The Dissection of Nitrogen Response Traits Using Drone Phenotyping and Dynamic Phenotypic Analysis to Explore N Responsiveness and Associated Genetic Loci in Wheat.

Inefficient nitrogen (N) utilization in agricultural production has led to many negative impacts such as excessive use of N fertilizers, redundant plant growth, greenhouse gases, long-lasting toxicity in ecosystem, and even effect on human health, indicating the importance to optimize N applications in cropping systems. Here, we present a multiseasonal study that focused on measuring phenotypic changes in wheat plants when they were responding to different N treatments under field conditions. Powered by drone-based aerial phenotyping and the AirMeasurer platform, we first quantified 6 N response-related traits as targets using plot-based morphological, spectral, and textural signals collected from 54 winter wheat varieties. Then, we developed dynamic phenotypic analysis using curve fitting to establish profile curves of the traits during the season, which enabled us to compute static phenotypes at key growth stages and dynamic phenotypes (i.e., phenotypic changes) during N response. After that, we combine 12 yield production and N-utilization indices manually measured to produce N efficiency comprehensive scores (NECS), based on which we classified the varieties into 4 N responsiveness (i.e., N-dependent yield increase) groups. The NECS ranking facilitated us to establish a tailored machine learning model for N responsiveness-related varietal classification just using N-response phenotypes with high accuracies. Finally, we employed the Wheat55K SNP Array to map single-nucleotide polymorphisms using N response-related static and dynamic phenotypes, helping us explore genetic components underlying N responsiveness in wheat. In summary, we believe that our work demonstrates valuable advances in N response-related plant research, which could have major implications for improving N sustainability in wheat breeding and production.

Tetrahydropalmatine: Orchestrating survival - Regulating autophagy and apoptosis via the PI3K/AKT/mTOR pathway in perforator flaps.

BACKGROUND: Introduced in clinical practice in 1989, perforator flaps are vital for tissue defect repair, but they are challenged by distal necrosis. Tetrahydropalmatine (THP) from celandine is renowned for its anti-inflammatory and analgesic effects. This study investigates THP's use in perforator flaps. METHODS: Thirty rats were divided into a control group and four THP concentration groups, while seventy-eight rats were categorized as control, THP, THP combined with rapamycin (RAP), and RAP alone. We created 11 cm by 2.5 cm multi-regional perforator flaps on rat backs, assessing survival blood flow and extracting skin flap tissue for autophagy, oxidative stress, apoptosis, and angiogenesis markers. RESULTS: The THP group exhibited significantly reduced distal necrosis, increased blood flow density, and survival area on the seventh day compared to controls. Immunohistochemistry and Western blot results demonstrated improved anti-oxidative stress and angiogenesis markers, along with decreased autophagy and apoptosis indicators. Combining THP with RAP diminished flap survival compared to THP alone. This was supported by protein expression changes in the PI3K-AKT-mTOR pathway. CONCLUSION: THP enhances flap survival by modulating autophagy, reducing tissue edema, promoting angiogenesis, and mitigating apoptosis and oxidative stress. THP offers a potential strategy for enhancing multi-regional perforator flap survival through the PI3K/AKT/mTOR pathway. These findings highlight THP's promise in combatting perforator flap necrosis, uncovering a novel mechanism for its impact on flap survival.

Panicle-Cloud: An Open and AI-Powered Cloud Computing Platform for Quantifying Rice Panicles from Drone-Collected Imagery to Enable the Classification of Yield Production in Rice.

