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BackgroundThis study aimed to synthesize the recommendations for prediction models in cardiovascular clinical practice guidelines (CPGs) and assess the methodological quality of the relevant primary modeling studies.MethodsWe performed a systematic literature search of all available cardiovascular CPGs published between 2018 and 2023 that presented specific recommendations (whether in support or non-support) for at least one multivariable clinical prediction model. For the guideline-recommended models, the assessment of the methodological quality of their primary modeling studies was conducted using the Prediction model Risk Of Bias ASsessment Tool (PROBAST).ResultsIn total, 46 qualified cardiovascular CPGs were included, with 69 prediction models and 80 specific recommendations. Of the 80 specific recommendations, 74 supported 57 models (53 were fully recommended and 4 were conditionally recommended) in cardiovascular practice with moderate to strong strength. Most of the guideline-recommended models were focused on predicting prognosis outcomes (53/57, 93%) in primary and tertiary prevention, focusing primarily on long-term risk stratification and prognosis management. A total of 10 conditions and 7 types of target population were involved in the 57 models, while heart failure (14/57, 25%) and a general population with or without cardiovascular risk factor(s) (12/57, 21%) received the most attention from the guidelines. The assessment of the methodological quality of 57 primary studies on the development of the guideline-recommended models revealed that only 40% of the modeling studies had a low risk of bias (ROB). The causes of high ROB were mainly in the analysis and participant domains.ConclusionsGlobal cardiovascular CPGs presented an unduly positive appraisal of the existing prediction models in terms of ROB, leading to stronger recommendations than were warranted. Future cardiovascular practice may benefit from well-established clinical prediction models with better methodological quality and extensive external validation.

Ultraviolet B (UVB) light exposure accelerates skin photoaging. Human adipose-derived stem cell exosomes (hADSC-Exos) and some antioxidants may have anti-photoaging effects. However, it is unknown whether the combination of hADSC-Exos and antioxidants plays a synergistic role in anti-photoaging. In cellular and 3D skin models, we showed that vitamin E (VE) and hADSC-Exos were optimal anti-photoaging combinations. In vivo, VE and hADSC-Exos increased skin tightening and elasticity in UVB-induced photoaging mice Combined treatment with VE and hADSC-Exos inhibited SIRT1/NF-κB pathway. These findings contribute to the understanding of hADSC-Exos in conjunction with other antioxidants, thereby providing valuable insights for the future pharmaceutical and cosmetic industries.

Background: This study aimed to investigate whether dexmedetomidine provides survival benefit in critically ill patients with sepsis-induced coagulopathy (SIC).Methods: Patients with sepsis-induced coagulopathy admitted to the ICU were identified from the Medical Information Marketplace for Intensive Care (MIMIC)-IV database. They were divided into two groups: patients who started dexmedetomidine within 48 h of ICU admission and lasted for more than 4 h and patients who did not receive dexmedetomidine as a control group. The primary outcome was 28-day hospital mortality, the secondary outcome was in-hospital mortality, and the extended outcomes included duration of mechanical ventilation and vasopressor use, ICU stay, and hospital stay. Propensity score matching (PSM) analysis was used to match patients who received dexmedetomidine with those who did not, and multivariable Cox models and logistics models were used to account for baseline differences and unmeasured confounders. An external validation was performed with the Critical care database comprising patients with infection at Zigong Fourth People’s Hospital.Results: After PSM, 592 patients who received dexmedetomidine were matched with 592 patients who did not receive dexmedetomidine. In the primary and secondary endpoints, dexmedetomidine was associated with a lower risk of 28-day hospital mortality (19.3% vs. 14.2%, hazard ratio (HR) 0.71; P = 0.020) and in-hospital mortality (22.3% vs. 16.4%, odds ratio (OR) 0.68; P = 0.017) in patients with SIC. Regarding the extended outcome, dexmedetomidine was also associated with a longer length of hospital stay (median 12.54 days vs. 14.87 days, P = 0.002) and longer ICU stay (median 5.10 days vs. 6.22 days, P = 0.009). In addition, the duration of mechanical ventilation was significantly increased in the dexmedetomidine group (median 41.62 h vs. 48.00 h, p = 0.022), while the duration of vasopressor use was not significantly different (median 36.67 h vs. 39.25 h, p = 0.194). Within 48 h of ICU stay, receiving a dose of dexmedetomidine greater than 0.474 μg/kg/h and continuous dexmedetomidine administration for 24–48 h may be associated with 28-day hospitalization outcomes in patients with SIC. External cohort validation also found that the use of dexmedetomidine after admission to the ICU can reduce 28-day mortality in patients with SIC.Conclusion: Dexmedetomidine administration is associated with reduced 28-day hospital mortality and in-hospital mortality in critically ill patients with SIC, and these findings deserve further verification in randomized controlled trials.

Ethnopharmacological relevanceOphiocordyceps sinensis (O. sinensis), a genus of ascomycete fungi, has been widedly used in China as a dietary supplement or natural remedy and intensively studied in various disease models with its immunomodulatory potentials. It is a rich source of various bioactive compounds and used for treating end-stage renal disease. This systematic review with clinical evidence aimed to highlight the efficacy and safety of O. Sinensis as an adjuvant treatment for patients undergoing dialysis.Materials and methodsA systematic search through nine electronic databases up to 31 April 2024, was conducted for related studies. The Cochrane risk-of-bias tool was used to evaluate the quality of studies. The Grading of Recommendations Assessment, Development, and Evaluation system was used to assess the certainty of evidence. Two researchers independently searched the literature and evaluated the risk of bias.ResultsAfter the screening, 35 randomized controlled trials (RCTs) involving 2,914 patients were eventually included. The meta-analysis showed that using O. sinensis effectively reduced the following outcomes in patients undergoing dialysis: C-reactive protein (15RCTs, MD = −2.22, 95% CI −3.24 to −1.20; very low certainty evidence); creatinine (22RCTs, MD =1.33, 95% CI −1.79 to −0.87; very low certainty evidence); blood urea nitrogen (21RCTs, MD = −1.57, 95% CI −2.07 to −1.07; low certainty evidence);. It could also effectively improve the following outcomes in patients undergoing dialysis: albumin (20RCTs, MD = −0.81, 95% CI −1.21 to −0.41; low certainty evidence); hemoglobin (19RCTs, MD = −1.00, 95% CI −1.43 to −0.57; low certainty evidence). The rate of adverse drug reactions was higher in the control group than in the experimental group (4RCTs, MD = 1.81, 95% CI 0.88–3.74).ConclusionThe current evidence indicates that patients with dialysis receiving O. sinensis in the adjuvant treatment may improve nutritional and micro-inflammatory status and renal function for both hemodialysis and peritoneal dialysis patients. However, some limitation affected the generalizability of our findings. High-quality studies evaluating mortality outcomes of patients with different dialytic modalities in CKD are warranted in future.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022324508, registration number CRD42022324508.

