provides a basis for future research and clinical applications.

As a biodegradable and renewable material, polylactic acid is considered a major environmentally friendly alternative to petrochemical plastics. Microbial fermentation is the traditional method for lactic acid production, but it is still too expensive to compete with the petrochemical industry. Agro-industrial wastes are generated from the food and agricultural industries and agricultural practices. The utilization of agro-industrial wastes is an important way to reduce costs, save energy and achieve sustainable development. The present study aimed to develop a method for the valorization of Zizania latifolia waste and cane molasses as carbon sources for L-lactic acid fermentation using Rhizopus oryzae LA-UN-1. The results showed that xylose derived from the acid hydrolysis of Z. latifolia waste was beneficial for cell growth, while glucose from the acid hydrolysis of Z. latifolia waste and mixed sugars (glucose and fructose) from the acid hydrolysis of cane molasses were suitable for the accumulation of lactic acid. Thus, a three-stage carbon source utilization strategy was developed, which markedly improved lactic acid production and productivity, respectively reaching 129.47 g/L and 1.51 g/L·h after 86 h of fermentation. This work demonstrates that inexpensive Z. latifolia waste and cane molasses can be suitable carbon sources for lactic acid production, offering an efficient utilization strategy for agro-industrial wastes.

Long non-coding RNAs (lncRNAs) play important roles in many biological processes. Knocking out or knocking down some lncRNAs will lead to lethality or infertility. These lncRNAs are called essential lncRNAs. Knowledges of essential lncRNAs are important in establishing minimal genomes of living cells, developing drug therapies and early diagnostic approaches for complex diseases. However, existing databases focus on collecting essential coding genes. Essential non-coding gene records are rare in existing databases. A comprehensive collection of essential non-coding genes, particularly essential lncRNA genes, is demanded. We manually curated 207 essential lncRNAs from literatures for establishing a database on essential lncRNAs, which is named as dbEssLnc (Database of essential lncRNAs). The dbEssLnc database has a web-based user-friendly interface for the users to browse, to search, to visualize and to blast search records in the database. The dbEssLnc database is freely accessible at https://esslnc.pufengdu.org. All data and source codes for mirroring the dbEssLnc database have been deposited in GitHub (https://github.com/yyZhang14/dbEssLnc).

Antibiotic-producing organisms need to co-evolve self-protection mechanisms to avoid any damage to themselves caused by the antibiotic pharmacophore (the reactive part of the compound). In this study, the authors report a self-defense strategy in naphthyridinomycin (NDM)-producing Streptomyces lusitanus, that comprises reductive inactivation of the hemiaminal pharmacophore by short-chain dehydrogenases/reductases (SDRs) NapW and HomW.

Abstract Background The interactions between nanoparticles (NPs) and plasma proteins form a protein corona around NPs after entering the biological environment, which provides new biological properties to NPs and mediates their interactions with cells and biological barriers. Given the inevitable interactions, we regard nanoparticle‒protein interactions as a tool for designing protein corona-mediated drug delivery systems. Herein, we demonstrate the successful application of protein corona-mediated brain-targeted nanomicelles in the treatment of glioma, loading them with paclitaxel (PTX), and decorating them with amyloid β-protein (Aβ)-CN peptide (PTX/Aβ-CN-PMs). Aβ-CN peptide, like the Aβ1–42 peptide, specifically binds to the lipid-binding domain of apolipoprotein E (ApoE) in vivo to form the ApoE-enriched protein corona surrounding Aβ-CN-PMs (ApoE/PTX/Aβ-CN-PMs). The receptor-binding domain of the ApoE then combines with low-density lipoprotein receptor (LDLr) and LDLr-related protein 1 receptor (LRP1r) expressed in the blood–brain barrier and glioma, effectively mediating brain-targeted delivery. Methods PTX/Aβ-CN-PMs were prepared using a film hydration method with sonication, which was simple and feasible. The specific formation of the ApoE-enriched protein corona around nanoparticles was characterized by Western blotting analysis and LC–MS/MS. The in vitro physicochemical properties and in vivo anti-glioma effects of PTX/Aβ-CN-PMs were also well studied. Results The average size and zeta potential of PTX/Aβ-CN-PMs and ApoE/PTX/Aβ-CN-PMs were 103.1 nm, 172.3 nm, 7.23 mV, and 0.715 mV, respectively. PTX was efficiently loaded into PTX/Aβ-CN-PMs, and the PTX release from rhApoE/PTX/Aβ-CN-PMs exhibited a sustained-release pattern in vitro. The formation of the ApoE-enriched protein corona significantly improved the cellular uptake of Aβ-CN-PMs on C6 cells and human umbilical vein endothelial cells (HUVECs) and enhanced permeability to the blood–brain tumor barrier in vitro. Meanwhile, PTX/Aβ-CN-PMs with ApoE-enriched protein corona had a greater ability to inhibit cell proliferation and induce cell apoptosis than taxol. Importantly, PTX/Aβ-CN-PMs exhibited better anti-glioma effects and tissue distribution profile with rapid accumulation in glioma tissues in vivo and prolonged median survival of glioma-bearing mice compared to those associated with PMs without the ApoE protein corona. Conclusions The designed PTX/Aβ-CN-PMs exhibited significantly enhanced anti-glioma efficacy. Importantly, this study provided a strategy for the rational design of a protein corona-based brain-targeted drug delivery system. More crucially, we utilized the unfavorable side of the protein corona and converted it into an advantage to achieve brain-targeted drug delivery. Graphical Abstract

