Background and aim:Hepatic ischemia-reperfusion injury(IRI)is a significant challenge in liver trans-plantation,trauma,hypovolemic shock,and hepatectomy,with limited effective interventions available.This study aimed to investigate the role of leukocyte cell-derived chemotaxin 2(LECT2)in hepatic IRI and assess the therapeutic potential of Lect2-short hairpin RNA(shRNA)delivered through adeno-associated virus(AAV)vectors. Materials and methods:This study analyzed human liver and serum samples from five patients under-going the Pringle maneuver.Lect2-knockout and C57BL/6J mice were used.Hepatic IRI was induced by clamping the hepatic pedicle.Treatments included recombinant human LECT2(rLECT2)and AAV-Lect2-shRNA.LECT2 expression levels and serum biomarkers including alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine,and blood urea nitrogen(BUN)were measured.Histological analysis of liver necrosis and quantitative reverse-transcription polymerase chain reaction were performed. Results:Serum and liver LECT2 levels were elevated during hepatic IRI.Serum LECT2 protein and mRNA levels increased post reperfusion.Lect2-knockout mice had reduced weight loss;hepatic necrosis;and serum ALT,AST,creatinine,and BUN levels.rLECT2 treatment exacerbated weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN).AAV-Lect2-shRNA treatment significantly reduced weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN),indicating thera-peutic potential. Conclusions:Elevated LECT2 levels during hepatic IRI increased liver damage.Genetic knockout or shRNA-mediated knockdown of Lect2 reduced liver damage,indicating its therapeutic potential.AAV-mediated Lect2-shRNA delivery mitigated hepatic IRI,offering a potential new treatment strategy to enhance clinical outcomes for patients undergoing liver-related surgeries or trauma.

Eleutherococcus senticosus is one of the Dao-di herbs in northeast China. In this study, the chloroplast genomes of three E. senticosus samples from different genuine producing areas were sequenced and then used for the screening of specific DNA barcodes. The germplasm resources and genetic diversity of E. senticosus were analyzed basing on the specific DNA barcodes. The chloroplast genomes of E. senticosus from different genuine producing areas showed the total length of 156 779-156 781 bp and a typical tetrad structure. Each of the chloroplast genomes carried 132 genes, including 87 protein-coding genes, 37 tRNAs, and 8 rRNAs. The chloroplast genomes were relatively conserved. Sequence analysis of the three chloroplast genomes indicated that atpI, ndhA, ycf1, atpB-rbcL, ndhF-rpl32, petA-psbJ, psbM-psbD, and rps16-psbK can be used as specific DNA barcodes of E. senticosus. In this study, we selected atpI and atpB-rbcL which were 700-800 bp and easy to be amplified for the identification of 184 E. senticosus samples from 13 genuine producing areas. The results demonstrated that 9 and 10 genotypes were identified based on atpI and atpB-rbcL sequences, respectively. Furthermore, the two barcodes identified 23 genotypes which were named H1-H23. The haplotype with the highest proportion and widest distribution was H10, followed by H2. The haplotype diversity and nucleotide diversity were 0.94 and 1.82×10~(-3), respectively, suggesting the high genetic diversity of E. senticosus. The results of the median-joining network analysis showed that the 23 genotypes could be classified into 4 categories. H2 was the oldest haplotype, and it served as the center of the network characterized by starlike radiation, which suggested that population expansion of E. senticosus occurred in the genuine producing areas. This study lays a foundation for the research on the genetic quality and chloroplast genetic engineering of E. senticosus and further research on the genetic mechanism of its population, providing new ideas for studying the genetic evolution of E. senticosus.
DNA Barcoding, Taxonomic ; Eleutherococcus/genetics* ; Base Sequence ; Chloroplasts/genetics* ; Genetic Variation ; Phylogeny