Abstract Background The transplantation of exosomes derived from human adipose-derived mesenchymal stem cells (hADSCs) has emerged as a prospective cellular-free therapeutic intervention for the treatment of neurodevelopmental disorders (NDDs), as well as autism spectrum disorder (ASD). Nevertheless, the efficacy of hADSC exosome transplantation for ASD treatment remains to be verified, and the underlying mechanism of action remains unclear. Results The exosomal long non-coding RNAs (lncRNAs) from hADSC and human umbilical cord mesenchymal stem cells (hUCMSC) were sequenced and 13,915 and 729 lncRNAs were obtained, respectively. The lncRNAs present in hADSC-Exos encompass those found in hUCMSC-Exos and are associated with neurogenesis. The biodistribution of hADSC-Exos in mouse brain ventricles and organoids was tracked, and the cellular uptake of hADSC-Exos was evaluated both in vivo and in vitro. hADSC-Exos promote neurogenesis in brain organoid and ameliorate social deficits in ASD mouse model BTBR T + tf/J (BTBR). Fluorescence in situ hybridization (FISH) confirmed lncRNA Ifngas1 significantly increased in the prefrontal cortex (PFC) of adult mice after hADSC-Exos intraventricular injection. The lncRNA Ifngas1 can act as a molecular sponge for miR-21a-3p to play a regulatory role and promote neurogenesis through the miR-21a-3p/PI3K/AKT axis. Conclusion We demonstrated hADSC-Exos have the ability to confer neuroprotection through functional restoration, attenuation of neuroinflammation, inhibition of neuronal apoptosis, and promotion of neurogenesis both in vitro and in vivo. The hADSC-Exos-derived lncRNA IFNG-AS1 acts as a molecular sponge and facilitates neurogenesis via the miR-21a-3p/PI3K/AKT signaling pathway, thereby exerting a regulatory effect. Our findings suggest a potential therapeutic avenue for individuals with ASD. Graphical Abstract

Naoxintong Capsule (NXT), a renowned traditional Chinese medicine (TCM) formulation, has been broadly applied in China for more than 30 years. Over decades, accumulating evidences have proven satisfactory efficacy and safety of NXT in treating cardiovascular and cerebrovascular diseases (CCVD). Studies have been conducted unceasingly, while this growing latest knowledge of NXT has not yet been interpreted properly and summarized comprehensively. Hence, we systematically review the advancements in NXT research, from its chemical constituents, quality control, pharmacokinetics, to its profound pharmacological activities as well as its clinical applications in CCVD. Moreover, we further propose specific challenges for its future perspectives: 1) to precisely clarify bioactivities of single compound in complicated mixtures; 2) to evaluate the pharmacokinetic behaviors of NXT feature components in clinical studies, especially drug-drug interactions in CCVD patients; 3) to explore and validate its multi-target mechanisms by integrating multi-omics technologies; 4) to re-evaluate the safety and efficacy of NXT by carrying out large-scale, multicenter randomized controlled trials. In brief, this review aims to straighten out a paradigm for TCM modernization, which help to contribute NXT as a piece of Chinese Wisdom into the advanced intervention strategy for CCVD therapy.

Improving the nutrient content of red soils in southern China is a priority for efficient rice production there. To assess the effectiveness of oilseed rape as green manure for the improvement of soil phosphorus nutrient supply and rice yield in red soil areas, a long-term field plot experiment was conducted comparing two species of rape, Brassica napus (BN) and Brassica juncea (BJ). The effects of returning oilseed rape on soil phosphorus availability, phosphorus absorption, and yield of subsequent rice under rice–green manure rotation mode were analyzed, using data from the seasons of 2020 to 2021. The study found that compared with winter fallow treatment (WT) and no-tillage treatment (NT), the soil available phosphorus content of BN was increased, and that of BJ was significantly increased. The content of water-soluble inorganic phosphorus of BJ increased, and that of BN increased substantially. Compared with the WT, the soil organic matter content and soil total phosphorus content of BN significantly increased, as did the soil available potassium content of BJ, and the soil total phosphorus content of BJ was significantly increased compared with NT. The soil particulate phosphorus content of BJ and BN was significantly increased by 14.00% and 16.00%, respectively. Compared with the WT, the phosphorus activation coefficient of BJ was significantly increased by 11.41%. The rice plant tiller number under the green manure returning treatment was significantly increased by 43.16% compared with the winter fallow treatment. The green manure returning measures increased rice grain yield by promoting rice tiller numbers; BN increased rice grain yield by 9.91% and BJ by 11.68%. Based on these results, returning oilseed rape green manure could augment the phosphorus nutrients of red soil and promote phosphorus availability. Rice–oilseed rape green manure rotation could increase rice grain yield.

BackgroundUnexplained recurrent implantation failure and the high cost of assisted reproductive techniques for those experiencing infertility have increasingly resulted in the use of acupuncture. However, the trends and research status of acupuncture on infertility resulting in natural conception have not been systematically summarized. This scoping review and knowledge graph analysis aimed to summarize existing clinical studies on acupuncture for infertility that resulted in natural conception.MethodsSeven databases, namely, PubMed, Embase, the Cochrane Library, CNKI, VIP, Wanfang Data, and SinoMed, were searched up to August 2023 (updated on 1 April). Two authors independently identified related clinical studies and systematic reviews, and extracted data from included studies on acupuncture for infertility; any discrepancies were resolved by discussion or judged by a third author. A meta-analysis was conducted based on randomized controlled trials (RCTs), and data were synthesized using risk ratios with 95% confidence intervals.ResultsOf the 310 articles meeting the inclusion criteria, 274 were primary studies, 7 were systematic reviews, and 29 were case reports. Reported adverse events included mild ovarian irritation and early signs of miscarriage. Out of the 274 primary studies, there were 40 (14.60%) cases of male infertility and 234 (85.40%) cases of female infertility. Current research highlights on acupuncture for infertility focused on female infertility caused by polycystic ovary syndrome, ovulation disorder, and luteinized unruptured follicle syndrome (LUFS), while acupuncture for male infertility was a hotspot in the early research stage. The meta-analysis also suggested that acupuncture was more effective than human chorionic gonadotropin (HCG) [RR = 1.89, 95% CI (1.47, 2.42), 11 RCTs, 662 participants]. Acupuncture combined with HCG was comparable to HCG [RR = 2.33, 95% CI (1.53, 3.55), four RCTs, 259 participants]. Compared with no treatment, acupuncture resulted in a higher pregnancy rate [RR = 22.12, 95% CI (1.39, 353.09), one RCT, 47 participants]. There was no statistical difference between acupuncture combined with HCG plus letrozole and HCG plus letrozole [RR = 1.56, 95% CI (0.84, 2.89), one RCT, 84 participants].ConclusionCurrent research highlights on acupuncture for infertility resulting in natural conception focused on female infertility caused by polycystic ovary syndrome, ovulation disorder, and LUFS, while studies on male infertility and female infertility caused by blockage in the fallopian tube, thin endometrium, and other factors were insufficient. Well-designed confirmatory clinical studies are still needed as the research hypotheses of most studies were unclear.

To meet the requirement of autonomous driving development, high-quality point cloud generation of the environment has become the focus of 4D mmWave radar development. On the basis of mass producibility and physical verifiability, a design method for improving the quality and density of point cloud imagery is proposed in this paper, including antenna design, array design, and the dynamic detection method. The utilization of apertures is promoted through antenna design and sparse MIMO array optimization using the genetic algorithm (GA). The hybrid strategy for complex point clouds is adopted using the proposed dynamic CFAR algorithm, which enables dynamic adjustment of the threshold by discriminating and calculating different scanning regions. The effectiveness of the proposed method is verified by simulations and practical experiments. Aiming at system manufacture, analysis methods for the ambiguity function (AF) and shooting and bouncing rays (SBR) tracing are introduced, and an mmWave radar system is realized based on the proposed method, with its performance proven by practical experiments.

