Epidemiological and etiological characteristics of 1266 patients with severe acute respiratory infection in central China, 2018-2020: a retrospective survey.

BACKGROUND: Severe acute respiratory infection (SARI), a significant global health concern, imposes a substantial disease burden. In China, there is inadequate data concerning the monitoring of respiratory pathogens, particularly bacteria, among patients with SARI. Therefore, this study aims to delineate the demographic, epidemiological, and aetiological characteristics of hospitalised SARI patients in Central China between 2018 and 2020. METHODS: Eligible patients with SARI admitted to the First Affiliated Hospital of Zhengzhou University between 1 January 2018 and 31 December 2020 were included in this retrospective study. Within the first 24 h of admission, respiratory (including sputum, nasal/throat swabs, bronchoalveolar lavage fluid, thoracocentesis fluid, etc.), urine, and peripheral blood specimens were collected for viral and bacterial testing. A multiplex real-time polymerase chain reaction (PCR) diagnostic approach was used to identify human influenza virus, respiratory syncytial virus, parainfluenza virus, adenovirus, human bocavirus, human coronavirus, human metapneumovirus, and rhinovirus. Bacterial cultures of respiratory specimens were performed with a particular focus on pathogenic microorganisms, including S. pneumoniae, S. aureus, K. pneumoniae, P. aeruginosa, Strep A, H. influenzae, A. baumannii, and E. coli. In cases where bacterial culture results were negative, nucleic acid extraction was performed for PCR to assay for the above-mentioned eight bacteria, as well as L. pneumophila and M. pneumoniae. Additionally, urine specimens were exclusively used to detect Legionella antigens. Furthermore, epidemiological, demographic, and clinical data were obtained from electronic medical records. RESULTS: The study encompassed 1266 patients, with a mean age of 54 years, among whom 61.6% (780/1266) were males, 61.4% (778/1266) were farmers, and 88.8% (1124/1266) sought medical treatment in 2020. Moreover, 80.3% (1017/1266) were housed in general wards. The most common respiratory symptoms included fever (86.8%, 1122/1266) and cough (77.8%, 986/1266). Chest imaging anomalies were detected in 62.6% (792/1266) of cases, and 58.1% (736/1266) exhibited at least one respiratory pathogen, with 28.5% (361/1266) having multiple infections. Additionally, 95.7% (1212/1266) of the patients were from Henan Province, with the highest proportion (38.3%, 486/1266) falling in the 61-80 years age bracket, predominantly (79.8%, 1010/1266) seeking medical aid in summer and autumn. Bacterial detection rate (39.0%, 495/1266) was higher than viral detection rate (36.9%, 468/1266), with the primary pathogens being influenza virus (13.8%, 175/1266), K. pneumoniae (10.0%, 127/1266), S. pneumoniae (10.0%, 127/1266), adenovirus (8.2%, 105/1266), P. aeruginosa (8.2%, 105/1266), M. pneumoniae (7.8%, 100/1266), and respiratory syncytial virus (7.7%, 98/1266). During spring and winter, there was a significant prevalence of influenza virus and human coronavirus, contrasting with the dominance of parainfluenza viruses in summer and autumn. Respiratory syncytial virus and rhinovirus exhibited higher prevalence across spring, summer, and winter. P. aeruginosa, K. pneumoniae, and M. pneumoniae were identified at similar rates throughout all seasons without distinct spikes in prevalence. However, S. pneumoniae showed a distinctive pattern with a prevalence that doubled during summer and winter. Moreover, the positive detection rates of various other viruses and bacteria were lower, displaying a comparatively erratic prevalence trend. Among patients admitted to the intensive care unit, the predominant nosocomial bacteria were K. pneumoniae (17.2%, 43/249), A. baumannii (13.6%, 34/249), and P. aeruginosa (12.4%, 31/249). Conversely, in patients from general wards, predominant pathogens included influenza virus (14.8%, 151/1017), S. pneumoniae (10.4%, 106/1017), and adenovirus (9.3%, 95/1017). Additionally, paediatric patients exhibited significantly higher positive detection rates for influenza virus (23.9%, 11/46) and M. pneumoniae (32.6%, 15/46) compared to adults and the elderly. Furthermore, adenovirus (10.0%, 67/669) and rhinovirus (6.4%, 43/669) were the primary pathogens in adults, while K. pneumoniae (11.8%, 65/551) and A. baumannii (7.1%, 39/551) prevailed among the elderly, indicating significant differences among the three age groups. DISCUSSION: In Central China, among patients with SARI, the prevailing viruses included influenza virus, adenovirus, and respiratory syncytial virus. Among bacteria, K. pneumoniae, S. pneumoniae, P. aeruginosa, and M. pneumoniae were frequently identified, with multiple infections being very common. Additionally, there were substantial variations in the pathogen spectrum compositions concerning wards and age groups among patients. Consequently, this study holds promise in offering insights to the government for developing strategies aimed at preventing and managing respiratory infectious diseases effectively.