The development of chemoresistance which results in a poor prognosis often renders current treatments for colorectal cancer(CRC).In this study,we identified reduced microvessel density(MVD)and vascular immaturity resulting from endothelial apoptosis as therapeutic targets for overcoming chemoresistance.We focused on the effect of metformin on MVD,vascular maturity,and endothelial apoptosis of CRCs with a non-angiogenic phenotype,and further investigated its effect in overcoming chemoresistance.In situ transplanted cancer models were established to compare MVD,endothelial apoptosis and vascular maturity,and function in tumors from metformin-and vehicle-treated mice.An in vitro co-culture system was used to observe the effects of metformin on tumor cell-induced endothelial apoptosis.Transcriptome sequencing was performed for genetic screening.Non-angiogenic CRC developed inde-pendently of angiogenesis and was characterized by vascular leakage,immaturity,reduced MVD,and non-hypoxia.This phenomenon had also been observed in human CRC.Furthermore,non-angiogenic CRCs showed a worse response to chemotherapeutic drugs in vivo than in vitro.By suppressing endo-thelial apoptosis,metformin sensitized non-angiogenic CRCs to chemo-drugs via elevation of MVD and improvement of vascular maturity.Further results showed that endothelial apoptosis was induced by tumor cells via activation of caspase signaling,which was abrogated by metformin administration.These findings provide pre-clinical evidence for the involvement of endothelial apoptosis and subsequent vascular immaturity in the chemoresistance of non-angiogenic CRC.By suppressing endothelial apoptosis,metformin restores vascular maturity and function and sensitizes CRC to chemotherapeutic drugs via a vascular mechanism.

OBJECTIVE: To investigate the association between current and former smoking and the risk of mortality in elderly Chinese men. METHODS: Our study participants were elderly (≥ 60 years) men recruited in a suburban town of Shanghai. Cigarette smoking status was categorized as never smoking, remote (cessation > 5 years) and recent former smoking (cessation ≤ 5 years), and light-to-moderate (≤ 20 cigarettes/day) and heavy current smoking (> 20 cigarettes/day). Cox proportional hazards models and restricted cubic splines were used to examine the associations of interest. RESULTS: The 1568 participants had a mean age of 68.6 ± 7.1 years. Of all participants, 311 were never smokers, 201 were remote former smokers, 133 were recent former smokers, 783 were light-to-moderate current smokers and 140 were heavy current smokers. During a median follow-up of 7.9 years, all-cause, cardiovascular and non-cardiovascular deaths occurred in 267, 106 and 161 participants, respectively. Heavy current smokers had the highest risk of all-cause and non-cardiovascular mortality, with an adjusted hazard ratio (HR) of 2.30 (95% CI: 1.34-4.07) and 3.98 (95% CI: 2.03-7.83) versus never smokers, respectively. Recent former smokers also had a higher risk of all-cause (HR = 1.62, 95% CI: 1.04-2.52) and non-cardiovascular mortality (HR = 2.40, 95% CI: 1.32-4.37) than never smokers. Cox regression restricted cubic spline models showed the highest risk of all-cause and non-cardiovascular mortality within 5 years of smoking cessation and decline thereafter. Further subgroup analyses showed interaction between smoking status and pulse rate (≥ 70 beats/min vs. < 70 beats/min) in relation to the risk of all-cause and non-cardiovascular mortality, with a higher risk in current versus never smokers in those participants with a pulse rate below 70 beats/min. CONCLUSIONS Cigarette smoking in elderly Chinese confers significant risks of mortality, especially when recent former smoking is considered together with current smoking.

Cinnamomum camphora is an important economic tree species in China. According to the type and content of main components in the volatile oil of leaf, C. camphora were divided into five chemotypes, including borneol-type, camphor-type, linalool-type, cineole-type, and nerolidol-type. Terpene synthase(TPS) is the key enzyme for the formation of these compounds. Although several key enzyme genes have been identified, the biosynthetic pathway of(+)-borneol, which has the most economic value, has not been reported. In this study, nine terpenoid synthase genes CcTPS1-CcTPS9 were cloned through transcriptome analysis of four chemical-type leaves. After the recombinant protein was induced by Escherichia coli, geranyl pyrophosphate(GPP) and farnesyl pyrophosphate(FPP) were used as substrates for enzymatic reaction, respectively. Both CcTPS1 and CcTPS9 could catalyze GPP to produce bornyl pyrophosphate, which could be hydrolyzed by phosphohydrolase to obtain(+)-borneol, and the product of(+)-borneol accounted for 0.4% and 89.3%, respectively. Both CcTPS3 and CcTPS6 could catalyze GPP to generate a single product linalool, and CcTPS6 could also react with FPP to generate nerolidol. CcTPS8 reacted with GPP to produce 1,8-cineol(30.71%). Nine terpene synthases produced 9 monoterpene and 6 sesquiterpenes. The study has identified the key enzyme genes responsible for borneol biosynthesis in C. camphora for the first time, laying a foundation for further elucidating the molecular mechanism of chemical type formation and cultivating new varieties of borneol with high yield by using bioengineering technology.
Cinnamomum camphora/enzymology* ; Alkyl and Aryl Transferases/chemistry*

