[Newborn screening, clinical features and genetic analysis for Citrin deficiency in Henan province].

OBJECTIVE: To explore the prevalence, clinical features, genetic characteristics and prognosis of Citrin deficiency in Henan province of China. METHODS: A total of 986 565 neonates screened by tandem mass spectrometry at the Third Affiliated Hospital of Zhengzhou University from January 2013 to December 2021 were retrospectively analyzed. Analysis of SLC25A13 gene variants and parental verification were carried out for neonates suspected for Citrin deficiency by next-generation sequencing. The clinical, biochemical and genetic characteristics of Citrin deficiency patients were integrated to guide the diet treatment and follow up the growth and development. Paired-t test was used to compare the amino acid levels in the peripheral blood samples before and after the treatment. RESULTS: Nine cases of Citrin deficiency were diagnosed among the 986 565 neonates. Specific elevation of citrulline was observed in all of the 9 cases. Six variants were detected by genetic sequencing, among which c.852_855delTATG, c.615+5G>A, c.550C>T and IVS16ins3kb were known pathogenic variants, whilst c.1111_1112delAT and c.837T>A were unreported previously. The detection rate for c. 852_855delTATG was the highest (61.6%, 11/18), followed by IVS16ins3kb (16.7%, 3/18). The clinical symptoms of all patients were relieved after the treatment, and the blood amino acid profile and biochemical parameters were significantly improved by gradually falling within the normal range. By June 2022, all patients had shown a good prognosis. CONCLUSION: The prevalence of Citrin deficiency among neonates from Henan Province by tandem mass spectrometry is 1/109 618, and the carrier rate for the pathogenic variants of the SLC25A13 gene was 1/166. The c.852_855delTATG may be a hot spot variant among the patients. Discovery of the novel variants has enriched the mutational spectrum of the SLC25A13 gene. Above results have provided a basis for the early diagnosis, treatment, prognosis and genetic counseling for the affected families.

Mechanism insights into the pleiotropic effects of nobiletin as a potential therapeutic agent on non-alcoholic fatty liver disease (NAFLD).

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases and is emerging as one of the fastest-growing causes of liver-related deaths worldwide. It is necessary to find strategies to effectively prevent and treat NAFLD, as no definitive drug has been approved. Nobiletin (NOB) is the critical active ingredient of Chinese herbal medicines such as Citrus aurantium and Citri Reticulatae Pericarpium, which have anti-inflammatory, antioxidant, lipid regulating, and insulin resistance regulating effects. Numerous studies have demonstrated that NOB can prevent and treat the onset and progression of NAFLD. In this review, the mechanisms of NOB for treating NAFLD have been summarized, hoping to provide a basis for subsequent studies of NOB and to provide a research ground for the development of therapeutic drugs for NAFLD.

Genetic analysis of isolated methylmalonic acidemia in Henan, China: c.1663G>A variant of MMUT prevalent in the Henan population.

BACKGROUND: Methylmalonic acidemia (MMA) is the most common organic acidemia in China, and isolated MMA accounts for approximately 30 % of all types of MMA. Common variants of the MMUT gene vary greatly around the world. The present study aims to determine the high-frequency and novel genetic variants of the MMUT gene in the Henan population of China and evaluate the prognosis of patients carrying the c.1663G>A (p.Ala555Thr) variant. METHODS: We performed next-generation sequencing for 41 patients with isolated MMA screened by tandem mass spectrometry (MS/MS) and analysed the genetic results. We also evaluated the prognosis of patients with the c.1663G>A variant. We used Jalview software for multispecies sequence alignment and Missense3D and DynaMut to predict the protein function of the detected novel variants. RESULTS: A total of 43 variants from 41 patients with isolated MMA were detected, of which c.1663G>A (14.63 %), c.729_730insTT (10.98 %), and c.1106G>A (8.53 %) are high-frequency variants of the MMUT gene in the Henan population. The patients carrying the c.1663G>A variant tended to be responsive to vitamin B12, have a low mortality rate. We also identified 5 novel variants (c.479C>T, c.811G>C, c.965T>A, c.1142G>A and c.1667C>T). CONCLUSION: The rare variant c.1663G>A is prevalent in the Henan population, and infants with this variant tend to have good prognosis. Our findings, especially novel variants, will help broaden the spectrum of genetic variants and facilitate clinical diagnosis and genetic counselling for affected families.

