Promising Therapeutic Candidate for Myocardial Ischemia/Reperfusion Injury: What Are the Possible Mechanisms and Roles of Phytochemicals?

Percutaneous coronary intervention (PCI) is one of the most effective reperfusion strategies for acute myocardial infarction (AMI) despite myocardial ischemia/reperfusion (I/R) injury, causing one of the causes of most cardiomyocyte injuries and deaths. The pathological processes of myocardial I/R injury include apoptosis, autophagy, and irreversible cell death caused by calcium overload, oxidative stress, and inflammation. Eventually, myocardial I/R injury causes a spike of further cardiomyocyte injury that contributes to final infarct size (IS) and bound with hospitalization of heart failure as well as all-cause mortality within the following 12 months. Therefore, the addition of adjuvant intervention to improve myocardial salvage and cardiac function calls for further investigation. Phytochemicals are non-nutritive bioactive secondary compounds abundantly found in Chinese herbal medicine. Great effort has been put into phytochemicals because they are often in line with the expectations to improve myocardial I/R injury without compromising the clinical efficacy or to even produce synergy. We summarized the previous efforts, briefly outlined the mechanism of myocardial I/R injury, and focused on exploring the cardioprotective effects and potential mechanisms of all phytochemical types that have been investigated under myocardial I/R injury. Phytochemicals deserve to be utilized as promising therapeutic candidates for further development and research on combating myocardial I/R injury. Nevertheless, more studies are needed to provide a better understanding of the mechanism of myocardial I/R injury treatment using phytochemicals and possible side effects associated with this approach.

Precise diagnosis of Neisseria macacae infective endocarditis assisted by nanopore sequencing.

Infective endocarditis caused by Neisseria macacae in humans is extremely rare. We presented here a case of N. macacae infective endocarditis in a 61-year-old man with a native aortic valve infection. N. macacae was isolated from blood culture and was detected by nanopore-based metagenomic sequencing in the vegetations. Finally, the patient recovered completely after surgery and antibiotic therapy.

Improving Pulmonary Infection Diagnosis with Metagenomic Next Generation Sequencing.

Pulmonary infections are among the most common and important infectious diseases due to their high morbidity and mortality, especially in older and immunocompromised individuals. However, due to the limitations in sensitivity and the long turn-around time (TAT) of conventional diagnostic methods, pathogen detection and identification methods for pulmonary infection with greater diagnostic efficiency are urgently needed. In recent years, unbiased metagenomic next generation sequencing (mNGS) has been widely used to detect different types of infectious pathogens, and is especially useful for the detection of rare and newly emergent pathogens, showing better diagnostic performance than traditional methods. There has been limited research exploring the application of mNGS for the diagnosis of pulmonary infections. In this study we evaluated the diagnostic efficiency and clinical impact of mNGS on pulmonary infections. A total of 100 respiratory samples were collected from patients diagnosed with pulmonary infection in Shanghai, China. Conventional methods, including culture and standard polymerase chain reaction (PCR) panel analysis for respiratory tract viruses, and mNGS were used for the pathogen detection in respiratory samples. The difference in the diagnostic yield between conventional methods and mNGS demonstrated that mNGS had higher sensitivity than traditional culture for the detection of pathogenic bacteria and fungi (95% vs 54%; p<0.001). Although mNGS had lower sensitivity than PCR for diagnosing viral infections, it identified 14 viral species that were not detected using conventional methods, including multiple subtypes of human herpesvirus. mNGS detected viruses with a genome coverage >95% and a sequencing depth >100× and provided reliable phylogenetic and epidemiological information. mNGS offered extra benefits, including a shorter TAT. As a complementary approach to conventional methods, mNGS could help improving the identification of respiratory infection agents. We recommend the timely use of mNGS when infection of mixed or rare pathogens is suspected, especially in immunocompromised individuals and or individuals with severe conditions that require urgent treatment.

Tracking Carbapenem-Producing Klebsiella pneumoniae Outbreak in an Intensive Care Unit by Whole Genome Sequencing.