Rice (Oryza sativa) is an essential stable food for many rice consumption nations in the world and, thus, the importance to improve its yield production under global climate changes. To evaluate different rice varieties' yield performance, key yield-related traits such as panicle number per unit area (PNpM2) are key indicators, which have attracted much attention by many plant research groups. Nevertheless, it is still challenging to conduct large-scale screening of rice panicles to quantify the PNpM2 trait due to complex field conditions, a large variation of rice cultivars, and their panicle morphological features. Here, we present Panicle-Cloud, an open and artificial intelligence (AI)-powered cloud computing platform that is capable of quantifying rice panicles from drone-collected imagery. To facilitate the development of AI-powered detection models, we first established an open diverse rice panicle detection dataset that was annotated by a group of rice specialists; then, we integrated several state-of-the-art deep learning models (including a preferred model called Panicle-AI) into the Panicle-Cloud platform, so that nonexpert users could select a pretrained model to detect rice panicles from their own aerial images. We trialed the AI models with images collected at different attitudes and growth stages, through which the right timing and preferred image resolutions for phenotyping rice panicles in the field were identified. Then, we applied the platform in a 2-season rice breeding trial to valid its biological relevance and classified yield production using the platform-derived PNpM2 trait from hundreds of rice varieties. Through correlation analysis between computational analysis and manual scoring, we found that the platform could quantify the PNpM2 trait reliably, based on which yield production was classified with high accuracy. Hence, we trust that our work demonstrates a valuable advance in phenotyping the PNpM2 trait in rice, which provides a useful toolkit to enable rice breeders to screen and select desired rice varieties under field conditions.

Clinical Uncertainty Influences Antibiotic Prescribing for Upper Respiratory Tract Infections: A Qualitative Study of Township Hospital Physicians and Village Doctors in Rural Shandong Province, China.

OBJECTIVE: This study aimed to explore how clinical uncertainty influences antibiotic prescribing practices among township hospital physicians and village doctors in rural Shandong Province, China. METHODS: Qualitative semi-structured interviews were conducted with 30 township hospital physicians and 6 village doctors from rural Shandong Province, China. A multi-stage random sampling method was used to identify respondents. Conceptual content analysis together with Colaizzi's method were used to generate qualitative codes and identify themes. RESULTS: Three final thematic categories emerged during the data analysis: (1) Incidence and treatment of Upper Respiratory Tract Infections (URTIs) in township hospitals and village clinics; (2) Antibiotic prescribing practices based on the clinical experience of clinicians; (3) Influence of clinical uncertainty on antibiotic prescribing. Respondents from both township hospitals and village clinics reported that URTIs were the most common reason for antibiotic prescriptions at their facilities and that clinical uncertainty appears to be an important driver for the overuse of antibiotics for URTIs. Clinical uncertainty was primarily due to: (1) Diagnostic uncertainty (establishing a relevant diagnosis is hindered by limited diagnostic resources and capacities, as well as limited willingness of patients to pay for investigations), and (2) Insufficient prognostic evidence. As a consequence of the clinical uncertainty caused by both diagnostic and prognostic uncertainty, respondents stated that antibiotics are frequently prescribed for URTIs to prevent both prolonged courses or recurrence of the disease, as well as clinical worsening, hospital admission, or complications. CONCLUSION: Our study suggests that clinical uncertainty is a key driver for the overuse and misuse of prescribing antibiotics for URTIs in both rural township hospitals and village clinics in Shandong province, China, and that interventions to reduce clinical uncertainty may help minimize the unnecessary use of antibiotics in these settings. Interventions that use clinical rules to identify patients at low risk of complications or hospitalization may be more feasible in the near-future than laboratory-based interventions aimed at reducing diagnostic uncertainty.

Antibiotic use in township hospitals during the COVID-19 pandemic in Shandong, China.