Objective: This scoping review aims to document Chinese Patent Medicines (CPMs) for Type 2 Diabetes Mellitus, explore whether CPMs can improve patients’ health outcomes, and set priorities in addressing research gaps in this area. Methods: Following the framework of PRISMA-SCr, we proposed the research questions based on PICOS principle, and searched the CPMs for T2DM from three drug lists, followed by a systematic search of the literature in eight databases from their inception to June 22, 2023. Then, we developed the eligibility criteria and systematically reviewed the relevant studies, retained the studies about CPMs for T2DM, extracted the related data, and identified the differences across studies in structured charts. Results: A total of 25 types of CPMs were extracted from the three drug lists. Radix astragali appeared most frequently (19 times) among the herbal medicinal ingredients of CPMs. A total of 449 articles were included in the full-paper analysis ultimately, all of which were about 20 types of CPMs, and there were no related reports on the remaining five CPMs. Except about a quarter (25.39 %, 114/449) using CPMs alone, the remaining studies all involved the combination with oral hypoglycemics for T2DM. Biguanides are the most common drugs used in combination with CPMs (50.14 %, 168/335). Fasting plasma glucose (FPG) is the most frequently reported outcomes in efficacy evaluation (82.41 %, 370/449). Conclusion: There are a total of 25 types of CPMs currently available for T2DM patients. However, the volume of related evidence on these CPMs varies. It is necessary to standardize the combined use of CPMs and conventional medicine and select appropriate outcomes in future studies.

BackgroundThe profiles of bile acids (BAs) in patients with gallstone disease (GSD) have been found to be altered markedly though in an inconsistent pattern. This study aims to characterize the variation of the BA profiles in GSD patients, thereby to discover the potential metabolite biomarkers for earlier detection of GSD.MethodsLiterature search of eight electronic database in both English and Chinese was completed on May 11, 2023. The qualitative and quantitative reviews were performed to summarize the changes of BA profiles in GSD patients compared with healthy subjects. The concentrations of BAs were adopted as the primary outcomes and the weighted mean differences (WMDs) and 95% confidence interval (CI) were generated by random-effects meta-analysis models.ResultsA total of 30 studies were enrolled which included 2313 participants and reported the 39 BAs or their ratios. Qualitative review demonstrated serum Taurocholic Acid (TCA), Glycochenodeoxycholic acid (GCDCA), Glycocholic acid (GCA), Taurochenodeoxycholic acid (TCDCA), Glycodeoxycholic acid (GDCA) and Deoxycholic acid (DCA) were significantly increased in GSD patients compared with healthy subjects. Meta analysis was performed in 16 studies and showed that serum Total BAs (TBA) (WMD = 1.36μmol/L, 95%CI = 0.33; 2.4) was elevated however bile TBA (WMD = -36.96mmol/L, 95%CI = -52.32; -21.6) was declined in GSD patients. GCA (WMD = 0.83μmol/L, 95%CI = 0.06; 1.6) and TCA (WMD = 0.51μmol/L; 95%CI = 0.18; 0.85) were both increased in serum sample; TCDCA (WMD = 2.64mmol/L, 95%CI = 0.16; 5.12) was rising, however GCDCA (WMD = -13.82mmol/L, 95%CI = -21.86; -5.78) was falling in bile sample of GSD patients. The level of serum DCA in the GSD patients was found to be increased by using chromatography, yet decreased by chromatography mass spectrometry.ConclusionThe profiles of BAs demonstrated distinctive changes in GSD patients compared with healthy control subjects. Serum GCA, TCA and GCDCA, as the typically variant BAs, presented as a potential marker for earlier diagnosis of GSD, which could facilitate early prophylactic intervention. Yet, further validation of these biomarkers by longitudinal studies is still warranted in the future. PROSPERO registration number CRD42022339649.

Objective: To rapidly assess the effectiveness, safety, economy, and applicability of Shaoma Zhijing granule (SZG) for the treatment of children with tic disorders (TD), and provide currently available best evidence for decision-makers of health policies. Methods: We conducted a rapid health technology assessment (RHTA) to explore the value of SZG. A systematic literature search in eight literature databases and on three clinical trial registration platforms was performed. The literature was screened according to eligibility criteria. The screening process and data extraction were conducted by two reviewers, and the quality of the literature was also assessed. The results were summarized, analyzed, and presented in tables or figures. Results: A total of five randomized controlled trials (RCTs) were included in this study, of which one was published in English (in the Journal of Child Psychology and Psychiatry) and four in Chinese journals. The overall risk of bias for the five RCTs was evaluated as “some concerns.” SZG monotherapy or in combination with tiapride was better than tiapride alone in improving traditional Chinese medicine (TCM) syndromes and tic symptoms, with a daily cost of ¥67.50–107.22. Adverse events were mainly related to the digestive, respiratory, and neurological systems, but all were mild. Conclusion: Overall, the current RHTA of published, peer-reviewed literature has located a small body of evidence evaluating the use of SZG for the treatment of TD in children. SZG has effects on improving TCM syndromes and tic symptoms; the daily cost is ¥67.50–107.22; and all adverse events are mild. High-quality studies with long-term follow-up should be conducted, so as to provide local evidence and consistently guide and improve scientific decision-making.

BackgroundYoga is a non-pharmacological conservative therapeutic modality that can be employed for the management of chronic low back pain (CLBP). In this overview, we have summarized and evaluated data from current systematic reviews (SRs) on the use of yoga for CLBP.MethodsWe comprehensively searched SRs on the use of yoga for CLBP in nine electronic databases from inception to September 2023. The methodological quality was evaluated using the Assessment of Multiple Systematic Review Scale-2 (AMSTAR-2). The reporting quality of the included SRs was evaluated using the Preferred Reporting Item for Systematic Review and Meta-Analysis-2020 (PRISMA-2020), and the quality of data was graded using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Two independent researchers performed the screening, data extraction, and quality assessment process of SRs.ResultsA total of 13 SRs were included. The results of the AMSTAR-2 indicated that the methodological quality of the included studies was relatively low. The PRISMA-2020 checklist evaluation results indicated that methodological limitations in reporting, especially regarding data processing and presentation, were the main weaknesses. The GRADE assessment indicated that 30 outcomes were rated moderate, 42 were rated low level, and 20 were rated very low level. Downgrading factors were mainly due to the limitations of the included studies.ConclusionYoga appears to be an effective and safe non-pharmacological therapeutic modality for the Management of CLBP. Currently, it may exhibit better efficacy in improving pain and functional disability associated with CLBP. However, the methodological quality and quality of evidence for SRs/MAs in the included studies were generally low, and these results should be interpreted cautiously.

Objective: To evaluate the efficacy of traditional Chinese medicine (TCM) for preventing acute mountain sickness (AMS). Methods: We included randomized controlled trials (RCTs) which evalueded the effect of TCM for preventing AMS, compared with a placebo, no treatment or acetazolamide. The literature was searched in 6 major databases. RevMan 5.4 software was used for the meta-analysis. The relative risk for discrete variables and the mean difference for continuous variables with 95% confidence intervals (CIs) were applied to express the effect size. The risk of bias in the included studies was evaluated using the Cochrane risk assessment tool 2.0 (RoB 2.0), and the evidence certainty was assessed using the Grading of Recommendations Assessment and the Development and Evaluation (GRADE) approach. Results: Twenty RCTs involving 3015 participants and 16 TCM patent drugs were included. The overall risk of bias in the majority of studies (15/20) was of some concerns. In terms of the AMS incidence, Rhodiola rosea (R. rosea, Hong Jing Tian) and Ginkgo biloba (G. biloba, Yin Xing Ye) were equivalent to the placebo/no treatment [RR (95% CI): 0.66 (0.43–1.01), 0.82 (0.63–1.06), respectively]. The AMS incidence in the G. biloba group was higher than that in the acetazolamide group [RR (95% CI): 2.92 (1.69–5.06)]. In terms of improving the AMS symptom score on days 1 and 3 in the plateau, R. rosea and G. biloba were superior to the placebo or no treatment [MD (95% CI): -0.98 (-1.71, -0.25), -2.05 (-3.14, -0.95), respectively]. The other 14 Chinese patent medicines were evaluated in a single trial, and the majority of the results were negative. The subgroup analysis showed that the effect of R. rosea was related to the intervention time, way of ascending, and altitude. Conclusion: R. rosea and G. biloba were effective in improving AMS symptoms but had no effect in reducing the AMS incidence. There was insufficient evidence to support the use of other TCM patent drugs to prevent AMS. More randomized double-blind placebo-controlled trials are warranted to evaluate and screen effective Chinese patent medicines for AMS prevention.

