Chronic heart failure （CHF） is an end-stage cardiac syndrome driven by multiple factors. Its pathological process involves interactions of multiple pathways such as energy metabolism dysfunction， neuroendocrine dysregulation， and myocardial fibrosis. Although current clinical medicine can alleviate symptoms through single-target approaches， significant limitations in reversing cardiac remodeling and disease progression remain. Puerarin， a major bioactive isoflavone constituent derived from Pueraria lobata， exhibits multidimensional pharmacological effects， such as vasodilatory effects， regulation of neuroendocrine balance， enhancement of metabolic homeostasis， and suppression of myocardial apoptosis. This review systematically integrated puerarin's multi-target regulatory network， elucidating its mechanisms such as improving energy metabolism by AMP-activated protein kinase/mechanistic target of rapamycin （AMPK/mTOR） pathway， inhibiting fibrosis mediated by transforming growth factor-β （TGF-β）/Smad signals， and attenuating oxidative-inflammatory cascades by regulating nuclear factor erythroid 2 （E₂）-related factor 2/nuclear transcription factor-κB（Nrf2/NF-κB） axis. Clinical research data was used to validate its efficacy in improving the left ventricular ejection function and reducing the therapeutic potential of cardiovascular events' risks. The study proposed that puerarin's "systemic regulation" characteristic breaks through the limitations of traditional single-target drugs and prospected its clinical translation pathway based on metabolomics and nano-delivery technology， offering an integrative perspective from molecular mechanisms to precise therapy for the research on modernization of traditional Chinese medicine.

Chronic heart failure （CHF） is an end-stage cardiac syndrome driven by multiple factors. Its pathological process involves interactions of multiple pathways such as energy metabolism dysfunction， neuroendocrine dysregulation， and myocardial fibrosis. Although current clinical medicine can alleviate symptoms through single-target approaches， significant limitations in reversing cardiac remodeling and disease progression remain. Puerarin， a major bioactive isoflavone constituent derived from Pueraria lobata， exhibits multidimensional pharmacological effects， such as vasodilatory effects， regulation of neuroendocrine balance， enhancement of metabolic homeostasis， and suppression of myocardial apoptosis. This review systematically integrated puerarin's multi-target regulatory network， elucidating its mechanisms such as improving energy metabolism by AMP-activated protein kinase/mechanistic target of rapamycin （AMPK/mTOR） pathway， inhibiting fibrosis mediated by transforming growth factor-β （TGF-β）/Smad signals， and attenuating oxidative-inflammatory cascades by regulating nuclear factor erythroid 2 （E₂）-related factor 2/nuclear transcription factor-κB（Nrf2/NF-κB） axis. Clinical research data was used to validate its efficacy in improving the left ventricular ejection function and reducing the therapeutic potential of cardiovascular events' risks. The study proposed that puerarin's "systemic regulation" characteristic breaks through the limitations of traditional single-target drugs and prospected its clinical translation pathway based on metabolomics and nano-delivery technology， offering an integrative perspective from molecular mechanisms to precise therapy for the research on modernization of traditional Chinese medicine.