BACKGROUND: The overuse of antibiotics in primary healthcare settings (PHSs) has caused a serious public health problem in China. The outbreak of the Coronavirus Disease-19 (COVID-19) pandemic brought about dramatic changes in the supply of and demand for medical services in PHSs, possibly resulting in unprecedented changes in antibiotic use. OBJECTIVE: This study aims to assess the immediate and long-term impacts of the COVID-19 pandemic on the changes in antibiotic consumption in PHSs. METHOD: The data on antibiotic consumption were collected from selected township hospitals in Shandong, China from January 2019 to December 2021. Antibiotic consumption was quantified by using the defined daily doses (DDDs) and the WHO Access, Watch, Reserve category. A segmented regression model was established to analyze the immediate and long-term impacts of the COVID-19 pandemic on antibiotic use by using the interrupted time series analysis. RESULTS: The overall antibiotic consumption in all PHSs decreased by 32.04% and 16.69% in 2020 and 2021 respectively compared to the corresponding period in 2019. Over the entire study period, the use of penicillins (J01C) and cephalosporins (J01D) accounted for more than 50% of the total antibiotic consumption. The average annual consumption of Watch category antibiotics decreased by 42.02% and 33.47% in 2020 and 2021 respectively compared to that in 2019. According to the interrupted time series analysis, the total antibiotic consumption decreased significantly immediately after the COVID-19 pandemic outbreak (coef. = - 2.712, p = 0.045), but it then increased significantly over a long-term (coef. = 0.205, p = 0.005). Additionally, the consumption of Access category antibiotics increased significantly in PHSs in the long-term (coef. = 0.136, p = 0.018). However, the consumption of Watch category antibiotics declined sharply immediately after the pandemic (coef. = - 1.222, p < 0.001), but then it increased slightly over a long-term (coef. = 0.073, p < 0.001). CONCLUSION: The extensive use of penicillin and cephalosporins should be of great concern. After the outbreak of COVID-19 pandemic, the total antibiotic consumption decreased generally and the use pattern was improved to some extent in the PHSs in Shandong, China. This provides an opportunity for improving the misuse of antibiotics in PHSs in China.

Clinical detection, diagnosis and treatment of morphological abnormalities of sperm flagella: A review of literature.

Sperm carries male genetic information, and flagella help move the sperm to reach oocytes. When the ultrastructure of the flagella is abnormal, the sperm is unable to reach the oocyte and achieve insemination. Multiple morphological abnormalities of sperm flagella (MMAF) is a relatively rare idiopathic condition that is mainly characterized by multiple defects in sperm flagella. In the last decade, with the development of high-throughput DNA sequencing approaches, many genes have been revealed to be related to MMAF. However, the differences in sperm phenotypes and reproductive outcomes in many cases are attributed to different pathogenic genes or different pathogenic mutations in the same gene. Here, we will review information about the various phenotypes resulting from different pathogenic genes, including sperm ultrastructure and encoding proteins with their location and functions as well as assisted reproductive technology (ART) outcomes. We will share our clinical detection and diagnosis experience to provide additional clinical views and broaden the understanding of this disease.

Interventions to optimize the use of antibiotics in China: A scoping review of evidence from humans, animals, and the environment from a One Health perspective.

Objectives: The overuse and misuse of antibiotics has accelerated the rapid emergence of antibiotic resistance. The aim of the study was to review interventions conducted in China to optimize use of antibiotics in humans, animals, and the environment from a One Health perspective. Methods: The literature review for this study was limited to English and Chinese articles published from January 1985 to May 2021. Literature review searches were conducted using Web of Science, Scopus, PubMed and three biomedical databases from China (the Chinese Scientific Journals database, the Wanfang Database, and China National Knowledge Infrastructure). We used Arksey and O'Malley's step-wise methodological framework as the basis for our scoping review. Results: A total of 53 studies met our inclusion criteria, of which 51 (96%) were from human healthcare settings, one from environment health that pertained to rural ponds, and no studies were found that met our criteria on interventions used to improve antibiotic use in animals. For human health, the majority of the research was related to antibiotic intervention programs performed in public institutions, and only one policy assessment study included private institutions. Interventions were classified into four broad categories: 1) Knowledge interventions; 2) decision support; 3) financial incentives; and 4) organizational/management systems. Our findings indicated that combinations of multiple interventions were more effective in promoting the rational use of antibiotics in China. Conclusions: China has made major efforts on improving rational use of antibiotics in the past decades. Most policies or interventions, however, focused mainly on the human health aspect, less effort targeted toward the environment and animal health sectors. For further optimizing use of antibiotics, the cross-disciplinary and coordinated multi-faceted interventions guided by the One Health perspective should be developed and implemented. Meanwhile, the cross-departmental collaborative mechanism leading by the Chinese central government should be further strengthened to play a greater and more active role in fighting against antibiotic resistance wholly.