Construction of Data-Driven Performance Digital Twin for a Real-World Gas Turbine Anomaly Detection Considering Uncertainty.

Anomaly detection and failure prediction of gas turbines is of great importance for ensuring reliable operation. This work presents a novel approach for anomaly detection based on a data-driven performance digital twin of gas turbine engines. The developed digital twin consists of two parts: uncertain performance digital twin (UPDT) and fault detection capability. UPDT is a probabilistic digital representation of the expected performance behavior of real-world gas turbine engines operating under various conditions. Fault detection capability is developed based on detecting UPDT outputs that have low probability under the training distribution. A novel anomaly measure based on the first Wasserstein distance is proposed to characterize the entire flight data, and a threshold can be applied to this measure to detect anomaly flights. The proposed UPDT with uncertainty quantification is trained with the sensor data from an individual physical reality and the outcome of the UPDT is intended to deliver the health assessment and fault detection results to support operation and maintenance decision-making. The proposed method is demonstrated on a real-world dataset from a typical type of commercial turbofan engine and the result shows that the F1 score reaches a maximum of 0.99 with a threshold of 0.45. The case study demonstrated that the proposed novel anomaly detection method can effectively identify the abnormal samples, and it is also possible to isolate anomalous behavior in a single performance signal, which is helpful for further fault diagnosis once an anomaly is detected.

Tensor Recovery Based on a Novel Non-Convex Function Minimax Logarithmic Concave Penalty Function.

Non-convex relaxation methods have been widely used in tensor recovery problems, compared with convex relaxation methods, and can achieve better recovery results. In this paper, a new non-convex function, Minimax Logarithmic Concave Penalty (MLCP) function, is proposed, and some of its intrinsic properties are analyzed, among which it is interesting to find that the Logarithmic function is an upper bound of the MLCP function. The proposed function is generalized to tensor cases, yielding tensor MLCP and weighted tensor Lγ -norm. Consider that its explicit solution cannot be obtained when applying it directly to the tensor recovery problem. Therefore, the corresponding equivalence theorems to solve the such problem are given, namely, tensor equivalent MLCP theorem and equivalent weighted tensor Lγ -norm theorem. In addition, we propose two EMLCP-based models for classic tensor recovery problems, namely low-rank tensor completion (LRTC) and tensor robust principal component analysis (TRPCA), and design proximal alternate linearization minimization (PALM) algorithms to solve them individually. Furthermore, based on the Kurdyka-Åasiwicz property, it is proved that the solution sequence of the proposed algorithm has a finite length and converges to the critical point globally. Finally, extensive experiments show that the proposed algorithm achieves good results, and it is confirmed that the MLCP function is indeed better than the Logarithmic function in the minimization problem, which is consistent with the analysis of theoretical properties.

Newborn screening and genomic analysis of duchenne muscular dystrophy in Henan, China.