Could extracellular vesicles derived from mesenchymal stem cells be a potential therapy for acute pancreatitis-induced cardiac injury?

Acute pancreatitis (AP) often leads to a high incidence of cardiac injury, posing significant challenges in the treatment of severe AP and contributing to increased mortality rates. Mesenchymal stem cells (MSCs) release bioactive molecules that participate in various inflammatory diseases. Similarly, extracellular vesicles (EVs) secreted by MSCs have garnered extensive attention due to their comparable anti-inflammatory effects to MSCs and their potential to avoid risks associated with cell transplantation. Recently, the therapeutic potential of MSCs-EVs in various inflammatory diseases, including sepsis and AP, has gained increasing recognition. Although preclinical research on the utilization of MSCs-EVs in AP-induced cardiac injury is limited, several studies have demonstrated the positive effects of MSCs-EVs in regulating inflammation and immunity in sepsis-induced cardiac injury and cardiovascular diseases. Furthermore, clinical studies have been conducted on the therapeutic application of MSCs-EVs for some other diseases, wherein the contents of these EVs could be deliberately modified through prior modulation of MSCs. Consequently, we hypothesize that MSCs-EVs hold promise as a potential therapy for AP-induced cardiac injury. This paper aims to discuss this topic. However, additional research is essential to comprehensively elucidate the underlying mechanisms of MSCs-EVs in treating AP-induced cardiac injury, as well as to ascertain their safety and efficacy.

Etiology of lower respiratory tract in pneumonia based on metagenomic next-generation sequencing: a retrospective study.

Introduction: Pneumonia are the leading cause of death worldwide, and antibiotic treatment remains fundamental. However, conventional sputum smears or cultures are still inefficient for obtaining pathogenic microorganisms.Metagenomic next-generation sequencing (mNGS) has shown great value in nucleic acid detection, however, the NGS results for lower respiratory tract microorganisms are still poorly studied. Methods: This study dealt with investigating the efficacy of mNGS in detecting pathogens in the lower respiratory tract of patients with pulmonary infections. A total of 112 patients admitted at the First Affiliated Hospital of Zhengzhou University between April 30, 2018, and June 30, 2020, were enrolled in this retrospective study. The bronchoalveolar lavage fluid (BALF) was obtained from lower respiratory tract from each patient. Routine methods (bacterial smear and culture) and mNGS were employed for the identification of pathogenic microorganisms in BALF. Results: The average patient age was 53.0 years, with 94.6% (106/112) obtaining pathogenic microorganism results. The total mNGS detection rate of pathogenic microorganisms significantly surpassed conventional methods (93.7% vs. 32.1%, P < 0.05). Notably, 75% of patients (84/112) were found to have bacteria by mNGS, but only 28.6% (32/112) were found to have bacteria by conventional approaches. The most commonly detected bacteria included Acinetobacter baumannii (19.6%), Klebsiella pneumoniae (17.9%), Pseudomonas aeruginosa (14.3%), Staphylococcus faecium (12.5%), Enterococcus faecium (12.5%), and Haemophilus parainfluenzae (11.6%). In 29.5% (33/112) of patients, fungi were identified using mNGS, including 23 cases of Candida albicans (20.5%), 18 of Pneumocystis carinii (16.1%), and 10 of Aspergillus (8.9%). However, only 7.1 % (8/112) of individuals were found to have fungi when conventional procedures were used. The mNGS detection rate of viruses was significantly higher than the conventional method rate (43.8% vs. 0.9%, P < 0.05). The most commonly detected viruses included Epstein-Barr virus (15.2%), cytomegalovirus (13.4%), circovirus (8.9%), human coronavirus (4.5%), and rhinovirus (4.5%). Only 29.4% (33/112) of patients were positive, whereas 5.4% (6/112) of patients were negative for both detection methods as shown by Kappa analysis, indicating poor consistency between the two methods (P = 0.340; Kappa analysis). Conclusion: Significant benefits of mNGS have been shown in the detection of pathogenic microorganisms in patients with pulmonary infection. For those with suboptimal therapeutic responses, mNGS can provide an etiological basis, aiding in precise anti-infective treatment.