Nelumbo nucifera Gaertn. is an aquatic plant in the family Nelumbonaceae, and almost every part has medicinal uses. It has been established that alkaloids are one of the main components in N. nucifera. This review focuses on the traditional uses of N. nucifera, the alkaloid constituents in each part of the plant and their structural classification, providing a comprehensive overview of the profiles of alkaloids isolated from N. nucifera and their antitumor activities. The efficiency and molecular mechanism of the alkaloids against specific tumors are reported, and their effects are discussed according to the hallmarks of cancer, highlighting their significance during cancer treatment. Furthermore, with the discovery of a new structural type of tribenzylisoquinolines alkaloid, neoliensinine, the antitumor effect of alkaloids in N. nucifera can be inferred from the structure of isoquinolines. This review aims to provide a theoretical basis for further development of natural products and new therapeutic agents in clinical practice and research on the mechanism of alkaloids in N. nucifera.

The endosomal sorting complex required for transport (ESCRT) machinery plays a key role in the repair of damaged plasma membranes with puncta form and removes pores from the plasma membrane in regulated cell death, apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy. ESCRT-I overexpression and ESCRT-III-associated charged multivesicular body protein (CHMP) 4B participate in apoptosis, and the ESCRT-1 protein TSG 101 maintains low levels of ALIX and ALG-2 and prevents predisposition to apoptosis. The ESCRT-III components CHMP2A and CHMP4B are recruited to broken membrane bubble sites with the requirement of extracellular Ca2+, remove membrane vesicles from cells, and delay the time required for active MLKL to mediate necroptosis, thus preserving cell survival. CHMP4B disturbed pyroptosis by recruiting around the plasma membrane neck to remove the GSDMD pores and preserve plasma membrane integrity depending on Ca2+ influx. The accumulation of the ESCRT-III subunits CHMP5 and CHMP6 in the plasma membrane is increased by the classical ferroptosis activators erastin-1 and ras-selective lethal small molecule 3 (RSL3) upon cytosolic calcium influx and repairs the ferroptotic plasma membrane. ESCRT-III- and VPS4-induced macroautophagy, ESCRT-0-initiated microautophagy. ESCRT-I, ESCRT-II, ESCRT-III, ALIX, and VPS4A are recruited to damaged lysosomes and precede lysophagy, indicating that ESCRT is a potential target to overcome drug resistance during tumor therapy.

Abstract Background Treatment of perforator involving aneurysm (piAN) remains a challenge to open and endovascular neurosurgeons. Our aim is to demonstrate a primary outcome of endovascular therapy for piANs with the use of perforator preservation technologies (PPT) based on a new neuro-interventional classification. Methods The piANs were classified into type I: aneurysm really arises from perforating artery, type II: saccular aneurysm involves perforating arteries arising from its neck (IIa) or dome (IIb), and type III: fusiform aneurysm involves perforating artery. Stent protection technology of PPT was applied in type I and III aneurysms, and coil-basket protection technology in type II aneurysms. An immediate outcome of aneurysmal obliteration after treatment was evaluated (satisfactory obliteration: the saccular aneurysm body is densely embolized (I), leaving a gap in the neck (IIa) or dome (IIb) where the perforating artery arising; fusiform aneurysm is repaired and has a smooth inner wall), and successful perforating artery preservation was defined as keeping the good antegrade flow of those perforators on postoperative angiography. The periprocedural complication was closely monitored, and clinical and angiographic follow-ups were performed. Results Six consecutive piANs (2 ruptured and 4 unruptured; 1 type I, 2 type IIa, 2 type IIb, and 1 type III) in 6 patients (aged from 43 to 66 years; 3 males) underwent endovascular therapy between November 2017 and July 2019. The immediate angiography after treatment showed 6 aneurysms obtained satisfactory obliteration, and all of their perforating arteries were successfully preserved. During clinical follow-up of 13–50 months, no ischemic or hemorrhagic event of the brain occurred in the 6 patients, but has one who developed ischemic event in the territory of involving perforators 4 h after operation and completely resolved within 24 h. Follow-up angiography at 3 to 10M showed patency of the parent artery and perforating arteries of treated aneurysms, with no aneurysmal recurrence. Conclusions Our perforator preservation technologies on the basis of the new neuro-interventional classification seem feasible, safe, and effective in protecting involved perforators while occluding aneurysm.

