Evaluating the effectiveness and safety of acupuncture on serum uric acid in asymptomatic hyperuricemia population: a randomized controlled clinical trial study protocol.

Background: The clinical dangers of asymptomatic hyperuricemia to human health have become increasingly prominent over the past 20 years. Previous studies have shown the potential benefits of acupuncture on uric acid levels in the body. However, definitive evidence is lacking. Our objective is to evaluate the efficacy and safety of acupuncture on serum uric acid (SUA) in individuals with asymptomatic hyperuricemia. Methods: This is a randomized, single-blind, sham-controlled trial. A total of 180 eligible patients with asymptomatic hyperuricemia will be recruited at three hospitals in China. Patients will be randomly assigned in a 1:1 ratio to receive 16 sessions of manual acupuncture or sham acupuncture for 8 weeks. Patients will be followed up for 12 weeks. The primary outcome will be the change in SUA levels at week 8 after randomization. Secondary outcomes will include dynamic changes in SUA levels, efficacy rates, proportion of gout flare, body weight, and acute medication intake. The MGH Acupuncture Sensation Scale and adverse events related to acupuncture will be measured after each treatment. A blinding assessment will be performed on patients who receive at least one session of acupuncture. Data analyses will be performed on a full analysis set and a per-protocol set. Ethics and dissemination: Ethics approval has been obtained from the Clinical Trial Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology (approval no. 2021-S135). Written informed consent will be obtained from enrolled patients. The findings will be disseminated in a peer-reviewed journal. Clinical trial registration: ClinicalTrials.gov identifier, NCT05406830.

Genomic characterization of three bacteriophages infecting donkey-derived Escherichia coli.

Bacteriophages are an important source of novel genetic diversity. Sequencing of phage genomes can reveal new proteins with potential uses in phage therapy and help unravel the diversity of biological mechanisms by which phages take over the machinery of the host during infection. To expand the available collection of phage genomes, we have isolated, sequenced, and assembled the genome sequences of three phages that infect three pathogenic Escherichia coli strains: vB_EcoM_DE15, vB_EcoM_DE16, and vB_EcoM_DE17. Morphological characterization and genomic analysis indicated that all three phages were strictly lytic and free from integrases, virulence factors, toxins, and antimicrobial resistance genes. All three phages contained tRNAs, and especially, vB_EcoM_DE17 contained 25 tRNAs. The genomic features of these phages indicate that natural phages are capable of lysing pathogenic E.coli and have great potential in the biocontrol of bacteria.

Meta-analysis of the prevalence of Giardia duodenalis in sheep and goats in China.

Giardia duodenum (G. duodenalis) can cause giardiasis and infect a variety of hosts. So far, there have been no detailed data regarding the positive rate of G. duodenalis in sheep and goats in China. Here, a systematic literature review was carried out to investigate the epidemiology of G. duodenalis in sheep and goats in China. To perform the meta-analysis, the databases CNKI, VIP, WanFang, PubMed, Web of science and ScienceDirect were employed for screening studies related to the prevalence of G. duodenalis in sheep and goats in China. The total prevalence of G. duodenalis in sheep and goats was estimated to be 7.00% (95% CI: 4.00-10.00). In the age subgroup, the prevalence of G. duodenalis in sheep and goats of >12 months (11.29%; 95% CI: 8.08-14.97) was higher than that in sheep and goats of ≤12 months (7.57%; 95% CI: 3.95-12.24). An analysis based on seasons showed that the prevalence of G. duodenalis in sheep and goats was higher in summer (11.90%; 95% CI: 0.50-35.05) than that in other seasons. The prevalence of G. duodenalis in sheep and goats after 2016 was 8.57% (95% CI: 5.34-11.79), which was higher than others. The highest prevalence of G. duodenalis in sheep and goats was 13.06% (95% CI: 6.26-19.86) recorded in Southwestern China. The prevalence of Giardia infection in sheep (7.28%; 95% CI: 2.30-14.73) was higher than that in goats (5.43%; 95% CI: 2.73-8.98). The NOAA's National Center for Environmental Information (https://gis.ncdc.noaa.gov/maps/ncei/cdo/monthly) was used to extract relevant geoclimatic data (latitude, longitude, elevation, temperature, precipitation, humidity, and climate). By analyzing the data of each subgroup, it was shown that region, genetype, and climate were potential risk factors for giardiasis prevalence in sheep and goats. Based on the analysis of common factors and geographical factors, it is recommended to strengthen effective management measures (e.g. ventilation and disinfection in warm and humid areas) and formulate relevant policies according to local conditions. Breeders should strengthen the detection of G. duodenalis in sheep and goats, customize corresponding control measures according to the diet and living habits of sheep and goats, and strengthen the protection of sheep and lamb calves, so as to reduce the incidence rate and reduce the economic loss of China's animal husbandry.