Genetic analysis and intracytoplasmic sperm injection outcomes of Chinese patients with congenital bilateral absence of vas deferens.

PURPOSE: Congenital bilateral absence of the vas deferens (CBAVD) is a major cause of obstructive azoospermia and male factor infertility. CBAVD is mainly caused by mutations in the genes encoding CFTR (cystic fibrosis transmembrane conductance regulator) and ADGRG2 (adhesion G protein-coupled receptor G2). This study aimed to describe CFTR and ADGRG2 variations in 46 Chinese CBAVD patients and evaluated sperm retrieval and assisted reproductive technology outcomes. METHODS: The CFTR and ADGRG2 genes were sequenced and analyzed by whole-exome sequencing (WES), and variations were identified by Sanger sequencing. Bioinformatic analysis was performed. We retrospectively reviewed the outcomes of patients undergoing sperm retrieval surgery and intracytoplasmic sperm injection (ICSI). RESULTS: In total, 35 of 46 (76.09%) patients carried at least one variation in CFTR, but no copy number variants or ADGRG2 variations were found. In addition to the IVS9-5 T allele, there were 27 CFTR variations, of which 4 variations were novel and predicted to be damaging by bioinformatics. Spermatozoa were successfully retrachieved in 46 patients, and 39 of the patients had their own offspring through ICSI. CONCLUSION: There are no obvious hotspot CFTR mutations in Chinese CBAVD patients besides the IVS9-5 T allele. Therefore, WES might be the best detection method, and genetic counseling should be different from that provided to Caucasian populations. After proper counseling, all patients can undergo sperm retrieval from their epididymis or testis, and most of them can have their own children through ICSI.

Influencing Factors and Cumulative Risk Analysis of Cervical Lymph Node Metastasis of Papillary Thyroid Microcarcinoma.

OBJECTIVE: To explore the influencing factors and cumulative risk of lymph node metastasis (LNM) in papillary thyroid microcarcinoma (PTMC) patients. METHODS: 607 patients confirmed PTMC pathologically after thyroidectomy were enrolled in this retrospective study. The rate of LNM was calculated. Different clinicopathological characteristics were compared in PTMC patients with and without LNM and in different subgroups of LNM, respectively. Correlation between clinicopathological characteristics and LNM was analyzed and the cumulative risk of LNM according to different clinicopathological characteristics was calculated. RESULTS: (1) There were 228 cases (37.56%) of PTMC combined with LNM. Compared with the non-lymph node metastasis group, the proportion of age <55 years, male, multiple foci, bilateral foci, diameter>0.5cm, extracapsular invasion, HT and intermediate-to-high risk stratification for recurrence of the LNM group was significantly increased (all p<0.05);(2) Multivariate logistic regression analysis showed that age <55years, male, multiple foci, diameter>0.5cm,HT were independently positively correlated with LNM (all p <0.05); (3) Subgroup analysis showed that women aged <55 years combined with HT and aged≥55 years combined with BMI≥25 kg/m2 were independently positively associated with LNM; (4) With the increase of the tumor diameter, the cumulative risk of LNM in group of age <55 years, males, and multiple foci increased gradually, and was higher than those of age≥55 years, females and single foci, respectively. (5) Among the 228 cases of LNM, the proportion of lymph nodes (LN) >5 and the positive rate of LN were both higher in male group than that in the female group. The proportion of multiple foci and HT in LLNM group was higher than that in CLNM group (all P<0.05). CONCLUSION: Age <55 years, males, multiple foci, diameter >0.5cm and HT were independent risk factors of LNM; HT was an independent risk factor for LNM in female <55 years old, and BMI≥25 kg/m2 was an independent risk factor for LNM in female ≥55 years old; The increase of tumor diameter in age <55 years, males, multiple foci, and bilateral foci increased the cumulative risk of LNM, respectively; The number of LNM and the positive rate of LNM were both higher in male, and patients with multiple foci or HT were more likely to develop into LLNM.