Abstract Background Dyslipidemia is a major risk factor for atherosclerotic cardiovascular disease and a leading cause of death worldwide. The clinical utility of commonly used lipid-lowering drugs such as statins and fibrates is sometimes limited by the occurrence of various adverse reactions. Recently, berberine (BBR) has received increasing attention as a safer and more cost-effective option to manage dyslipidemia. Thus, a high-quality randomized controlled trial to evaluate the efficacy and safety of BBR in the treatment of dyslipidemia is deemed necessary. Methods/design This is a randomized, double-blind, and placebo-controlled clinical trial. A total of 118 patients with dyslipidemia will be enrolled in this study and randomized into two groups at a ratio of 1:1. BBR or placebo will be taken orally for 12 weeks. The primary outcome is the percentage of low-density lipoprotein cholesterol reduction at week 12. Other outcome measures include changes in other lipid profiles, high sensitivity C-reactive protein, blood pressure, body weight, Bristol Stool Chart, traditional Chinese medicine symptom form, adipokine profiles, and metagenomics of intestinal microbiota. Safety assessment includes general physical examination, blood and urine routine test, liver and kidney function test, and adverse events. Discussion This trial may provide high-quality evidence on the efficacy and safety of BBR for dyslipidemia. Importantly, the findings of this trial will help to identify patient and disease characteristics that may predict favorable outcomes of treatment with BBR and optimize its indication for clinical use. Trial registration Chinese Clinical Trial Registry ChiCTR1900021361 . Registered on 17 February 2019.

Introduction The contribution made by e-cigarettes to smoking cessation continues to be controversial. Reports suggest that teenagers are becoming increasingly addicted to e-cigarettes and that e-cigarette use in adolescents is associated with subsequent cigarette smoking. Methods Systematic searches of eleven databases were conducted (January 2015 to June 2020). Systematic reviews, randomized controlled trials (RCTs) and cohort studies comparing e-cigarettes with placebo e-cigarettes, nicotine replacement therapy (NRT) or no e-cigarette use were included. The two primary outcomes were smoking cessation among smokers and smoking initiation among non-smoking teenagers. The secondary outcome was adverse events. Data were synthesized using risk ratio (RR) or adjusted odds ratio (AOR) with 95% confidence interval (CI). Results Six systematic reviews, 5 RCTs and 24 cohort studies were identified. For smoking cessation, findings from 4 systematic reviews indicated that e-cigarettes contributed to cessation while one found the opposite. Meta-analysis of 5 RCTs suggested that e-cigarettes were superior to NRT or placebo for smoking cessation (RR=1.55; 95% CI: 1.00–2.40; I 2 =57.6%; low certainty; 5 trials, n=4025). Evidence from 9 cohort studies showed that e-cigarette use was not associated with cessation (AOR=1.16; 95% CI: 0.88–1.54; I 2 =69.0%; n=22220). Subgroup analysis suggested that intensive e-cigarette use may be associated with cessation. In terms of smoking initiation, adolescents who ever used e-cigarettes had a greater risk for smoking initiation than non-users (AOR=2.91; 95% CI: 2.61–3.23; I 2 =61.0%; 15 trials, n=68943), the findings were consistent with one included systematic review. No serious adverse events were reported in the included studies. Conclusions Low certainty evidence suggests that e-cigarettes appear to be potentially effective for smoking cessation. The use of e-cigarettes in adolescents may be associated with smoking initiation. No serious adverse events were reported.

ObjectivesWe aim to build a students' own engagement in original microbiological course-based undergraduate research experience (CUREs) model served two research and teaching scientific purposes including students' scientific literacy skills and instructors' role, which could further be applied as contribution to broader scientific knowledge and conduct novel research in their future research experience and careers.MethodsWe describe a student-driven CUREs model on the microorganism species in female vaginal using general bacterial culture techniques and high-throughput 16S rRNA gene amplicon sequencing to enable students to center experimental research method under the direction of instructors. A total of 8 undergraduate students and 5 instructors from Shanghai Jiao Tong University School of Medicine participated in the project. The CUREs were divided in four operating scopes: project planning, implementation, summarizing and feedback phases. Instructors help students to develop learning research goals.ResultsThis project helped students to gain “hard skills” experiences in scientific theoretical research process and technical practices. Students reached the conclusion that Lactobacillus species dominated the primary vaginal microbiota in reproductive-age women, 16S rRNA sequencing is a method widely applied for microbiology detection. CUREs also increased students' engagement in scientific experiments and promote 3 learning goals in “soft skills”: (1) Develop students' self-study and efficacy ability, expression capability and professional research communication skills; (2) Strengthen students' motivation and ownership in science research, overcoming failure, benefitting persistence and patience, building professional science identity, competence, and confidence in collaboration, implement spirit of rigorous and carefulness; (3) Obtain authorship, independent and logical thinking capability, summarizing ability and confidence enhancement. Instructors proposed guiding research question for the students and determine evidence in achieving pedagogical goals in CUREs.ConclusionsOur microbiological CUREs project served two scientific purposes: research and teaching, which increase students' engagement in promoting learning gains in scientific research skills, ownership, identity development, and spirit of motivation, self-efficacy, persistence, collaboration, communication, as well as opportunities to make relevant scientific discoveries. These abilities equipped them with essential foundation for the subsequent collaborative experiments and future scientific study.