Abstract Background Intracerebral hemorrhage (ICH) is a devastating disease, its mortality and disability rate are high. In China, hypertensive intracerebral hemorrhage (HICH) is responsible for 75% of all the cases of primary ICH. A lot of randomized controlled trials (RCTs) of traditional Chinese medicine (TCM) for treating HICH have been carried out. However, these RCTs have a lot of problems, such as heterogeneous outcomes, non-uniform point of measurement. These lead to systematic review/meta-analysis only can include a small number of studies. And outcome measures did not take the wishes of patients and other stakeholders into account. The aim of this study is to establish the core outcome set (COS) for future TCM clinical trials of HICH. Methods and analysis First, we will develop a long list of general outcomes by making systematic literature review and semi-structured interviews. Then healthcare professionals and patients with HICH will be invited to participate in two rounds of the Delphi survey to determine the importance of the outcome. Finally, a face-to-face consensus meeting will be conducted to determine the final COS of HICH, including what outcomes should be measured and when and how to measure the outcomes. Results We aim to develop a COS that includes TCM core syndrome for HICH to determine what outcomes should be reported and when and how to measure them. Conclusion By doing this, we can increase the reporting consistency and reduce the reporting bias in the outcome, which leads to the reuse of research data in meta-analysis and the making of informed healthcare decisions. Ethics and dissemination The entire project has received approval from the Ethics Committee of Xiyuan Hospital, China Academy of Chinese Medical Sciences. The final COS will be published and reported at the national and international conferences. Trial registration This study is registered with the Core Outcome Measures in Effectiveness Trials database as study 1475 . Registered on December 2019.

Abstract Background Large area skin trauma has always been a great challenge for both patients and clinicians. Exosomes originating from human adipose-derived mesenchymal stem cells (hADSCs) have been a novel promising cell-free treatment in cutaneous damage repair. Nevertheless, the low retention rate of exosomes post-transplantation in vivo remains a significant challenge in clinical applications. Herein, we purposed to explore the potential clinical application roles of hADSCs-Exos encapsulated in functional PF-127 hydrogel in wound healing. Methods hADSCs-Exos were isolated from human hADSCs by ultracentrifugation. An injectable, biocompatible, and thermo-sensitive hydrogel Pluronic F-127 hydrogel was employed to encapsulate allogeneic hADSCs-Exos, and this complex was topically applied to a full-thickness cutaneous wound in mice. On different days post-transplantation, the mice were sacrificed, and the skin tissue was excised for histological and immunohistochemical analysis. Results Compared with hADSCs-Exos or PF-127 only, PF-127/hADSCs-Exos complexes enhanced skin wound healing, promoted re-epithelialization, increased expression of Ki67, α-SMA, and CD31, facilitated collagen synthesis (Collagen I, Collagen III), up-regulated expression of skin barrier proteins (KRT1, AQP3), and reduced inflammation (IL-6, TNF-α, CD68, CD206). By using PF-127/hADSCs-Exos complexes, hADSCs-Exos can be administrated at lower doses frequency while maintaining the same therapeutic effects. Conclusion Administration of hADSCs-Exos in PF-127 improves the efficiency of exosome delivery, maintains the bioactivity of hADSCs-Exos, and optimizes the performance of hADSCs-Exos. Thus, this biomaterial-based exosome will be a promising treatment approach for the cutaneous rejuvenation of skin wounds.

Abstract Background Obesity leads to a decline in the exercise capacity of skeletal muscle, thereby reducing mobility and promoting obesity-associated health risks. Dietary intervention has been shown to be an important measure to regulate skeletal muscle function, and previous studies have demonstrated the beneficial effects of docosahexaenoic acid (DHA; 22:6 ω-3) on skeletal muscle function. At the molecular level, DHA and its metabolites were shown to be extensively involved in regulating epigenetic modifications, including DNA methylation, histone modifications, and small non-coding microRNAs. However, whether and how epigenetic modification of mRNA such as N6-methyladenosine (m6A) mediates DHA regulation of skeletal muscle function remains unknown. Here, we analyze the regulatory effect of DHA on skeletal muscle function and explore the involvement of m6A mRNA modifications in mediating such regulation. Results DHA supplement prevented HFD-induced decline in exercise capacity and conversion of muscle fiber types from slow to fast in mice. DHA-treated myoblasts display increased mitochondrial biogenesis, while slow muscle fiber formation was promoted through DHA-induced expression of PGC1α. Further analysis of the associated molecular mechanism revealed that DHA enhanced expression of the fat mass and obesity-associated gene (FTO), leading to reduced m6A levels of DNA damage-induced transcript 4 (Ddit4). Ddit4 mRNA with lower m6A marks could not be recognized and bound by the cytoplasmic m6A reader YTH domain family 2 (YTHDF2), thereby blocking the decay of Ddit4 mRNA. Accumulated Ddit4 mRNA levels accelerated its protein translation, and the consequential increased DDIT4 protein abundance promoted the expression of PGC1α, which finally elevated mitochondria biogenesis and slow muscle fiber formation. Conclusions DHA promotes mitochondrial biogenesis and skeletal muscle fiber remodeling via FTO/m6A/DDIT4/PGC1α signaling, protecting against obesity-induced decline in skeletal muscle function.

Here, the authors use a tapered optical fibre to create a dynamic, reversible strain in a suspended WSe2 monolayer, and observe that dark excitons are funnelled to high-strain regions and are the principal participants in drift and diffusion at cryogenic temperatures.

BackgroundPlenty of studies have focused on the bile acids profile in gallstones. The objective of our systematic review is to provide a comprehensive summary about bile acids profiles in gallstones and analyzes the difference between gallstones and control group in diverse samples, determining the characteristic bile acids as the metabolite biomarkers for predicting gallstone.MethodsEMBASE, the Cochrane Library, PubMed, Web of Science, Wanfang databases, China National Knowledge Infrastructure (CNKI), VIP Information Resource Integration Service Platform (CQVIP), and China Biology Medicine Disc (SinoMed) will be searched with the keywords of gallstones and metabolomics. The screening process will be performed strictly according to inclusion and exclusion criteria. The CONSORT checklist and the Newcastle-Ottawa Scale (NOS) will assess the risk of bias for randomized controlled trials and observational studies, respectively. The qualitative review will be conducted to summarize the bile acids profile in gallstones. The concentrations of bile acids in both case group and control group will be the primary outcomes to perform the meta-analyses.Expected resultsOur systematic review will find the characteristic bile acids as the candidate metabolite biomarkers which equipped potential value to predict gallstones.ConclusionExpanding the current knowledge on the physiopathology of gallstones and identifying novel predictive biomarkers can help to facilitate the detection and management of gallstones. Consequently, we expect this protocol to be a reasonable method to filtrate candidate differential bile acids which have potential value to predict gallstones.Prospero registration numberCRD42022339649.