The presence of carbapenem-producing Klebsiella pneumoniae (CP-Kp) is a serious threat to the control of nosocomial infections. Plasmid-mediated horizontal transfer of the resistance gene makes it difficult to control hospital-acquired CP- Kp infections. Nine CP- Kp strains were isolated during an outbreak in the intensive care unit of Shanghai Huashan hospital in east China. We conducted a retrospective study to identify the origin and route of transmission of this CP-Kp outbreak. Whole-genome sequencing (WGS) analysis was performed on 9 clinical isolates obtained from 8 patients, and the results were compared to clinical and epidemiological records. All isolates were ST11 CP-Kp. Single-nucleotide polymorphisms and the presence and structure of plasmids indicated that this CP-Kp outbreak had different origins. These 9 isolates were partitioned into two clades according to genetic distance. Four plasmids, CP002474.1, CP006799.1, CP018455.1, and CP025459.1, were detected among the 9 isolates. The plasmid phylogeny and antibiotic resistance (AR) gene profile results were consistent with the sequencing results. We found that two clades of CP-Kp were responsible for this nosocomial outbreak and demonstrated the transmission route from two index patients. Plasmid carriage and phylogeny are a useful tool for identifying clades involved in disease transmission.

Case report: lactic acidosis and rhabdomyolysis during telbivudine and tenofovir treatment for chronic hepatitis B.

BACKGROUND: Current treatment options for chronic hepatitis B (CHB) are pegylated interferon alpha and nucleoside analogues (NAs). NAs have relatively fewer side effects than interferon alpha, and generally well tolerated. Previously 12.9% of patients on telbivudine treatment were reported to develop severe elevation of serum creatine phosphokinase (CPK) levels, but related clinical disease, like lactic acidosis (LA) and rhabdomyolysis (RM) were rare. The pathophysiology may be mitochondrial toxicity, for the NAs inhibit not only hepatitis B virus (HBV) polymerase, but also the host mitochondrial DNA polymerase γ. As mitochondria are the main sites of oxidative phosphorylation, there will be an increase of pyruvate reduction to lactic acid and insufficient adenosine triphosphate. The accumulation of lactic acid causes LA, while lack of energy leads to cell dysfunction and mitochondria-associated disease, including RM. All five NAs, except tenofovir, have been reported causing LA and RM. Here we report the first case of CHB patients developing fatal LA and RM during telbivudine and tenofovir treatment. CASE PRESENTATION: The patient is a 51-year-old man who was hospitalized in November 2015. He had taken telbivudine regularly because of CHB. Later, tenofovir was added to antiviral treatment because of HBV resistance. Then he had myalgia, chest tightness and anorexia. The blood lactate was 12.7 mmol/L. The arterial blood gas analysis showed pH 7.25, base excess 21.1 mmol/L. CPK was 991 U/L, myoglobin was 1745 ng/ml and creatine was 83 µmol/L. Abdomen magnetic resonance revealed cirrhosis. Muscle biopsy revealed myogenic lesion with abnormality of mitochondria and fat metabolism. The patient was diagnosed with Hepatitis B envelope Antigen positive CHB, cirrhosis, LA and RM characterized by myalgia and elevated myoglobin. He was given tenofovir alone as antiviral treatment instead. After hemodialysis and 4 weeks` treatment of corticosteroids, his symptoms recovered, and blood lactate gradually returned to a normal range. CONCLUSIONS: This case shows that tenofovir may trigger muscle damage and fatal RM in combination with telbivudine treatment in CHB patients. Thus, patients receiving tenofovir and telbivudine should be closely monitored for muscular abnormalities, blood lactate level and other mitochondrial toxicity associated side effects.

Biofilm Formation in Klebsiella pneumoniae Bacteremia Strains Was Found to be Associated with CC23 and the Presence of wcaG.

Klebsiella pneumoniae bacteremia biofilm traits and distribution characteristics have not been clarified. This study aimed to determine the prevalence and characteristics of K. pneumoniae bacteremia biofilm formation (BF) and to explore the virulence factors associated with K. pneumoniae BF. A total of 250 K. pneumoniae bacteremia isolates were collected from patients in Shenzhen and Shanghai, China. Virulence genes in their genomes were detected by PCR. The isolates were subjected to multilocus sequence typing (MLST) and clonal complex (CC) classification based on housekeeping genes. Biofilms were detected by crystal violet staining. Greater BF was observed in isolates from young adults (<40 years old) than in those from seniors (≥65 years old; P = 0.002). MLST yielded 65 different sequence types (STs), with the most represented STs being ST11, ST23, and ST65, and the main CCs were CC23 and CC65; CC23 isolates exhibited greater BF than CC65 or ST11 isolates (both P < 0.001). BF was more pronounced among magA(K1), aero+, rmpA+, rmpA2+, allS+, wcaG+, and iutA+ isolates than in isolates that were negative for these virulence factors. Multivariate regression analysis revealed only wcaG as an independent risk factor for BF (odds ratio 11.426, P < 0.001), and BF was decreased when wcaG was silenced by antisense RNA. In conclusion, BF in K. pneumoniae bacteremia isolates was found to be associated with CC23 classification and the presence of the wcaG virulence factor gene.

