LC-MS/MS methods for simultaneous determination of youkenafil and its metabolite M1 in human seminal plasma and plasma: Application to evaluate the acute effect of youkenafil on semen quality and its pharmacokinetics in human.

Youkenafil is a novel Phosphodiesterase type 5 inhibitor used for treating erectile dysfunction. N-desethyl compound of youkenafil (M1) is its main active metabolite. In this study, two methods were developed and validated for the simultaneous determination of youkenafil and M1 by HPLC-MS/MS in human matrices including seminal plasma and plasma, in which the multiple reaction monitoring and electrospray ionization in positive mode were adopted, and the deuterated youkenafil (youkenafil-d5) was selected as the internal standard. The collected semen sample was kept at room temperature for approximately 30 min until fully liquefied. The volume of the liquefied semen was measured and then divided into two parts. One part was centrifuged to obtain the seminal plasma for the content detection of youkenafil and M1, while the other part was used for routine semen analysis. The chromatographic separation was accomplished with the column of Poroshell 120 EC-C18 (5 × 2.1 mm, 2.7 µm, Agilent). Protein precipitation with methanol was used for the pretreatment of seminal plasma and plasma. The intra-run and inter-run precisions were less than 6.4 % (relative standard deviation) and accuracies were all within -4.7 %-6.8 % (relative error) in both matrices. All other validated bioanalytical parameters were within the acceptance criteria set by the FDA. The methods were successfully applied to different clinical studies of youkenafil. In the clinical study of the acute effect of youkenafil on semen quality in healthy males, the content of youkenafil in seminal plasma was extremely low. Concentrations of youkenafil and M1 in seminal plasma were lower than those in plasma, at 20.7 % and 4.49 % of the plasma concentration, respectively. There was no significant acute effect of youkenafil on semen quality. In the pharmacokinetic study of youkenafil after single dose-escalation administration, the exposure to youkenafil and M1 was non-linear with the dose in the range of 100-400 mg.

A meta-analysis of adverse effects of retinopathy of prematurity on neurodevelopment in preterm infants.

BACKGROUND: Retinopathy of prematurity (ROP) increases with the survival of late preterm infants, but its relationship with neurodevelopmental outcomes in preterm infants remains controversial. To investigate the relationship between ROP and its severity and adverse neurodevelopmental outcomes in preterm infants. METHODS: We conducted a meta-analysis. All relevant literature before November 2022 were retrieved from PubMed, Embase, Cochrane Library Web of Science, CNKI, CBM, Wan fang Data, and VIP Database. According to the inclusion criteria and exclusion criteria, eligible literature were included to conduct clinical trial quality assessment, and the Newcastle-Ottawa scale was used to evaluate the quality of evidence. Meta-analysis was performed using RevMan5.3. Data extraction, quality assessment, and meta-analysis were performed independently by 2 people. Mean difference or standardized mean difference of motor, language and cognitive scores (Bayley III or Bayley II) were used as effect sizes for continuous data analysis, all of which were represented by 95% CI. For heterogeneity (I2 ≥ 50% or P < .10), a random effects model was used, otherwise a fixed effects model was used. RESULTS: A total of 6 literature were included. The results of the ROP group for motor (comprehensive motor, proportional motor, and fine motor), language and cognitive scores were -5.57 (95%CI, -1.43 to 0.04), -0.95 (95%CI, 1.4-0.50), -1.34 (95% CI, 1.77-0.92), -1.75 (95% CI, 2.26-1.24) and -5.56 (95% CI, 9.56-1.57). Additionally, the results of severe ROP group for motor (comprehensive motor, proportional motor, fine motor), language and cognitive scores were -8.32 (95%CI, -8.91 to 7.74), -1.10 (95%CI, -1.83 to -0.36), -1.08 (95%CI, -1.75 to -0.41), -7.03 (95%CI, -7.71 to 6.35), and -7.96 (95%CI, -8.5 to -7.42). CONCLUSIONS: The Bayley Scale scores of the ROP group were lower than those of the not ROP group, and the scores of the severe ROP were significantly lower than those of the not severe ROP group. These findings suggest that ROP can indeed delay motor, language and cognitive, especially in severe cases.

Mechanisms involved in the HMGB1 modulation of tumor multidrug resistance (Review).