IntroductionCandida albicans is an opportunistic pathogenic fungus, which frequently causes systemic or local fungal infections in humans. The evolution of its drug-resistant mutants necessitate an urgent development of novel antimicrobial agents.ResultsHere, we explored the antimicrobial activity and inhibitory mechanisms of X33 antimicrobial oligopeptide (X33 AMOP) against C. albicans. The oxford cup test results showed that X33 AMOP had strong inhibitory activity against C. albicans, and its MIC and MFC were 0.625 g/L and 2.5 g/L, respectively. Moreover, SEM and TEM showed that X33 AMOP disrupted the integrity of cell membrane. The AKP, ROS, H2O2 and MDA contents increased, while the reducing sugar, soluble protein, and pyruvate contents decreased after the X33 AMOP treatment. This indicated that X33 AMOP could damage the mitochondrial integrity of the cells, thereby disrupting the energy metabolism by inducing oxidative stress in C. albicans. Furthermore, transcriptome analysis showed that X33 AMOP treatment resulted in the differential expression of 1140 genes, among which 532 were up-regulated, and 608 were down-regulated. These DEGs were related to protein, nucleic acid, and carbohydrate metabolism, and their expression changes were consistent with the changes in physiological characteristics. Moreover, we found that X33 AMOP could effectively inhibit the virulence attributes of C. albicans by reducing phospholipase activity and disrupting hypha formation.DiscussionThese findings provide the first-ever detailed reference for the inhibitory mechanisms of X33 AMOP against C. albicans and suggest that X33 AMOP is a potential drug candidate for treating C. albicans infections.

AIM: To observe the visual quality after implantation of regional refractive multifocal intraocular lens(MIOL)SBL-3. METHODS: A retrospective and controlled study. Fifty-seven cataract patients(68 eyes)in our hospital from September 2019 to July 2020 were enrolled. Totally 33 cases(36 eyes)received regional refractive MIOL SBL-3(SBL-3 group), while 24 cases(32 eyes)received aspheric single focal intraocular lens(SIOL)ZCB00(ZCB00 group). Uncorrected and corrected distance, middle and near visual acuity, defocus curve, OPDⅢ objective visual quality, the quality of vision(QoV)questionnaire, patient satisfaction and spectacle independence were evaluated 3mo postoperatively.RESULTS: No significant differences were found between the SBL-3 group and the ZCB00 group in terms of LogMAR value of corrected and uncorrected distance visual acuity(UDVA)at 3mo after the operation(0.13±0.09 vs 0.10±0.08, 0.06±0.06 vs 0.08±0.08, all P>0.05)and the UDVA was significantly improved compared with that before the operation(P

Cardiovascular diseases, mainly characterized by atherosclerosis (AS), and depression have a high comorbidity rate. However, previous studies have been conducted under a single disease, and there is a lack of studies in comorbid states to explore the commonalities in the pathogenesis of both diseases. Modern high-throughput technologies have made it clear that the gut microbiome can affect the development of the host’s own disorders and have shown that their metabolites are crucial to the pathophysiology of AS and depression. The aim of this review is to summarize the current important findings on the role of gut microbiome metabolites such as pathogen-associated molecular patterns, bile acids, tryptophan metabolites, short-chain fatty acids, and trimethylamine N -oxide in depression and AS disease, with the aim of identifying potential biological targets for the early diagnosis and treatment of AS co-depression disorders.

This research presents a design method of the nonlinear periodic gradient triply periodic minimal surface structures (NL-TPMS). The gradient porosity of NL-TPMS was controlled by a sinusoidal function and the influence of the number of cycles on the compression failure mechanism has been investigated. Homogenous TPMS and NL-TPMS were manufactured by laser powder bed fusion (LPBF) with 316L stainless steel powder. Digital image correlation (DIC) and finite element analysis (FEA) were applied to explore the compression behavior of NL-TPMS. The strain of the plateau end of homogenous TPMS decreases as the porosity increases, and the DIC results show that homogenous TPMS deformed with a 45° diagonal shear band. The compression results show that anisotropy of mechanical properties exists in NL-TPMS. The length of the first plateau and compressive proof strength increase as the number of cycles of porosity increases. The cycle of gradient porosity also influences the compression behavior of NL-TPMS, and a periodic failure deformation was observed in the NL-TPMS rather than a layer-by-layer compression deformation in normal gradient porous structures. The maximum principal strain of NL-TPMS detected by DIC presents a periodic distribution, which corresponds to the sinusoidal period designed function of NL-TPMS.

Abstract Objectives Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in childhood, which may be related to adverse childhood experiences (ACEs). Our study aims to explore the association between ACEs and subsequent ADHD, and analyze the potential moderators. Methods Literature search was conducted by a combined computer‐assisted and manual method. Studies were included if they had reported the association between ACEs and subsequent ADHD. Overall estimates of odds ratios (ORs) were obtained using random‐effects meta‐analyses, meta‐regressions and further stratified analyses were conducted to examine potential moderator variables. Results Totals of 70 studies involving nearly 4 million participants from among 6,452 unique articles were included. In the primary analyses, ACEs were found to be associated with subsequent ADHD (OR = 1.68, 95% CI: 1.54–1.83), and the negative effects of different forms of ACEs for ADHD were nonequivalent. Such as lived in the stepfamily, been adopted or fostered, and experienced sexual abuse were more deleterious than others. It was found that individuals who had experienced multiple ACEs or who are female were more vulnerable to ADHD. Conclusions The findings provide critical evidence for understanding the association between ACEs and ADHD. ACEs could increase the susceptibility of ADHD, especially for individuals who ever experienced multiple ACEs and females.

Abstract Background Traditional Chinese Medicine (TCM) has been a proposed treatment option for ulcerative colitis (UC), however it has been difficult to understand the breadth and depth of evidence as various Chinese medicine therapies may produce effects differently. The aim of this evidence mapping is to visually understand the available evidence in the use of TCM in the treatment of UC, and to identify gaps in evidence to inform priorities of future research. Methods A systematic electronic literature search of six databases were performed to identify systematic reviews (SRs) on different Chinese medicine therapies in the treatment in UC. Methodological quality of the included SRs was assessed using AMSTAR 2. Results The mapping was based on 73 SRs, which included nine interventions that met eligibility criteria. The quality of the included SRs was very low. The diseases stages of patients with UC varied greatly, from active to remission, to non-acute outbreak, to not reported. The results mostly favored the method of intervention. Oral administration combined with enema was the most widely used route of administration in secondary research. Conclusion Based on the current evidence, the treatment of UC with TCM can only be recommended cautiously. A majority of included SRs did not report the location of the disease, the disease classification, and the route of administration of the intervention. Further research is needed on the effectiveness of Chinese medicine alone in the treatment of UC. The effectiveness of combined Chinese and conventional medicine combined with different routes of administration cannot be confirmed. Attention should be paid to the methodological quality of the systematic review. Unifies the outcome indicators used in the evaluation of effectiveness.