Prevalence and risk factors for antibiotic utilization in Chinese children.

BACKGROUND: Antibiotic resistance poses a significant threat to public health globally. Irrational utilization of antibiotics being one of the main reasons of antibiotic resistant. Children as a special group, there's more chance of getting infected. Although most of the infection is viral in etiology, antibiotics still are the most frequently prescribed medications for children. Therefore, high use of antibiotics among children raises concern about the appropriateness of antibiotic prescribing. This systematic review aims to measuring prevalence and risk factors for antibiotic utilization in children in China. METHODS: English and Chinese databases were searched to identify relevant studies evaluating the prevalence and risk factors for antibiotic utilization in Chinese children (0-18 years), which were published between 2010 and July 2020. A Meta-analysis of prevalence was performed using random effect model. The Agency for Healthcare Research and Quality (AHRQ) and modified Jadad score was used to assess risk of bias of studies. In addition, we explored the risk factors of antibiotic utilization in Chinese children using qualitative analysis. RESULTS: Of 10,075 studies identified, 98 eligible studies were included after excluded duplicated studies. A total of 79 studies reported prevalence and 42 studies reported risk factors for antibiotic utilization in children. The overall prevalence of antibiotic utilization among outpatients and inpatients were 63.8% (35 studies, 95% confidence interval (CI): 55.1-72.4%), and 81.3% (41 studies, 95% CI: 77.3-85.2%), respectively. In addition, the overall prevalence of caregiver's self-medicating of antibiotics for children at home was 37.8% (4 studies, 95% CI: 7.9-67.6%). The high prevalence of antibiotics was associated with multiple factors, while lacking of skills and knowledge in both physicians and caregivers was the most recognized risk factor, caregivers put pressure on physicians to get antibiotics and self-medicating with antibiotics at home for children also were the main factors attributed to this issue. CONCLUSION: The prevalence of antibiotic utilization in Chinese children is heavy both in hospitals and home. It is important for government to develop more effective strategies to improve the irrational use of antibiotic, especially in rural setting.

One-step dynamic fabrication of asymmetric multi-layered porous films for sustained drug delivery.

Asymmetric multi-layered porous films were prepared by casting inverse emulsion following the breath figure method. The porous morphologies both on the surface and in the bulk of the fabricated film could be dynamically manipulated by tuning the emulsion composition as well as the environmental conditions. The model drug was efficiently loaded into the porous film by direct encapsulation during film fabrication, and remarkable sustained drug release from the porous film for more than 28 days was achieved.

Formulation and evaluation of a α-linolenic acid and vitamin E succinate microemulsion with low surfactant content and free of co-surfactant for use as a nutritional supplement.

Herein, we have designed an alcohol-free and low-surfactant microemulsion to safely and effectively supply α-linolenic acid (ALA) and vitamin E (VE). Ternary phase diagrams show that the use of medium- or short-chain alcohols as the co-surfactant (CoS) was unfavorable for the formation of the ALA microemulsion due to the competitive hydrogen bonding effect and vitamin E succinate (VES) significantly increased the ALA microemulsion region by improving the hydrophilicity of the oil phase. The optimal microemulsion formulation (Mav) was 6.86% ALA, 1.14% VES, 12% surfactant and 80% water, with uniformly dispersed spherical particles with diameters of ~ 25.41 nm and viscosity of 35.17 mPa·s. The Mav was stable to high temperature, ionic strength and pH, and exhibited good physical and anti-oxidation stability. The Mav facilitated the release and hydrolysis of VES, indicating that the CoS-free microemulsion with low surfactant content is promising for the safe and effective supply of ALA and VE.