The Influence of Different Extraction Techniques on the Chemical Profile and Biological Properties of Oroxylum indicum: Multifunctional Aspects for Potential Pharmaceutical Applications.

Oroxylum indicum (L.) Kurz (Bignoniaceae), a traditional Chinese herbal medicine, possesses various biological activities including antioxidant, anti-inflammatory, antibacterial, and anticancer. In order to guide the practical application of O. indicum in the pharmaceutical, food, and cosmetic industries, we evaluated the effects of five different extraction techniques (maceration extraction (ME), oxhlet extraction (SOXE), ultrasound-assisted extraction (UAE), tissue-smashing extraction (TSE), and accelerated-solvent extraction (ASE)) with 70% ethanol as the solvent on the phytochemical properties and biological potential. The UHPLC-DAD Orbitrap Elite MS technique was applied to characterize the main flavonoids in the extracts. Simultaneously, the antioxidant and enzyme inhibitory activities of the tested extracts were analyzed. SOXE extract showed the highest total phenolic content (TPC, 50.99 ± 1.78 mg GAE/g extract), while ASE extract displayed the highest total flavonoid content (TFC, 34.92 ± 0.38 mg RE/g extract), which displayed significant correlation with antioxidant activity. The extract obtained using UAE was the most potent inhibitor of tyrosinase (IC50: 16.57 ± 0.53 mg·mL-1), while SOXE extract showed the highest activity against α-glucosidase (IC50: 1.23 ± 0.09 mg·mL-1), succeeded by UAE, ME, ASE, and TSE extract. In addition, multivariate analysis suggested that different extraction techniques could significantly affect the phytochemical properties and biological activities of O. indicum. To sum up, O. indicum displayed expected biological potential and the data collected in this study could provide an experimental basis for further investigation in practical applications.

Is rosuvastatin protective against sepsis-associated encephalopathy? A secondary analysis of the SAILS trial.

BACKGROUND: Sepsis is a common cause of death in emergency departments and sepsis-associated encephalopathy (SAE) is a major complication. Rosuvastatin may play a neuroprotective role due to its protective effects on the vascular endothelium and its anti-inflammatory functions. Our study aimed to explore the potential protective function of rosuvastatin against SAE. METHODS: Sepsis patients without any neurological dysfunction on admission were prospectively enrolled in the "Rosuvastatin for Sepsis-Associated Acute Respiratory Distress Syndrome" study (SAILS trial, ClinicalTrials.gov number: NCT00979121). Patients were divided into rosuvastatin and placebo groups. This is a secondary analysis of the SAILS dataset. Baseline characteristics, therapy outcomes, and adverse drug events were compared between groups. RESULTS: A total of 86 patients were eligible for our study. Of these patients, 51 were treated with rosuvastatin. There were significantly fewer cases of SAE in the rosuvastatin group than in the placebo group (32.1% vs. 57.1%, P=0.028). However, creatine kinase levels were significantly higher in the rosuvastatin group than in the placebo group (233 [22-689] U/L vs. 79 [12-206] U/L, P=0.034). CONCLUSION: Rosuvastatin appears to have a protective role against SAE but may result in a higher incidence of adverse events.

Recent advance in the discovery of tyrosinase inhibitors from natural sources via separation methods.