In β-thalassemia, free α-globin chains are unstable and tend to aggregate or degrade, releasing toxic heme, porphyrins and iron, which produce reactive oxygen species (ROS). α-Hemoglobin-stabilizing protein (AHSP) is a potential modifier of β-thalassemia due to its ability to escort free α-globin and inhibit the cellular production of ROS. The influence of AHSP on the redox equilibrium raises the question of whether AHSP expression is regulated by components of ROS signaling pathways and/or canonical redox proteins. Here, we report that AHSP expression in K562 cells could be stimulated by NFE2-related factor 2 (Nrf2) and its agonist tert-butylhydroquinone (tBHQ). This tBHQ-induced increase in AHSP expression was also observed in Ter119+ mouse erythroblasts at each individual stage during terminal erythroid differentiation. We further report that the AHSP level was elevated in α-globin-overexpressing K562 cells and staged erythroblasts from βIVS-2-654 thalassemic mice. tBHQ treatment partially alleviated, whereas Nrf2 or AHSP knockdown exacerbated, α-globin precipitation and ROS production in fetal liver-derived thalassemic erythroid cells. MafG and Nrf2 occupancy at the MARE-1 site downstream of the AHSP transcription start site was detected in K562 cells. Finally, we show that MafG facilitated the activation of the AHSP gene in K562 cells by Nrf2. Our results demonstrate Nrf2-mediated feedback regulation of AHSP in response to excess α-globin, as occurs in β-thalassemia.

Long noncoding RNAs (lncRNAs) play important roles in a variety of biological processes. Knocking out or knocking down some lncRNA genes can lead to death or infertility. These lncRNAs are called essential lncRNAs. Identifying the essential lncRNA is of importance for complex disease diagnosis and treatments. However, experimental methods for identifying essential lncRNAs are always costly and time consuming. Therefore, computational methods can be considered as an alternative approach. We propose a method to identify essential lncRNAs by combining network centrality measures and lncRNA sequence information. By constructing a lncRNA-protein-protein interaction network, we measure the essentiality of lncRNAs from their role in the network and their sequence together. We name our method as the systematic gene importance index (SGII). As far as we can tell, this is the first attempt to identify essential lncRNAs by combining sequence and network information together. The results of our method indicated that essential lncRNAs have similar roles in the LPPI network as the essential coding genes in the PPI network. Another encouraging observation is that the network information can significantly boost the predictive performance of sequence-based method. All source code and dataset of SGII have been deposited in a GitHub repository (https://github.com/ninglolo/SGII).

ObjectiveThe aim of this study is to investigate the safety and efficiency of a Jrecan® flow restoration system, a novel thrombectomy device, in an arterial thromboembolic occlusion model of Beagle dogs.MethodsA total of 12 Beagle dogs with acute thromboembolism were randomized to receive mechanical thrombectomy with either Jrecan® flow restoration device or TrevoTM PROVUE Device (2:1). The efficacy and safety of the two devices, including recanalization rate, the presence of distal embolism, vasospasm, vessel perforation, and vessel injuries were evaluated through DSA and microscopic examination.ResultA 100% recanalization rate (mTICI 2b/3) was achieved in both groups. Endothelial and subendothelial injuries occurred in all target vessels. Focal disruption of internal elastic lamina was observed in 4 cases. The mean vessel injury score of the Jrecan® group was 1.16 ± 0.48, significantly lower than that of the TrevoTM group (1.54 ± 0.8) (P < 0.001).ConclusionThe Jrecan® and TrevoTM devices demonstrated an equally high recanalization rate in Beagle dogs with acute thromboembolism. However, histological findings revealed that the Jrecan® stent seemed to be safer than the TrevoTM device during clot retrieval, which might be related to a more appropriate radial force provided by the Jrecan® stent that resulted from its wider cell design.

The mechanism of the papaverine (PV) for the treatment of cerebral ischemia remains unclear. A total of 42 mice induced with focal cerebral ischemia were randomly divided into three groups: PV,baicalin (BA)and vehicle group. Both PV and BA could significantly reduce the ischemic infarct volume (P

The rice mutant ossac4 (starch accumulating 4) was raised from seeds of the rice (Oryza sativa L.) indica maintainer line Xinong 1B treated with ethyl methanesulfonate. The distal and medial portions of the second leaf displayed premature senescence in the ossac4 mutant at the four-leaf stage. Physiological and biochemical analysis, and cytological examination revealed that the ossac4 mutant exhibited the premature leaf senescence phenotype. At the four-leaf stage, the leaves of the ossac4 mutant exhibited significantly increased contents of starch compared with those of the wild type (WT). Quantitative real-time PCR analysis showed that the expression levels of photosynthesis-associated genes were down-regulated and the expression levels of glucose metabolism-associated genes were abnormal. Genetic analysis indicated that the ossac4 mutation was controlled by a single recessive nuclear gene. The OsSAC4 gene was localized to a 322.7-kb interval between the simple-sequence repeat marker XYH11-90 and the single-nucleotide polymorphism marker SNP5300 on chromosome 11. The target interval contained 20 annotated genes. The present results demonstrated that ossac4 represents a novel starch accumulation and premature leaf senescence mutant, and lays the foundation for cloning and functional analysis of OsSAC4.