Mutation of the novel acetylation site at K414R of BECN1 is involved in adipocyte differentiation and lipolysis.

BECN1, a protein essential for autophagy, is involved in adipocyte differentiation, lipolysis and insulin resistance. The discovery of new mechanisms for modifying BECN1 in adipocytes may provide novel therapeutic targets for obesity. This study aimed to investigate the impact of mutations at the acetylation sites of BECN1 on adipocyte differentiation and lipolysis. We found that Ace-BECN1 levels were increased in 3T3-L1 adipocyte differentiation and isoproterenol-/TNF-α-stimulated lipolysis and in subcutaneous and visceral adipose tissues of high-fat diet mice. K414 was identified as an acetylation site of BECN1, which affects the stability of the BECN1 protein. Mutation at K414 of BECN1 affected autophagy, differentiation and lipolysis in 3T3-L1 adipocytes. These data indicated the potential of BECN1 K414 as a key molecule and a drug target for regulating autophagy and lipid metabolism in adipocytes.

Erratum: Microporous polysaccharide multilayer coated BCP composite scaffolds with immobilised calcitriol promote osteoporotic bone regeneration both in vitro and in vivo: Erratum.

[This corrects the article DOI: 10.7150/thno.29566.].

The Effectiveness of an Educational Intervention on Knowledge, Attitudes and Reported Practices on Antibiotic Use in Humans and Pigs: A Quasi-Experimental Study in Twelve Villages in Shandong Province, China.

Our aim was to evaluate the effectiveness of an intervention for residents in rural China on knowledge, attitudes and reported practices (KAP) on antibiotic use in humans and pigs. A quasi-experimental study was conducted in 12 villages in rural Shandong province, divided into intervention and control groups, covering a two-year period from July 2015 to June 2017. A package of health education-based interventions including training sessions, speakerphone messages, posters and handbooks for residents was developed and implemented over a one-year period to improve the use of antibiotics in humans and pigs. The intervention net effects were evaluated by Difference-in-Difference (DID) analysis based on responses to a questionnaire concerning KAP towards antibiotic use in humans and pigs. A total of 629 participants completed both baseline and post-trial questionnaires, including 127 participants with backyard pig farms. Significant improvements were found in KAP towards antibiotic use in humans, but changes related to antibiotic use for pigs were not significant. Participants who were in the intervention group (p < 0.001) were more likely to have improved their knowledge on antibiotic use in humans. Participants who had higher attitude scores were less likely to report self-medicating with stored antibiotics in the previous year (p < 0.001). Our results suggest that our health education-based intervention was effective in improving KAP on human antibiotic use, but it had little effect regarding antibiotic use for pigs.

Comparison of cecal microbiota composition in hybrid pigs from two separate three-way crosses.

OBJECTIVE: The intestinal microbiota plays an important role in host physiology, metabolism, immunity, and behavior. And host genetics could influence the gut microbiota of hybrid animals. The three-way cross model is commonly utilized in commercial pig production; however, the use of this model to analyse the gut microbial composition is rarely reported. METHODS: Two three-way hybrid pigs were selected, with Saba pigs as the starting maternal pig: Duroc× (Berkshire×Saba) (DBS) pig, Berkshire×(Duroc×Saba) (BDS) pig. One hundred pigs of each model were reared from 35 days (d) to 210 d. The body weight or feed consumption of all pigs were recorded and their feed/gain (F/G) ratio was calculated. On day 210, 10 pigs from each three-way cross were selected for slaughter, and cecal chyme samples were collected for 16S rRNA gene sequencing. RESULTS: The final body weight (FBW) and average daily gain (ADG) of DBS pigs were significantly higher than those of BDS pigs (p<0.05), while the F/G ratios of DBS pigs were significantly lower than those of BDS pigs (p<0.05). The dominant phyla in DBS and BDS pigs were Bacteroidetes (55.23% vs 59%, respectively) and Firmicutes (36.65% vs 34.86%, respectively) (p>0.05). At the genus level, the abundance of Prevotella, Roseburia, and Anaerovibrio in DBS pigs was significantly lower than in BDS pigs (p<0.01). The abundance of Eubacterium, Clostridium XI, Bacteroides, Methanomassiliicoccus, and Parabacteroides in DBS pigs was significantly higher than in BDS pigs (p<0.05). The FBWs and ADGs were positively correlated with Bacteroides, ClostridiumXI, and Parabacteroides but negatively correlated with the Prevotella, Prevotella/Bacteroides (P/B) ratio, Roseburia, and Anaerovibrio. CONCLUSION: These results indicated that host genetics affect the cecal microbiota composition and the porcine gut microbiota is associated with growth performance, thereby suggesting that gut microbiota composition may be a useful biomarker in porcine genetics and breeding.