Lactic acidosis during telbivudine treatment for HBV: a case report and literature review.

All oral nucleoside analogues against hepatitis B virus, with an exception of telbivudine, have been reported causing lactic acidosis (LA). Here we report the first case of chronic hepatitis B developing severe refractory LA during telbivudine monotherapy. A 36-year-old man of Chinese origin received telbivudine antiviral treatment for chronic hepatitis B. After 11 mo of therapy, he developed anorexia, nausea, and vomiting with mild muscle weakness. The patient was found with elevated serum creatine phosphokinase up to 3683 U/L (upper limit of normal 170 U/L) and marked LA. LA did not resolve immediately following discontinuation of telbivudine. His condition began to improve after hemodialysis treatment for 16 times and usage of glucocorticosteroid. The patient fully recovered after 16 wk of treatment. This is the first documented case with severe LA caused by telbivudine monotherapy. Besides serum creatine phosphokinase, blood lactate level should also be closely monitored in patients receiving telbivudine.

[Evaluation of low-dose amphotericin B and flucytosine in the treatment of cryptococcal meningitis].

OBJECTIVE: To evaluate the efficacy and safety of low-dose amphotericin B (< 0.7 mg x kg(-1) x d(-1)) and flucytosine in patients with non-AIDS-associated cryptococcal meningitis. METHODS: In non-AIDS patients with cryptococcal meningitis admitted to Huashan Hospital, Fudan University in Shanghai from January 1998 to December 2007, 31 were initially treated with low-dose amphotericin B and flucytosine for more than 1 week. The clinical characteristics, clinical responses, drug-related adverse reactions and outcome of these patients were retrospectively evaluated. RESULTS: Among the 31 patients enrolled in this study, 8 patients had one or more predisposing factors. Headache, fever, meningeal irritation and vomiting were common clinical symptoms and signs when cryptococcal meningitis was diagnosed. The result of cranial CT scan and/or MRI showed abnormality in 22 cases (78.6%). When the therapy of low-dose amphotericin B and flucytosine ended, the complete response rate was 19.4% (6/31), partial response rate was 54.8% (17/31), and total effective rate was 74.2%. Except for 1 patient lost to follow-up, the 1-year attributable and all-cause mortality among the remaining 30 patients were 0 (0/30) and 10.0% (3/30) respectively. On the other hand, 26 (83.9%) patients had amphotericin B-related adverse reactions, including renal impairment, liver injury, arrhythmia, and anemia, etc. However, most of these reactions were tolerable. CONCLUSION: Low-dose amphotericin B and flucytosine can be used in non-AIDS-associated cryptococcal meningitis with both acceptable efficacy and safety.

[A new multiplex allele-specific polymerase chain reaction assay for detection of rifampin-resistant Mycobacterium tuberculosis].

OBJECTIVE: To develop a new multiplex allele-specific polymerase chain reaction (MAS-PCR) assay to detect the main mutations in the rifampin resistance dependent region, which has been reported to account for the majority of clinic Mycobacterium tuberculosis resistant to rifampin. METHODS: Based on the sequence of rpoB gene, three specific primers were designed for the MAS-PCR to detect the most common mutations in codons 531, 526, 516 of rpoB gene. RESULTS: The purified DNA preparations of 91 clinical strains of Mycobacterium tuberculosis were used to optimize the PCR. The mutations in codon 531, 526, 516 were detected by the MAS-PCR. Compared with the results of direct sequencing of rpoB gene, no mutation was detected in the sensitive strains. For rifampin-resistant strains, the total sensitivity was 81.5% (66/81). CONCLUSIONS: MAS-PCR is a new molecular method with a high sensitivity and specificity, which can be used to detect the 3 main mutations of rpoB gene rapidly and economically. It can be used in clinical laboratories to detect the rifampin-resistant strains of Mycobacterium tuberculosis.

[Testosterone and male osteoporosis].

There are various causes for male osteoporosis. The low testosterone level is one of the important reasons. Androgen does not only play an important role in gaining the peak bone mass and maintaining the bone mass, but also has an intimate correlation with the bone loss with ageing. Androgen affects osteoblasts through androgen receptors. Various local cell factors play regulating roles. The partial testosterone replacement therapy in aging men could elevate the bone mass density, but the advantages and the disadvantages should be observed further. The function of the estrogen in male osteoporosis is being noted as well.