BACKGROUND: Duchenne Muscular Dystrophy (DMD) is a rare disorder caused by mutations in the dystrophin gene. Recent availability in treatment for DMD raised the need of early screening in our center, but newborn screening (NBS) for DMD has not been carried out in Henan Province. OBJECTIVES: To determine an optimal cutoff value through the quantitative determination of the creatine kinase isoform MM (CK-MM) concentration dried blood spot (DBS) to identify male DMD, and to evaluate assess the detection rate and mutation spectrum of DMD in Henan, China. METHODS: The CK-MM level in DBS was measured using with a GSP® neonatal creatine kinase -MM kit from 13,110 male newborns to establish the cut-off value for CK-MM. Multiplex ligation-dependent probe amplification (MLPA) were carried out for infants with elevated CK levels to detect DMD gene deletions/ duplications, NGS and sanger sequencing were then applied to exclude MLPA-negative samples to single-nucleotide variants. Phenotype-genotype correlations were analyzed using REVEL For novel missense mutations. RESULTS: Statistical analysis of CK-MM value of the 13,110 neonates suggested that the cut-off value may be set as 472 ng/mL. 3 cases of DMD were screened among 13,110 newborns, all of whom had CK-MM levels >600 ng/mL. We detected 4 rare variants in DMD gene, including 2 exon deletions (deletion of exon 52 and deletion from exon 3 to exon 7) and 2 point variants (c.9568C>T and c.4030C>T). Two cases were all exon deletions, one case was compound heterozygous variants. CONCLUSIONS: The estimated incidence of male neonatal DMD was 1:4,370 in Henan province. NBS is of great value to the early intervention and treatment of the disease, and is fundamental to support public health decision-making. The experience from this study provided a model that will allow further expansion and facilitate establishment a universal public health screening in Henan hospital systems.

Effect of transcutaneous electrical acupoint stimulation on pregnancy outcomes in women with in vitro fertilization-embryo transfer: A systematic review and meta-analysis.

Objective: The purpose of this systematic review and meta-analysis was to evaluate the efficacy and safety of transcutaneous electrical acupoint stimulation (TEAS) on pregnancy outcomes in women undergoing in vitro fertilization-embryo transfer (IVF-ET), in order to provide evidence-based medical support. Methods: We searched the Cochrane Library, Embase, PubMed, Web of Science, SinoMed, and CNKI for relevant randomized controlled trials (RCTs) from inception to 31 May 2022, using the search terms "transcutaneous electrical acupoint stimulation," "TEAS," "in vitro fertilization-embryo transfer," "IVF-ET," "randomized controlled trial," and "clinical trials." The experimental group was treated with TEAS or combined with ovulation-inducing medication, and the control group was treated with mock TEAS (mTEAS), ovulation-inducing medication, or no intervention. The main outcome was the clinical pregnancy rate. Secondary outcomes were the embryo implantation rate, live birth rate, biochemical pregnancy rate, and number of oocytes retrieved. Stata15.1 software was used for data summary and analysis. Results: This review involved 15 RCTs and 4,281 participants. TEAS were superior to the control group for improving the clinical pregnancy rate [RR: 1.29, 95% CI: 1.19 to 1.40; p < 0.001; I2 = 23.0%], embryo implantation rate [RR: 1.43, 95% CI: 1.22 to 1.69; p < 0.001; I2 = 35.9%], live birth rate [RR: 1.33, 95% CI: 1.14 to 1.54; p < 0.001; I2 = 47.3%], and biochemical pregnancy rate [RR: 1.15, 95% CI: 1.05 to 1.26; p = 0.003; I2 = 49.1%], without significant heterogeneity. TEAS had no statistically significant effect on the number of oocytes retrieved as compared with the control group, and the heterogeneity was high [SMD: 0.34, 95% CI: -0.04 to 0.72; p = 0.081; I2 = 77.6%]. We performed subgroup analysis based on the sample size, interventions and intervention time-point. The results showed that the sample size had no effect on the results. There was no significant difference between TEAS and ovulation-inducing medication in the clinical pregnancy rate or the embryo implantation rate. In addition, TEAS did not significantly increase the embryo implantation rate or the live birth rate, compared with no intervention. In terms of safety, mild allergic symptoms were found in both the experimental group and the control group. Conclusion: In general, existing evidence supports the potential value of TEAS as an adjunctive treatment for improving pregnancy outcomes. High-quality, large-sample RCTs are needed to further support this conclusion. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=334892, identifier PROSPERO CRD42022334892.

Comparison of hospitalized patients with severe pneumonia caused by COVID-19 and influenza A (H7N9 and H1N1): A retrospective study from a designated hospital.