Prevalence of bovine coronavirus in cattle in China: A systematic review and meta-analysis.

Bovine coronavirus (BCoV) is one of the important pathogens that cause calf diarrhea (CD), winter dysentery (WD), and the bovine respiratory disease complex (BRDC), and spreads worldwide. An infection of BCoV in cattle can lead to death of young animals, stunted growth, reduced milk production, and milk quality, thus bringing serious economic losses to the bovine industry. Therefore, it is necessary to prevent and control the spread of BCoV. Here, a systematic review and meta-analysis was conducted to assess the prevalence of BCoV in cattle in China before 2022. A total of 57 articles regarding the prevalence of BCoV in cattle in China were collected from five databases (PubMed, ScienceDirect, CNKI, VIP, and Wan Fang). Based on the inclusion criteria, a total of 15,838 samples were included, and 6,136 were positive cases. The overall prevalence of BCoV was 30.8%, with the highest prevalence rate (60.5%) identified in South China and the lowest prevalence (15.6%) identified in Central China. We also analyzed other subgroup information, included sampling years, sample sources, detection methods, breeding methods, age, type of cattle, presence of diarrhea, and geographic and climatic factors. The results indicated that BCoV was widely prevalent in China. Among all subgroups, the sample sources, detection methods, breeding methods, and presence or absence of diarrheal might be potential risk factors responsible for BCoV prevalence. It is recommended to strengthen the detection of BCoV in cattle, in order to effectively control the spread of BCoV.

Prevalence and risk factors of stroke in China: a national serial cross-sectional study from 2003 to 2018.

Stroke imposes a substantial burden worldwide. With the rapid economic and lifestyle transition in China, trends of the prevalence of stroke across different geographic regions in China remain largely unknown. Capitalizing on the data in the National Health Services Surveys (NHSS), we assessed the prevalence and risk factors of stroke in China from 2003 to 2018. In this study, data from 2003, 2008, 2013, and 2018 NHSS were collected. Stroke cases were based on participants' self-report of a previous diagnosis by clinicians. We estimated the trends of stroke prevalence for the overall population and subgroups by age, sex, and socioeconomic factors, then compared across different geographic regions. We applied multivariable logistic regression to assess associations between stroke and risk factors. The number of participants aged 15 years or older were 154,077, 146,231, 230,067, and 212,318 in 2003, 2008, 2013, and 2018, respectively, among whom, 1435, 1996, 3781, and 6069 were stroke patients. The age and sex standardized prevalence per 100,000 individuals was 879 in 2003, 1100 in 2008, 1098 in 2013, and 1613 in 2018. Prevalence per 100,000 individuals in rural areas increased from 669 in 2003 to 1898 in 2018, while urban areas had a stable trend from 1261 in 2003 to 1365 in 2018. Across geographic regions, the central region consistently had the highest prevalence, but the western region has an alarmingly increasing trend from 623/100,000 in 2003 to 1898/100,000 in 2018 (P trend<0.001), surpassing the eastern region in 2013. Advanced age, male sex, rural area, central region, hypertension, diabetes, depression, low education and income level, retirement or unemployment, excessive physical activity, and unimproved sanitation facilities were significantly associated with stroke. In conclusion, the increasing prevalence of stroke in China was primarily driven by economically underdeveloped regions. It is important to develop targeted prevention programs in underdeveloped regions. Besides traditional risk factors, more attention should be paid to nontraditional risk factors to improve the prevention of stroke.

