Ibuprofen treatment for patent ductus arteriosus in preterm infants:a retrospective cohort study in a leading Chinese center

Objective There is a dilemma of ibuprofen treatment with patent ductus arteriosus(PDA)as to how and when to treat.We aimed to clarify this issue in very preterm infants(VPIs;<32 weeks).Methods:This retrospective study included 1659 VPIs who were diagnosed with PDA according to echocardiographic examinations and cardiovascular dysfunction scoring system(the CVD scoring).The VPIs were classified into six groups(A1,A2,A3,B1,B2,and B3)based on CVD scores(A,<3,and B,≥3),and treatment with ibuprofen for PDA(1,conservational management;2,early ibuprofen treatment;and 3,late ibuprofen treatment).Treatment was stopped when PDA was closed,CVD score was zero or PDA needed ligation.Results:VPIs with CVD scores<3 had most PDA closure without surgery,and early ibuprofen treatment did not significantly affect PDA closure.VPIs with CVD scores≥3 had some PDA closure after 2 courses of treatment,but closure rates decreased linearly with ibuprofen course(1^(st)75.2%,2^(nd)62.3%,3^(rd)50.0%,P<0.0001),and early ibuprofen treatment(group B2)did not increase PDA closure compared to late ibuprofen treatment(group B3).In these same infants,the longer they were in CVD scores≥3,the more the complications of preterm were increased(retinopathy of prematurity ROP 1^(st)16.5%,2^(nd)23.8%,3^(rd)29.6%,P=0.016;bronchopulmonary dysplasia BPD 1^(st)15.5%,2^(nd)26.7%,3^(rd)33.8%,P<0.0001;intraventricular hemorrhage IVH 1^(st)20.4%,2^(nd)32.4%,3^(rd)23.8%,P=0.015).Conclusion:Ibuprofen is suggested for PDA closure when the PDA reopens or has developed into the stage when the CVD score≥3.

Ecosystem service multifunctionality of mixed conifer-broad-leaved forests under climate change and forest management based on matrix growth modelling

Climate change and forest management are recognized as pivotal factors influencing forest ecosystem services and thus multifunctionality.However,the magnitude and the relative importance of climate change and forest management effects on the multifunctionality remain unclear,especially for natural mixed forests.In this study,our objective is to address this gap by utilizing simulations of climate-sensitive transition matrix growth models based on national forest inventory plot data.We evaluated the effects of seven management scenarios(combinations of various cutting methods and intensities)on the future provision of ecosystem services and multifunctionality in mixed conifer-broad-leaved forests in northeastern China,under four climate scenarios(SSP1-2.6,SSP2-4.5,SSP5-8.5,and constant climate).Provisioning,regulating,cultural,and supporting services were described by timber production,carbon storage,carbon sequestration,tree species diversity,deadwood volume,and the number of large living trees.Our findings indicated that timber production was significantly influenced by management scenarios,while tree species diversity,deadwood volume,and large living trees were impacted by both climate and management separately.Carbon storage and sequestration were notably influenced by both management and the interaction of climate and management.These findings emphasized the profound impact of forest management on ecosystem services,outweighing that of climate scenarios alone.We found no single management scenario maximized all six ecosystem service indicators.The upper story thinning by 5%intensity with 5-year interval(UST5)management strategy emerged with the highest multifunctionality,surpassing the lowest values by more than 20%across all climate scenarios.In conclusion,our results underlined the potential of climate-sensitive transition matrix growth models as a decision support tool and provided recommendations for long-term strategies for multifunctional forest management under future climate change context.Ecosystem services and multifunctionality of forests could be enhanced by implementing appropriate management measures amidst a changing climate.

Two New Compounds from Schisandra propinqua var.propinqua

Schisanpropinoic acid(1),a new bergamotane sesquiterpenoid,and schisanpropinin(2),a new tetrahydrofuran lignan with a rare epoxyethane unit,were identified from the stems and leaves of Schisandra propinqua var.propinqua.Their structures were determined based on comprehensive spectroscopic and mass spectrometric analysis.The absolute configuration of 1 was determined by X-ray analysis.Compounds 1 and 2 were tested for their cytotoxic activity against five human tumor cell lines.