Considerable attention has been focused on the clinical features of coronavirus disease 2019 (COVID-19), but it is also important for clinicians to differentiate it from influenza virus infections. In the present study, the rate of coexisting disease was lower in the severe COVID-19 group than in the influenza A group (p = 0.003). Radiologically, severe COVID-19 patients had fewer instances of pleural effusion (p < 0.001). Clinically, severe COVID-19 patients had relatively better disease severity scores, less secondary bacterial infections, shorter times to beginning absorption on computed tomography, but longer durations of viral shedding from the time of admission (p < 0.05). Although the more severe influenza A patients required noninvasive respiratory support, these two groups ultimately yielded comparable mortalities. Based on the multiple logistic regression analysis, severe COVID-19 infection was associated with a lower risk of severe acute respiratory distress syndrome [odds ratio (OR) 1.016, 95% [confidence interval (CI)] 1.001-1.032, p = 0.041] and a better pneumonia severity index (OR 0.945, 95% [CI] 0.905-0.986, p = 0.009); however, these patients exhibited longer durations of viral shedding (OR 1.192, 95% [CI] 1.047-1.357, p = 0.008) than patients with severe influenza A infection. In conclusion, the conditions of severe influenza A patients appeared to be more critical than that of severe COVID-19 patients. However, relatively lower mortalities of these two severe cases are expected in the context of sufficient medical supplies.

Risk Factors and Impact on Outcomes of Lung Cancer Patients Concurrent with Deep Vein Thrombosis.

PURPOSE: Many investigations on prognostic factors in lung cancer have been conducted; however, little is known regarding the outcomes of lung cancer cases complicated by deep vein thrombosis (DVT). This study aimed to determine the risk factors and impact on outcomes of lung cancer patients concurrent with DVT. METHODS: Lung cancer patients who underwent lower-extremity venous ultrasound were enrolled in this study. The patients were divided into a DVT group and a non-DVT group. Demographic information, clinical characteristics, and survival were analyzed by t-test, Wilcoxon test, chi-squared test, and logistic regression analysis. RESULTS: Of the 160 enrolled lung cancer patients, DVT was detected in 30 patients. Among the DVT group, adenocarcinoma was the most common histological type (27/30, 90.00%). Lung cancer complicated with DVT was associated with advanced stage, more severe myocardial injury, and a hypercoagulable state (P < .05). Differences in driver genes between the two groups were not significant. Radiologically, lung cancer patients with DVT were more likely to present with pericardial effusion and pleural effusion than patients without DVT (P < .05). Following multivariable logistic regression analysis, advanced stage (OR 5.368, [95%CI 1.871-18.165], P = .021), NT-proBNP >300 pg/ml (OR 5.575, [95%CI 1.733-3.722], P = .018), D-dimer >5 mg/L (OR 8.449, [95%CI 4.323-18.536], P = .004), CRP >12 mg/L (OR 6.687, [95%CI 1.967-13.617], P = .010), and serum CEA >25 ng/ml (OR 4.755, [95%CI 1.358-3.123], P = .029) were independent risk factors for adenocarcinoma complicated with DVT. Finally, survival analysis revealed that the occurrence of DVT resulted in a poorer prognosis despite anticoagulant therapy (P < .05). CONCLUSION: DVT is a potential complication in patients with lung adenocarcinoma and could represent a prognostic marker for unfavorable outcome. It is essential to screen for DVT in high-risk adenocarcinoma patients.

Acupuncture combined with metformin versus metformin alone to improve pregnancy rate in polycystic ovary syndrome: A systematic review and meta-analysis.