Characterization and complete genome analysis of a bacteriophage vB_EcoM_DE7 infecting donkey-derived Escherichia coli.

A lytic bacteriophage vB_EcoM_DE7 (hereafter designated DE7) that could infect donkey-derived Escherichia coli was isolated. The bacteriophage was examined by transmission electron microscopy, and the result showed that DE7 belonged to the family Myoviridae. The microbiological characterization revealed that DE7 was stable over a broad range of pHs (3 ∼10) at 40-50 °C. The latent period was 10 min, and the burst size was 43 PFUs/infected cell. The whole-genome sequencing showed that DE7 was a dsDNA virus and had a genome of 86,130 bp. The genome contained 124 predicted open reading frames (ORFs), 35 of which had known functions, including DNA replication and modification, transcriptional regulation, structural and packaging proteins, and host cell lysis. Twenty tRNA genes were identified, but no genes associated with bacterial pathogenicity, lysogeny and drug resistance were identified. BLASTN analysis revealed that phage DE7 had a high sequence identity (96%) with Salmonella phage vB_SPuM_SP116, but it could not lyse any Salmonella strain tested in this study. DE7 was classified as a Felix O1-like virus based on its general characterization and genomic information. Since phage DE7 exhibited high efficacy in lysing E. coli and lacked genes associated with bacterial virulence, antimicrobial resistance and lysogeny, it could be potentially used to control foal diarrhoea caused by E. coli.

Renal Interstitial Inflammation Predicts Nephropathy Progression in IgA Nephropathy: A Two-Center Cohort Study.

INTRODUCTION: Renal interstitial inflammation often presents in immunoglobulin A nephropathy (IgAN), but its predictive role in kidney disease progression remains controversial. METHODS: This retrospective two-center cohort study included 1,420 adult IgAN patients between January 2003 and May 2018 followed for a median of approximately 7 years at two Chinese hospitals. The predictor was renal interstitial inflammation within the total cortical interstitium (none/mild [0-25%], moderate [26-50%], or severe [>50%]). For the further propensity score matching analyses, the participants with moderate and severe level of interstitial inflammation were pooled to match those with none/mild level of interstitial inflammation. The outcomes included the rate of kidney function decline, and the composite kidney endpoint event defined as a >40% reduction in the estimated glomerular filtration rate, end-stage kidney disease. Linear regression and Cox proportional hazards regression analyses were used to examine the association between interstitial inflammation and the outcomes. The predictive performance of the model also assessed using multivariate logistic regression analyses with the receiver operating characteristic curve analysis. Reclassification was assessed using the continuous net reclassification improvement and integrated discrimination improvement adapted for censoring for the assessment of the model with or without interstitial inflammation. RESULTS: For the check of reproducibility, the kappa statistic was 0.71, and intraclass correlation coefficient was 0.77. After adjustment for relating covariates, a higher level of interstitial inflammation was associated with a faster rate of kidney function decline (eGFR slope [mL/min/1.73 m2] of 1.34 [95% CI: -2.56 to 5.23], 3.50 [95% CI: -0.40 to 7.40], and 7.52 [95% CI: 3.02 to 12.01]) in the patients with none/mild, moderate, and severe interstitial inflammation, respectively, in the multivariable linear regression models and with an increased risk of kidney disease progression (HR for moderate vs. none/mild, 1.85; 95% CI: 1.10-3.13; HR for severe vs. none/mild, 2.95; 95% CI: 1.52-5.73) in the multivariable Cox proportional hazards models. Analyses in the propensity score-matched cohort, subgroups, and the sensitive analyses yielded consistent results. The receiver operating curves indicated a higher area under the curve of 0.83 in the model with interstitial inflammation compared with 0.81 in that without interstitial inflammation. In addition, incorporating interstitial inflammation into the International IgAN Risk Prediction Tool improved the diagnostic power of the algorithm to predict risk of progression. CONCLUSION: Interstitial inflammation is a reproducible pathologic parameter that may be adopted as a predictor for kidney disease progression in patients with IgAN.