ObjectiveTo explore the mechanism of action of Wendantang on ApoE^-/- hyperlipidemic mice using non-targeted metabolomics technology. MethodsMale C57BL/6J mice served as the normal control group （n=6）， and they were fed with regular chow， while male ApoE^-/- mice constituted the high-fat group （n=30）， and they were fed with a 60% high-fat diet. After 11 weeks of model establishment， the mice in the high-fat group were randomly divided into the model group， simvastatin group （3.3 mg·kg^-1）， and high-dose， medium-dose， and low-dose groups of Wendantang （26， 13， 6.5 g·kg^-1， respectively， in terms of crude drug amount）， with six mice in each group. The normal control group and the model group were gavaged with an equivalent volume of normal saline， and all groups continued to be fed their respective diets， receiving daily medication for 10 weeks with weekly body weight measurements. Serum levels of total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， free fatty acids （NEFA）， blood glucose （GLU）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） were detected in the mice. Pathological changes in liver tissue were observed using hematoxylin-eosin （HE） staining， and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS/MS） was employed for metabolomic analysis of mouse liver tissue. ResultsCompared to the normal control group， the model group exhibited significantly increased body weight， blood lipid levels， and liver function （P<0.05， P<0.01）， with disordered liver tissue structure， swollen hepatocytes， and accompanying vacuolar fatty degeneration and inflammatory cell infiltration. Compared to the model group， the simvastatin group and Wendantang groups showed significantly reduced body weight， TG， NEFA， GLU， ALT， and AST levels （P<0.05， P<0.01）， with a significant increase in HDL-C levels （P<0.05， P<0.01）， demonstrating a dose-dependent effect. The lesion of the liver tissue section was obviously improved after administration， tending towards a normal liver tissue morphology. Analysis of liver metabolites revealed 86 differential metabolites between the normal control group and the model group， with the high-dose group of Wendantang able to regulate 56 of these metabolites. Twenty-two differential metabolites associated with hyperlipidemia were identified， mainly including chenodeoxycholic acid， hyocholic acid， taurine， glycocholic acid， dihydroceramide， hydroxy sphingomyelin C14∶1， arachidonic acid， and linoleic acid， enriching 22 metabolic pathways， with 4 being the most significant （P<0.05）， namely primary bile acid biosynthesis， sphingolipid metabolism， unsaturated fatty acid biosynthesis， and linoleic acid metabolism pathways. ConclusionWendantang can improve blood lipid levels and liver function in ApoE^-/- hyperlipidemic mice， which may be related to the regulation of primary bile acid biosynthesis， sphingolipid metabolism， unsaturated fatty acid biosynthesis， and linoleic acid metabolism pathways.

A 55-year-old male patient was treated with tacrolimus (2.5 mg in the morning and 2 mg at night) for 6 months after lung transplantation to prevent rejection. The blood trough concentration of tacrolimus was stable at 8.0-10.0 μg/L. The patient received antiviral treatment due to corona virus disease 2019 (nirmatrelvir/ritonavir 300 mg/100 mg twice daily orally for a total of 5 days). During the antiviral treatment, the patient continued the anti-rejection treatment. On the second day of antiviral treatment, the patient′s blood trough concentration of tacrolimus increased to >40.0 μg/L, which was considered to be caused by the interaction between nirmatrelvir/ritonavir and tacrolimus. Tacrolimus was withdrawn and antiviral therapy was continued. After discontinuation of tacrolimus for 8 days and nirmatrelvir/ritonavir for 3 days, the blood trough concentration of tacrolimus decreased to 25.7 μg/L. After re-giving tacrolimus at reducing dosage for 3 days, the blood trough concentration of tacrolimus was 8.3 μg/L. After 13 days of resuming administration of tacrolimus at the original dose and frequency, the patient′s blood trough concentration of tacrolimus was 9.2 μg/L. Since then, the blood trough concentration of tacrolimus in the patient was not abnormal again.

A 55-year-old male patient was treated with tacrolimus (2.5 mg in the morning and 2 mg at night) for 6 months after lung transplantation to prevent rejection. The blood trough concentration of tacrolimus was stable at 8.0-10.0 μg/L. The patient received antiviral treatment due to corona virus disease 2019 (nirmatrelvir/ritonavir 300 mg/100 mg twice daily orally for a total of 5 days). During the antiviral treatment, the patient continued the anti-rejection treatment. On the second day of antiviral treatment, the patient′s blood trough concentration of tacrolimus increased to >40.0 μg/L, which was considered to be caused by the interaction between nirmatrelvir/ritonavir and tacrolimus. Tacrolimus was withdrawn and antiviral therapy was continued. After discontinuation of tacrolimus for 8 days and nirmatrelvir/ritonavir for 3 days, the blood trough concentration of tacrolimus decreased to 25.7 μg/L. After re-giving tacrolimus at reducing dosage for 3 days, the blood trough concentration of tacrolimus was 8.3 μg/L. After 13 days of resuming administration of tacrolimus at the original dose and frequency, the patient′s blood trough concentration of tacrolimus was 9.2 μg/L. Since then, the blood trough concentration of tacrolimus in the patient was not abnormal again.