Abstract Background Hyaluronan (HA) metabolism by chondrocytes is important for cartilage development and homeostasis. However, information about the function of circular RNAs (circRNAs) in HA metabolism is limited. We therefore profiled the role of the novel HA-related circRNA circHYBID in the progression of osteoarthritis (OA). Methods CircHYBID function in HA metabolism in chondrocytes was investigated using gain-of-function experiments, and circHYBID mechanism was confirmed via bioinformatics analysis and luciferase assays. The expression of circHYBID–hsa-miR-29b-3p–transforming growth factor (TGF)-β1 axis was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. CircHYBID, TGF-β1, and HA levels in cartilage samples were evaluated using qRT-PCR and pathological examination. Enzyme-linked immunosorbent assay was used to assess HA accumulation in chondrocyte supernatant. Results CircHYBID expression was significantly downregulated in damaged cartilage samples compared with that in the corresponding intact cartilage samples. CircHYBID expression was positively correlated with alcian blue score. Interleukin-1β stimulation in chondrocytes downregulated circHYBID expression and decreased HA accumulation. Gain-of-function experiments revealed that circHYBID overexpression in chondrocytes increased HA accumulation by regulating HA synthase 2 and HYBID expression. Further mechanism analysis showed that circHYBID upregulated TGF-β1 expression by sponging hsa-miR-29b-3p. Conclusions Our results describe a novel HA-related circRNA that could promote HA synthesis and accumulation. The circHYBID–hsa-miR-29b-3p–TGF-β1 axis may play a powerful regulatory role in HA metabolism and OA progression. Thus, these findings will provide new perspectives for studies on OA pathogenesis, and circHYBID may serve as a potential target for OA therapy.

AIM:To evaluate the clinical efficacy of different interventions of traditional Chinese medicine in the treatment of traumatic optic neuropathy by means of mesh Meta-analysis.METHODS:The Computer searched of Chinese databases(CNKI, VIP, WanFang, SinoMed)and English databases(PubMed, Embase, Cochrane Library). Search time was limited from their inception to March 2020. Randomized controlled clinical trials of traditional Chinese medicine for treatment of traumatic optic neuropathy were subjected to Meta-analysis. Cochrane evaluation tool was used to evaluate the quality of the included studies and Stata 14.2 software was used to conduct network Meta-analysis.RESULTS: Twenty-one RCT studies involving 1 297 patients were included and 7 interventions were involved. Among them, Chinese medicine, Chinese medicine+hormone drugs, acupuncture+Chinese medicine+neurotrophic drugs were better than those with neurotrophic drugs alone. Chinese medicine+hormone drugs, acupuncture+Chinese medicine+neurotrophic drugs, acupuncture+Chinese medicine+hormone drugs were better than that of hormone drugs alone(P

Hospital-based health technology assessment (HB-HTA) is highly valuable in the application of hospital medical technology, cost control, improvement of medical quality, and protection of medical safety, and its use is increasing daily globally. However, in China, HB-HTA is still in its infancy, and it is yet to be adopted in traditional Chinese medicine (TCM). Therefore, this article introduces the application and development of HB-HTA, as well as discusses the current situation of TCM and related future development strategies to provide ideas and references for the development of HB-HTA in TCM. We conclude and recommend that all major stakeholders, including the state, health departments, and hospital leaders, support and promote the exploration and development of HB-HTA in TCM hospitals and integrative medicine hospitals. We also suggest the utilization of existing talents and introduction of other necessary talents to promote better and faster organizational development, as well as suggest the formation of a national and internationally recognized HB-HTA guidance manual and toolkit for TCM hospitals based on both the national HTA guidelines and the evaluation of TCM hospitals pilot projects. Moreover, we recommend that HB-HTA pilot study should be executed with Chinese patent medicine as the starting point to form the implementation process and framework in the TCM arena.

Objectives: To investigate the association of altered serum ferritin during pregnancy with chorioamnionitis and neonatal sepsis. Methods: This retrospective cohort study included 78,521 pregnant women who attended antenatal check-ups at maternal and child health centers in Fujian Province, China. Study lasted from January 2014 to January 2019. A total of 59,812 pregnant women were followed up. Patients with suspected infection before the delivery were selected and divided into the chorioamnionitis and non-chorioamnionitis groups according to placental pathology. Differences in late and early pregnancy serum ferritin between the two groups were compared. Multiple logistics regression was used to adjust for confounding factors and to analyze the association between serum ferritin changes and pregnancy outcomes. Importance of altered serum ferritin during pregnancy was assessed by receiver operating characteristic (ROC) curve and net reclassification index (NRI). Results: Clinical records of 8506 pregnant women were included in the study. there were 1010 (11.9%) cases of confirmed chorioamnionitis and 263 (3.1%) cases of neonatal sepsis. There was a significant difference in maternal serum ferritin changes between the groups with and without chorioamnionitis. No significant difference was detected in cases with or without neonatal sepsis. Multiple logistic regressions, corrected for confounding factors yielded similar conclusions. Maternal serum ferritin difference NRI 12.18% (p = 0.00014) was similar to the ROC results in predicting the occurrence of chorioamnionitis. Conclusion: Differential serum ferritin during pregnancy may predict chorioamnionitis but does not correlate well with neonatal sepsis. [ABSTRACT FROM AUTHOR]

ObjectiveMulticriteria decision analysis (MCDA) is a useful tool in complex decision-making situations, and has been used in medical fields to evaluate treatment options and drug selection. This study aims to provide valuable insights into MCDA in healthcare through examining the research focus of existing studies, major fields, major applications, most productive authors and countries, and most common journals in the domain.MethodsA bibliometric analysis was conducted on the publication related to MCDA in healthcare from the Web of Science Core Collection (WoSCC) database on 14 July 2021. Three bibliometric software (VOSviewer, R-bibliometrix, and CiteSpace) were used to conduct the analysis including years, countries, institutes, authors, journals, co-citation references, and keywords.ResultsA total of 410 publications were identified with an average yearly growth rate of 32% (1999–2021), from 196 academic journals with 23,637 co-citation references by 871 institutions from 70 countries/regions. The United States was the most productive country (n = 80). Universiti Pendidikan Sultan Idris (n = 16), Université de Montréal (n = 13), and Syreon Research Institute (n = 12) were the top productive institutions. A A Zaidan, Mireille Goetghebeur and Zoltan Kalo were the biggest nodes in every cluster of authors' networks. The top journals in terms of the number of articles (n = 17) and citations (n = 1,673) were Value in Health and Journal of Medical Systems, respectively. The extant literature has focused on four aspects, including the analytic hierarchy process (AHP), decision-making, health technology assessment, and healthcare waste management. COVID-19 and fuzzy TOPSIS received careful attention from MCDA applications recently. MCDA in big data, telemedicine, TOPSIS, and fuzzy AHP is well-developed and an important theme, which may be the trend in future research.ConclusionThis study uncovers a holistic picture of the performance of MCDA-related literature published in healthcare. MCDA has a broad application on different topics and would be helpful for practitioners, researchers, and decision-makers working in healthcare to advance the wheel of medical complex decision-making. It can be argued that the door is still open for improving the role of MCDA in healthcare, whether in its methodology (e.g., fuzzy TOPSIS) or application (e.g., telemedicine).