Four new indole alkaloids from Plantago asiatica

Four new indole alkaloids,plasiaticines A-D(1-4),together with two known ones,were isolated from the seeds of Plantago asiatica.The structures of the new compounds were elucidated on the basis of comprehensive analysis of spectroscopic data.All compounds were tested for their cytotoxic activity,and all compounds except 4 were tested for their acetylcholinesterase(AChE)inhibitory activities.

Effect of berberine on hyperglycaemia and gut microbiota composition in type 2 diabetic Goto-Kakizaki rats

BACKGROUND A recent investigation showed that the prevalence of type 2 diabetes mellitus(T2DM)is 12.8%among individuals of Han ethnicity.Gut microbiota has been reported to play a central role in T2DM.Goto-Kakizaki(GK)rats show differences in gut microbiota compared to non-diabetic rats.Previous studies have indicated that berberine could be successfully used to manage T2DM.We sought to understand its hypoglycaemic effect and role in the regulation of the gut microbiota.AIM To determine whether berberine can regulate glucose metabolism in GK rats via the gut microbiota.METHODS GK rats were acclimatized for 1 wk.The GK rats were randomly divided into three groups and administered saline(Mo),metformin(Me),or berberine(Be).The observation time was 8 wk,and weight,fasting blood glucose(FBG),insulin,and glucagon-like peptide-1(GLP-1)were measured.Pancreatic tissue was observed for pathological changes.Additionally,we sequenced the 16S rRNA V3-V4 region of the gut microbiota and analysed the structure.RESULTS Compared with the Mo group,the Me and Be groups displayed significant differences in FBG(P<0.01)and GLP-1(P<0.05).A significant decrease in weight and homeostatic model assessment-insulin resistance was noted in the Be group compared with those in the Me group(P<0.01).The pancreatic islets of the Me-and Be-treated rats showed improvement in number,shape,and necrosis compared with those of Mo-treated rats.A total of 580 operational taxonomic units were obtained in the three groups.Compared to the Mo group,the Me and Be groups showed a shift in the structure of the gut microbiota.Correlation analysis indicated that FBG was strongly positively correlated with Clostridia_UCG-014(P<0.01)and negatively correlated with Allobaculum(P<0.01).Body weight showed a positive correlation with Desulfovibrionaceae(P<0.01)and a negative correlation with Akkermansia(P<0.01).Importantly,our results demonstrated that Me and Be could significantly decrease Bacteroidetes(P<0.01)and the Bacteroidetes/Firmicutes ratio(P<0.01).Furthermore,Muribaculaceae(P<0.01;P<0.05)was significantly decreased in the Me and Be groups,and Allobaculum(P<0.01)was significantly increased.CONCLUSION Berberine has a substantial effect in improving metabolic parameters and modulating the gut microbiota composition in T2DM rats.

Comparison of demographic features and laboratory parameters between COVID-19 deceased patients and surviving severe and critically ill cases

BACKGROUND Coronavirus disease 2019(COVID-19) has been far more devastating than expected, showing no signs of slowing down at present. Heilongjiang Province is the most northeastern province of China, and has cold weather for nearly half a year and an annual temperature difference of more than 60℃, which increases the underlying morbidity associated with pulmonary diseases, and thus leads to lung dysfunction. The demographic features and laboratory parameters of COVID-19 deceased patients in Heilongjiang Province, China with such climatic characteristics are still not clearly illustrated.AIM To illustrate the demographic features and laboratory parameters of COVID-19 deceased patients in Heilongjiang Province by comparing with those of surviving severe and critically ill cases.METHODS COVID-19 deceased patients from different hospitals in Heilongjiang Province were included in this retrospective study and compared their characteristics with those of surviving severe and critically ill cases in the COVID-19 treatment center of the First Affiliated Hospital of Harbin Medical University. The surviving patients were divided into severe group and critically ill group according to the Diagnosis and Treatment of New Coronavirus Pneumonia(the seventh edition).Demographic data were collected and recorded upon admission. Laboratory parameters were obtained from the medical records, and then compared among the groups.RESULTS Twelve COVID-19 deceased patients, 27 severe cases and 26 critically ill cases were enrolled in this retrospective study. No differences in age, gender, and number of comorbidities between groups were found. Neutrophil percentage(NEUT%), platelet(PLT), C-reactive protein(CRP), creatine kinase isoenzyme(CK-MB), serum troponin I(TNI) and brain natriuretic peptides(BNP) showed significant differences among the groups(P = 0.020, P = 0.001, P < 0.001, P = 0.001, P < 0.001, P <0.001, respectively). The increase of CRP, D-dimer and NEUT% levels, as well as the decrease of lymphocyte count(LYMPH) and PLT counts, showed significant correlation with death of COVID-19 patients(P = 0.023, P = 0.008, P = 0.045, P = 0.020, P = 0.015, respectively).CONCLUSION Compared with surviving severe and critically ill cases, no special demographic features of COVID-19 deceased patients were observed, while some laboratory parameters including NEUT%, PLT, CRP, CK-MB, TNI and BNP showed significant differences. COVID-19 deceased patients had higher CRP, D-dimer and NEUT% levels and lower LYMPH and PLT counts.

