The alleviation effect and its mechanism of Niuhuang Jiedu prescription on realgar-induced genotoxicity in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Realgar (As2S2 or As4S4) is a traditional Chinese medicine (TCM) containing arsenic. Existing studies have shown that it has genotoxicity under long-term use with large doses. Niuhuang Jiedu (NHJD) is a Chinese medicine prescription containing realgar and seven other TCMs. Whether the multiple TCMs combination in NHJD can reduce the genotoxicity induced by realgar in equivalent doses is still unknown. AIM OF THE STUDY: To research the effect of NHJD on realgar's genotoxicity and the possible mechanism involved based on the arsenic methylation metabolic pathway. MATERIAL AND METHODS: Six groups (control, realgar (0.8 g/kg), NHJD (12.48 g/kg), as well as Glycyrrhiza uralensis Fisch (GU), Scutellaria baicalensis Georg (SB), Rheum palmatum L (RP) plus equivalent doses of realgar, respectively) were set up. ICR mice were intragastric administered for 12 weeks. First, genotoxicology tests were conducted to evaluate the effect of NHJD, GU, SB, and RP on reducing realgar's genotoxicity. The inorganic arsenic (iAs), dimethyl arsenic acid (DMA), and monomethyl arsenic acid (MMA) were determined by HPLC-AFS, and the iAs%, MMA%, DMA%, primary methylation index (PMI), etc. Were calculated. Meanwhile, the S-adenosyl methionine (SAM) and arsenate reductase (ARR) levels, the arsenic (+3)methyltransferase (As3MT), purine-nucleoside phosphorylase (PNP), glutathione S-transfer omega1 (GSTO1) gene expression were detected, aimed to explore the possible alleviation mechanisms of NHJD. RESULTS: The combination of multiple TCMs in NHJD decreased the levels of MN‰, SPA%, and DNA damage caused by realgar, with similar effects observed when SB, RP, and GU were used separately with realgar. Notably, the iAs% significantly decreased, while DMA% and PMI notably increased in the NHJD and realgar + SB (or RP) groups compared to the realgar-only group (P < 0.05). Increases in SAM and ARR levels were observed across various groups, but only the ARR increase in the NHJD group was statistically significant. Moreover, significant increases in As3MT mRNA and GSTO1 mRNA were noted in the NHJD group, and PNP mRNA levels significantly rose in the realgar + SB group. CONCLUSIONS: This study revealed that NHJD could attenuate the genotoxic effects of realgar. The botanicals SB, RP, and GU within NHJD may be key contributors to this effect. Enhancements in arsenic methylation capabilities through increased levels of SAM and ARR and elevated gene expressions of As3MT, PNP, and GSTO1 suggest potential mechanisms behind these findings.

Proteomic characteristics of six snake venoms from the Viperidae and Elapidae families in China and their relation to local tissue necrosis.

Patients envenomed by snakes from the Viperidae and Elapidae families in China often have varying degrees of local tissue necrosis. Due to the relative clinical characteristics of local tissue necrosis and ulceration following envenoming, this study has analyzed the proteome of six snake venoms from the Viperidae and Elapidae family, and the toxin profiles of each snake were compared and correlated with the clinical manifestations that follow cytotoxic envenoming. Deinagkistrodon acutus and Naja atra envenomation induce severe ulceration, which is absent in Bungarus multicinctus envenomation and mild in the other three vipers. It is interesting to note that the proportion of c-type lectins (CTL) (20.63%) in Deinagkistrodon acutus venom was relatively high, which differs from the venom of other vipers. In addition, three-fingered toxin (3FTx) (2.15%) is present in the venom of Deinagkistrodon acutus, but has not been detected in the remaining three vipers. Snake venom metalloprotease (SVMP) (34.4%-44.7%), phospholipase A2 (PLA2) (9.81%-40.83%), and snake venom serine protease (SVSP) (9.44%-16.2%) represent the most abundant families of toxin in Viperidae venom. The Elapidae venom proteome was mainly composed of neurotoxins and cytotoxins, including 3FTx (39.28%-60.08%) and PLA2 (8.24%-58.95%) toxins, however, the proportion of CRISPS (26.36%) in Naja atra venom was relatively higher compared to Bungarus multicinctus venom. Significant differences in SVMP, SVSP, and 3FTx expression levels exist between the Viperidae and the Elapidae family. The main toxins responsible for the development of tissue necrosis and ulcerations following Viperidae envenoming are hematotoxins (SVSMP, SVSP) and myotoxins (PLA2). Deinagkistrodon acutus venom contains high levels of CTL and traces of 3FTx, leading to more severe local necrosis. However, Naja atra venom can also cause severe local necrosis through the effects of myotoxin (3FTx, CRISP, PLA2). Bungarus multicinctus venom does not contain myotoxins, resulting in pure systemic neurological manifestations no obvious necrosis of local tissue in patients.