Background: The diagnosis, treatment, and prevention of atherosclerosis co-depression are poor, so it is urgent to explore new targets. Based on the “microbiota-gut-brain axis,” this study aimed to investigate the changes of lipid metabolites in the prefrontal cortex and hippocampus regions and the characteristics of the gut microbiota in ApoE−/− mice with atherosclerosis co-depression.Methods: ApoE−/− mice (hyperlipid feeding combined with binding, HFB group, n = 14, male) fed a high-fat diet for 16 weeks with binding stimulation were used as an animal model for atherosclerosis co-depression. The depression degree of mice was evaluated by body weight, sucrose preference test, open field test, and tail suspension test. Oil-red O staining, HE staining, and biochemical parameters were used to evaluate the damage degree of atherosclerosis in mice. LC-MS/MS technique for non-targeted lipidomics analysis was used to analyze the differential lipid metabolites in the prefrontal cortex and hippocampus regions of mice. 16S rDNA amplification sequencing was used to screen the differential gut microbial, and association analysis was performed with the differential lipid metabolites.Results: Compared with the normal control group (NC group), the HFB group showed depression-like behaviors and atherosclerosis-related pathological indicators. The differential lipid metabolites in the prefrontal cortex and hippocampus regions were mainly LPC, LPE, LPS, PC, PE, PS, PI, and GD1a, and were mainly enriched in the glycerophospholipid metabolism pathway and the retrograde endocannabinoid signaling pathway. At the same time, there were significant differences in the structure of the gut microbial community between the two groups. The abundance of Deferribacteres and Proteobacteria in the HFB group increased, while the abundance of Verrucomicrobia and Actinobacteria decreased at the phylum level; the abundance of Desulfovibrio, Clostridium_IV, Helicobacter and Pseudoflavonifractor increased, while the abundance of Akkermansia decreased at the genus level.Conclusion: Atherosclerosis co-depression of ApoE−/− mice of the prefrontal cortex and hippocampus lipid metabolism pathways of disorder and the changes of to the gut microbiota, which leads to abnormal white matter and synaptic dysfunction, increased gut inflammation, and decreased gut permeability, leading to the release of inflammatory cytokines, there is a strong correlation between both, it further confirmed the existence of the “microbiota-gut-brain axis.”

Background: There is growing evidence that a number of lncRNAs are involved in the pathogenesis of non-small-cell lung cancer (NSCLC). However, studies on lncRNA expression in NSCLC patients are far from conclusive. Therefore, we performed a systematic review of such studies to collect and examine the evidence on the potential role of lncRNAs in the development of NSCLC.Methods: We systematically searched seven literature databases to identify all published studies that evaluated the expression of one or more lncRNAs in human samples with NSCLC (cases) and without NSCLC (controls) from January 1, 1995 to May 24, 2021. Quality assessment of studies was conducted by using the “Quality in Prognosis Studies” (QUIPS) tool, and the heterogeneity across studies was analyzed with the I-squared statistic and chi-square-based Q-tests. Either fixed or random-effect meta-analysis was performed to summarize effect size to investigate the association between lncRNA expression and overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and clinicopathological features. The R statistical software program was used to conduct standard meta-analysis.Results: We finally obtained 48 studies with 5,211 patients included in this review after screening. Among the 48 lncRNAs, 38 lncRNAs were consistently upregulated, and 10 were deregulated in patients with NSCLC compared with the control groups. The upregulated lncRNAs were positively associated with histological type: study number (n) = 18, odds ratio (OR) = 0.78, 95% CI: 0.65–0.95 and OR = 1.30, 95% CI: 1.08–1.57, p

Background: The constitution theory of traditional Chinese medicine (TCM) states that body constitution and disease are associated; therefore, the identification of body constitution can provide reference for disease prevention and treatment. A series of clinical studies evaluating the association between TCM constitution and metabolic syndrome (MetS) have been conducted in recent years. The aim of this systematic review is to summarize and evaluate the clinical evidence of the relationship between constitution and MetS. Methods: The PubMed, Embase, China National Knowledge Infrastructure (CNKI), Chongqing VIP, and Wanfang Data electronic databases were searched from April 2009 to July 2020. The search terms included “metabolic syndrome,” “constitution,” and “Chinese medicine.” Observational studies evaluating the relationship between body constitution of TCM and MetS were included. The primary outcome included the distribution of constitutional types in the MetS population, and odds ratio (OR) or relative risk (RR) between constitution and MetS. Effect size was expressed as proportion or OR with 95% confidence interval (CI). Methodological quality of included studies was evaluated by the Newcastle–Ottawa Scale (NOS) or the American Agency for Healthcare Research and Quality (AHRQ) criteria. Results: Three case–control and 26 cross-sectional studies involving 30 435 cases were included. Phlegm-dampness, qi-deficiency, and damp-heat were the main constitution types in patients with MetS, accounting for 29% (22%–39%), 18% (13%–24%), and 12% (9%–17%) of the population, respectively; the risk of MetS in people with phlegm-dampness and qi-deficiency constitution was 1.74 [1.27, 2.38] and 1.29 [1.01, 1.65] times higher than that in those with other constitutions. There were sex- and age-related differences in the distribution of TCM constitution in patients with MetS. Conclusion: Phlegm-dampness and qi-deficiency were associated with the occurrence of MetS. Well-designed cohort and case–control studies are needed to provide evidence for the use of TCM to prevent and treat MetS.

The removal process of waste water sludge formed in tomato sauce processing plants was analyzed and explored. The operation mode of sequencing batch reactors (SBR) was used to explore the changes in particle sizes and the removal capacity of COD, N and P in the process of granulation; the sludge characteristics, water quality, organic pollutant degradation capacity and the optimal proportion of sludge in the mixed sludge system were analyzed when the particle sludge and flocculent sludge coexisted in different proportions. The majority of particle sizes of granular sludge are in the range of 0.45‒3 mm, and the removal rates of COD, \begin{document}${{\rm{NH}}_{4}^{+}} $\end{document}—N and \begin{document}${{\rm{PO}}_{4}^{3-}} $\end{document}—P are over 98%, 90% and 90% respectively. When the quality ratio of granular sludge accounts for 50% of the total sludge, the removal rate of COD is the highest, which is more than 98%, the removal rate of \begin{document}${{\rm{NH}}_{4}^{+}} $\end{document}—N is 78.72%, and the concentration of \begin{document}${{\rm{PO}}_{4}^{3-}} $\end{document}—P in the effluent is about 1.0 mg·L−1, the removal rate of can reach 70.68%. The removal of nitrogen and phosphorus is also good. When the quality proportion of granular sludge is more than 75%, the removal rate of COD is higher than 98%, and the removal rate of \begin{document}${{\rm{NH}}_{4}^{+}} $\end{document}—N and \begin{document}${{\rm{PO}}_{4}^{3-}} $\end{document}—P is higher than 90%. SVI30 value is lower than 35 mL·g−1, SVI5/SVI30 is close to 1, MLVSS/MLSS is 0.90, with high activity, good sludge settling performance, and vigorous growth of microorganisms. Therefore, SBR is expected to discharge aged particles, control the quality proportion of granular sludge ≥75%, and maintain the required proportion of flocculent sludge and granular sludge of 10%–25%. At the same time, the particle size range is controlled at 0.45–3.00 mm. Two way sludge discharge is used to remove particles larger than 3.0 mm together with excess flocculent sludge. The reactor has excellent organic matter removal performance. It can realize the long-term stable operation, effectively remove the granular sludge, and solve the problem of granular sludge disintegration.

