Blood transfusion is correlated with elevated adult all-cause mortality and cardiovascular mortality in the United States: NHANES 1999 to 2018 population-based matched propensity score study.

BACKGROUND AND AIMS: The association of blood transfusion with an increase in medium- and short-term mortality in specific populations has been confirmed. However, the correlation between blood transfusion and long-term mortality in the general population remains unclear. This cohort study evaluated the correlation between blood transfusion and overall and cause-specific mortality in the general American adult population. METHODS: The authors utilized 10 sets of 2-year cycle data (1999-2018) from the National Health and Nutrition Examination Survey on the outcomes of adults who did and did not receive blood transfusions. Propensity score-matching (1:1) was performed based on age, sex, race, education level, marital status, poverty-income ratio, arteriosclerotic cardiovascular disease, cancer, anemia, hypertension, and diabetes status. After controlling for demographic characteristics and clinical risk factors, Cox regression analysis was performed to evaluate the correlation between blood transfusion and all-cause and cause-specific mortality. RESULTS: The study included 48,004 adult participants. The risk of all-cause mortality increased by 101 % with blood transfusion, and the risk of cardiovascular mortality increased by 165 %. After propensity score-matching, 6,116 pairs of cases were retained, and the risk of all-cause mortality increased by 84 % with blood transfusion, and the risk of cardiovascular mortality increased by 137 %. The sensitivity analysis results were robust. CONCLUSIONS: In the general American population, blood transfusion significantly impacts long-term all-cause and cardiovascular mortality and may be an unacknowledged risk factor for death. Thus, the effective management of blood transfusion in the general population may be beneficial.

Preventive effect of Cleome spinosa against cucumber Fusarium wilt and improvement on cucumber growth and physiology.

Cucumber wilt is an important soil borne disease in cucumber production, which seriously affects the development of the cucumber industry. Cleome spinosa also has pharmacological effects such as antibacterial, analgesic, anti-inflammatory, and insect repellent. To study the control effect and mechanism of Cleome spinosa fumigation on cucumber wilt disease, different concentrations of Cleome spinosa fragments were applied on cucumber plants infected with Fusarium oxysporum. Cleome spinosa fumigation significantly reduced the incidence rate of cucumber Fusarium wilt. Under the fumigation treatment of 7.5 g kg-1 Cleome spinosa fragments, the preventive effects were 74.7%. Cleome spinosa fragments fumigation can promote cucumber growth and synthesis of photosynthetic pigments, thereby improving individual plant yield and fruit quality. At 7.5 g kg-1 Cleome spinosa fragments fumigation treatment, the plant height and individual plant yield of cucumber increased by 20.3% and 34.3%, respectively. Cleome spinosa fumigation can enhance the activity of antioxidant enzymes in cucumber, maintain a balance of reactive oxygen species metabolism, and enhance the plant disease resistance. Moreover, Cleome spinosa can also regulate the activities of Mg2+-ATPase and Ca2+-ATPase, enhancing its resistance to Fusarium oxysporum. Moreover, number of bacteria and fungi significantly decreased under Cleome spinosa fumigation. Those results suggested that Cleome spinosa could effectively restrain cucumber Fusarium wilt. This study will provide a new idea for the further use of biological fumigation to prevent soil-borne diseases.

Whole-exome sequencing of pathogenic genes in a family with congenital heart disease: A case report.

RATIONALE: Congenital heart disease (CHD) is the most common birth defect and an important cause of noninfectious deaths in infants and children. It has high prevalence globally, placing an enormous burden on society and families. Studies of individuals with hereditary or sporadic CHD have provided strong evidence for its genetic basis. The aim of this study was to identify causative gene variants in a Chinese family with congenital heart disease. PATIENT CONCERNS AND DIAGNOSES: Three generations of a CHD family were recruited. Proband III.9 was diagnosed with congenital heart disease at age 11 months, and the echocardiogram showed arterial ductus arteriosus, with a left-to-right shunt at the level of the arteries. Precedent III.10 was a twin of Proband III.9 who was diagnosed with congenital heart disease at age 11 months, in whom the echocardiogram revealed an arterial ductus arteriosus, an unenclosed patent ductus arteriosus, and a left to right shunt at the level of the arteries (second figure). III.8 was diagnosed with congenital heart disease at age 15, but echocardiography in this study showed no abnormalities. No cardiac abnormalities were detected in any of his parents, grandparents, or maternal grandparents. We performed whole-exome sequencing on CHD sufferers and their unexpressing family members to investigate the genetic causes of CHD in this family line. Exome sequencing identified 4 mutation sites in this family line. The variant c.3245A>G (p.His1082Arg) of the AMER1 gene was consistent with concomitant X-chromosome recessive inheritance, the variant c.238G>C (p.Val80Leu) of the KCNE1 gene was consistent with autosomal accessory inheritance, and the other 2 variants did not conform to the law of the mode of inheritance of the disease. OUTCOMES: The first identified variant, c.3245A>G (p.His1082Arg) of the AMER1 gene, with X-chromosome recessive inheritance, and the variant c.238G>C (p.Val80Leu) of the KCNE1 gene, which has been reported as autosomal dominant, may be the causative agent of CHD in this family line. These findings broaden the genetic scope of congenital heart disease and could help in the development of targeted drugs for the treatment of congenital heart disease.