Factors Influencing Long-Term Behavioral Intervention Outcomes in Preschool Children with Attention-Deficit Hyperactivity Disorder in Southeast China.

Introduction: Previous studies have demonstrated the long-term effectiveness of behavioral interventions for attention-deficit hyperactivity disorder (ADHD) in preschool children. We continue to design a case‒control study to further investigate the factors influencing the long-term effect of behavioral intervention. Methods: From May 2020 to August 2021, children who were newly diagnosed with ADHD and not receiving any treatment received a one-year behavioral intervention. A total of 86 children completed the behavioral intervention and assessment. Results: 50 children (58.140%) were in the effective group, and 36 children (41.860%) were in the ineffective group. Attention retention time (OR=0.559, 0.322-0.969), Swanson, Nolan, and Pelham total score (OR=1.186, 1.024-1.374) at baseline, performance score for parents (OR=0.631, 0.463-0.859), and teacher coordination (OR=0.032, 0.002-0.413) were the influencing factors of behavioral intervention effects. The area under the receiver operating curve was 0.979 (p<0.001). The comprehensive nomogram model showed that the discrimination and mean absolute error were 0.979 and 0.023, respectively. Discussion: During behavioral intervention, the implementation skills of parents should be evaluated in a timely manner. The behavioral intervention effect can be predicted based on a child's attention retention time at baseline, teacher involvement, behavioral scale score, and performance score for parents, which can guide clinicians in adjusting personalized treatment plans and provide a basis for clinical decision-making. The treatment of ADHD in preschool children requires a systematic framework that integrates family, school, and society.

Nitrite and nitrate in meat processing: Functions and alternatives.

Meat and meat products are important foods in the human diet, but there are concerns about their quality and safety. The discovery of carcinogenic and genotoxic N-nitroso compounds (NOCs) in processed meat products has had serious negative impacts on the meat industry. In order to clarify the relationship between the use of nitrite or nitrate and the safety of meat or meat products, we reviewed NOCs in meat and meat products, the origin and safety implications of NOCs, effects of nitrite and nitrate on meat quality, national regulations, recent publications concerning the using of nitrite and nitrate in meat or meat products, and reduction methods. By comparing and analyzing references, (1) we found antioxidant, flavor improvement and shelf-life extension effects were recently proposed functions of nitrite and nitrate on meat quality, (2) the multiple functions of nitrite and nitrate in meat and meat products couldn't be fully replaced by other food additives at present, (3) we observed that the residual nitrite in raw meat and fried meat products was not well monitored, (4) alternative additives seem to be the most successful methods of replacing nitrite in meat processing, currently. The health risks of consuming processed meat products should be further evaluated, and more effective methods or additives for replacing nitrite or nitrate are needed.

Real-World Prescribing Patterns for Hypertensive Children in China from 2018 to 2021: A Cross-Sectional Multicenter Study.