Tumor multidrug resistance (MDR) remains one of the most challenging barriers to successful cancer treatment. Several previous studies have suggested that high mobility group box 1 (HMGB1) may be a promising therapeutic target for overcoming cancer drug resistance. Emerging evidence has indicated that HMGB1 functions as a 'double­edged sword' that plays both pro­ and anti­tumor roles in the development and progression of multiple types of cancer. HMGB1 has also been found to be a key regulator of several cell death and signaling pathways, and is involved in MDR by mediating cell autophagy and apoptosis, ferroptosis, pyroptosis and multiple signaling pathways. Additionally, HMGB1 is regulated by a variety of non­coding RNAs (ncRNAs), such as microRNAs, long ncRNAs and circular RNAs that are involved in MDR. Thus far, studies have been conducted to identify strategies with which to overcome HMGB1­mediated MDR by the targeted silencing of HMGB1 and the targeted interference of HMGB1 expression using drugs and ncRNAs. Therefore, HMGB1 is closely associated with tumor MDR and is a promising therapeutic target.

The Effect and Safety of Thunder-Fire Moxibustion for Low Back Pain: A Meta-Analysis of Randomized Controlled Trials.

Background: Low back pain (LBP) is considered the leading cause of people living with years of disability worldwide. Notably, thunder-fire moxibustion (TFM) is a new type of moxibustion, which has been widely applied to treat pain syndromes for thousands of years. This study aims to provide evidence to evaluate the effect and safety of TFM in treating LBP. Methods: A systematic search of PubMed, Web of Science, the Cochrane Library, Embase, EBSCO, CNKI, Wanfang Data, CBM, and VIP (until April 2021) was used to identify studies reporting pain intensity, disability, Japanese Orthopedic Association (JOA) score, and quality of life in patients with LBP. Randomized controlled trials (RCTs), which compared TFM and other therapies in LBP, were included. Meanwhile, methodological quality was evaluated using the Cochrane criteria for risk of bias, and the level of evidence was rated utilizing the GRADE approach. Results: Twenty-one RCTs, including 2198 patients, satisfied the inclusion criteria. Compared with other therapies, the effect of TFM was statistically significant, pain intensity decreased (SMD = 0.94; 95% CI (0.74, 1.14); p < 0.00001), disability improved (SMD = 1.39; 95% CI (0.19, 2.59); p=0.02), and the JOA score increased (SMD = -1.34; 95% CI (-1.88, -0.80); p < 0.00001). It was also reported that the patient's quality of life improved after treatment for a period of 4 weeks (SMD = -0.29; 95% CI (-0.42, -0.16); p < 0.0001) and after a follow-up of 1 month (SMD = -0.20; 95% CI (-0.34, -0.07); p=0.003). The evidence level of the results was determined to be very low to low. Conclusions: Based on the existing evidence, it can be concluded that TFM may have a better effect than other treatments on LBP. However, it is not yet possible to assess the safety level of TFM therapy. Due to the universal low quality of the eligible trials and low evidence level, rigorously designed large-scale RCTs must be conducted in order to further confirm the results in this review.

Gut microbial dysbiosis in rheumatoid arthritis: a systematic review protocol of case-control studies.

INTRODUCTION: Rheumatoid arthritis (RA) has a huge societal impact due to the high prevalence, irreversible joint damage and systemic complications. Gut microbiota plays an important role in the pathogenesis and progression of RA by regulating the host immune system. Restoring intestinal homeostasis by altering the microbiota could be an attractive strategy for the prevention and treatment of RA. However, the signature features of microbial dysbiosis in RA are still controversial. Therefore, we aim to elucidate the characteristic change in the diversity and composition of gut microbiota in RA. METHODS AND ANALYSIS: We will systematically search through PubMed, EMBASE, Web of Science and Cochrane Library, as well as dissertations and conference proceedings. The reference lists of all included studies will be also reviewed to retrieve additional relevant studies. The case-control studies that reported either the relative abundance of bacteria at the phylum or genus level or at least one of the alpha-diversity, beta-diversity indexes in both RA and healthy controls will be included. Eligible studies will be screened independently by two reviewers according to the inclusion criteria. The Newcastle-Ottawa Quality Assessment Scale will be used to assess the quality of the included studies. Data extraction, qualitative and quantitative analysis will be performed within the gut microbial dysbiosis in RA. The expected outcomes will be the identification of the specific changes in composition and diversity of the gut microbiota in patients with RA. The quality of evidence will be assessed by the Grading of Recommendations Assessment, Development and Evaluation framework. ETHICS AND DISSEMINATION: Ethical approval is unnecessary as this review does not address the data and privacy of patients. The results will be published in a peer-reviewed scientific journal and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42021225229.

Nursing students' attitudes toward mobile learning: An integrative review.