Objective:To investigate the clinical characteristics and prognosis of the patients with nocardiosis.Methods:From January 2013 to July 2019, 44 patients with nocardiosis in Department of Infectious Diseases, Huashan Hospital, Fudan University in Shanghai were enrolled, and their clinical data were retrospectively analyzed, including baseline characteristics, clinical manifestations, underlying diseases history of glucocorticoid therapy, laboratory data (blood routine examination, procalcitonin, C-reactive protein, lymphocytes subsets, etc.), imaging changes, bacterial strain identification, treatment regimens and outcomes. According to the locations of infection, patients were divided into pulmonary nocardiosis, extrapulmonary single-organ nocardiosis and disseminated nocardiosis. The Mann-Whitney U test was used for comparison between two groups, and the Kruskal-Wallis H test was used for comparison among multiple groups. Results:Among the 44 cases of nocardiosis, 14 cases were pulmonary nocardiosis, 17 cases were extrapulmonary single-organ nocardiosis (including nine cases with central nervous system infection, six cases with skin and soft tissue infection, one case with abdominal abscess and one case with urinary tract infection) and 13 cases were disseminated nocardiosis (including four cases with bloodstream infection, six cases with central nervous system and lung or skin and soft tissue infection, three cases of lung and skin and soft tissue infection). Thirty-four cases had underlying diseases, and 27 cases received glucocorticoid or immunosuppressant treatment. The main symptom of 11 patients in pulmonary nocardiosis group was productive cough, while that of the patients in other two groups was fever. Nocardia species were mainly Nocardia brasiliensis, Nocardia nova and Nocardia farcinicaia. The white blood cell counts and neutrophils proportion were normal or slightly increased in 42 cases, and the platelets were normal or slightly decreased in 41 cases. Erythrocyte sedimentation rate increased in 19 cases, procalcitonin increased in 21 cases, C-reactive protein increased in 34 cases, and ferritin increased in 18 cases. A total of 34 patients were tested for lymphocyte subsets, of which 15 had CD4 + T lymphocytes decreased, 14 had CD8 + T lymphocytes increased, seven had B lymphocytes increased, seven had B lymphocytes decreased, and eight had natural killer cells decreased. The hemoglobin of patients with pulmonary nocardiosis was higher than that of patients with extrapulmonary infection, and the difference was statistically significant ( U=0.095, P=0.025). The imaging manifestations were mainly abscess and inflammatory exudation. Forty cases were cured or improved, one case was still on treatment, and three cases died. Conclusions:The clinical manifestations of nocardiosis involving various organs are non-specific. Standardized treatment could reduce the mortality of nocardiosis.

Objective:To understand the characteristics of the HIV-1 molecular networks in injected drug users (IDUs) in Guangzhou from 2008 to 2017, and provide reference for the prevention and control of AIDS in this population.Methods:The serum samples of newly diagnosed HIV-1 positive IDUs in Guangzhou from 2008 to 2017 were collected, HIV-1 RNA was extracted for pol gene amplification and sequencing. The molecular cluster in the phylogenetic tree was identified by Cluster Picker 1.2.3 for cluster analysis. TN93 model in HyPhy2.2.4 was used to calculate the gene distance between the cluster sequences. Software Cytoscape3.8.2 was used to visualize the molecular network, and χ2 test or exact probability method was used for cluster analysis and centrality analysis. Results:A total of 586 sequences were successfully amplified (73.9%, 586/793), and 80 molecular clusters were produced, with a clustering rate of 46.6% (273/586). In molecular clusters, the proportions of the strains from IDUs in Han ethnic group (48.4%, 260/537), IDUs who were local residents in Guangdong (52.7%, 146/277) and IDUs whose strain sequence subtype was CRF55_01B (93.3%, 14/15) were higher. In the molecular network, the degree range was 1-7, and nodes with degree ≥3 accounted for 12.8% (24/187), which was associated with another 81 nodes in the molecular network (43.3%, 81/187). The centrality analysis showed that the proportions of housework/unemployed with high degree centrality (19.0%, 19/100), high intermediary (22.0%, 22/100), and high proximity centrality (32.0%, 32/100) were higher in IDUs infected with HIV-1.Conclusion:The risk of HIV-1 clustering in IDUs in Guangzhou was high, suggesting that IDUs who were from both Guangdong and Guangxi and were house workers or unemployed should be viewed as the key targets, and precise intervention should be implemented to reduce the HIV-1 infection rate in this population.