[Efficacy of bronchoalveolar lavage combined with prone positioning in children with Mycoplasma pneumoniae pneumonia and atelectasis: a prospective randomized controlled study]. / æ”¯æ°”ç®¡è‚ºæ³¡çŒæ´—è”åˆä¿¯å§ä½æ²»ç–—å„¿ç«¥è‚ºç‚Žæ”¯åŽŸä½“è‚ºç‚Žä¼´è‚ºä¸å¼ ç–—æ•ˆçš„å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To study the efficacy of bronchoalveolar lavage (BAL) combined with prone positioning in children with Mycoplasma pneumoniae pneumonia (MPP) and atelectasis and its effect on pulmonary function. METHODS: A prospective study was conducted on 94 children with MPP and atelectasis who were hospitalized in Ordos Central Hospital of Inner Mongolia from November 2020 to May 2023. The children were randomly divided into a treatment group and a control group, with 47 children in each group. The children in the treatment group were given conventional treatment, BAL, and prone positioning, and those in the control group were given conventional treatment and BAL. The two groups were compared in terms of fever, pulmonary signs, length of hospital stay, lung recruitment, and improvement in pulmonary function. RESULTS: Compared with the control group, the treatment group had significantly shorter time to improvement in pulmonary signs and length of hospital stay and a significantly higher rate of lung recruitment on day 7 of hospitalization, on the day of discharge, and at 1 week after discharge (P<0.05). Compared with the control group, the treatment group had significantly higher levels of forced vital capacity (FVC) as a percentage of the predicted value, forced expiratory volume (FEV) in 1 second as a percentage of the predicted value, ratio of FEV in 1 second to FVC, forced expiratory flow at 50% of FVC as a percentage of the predicted value, forced expiratory flow at 75% of FVC as a percentage of the predicted value, and maximal mid-expiratory flow as a percentage of the predicted value on the day of discharge and at 1 week after discharge (P<0.05). There was no significant difference in the time for body temperature to return to normal between the two groups (P>0.05). CONCLUSIONS: In the treatment of children with MPP and atelectasis, BAL combined with prone positioning can help to shorten the time to improvement in pulmonary signs and the length of hospital stay and promote lung recruitment and improvement in pulmonary function.

Vonoprazan and amoxicillin dual therapy as the first-line treatment of Helicobacter pylori infection: A systematic review and meta-analysis.

BACKGROUND: Recent clinical trials have evaluated the efficacy of vonoprazan-amoxicillin (VA) dual therapy as the first-line treatment for Helicobacter pylori infection in different regions with inconsistent results reported. In this systematic review and meta-analysis, we aimed to evaluate the efficacy of VA dual therapy compared to the currently recommended therapy for eradicating H. pylori. MATERIALS AND METHODS: A comprehensive search of the PubMed, Cochrane, and Embase databases was performed using the following search terms: ("Helicobacter" OR "H. pylori" OR "Hp") AND ("vonoprazan" OR "potassium-competitive acid blocker" OR "P-CAB") AND ("amoxicillin" OR "penicillin") AND ("dual"). The primary outcome was to evaluate the eradication rate according to intention-to-treat and per-protocol analysis. The secondary outcomes were adverse events and compliance. RESULTS: A total of 15 studies involving 4, 568 patients were included. The pooled eradication rate of VA dual therapy was 85.0% and 90.0% by intention-to-treat and per-protocol analysis, respectively. The adverse events rate and compliance of VA dual therapy were 17.5% and 96%, respectively. The efficacy of VA dual therapy was superior to proton pump inhibitors-based triple therapy (82.0% vs. 71.4%, p < 0.01) but lower than vonoprazan-containing quadruple therapy (83.1% vs. 93.3%, p = 0.02). 7-day VA dual therapy showed lower eradication rates than 10-day (χ2 = 24.09, p < 0.01) and 14-day VA dual therapy (χ2 = 11.87, p < 0.01). The adverse events rate of VA dual therapy was lower than vonoprazan triple therapy (24.6% vs. 30.9%, p = 0.01) and bismuth-containing quadruple therapy (20.5% vs. 47.9%, p < 0.01). No significant difference of compliance was observed between VA dual therapy and each subgroup. CONCLUSION: VA dual therapy, a novel regimen, showed high efficacy as the first-line treatment for H. pylori eradication, which should be optimized before application in different regions.