Objective: The aim of this study was to evaluate the comparison between acupuncture combined with metformin versus metformin alone in improving the pregnancy rate of people with polycystic ovary syndrome (PCOS). Methods: A literature search of eight databases resulted in nine randomized controlled trials (RCTs) that assessed the effect of acupuncture combined with metformin on pregnancy rate in PCOS patients compared with metformin alone. Subsequently, data extraction and analysis were conducted to evaluate the quality and risk of bias of the methodological design of the study, and meta-analysis was conducted on the RCT data. Results: Nine RCTs and 1,159 women were included. Acupuncture can improve pregnancy rate. It was analyzed according to the diagnostic criteria of PCOS [Z = 2.72, p = 0.007, relative risk (RR) 1.31, 95% CI 1.08 to 1.60, p = 0.15, I 2 = 41%]. Analysis was performed according to different diagnostic criteria of pregnancy (Z = 3.22, p = 0.001, RR 1.35, 95% CI 1.13 to 1.63, p = 0.12, I 2 = 42%). Acupuncture can improve ovulation rate. Subgroup analysis was performed according to the number of ovulation patients (Z = 2.67, p = 0.008, RR 1.31, 95% CI 1.07 to 1.59, p = 0.04, I 2 = 63%) and ovulation cycle (Z = 3.57; p = 0.0004, RR 1.18, 95% CI 1.08 to 1.29, p = 0.57, I 2 = 0%). Statistical analysis also showed that acupuncture combined with metformin could improve homeostatic model assessment of insulin resistance (HOMA-IR) [mean difference (MD) -0.68, 95% CI -1.01 to -0.35, p = 0.003, I 2 = 83%]. Conclusions: Based on the results of this study, compared with metformin alone, acupuncture combined with metformin has a positive effect on pregnancy rate, ovulation rate, and insulin resistance in PCOS. However, due to the limitations regarding the number and quality of the included studies, the above conclusions need to be verified by further high-quality studies. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#myprospero.

Analysis of gene mutations of medium-chain acyl-coenzyme a dehydrogenase deficiency (MCADD) by next-generation sequencing in Henan, China.

BACKGROUND: Medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) is a rare inherited metabolic disorder of fatty acid ß-oxidation and one of the most common inborn errors of metabolism. The incidence of MCADD varies among regions and ethnic groups. To date, few cases of MCADD have been documented in China. OBJECTIVE: The present study aimed to find out the novel genetic pathogenic variants in the Chinese patients and evaluate the detection rate of the disease of high-frequency ACADM pathogenic variants in different regions of China. METHODS: 6 cases of MCADD were screened by tandem mass spectrometric (MS/MS) among 245 054 newborns. We performed next-generation sequencing on 6 families of infants with MCADD. We used the REVEL method to predict the protein function of the detected missense variants and used SPDBV 4.10 to predict the protein 3D structure model. We identified pathogenic variants of ACADM gene in 6 cases of MCADD, and then assessed these variants through Sanger sequencing and association analysis. RESULTS: The incidence of neonatal MCADD was 1/40,842 in Henan province. Among the 6 patients, five cases were compound heterozygous variants, one case was homozygous variants. DNA sequencing revealed 4 known (c.449_452del, c.1085G > A, c.1229 T > C, c.589A > G) and 3 novel mutations (c.849 + 5_849 + 8del, c.427A > G, c.1181C > T) in the ACADM gene. Mutation c.1085G > A (p.G362E) was most frequent among Henan people and shows obvious differences between North and South of China. CONCLUSION: MCADD is relatively rare in China, and c.1085G > A (p.G362E) is a common mutation in Henan population. Our findings, especially novel variants, will help improve the understanding of the genetic background and have facilitated clinical diagnosis and genetic counseling for the affected families.

Comparison of initial clinic characteristics of hospitalized patients in Suzhou City during the COVID-19 Omicron wave with ancestral variant wave.

BACKGROUND: Recently, the SARS-CoV-2 variant of concern, Omicron (B.1.1.529), was identified as responsible for a novel wave of COVID-19 worldwide. Here, we compared initial clinical features of hospitalized COVID-19 patients during recent wave (Omicron Variant) with those in ancestral variant wave (2020). METHODS: This is a cohort study of electronic health record (EHR) data from a signal center in the China. The clinical data of 116 cases of Omicron hospitalized in 2022 and 87 cases hospitalized in 2020 were collected. The comparisons were performed with the Mann-Whitney U test, Fisher exact test or the chi-square test, and multivariable logistic regression analysis. RESULTS: Clinically, compared with 2020-cohort, Omicron-cohort was more inclined to cluster in younger population and had more nonsymptomatic (25.0%) and nonsevere cases, as well as suffered from comparable extrapulmonary complication. Radiologically, although the major computed tomography (CT) findings of both cohorts were ground-glass opacities (GGOs), crazy-paving pattern was relatively less seen in the Omicron-cohort. Based on multiple logistic regression analysis, Omicron-cohort was associated with a lower risk of complaining with fever, the presence of lung opacity, and increased Sequential Organ Failure Assessment (SOFA) score. CONCLUSION: This study provided the data of different patterns of clinic characteristics and reduced severity from infections that occurred in Omicron variant as compared with the outbreak of the epidemic in 2020 wave (ancestral variant).