Well-dispersed platelet lysate entrapped nanoparticles incorporate with injectable PDLLA-PEG-PDLLA triblock for preferable cartilage engineering application.

Platelet lysate (PL) as a cost-effective cocktail of growth factors is an emerging ingredient in regenerative medicine, especially in cartilage tissue engineering. However, most studies fail to pay attention to PL's intrinsic characteristics and incorporate it directly with scaffolds or hydrogels by simple mixture. Currently, the particle size distribution of PL was determined to be scattered. Directly introducing PL into a thermosensitive poly(d,l-lactide)-poly(ethylene glycol)-poly(d,l-lactide) (PLEL) hydrogel disturbed its sol-gel transition. Electrostatic self-assembly heparin (Hep) and ε-poly-l-lysine (EPL) nanoparticles (NPs) were fabricated to improve the dispersity of PL. Such PL-NPs-incorporated PLEL gels retained the initial gelling capacity and showed a long-term PL-releasing ability. Moreover, the PL-loaded composite hydrogels inhibited the inflammatory response and dedifferentiation of IL-1ß-induced chondrocytes. For in vivo applications, the PLEL@PL-NPs system ameliorated the early cartilage degeneration and promoted cartilage repair in the late stage of osteoarthritis. RNA sequencing analysis indicated that PL's protective effects might be associated with modulating hyaluronan synthase 1 (HAS-1) expression. Taken together, these results suggest that well-dispersed PL by Hep/EPL NPs is a preferable approach for its incorporation into hydrogels and the constructed PLEL@PL-NPs system is a promising cell-free and stepwise treatment option for cartilage tissue engineering.

The effects of the primary health care providers' prescription behavior interventions to improve the rational use of antibiotics: a systematic review.

Background: Irrational antibiotics use in clinical prescription, especially in primary health care (PHC) is accelerating the spread of antibiotics resistance (ABR) around the world. It may be greatly useful to improve the rational use of antibiotics by effectively intervening providers' prescription behaviors in PHC. This study aimed to systematically review the interventions targeted to providers' prescription behaviors in PHC and its' effects on improving the rational use of antibiotics. Methods: The literatures were searched in Ovid Medline, Web of Science, PubMed, Cochrane Library, and two Chinese databases with a time limit from January 1st, 1998 to December 1st, 2018. The articles included in our review were randomized control trial, controlled before-and-after studies and interrupted time series, and the main outcomes measured in these articles were providers' prescription behaviors. The Cochrane Collaboration criteria were used to assess the risk of bias of the studies by two reviewers. Narrative analysis was performed to analyze the effect size of interventions. Results: A total of 4422 studies were identified in this study and 17 of them were included in the review. Among 17 included studies, 13 studies were conducted in the Europe or in the United States, and the rest were conducted in low-income and-middle-income countries (LMICs). According to the Cochrane Collaboration criteria, 12 studies had high risk of bias and 5 studies had medium risk of bias. There was moderate-strength evidence that interventions targeted to improve the providers' prescription behaviors in PHC decreased the antibiotics prescribing and improved the rational use of antibiotics. Conclusions: Interventions targeted PHC providers' prescription behaviours could be an effective way to decrease the use of antibiotics in PHC and to promote the rational use of antibiotics. However, we cannot compare the effects between different interventions because of heterogeneity of interventions and outcome measures.