Secondary Metabolites from the Endophytic Fungus Xylaria sp.hg1009

A detailed chemical investigation of the secondary metabolites produced by the endophytic fungus Xylaria sp.isolated from the stems of Isodon sculponeatus afforded six new compounds,xylariahgins A-F(1-6),two new natural products(7 and 8),along with two known compounds(9 and 10)(Fig.1).The structures of all compounds were unambiguously established by analyzing their spectroscopic data or referring to pertinent literature.Compounds 1-8 were tested for their cytotoxic activity against five human tumor cell lines.

Four new lignans from the leaves and stems of Schisandra propinqua var.sinensis

Four new tetrahydrofuran lignans,schpropinrins A-D(1-4),together with five known ones,were isolated from the leaves and stems of Schisandra propinqua var.sinensis.Their structures,including absolute configurations,were characterized by means of spectroscopic analysis and ECD calculation.Compounds 1-4 featured a ketal or hemiketal substructure at C-7 and all of the isolates were tested for their anti-HIV integrase activity.

Four new diterpenoids from Isodon eriocalyx var.laxiflora

Four new diterpenoids,laxiflorins S-V(1-4),bearing four different types,and one known compound,laxiflorin O(5),were isolated from Isodon eriocalyx var.laxiflora.Compound 1 was the first example of ent-kauranoids bearing a unique C_(24) carbon framework and compound 4 was the first example of 3,4-seco-ent-abietane diterpenoids from the Isodon genus.Their structures were determined by spectroscopic methods(UV,IR,MS,NMR).

Observation and mitigation of image distortion in high-energy electron radiography

Image distortion caused by the angular misalignment of quadrupole magnets in high-energy electron radiography has been studied systematically.We propose that the distortion originates from the coupling of the electron motions in the transverse directions,based on a theoretical analysis and the transfer-matrix method.The relative angular rotation between the second and third magnetic quadrupoles was identified as the main contributor to image distortion.This was verified by both a beam-dynamics simulation and experiments.Different strategies to mitigate this image distortion are also explored,including magnets online tuning,higher beam energy and larger magnification factor.This study provides criteria for designing experiments and paves the way for achieving higher image precision.