Background: Pediatric hypertension become an early marker of cardiovascular diseases, but their antihypertensive drug use patterns are rarely known. Purpose: To investigate the epidemiological characteristics of pediatric hypertension and the use of antihypertensive drugs in the real world in China. Methods: In this study, the demographic, diagnosis, and medication prescription data including the antihypertensive drug types and comorbidities, were analyzed. The antihypertensive drugs use were evaluated according to the Chinese guidelines for hypertension. Results: 1301 prescriptions (number of visits) containing 1880 antihypertensive medical orders were collected. The average number of antihypertensive drugs per prescription was 1.45 (±0.75). The patients aged 16 to 18 (70.18%) accounted for the highest proportion. Kidney diseases (33.28%) were the most common comorbidities. Calcium channel blocker (CCB), angiotensin II receptor blocker (ARB), and ß receptor blocker (BB) were the most used antihypertensive drugs. The most frequent monotherapy was CCB, while that of two and three drugs combination were ARB+CCB and ARB+BB+CCB, respectively. Metoprolol (11.44%), nifedipine (10.64%), amlodipine (10.59%), valsartan (6.12%) were the most commonly used antihypertensive drugs. The utilization rate of fixed compound preparations was 7.34%. However, the percentage of recommended antihypertensive drugs was just 14.20%, while the recommended drug combination was 84.93% according to the guidelines. Conclusion: For the first time ever we reported the antihypertensive prescription analysis in children in a large area of China. Our data provided new insights into the epidemiological characteristics and drug use in hypertensive children. We found that the guidelines for medication management in hypertensive children were not routinely followed. The wide use of antihypertensive drugs in children and those with weak clinical evidence raised concerns regarding its rational use. The findings could lead to more effective management of hypertension in children.

Effect of 4 °C and ice temperature on umami-enhancing nucleotides of conditioned pork.

To study new methods to delay the umami taste attenuation of the conditioned pork, the ice temperature of pork, the content of nucleotides, lactic acid, pyruvate, glycogen, and activity of key endogenous enzymes were determined for the conditioned pork stored at 4 °C and ice temperature. The results indicated that the ice temperature of the pork ham bicipital muscle was -1.4 °C. The content of umami-enhancing nucleotides in pork stored at 4 °C decreased significantly (p < 0.05) with increasing aging time, but all umami-enhancing nucleotides in pork stored at ice temperature were decreased significantly (p < 0.05), but the decrease rates were lower than those in pork stored at 4 °C. A possible reason for this was that the storage temperature influenced the activity of endogenous enzymes and glycolysis. Ice temperature storage was an effective method to inhibit the decrease in umami taste nucleotides in conditioned pork.

Comparison of Nutrition and Flavor Characteristics of Five Breeds of Pork in China.

To characterize the quality of widely consumed pork in China, the chemical compositions and other indexes of five breeds of pork were compared. The results indicated that the moisture content, sensory flavor, and overall acceptability of Pipa pork (PPP) were superior to other breeds. The fat content and essential amino acids (EAA) of Yihao native pork (YNP) were significantly (p < 0.05) higher than in other breeds. The protein content, the total amount of amino acids, and perceptible flavor of Tibetan black pork (TBP) were higher than in other breeds. The protein nutrition profiles of manor black pork (MBP) and TBP were better than in others. The equivalent umami concentration (EUC) value of white pork (WP) was significantly (p < 0.05) higher than in others; however, the health risk of its fatty acid content was higher. There were unique protein and flavor chemicals in YNP, TBP, and PPP, which may be useful for distinguishing their authenticity.

Target RNA expression omics approach to reveal the liver detoxification effect induced by Chinese medicine prescription Niu Huang Jie Du against realgar overexposure to mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Niu Huang Jie Du prescription (NHJD) is a traditional Chinese medicine (TCM) widely used in patients suffering from excessive inner fire toxin (Huo Du Nei Sheng) syndrome, such as sore throat, gingival swelling, and pain, mouth and tongue sores, etc. This formula contains realgar (As4S4) which is one of the 28 toxic medicinal materials promulgated by the Chinese Ministry of Health. Many studies reported its toxicity on the liver and kidney, and the detoxification effect of NHJD. However, its detoxification mechanism is still unclear. AIM OF THE STUDY: To clarify the detoxification mechanism of NHJD to realgar, this study evaluated the detoxification effect of NHJD on realgar exposure in mice, and analyzed differences in mRNA expression profiles in liver tissues and associated functional predictions. MATERIAL AND METHODS: ICR mice were administered with NHJD, realgar, and CMC-Na as blank control for 12 weeks, respectively. Liver injury was evaluated by histopathologic examination and liver mRNA gene were sequenced by Illumina. Differentially expressed gene, functionally enrichment and protein association network analysis were conducted. RESULTS: 43 genes were screened out, among which 15 genes in the realgar group were decreased, but the extent of the decline has been restored in the NHJD group. The remaining 28 genes have exactly the opposite trends. Functional module analysis revealed that those detoxification function-related genes were primarily for positive regulation of glutathione metabolism, P450 on the metabolism of exogenous compounds, oxidative stress and immune-related, etc. CONCLUSIONS: The results indicated that realgar mainly causes liver damage by changing the common enzymes of drug metabolism, especially the expression of genes related to CYPs, GSTs family, oxidative stress, and complement immunity, while the TCM prescription NHJD has a regulatory effect on the abnormal expression of corresponding genes. Our results will provide some clues for the detoxification mechanism of arsenic-containing TCM prescriptions.