Intermediate risk pulmonary embolism concomitant with or without lung cancer: a wide spectrum of features.

OBJECTIVES: We aimed to investigate the differences in clinical features between pulmonary embolism (PE) patients concomitant with lung cancer and without lung cancer (LC) and gain further understanding of the impact of lung cancer on pulmonary embolism. METHODS: This retrospective study sampled 114 patients diagnosed with pulmonary embolism from January 2017 to April 2021 in the First Affiliated Hospital of Soochow University. The patients were categorized into the LC group (n = 22) or non-LC group (n = 92). Myocardial injury, coagulation and blood cell parameters, along with imaging findings, were analyzed for the two groups. The primary outcome measure was the 90-day mortality. RESULTS: Of the 114 patients with pulmonary embolism in the present study, the 90 intermediate-risk patients were enrolled for further investigations. Compared to the non-LC group, patients in the LC group had milder myocardial injury, more severe coagulation function disorder, a higher incidence of central PE and a smaller change in diameter of the main pulmonary artery. We found that the occurrence of pericardial effusion created the risk of lung cancer in patients with pulmonary embolism, but there was no increase in the 90-day mortality for non-LC group versus LC group. CONCLUSION: Intermediate risk PE patients concomitant with lung cancer seem to be more likely to present specific clinical features, accordingly, clinicians must pay great attention to PE patients concomitant with lung cancer and implement effective treatments to simultaneously manage the two conditions.

Dynamic Ensemble Bayesian Filter for Robust Control of a Human Brain-Machine Interface.

OBJECTIVE: Brain-machine interfaces (BMIs) aim to provide direct brain control of devices such as prostheses and computer cursors, which have demonstrated great potential for motor restoration. One major limitation of current BMIs lies in the unstable performance due to the variability of neural signals, especially in online control, which seriously hinders the clinical availability of BMIs. METHOD: We propose a dynamic ensemble Bayesian filter (DyEnsemble) to deal with the neural variability in online BMI control. Unlike most existing approaches using fixed models, DyEnsemble learns a pool of models that contains diverse abilities in describing the neural functions. In each time slot, it dynamically weights and assembles the models according to the neural signals in a Bayesian framework. In this way, DyEnsemble copes with variability in signals and improves the robustness of online control. RESULTS: Online BMI experiments with a human participant demonstrate that, compared with the velocity Kalman filter, DyEnsemble significantly improves the control accuracy (increases the success rate by 13.9% in the random target pursuit task) and robustness (performs more stably over different experiment days). CONCLUSION: Experimental results demonstrate the superiority of DyEnsemble in online BMI control. SIGNIFICANCE: DyEnsemble frames a novel and flexible dynamic decoding framework for robust BMIs, beneficial to various neural decoding applications.

Genomic analysis of 9 infants with hypermethioninemia by whole-exome sequencing among in Henan, China.