Importance of a semen analysis report for determining the relationship between SCSA sperm DNA fragmentation index and assisted reproductive technology pregnancy rate.

In the past, semen parameters have been the primary diagnostic criteria used to establish male infertility. However, with the exception of sperm motility, which is known to be linked to rates of in vitro fertilization success, these parameters are generally unreliable at accurately predicting the potential fertility of a couple. More recent research has suggested that sperm DNA fragmentation index (DFI) may be a more robust and reliable means of predicting assisted reproductive outcomes. The present study aimed to assess the relationship between sperm motility, sperm DFI, and rates of clinical pregnancy by analyzing data from 3000 couples dealing with infertility. Using the most recent semen analysis reports available from male partners in these couples, we assessed these parameters and found that the lower the sperm DFI value, the higher the rate of clinical pregnancy. When we assessed the correlation between sperm DFI, sperm motility, and clinical pregnancy, we observed a strong negative correlation between DFI and motility, but observed no significant relationship between sperm motility and pregnancy rates. These results thus indicate that the measurement of DFI via a sperm chromatin structure assay (SCSA) may be a valuable tool for analyzing semen in order to better predict and improve pregnancy rates in infertile couples.

Comorbidities and the risk of severe or fatal outcomes associated with coronavirus disease 2019: A systematic review and meta-analysis.

OBJECTIVES: Existing findings regarding the relationship between comorbidities and the severity of coronavirus disease 2019 (COVID-19) are inconsistent and insufficient. The aim of this study was to evaluate the association between different comorbidities and the severity of COVID-19. METHODS: The PubMed, Embase, and Cochrane Library databases were searched to identify studies reporting the rates of comorbidities in COVID-19 patients with severe/fatal outcomes. Subgroup analyses were conducted according to disease severity and the country of residence. Odds ratios (OR) with 95% confidence intervals (CI) were pooled using random-effects models. RESULTS: A total of 34 eligible studies were identified. In patients with severe/fatal COVID-19, the most prevalent chronic comorbidities were obesity (42%, 95% CI 34-49%) and hypertension (40%, 95% CI 35-45%), followed by diabetes (17%, 95% CI 15-20%), cardiovascular disease (13%, 95% CI 11-15%), respiratory disease (8%, 95% CI 6-10%), cerebrovascular disease (6%, 95% CI 4-8%), malignancy (4%, 95% CI 3-6%), kidney disease (3%, 95% CI 2-4%), and liver disease (2%, 95% CI 1-3%). In order of the prediction, the pooled ORs of the comorbidities in patients with severe or fatal COVID-19 when compared to patients with non-severe/fatal COVID-19 were as follows: chronic respiratory disease, OR 3.56 (95% CI 2.87-4.41); hypertension, OR 3.17 (95% CI 2.46-4.08); cardiovascular disease, OR 3.13 (95% CI 2.65-3.70); kidney disease, OR 3.02 (95% CI 2.23-4.08); cerebrovascular disease, OR 2.74 (95% CI 1.59-4.74); malignancy, OR 2.73 (95% CI 1.73-4.21); diabetes, OR 2.63 (95% CI 2.08-3.33); and obesity, OR 1.72 (95% CI 1.04-2.85). No correlation was observed between liver disease and COVID-19 aggravation (OR 1.54, 95% CI 0.95-2.49). CONCLUSIONS: Chronic comorbidities, including obesity, hypertension, diabetes, cardiovascular disease, cerebrovascular disease, respiratory disease, kidney disease, and malignancy are clinical risk factors for a severe or fatal outcome associated with COVID-19, with obesity being the most prevalent and respiratory disease being the most strongly predictive. Knowledge of these risk factors could help clinicians better identify and manage the high-risk populations.