Significantly increasing crop yield is a major and worldwide challenge for food supply and security. It is well-known that rice cultivated at Taoyuan in Yunnan of China can produce the highest yield worldwide. Yet, the gene regulatory mechanism underpinning this ultrahigh yield has been a mystery. Here, we systematically collected the transcriptome data for seven key tissues at different developmental stages using rice cultivated both at Taoyuan as the case group and at another regular rice planting place Jinghong as the control group. We identified the top 24 candi-date high-yield genes with their network modules from these well-designed datasets by developing a novel computational systems biology method, i.e., dynamic cross-tissue (DCT) network analysis. We used one of the candidate genes, OsSPL4, whose function was previously unknown, for gene editing experimental validation of the high yield, and confirmed that OsSPL4 significantly affects panicle branching and increases the rice yield. This study, which included extensive field phenotyping, cross-tissue systems biology analyses, and functional validation, uncovered the key genes and gene regulatory networks underpinning the ultrahigh yield of rice. The DCT method could be applied to other plant or animal systems if different phenotypes under various environments with the common genome sequences of the examined sample. DCT can be downloaded from https://github.com/zt-pub/DCT.

Objective To investigate the antimicrobial resistance and genotype distribution of staphylococcal cassette chromosome mec (SCCmec) of staphylococcus aureus (S.aureus) isolated from children hospitalized at Pediatric People's Hospital of Zhongjiang County.Methods Seventy-seven strains of S.aureus were collected by nasopharyngeal swabs at the Pediatric Department of People's Hospital of Zhongjiang County from January to December 2015.Methicillin-resistant staphylococcus aureus (MRSA) and methicillin-susceptible staphylococcus aureus (MSSA) were identified by cefoxitin disc diffusion and detection of mecA method.The minimum inhibitory concentrations (MIC) of antibiotics were determined by E-test method.SCCmec typing on MRSA strains was performed by using multiplex PCR.Results MRSA accounted for 54.5％ (42 strains) strains of 77 strains.All MRSA strains were resistant to Penicillin,and the rates of antibiotic resistance to Cefuroxime,Ceftriaxone,Erythromycin were 78.6％,95.2％ and 97.6％,respectively.The rates of antibiotic resistance of 35 MSSA to Penicillin and Erythromycin were 97.1％ and 62.9％,and they were also sensitive to other antibiotics.In 42 strains of MRSA,SCCmec type Ⅳa was the predominant type (27 strains,64.3 ％),which was followed by type Ⅳ g and Ⅴ (each 5 strains,11.9％),type Ⅳ c and Ⅳh (each 1strain,2.4％).Non-susceptibility rate of SCCmec Ⅳ to cefuroxime was significantly higher than that of other SCCmec types (P ＜ 0.05).Conclusions All strains from children hospitalized in People's Hospital of Zhongjiang County are often resistant to Penicillin and Erythromycin.The proportion of MRSA isolated from hospitalized children was high.SCCmec type Ⅳa is the main genotype of MRSA.

Objective To investigate the feasibility of low-c oncentration iso_osmolar contrast agent together with low tube voltage and iterative reconstruction algorithm in rabbit liver computed tonography (CT) perfusion imaging.Methods A total of 15 bealthy New Zealand rabbits were scanned twice of liver CT perfusion scans each with 24 hours interval.The first scan (routine group) was acquired at 100 kV and 100 mAs with ultravist (370 mg/ml),while the second (double low group) was acquired at 80 kV and 100 mAs with iodixanol (270 mg/ml) at 24 hours after the first scan.The obtained images were reconstructed with filtered back projection (FBP) and adaptive iterative dose reduction (AIDR-3D)algorithms in the controlled and experimental groups,respectively.The perfusion parameters including hepatic artery perfusion(HAP),portal vein perfasion(PVP),hepatic perfusion index(HPI),and total liver perfusion(TLP) and image quality as image quality score,average CT value of abdomen aorta,signalto-noise ratio(SNR),carrier-to-noise ratio(CNR),and figure of merit(FOM) were compared used pair ttest or Mann-Whitney U-test between the two groups wherever appropriate.The effective radiation dose and iodine intake were also recorded and compared.Results The image quality and perfusion parameters had no significantly different between the two groups except for FOM.The effective radiation dose and iodine intake were 38.79％ and 27.03％ lower in the double low group.Conclusions Low concentration iso _osmolar contrast agent (iodixanol,270 mg/ml) together with low tube voltage (80 kV) helps to reduce radiation dose and iodine intake without compromising perfusion parameters and image quality in liver CT perfusion imaging.