PURPOSE: This study aimed to explore whether the attitudes of nursing students toward the use of mobile learning are positive or negative and to identify the factors influencing their attitudes by reviewing the literature. METHODS: Electronic search of six databases, including PubMed, the Cumulative Index of Nursing and Allied Health Literature, ProQuest, Web of Science, EMBASE, and Cochrane Library, was conducted, and relevant references within articles were manually searched. Retrieval time was from inception to October 21, 2020. The literature review was conducted in accordance with the PRISMA guidelines and the integrative review method. The Mixed Method Appraisal Tool (MMAT) was used for quality assessment. RESULTS: A total of 316 articles were identified, and 18 English-language studies were finally included by reviewing titles, abstracts, and full text. Six quantitative, five qualitative, and seven mixed-method articles related to nursing students' attitudes toward the use of mobile learning were identified. The results showed that most nursing students had positive attitudes toward mobile learning. Although students expressed strong intentions for mobile learning, the actual usage rate in practical settings was low. Several advantageous factors included usefulness, convenience, and ease of use, whereas disadvantageous factors included hardware facility, updated content, and software stability. CONCLUSION: Most nursing students have positive attitudes and willingness to mobile learning, but the actual use rate remains low. Advantageous and disadvantageous factors coexist. Further studies are needed to assess how mobile learning improves nursing students' clinical knowledge and improves patient care.

On the Evaluation of Rhamnolipid Biosurfactant Adsorption Performance on Amberlite XAD-2 Using Machine Learning Techniques.

Biosurfactants are a series of organic compounds that are composed of two parts, hydrophobic and hydrophilic, and since they have properties such as less toxicity and biodegradation, they are widely used in the food industry. Important applications include healthy products, oil recycling, and biological refining. In this research, to calculate the curves of rhamnolipid adsorption compared to Amberlite XAD-2, the least-squares vector machine algorithm has been used. Then, the obtained model is formed by 204 adsorption data points. Various graphical and statistical approaches are applied to ensure the correctness of the model output. The findings of this study are compared with studies that have used artificial neural network (ANN) and data group management method (GMDH) models. The model used in this study has a lower percentage of absolute mean deviation than ANN and GMDH models, which is estimated to be 1.71%.The least-squares support vector machine (LSSVM) is very valuable for investigating the breakthrough curve of rhamnolipid, and it can also be used to help chemists working on biosurfactants. Moreover, our graphical interface program can assist everyone to determine easily the curves of rhamnolipid adsorption on Amberlite XAD-2.

Effects of mobile learning for nursing students in clinical education: A meta-analysis.

The objective of this meta-analysis was to assess the effects of mobile learning for nursing students in clinical nursing education. Five electronic databases including PubMed, CINAHL, EMBASE, the Cochrane library and Web of Science were searched for English language articles published on or before February 10, 2020. Two reviewers retrieved articles, evaluated quality and extracted data independently. Review Manager (RevMan) version 5.3 software was used to perform meta-analysis. A total of 9 studies including 580 nursing students receiving clinical nursing education met the inclusion criteria. The mobile learning intervention led to significant improvements in nursing students' skills (SMD = 1.22, 95% CI [0.29, 2.14], P = 0.009), knowledge (SMD = 0.43, 95% CI [0.11, 0.76], P = 0.009), satisfaction (SMD = 0.31, 95% CI [0.05, 0.56], P = 0.020), and confidence (SMD = 0.4, 95% CI [0.16, 0.63], P < 0.001) compared with the control group. Due to differences in experimental design among studies and limited data availability, we cautiously conclude that mobile learning has a beneficial effect on clinical nursing education for nursing students compared with conventional methods.

Effectiveness of Virtual Reality in Nursing Education: Meta-Analysis.

BACKGROUND: Virtual reality (VR) is the use of computer technology to create an interactive three-dimensional (3D) world, which gives users a sense of spatial presence. In nursing education, VR has been used to help optimize teaching and learning processes. OBJECTIVE: The purpose of this study was to evaluate the effectiveness of VR in nursing education in the areas of knowledge, skills, satisfaction, confidence, and performance time. METHODS: We conducted a meta-analysis of the effectiveness of VR in nursing education based on the Cochrane methodology. An electronic literature search using the Cochrane Library, Web of Science, PubMed, Embase, and CINAHL (Cumulative Index to Nursing and Allied Health Literature), up to December 2019 was conducted to identify studies that reported the effectiveness of VR on knowledge, skills, satisfaction, confidence, and performance time. The study selection and data extraction were carried out by two independent reviewers. The methodological quality of the selected studies was determined using the Cochrane criteria for risk-of-bias assessment. RESULTS: A total of 12 studies, including 821 participants, were selected for the final analysis. We found that VR was more effective than the control conditions in improving knowledge (standard mean difference [SMD]=0.58, 95% CI 0.41-0.75, P<.001, I2=47%). However, there was no difference between VR and the control conditions in skills (SMD=0.01, 95% CI -0.24 to 0.26, P=.93, I2=37%), satisfaction (SMD=0.01, 95% CI -0.79 to 0.80, P=.99, I2=86%), confidence (SMD=0.00, 95% CI -0.28 to 0.27, P=.99, I2=0%), and performance time (SMD=-0.55, 95% CI -2.04 to 0.94, P=.47, I2=97%). CONCLUSIONS: The results of this study suggest that VR can effectively improve knowledge in nursing education, but it was not more effective than other education methods in areas of skills, satisfaction, confidence, and performance time. Further rigorous studies with a larger sample size are warranted to confirm these results.