Physiological mechanism beneath the inhibition of Cleome spinosa against the morphology and reproduction of Fusarium oxysporum.

Fusarium oxysporum is a soil-borne plant pathogen that can cause various plant diseases including cucumber wilt. An experiment was conducted to explore the physiological mechanism underlying the inhibitory activity of Cleome spinosa against the morphology and reproduction of F. oxysporum. Different concentrations of C. spinosa extracts. -0 (Z0), 5 (Z5), 15 (Z15), 30 (Z30), 45 (Z45), and 60 (Z60) mg·mL-1 were applied to F. oxysporum. Cleome spinosa extract significantly reduced the colony diameter (89.7 %) and dry mass (78.9 %) of F. oxysporum under the Z45 treatment. Moreover, spore formation was also significantly inhibited by C. spinosa extract. The spore number and germination rate decreased by 73.5 % and 83.0 %, respectively, under the Z45 treatment. The number of mycelia in the unit field of view was significantly reduced, and the mycelia were wizened with rough surfaces and more bends under the Z45 treatment. Hence, C. spinosa extracts severely damaged the morphology of F. oxysporum mycelia. Additionally, F. oxysporum could not adjust to the osmotic changes caused by C. spinosa extract, leading to membrane injury and electrolyte leakage. Finally, they impaired the antioxidant system in F. oxysporum, resulting in cell membrane injury.

Association of serum uric acid with risk of stroke in US adults: A cross-sectional study from NHANES 1999-2020.

BACKGROUND AND AIMS: The validity of high uric acid levels as an independent cause of stroke remains controversial, and the association between its low concentration and stroke is unclear. This study determines how different serum uric acid (SUA) levels are associated with stroke risk. METHODS: This cross-sectional study used continuous National Health and Nutrition Examination Survey data in the United States during 1999-2020. The SUA levels of 6.0, 6.8, and 9.0 mg/dL were all considered as cut-off points. Restricted cubic spline interpolation and logistic regression models were used to evaluate the different associations. Subgroup analyses and sensitivity analyses were conducted to evaluate the influence of multiple factors on the outcomes. RESULTS: The study included 23,413 participants aged ≥ 20 years. A J-shaped curve existed between SUA and stroke risk, and the risk of stroke was positively correlated with SUA levels in the overall population. Subgroup analysis of all adults in the SUA 6.8-9.0 mg/dL group showed that stroke risk for non-Hispanic white, obese, ex-smoker, and heavy drinking groups was increased, but for the other Hispanic group was reduced. In the SUA < 6.0 mg/dL group, stroke risk for ex-smoker, heavy drinkers, and no chronic kidney disease groups was increased. CONCLUSION: Our findings indicate a J-shaped relationship between SUA levels and stroke risk. Low and high SUA levels increased stroke risk for different populations, except in the other Hispanic population. Early SUA management is highly significant for stroke prevention in high-risk populations.

Iodine values, peroxide values and acid values of Bohai algae oil compared with other oils during the cooking.