Storage Stability and Flavor Change of Marinated Pork.

To evaluate the storage stability and flavor changes of marinated pork treated with chili and pepper essential oils, the contents of total sulfhydryl, malondialdehyde, total volatile base nitrogen (TVBN), Ca2+ATPase activity, and total viable counts of marinated pork were determined. Further, the non-volatile (umami, numb, and spicy) and volatile flavor compounds of marinated pork were analyzed. Based on the results, the chili and pepper essential oils had limited effects on the storage stability of marinated pork. However, these essential oils could inhibit the oxidation of lipids and proteins and reduce the number of microorganisms and TVBN in marinated pork within 6 days. The non-volatile flavors of the marinated pork decreased as the refrigeration time increased. It was concluded that the decomposition of umami-enhancing nucleotides (GMP, IMP, XMP), the number of flavor substances (hydroxyl-α-sanshool, hydroxyl-ß-sanshool), and spicy (capsaicin) tasting compounds caused the decrease in non-volatile flavors.

Preoperative Clinical Characteristics Predict Recurrent Laryngeal Nerve Lymph Node Metastasis and Overall Survival in Esophageal Squamous Cell Carcinoma: A Retrospective Study With External Validation.

Background: Recurrent laryngeal nerve (RLN) lymph node metastasis (LNM) is not rare in patients with esophageal squamous cell carcinoma (ESCC). We aimed to develop and externally validate a preoperative nomogram using clinical characteristics to predict RLN LNM in patients with ESCC and evaluate its prognostic value. Methods: A total of 430 patients with ESCC who underwent esophagectomy with lymphadenectomy of RLN LNs at two centers between May 2015 and June 2019 were reviewed and divided into training (center 1, n = 283) and external validation cohorts (center 2, n = 147). Independent risk factors for RLN LNM were determined by multivariate logistic regression, and a nomogram was developed. The performance of the nomogram was assessed in terms of discrimination, calibration, clinical usefulness, and prognostic value. The nomogram was internally validated by the bootstrap method and externally validated by the external validation cohort. Results: Multivariate analysis indicated that clinical T stage (P <0.001), endoscopic tumor length (P = 0.003), bioptic tumor differentiation (P = 0.004), and preoperative carcinoembryonic antigen level (P = 0.001) were significantly associated with RLN LNM. The nomogram had good discrimination with the area under the curve of 0.770 and 0.832 after internal and external validations. The calibration curves and decision curve analysis confirmed the good calibration and clinical usefulness of this model. High-risk of RLN LNM predicted by the nomogram was associated with worse overall survival in the external validation cohort (P <0.001). Conclusion: A nomogram developed by preoperative clinical characteristics demonstrated a good performance to predict RLN LNM and prognosis for patients with ESCC.

A prospective study of the decision tree prediction model for attention deficit hyperactivity disorder in preschool children. / å­¦é¾„å‰å„¿ç«¥æ³¨æ„ç¼ºé™·å¤šåŠ¨éšœç¢å†³ç­–æ ‘é¢„æµ‹æ¨¡åž‹çš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To study the clinical value of attention time combined with behavior scale in the screening of attention deficit hyperactivity disorder (ADHD) in preschool children. METHODS: A total of 200 preschool children with ADHD diagnosed in Fujian Maternal and Child Health Hospital from February 2019 to March 2020 were enrolled as the ADHD group. A total of 200 children who underwent physical examination in the hospital or kindergartens during the same period were enrolled as the control group. Attention time was recorded. Chinese Version of Swanson Nolan and Pelham, Version IV Scale-Parent Form (SNAP-IV) scale was used to evaluate symptoms. With clinical diagnosis as the gold standard, the decision tree analysis was used to evaluate the clinical value of attention time combined with behavior scale in the screening of ADHD. RESULTS: Compared with the control group, the ADHD group had significantly higher scores of SNAP-IV items 1, 4, 7, 8, 10, 11, 14, 15, 16, 18, 20, 21, and 22 (P<0.05) and a significantly shorter attention time (P<0.05). The variables with statistically significant differences between the two groups in univariate analysis were used as independent variables to establish a decision tree model. The accuracy of the model in predicting ADHD was 81%, that in predicting non-ADHD was 69%, and the overall accuracy was 75%, with an area under the ROC curve of 0.816 (95% CI: 0.774-0.857, P<0.001). CONCLUSIONS: The decision tree model for screening ADHD in preschool children based on attention time and assessment results of behavior scale has a high accuracy and can be used for rapid screening of ADHD among children in clinical practice.