For the normal model with a known mean, the Bayes estimation of the variance parameter under the conjugate prior is studied in Lehmann and Casella (1998) and Mao and Tang (2012). However, they only calculate the Bayes estimator with respect to a conjugate prior under the squared error loss function. Zhang (2017) calculates the Bayes estimator of the variance parameter of the normal model with a known mean with respect to the conjugate prior under Stein’s loss function which penalizes gross overestimation and gross underestimation equally, and the corresponding Posterior Expected Stein’s Loss (PESL). Motivated by their works, we have calculated the Bayes estimators of the variance parameter with respect to the noninformative (Jeffreys’s, reference, and matching) priors under Stein’s loss function, and the corresponding PESLs. Moreover, we have calculated the Bayes estimators of the scale parameter with respect to the conjugate and noninformative priors under Stein’s loss function, and the corresponding PESLs. The quantities (prior, posterior, three posterior expectations, two Bayes estimators, and two PESLs) and expressions of the variance and scale parameters of the model for the conjugate and noninformative priors are summarized in two tables. After that, the numerical simulations are carried out to exemplify the theoretical findings. Finally, we calculate the Bayes estimators and the PESLs of the variance and scale parameters of the S&P 500 monthly simple returns for the conjugate and noninformative priors.

A series of new complexes, [Ln (2,4-DMBA)3(5,5′-DM-2,2′-bipy)]2 (Ln = Sm(1), Eu (2)), [Pr (2,4-DMBA)3 (5,5′-DM-2,2′-bipy)]2·0.5(C2H5OH) (3), [Ln (2,4-DMBA)3 (5,5′-DM-2,2′-bipy)]2·0.5(2,4-DMBAH)·0.25(5,5′-DM-2,2′-bipy) (Ln = Tb (4), Dy (5)) (2,4-DMBA = 2,4-dimethylbenzoate, 5,5′-DM-2,2′-bipy = 5,5′-dimethy-2,2′-bipyridine) were synthesized via hydrothermal reaction conditions. The complexes were characterized through elemental analysis, Infrared spectra (IR), Raman (R) spectra, UV-Vis spectra, single X-ray diffraction. Single crystal data show that complexes 1–5 are binuclear complexes, but they can be divided into three different crystal structures. The thermal decomposition mechanism of complexes 1–5 were investigated by the technology of simultaneous TG/DSC-FTIR. What’s more, the luminescent properties of complexes 1–2 and 4 were discussed, and the luminescence lifetime (τ) of complexes 2 and 4 were calculated.

Background: Shufeng Jiedu capsule has been widely used in China for acute upper respiratory tract infections (AURTIs). The aim of this study was to evaluate its effectiveness and safety for AURTIs.Methods: Randomized controlled trials comparing SFJD with conventional drug for patients with AURTIs were included. Eight databases were searched from their inceptions to February 2021. Data was synthesized using risk ration (RR) or mean difference (MD) with their 95% confidence interval (CI). The primary outcome was resolution time of typical symptoms.Results: Twenty-five RCTs involving 3410 patients were included. SFJD in combination with conventional drug was associated with; in common cold shortening the duration of fever (MD −1.54 days, 95% CI [−2.15,−0.92], I2 = 80%, n = 385, 3 trials) and cough (MD −1.22 days, 95% CI [−1.52, −0.93]); in herpangina, shortening the duration of fever (MD -0.68 days, 95% CI [−1.15, −0.21], I2 = 68%, n = 140, 2 trials) and blistering (MD −0.99 days, 95% CI [−1.23, −0.76], n = 386, 3 trials); in acute tonsillitis and acute pharyngitis shortening the duration of fever (MD −1.13 days, 95% CI [−1.36, −0.90], I2 = 33%, n = 688, 7 trials) and sore throat (MD −1.13 days, 95% CI [−1.40, −0.86], I2 = 84.1%, n = 1194, 10 trials). SFJD also improving their cure rate with a range (1–5 days). No serious adverse events were reported.Conclusion: Low certainty evidence suggests that SFJD appears to shorten the duration of symptoms in AURTIs, improve cure rate and seems safe for application. However, high quality placebo controlled trials are warranted to confirm its benefit.

Positive, continuous, and right-skewed data are fit by a mixture of gamma and inverse gamma distributions. For 16 hierarchical models of gamma and inverse gamma distributions, there are only 8 of them that have conjugate priors. We first discuss some common typical problems for the eight hierarchical models that do not have conjugate priors. Then, we calculate the Bayesian posterior densities and marginal densities of the eight hierarchical models that have conjugate priors. After that, we discuss the relations among the eight analytical marginal densities. Furthermore, we find some relations among the random variables of the marginal densities and the beta densities. Moreover, we discuss random variable generations for the gamma and inverse gamma distributions by using the R software. In addition, some numerical simulations are performed to illustrate four aspects: the plots of marginal densities, the generations of random variables from the marginal density, the transformations of the moment estimators of the hyperparameters of a hierarchical model, and the conclusions about the properties of the eight marginal densities that do not have a closed form. Finally, we illustrate our method by a real data example, in which the original and transformed data are fit by the marginal density with different hyperparameters.