Objective: Bohai algae oil contains polyunsaturated fatty acids, such as EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), which are the very important polyunsaturated fatty acids for the human body. In Traditional Chinese Cooking, all cooking methods cannot do without oils. However, the heat of cooking may always lead to formation of large amounts of decomposition products that affect the sensory, nutritional and functional quality of the oils to be unhealthy and the products being cooked, especially the food or edible oil rich in polyunsaturated fatty acids. Therefore, the objective of this study was to research the effect and change of heating on the quality characteristics of Bohai algae oil comparison with soybean oil and olive oil. Method: Quality characteristics such as the iodine values (IVs), peroxide values (POVs) and acid values (AVs) of Bohai algae oil, soybean oil and olive oil were measured, cooking conditions as factors of the study. Result: The POVs percentage changes of Bohai algae oil were larger than the IVs and AVs percentage changes. Bohai algae oil was better heated in a microwave oven at microwave P-20 within 3min, microwave P-60 and P-H1 within 2min, or in induction cooker at 1500w within 1min, or on electric stove (direct heated) within 2min. Conclusion: Bohai algae oil was suitable used for low-temperature and short-time cooking or for salad. This study has important significance for promoting the commercial value and extensive application of Bohai algae oil in daily cooking. It plays a theoretical significance role in Bohai algae oil's better processing and traditional chinese cooking. It can improve product quality to further expand the food processing research scope of Bohai algae oil and increase the richness, diversity and universality of edible methods of Bohai algae oil.

High TXNIP expression accelerates the migration and invasion of the GDM placenta trophoblast.

INTRODUCTION: Our previous study has proofed the glucose sensitive gene-thioredoxin-interacting protein (TXNIP) expression was up in the placenta of the patients with gestational diabetes mellitus (GDM), but the pathological mechanisms underlying abnormal TXNIP expression in the placenta of patients with GDM is completely unclear and additional investigations are required to explain the findings we have observed. In the present study, we simulated the high TXNIP expression via introducing the Tet-On "switch" in vitro, approximate to its expression level in the real world, to explore the following consequence of the abnormal TXNIP. METHODS: The expression and localization of TXNIP in the placenta of GDM patients and the health control was investigated via immunofluorescent staining, western blot and RT-qPCR. Overexpression of TXNIP was achieved through transfecting Tet-on system to the human trophoblastic cell line-HTR-8/Svneo cell. TXNIP knockout was obtained via CRISPR-Cas9 method. The cell phenotype was observed via IncuCyte Imaging System and flow cytometry. The mechanism was explored via western blot and RT-qPCR. RESULTS: The expression level of TXNIP in the GDM placenta was nearly 2-3 times higher than that in the control. The TXNIP located at trophoblastic cells of the placenta. When the expression of TXNIP was upregulated, the migration and invasion of the cells accelerated, but cell apoptosis and proliferation did not changed compared with the control group. Furthermore, the size of the TetTXNIP cells became larger, and the expression level of Vimentin and p-STAT3 increased in the TetTXNIP cells. All the changes mentioned above were opposite in the TXNIP-KO cells. CONCLUSIONS: Abnormal expression of TXNIP might be related to the impairment of the GDM placental function, affecting the migration and invasion of the placental trophoblast cells through STAT3 and Vimentin related pathway; thus, TXNIP might be the potential therapeutic target for repairing the placental dysfunction deficient in GDM patients.

Prevalence, awareness, treatment, and control of hypertension and their risk factors in Shaanxi Province in 2004-18.

To investigate trends in the prevalence, awareness, treatment and control of hypertension and their demographic determinants in Shaanxi Province. Six successive cross-sectional surveys on non-communicable chronic diseases and their risk factors were conducted between 2004 and 2018 in Shaanxi. Complex multistage stratified sampling was adopted to select participants. The information was collected through face-to-face interviews and on-site health examinations. Changes in hypertension prevalence and its management across survey years were estimated. Demographics associated with hypertension prevalence and its management was explored by multivariable logistic regression using pooled data from 2004 to 2018. The prevalence of hypertension increased from 16.71% in 2004 to 31.96% in 2018 with an estimated increase of 1.09% (95% CI 0.31-1.87) per year. However, the rate of awareness, treatment and control among these with hypertension was unexpectedly low and there were no significant change from 2004 to 2018. The corresponding changes were - 0.08% (95% CI - 0.85-0.69) per year for awareness, - 0.06% (95% CI - 1.11-1.00) per year for treatment, and - 0.23% (95% CI - 0.53-0.07) per year for control, respectively. Sensitivity analysis showed the same trend. Adults who were old, male, divorced/Widowed/Separated, retired were more likely to develop hypertension. Among these with hypertension, those who were more educated and retired were more likely to manage their hypertension compared with their counterparts. The overall hypertension prevalence from 2004 to 2018 increased rapidly, while awareness, treatment and control of hypertension remained unexpectedly low. This suggested urgent intervention should be implemented to improve hypertension control in Shaanxi Province.