Efficacy and Prognosis of Hyperbaric Oxygen as Adjuvant Therapy for Neonatal Hypoxic-Ischemic Encephalopathy: A Meta-Analysis Study.

Background: Preclinical and clinical evidence suggests that hyperbaric oxygen therapy (HBOT) may benefit newborns. The effectiveness of HBOT for neonatal hypoxic-ischemic encephalopathy (HIE) remains controversial. We conducted a meta-analysis to evaluate the efficacy and prognosis of HBOT in neonates with HIE. Methods: A systematic search of eight databases was performed for available articles published between January 1, 2015, and September 30, 2020, to identify randomized controlled clinical trials (RCTs) on HBOT for neonatal HIE. Methodological quality assessment was performed by applying the simple procedure detailed by the Cochrane collaboration. Afterward, quality assessment and data analysis were performed using Revman 5.3 software. STATA 15 software was used to detect publication bias as well as for sensitivity analysis. Results: A total of 46 clinical RCTs were selected for the study and included 4,199 patients with neonatal HIE. The results indicated that HBOT significantly improved the total efficiency (TEF) of treatment for neonatal HIE patients [odds ratio (OR) = 4.61, 95% confidence interval (CI) (3.70, 5.75), P < 0.00001] and reduced the risk of sequelae (OR = 0.23, 95% CI (0.16, 0.33), P < 0.00001) and the neonatal behavioral neurological assessment (NBNA) scores [mean difference (MD) = 4.51, 95%CI (3.83,5.19, P < 0.00001)]. Conclusion: In light of the effectiveness of HBOT neonatal HIE, this meta-analysis suggested that HBOT can be a potential therapy for the treatment of neonatal HIE. Due to the heterogeneity of studies protocol and patient selection being only from China, more research is needed before this therapy can be widely implemented in the clinic. Protocol Registration: PROSPERO (ID: CRD42020210639). Available online at: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020210639.

Association Between Time to Endovascular Therapy and Outcomes in Patients With Acute Basilar Artery Occlusion.

OBJECTIVE: To characterize the association of onset to puncture time (OPT) with clinical outcomes among patients with acute basilar artery occlusion receiving endovascular therapy (EVT) in clinical practice. METHODS: Using the EVT for Acute Basilar Artery Occlusion (BASILAR) study, we identified consecutive patients with acute basilar artery occlusion receiving EVT in 47 comprehensive stroke centers in China from January 2014 to May 2019. The primary outcome was favorable functional outcome (defined as modified Rankin Scale score [mRS] 0-3) at 90 days. Secondary outcomes included function independence (mRS 0-2), mortality, and symptomatic intracerebral hemorrhage. The associations of OPT with clinical outcomes were analyzed using multivariable logistic regression (OPT as a categorical variable) and restricted cubic spline regression (OPT as a continuous variable). RESULTS: Among 639 eligible patients, the median age was 64 years, and median OPT was 328 minutes (interquartile range 220-490). Treatment within 4-8 hours and 8-12 hours was associated with lower rates of favorable outcome (adjusted odds ratio, 0.63 [95% confidence interval (CI), 0.40-0.98] and 0.47 [95% CI, 0.23-0.93], respectively) compared with treatment within 4 hours. Restricted cubic spline regression analysis showed that the OPT had L-shaped associations with favorable outcome (p nonlinearity = 0.028) and functional independence (p nonlinearity = 0.025), with significant benefit loss throughout the first 9 hours, but then appeared relatively flat. The odds of mortality increased relatively for OPT up to 9 hours, but then leveled off (p nonlinearity = 0.042). The association between symptomatic intracerebral hemorrhage and OPT was not significant. CONCLUSION: Among patients with acute basilar artery occlusion in routine practice, earlier treatment with EVT was associated with better outcomes throughout the first 9 hours after onset, but benefit may sustain unchanged afterwards. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with acute ischemic stroke due to basilar artery occlusion, earlier EVT is associated with better outcomes.