Tyrosinase (TYR) inhibitors are in great demand in the food, cosmetic and medical industrials due to their important roles. Therefore, the discovery of high-quality TYR inhibitors is always pursued. Natural products as one of the most important sources of bioactive compounds discovery have been increasingly used for TYR inhibitors screening. However, due to their complex compositions, it is still a great challenge to rapid screening and identification of biologically active components from them. In recent years, with the help of separation technologies and the affinity and intrinsic activity of target enzymes, two advanced approaches including affinity screening and inhibition profiling showed great promises for a successful screening of bioactive compounds from natural sources. This review summarises the recent progress of separation-based methods for TYR inhibitors screening, with an emphasis on the principle, application, advantage, and drawback of each method along with perspectives in the future development of these screening techniques and screened hit compounds.

Colonization Characteristics of Poplar Fungal Disease Biocontrol Bacteria N6-34 and the Inhibitory Effect on Pathogenic Fungi by Real-Time Fluorescence Quantitative PCR Detection.

Botryosphaeria dothidea is one of the most important diseases which can cause poplar canker. In our previous study, the endophytic Bacillus subtilis N6-34 screened from poplar tissue was found to be an antagonistic strain against B. dothidea. In order to ascertain the colonization rule of B. subtilis N6-34 in poplar plants, colonization of B. subtilis N6-34 labeled with a green fluorescent protein (GFP) was investigated in poplar plants and the rhizosphere soil. To confirm the inhibitory effect of the strain N6-34 on pathogenic fungi, real-time fluorescent quantitative PCR experiment with Fusarium oxysporum as the target strain was carried out. Firstly, a plasmid (pHT01-P43GFPmut3a) containing gfp gene was successfully transformed into wild B. subtilis N6-34, which has the similar characteristics with the strain N6-34 in cell growth and antifungal activity. The poplar pot experiments were carried out to examine the colonization rules and colonization quantity in poplar plants and rhizosphere soil. Observation with a confocal laser scanning microscope showed that GFP-labeled B. subtilis N6-34 (N6-34-GFP) could colonize in primary root, lateral root and adventitious root. With the extension of inoculation time, the colonization quantity of N6-34-GFP in the rhizosphere soil and poplar plants showed a trend of first increasing, then stabilizing for a period of time and then decreasing. The real-time fluorescent quantitative PCR result showed a gradual decrease in the number of F. oxysporum with increasing inoculation time. Therefore, N6-34-GFP exhibited colonization in the rhizosphere soil and different parts of poplar plants. In addition, the strain N6-34 could inhibit the growth of pathogenic fungi. The ability of B. subtilis N6-34 to colonize in the rhizosphere soil and poplar plants and to inhibit fungal growth in vitro suggest a potential application of this strain as a biological control agent.

Efficacy and safety of corticosteroids in immunocompetent patients with septic shock.

BACKGROUND: The use of corticosteroids in septic shock has been studied for many decades but yielded conflicting results. We conducted a systematic review to evaluate the efficacy and the safety of corticosteroids in immunocompetent patients with septic shock. METHODS: Medline via PubMed, Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, and EMBASE were searched from inception to March 2020. Two reviewers independently identified randomized controlled trials (RCTs) comparing corticosteroids with a control group for immunocompetent patients with septic shock. Data were abstracted and reported following the Cochrane Handbook for Systematic Review of Intervention and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The efficacy outcome included mortality and shock reversal. The safety outcomes were infection, gastrointestinal bleeding, and hyperglycemia. RESULTS: Nine RCTs with a total of 1,298 patients were included. Compared with the control group, corticosteroid group did not lower the short-term (28 or 30 days) mortality (risk ratio [RR] 0.95, 95% confidence interval (CI) 0.85 to 1.06, inconsistency [I 2]=0%, trial sequential analysis [TSA]-adjusted CI 0.83 to 1.09, moderate-certainty evidence). Corticosteroids significantly shortened the time to shock reversal compared with the control group (mean difference [MD] -21.56 hours; 95% CI -32.95 to -10.16, I 2=0%; TSA-adjusted CI -33.33 to -9.78, moderate-certainty evidence). The corticosteroid treatment was associated with an increased risk of hyperglycemia but not the infection or gastrointestinal bleeding. CONCLUSIONS: The corticosteroid treatment is not associated with lower short- or long- term mortality compared with placebo in immunocompetent patients with septic shock. However, corticosteroids significantly shorten the time to shock reversal without increasing the risk of infection. The patient's immune status should also be considered during clinical treatment and clinical trials in future.