Imprecision is commonly encountered with respect to powers and predictive powers in clinical trials. In this article, we investigate the imprecision issues of four powers (Classical Power, Classical Conditional Power, Bayesian Power, and Bayesian Conditional Power) and eight predictive powers. To begin with, we derive the probabilities of Control Superior (CS), Treatment Superior (TS), and Equivocal (E) of the four powers and the eight predictive powers, and evaluate the limits of the probabilities at point 0. Moreover, we conduct extensive numerical experiments to exemplify the imprecision issues of the four powers and the eight predictive powers. In the numerical experiments, first, we compute the probabilities of CS, TS, and E for the four powers as functions of the sample size of the future data when the true treatment effect favors control, treatment, and equivocal, respectively. Second, we compute the probabilities of CS, TS, and E for the eight predictive powers as functions of the sample size of the future data under the sceptical prior and the optimistic prior, respectively. Finally, we carry out a real data example to show the prominence of the methods.

PURPOSEWe aimed to study the technical and clinical outcome of urgent transcatheter arterial embolization (TAE) for postoperative arterial complications after pelvic or hip surgery, and to accumulate additional experience about the role of embolization for these injuries.METHODSPatients who received TAE procedure for arterial complications after pelvic or hip surgery between September 1st, 2002 and December 1st, 2014 were screened on medical records and included in the analysis. Angiographic findings included active contrast agent extravasation, pseudoaneurysm formation, arteriovenous fistula, and other suspicious signs such as sighting of coarse margin or distortion of vessels. Embolic agents consisted of coils, gelatin sponge, and polyvinyl alcohol. Technical success was defined as complete occlusion of targeted artery through angiography, and clinical success as sustained resolution of symptoms.RESULTSA total of 22 patients (15 males, 19–76 years old) were enrolled. Prior to TAE, 12 patients developed hemorrhagic shock and the remaining 10 patients had hemorrhage-related pain, hematoma, or anemia. Contrast agent extravasation occurred in 12 cases, pseudoaneurysm formation in 5 cases, and other suspicious signs in 5 cases. Injury occurred in the internal iliac artery stem in 6 cases, inferior gluteal artery in 6 cases and superior gluteal artery in 6 cases. Multiple vascular lesions appeared in 5 cases. After TAE, technical success occurred in 22 patients and clinical success in 21 patients (95.5%). A 36-year-old woman died of irreversible multiple organ failure; no other severe procedure-related complications were recorded.CONCLUSIONTAE is safe and effective for postoperative arterial complications after pelvic or hip surgery.

Transforming growth factor-β (TGF-β) is a crucial pathogenic mediator of inflammatory diseases. In tissue fibrosis, TGF-β regulates the pathogenic activity of infiltrated immunocytes and promotes extracellular matrix production via de novo myofibroblast generation and kidney cell activation. In cancer, TGF-β promotes cancer invasion and metastasis by enhancing the stemness and epithelial mesenchymal transition of cancer cells. However, TGF-β is highly pleiotropic in both tissue fibrosis and cancers, and thus, direct targeting of TGF-β may also block its protective anti-inflammatory and tumor-suppressive effects, resulting in undesirable outcomes. Increasing evidence suggests the involvement of long non-coding RNAs (lncRNAs) in TGF-β-driven tissue fibrosis and cancer progression with a high cell-type and disease specificity, serving as an ideal target for therapeutic development. In this review, the mechanism and translational potential of TGF-β-associated lncRNAs in tissue fibrosis and cancer will be discussed.

Chronic kidney disease (CKD) is a major cause of morbidity and mortality worldwide, imposing a great burden on the healthcare system. Regrettably, effective CKD therapeutic strategies are yet available due to their elusive pathogenic mechanisms. CKD is featured by progressive inflammation and fibrosis associated with immune cell dysfunction, leading to the formation of an inflammatory microenvironment, which ultimately exacerbating renal fibrosis. Transforming growth factor β1 (TGF-β1) is an indispensable immunoregulator promoting CKD progression by controlling the activation, proliferation, and apoptosis of immunocytes via both canonical and non-canonical pathways. More importantly, recent studies have uncovered a new mechanism of TGF-β1 for de novo generation of myofibroblast via macrophage-myofibroblast transition (MMT). This review will update the versatile roles of TGF-β signaling in the dynamics of renal immunity, a better understanding may facilitate the discovery of novel therapeutic strategies against CKD.