Long-term effectiveness of behavioural intervention in preschool children with attention deficit hyperactivity disorder in Southeast China - a randomized controlled trial.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is the most common behavioral disorder. Behavioural intervention in preschool children with ADHD is considered effective. This study discussed the long-term effectiveness of behavioural intervention in the context of nondrug therapy. METHODS: The study was a prospective, randomised controlled trial in which 201 preschoolers diagnosed with ADHD who were not receiving any treatment were assigned to two groups from January 2018 to May 2019, 101 were assigned to the conventional group and 100 to the behavioural intervention group. The behavioural intervention group included parental training, behavioural therapy, attention training, relief therapy and game therapy, in addition to the conventional group offerings. Children were evaluated at a baseline, at the end of the 12-month intervention and six months after the intervention. The primary and secondary outcome variables included attention time, the impulse-hyperactivity and hyperactivity index from Conners parent symptom questionnaire (PSQ), full-scale attention quotient (FAQ) and full-scale response control quotient (FRCQ) from integrated visual and auditory comprehensive continuous performance tests. The attention time was observed and recorded by parents, and others were performe(PSQ)d by physicians in the clinic. All statistical analyses were conducted using SPSS V26.0 (IBM), including the descriptive statistics and mixed-effects models and so on. RESULTS: The participants' mean age was (66.17±9.00) months in the behavioural group and (67.54±6.22) months in the conventional group .A total of 190 participants completed a follow-up six months after the intervention. The attention time, Conners parent symptom questionnaire (PSQ), full-scale attention quotient (FAQ) and full-scale response control quotient (FRCQ) increased significantly over time, and the behavioural group improvements were higher than those of conventional group. There was a significant main effect of time (pretest/posttest/follow-up) and group on all outcome measures (t =-12.549-4.069, p<0.05), and a significant interaction of time and group on attention time, impulsivity/hyperactivity, FAQ and FRCQ (t =-3.600-3.313, p<0.05). CONCLUSION: Behavioural intervention can effectively improve behaviour management and relieve symptoms in children with ADHD. These effects lasted at least six months. This study provides a promising approach for improving clinical efficacy with preschool children with ADHD.

Use of the alkaline comet assay for monitoring genotoxic effects of arsenic in human populations.

The alkaline comet assay has been widely used to determine genotoxicity in human populations exposed to arsenic. The sample sizes of earlier studies were usually small, and inconsistent results were found. Meta-analyses can merge the results of multiple studies of the same type and increase the credibility of the conclusion by increasing the sample size. Thus, to investigate the monitoring effect of alkaline comet assay on genotoxicity for arsenic exposed population, meta-analyses were performed. Thirteen studies were found to meet the inclusion criteria and were included in this study; of them, twelve articles were of medium quality (15-20 points), only one study was of high quality (21-27 points). Meta-analyses showed that the overall estimates of Mean Ratio (MR, defined as the mean value of the response in the exposed group divided by that in the reference group) were 2.81(95 % confidence interval (CI) 1.93-4.10); 2.37(95 % CI, 1.73-3.26), and 1.69(95 %CI, 1.29-2.20) for comet tail length, % tail DNA, and tail moment, respectively. This shows that the level of DNA damage in arsenic exposed population is significantly higher than that in control populations. A meta-analysis of the correlation coefficients showed that the overall estimate was 0.52 (95 %CI, 0.48∼0.56, P<0.05) with all correlation coefficients included, but it changed to 0.24 (95 %CI, 0.17∼0.28, P<0.05) when two abnormal correlation coefficients were excluded, suggesting there was a positive correlation between arsenic load in vivo and DNA damage, but the overall estimate value of coefficients was unstable. Therefore, we conclude that the alkaline comet assay can be used as an effective genotoxic biomonitoring tool for arsenic-exposed populations. However, more and higher-quality studies are still needed to verify its actual application value.