COVID-19 patient with an incubation period of 27 d:A case report

BACKGROUND As a highly contagious disease,coronavirus disease 2019(COVID-19)is wreaking havoc around the world due to continuous spread among close contacts mainly via droplets,aerosols,contaminated hands or surfaces.Therefore,centralized isolation of close contacts and suspected patients is an important measure to prevent the transmission of COVID-19.At present,the quarantine duration in most countries is 14 d due to the fact that the incubation period of severe acute respiratory syndrome coronavirus type 2(SARS-CoV-2)is usually identified as 1-14 d with median estimate of 4-7.5 d.Since COVID-19 patients in the incubation period are also contagious,cases with an incubation period of more than 14 d need to be evaluated.CASE SUMMARY A 70-year-old male patient was admitted to the Department of Respiratory Medicine of The First Affiliated Hospital of Harbin Medical University on April 5 due to a cough with sputum and shortness of breath.On April 10,the patient was transferred to the Fever Clinic for further treatment due to close contact to one confirmed COVID-19 patient in the same room.During the period from April 10 to May 6,nucleic acid and antibodies to SARS-CoV-2 were tested 7 and 4 times,respectively,all of which were negative.On May 7,the patient developed fever with a maximum temperature of 39℃,and his respiratory difficulties had deteriorated.The results of nucleic acid and antibody detection of SARS-CoV-2 were positive.On May 8,the nucleic acid and antibody detection of SARS-CoV-2 by Heilongjiang Provincial Center for Disease Control were also positive,and the patient was diagnosed with COVID-19 and reported to the Chinese Center for Disease Control and Prevention.CONCLUSION This case highlights the importance of the SARS-CoV-2 incubation period.Further epidemiological investigations and clinical observations are urgently needed to identify the optimal incubation period of SARS-CoV-2 and formulate rational and evidence-based quarantine policies for COVID-19 accordingly.

Characterization of gut microbial and metabolite alterations in faeces of Goto Kakizaki rats using metagenomic and untargeted metabolomic approach

BACKGROUND In recent years,the incidence of type 2 diabetes(T2DM)has shown a rapid growth trend.Goto Kakizaki(GK)rats are a valuable model for the study of T2DM and share common glucose metabolism features with human T2DM patients.A series of studies have indicated that T2DM is associated with the gut microbiota composition and gut metabolites.We aimed to systematically characterize the faecal gut microbes and metabolites of GK rats and analyse the relationship between glucose and insulin resistance.AIM To evaluate the gut microbial and metabolite alterations in GK rat faeces based on metagenomics and untargeted metabolomics.METHODS Ten GK rats(model group)and Wistar rats(control group)were observed for 10 wk,and various glucose-related indexes,mainly including weight,fasting blood glucose(FBG)and insulin levels,homeostasis model assessment of insulin resistance(HOMA-IR)and homeostasis model assessment ofβcell(HOMA-β)were assessed.The faecal gut microbiota was sequenced by metagenomics,and faecal metabolites were analysed by untargeted metabolomics.Multiple metabolic pathways were evaluated based on the differential metabolites identified,and the correlations between blood glucose and the gut microbiota and metabolites were analysed.RESULTS The model group displayed significant differences in weight,FBG and insulin levels,HOMA-IR and HOMA-βindexes(P<0.05,P<0.01)and a shift in the gut microbiota structure compared with the control group.The results demonstrated significantly decreased abundances of Prevotella sp.CAG:604 and Lactobacillus murinus(P<0.05)and a significantly increased abundance of Allobaculum stercoricanis(P<0.01)in the model group.A correlation analysis indicated that FBG and HOMA-IR were positively correlated with Allobaculum stercoricanis and negatively correlated with Lactobacillus murinus.An orthogonal partial least squares discriminant analysis suggested that the faecal metabolic profiles differed between the model and control groups.Fourteen potential metabolic biomarkers,including glycochenodeoxycholic acid,uric acid,13(S)-hydroxyoctadecadienoic acid(HODE),N-acetylaspartate,β-sitostenone,sphinganine,4-pyridoxic acid,and linoleic acid,were identified.Moreover,FBG and HOMA-IR were found to be positively correlated with glutathione,13(S)-HODE,uric acid,4-pyridoxic acid and allantoic acid and negatively correlated with 3-α,7-α,chenodeoxycholic acid glycine conjugate and 26-trihydroxy-5-β-cholestane(P<0.05,P<0.01).Allobaculum stercoricanis was positively correlated with linoleic acid and sphinganine(P<0.01),and 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate was negatively associated with Prevotella sp.CAG:604(P<0.01).The metabolic pathways showing the largest differences were arginine biosynthesis;primary bile acid biosynthesis;purine metabolism;linoleic acid metabolism;alanine,aspartate and glutamate metabolism;and nitrogen metabolism.CONCLUSION Metagenomics and untargeted metabolomics indicated that disordered compositions of gut microbes and metabolites may be common defects in GK rats.