Objective: To present the evidence of the therapeutic effects and safety of Chinese herbal medicine (CHM) used with or without conventional western therapy for COVID-19.Methods: Clinical studies on the therapeutic effects and safety of CHM for COVID-19 were included. We summarized the general characteristics of included studies, evaluated methodological quality of randomized controlled trials (RCTs) using the Cochrane risk of bias tool, analyzed the use of CHM, used Revman 5.4 software to present the risk ratio (RR) or mean difference (MD) and their 95% confidence interval (CI) to estimate the therapeutic effects and safety of CHM.Results: A total of 58 clinical studies were identified including RCTs (17.24%, 10), non-randomized controlled trials (1.72%, 1), retrospective studies with a control group (18.97%, 11), case-series (20.69%, 12) and case-reports (41.38%, 24). No RCTs of high methodological quality were identified. The most frequently tested oral Chinese patent medicine, Chinese herbal medicine injection or prescribed herbal decoction were: Lianhua Qingwen granule/capsule, Xuebijing injection and Maxing Shigan Tang. In terms of aggravation rate, pooled analyses showed that there were statistical differences between the intervention group and the comparator group (RR 0.42, 95% CI 0.21 to 0.82, six RCTs; RR 0.38, 95% CI 0.23 to 0.64, five retrospective studies with a control group), that is, CHM plus conventional western therapy appeared better than conventional western therapy alone in reducing aggravation rate. In addition, compared with conventional western therapy, CHM plus conventional western therapy had potential advantages in increasing the recovery rate and shortening the duration of fever, cough and fatigue, improving the negative conversion rate of nucleic acid test, and increasing the improvement rate of chest CT manifestations and shortening the time from receiving the treatment to the beginning of chest CT manifestations improvement. For adverse events, pooled data showed that there were no statistical differences between the CHM and the control groups.Conclusion: Current low certainty evidence suggests that there maybe a tendency that CHM plus conventional western therapy is superior to conventional western therapy alone. The use of CHM did not increase the risk of adverse events.

Background: The World Health Organization characterized the Coronavirus disease 2019 (COVID-19) as a pandemic on March 11th. Many clinical trials on COVID-19 have been registered, and we aim to review the study characteristics and provide guidance for future trials to avoid duplicated effort. Methods: Studies on COVID-19 registered before March 3rd, 2020 on eight registry platforms worldwide were searched and the data of design, participants, interventions, and outcomes were extracted and analyzed. Results: Three hundred and ninety-three studies were identified and 380 (96.7%) were from mainland China, while 3 in Japan, 3 in France, 2 in the US, and 3 were international collaborative studies. Two hundred and sixty-six (67.7%) aimed at therapeutic effect, others were for prevention, diagnosis, prognosis, etc. Two hundred and two studies (51.4%) were randomized controlled trials. Two third of therapeutic studies tested Western medicines including antiviral drugs (17.7%), stem cell and cord blood therapy (10.2%), chloroquine and derivatives (8.3%), 16 (6.0%) on Chinese medicines, and 73 (27.4%) on integrated therapy of Western and Chinese medicines. Thirty-one studies among 266 therapeutic studies (11.7%) used mortality as primary outcome, while the most designed secondary outcomes were symptoms and signs (47.0%). Half of the studies (45.5%) had not started recruiting till March 3rd. Conclusion: Inappropriate outcome setting, delayed recruitment and insufficient numbers of new cases in China implied many studies may fail to complete. Strategies and protocols of the studies with robust and rapid data sharing are warranted for emergency public health events, helping the timely evidence-based decision-making.

The synthesis of high-molecular-weight poly(ε-caprolactone)s (PCLs) with enhanced mechanical properties remains challenging. Here we demonstrate the heterogeneous catalysis for the ring-opening polymerization (ROP) of ε-caprolactone (ε-CL). Using a zinc-cobalt double-metal cyanide complex [Zn-Co(III) DMCC] in the presence of around 1% mol epoxides, PCLs are achieved with high number-average molecular weights (Mns) of up to 177.7 kDa determined by the gel permeation chromatography. The [Zn]-OH active site of the complex triggers the cleavage of the epoxide at first, which is considered as the rate-determining step of the polymerization. The formed zinc-alkoxide species then initiates the ROP of ε-CL, affording most of the PCLs possessing one epoxide molecule embedded in the polymer chain and dihydroxyl terminals as revealed by the 1H NMR and MALDI-TOF MS spectroscopy. The PCL specimen with a corrected Mn of 110.4 kDa exhibits the tensile strength and elongation at break of as high as 40.2 MPa and 1060%, respectively. This work provides a facile and practical method for the synthesis of high-molecular-weight PCLs.

Long non-coding RNAs (lncRNAs) may be a regulatory factor of tumorigenesis. However, it is unclear what its biomechanisms are in breast cancer. In this study, different lncRNAs were detected in breast cancer through microarray analysis (GSE119233) and LINC01705 was selected for further study. qRT-PCR was then utilized for the detection of LINC01705 expression in breast cancer cells. A transwell assay, flow cytometry, 5-ethynyl-2′-deoxyuridine (EdU), a cell counting Kit-8 (CCK-8), and a wound-healing assay were performed to determine cell migration, invasion, apoptosis, and proliferation in breast cancer, respectively. For the identification of potential targets of LINC01705, dual-luciferase reporter gene and bioinformatics assays were conducted. Moreover, for the clarification of their interaction and roles in the regulation of the occurrence of breast cancer, Western blotting and RIP assays were conducted. Our findings revealed high LINC01705 expression in breast cancer tissues relative to adjacent non-cancerous tissues (n = 40, P < 0.001). Overexpression of LINC01705 notably enhanced cell migration and proliferation in breast cancer. In addition, LINC01705 positively regulated the translocated promoter region, nuclear basket protein (TPR) through competition with miR-186-5p. In conclusion, our results suggest that LINC01705 is implicated in the progression of breast cancer via competitively binding to miR-186-5p as a competing endogenous RNA (ceRNA), thereby regulating TPR expression.