[Effect of Competitive Antagonist of Transmembrane Glutamine Flux V-9302 on Apoptosis of Acute Myeloid Leukemia Cell Lines HL-60 and KG-1].

OBJECTIVE: To investigate the effect of V-9302 (an antagonist of transmembrane glutamine flux) on the proliferation and apoptosis of acute myeloid leukemia cells HL-60 and KG-1. METHODS: HL-60 and KG-1 cells at logarithmic phase were treated by different concentrations of V-9302. CCK-8 assay was used to detect the proliferation of the cells. Annexin V-FITC / PI double staining flow cytometry was used to detect the apoptosis of HL-60 and KG-1 cells. The expressions of BAX, BCL-2 and Caspase3 were detected by RT-qPCR and Western blot. RESULTS: V-9302 could significantly inhibit the growth of HL-60 and KG-1 cells. The concentration of V-9302 at 10, 20 µmol/L could significantly promote the apoptosis of HL-60 and KG-1 cells(P<0.05). The results of apoptosis related gene detection showed that when V-9302 was applied to HL-60 and KG-1 cell lines at 10 and 20 µmol/L, the expression levels of Pro-apoptotic protein genes BAX and Caspase3 in HL-60 and KG-1 were significantly higher than those in control group (P<0.05), while the expression level of anti-apoptotic protein gene BCL-2 was significantly lower than that in the control group (P<0.05). The results of Western blot were basically consistent with that of RT-qPCR. CONCLUSION: Competitive antagonist of transmembrane glutamine flux V-9302 can significantly promote the apoptosis of acute myeloid leukemia cell lines HL-60 and KG-1.

Synergistic Network Pharmacology for Traditional Chinese Medicine Liangxue Tongyu Formula in Acute Intracerebral Hemorrhagic Stroke.

Background: Nowadays, acute intracerebral hemorrhage stroke (AICH) still causes higher mortality. Liangxue Tongyu Formula (LXTYF), originating from a traditional Chinese medicine (TCM) prescription, is widely used as auxiliary treatment for AICH. Objective: To dig into the multicomponent, multitarget, and multipathway mechanism of LXTYF on treating AICH via network pharmacology and RNA-seq. Methods: Network pharmacology analysis was used by ingredient collection, target exploration and prediction, network construction, and Gene Ontology (GO) and KEGG analysis, with the Cytoscape software and ClusterProfiler package in R. The RNA-seq data of the AICH-rats were analyzed for differential expression and functional enrichments. Herb-Compound-Target-Pathway (H-C-T-P) network was shown to clarify the mechanism of LXTYF for AICH. Results: 76 active ingredients (quercetin, Alanine, kaempferol, etc.) of LXTYF and 376 putative targets to alleviate AICH (PTGS2, PTGS1, ESR1, etc.) were successfully identified. The protein-protein interaction (PPI) network indicated the important role of STAT3. The functional enrichment of GO and KEGG pathway showed that LXTYF is most likely to influence MAPK and PI3K-Akt signaling pathways for AICH treatment. From the RNA-seq of AICH-rats, 583 differential mRNAs were identified and 14 of them were consistent with the putative targets of LXTYF for AICH treatment. The KEGG pathway enrichment also implied that the MAPK signaling pathway was the most correlated one among all the related signaling pathways. Many important targets with expression changes of LXTYF for AICH treatment and their related pathways are great markers of antioxidation, anti-inflammatory, antiapoptosis, and lowering blood pressure, which indicated that LXTYF may play mutiroles in the mechanisms for AICH treatment. Conclusion: The LXTYF attenuates AICH partially by antioxidation, anti-inflammatory, and antiapoptosis and lowers blood pressure roles through regulating the targets involved MAPK, calcium, apoptosis, and TNF signaling pathway, which provide notable clues for further experimental validation.

Risk of Cardiovascular and Cerebrovascular Events in Polycystic Ovarian Syndrome Women: A Meta-Analysis of Cohort Studies.