Immunosuppressive drugs to reduce the mortality rate in patients with moderate to severe paraquat poisoning: A Meta-analysis.

The benefits and adverse effects of immunosuppressive drugs (ISDs) in patients with paraquat (PQ) poisoning have not been thoroughly assessed. This meta-analysis study aims to evaluate the effect of ISDs in patients with moderate to severe PQ poisoning. We searched PubMed, Embase, Cochrane Library, Ovid Medline, CNKI and Wanfang Data from inception to January 2019. The Mantel-Haenszel method with a random-effects model was used to calculate the pooled relative risks (RRs) and 95% Confidence Intervals (CIs) as described by DerSimonian and Laird. An L'Abbé plot was drawn to explore the relationship between the degree of poisoning and mortality. Four randomized controlled trials, two prospective and seven retrospective studies were identified. ISDs were significantly associated with reduced mortality (RR 0.76; 95% CI, 0.58-0.99) and the incidence rate of multiple-organ dysfunction syndrome (MODS) (RR 0.63; 95% CI, 0.48-0.83) in patients with moderate to severe PQ poisoning. They were not associated with an increased incidence rate of hepatitis and reduced incidence rate of acute renal failure and hypoxia. The L'Abbé plot results showed a slight increase in mortality rate in the ISD group with increased mortality in the placebo group. This indicates a possible advantage of ISDs in most of the patients with severe PQ poisoning. These findings suggest that ISDs may reduce the mortality and incidence rate of MODS in moderate to severe PQ poisoning patients, and severe PQ poisoning patients might benefit more from ISDs.

Role of penehyclidine in acute organophosphorus pesticide poisoning.

BACKGROUND: Penehyclidine is a newly developed anticholinergic agent. We aimed to investigate the role of penehyclidine in acute organophosphorus pesticide poisoning (OP) patients. METHODS: We searched the Pubmed, Cochrane library, EMBASE, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical literature (CBM) and Wanfang databases. Randomized controlled trials (RCTs) recruiting acute OP patients were identified for meta-analysis. Main outcomes included cure rate, mortality rate, time to atropinization, time to 60% normal acetylcholinesterase (AchE) level, rate of intermediate syndrome (IMS) and rate of adverse drug reactions (ADR). RESULTS: Sixteen RCTs involving 1,334 patients were identified. Compared with the atropine- or penehyclidine-alone groups, atropine combined with penehyclidine significantly increased the cure rate (penehyclidine+atropine vs. atropine, 0.97 vs. 0.86, RR 1.13, 95% CI [1.07-1.19]; penehyclidine+atropine vs. penehyclidine, 0.93 vs. 0.80, RR 1.08, 95% CI [1.01-1.15]) and reduced the mortality rate (penehyclidine+atropine vs. atropine, 0.015 vs. 0.11, RR 0.17, 95% CI [0.06-0.49]; penehyclidine+atropine vs. penehyclidine, 0.13 vs. 0.08, RR 0.23, 95% CI [0.04-1.28]). Atropine combined with penehyclidine in OP patients also helped reduce the time to atropinization and AchE recovery, the rate of IMS and the rate of ADR. Compared with a single dose of atropine, a single dose of penehyclidine also significantly elevated the cure rate, reduced times to atropinization, AchE recovery, and rate of IMS. CONCLUSION: Atropine combined with penehyclidine benefits OP patients by enhancing the cure rate, mortality rate, time to atropinization, AchE recovery, IMS rate, total ADR and duration of hospitalization. Penehyclidine combined with atropine is likely a better initial therapy for OP patients than atropine alone.

Identification and characterisation of tumour necrosis factor receptor (TNFR) associated factor 3 from Nile tilapia, Oreochromis niloticus.

In this study, we cloned the complementary (c)DNA sequences of tumour necrosis factor receptor (TNFR)-associated factor 3 (traf3) in Nile tilapia, Oreochromis niloticus. The expression patterns of the traf3 gene were investigated and preliminary functional analyses were performed. In healthy fish, traf3 transcript was broadly expressed in all examined tissues, with the highest expression level in the blood and the lowest in the liver. The traf3 gene reached its highest expression at 8 days post-fertilisation (dpf) during embryonic development. Moreover, we found that expression of traf3 was clearly altered following stimulation with Streptococcus agalactiae in vivo and that traf3 could be induced by lipopolysaccharides (LPS), Poly I: C and S. agalactiae WC1535 in Nile tilapia macrophages. Overexpression in 293T cells showed that Traf3 protein was mainly distributed in the cytoplasm and could significantly increase nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation. Taken together, these results implied that traf3 could play important roles in the immune response to pathogen invasion.