BACKGROUND: Hypermethioninemia is an inborn error of metabolism with elevated plasma methionine (Met) caused by methionine adenosyltransferase deficiency. Methionine adenosyltransferase (MAT) I/III deficiency is the most common cause of hypermethioninemia. Except for increased blood Met, most patients have no symptoms, but a small number have nervous system complications, including cognitive impairment and mental retardation. OBJECTIVE: To investigate the gene variation of patients with hypermethioninemia in newborns in Henan province. METHODS: 9 cases of hypermethioninemia were screened for amino acids profile and acyl carnitine by tandem mass spectrometric (MS/MS) among 245 054 newborns. We performed whole-exome sequencing on 9 families of infants with hypermethioninemia. We identified mutated genes under different models of inheritance and further assessed these mutations through Sanger sequencing and association analysis. RESULTS: The incidence of neonatal hypermethioninemia was 1:27 228 in Henan province. A total of ten mutations in the MAT1A gene in the 9 patients were identified, including nine reported mutations (c.1070C > T, c.895C > T, c.100 T > A, c.315C > A, c.529C > T, c.623A > C, c.407G > T, c.1066C > T, 867G > T) and one novel mutations (c.772G > C). c.772G > C was detected in 2 families and is the most common variant. 7 infants (7/9) with hypermethioninemia were genetically autosomal dominant, and 2 infants (2/9) with hypermethioninemia were genetically autosomal recessive. CONCLUSION: Our findings expand the mutational spectrum of hypermethioninemia, with the description of one new mutation. They improve the understanding of the genetic background and clinical manifestation of MAT1A in Chinese patients.

Acupuncture for Relieving Abdominal Pain and Distension in Acute Pancreatitis: A Systematic Review and Meta-Analysis.

Background: Clinical evidence suggests that acupuncture is effective for relieving abdominal pain and distension in acute pancreatitis (AP). However, there is a lack of systematic reviews and meta-analyses that provide high-quality evidence of the efficacy and safety of acupuncture in this context. Aim: To assess the efficacy and safety of acupuncture for relieving abdominal pain and distension in AP. Methods: We searched the PubMed, Web of Science, Embase, Cochrane Library, CNKI, Wanfang, VIP, and China Biomedical Literature databases. Randomized controlled trials of acupuncture plus routine treatment (RT) vs. RT alone or RT plus sham/placebo acupuncture were included. Primary outcomes included total effectiveness rate, VAS scores for abdominal pain and distension, and time until relief of abdominal pain and distension. Secondary outcomes included time until recovery of bowel sound, time until first defecation, length of hospital stay, and APACHE II score. Results: Nineteen eligible original studies (n = 1,503) were included. The results showed that acupuncture in combination with RT had a significant advantage in terms of increasing the total effectiveness rate [risk ratio: 1.15; 95% confidence interval (CI): 1.06-1.24; P = 0.001]. Acupuncture also reduced the VAS score for abdominal pain [weighted mean difference (WMD): -1.45; 95% CI: -1.71 to -1.19; P < 0.0001] and the VAS score for abdominal distension (WMD: -0.71; 95% CI: -1.04 to -0.37; P < 0.0001) in patients with AP. Other results also showed the efficacy of acupuncture. One study reported adverse events after acupuncture. Conclusion: Acupuncture in combination with RT has a better effect than RT alone for relieving abdominal pain and distension in AP. More rigorous studies are needed to confirm this result. Systematic Review Registration: PROSPERO CRD42019147503 (https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=147503).

The Phytochemical Rhein Mediates M6A-Independent Suppression of Adipocyte Differentiation.

Adipogenesis is mediated by the complex gene expression networks involving the posttranscriptional modifications. The natural compound rhein has been linked to the regulation of adipogenesis, but the underlying regulatory mechanisms remain elusive. Herein, we systematically analyzed the effects of rhein on adipogenesis at both the transcriptional and posttranscriptional levels. Rhein remarkably suppresses adipogenesis in the stage-specific and dose-dependent manners. Rhein has been identified to inhibit fat mass and obesity-associated (FTO) demethylase activity. Surprisingly, side-by-side comparison analysis revealed that the rhein treatment and Fto knockdown triggered the differential gene regulatory patterns, resulting in impaired adipocyte formation. Specifically, rhein treatment mildly altered the transcriptome with hundreds of genes dysregulated. N 6-methyladenosine (m6A) methylome profile showed that, although the supply of rhein induced increased m6A levels on a small subset of messenger RNAs (mRNAs), few of them showed dramatic transcriptional response to this compound. Moreover, the specific rhein-responsive mRNAs, which are linked to mitotic pathway, are barely methylated or contain m6A peaks without dramatic response to rhein, suggesting separate regulation of global m6A pattern and adipogenesis mediated by rhein. Further identification of m6A-independent pathways revealed a positive regulator, receptor expressing-enhancing protein 3 (REEP3), in guidance of adipogenesis. Hence, this study provides the mechanistic view of the cellular actions of rhein in the modulation of adipogenesis and identifies a potential novel target for obesity therapeutic research.