Long Noncoding RNA KCNMB2-AS1 Promotes SMAD5 by Targeting miR-3194-3p to Induce Bladder Cancer Progression.

PURPOSE: Bladder cancer is a common malignant tumor of the urinary system, with the fourth-highest incidence of male malignant tumors in Europe and the United States. So far, the mechanism of bladder cancer progression and metastasis has not been clarified. The aim of our study was to validate the way of long noncoding RNA (lncRNA) KCNMB2-AS1 on the metabolism and growth of bladder cancer cells by miR-3194-3p/SMAD5. PATIENTS AND METHODS: The Gene Expression was analyzed by qRT-PCR in bladder cancer tissues and cell lines, with the highly expressed KCNMB2-AS1 screened out. Cell proliferation was detected by Edu staining and clone formation assay, cell migration, and invasion by wound healing and transwell assays. Cell stemness was determined by assessing sphere-forming ability and stemness marker. Correlation between miRNA and lncRNA/gene was verified by dual-luciferase assay and RIP, and the effect of KCNMB2-AS1 on bladder cancer growth by nude mice tumor formation experiment. RESULTS: Here, we revealed the increased level of KCNMB2-AS1 in bladder cancer for the first time. Knockdown of KCNMB2-AS1 in vitro prevented the ability of proliferation, metastasis, and stemness of cancer cells. In vivo, the silencing of KCNMB2-AS1 also prevented tumor growth in vivo. Next, we revealed that KCNMB2-AS1 could interact with miR-3194-3p and uncovered that SAMD5 was a downstream target of miR-3194-3p. CONCLUSION: In conclusion, KCNMB2-AS1 mediated the bladder cancer cells progress by regulating the miR-3194-3p/SAMD5 signal pathway, which would provide a new target for bladder cancer research.

Saniculamin C, a new flavonoid from Sanicula lamelligera.

A new flavonoid named saniculamin C (1), together with six known compounds (2-7), were isolated from the whole plants of Sanicula lamelligera Hance. The chemical structures were elucidated by spectroscopic and physico-chemical analyses. All isolates were evaluated for in vitro cytotoxic activities against four human cancer cell lines, HepG2, SGC-7901 gastric cancer, Hela and A-549 lung cancer. Compound 1 showed potent antiproliferative activities against SGC-7901 cells with IC50 value of 7.45 µM. In addition, compound 6 exhibited weak antiproliferative activities against HepG2, SGC-7901, Hela cancer cells with IC50 values of 10.43, 8.24 and 15.32 µM, respectively.[Formula: see text].

Correlation analysis between disease severity and inflammation-related parameters in patients with COVID-19: a retrospective study.

BACKGROUND: COVID-19 is highly contagious, and the crude mortality rate could reach 49% in critical patients. Inflammation concerns on disease progression. This study analyzed blood inflammation indicators among mild, severe and critical patients, helping to identify severe or critical patients early. METHODS: In this cross-sectional study, 100 patients were included and divided into mild, severe or critical groups according to disease condition. Correlation of peripheral blood inflammation-related indicators with disease criticality was analyzed. Cut-off values for critically ill patients were speculated through the ROC curve. RESULTS: Significantly, disease severity was associated with age (R = -0.564, P < 0.001), interleukin-2 receptor (IL2R) (R = -0.534, P < 0.001), interleukin-6 (IL-6) (R = -0.535, P < 0.001), interleukin-8 (IL-8) (R = -0.308, P < 0.001), interleukin-10 (IL-10) (R = -0.422, P < 0.001), tumor necrosis factor α (TNFα) (R = -0.322, P < 0.001), C-reactive protein (CRP) (R = -0.604, P < 0.001), ferroprotein (R = -0.508, P < 0.001), procalcitonin (R = -0.650, P < 0.001), white cell counts (WBC) (R = -0.54, P < 0.001), lymphocyte counts (LC) (R = 0.56, P < 0.001), neutrophil count (NC) (R = -0.585, P < 0.001) and eosinophil counts (EC) (R = 0.299, P < 0.001). With IL2R > 793.5 U/mL or CRP > 30.7 ng/mL, the progress of COVID-19 to critical stage should be closely observed and possibly prevented. CONCLUSIONS: Inflammation is closely related to severity of COVID-19, and IL-6 and TNFα might be promising therapeutic targets.