A bibliometric analysis of research progress on pharmacovigilance and cancer from 2002 to 2021.

The complexity of cancer itself and treatment makes pharmacovigilance critical in oncology. Despite rapid progress on pharmacovigilance and cancer research in the past two decades, there has been no bibliometric analysis in this field. Therefore, based on the Web of Science database, we used CiteSpace, VOS-viewer and R-bibliometrix to analyze and visualize publications, and described the development trend and research hot spots in this field. 502 publications were included. The development of pharmacovigilance and cancer research has continued to grow. The USA has the largest number of publications and citations, followed by France and UK. Vanderbilt University and Sorbonne University are the institutions that contribute the most papers, and 5 of the top 10 high-yield institutions are from France. Salem JE and Lebrun-Vignes B of Sorbonne University have published the most papers, and they have a strong cooperative relationship. Salem JE has the highest H index. Drug Safety has the largest number of publications in the field of pharmacovigilance and cancer, with a high impact factor (IF). In recent years, immune checkpoint inhibitors (ICIs) have been identified as a hot topic and will continue to be maintained. This paper can help researchers get familiar with the current situation and trend of pharmacovigilance and cancer research, and provide valuable reference for the selection of future research directions.

Prevalence of Helicobacter pylori Virulence Genes and Their Association with Chronic Gastritis in Beijing, China.

Helicobacter pylori is closely related to chronic gastritis. The aim of the study was to investigate the correlation between H. pylori virulence genes and chronic gastritis in order to determine the pathogenic role of H. pylori virulence genes in chronic gastritis. Gastric mucosal tissues were obtained from 142 patients with chronic gastritis at three Beijing hospitals. The presence of virulence genes was determined by polymerase chain reaction (PCR) from H. pylori DNA. Multilocus sequence typing (MLST) and a phylogenetic tree were performed to characterize the overall genetic diversity. 91 new sequence types were identified by MLST in this study, and all strains showed high genetic diversity. The H. pylori isolates were divided into three types: hspEAsia strains (61 strains), hpEurope strains (15 strains), and mixed strains (16 strains). Some virulence genes were found to be significantly different between strains. The highest positive rates were found for dupA in chronic atrophic gastritis (AG), iceA1 in chronic non-atrophic gastritis with erosions, and iceA2 in chronic non-atrophic gastritis. The presence of dupA was found to be inversely related to the risk of AG. The H. pylori strains display high genetic diversity. Some virulence genes were found to be significantly different between diseases. The detection of various virulence genes is critical for screening high-risk populations for precancerous lesions and for the early prevention and control of gastric cancer.

Potential cardiotoxicity induced by Euodiae Fructus: In vivo and in vitro experiments and untargeted metabolomics research.

Background: Euodiae Fructus, a well-known herbal medicine, is widely used in Asia and has also gained in popularity in Western countries over the last decades. It has known side effects, which have been observed in clinical settings, but few studies have reported on its cardiotoxicity. Methods: In the present study, experiments using techniques of untargeted metabolomics clarify the hazardous effects of Euodiae Fructus on cardiac function and metabolism in rats in situations of overdosage and unsuitable syndrome differentiation. In vitro assays are conducted to observe the toxic effects of evodiamine and rutaecarpine, two main chemical constituents of Euodiae Fructus, in H9c2 and neonatal rat cardiomyocytes (NRCMs), with their signaling mechanisms analyzed accordingly. Results: The cardiac cytotoxicity of evodiamine and rutaecarpine in in vivo experiments is associated with remarkable alterations in lactate dehydrogenase, creatine kinase, and mitochondrial membrane potential; also with increased intensity of calcium fluorescence, decreased protein expression of the cGMP-PKG pathway in H9c2 cells, and frequency of spontaneous beat in NRCMs. Additionally, the results in rats with Yin deficiency receiving a high-dosage of Euodiae Fructus suggest obvious cardiac physiological dysfunction, abnormal electrocardiogram, pathological injuries, and decreased expression of PKG protein. At the level of endogenous metabolites, the cardiac side effects of overdose and irrational usage of Euodiae Fructus relate to 34 differential metabolites and 10 metabolic pathways involving among others, the purine metabolism, the glycerophospholipid metabolism, the glycerolipid metabolism, and the sphingolipid metabolism. Conclusion: These findings shed new light on the cardiotoxicity induced by Euodiae Fructus, which might be associated with overdose and unsuitable syndrome differentiation, that comes from modulating the cGMP-PKG pathway and disturbing the metabolic pathways of purine, lipid, and amino acid. Continuing research is needed to ensure pharmacovigilance for the safe administration of Chinese herbs in the future.