Two new neolignans from Manglietia insignis

Two new neolignans,manneoinsigins A(1)and B(2),together with four known lignans,were isolated from the leaves and stems of Manglietia insignis.The new compounds were established on the basis of extensive spectroscopic analyses.All compounds except 2 were tested for their cytotoxic activity.Compound 3 showed weak cytotoxic activity against the HL-60 human tumor cell line with the IC50 value of 23.5μM.

Isorosthornins A-C,new ent-kaurane diterpenoids from Isodon rosthornii

Three new ent-kauranoids,isorosthornins A-C(1-3),and a new natural product,dihydroponicidin(4),together with five known ones were isolated from the aerial parts of Isodon rosthornii.The structures were determined by means of extensive spectroscopic analysis.All diterpenoids isolated were evaluated for their cytotoxicity against HL-60,SMMC-7721,A-549,MCF-7,and SW480 cell lines,and compounds 5 and 7 showed significant inhibitory effects on all cell lines.

Effects of Geldanamycin on Expression of Bcl-2 in Human Cervical Cancer HeLa Cells

OBJECTIVE Geldanamycin,a natural product of Streptomyces geldanus,binds the heat shock protein 90(Hsp90),a cell chaperone protein that interacts with Bcl-2.In this study,we investigated whether geldanamycin(GA)inhibits proliferation of HeLa cells through induction of apoptosis by decreasing the level of Bcl-2 expression. METHODS HeLa cells,a human cervical cell line,were cultured in vitro and treated with different concentrations of GA(0,0.02,0.2, 2,10μmol/L)for 24 h.or were treated for different lengths of time at a GA concentration of 10μmol/L.Proliferation of the cells was analyzed by an MTT assay,and cell apoptosis was determined by staining the cells with annexin V.In addition,cellular mRNA levels for Bcl-2 and Hsp90 were determined by the semiquantitative polymerase chain reaction(PCR),and the levels of Bcl-2 and Hsp90 protein expression were determined by Western blots. RESULTS Treatment of cells with GA was found to inhibit HeLa cell proliferation in a concentration and time-dependent manner.The inhibition was a result of increased cellular apoptotic levels.Further analyses showed that while the mRNA and protein expression levels of Hsp90 were not affected,GA treatment significantly reduced the level of Bcl-2 mRNA and protein expression in a concentration-dependent manner that correlated with the observed inhibition of cell proliferation. CONCLUSION GA can inhibit proliferation and increase apoptosis of HeLa cells by decreasing the transcription and expression of an anti-apoptotic gene bcl-2,probably through interaction and functional inhibition of Hsp90.

Differential effectiveness of COVID-19 health behaviors:The role of mental health conditions in mask-wearing,social distancing,and hygiene practice

Background:Mental health conditions are known to increase susceptibility to infectious diseases,including coronavirus disease 2019(COVID-19).Health behaviors play a crucial role in mitigating this susceptibility.We aim to examine the differential effectiveness of COVID-19 preventive health behaviors among individuals,considering the presence or absence of specific mental health disorders.Methods:Multivariable logistic regression with interaction terms was performed to examine whether associations between adherence to health behaviors and COVID-19 infection were conditional on depression,anxiety,or eating disorders in a national sample of adults(N=61,891)from 140 US universities,2020–2021.Results:Adjusting for age,race/ethnicity,and gender/sex,the effectiveness of mask-wearing was significant and comparable among individuals with and without depression,anxiety,or eating disorders.Social distancing provided significantly less protection among individuals with depression,anxiety,or eating disorders.Hygiene practice provided significantly less protection among individuals with anxiety.Conclusion:Mask-wearing is robustly effective in the prevention of COVID-19 among individuals.However,social distancing and hygiene practice provide less significant protection among individuals with certain mental health conditions,suggesting the importance of prioritizing these individuals for additional preventive measures(e.g.,vaccines targeting variants)and mitigation strategies(e.g.,financial assistance,targeted mental health care,health education).