Ginkgetin Alleviates Inflammation, Oxidative Stress, and Apoptosis Induced by Hypoxia/Reoxygenation in H9C2 Cells via Caspase-3 Dependent Pathway.

Ginkgetin, the extract of Ginkgo biloba leaves, has been reported to exert preventive and therapeutic effects on cardiovascular disease. However, little is known about its role in myocardial ischemia-reperfusion injury (MIRI). The present study aimed to unveil the function of ginkgetin in cardiomyocytes subjected to hypoxia/reoxygenation (H/R) injury. Cell Counting Kit-8 (CCK-8) was employed to evaluate the impact of ginkgetin on cell viability in the absence or presence of H/R. Proinflammatory cytokines and malondialdehyde (MDA), reactive oxygen species (SOD), and lactate dehydrogenase (LDH) were determined via corresponding kits. In addition, flow cytometry was performed to detect apoptotic level. Western blot analysis was utilized to estimate caspase-3 and cytochrome C. Ginkgetin had no significant effect on cell viability; however, it could enhance viability of H9C2 cells exposed to H/R. Inflammation and oxidative stress induced by H/R injury were relieved via pretreatment with ginkgetin. Preconditioning of ginkgetin also decreased apoptotic rate and the protein levels of caspase-3, cytochrome C under H/R condition. Furthermore, 2-HBA, an inducer of caspase-3, was used for the activation of caspase-3 signaling pathway. It was found that induction of caspase-3 eliminated the protective effect of ginkgetin on H9C2 cells exposed to H/R. These results indicated that ginkgetin attenuated inflammation, oxidative stress, and apoptosis. These protective roles of ginkgetin may attribute to caspase-3 dependent pathway.

Applying network analysis to investigate the links between dimensional schizotypy and cognitive and affective empathy.

BACKGROUND: Although impairment in empathy has been reported in schizophrenia spectrum disorders, little is known about the relationship between empathy and schizotypal traits. This study examines this relationship by applying network analysis to a large sample collected at 18-months follow-up in a longitudinal dataset. METHODS: One thousand four hundred and eighty-six college students were recruited and completed a set of self-reported questionnaires on empathy, schizotypy, depression, anxiety and stress. Networks were constructed by taking the subscale scores of these measures as nodes and partial correlations between each pair of nodes as edges. Network Comparison Tests were performed to investigate the differences between individuals with high and low schizotypy. RESULTS: Cognitive and affective empathy were strongly connected with negative schizotypy in the network. Physical and social anhedonia showed high centrality measured by strength, closeness and betweenness while anxiety and stress showed high expected influence. Predictability ranged from 22.4% (personal distress) to 79.9% (anxiety) with an average of 54.4%. Compared with the low schizotypy group, the high schizotypy group showed higher global strength (S = 0.813, p < 0.05) and significant differences in network structure (M = 0.531, p < 0.001) and strength of edges connecting empathy with schizotypy (adjusted ps < 0.05). LIMITATIONS: Only self-rating scales were used, and disorganized schizotypy was not included. CONCLUSIONS: Our findings suggest that the cognitive and affective components of empathy and dimensions of schizotypy are closely related in the general population and their network interactions may play an important role in individuals with high schizotypy.

The Association of Low Hemoglobin Levels with IgA Nephropathy Progression: A Two-Center Cohort Study of 1,828 Cases.