Efficacy of initial haemopurification strategy for acute paraquat poisoning in adults: study protocol for a randomised controlled trial (HeSAPP).

INTRODUCTION: Paraquat (PQ) is a widely used herbicide which is inexpensive and easily accessible for people in rural areas. A small amount of PQ ingestion could be lethal, yet currently, the optimal treatment is still controversial. Extracorporeal therapies (ECTR) have been practised in PQ poisoning management, though limited evidence could be obtained to suggest its superiority over conservative therapy. Haemodialysis (HD) and haemoperfusion (HP) are most commonly used, while some institutions also choose HP-HD concurrent therapy. The object of the present trial is to investigate whether haemopurification therapy can reduce mortality compared with conservative therapy. METHODS AND ANALYSIS: This is a planned single-centre, non-blinded, randomised controlled trial. Acute PQ poisoned adults who have orally ingested PQ within 24 hours would be recruited. A total of 360 patients would be recruited and randomly assigned to four groups, that is, HP, HD, concurrent HP-HD and control, at a 1:1:1:1 ratio. Subjects would be also stratified by their urine dithionite test results. Primary outcome is 28-day all-cause mortality. Secondary outcomes include survival time, all-cause mortality at the 3rd, 7th and 60th day, rate of major complications, Acute Physiologic and Chronic Health Evaluation score and Poisoning Severity Score, etc. ETHICS AND DISSEMINATION: The protocol and informed consent documents have been approved by the Ethics Committee of The First Affiliated Hospital of Zhengzhou University in September 2017 (approval number: 2017-KY-10). The result of this trial would be submitted to peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT03314909; Pre-results.

Downregulation of Akt2 attenuates ER stress-induced cytotoxicity through JNK-Wnt pathway in cardiomyocytes.

Akt, also known as protein kinase B (PKB), is a serine/threonine kinase that promotes survival and growth in response to extracellular signals. Akt1 has been demonstrated to play vital roles in cardiovascular diseases, but the role of Akt2 in cardiomyocytes is not fully understood. This study investigated the effect of Akt2 knockdown on tunicamycin (TM)-induced cytotoxicity in cardiomyocytes and the underlying mechanisms with a focus on the JNK-Wnt pathway. TM treatment significantly increased the expression of Akt2 at both mRNA and protein levels, which was shown to be mediated by the induction of reactive oxygen species (ROS). Knockdown of Akt2 expression via siRNA transfection markedly increased cell viability, decreased lactate dehydrogenase (LDH) release and reduced cell apoptosis after TM exposure. The results of western blot showed that downregulation of Akt2 also attenuated the TM-induced activation of the unfolded protein response (UPR) factors and ER stress associated pro-apoptotic proteins. In addition, Si-Akt2 transfection partially prevented the TM-induced decrease in nuclear localization of ß-catenin. By using the selective inhibitor SP-600,125 to inhibit JNK phosphorylation, we found that knockdown of Akt2-induced protection and inhibition of ER stress was mediated by reversing TM-induced decrease of Wnt through the JNK pathway. In summary, these data suggested that Akt2 play a pivotal role in regulating cardiomyocyte survival during ER stress by modulating the JNK-Wnt pathway.

Complete Genome Sequence of Actinomyces hongkongensis HKU8T Isolated from Human Blood.

Members of the genus Actinomyces are strongly associated with human diseases. We present here the complete genome sequence of Actinomyces hongkongensis HKU8T, which consists of one circular chromosome. The strain characteristically contains various genes encoding for enzymes involved in arylamidase utilization.

Chemical constituents of Abies fabri.