Structural Asymmetry of Dorsolateral Prefrontal Cortex Correlates with Depressive Symptoms： Evidence from Healthy Individuals and Patients with Major Depressive Disorder

In this study,we investigated the role of structural asymmetry of the dorsolateral prefrontal cortex（DLPFC） in the continuum of depression from healthy individuals to patients.Structural magnetic resonance imaging was performed in 70 patients with major depressive disorder（MDD）,49 matched controls,and 349 healthy university students to calculate structural asymmetry indexes of the DLPFC.First-episode,treatment-naive MDD patients showed a relatively lower asymmetry index than healthy controls,and their asymmetry index was negatively correlated with the depressive symptoms.This abnormality was normalized by antidepressants in medicated MDD patients.Furthermore,the asymmetry index was negatively correlated with the depressive symptoms in university students;this was replicated at two time points in a subgroup of students,suggesting good test-retest reliability.Our findings are consistent with previous studiesthat support the imbalance hypothesis of MDD and suggest a potential structural basis underlying the functional asymmetry of the DLPFC in depression.In future,the structural index of the DLPFC may become a potential biomarker to evaluate individuals＇ risk for the onset of MDD.

Examining brain structures associated with attention networks in a large sample of young adults: a voxel-based morphometry study

Attention networks have three principal com- ponents supported by separate subprocesses, which include alerting, orienting, and executive control （EC） networks. Efficiently and accurately extracting useful information from the environment as the function of attention is pivotal to our survival. Previous brain imaging studies have examined activation patterns underlying the different attention networks in different cortical regions, yet focal differences in brain structures related to attention network components were not well understood. Therefore, in this study, voxel-based morphometry was used to investigate the relationship between gray matter volume （GMV） and different attention networks in a large young adult sample （n = 156）. As a result, multiple regression analysis revealed that higher alerting scores （stronger alerting ability） were negatively significantly correlated with region gray matter volume （rGMV） cingulate cortex/precuneus）, in the PCC/PreCu （posterior which might be associated with continuous maintenance of a vigilant state. Then, lower EC scores （stronger conflict resolution ability） were associated with larger rGMV in the dorsal anterior cingu- late cortex, which might be related to high-efficiency executive control processing. Together, findings of the present study provided a unique structural basis of GMV for individual differences in alerting and EC networks.

Ent-kaurane and ent-abietane diterpenoids from Isodon phyllostachys

Four new diterpenoids, phyllostachysins I-L （1-4）, along with a known one, hebeiabinin B （5）, were isolated from the aerial parts oflsodonphyllostachys （I.phyllostachys）. Compounds 1 and 2 feature an ent-kaurane backbone, and 3, 4 and 5 bear an ent-abietane skeleton. Their structures were elucidated by means of spectroscopic analysis. Compounds 3 and 4 exhibited significant cytotoxic activity against human tumor cell lines （HL-60, SMMC-7721, A-549, MCF-7 and SW-480）, and strongly inhibited NO production in LPS-stimulated RAW264.7 cells.

China Patient-centered Evaluative Assessment of Cardiac Events Prospective Study of Acute Myocardial Infarction： Study Design

Background： Despite the rapid growth in the incidence of acute myocardial infarction （AMI） in China, there is limited information about patients＇ experiences after AMI hospitalization, especially on long-tern1 adverse events and patient-reported outcomes （PROs）. Methods： The China Patient-centered Evaluative Assessment of Cardiac Events （PEACE）-Prospective AMI Study will enroll 4000 consecutive AM I patients from 53 diverse hospitals across China and follow them longitudinally for 12 months to docunlent their treatment, recovery, and outcomes. Details of patients＇ medical history, treatment, and in-hospital outcomes are abstracted from medical charts. Comprehensive baseline interviews are being conducted to characterize patient demographics, risk factors, presentation, and healthcare utilization. As part of these interviews, validated instruments are administered to measure PROs, including quality of life, symptoms, mood, cognition, and sexual activity. Follow-up interviews, measuring PROs, medication adherence, risk factor control, and collecting hospitalization events are conducted at 1, 6, and 12 months after discharge. Supporting documents for potential outcomes are collected for adjudication by clinicians at the National Coordinating Center. Blood and urine samples are also obtained at baseline, 1 - and 12-month follow-up. In addition, we are conducting a survey of participating hospitals to characterize their organizational characteristics. Conclusion： The China PEACE-Prospective AMI study will be uniquely positioned to generate new information regarding patient＇s experiences and outcomes alter AMI in China and seiwe as a foundation for quality improveinent activities.