AIM: To investigate the relationship between hemoglobin levels and the progression of IgA nephropathy (IgAN). METHODS: In a two-center cohort of 1,828 cases with biopsy-proven IgAN, we examined the association of hemoglobin levels with the primary outcome of a composite of all-cause mortality or kidney failure defined as a 40% decline in eGFR, or ESKD (defined as eGFR <15 mL/min/1.73 m2 or need for kidney replacement therapy including hemodialysis, peritoneal dialysis, or kidney transplantation), or the outcome of kidney failure, assessed using Cox and logistic regression models, respectively, with adjustment for confounders. RESULTS: At baseline, mean age, eGFR, and hemoglobin levels were 33.75 ± 11.03 years, 99.70 ± 30.40 mL/min/1.73 m2, and 123.47 ± 18.36 g/L, respectively. During a median of approximately 7-year follow-up, 183 cases reached the composite outcome. After adjustment for demographic and IgAN-specific covariates and treatments, a lower quartile of hemoglobin was nonlinearly associated with an increased risk of the primary outcome or kidney failure in the Cox proportional hazards models (primary outcome: HR for quartile 3 vs. 4, 1.37; 95% CI, 0.83-2.25; HR for quartile 2 vs. 4, 1.18; 95% CI, 0.68-2.07; HR for quartile 1 vs. 4, 1.91; 95% CI, 1.15-3.17; kidney failure: HR for quartile 3 vs. 4, 1.39; 95% CI, 0.84-2.31; HR for quartile 2 vs. 4, 1.20; 95% CI, 0.68-2.11; HR for quartile 1 vs. 4, 1.83; 95% CI, 1.09-3.07) in the fully adjusted model. Then, hemoglobin levels were transformed to a binary variable for fitting the model according to the criteria for anemia of 110 g/L in the women and 120 g/L in men in China. The participants in the anemia group had an increased risk of developing outcomes compared with the nonanemia group in both genders (primary outcome: male: HR, 1.64; 95% CI, 1.01-2.68; female: HR, 1.68; 95% CI, 1.02-2.76; kidney failure: male: HR, 1.60; 95% CI, 0.97-2.64; female: HR, 1.58; 95% CI, 0.95-2.61) in the fully adjusted model. CONCLUSIONS: A low level of hemoglobin was nonlinearly associated with IgAN progression. The anemic IgAN patients presented a higher risk of developing poor outcomes compared with the nonanemic patients.

Digestive solubilization of Cd in highly-contaminated sediment by marine deposit feeders: The roles of intestinal surfactants in Cd mobilization and Re-Adsorption processes.

Marine deposit feeders are of ecological significance in transferring sedimentary Cd along aquatic food chains. A key process for this transfer is these organisms' dietary uptake of Cd via solubilization of Cd present in ingested contaminated sediment. To better understand the bioavailability of sedimentary Cd to deposit feeders, the present study used in vitro extraction experiments to explore the contribution of different digestive agents (proteins, amino acids and surfactants) to the solubilization of Cd from sediment collected in a highly-contaminated Chinese bay. This was done for various commercially-available mimetic digestive agents (the protein BSA, a mixture of amino acids, and the surfactants rhamnolipid and SDS), and for proteins and surfactants collected from the gut juice of a sipunculan worm. The Cd mobilization capacity of BSA was significantly higher than that of the amino acids and the commercial surfactants. In the presence of BSA, > 70% of the released Cd became associated with this protein. In contrast, the digestive proteins from the sipunculan had a lower Cd mobilization capacity than was the case for the other digestive agents and the majority of the released Cd (∼80%) was associated with small molecular weight fractions. The differences in Cd mobilization between the BSA and the digestive proteins were attributed to differences in their sediment-adsorption tendencies and their Cd-complexing capacities. While the digestive surfactants had minor effects on the release of sedimentary Cd, they significantly enhanced Cd mobilization by the digestive proteins when both were present simultaneously. Our results suggest that the characteristics of proteins should be considered when using commercially-available mimetic digestive agents to explore Cd bioavailability in sediments. Furthermore, digestive surfactants seem to have important effects on the solubilization of Cd during gut passage by reducing the adsorption of the digestive proteins to the sediments.

Metformin Treatment Was Associated with Decreased Mortality in COVID-19 Patients with Diabetes in a Retrospective Analysis.