α-Terpineol has been widely used in daily chemical, pharmaceutical, food, and flavor industries due to its pleasant odor with high economic value and pharmacological action. Our previous study showed that Penicillium digitatum DSM 62840 was an efficient biocatalyst for the transformation of limonene to α-terpineol. Thus, it was meaningful to explore the genome features and the gene expression differences of strain DSM 62840 during limonene biotransformation, and the detailed bioconversion pathways. In this study, the functional genes related to limonene bioconversion were investigated using genome and transcriptome sequences analysis. The results showed that the P. digitatum DSM 62840 genome was estimated to be 29.09 Mb and it encoded 9,086 protein-encoding genes. The most annotated genes were associated to some protein metabolism and energy metabolism functions. When the threshold for differentially expressed genes (DEGs) was set at twofold ratio, a total of 4,128, and 4,148 DEGs were identified in P_L_12h (limonene-treated condition) compared with P_0h (blank) and P_12h (limonene-untreated blank), respectively. Among them, the expression levels of genes involved in the biosynthesis of secondary metabolites, energy metabolism and ATP-binding cassette (ABC) transporters were significantly altered during the biotransformation. And the reliability of these results was further confirmed by quantitative real-time polymerase chain reaction (RT-qPCR). Moreover, we found that the enzyme participated in limonene biotransformation was inducible. This enzyme was located in the microsome, and it was inhibited by cytochrome P450 inhibitors. This indicated that the cytochrome P450 may be responsible for the limonene bioconversion. Several differentially expressed cytochrome P450 genes were further identified, such as PDIDSM_85260 and PDIDSM_67430, which were significantly up-regulated with limonene treatment. These genes may be responsible for converting limonene to α-terpineol. Totally, the genomic and transcriptomic data could provide valuable information in the discovery of related-genes which was involved in limonene biotransformation, pathogenicity of fungi, and investigation of metabolites and biological pathways of strain DSM 62840.

Abstract Background Previous studies have disclosed up‐regulation of MIR‐378 in acute myeloid leukemia (AML), and might consequently affect the outcome of the patients. Correspondingly, hypomethylation of MIR‐378 was also identified in AML, particularly for FAB‐M2 subtype with t(8;21) chromosomal translocation. Nevertheless, the methylation status of MIR‐378 has not been illustrated in myelodysplastic syndrome (MDS). Herein we designed to understand the methylation pattern of MIR‐378 involved in MDS and clinical interrelation thereof. Methods Real‐time quantitative methylation‐specific PCR (RQ‐MSP) was performed to evaluate the methylation degree of MIR‐378 5’‐flanking region on bone marrow mononuclear cells collected from 95 de novo MDS patients. Five gene mutations (IDH1, IDH2, DNMT3A, U2AF1, and SF3B1) were detected by high‐resolution melting analysis to further evaluate the clinical relevance of hypomethylation of MIR‐378. Results Unmethylated level of MIR‐378 5’‐flanking region was significantly higher in MDS patients than that in controls (p = .034). Hypomethylated MIR‐378 was identified in 20 of 95 (21%) cases with MDS. Male patients appeared to be more frequent to harbor MIR‐378 hypomethylation compared to female patients (15/55, 27.3% vs. 4/40, 10.0%, p = .04). There was no significant difference in age, white blood cell counts, platelet counts, hemoglobin concentration, and karyotypes between the patients with and without MIR‐378‐hypomethylation. Distinct distribution of five gene mutations was not observed in the two groups as well. However, MIR‐378‐hypomethylated patients had significantly shorter overall survival than those without MIR‐378 hypomethylation (p = .036). Moreover, among patients

Cancer: Clocking the triggers for tumor progression Two proteins involved in regulating circadian rhythms may promote cancer tumor growth by changing the internal structures of cells. Circadian clock proteins play key roles in cell division, metabolism, and immune responses. Certain clock proteins are implicated in uncontrolled cell and tumor growth. Yong-xin Ma at Sichuan University in Chengdu, China and co-workers have shown that two clock proteins, CLOCK and BMAL1, regulate the arrangement of F-actin microfilaments in the cytoskeleton of cells. The researchers found that CLOCK and BMAL1 interact with an enzyme that promotes the formation of cellular fibers and regulates cell shape and motility. The overexpression of these clock proteins in cancers increases the levels of this enzyme, which changes F-actin structures inside cells. This promotes cancer cell proliferation, migration, and invasion.