Factors associated with delayed viral shedding in COVID-19 infected patients: A retrospective small-scale study.

BACKGROUND: The outbreak of COVID-19 has caused ever-increasing attention and public panic all over the world. Until now, data are limited about the risk factors to virus shedding in COVID-19 infected patients. METHODS: In this retrospective study, data were collected from 87 patients hospitalized with COVID-19 infection in Suzhou. Using Cox proportional hazards regression and Kaplan-Meier survival analysis, the risk factors to COVID-19 RNA shedding was to be established according to demographic information, clinical characteristics, epidemiological history, antiviral medicine and corticosteroid administration. RESULTS: The median duration of COVID-19 RNA shedding from admission was 13.11 ± 0.76 days. There was no significant difference in viral shedding duration in terms of gender, age, history of Hubei province stay, characteristics of chest CT on admission, lymphocytopenia and clinical severity. By Cox proportional hazards model, excessive 200 mg cumulative corticosteroid (HR, 3.425 [95% CI, 1.339-7.143]), time from illness onset to hospitalization (<5 days) (HR, 2.503 [95% CI, 1.433-4.371]) and arbidol-included therapy (HR, 2.073 [95% CI, 1.185-3.626]) were the independent risk factors to delay COVID-19 RNA shedding. Besides of excessive 200 mg of cumulative corticosteroid (HR, 2.825 [95% CI, 1.201-6.649]), admission within 5 days from illness onset (HR, 2.493 [95% CI, 1.393-4.462]) and arbidol-included therapy (HR, 2.102 [95% CI, 1.073-4.120]), lymphocytopenia (HR, 2.153 [95% CI, 1.097-4.225]) was further identified as another unfavorable factor to 10-day viral shedding. CONCLUSIONS: The potential risk factors could help clinicians to identify patients with delayed viral shedding, thereby providing the rational strategy of treatment and optimal anti-viral interventions.

Safety and effectiveness of acupuncture for POSEIDON patients in IVF/ICSI: A protocol for systematic review and meta-analysis.

INTRODUCTION: The purpose of this paper is to evaluate the efficacy and safety of acupuncture for POSEIDON patients undergoing IVF/ICSI. METHODS: and analysis We will electronically search Pubmed, Medline, Embase, Web of Science, the Cochrane Central Register of Controlled Trial, China National Knowledge Infrastructure, China Biomedical Literature Database, China Science Journal Database and Wan-fang Database from their inception. Also, we will manually retrieve other resources, including reference lists of identified publications, conference articles, and grey literature. The clinical randomized controlled trials or quasi randomized controlled trials related to acupuncture treatment for POSEIDON patients in IVF/ICSI will be included in the study. The language is limited to Chinese and English. Research selection, data extraction, and research quality assessment will be independently completed by two researchers. Data were synthesized by using a fixed effect model or random effect model depend on the heterogeneity test. The clinical pregnancy rate (CPR) and live birth rate (LBR) will be the primary outcomes. The ongoing pregnancy, miscarriage rate (MR) and adverse events will also be assessed as secondary outcomes. RevMan V.5.3 statistical software will be used for meta-analysis, and the level of evidence will be assessed by Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Continuous data will be expressed in the form of weighted mean difference or standardized mean difference with 95% confidence intervals (CIs), while dichotomous data will be expressed in the form of relative risk with 95% CIs. ETHICS AND DISSEMINATION: The protocol of this systematic review (SR) does not require ethical approval because it does not involve humans. We will publish this article in peer-reviewed journals and presented at relevant conferences. SYSTEMATIC REVIEW REGISTRATION: OSF Registries, DOI: 10.17605/OSF.IO/6WP2F (https://osf.io/6wp2f).