First Report of Enterobacter cloacae Causing Stem, Leaf and Fruit Rot on Tomato in China.

Tomato (Solanum lycopersicum L.), as one of the most economically important and highly nutritious vegetable crops across the world, is widely cultivated in China, one of the largest tomato-concuming countries in the world (Ye et al., 2020; Wang and Liu, 2021). At present, major bacterial diseases in tomato include bacterial speck disease, tomato bacterial wilt and bacterial canker, all of which affect the tomato production around the world (Rosli et al., 2021; Peritore-Galve et al., 2021; Wang et al., 2022). In April 2022, a new bacterial disease was discovered on leaves, stems and fruits of tomato in a farmer's greenhouse located in Longfeng District in DaQing (125°07`-125°15`E, 46°28`-46°32`N), Heilongjiang Province, China. This field had tomato disease incidences approximately 50%. Apparent brown discolorations were found on fruits, leaves and stems in tomato plants. Symptoms were similar to fungal brown spots caused by Phytophthora infestans of tomato (Zhi et al.,2021; Liu et al.,2021) (Supplementary Figure S1). To isolate and identify the pathogen, the tissues of infected fruits, leaves and stems with typical symptoms were excised from diseased plants separately, and were disinfected with 75% ethanol for 10 s followed by 2% NaClO for 3 min and then washed five to eight times with sterile water (Wang et al., 2017). Afterwards, the samples were plated on nutrient agar (NA) solid medium and incubated. After incubation at 30°C for 2-3 days, bacterial colonies were isolated, then purified on nutrient agar (NA) solid medium at least twice by a streak plate method (Dou et al., 2019; Li et al, 2021; Zhao et al., 2022). White colonies grew on the NA medium after incubating for 2 days, showing round, opaque and smooth, which was similar to characteristics described as Enterobacter cloacae (García-González et al., 2018; Li et al, 2021). To further confirm the speculation on the identity of the isolated bacterium, the fragments of 16S rRNA were amplified and sequenced. The sequence of 16S rRNA was uploaded into GeneBank with accession numbers (OP077195.1). BLAST analysis of the sequence showed 97.68% identity with one corresponding sequence of E. cloacae in GeneBank (namely MK937637.1). Furthermore, a phylogenetic tree based on the sequence of 16S rRNA gene revealed that the isolate was grouped in the same clade as E. cloacae (Supplementary Figure S2). Based on Koch postulates to test pathogenicity of isolated bacteria, bacteria were inoculated on 30 day-old healthy tomato plants with three leaves stages, and the re-isolation of bacteria were carried out after 2 days of inoculation. To confirm pathogenicity, the isolates were cultured on LB medium at 30℃ for 2 days to prepare suspensions and adjusted to an optical density (OD) of 0.2 at A600, with a final concentration of 1ⅹ108 CFU/ml. Eight potted tomato plants were sprayed with bacteria suspensions, and eight control potted plants were sprayed with sterile distilled water. These seedlings were incubated in a chamber at 30°C with a 12 h light/dark photoperiod, with 85% relative humidity. After 2 days, inoculated tomato seedlings showed irregular small spots in leaves and brown necrosis at blade tips, and 8 to 10 days later, the leaves of tomato plants browned and died. The symptoms were the same with those of the initial diseased leaves of tomato plants (Supplementary Figure S1). No symptoms were observed on the control leaves (Supplementary Figure S3). Pathogenicity tests were repeated three biological times with same results. Meanwhile, the bacteria strains were re-isolated from symptomatic inoculated seedlings and confirmed as E. cloacae by culture and sequence methods as above. In China, there are no detailed records about the causal agent of this disease on tomato in a published paper in Chinese and English. To our knowledge, this is the first report of Enterobacter leaf brown necrosis caused by E. cloacae on tomato in China. Those results are of great significance for the production and management of tomato in greenhouse and control of the disease.

Network Analysis of the Herb-Drug Interactions of Citrus Herbs Inspired by the "Grapefruit Juice Effect".