Aim: This systematic review and meta-analysis aimed to investigate the risk of cardiovascular disease (CVD) and cerebrovascular disease (CeVD) events in women with polycystic ovary syndrome (PCOS). Methods: We searched the literatures in Pubmed, Embase, and Web of Science to identify cohort studies reporting the association between PCOS and CVD/CeVD events from 1964 to June 1, 2020. Outcome variables, such as all-cause mortality, cardiovascular death, any cardiovascular diseases, myocardial infarction, ischemic heart disease, and stroke, were extracted from the identified literatures, and we reported the outcomes of the association in hazard ratios (HR) and odds ratios (OR). Results: Ten cohort studies comprising 166,682 samples are included in the review. Compared to non-PCOS women, the pooled risk of CVD events in PCOS women (OR: 1.66, 95% CI: 1.32-2.08). In addition, the risk of myocardial infarction (OR: 2.57, 95% CI: 1.37-4.82), ischemic heart disease (OR: 2.77, 95% CI: 2.12-3.61), and stroke (OR: 1.96, 95% CI: 1.56-2.47) are higher in the PCOS group. However, no significant difference in the overall mortality (HR: 1.04, 95% CI: 0.57-1.86) and CVD-related death (HR: 1.49, 95% CI: 0.99-2.23) was observed. Funnel plots of all outcomes are roughly symmetric, and no significant publication bias was found. Conclusion: Though this study identified an increased risk of CVD and CeVD among women with PCOS, including occurrence of myocardial infarction, ischemic heart disease, and stroke, there was no difference in the all-cause or CVD-related mortality observed. Further large-scale studies are warranted to strengthen the association between PCOS and CV events. Our study may require a larger sample size to further verify the conclusions.

Optimal switching time control of the hyperbaric oxygen therapy for a chronic wound.

Chronic wounds, defined as those wounds which fail to heal through the normally orderly process of stages and remain in a chronic inflammatory state, are a significant socioeconomic problem. This paper considers an optimal switching time control problem of the hyperbaric oxygen therapy for a chronic wound. First, we model the spatiotemporal evolution of a chronic wound by introducing oxygen, neutrophils, invasive bacteria, and chemoattractant. Then, we apply the method of lines to reduce the partial differential equations (PDEs) into ordinary differential equations (ODEs), which lead to an ODE optimization problem with the changed time switching points. The time-scaling transformation approach is applied to further transform the control problem with changed switching time into another new problem with fixed switching time. The gradient formulas of the cost functional corresponding to the time intervals are derived based on the sensitivity analysis. Finally, computational numerical analysis demonstrates the effectiveness of the proposed control strategy to inhibit the growth of bacterial concentration.

Micronucleus assay for monitoring the genotoxic effects of arsenic in human populations: A systematic review of the literature and meta-analysis.

The micronucleus (MN) assay has been used to determine the potential genotoxic effects in human populations exposed to arsenic. Some of these studies found an increase in MN frequency among exposed individuals, but others found no increase or inconclusive results. Thus, the main purpose of this current study was to investigate whether MN can be used as a biomarker for the arsenic exposure, as well as whether or not the different cell types that have been used to monitor MN frequency differ in their sensitivity to upon arsenic exposure. A systematic literature review was conducted followed by a meta-analysis. The review identified 25 useful studies with data from 3232 exposed individuals (15 studies assaying lymphocytes, 16 assaying buccal cells, and 9 assaying urothelial cells), with 18 studies measuring drinking water exposure, 5 measuring occupational exposure, one measuring coal burning, and one measuring dietary exposure. The meta-analysis indicated that the overall estimates of Mean Ratio (MR, defined as the mean value of the response in the exposed group divided by the mean value of the response in the reference group) were 2.95 (95% confidence interval (CI): 2.00 to 4.35), 2.36 (95% CI: 1.77 to 3.15), and 2.82 (95% CI: 1.86 to 4.28) for MN assays conducted with lymphocytes, buccal cells, and urothelial cells in the MN assay, respectively. Subgroup analysis showed that when the exposure method was drinking water, the MN frequencies increased significantly in lymphocytes (MR = 3.59, 95% CI: 2.30 to 5.60), in buccal cells (MR = 2.35, 95% CI: 1.76 to 3.15), and in urothelial cells (MR = 3.16, 95% CI: 2.02 to 4.97). However, when the exposure method was the occupational setting or others, the MN detection using the three types of cells did not find significant differences between groups. Subgroup analysis also showed that lymphocyte MN frequencies increased significantly in both routine-culture MN assays (MR = 2.88, 95% CI: 1.15 to 7.24) and cytokinesis-block MN assays (MR = 2.89, 95% CI: 1.84 to 4.55). The performance of the MN assay with different types of cells was also compared, but no significant differences were found. Therefore, our analysis indicates that MN can be used as an effective biomarker for monitoring arsenic-exposed populations, and that MN assays conducted with lymphocytes, buccal cells, and urothelial cells do not differ in their ability to detect the genetic damage from arsenic.