Metformin was proposed to be a candidate for host-directed therapy for COVID-19. However, its efficacy remains to be validated. In this study, we compared the outcome of metformin users and nonusers in hospitalized COVID-19 patients with diabetes. Hospitalized diabetic patients with confirmed COVID-19 in the Tongji Hospital of Wuhan, China, from January 27, 2020 to March 24, 2020, were grouped into metformin and no-metformin groups according to the diabetic medications used. The demographics, characteristics, laboratory parameters, treatments, and clinical outcome in these patients were retrospectively assessed. A total of 283 patients (104 in the metformin and 179 in the no-metformin group) were included in this study. There were no significant differences between the two groups in gender, age, underlying diseases, clinical severity, and oxygen-support category at admission. The fasting blood glucose level of the metformin group was higher than that of the no-metformin group at admission and was under effective control in both groups after admission. Other laboratory parameters at admission and treatments after admission were not different between the two groups. The length of hospital stay did not differ between the two groups (21.0 days for metformin versus 19.5 days for no metformin, P = 0.74). However, in-hospital mortality was significantly lower in the metformin group (3/104 (2.9%) versus 22/179 (12.3%), P = 0.01). Antidiabetic treatment with metformin was associated with decreased mortality compared with diabetics not receiving metformin. This retrospective analysis suggests that metformin may offer benefits in patients with COVID-19 and that further study is indicated.

Salvia miltiorrhiza Restrains Reactive Oxygen Species-Associated Pulmonary Fibrosis via Targeting Nrf2-Nox4 Redox Balance.

Pulmonary fibrosis (PF) is characterized by myofibroblast activation, which can be triggered by oxidative stress. In this study, we investigated the antifibrotic effect of the ethyl acetate extract of Salvia miltiorrhiza (EASM) on PF and examined the underlying molecular mechanism. EASM suppressed myofibroblast activation with reduced extracellular matrix deposition in the lungs of mice subjected to bleomycin (BLM) challenge, demonstrating the inhibitory effects on PF. EASM positively alleviated oxidative stress by upregulating nuclear factor-erythroid 2-related factor 2 (Nrf2) and concomitantly downregulating NADPH oxidase 4 (Nox4) in the lungs of BLM-treated mice. This effect was also observed in an in vitro model of transforming growth factor beta 1 (TGF-ß1)-stimulated fibroblast activation. EASM reduced reactive oxygen species (ROS) generation in fibroblasts by stabilizing Nrf2 protein with promoting kelch-like ECH-associated protein 1 (Keap1) degradation. Nrf2 knockdown in the lungs of BLM-treated mice diminished the inhibitory effects of EASM on fibrosis, providing evidence in vivo to address the unique role of Nrf2. Additionally, EASM inhibited TGF-ß1/Smad3 signaling by downregulating protein kinase C delta (PKC-δ) and Smad3 phosphorylation (p-Smad3), which led to suppression of the TGF-ß1-induced fibrogenic response. These results indicate that EASM exhibits potent antifibrotic activity in vitro and in vivo, which might be associated with activation of Nrf2 pathway and inhibition of TGF-ß1/Smad3 pathway. Our findings support that EASM may act as an effective antifibrotic remedy for PF.

Toxicological effects benzotriazole to the marine scallop Chlamys nobilis: a 2-month exposure study.

Benzotriazole and its associated derivatives (BTs) are widely used as ultraviolet stabilizers and corrosion inhibitors. They have been extensively found in marine environments and are bioaccumulative through the food chain. However, the toxicities of BTs to marine organisms are seldom identified and no assessment has been conducted for filter-feeding bivalves. In this study, a marine scallop Chlamys nobilis was exposed to 0, 0.01, 0.1, and 1.0 mg/L of BT for 60 days. Effects of BT on endocrine system, cytochrome P450 activity, antioxidant activity, and neural activity of C. nobilis were examined. The results showed that BT exerted significant estrogenic effects on both male and female scallops and inhibited EROD activities of C. nobilis even at 0.01 mg/L level. BT at ≥ 0.01 mg/L levels also caused significant oxidative stress on C. nobilis. Moreover, most of the adverse effects of BT to C. nobilis were found from day 35 and 0.01 mg/L was the lowest concentration with observed effects, showing the long-term toxic effects of BT to C. nobilis. Thus, the adverse effects of BT and its derivatives to marine benthic communities deserve more attention in future research.