Systematic phytochemical investigations on Abies fabri resulted in the isolation of 94 compounds, consisting of 68 terpenoids, six lignans, seven flavonoids, and 13 other miscellaneous chemical constituents. Their structures were elucidated on the basis of spectroscopic methods, and the absolute configurations of three of these previously unknown compounds were determined by Cu-Kα X-ray crystallographic analysis. Twelve previously unreported compounds, one artifact, and one potential artifact were identified, including six triterpenoids, four diterpenoids, two sesquiterpenoids, one lignan, and one phenol. 23-Hydroxy-3-oxolanosta-8,24-dien-26,23-olide showed weak cytotoxic activity against A549 and THP-1 cells with the IC50 values of 5.3 and 5.1 µM, respectively.

Chemical constituents of Abies nukiangensis.

During a survey on chemical constituents of Abies nukiangensis, seven previously unreported compounds, including six triterpenes (1-6) and one phenol (7) were isolated and characterized, together with 37 known miscellaneous chemical constituents. The structures of compounds 1-7 were established mainly by extensive analysis of the 1D and 2D NMR, as well as HRMS data. The absolute configurations of compounds 1 and 8 were confirmed unambiguously by the Cu-Kα X-ray crystallography. Compounds 3 and 8-10 showed significant anti-hepatitis C virus effects with EC50 values of 3.73, 2.67, 1.33 and 2.25µM, respectively.

ß-Receptor blocker influences return of spontaneous circulation and chemical examination in rats during cardiopulmonary resuscitation.

OBJECTIVE: We investigated the influence of ß-receptor blocker metoprolol on return of spontaneous circulation (ROSC) during cardiopulmonary resuscitation (CPR) in rats with induced myocardial infarction (MI). METHODS: Male Sprague-Dawley rats were randomly divided into three groups: the sham-operated group, the MI group without metoprolol, which was fed the vehicle, and the MI+metoprolol group receiving intragastric metoprolol. Each group was further divided randomly into three subgroups, depending on the dosage of epinephrine administered during subsequent CPR applied after the induction of asphyxial cardiac arrest. RESULTS: The ROSC rate was significantly decreased in the low dose subgroup of MI group, unchanged in the medium dose subgroup of MI group, and significantly decreased in the high dose subgroup of MI group, compared with the same dose subgroup of sham-operated group. MI+metoprolol group had a lower ROSC rate than MI group in the medium dose subgroup, and a higher ROSC rate than MI group in the high dose subgroup. There was no difference in blood K(+) values of successful rats between MI group and MI+metoprolol group. The rats with successful CPR had lower blood K(+) values than rats with unsuccessful CPR in each of the three treatment groups. CONCLUSIONS: Metoprolol administered to MI rats over a long period significantly improved ROSC rates under an appropriate dose of epinephrine during CPR. An increasing high blood K(+) value would attenuate the rate of a successful CPR.

[Prevention of non-acute stent thrombosis after drug-eluting stent implantation].

OBJECTIVE: To decrease acute myocardial infarction (AMI) and incidence of other cardiovascular event after drug-eluting stent (DES) implantation, so as to prevent non-acute stent thrombosis. METHODS: Patients who had undergone percutaneous coronary intervention with DES from January 2005 to September 2008 were enrolled. All patients were randomly assigned into two groups with different treatment protocols for anti-thrombosis. The patients in control group were treated with aspirin and clopidogrel for anti-thrombosis (double anti-treatment), while those in observation group were treated with tirofiban and warfarin on top of basic treatment with double anti-thromotic drugs. The latter group of patients received warfarin in addition for 6 months, with the international normalized ratio (INR) maintained at 1.5-2.0. The patients in both groups were followed up at 1-3 months after the treatment, and the deadline was October 2012. Stent thrombosis was assessed by the definition of Dublin for Academic Research Consortium. The main ending point indexes were main adverse cardiac and cerebral events (MACCE), and the secondary ending point indexes were incidence of bleeding and other adverse events. RESULTS: A total of 505 consecutive patients treated with DES implantation were enrolled, 245 in the observation group while 260 in the control. The rates of MACCE at 1- 48 months after operation in observational group were significantly lower than those in control group (1 month: 0.41% vs. 3.08%, 2-6 months: 0 vs. 2.31%, 7-12 months: 0.82% vs. 4.23%, 13-24 months: 1.22% vs. 8.85%, 25- 48 months: 2.04% vs. 12.31%, all P<0.05). Cardiac death (13-24 months: 0.41% vs. 3.08%, 25-48 months: 0.82% vs. 4.23%), non-lethal acute myocardial infarction unrelated with target vessels (25-48 months: 0.41% vs. 3.08%), and rates of revascularization of target vessels (13-24 months: 0.41% vs. 3.08%, 25-48 months: 0.82% vs. 4.23%) in observation group were significantly lower than those in the control group (all P<0.05). The rates of sub-acute stent thrombosis, late stent thrombosis, and very late stent thrombosis in observation group were significantly lower than those in control group (0 vs. 2.31%, 0.82% vs. 4.23%, 1.63% vs. 8.46%, all P<0.05). The rate of bleeding in observational group was a litter higher than control group (3.27% vs. 1.54%, P=0.167) and no severe bleeding occurred. Other severe adverse events were not found in both groups. CONCLUSION: The results indicate that tirofiban and warfarin combined with aspirin and clopidogrel could reduce the rates of MACCE and bleeding, and it could prevent non-acute stent thrombosis safely and effectively after percutaneous coronary intervention with DES.