Efficacy and safety of moxibustion for chronic low back pain: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: To systematically review and meta-analyze the efficacy of moxibustion in treating patients with chronic low back pain (CLBP). METHODS: A systematic search of the Cochrane Library, Web of Science, PubMed, Embase, EBSCO, CBM, Wanfang, CNKI and VIP (until November, 2019) was used to identify studies reporting pain intensity (VAS or NRS), disability (ODI or RMDQ), JOA score, and quality of life (SF-36) in patients with CLBP. Study selection, data extraction was performed critically and independently by two reviewers. Cochrane criteria for risk of bias was used to assess the methodological quality of the trials. The Grading of Recommendations Assessment, Development, and Evaluation Methodology (GRADE) was applied to test the quality of evidence from the quantitative analysis. RESULTS: Ten RCTs, including 987 patients, met the inclusion criteria. Moxibustion had a superior effect on VAS score when compared with western medicine [RR = -1.69, 95%CI(-2.40, -0.98), p < 0.00001] and acupuncture [RR = -0.47, 95%CI(-0.92, -0.02), p=0.04], but it failed to do so when compared with core stability training [RR = -0.41, 95%CI(-0.87, 0.05), p=0.08]. The result showed that moxibustion plus other active treatments (including western medicine, massage, acupuncture and core stability training) had better effects on low back pain relief compared with active treatments alone. Moxibustion showed favourable effects on disability [SMD = -3.80, 95%CI (-5.49, -2.11), p < 0.0001], JOA score [MD = 4.10, 95%CI(2.30, 5.90), p < 0.00001], and SF-36 score [MD = 13.41, 95%CI(9.68, 17.14), p < 0.00001]. The evidence level of the results from the ten studies was determined to be very low to low. CONCLUSIONS: It is difficult to draw firm conclusions that moxibustion is an effective intervention for treating CLBP due to the small sample size of eligible trails and the high risk of bias among the available articles. Rigorously designed large-scale RCTs are required to further confirm the results in this review.

Metabolomics in the development and progression of rheumatoid arthritis: A systematic review.

OBJECTIVE: A systematic review and analysis of data from several rheumatoid arthritis metabolomics studies attempts to determine which metabolites can be used as potential biomarkers for the diagnosis of rheumatoid arthritis and to explore the pathogenesis of rheumatoid arthritis. METHODS: We searched all the subject-related documents published by EMBASE, PubMed, Web of Science, and Cochrane Library from the database to the September 2019 publication. Two researchers independently screened the literature and extracted the data. QUADOMICS tool was used to assess the quality of studies included in this systematic review. RESULTS: A total of 10 studies met the inclusion criteria of systematic review, including 502 patients with rheumatoid arthritis and 373 healthy people. Among them, the biological samples utilised for metabolomic analysis include: serum (n=8), urine (n=1) and synovial fluid (n=1). Some metabolites play an important role in rheumatoid arthritis: glucose, lactic acid, citric acid, leucine, methionine, isoleucine, valine, phenylalanine, threonine, serine, proline, glutamate, histidine, alanine, cholesterol, glycerol, and ribose. CONCLUSIONS: Metabolomics provides important new opportunities for further research in rheumatoid arthritis and is expected to elucidate the pathogenesis of rheumatoid arthritis that has not been fully understood before.

Baicalin extracted from Huangqin (Radix Scutellariae Baicalensis) induces apoptosis in gastric cancer cells by regulating B cell lymphoma (Bcl-2)/Bcl-2-associated X protein and activating caspase-3 and caspase-9.