[Curative effect of progressively integrated sandplay therapy on core symptoms and sleep management in preschool children with mild-to-moderate autism spectrum disorder].

OBJECTIVE: To explore the curative effect of progressively integrated sandplay therapy on core symptoms and sleep management in preschool children with mild-to-moderate autism spectrum disorder (ASD). METHODS: A total of 50 mild-to-moderate ASD preschool children were randomly divided into an experimental group (n=25) and a control group (n=25). The control group was treated with structured teaching and auditory integration training (AIT). Based on these, the experimental group was treated with progressively integrated sandplay therapy. The Autism Behavior Checklist (ABC), Children Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), Children's Sleep Habit Questionnaire (CSHQ) and emotion recognition tools were used to evaluate the overall curative effect before treatment and 3 months after treatment. RESULTS: The experimental group had significantly lower scores of feeling, social interaction, somatic motor, language factor, total ABC and total CARS than the control group (P<0.05). The experimental group had also significantly lower scores of social cognition, social communication, social motivation, autistic behavior factor and total SRS than the control group (P<0.05). The experimental group had a significantly higher accurate rate of recognition of the upper facial expression and lower facial expression than the control group (P<0.05). The experimental group had significantly lower scores of bedtime resistance, sleep onset, sleep duration, night waking, daytime sleepiness, and total CSHQ than the control group (P<0.05). The experimental group had significantly reduced themes of wounding and significantly increased themes of healing after sandplay therapy (P<0.05). CONCLUSIONS: Progressively integrated sandplay therapy can effectively improve the core symptoms and sleep quality of preschool children with mild-to-moderate ASD, which can be used as an early rehabilitation measure.

[Clinical efficacy of interactive group sandplay versus individual sandplay in the treatment of preschool children with autism spectrum disorder].

OBJECTIVE: To study the clinical efficacy of interactive group sandplay versus individual sandplay in the treatment of preschool children with autism spectrum disorder (ASD). METHODS: A total of 80 ASD children, aged 4-6 years, were enrolled and randomly divided into experimental and control groups, with 40 children in each group. The children in the experimental group joined group sandplay with normal children at a ratio of 1: 3, and those in the control group were treated with individual sandplay. The Aberrant Behavior Checklist (ABC) and Autism Treatment Evaluation Checklist (ATEC) were used to evaluate the treatment outcome after three months of intervention. RESULTS: There were 33 children in the experimental group and 28 in the control group. After three months of intervention, the experimental group had significant reductions in the scores of irritability, social withdrawal, and stereotypic behavior and the total score of the ABC scale (P<0.05), and the control group had significant reductions in the scores of behavior and inappropriate speech and the total score of the ABC scale (P<0.05). Compared with the control group, the experimental group had significantly greater improvements in the score of social withdrawal and the total score of the ABC scale after three months of intervention (P<0.05). After three months of intervention, the experimental group had significant reductions in the scores of sociability, sensory and cognitive awareness, and physical/health behavior and the total score of the ATEC scale (P<0.05), and the control group had significant reductions in the scores of speech, sociability, and physical/health behavior and the total score of the ATEC scale (P<0.05). Compared with the control group, the experimental group had significantly greater improvements in the scores of speech, sociability, and sensory and cognitive awareness and the total score of the ATEC scale after intervention (P<0.01). Compared with the control group, the experimental group also had significantly greater improvements in eye contact and sand stereotyped arrangement (P<0.05). CONCLUSIONS: Both interactive group sandplay and individual sandplay are effective in the treatment of ASD in preschool children. Interactive group sandplay is better than individual sandplay in the treatment of ASD, with significant improvements in sociability, emotion and stereotypic behavior.