Cytotoxic triterpenoids from Abies recurvata.

Nine triterpenoids (neoabiestrines A-I, 1-9) including six rearranged lanostanes (1-6) and a rare cycloart-7-ene (7) were isolated from Abies recurvata together with ten known compounds. Their structures were determined by detailed analysis of NMR and MS spectroscopic data. The absolute configurations of 1 and 8 were determined by Cu-Ka X-ray crystallography. Compound 6 showed potent anti-proliferative effect against THP-1 tumor cells with an IC(50) value of 17.8 µg/mL.

[Effects of ulinastatin on myocardial injury induced by acute paraquat poisoning].

OBJECTIVE: To investigate the effects of ulinastatin (UTI) on myocardial injury induced by acute paraquat poisoning. METHODS: Twenty-four Japan white rabbits were divided into control group, model group (37 mg/kg paraquat intraperitoneally once), UTI low dosage group and high dosage group [25 kU×kg(-1)×d(-1) and 50 kU×kg(-1)×d(-1) UTI was intravenously injected respectively for 9 days beginning from 1 week before poisoning] through random number table. Rabbits were sacrificed 24 hours after the last UTI administration. Left ventricle of hearts were harvest, and tissue hydroxyproline (HYP) contents were determined. Matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) transcriptional levels were assayed respectively with reverse transcription-polymerase chain reaction (RT-PCR). Expression levels of MMP-2 in tissue of left ventricle were quantified with immunohistochemistry. RESULTS: Compared with normal myocardium, acute paraquat poisoning induced elevated HYP (mg/g) content significantly (3.85 ± 0.36 vs. 2.52 ± 0.29, P < 0.05); with RT-PCR and immunohistochemistry, it was shown that both mRNA expression levels and immunohistochemistry score of MMP-2 were much higher (mRNA: 2.07 ± 0.57 vs. 1.00 ± 0.35; immunohistochemistry score: 2.24 ± 0.82 vs. 1.40 ± 0.62, both P < 0.05). TIMP-2 appeared to be down-regulated in mRNA expression level (0.78 ± 0.24 vs. 1.00 ± 0.17, P > 0.05). Disorganized cardiocytes were observed. Compared with paraquat poisoning model, low and high UTI administration produced depression of tissue HYP contents (3.40 ± 0.48, 3.12 ± 0.43 vs. 3.85 ± 0.36, P > 0.05 and P < 0.05). With low or high dosage of UTI reduced mRNA expression levels and immunohistochemical scores of MMP-2 in left ventricle were observed (mRNA: 1.86 ± 0.44, 1.58 ± 0.46 vs. 2.07 ± 0.57, P > 0.05 and P < 0.05; immunohistochemical score: 1.93 ± 0.86, 1.75 ± 0.67 vs. 2.24 ± 0.82, both P < 0.05), and TIMP-2 mRNA level was increased slightly, though there was no significant differences (0.82 ± 0.35, 0.94 ± 0.33 vs. 0.78 ± 0.24, both P > 0.05). Improvements in disordered myocardium were demonstrated. CONCLUSIONS: UTI significantly attenuated myocardial injury induced by acute paraquat poisoning. Its mechanism might be related to a reduction of expression level of MMP-2 in tissue, with a dose-dependent manner.