OBJECTIVE: To evaluate the effects of baicalin in human gastric cancer cells, including apoptosis-inducing effects, and to investigate its underlying mechanisms of action. METHODS: Cell proliferation and apoptosis assays were performed to investigate the anti-proliferation effects of baicalin in human gastric cancer BGC-823 and MGC-803 cells. Real time-quantitative polymerase chain reaction and Western blotting analysis were performed to elucidate the molecular mechanisms underlying the anti-tumor properties of baicalin. RESULTS: In BGC-823 and MGC-803 gastric cancer cells treated with 80, 120, and 160 µmol/L baicalin for 48 h, a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay showed that baicalin significantly inhibited cell proliferation in a dose-dependent manner, while flow cytometric analysis demonstrated that baicalin could induce apoptosis, also in a dose-dependent manner. Moreover, baicalin up-regulated the expression of caspase-3, caspase-9, and B cell lymphoma (Bcl-2)-associated X protein and down-regulated the expression of Bcl-2 at both the mRNA and protein level. CONCLUSION: Baicalin has potential as a therapeutic agent for gastric cancer by inducing apoptosis in cancer cells.

[Effect of banxia xiexin decoction on gastric antral interstitial cells of Cajal and stem cell factor in diabetic rats].

OBJECTIVE: To observe the effect of Banxia Xiexin Decoction (BXD) on expression of the interstitial cells of Cajal (ICCs) and stem cell factor (SCF) in the antrum of rats with diabetes mellitus (DM). METHODS: Totally sixty healthy male SD rats were randomly divided into the control group, the model group, the BXD group, and the Western medicine group (WM, treated by domperidone), 15 in each group. Diabetic rat models were established by a single intraperitoneal injection of streptozotocin (STZ, 55 mg/kg). Those in the BXD group were perfused with BXD at the daily dose of 5.4 g/kg. An equal volume of distilled water was given by gastrogavage to those in the WM group and the control group for 8 successive weeks. The body weight and blood glucose of all rats were detected, and the gastric residual rates were detected with semisolid nutrient paste by gastrogavage. The expression of positive ICCs and SCF were observed by immunohistochemical method and quantified image analyzer. RESULTS: Compared with the control group,the body weight reduced, blood glucose and gastric residual rates increased, and the mean optical density of positive ICCs and SCF significantly decreased in the model group (P < 0.05). Compared with the model group,symptoms such as polydipsia, polyphagia, polyuria were relieved, spirits improved, the body weight and mean optical densities of positive ICCs and SCF significantly increased (P < 0.05), and gastric residual rates significantly decreased in the BXD group and the WM group (P < 0.05). The blood glucose significantly decreased (P < 0.05) in the BXD group. The mean optical density of positive ICCs was higher in the BXD group than in the WM group (P < 0.05). CONCLUSIONS: BXD could promote the expression of positive ICCs and SCF. It could improve the gastric motility in DM rats by partially inverting abnormal changes of gastric antral ICCs and SCF.

Determination of 10 ginsenosides in Panax ginseng of different harvest times based on HPLC fingerprints and principal component analysis.

A combinative method of HPLC fingerprinting and quantitative determination was successfully applied to monitor dynamic accumulation of ginsenosides in five-year-old Panax ginseng roots from different harvest times. The optimal chromatographic conditions were achieved on a C18 column with gradient elution using acetonitrile and 1 mmol · L(-1) KH2PO4 buffer solution at 203 nm. The result indicated that the contents of total ginsenosides showed significant variations, and a decrease tendency appeared in the growth period of the fifth year.

[Selective screening of inborn errors of metabolism by using the tandem mass spectrometry: pilot study of 552 children at high risk].

OBJECTIVE: To study the application of tandem mass spectrometry (MS/MS) in the selective screening of inborn errors of metabolism (IEM) in high risk children and to understand the positive rate and types of IEM. METHODS: MS/MS was used to examine 552 blood samples from high risk cases of IEM who came from 8 hospitals in Shijiazhuang, Hebei Province. RESULTS: Sixty-four children (11.6%) were confirmed with IEM by the MS/MS, including 33 cases of methylmalonic acidemia or propionic acidemias, 2 cases of phenylketonuria, 3 cases of carnitine palmotoyl transferase I deficiency, 1 case of long-chain acyl-CoA dehydrogenase deficiency, 2 cases of medium-chain acyl-CoA dehydrogenase deficiency, 6 cases of maple syrup urine disease, 2 cases of short-chain acyl-CoA dehydrogenase deficiency, 2 cases of glutaric acidemia type I, 2 cases of isovaleric acidemia, 2 cases of homocystinuria, 4 cases of carnitine deficiency, 1 case of tyrosinemia, 1 case of argininosuccinic aciduria, 2 cases of citrullinemia and 1 case of argininemia. CONCLUSIONS: MS/MS can be used to screen and classify IEM.