This study was performed to investigate the herb-drug interactions (HDIs) of citrus herbs (CHs), which was inspired by the "grapefruit (GF) juice effect". Based on network analysis, a total of 249 components in GF and 159 compounds in CHs exhibited great potential as active ingredients. Moreover, 360 GF-related genes, 422 CH-related genes, and 111 genes associated with drug transport and metabolism were collected, while 25 and 26 overlapping genes were identified. In compound-target networks, the degrees of naringenin, isopimpinellin, apigenin, sinensetin, and isoimperatorin were higher, and the results of protein-protein interaction indicated the hub role of UGT1A1 and CYP3A4. Conventional drugs such as erlotinib, nilotinib, tamoxifen, theophylline, venlafaxine, and verapamil were associated with GF and CHs via multiple drug transporters and drug-metabolizing enzymes. Remarkably, GF and CHs shared 48 potential active compounds, among which naringenin, tangeretin, nobiletin, and apigenin possessed more interactions with targets. Drug metabolism by cytochrome P450 stood out in the mutual mechanism of GF and CHs. Molecular docking was utilized to elevate the protein-ligand binding potential of naringenin, tangeretin, nobiletin, and apigenin with UGT1A1 and CYP3A4. Furthermore, in vitro experiments demonstrated their regulating effect. Overall, this approach provided predictions on the HDIs of CHs, and they were tentatively verified through molecular docking and cell tests. Moreover, there is a demand for clinical and experimental evidence to support the prediction.

Current Status and Trends of Research on Anthracycline-Induced Cardiotoxicity from 2002 to 2021: A Twenty-Year Bibliometric and Visualization Analysis.

Anthracyclines constitute the cornerstone of numerous chemotherapy regimens for various cancers. However, the clinical application of anthracyclines is significantly limited to their dose-dependent cardiotoxicity. A comprehensive understanding of the current status of anthracycline-induced cardiotoxicity is necessary for in-depth research and optimal clinical protocols. Bibliometric analysis is widely applied in depicting development trends and tracking frontiers of a specific field. The present study is aimed at revealing the status and trends of anthracycline-induced cardiotoxicity during the past two decades by employing bibliometric software including R-bibliometric, VOSviewer, and CiteSpace. A total of 3504 publications concerning anthracycline-induced cardiotoxicity from 2002 to 2021 were collected from the Web of Science Core Collection database. Results showed significant growth in annual yields from 90 records in 2002 to 304 papers in 2021. The United States was the most productive country with the strongest collaboration worldwide in the field. Charles University in the Czech Republic was the institution that contributed the most papers, while 7 of the top 10 productive institutions were from the United States. The United States Department of Health and Human Services and the National Institutes of Health are the two agencies that provide financial support for more than 50% of sponsored publications. The research categories of included publications mainly belong to Oncology and Cardiac Cardiovascular Systems. The Journal of Clinical Oncology had a comprehensive impact on this research field with the highest IF value and many publications. Simunek Tomas from Charles University contributed the most publications, while Lipshultz Steven E. from the State University of New York possessed the highest H-index. In addition, the future research frontiers of anthracycline-induced cardiotoxicity might include early detection, pharmacogenomics, molecular mechanism, and cardiooncology. The present bibliometric analysis may provide a valuable reference for researchers and practitioners in future research directions.

[Series of group standards of Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions].

Drug instructions,the statutory and technical documents recording effectiveness and safety information,are an important basis for guiding doctors,pharmacists,and patients to use drugs rationally,and their scientificity,standardization,and accuracy directly affect the medication safety of the public. The sections of adverse drug events,contraindications,precautions,warnings,and application for specific populations in drug instructions directly express safety information and measures for rational use of drugs. In the drug life cycle,marketing authorization holders( MAHs) need to update safety information in the instructions promptly to ensure the safety and effectiveness of clinical drug medication. At present,revising instructions is an important measure to control drug risks. In the drug life cycle,in order to standardize the revision of safety information in the instructions by MAHs and eliminate inexact terms such as " unclear",the Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions,a series of group standards,have been established under the guidance of Standardization Department,China Association of Chinese Medicine. Therefore,on the basis of the existing rules and regulations,the standardized technical procedures for revising instructions came into being to help clinical safe and rational medication of drugs,and implement the strategy of " Healthy China".

[Interpretation of Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions].

Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions,a series of group standards,were proposed by Professor ZHANG Bing from Research Center for Pharmacovigilance and Rational Use of Traditional Chinese Medicine,and underwent centralized management by Chinese Association of Chinese Medicine. They were officially released on July 23 and implemented on July 31,2021. The series of group standards consist of six sections,including general principles,adverse drug events,contraindications,precautions,application for special populations,and warnings. The section of general principles is comprised of holistic and programmatic expressions,which explain the general technical requirements for revising the marketed Chinese patent medicine instructions. The other five sections focus on information collection,screening,transformation,and illustration of specific items,forming a standardized revision technical process. This series of standards is the result of multiple rounds of research and the suggestions of more than 200 experts in different professional fields of " medicine-pharmacy-management-law-enterprise" have been gathered therein to reach a consensus. With the purposes of establishing standardized technical specifications for the revision of safety information in the marketed Chinese patent medicine instructions,guiding marketing authorization holders in revising the instructions,filling the gaps in the research of Chinese patent medicine instructions,promoting the deve-lopment of pharmaceutical care and academic research,and encouraging the rational and safe medication of Chinese patent medicine,the series of group standards is of great significance.

Integrative analysis of different low-light-tolerant cucumber lines in response to low-light stress.

Introduction: Low light stress inhibits plant growth due to a line of physiological disruptions in plants, and is one of the major barriers to protected cucumber cultivation in northern China. Methods: To comprehensively understand the responses of cucumber seedlings to low-light stress, the low-light-tolerant line (M67) and The low-light-sensitive line (M14) were conducted for the analysis of photosynthetic phenotype, RNA sequencing (RNA-seq) and the expression level of photosynthesis-related genes in leaves under low-light stress and normal light condition (control). Results: The results showed that there was a sharp decrease in the photosynthate accumulation in the leaves of the sensitive line, M14, resulting in a large decrease in the photosynthetic rate (Pn) (with 31.99%) of leaves compared to that of the control, which may have been caused by damage to chloroplast ultrastructure or a decrease in chlorophyll (Chl) content. However, under the same low-light treatment, there was no large drop in the photosynthate accumulation and even no decrease in Pn and Chl content for the tolerant line, M67. Moreover, results of gene expression analysis showed that the expression level of genes CsPsbQ (the photosystem II oxygen-evolving enhancer protein 3 gene) and Csgamma (ATPase, F1 complex gene) in the M14 leaves decreased sharply (by 35.04% and 30.58%, respectively) compared with the levels in the M67 leaves, which decreased by 14.78% and 23.61%, respectively. The expression levels of genes involved in Chl synthesis and carbohydrate biosynthesis in the leaves of M14 decreased markedly after low-light treatment; in contrast, there were no sharp decreases or changes in leaves of M67. Discussion: Over all, the ability of cucumber to respond to low-light stress, as determined on the basis of the degree of damage in leaf structure and chloroplast ultrastructure, which corresponded to decreased gene expression levels and ATP phosphorylase activity, significantly differed between different low-light-tolerant lines, which was manifested as significant differences in photosynthetic capacity between them. Results of this study will be a reference for comprehensive insight into the physiological mechanism involved in the low-light tolerance of cucumber.

CDK13-Mediated Cell Cycle Disorder Promotes Tumorigenesis of High HMGA2 Expression Gastric Cancer.

The inhibitor of CDK4/6 has been clinically used for treating certain types of cancer which are characterized by G0/G1 acceleration induced by the CDK4/6-RB1 pathway. On the contrary, the cell cycle-related molecules are abnormal in over 50% of the patients with gastric cancer (GC), but the efficiency of inhibiting CDK4/6 does not work well as it is expected. In our study, we found HMGA2 promotes GC through accelerating the S-G2/M phase transition, instead of G0/G1. We also found CDK13 is the direct target gene of HMGA2. Importantly, we analyzed 200 pairs of GC and the adjacent tissue and proved the positive relation between HMGA2 and CDK13; moreover, high expression of both genes predicts a poorer prognosis than the expression of single gene does. We explored the effect of the novel CDK12/13 inhibiting agent, SR-4835, on high HMGA2 expression GC and found inhibition of both genes jointly could reach a satisfied result. Therefore, we suggest that inhibition of CDK13 and HMGA2 simultaneously could be an effective strategy for high HMGA2 expression GC. To detect the expression of both genes simultaneously and individually could be of benefit to predict prognosis for GC.