Objective To establish an ultra-high performance liquid chromatography-tandem mass spectrometry for the determination of concentration of zanubrutinib in plasma.Method Multi-reaction ion(MRM)detection in positive mode is adopt in the method.The chromatographic column is ZORBAX Eclipse Plus C]8 column(1.8 μm,2.1 mm × 50.0 mm,I.D.Agilent Corporatio,MA,USA);Mobile phase:0.1％formic acid water and acetonitrile,gradient elution with a flow rate of 0.4 mL·min-1 and a volume of 2 μL was injected into the system.The plasma samples were prepared with acetonitrile for precipitation.After a single dose of 15 mg·kg-1 zanubrutinib for six adult male SD rats,blood was collected from the tail vein.The concentration of zanubrutinib in the rat plasma samples was measured,and the pharmacokinetic parameters were calculated by DAS 3.0.Result The linear range of zanubrutinib was 1-500 ng·mL-1 with good linearity.The intra-day and intra-day precision were less than 15％,and the relative recovery was 95.74％-99.19％.The absolution recovery,matrix effect and stability met the requirements;Pharmacokinetic parameters Cmax was(30.15±81.55)ng·mL-1,tmax was(0.32±0.16)h,t1/2 was(5.05±0.62)h,AUC0-t was(271.55±149.01)ng·h·mL-1.Conclusion The method for the determination of zanubrutinib in plasma established in this study has the characteristics of high sensitivity,rapid detection and good repeatability,and is suitable for the determination of zanubrutinib in plasma and the study of pharmacokinetics of zanubrutinib.

Humans ; Aortopulmonary Septal Defect/surgery* ; Septal Occluder Device

Humans ; Aortopulmonary Septal Defect/surgery* ; Septal Occluder Device

OBJECTIVE: To analyze the influenza vaccination trend of hospitalized elderly people (≥ 60 years old) in Beijing from 2013 to 2019. METHODS: The influenza vaccination status and hospitalization information of elderly people were extracted from the Beijing Elderly Influenza Vaccination database (2013-2019) and the Beijing Urban Employee Basic Medical Insurance database (2013-2019), se-parately. The influenza vaccine coverage rates and annual percentage change were calculated to compare the vaccination trends of elderly people hospitalized due to different diseases. The subjects in 2018-2019 influenza season were divided into different groups according to demographic status, health conditions and hospitalization outcomes to describe and compare the distribution of influenza vaccination rates. RESULTS: The influenza vaccine coverage rates among the elderly people hospitalized due to cardiovascular diseases, cerebrovascular diseases, respiratory diseases or diabetes mellitus were 14.6%, 13.4%, 13.4% and 11.8%, respectively. The influenza vaccination rate among those hospitalized for cardiovascular diseases remained the highest across six influenza seasons and those hospitalized for diabetes mellitus remained the lowest. The largest annual decline of influenza vaccine coverage rate was observed among the hospitalized elderly due to diabetes mellitus (-7.85%). The distribution of vaccinated population was significantly associated with age, gender, hospitalization outcome and comorbidities among the hospitalized elderly people with specific diseases in 2018-2019. Among the elderly people hospitalized due to four different diseases, the vaccination rate of the patients aged 70-79 years was higher than that of the other age groups and that of the patients aged 60-69 years was the lowest. Among the elderly people hospitalized due to respiratory diseases, the vaccination rate of men was higher than that of women, while the situation reversed among the elderly people hospitalized due to cardiovascular diseases and diabetes mellitus. Vaccination rates decreased among the older adults with poor hospitalization outcomes. Among the elderly people hospitalized due to diabetes mellitus, those with 0 comorbidity had the lowest vaccination rate (7.9%). CONCLUSION The trend of influenza vaccine coverage rates among the elderly people in Beijing from 2013 to 2019 was downward. We should pay more attention to influenza vaccination in elderly people with diabetes mellitus and aged 60-69 years, and carry out more research on the protective effects of influenza vaccine to promote influenza vaccine coverage among people with chronic diseases.
Aged ; Beijing ; Cardiovascular Diseases ; Female ; Hospitalization ; Humans ; Influenza Vaccines ; Influenza, Human/prevention & control* ; Male ; Middle Aged ; Vaccination

Hernia, Inguinal/surgery* ; Humans ; Mesothelioma/surgery* ; Mesothelioma, Malignant ; Peritoneal Neoplasms/surgery* ; Peritoneum