Abstract Background High-affinity nitrate transporter 2 (NRT2) genes have been implicated in nitrate absorption and remobilization under nitrogen (N) starvation stress in many plant species, yet little is known about this gene family respond to various stresses often occurs in the production of rapeseed (Brassica napus L.). Results This report details identification of 17 NRT2 gene family members in rapeseed, as well as, assessment of their expression profiles using RNA-seq analysis and qRT-PCR assays. In this study, all BnNRT2.1 members, BnNRT2.2a and BnNRT2.4a were specifically expressed in root tissues, while BnNRT2.7a and BnNRT2.7b were mainly expressed in aerial parts, including as the predominantly expressed NRT2 genes detected in seeds. This pattern of shoot NRT expression, along with homology to an Arabidopsis NRT expressed in seeds, strongly suggests that both BnNRT2.7 genes play roles in seed nitrate accumulation. Another rapeseed NRT, BnNRT2.5 s, exhibited intermediate expression, with transcripts detected in both shoot and root tissues. Functionality of BnNRT2s genes was further outlined by testing for adaptive responses in expression to exposure to a series of environmental stresses, including N, phosphorus (P) or potassium (K) deficiency, waterlogging and drought. In these tests, most NRT2 gene members were up-regulated by N starvation and restricted by the other stresses tested herein. In contrast to this overall trend, transcription of BnNRT2.1a was up-regulated under waterlogging and K deficiency stress, and BnNRT2.5 s was up-regulated in roots subjected to waterlogging. Furthermore, the mRNA levels of BnNRT2.7 s were enhanced under both waterlogging stress and P or K deficiency conditions. These results suggest that these three BnNRT2 genes might participate in crosstalk among different stress response pathways. Conclusions The results presented here outline a diverse set of NRT2 genes present in the rapeseed genome that collectively carry out specific functions throughout rapeseed development, while also responding not just to N deficiency, but also to several other stresses. Targeting of individual BnNRT2 members that coordinate rapeseed nitrate uptake and transport in response to cues from multiple stress response pathways could significantly expand the genetic resources available for improving rapeseed resistance to environmental stresses.

Abstract Breast cancer (BC) is the most common cancer among women worldwide and is the second leading cause of cancer‐related deaths in women. Increasing evidence has validated the vital role of the immune system in BC development and recurrence. In this study, we identified an immune‐related prognostic signature of BRCA that could help delineate risk scores of poor outcome for each patient. This prognostic signature comprised information on five danger genes—TSLP, BIRC5, S100B, MDK, and S100P—and three protect genes RARRES3, BLNK, and ACO1. Kaplan‐Meier survival curve showed that patients classified as low‐risk according to optimum cut‐off risk score had better prognosis than those identified within the high‐risk group. ROC analysis indicated that the identified prognostic signature had excellent diagnostic efficiency for predicting 3‐ and 5‐years relapse‐free survival (RFS). Multivariate Cox regression analysis proved that the prognostic signature is independent of other clinical parameters. Stratification analysis demonstrated that the prognostic signature can be used to predict the RFS of BC patients within the same clinical subgroup. We also developed a nomogram to predict the RFS of patients. The calibration plots exhibited outstanding performance. The validation sets (GSE21653, GSE20711, and GSE88770) were used to external validation. More convincingly, the real time RT‐PCR results of clinical samples demonstrated that danger genes were significantly upregulated in BC samples, whereas protect genes were downregulated. In conclusion, we developed and validated an immune‐related prognostic signature, which exhibited excellent diagnostic efficiency in predicting the recurrence of BC, and will help to make personalized treatment decisions for patients at different risk score.

Breast cancer is the most commonly diagnosed malignancy in female worldwide, over 70% of which are estrogen receptor α (ERα) positive. ERα has a crucial role in the initiation and progression of breast cancer and is an indicator of endocrine therapy, while endocrine resistance is an urgent problem in ER-positive breast cancer patients. In the present study, we identify a novel E3 ubiquitin ligase TRIM11 function to facilitate ERα signaling. TRIM11 is overexpressed in human breast cancer, and associates with poor prognosis. The protein level of TRIM11 is highly correlated with ERα. RNA-seq results suggest that ERα signaling may be an underlying target of TRIM11. Depletion of TRIM11 in breast cancer cells significantly decreases cell proliferation and migration. And the suppression effects can be reversed by overexpressing ERα. In addition, ERα protein level, ERα target genes expression and estrogen response element activity are also dramatically decreased by TRIM11 depletion. Further mechanistic analysis indicates that the RING domain of TRIM11 interacted with the N terminal of ERα in the cytoplasm and promotes its mono-ubiquitination, thus enhances ERα protein stability. Our study describes TRIM11 as a modulating factor of ERα and increases ERα stability via mono-ubiquitination. TRIM11 could be a promising therapeutic target for breast cancer treatment.

Abstract Background Accidentally removed parathyroid glands are still challenging in neck surgery, leading to hypoparathyroidism characterized with abnormally low levels of parathyroid hormone. Parathyroid auto-transplantation is usually applied in compensation. To improve the efficiency of parathyroid transplantation, we introduced a method by co-transplanting with adipose-derived cells, including stromal vascular fractions (SVFs) and adipose-derived stem cells (ADSCs), and investigated the underlying molecular mechanisms involved in parathyroid transplantation survival. Methods Rat and human parathyroid tissues were transplanted into nude mice as parathyroid transplantation model to examine the effects of SVFs and ADSCs on grafts angiogenesis and survival rates, including blood vessel assembly and parathyroid hormone levels. Several angiogenic factors, such as vascular endothelial growth factor (VEGF)-A and fibroblast growth factor (FGF) 2, were assessed in parathyroid grafts. The effects of hypoxia were investigated on ADSCs. The modulatory roles of the eyes absent homolog 1 (EYA1), which is vital in parathyroid development, was also investigated on angiogenic factor production and secretion by ADSCs. All experimental data were statistically processed. Student’s t test was used to assess significant differences between 2 groups. For multiple comparisons with additional interventions, two-way ANOVA followed by Tukey’s post hoc test was performed. P

The uveitis is a clinical common involving the iris, ciliary body, vitreous body, choroid, retina and retinal blood vessels, a group of inflammatory disease causes complex, due to the pathogenesis of uveitis did not clarify clearly, looking for effective treatment of uveitis drugs has been the main direction of ophthalmic research, in addition to the traditional glucocorticoid, cycloplegia agent, nonsteroidal anti-inflammatory drugs(nsaids), immune inhibitor has a good curative effect on uveitis, along with the development of molecular biology, a new type of biological agents, gene therapy, could fairly claim a place in the history of Chinese medicine in the treatment of uveitis. This article aims to review the latest progress in the treatment of uveitis.

BackgroundInterleukin-17 (IL-17) monoclonal antibody drugs have been increasingly significant in the treatment of psoriasis, but it is not clear whether the efficacy is equivalent across ethnicities.ObjectiveTo explore the differences of short-term efficacy of IL-17 inhibitors between Caucasians and Asians.MethodsThe pooled log risk ratio (logRR) between the groups was estimated. The meta-regression analysis on the logRR was performed, with the proportion of Caucasian patients as the covariate. The subgroup analysis was performed by specific IL-17 inhibitors.ResultsOf the 1,569 potentially relevant studies, sixteen randomized controlled trials (RCTs) were included. For the Psoriasis Area and Severity Index 75 (PASI 75) response at week 12, the pooled logRR of the Asian group and the Caucasian group was 2.81 (95% CI: 2.27–3.35, p < 0.001) and 2.93 (95% CI: 2.71–3.16, p < 0.001), respectively, indicating no significant difference of efficacy between Asians and Caucasians. The meta-regression analysis did not show an association of the proportion of Caucasians with the effect size (β = 0.3203, p = 0.334). In the subgroup analysis, the comparison results of secukinumab were consistent with the main analysis.LimitationsOnly the short-term efficacy was explored. The data from Asian countries were limited.ConclusionsThe short-term efficacy of IL-17 inhibitors in the treatment of psoriasis has no significant difference between Caucasians and Asians.Systematic Review RegistrationPROSPERO, identifier CRD42020201994, https://www.crd.york.ac.uk/prospero/.