Epidemiological characteristics, virulence potential, antimicrobial resistance profiles, and phylogenetic analysis of Aeromonas caviae isolated from extra-intestinal infections.

Objective: Aeromonas caviae (A. caviae) is one of the major etiological agents in human intestinal infections reported to be associated with a broad spectrum of extra-intestinal infections with increasing incidence over recent years. Although previous studies have established its significance as a causative agent of both bloodstream and gastrointestinal infections, the characteristics of A. caviae that cause extra-intestinal infections remain unilluminated.In this single-center retrospective study, we investigated epidemiological characteristics, antimicrobial resistance genes and phenotypes, virulence genes, and phyloevolution of 47 clinical A. caviae isolated from patients with extra-intestinal infections from 2017 to 2020. Methods: A. caviae strains were identified by biochemical tests and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF/MS), ultimately confirmed to species level by whole-genome sequencing (WGS). Antimicrobial resistance and virulence genes were identified using the Comprehensive Antibiotic Resistance Database (CARD) and the virulence factor database (VFDB), respectively. Phylogenetic analysis of 47 clinical strains was performed by combining with 521 A. caviae strains from NCBI database. Results: A. caviae was an opportunistic pathogen in immunocompromised patients, especially those with underlying hepatobiliary diseases and malignancies. 19 out of 47 isolates were identified as multidrug resistance (MDR) strains. Piperacillin-tazobactam, levofloxacin, gentamicin, amikacin with a resistance rate of less than 10% remained as options to treat extra-intestinal infections. 24 out of 47 isolates exhibited non-susceptibility to cephalosporins and cephamycins, all of which carried ß-lactamase gene, including bla MOX, bla PER-3, bla OXA, bla NDM, and bla CphA. Most stains (98%, 46/47) carried at least one of the virulence genes, but extra-intestinal infections had a low mortality rate. Phylogenetic analysis indicated the risk of nosocomial transmission but revealed no outbreak. However, the emergence of MDR and ß-lactamase resistance genes in extra-intestinal isolates of A. caviae is becoming an increasing risk to public health and requires attention. Conclusions: This study strengthen our understanding of A.caviae isolated from extra-intestinal infections. It may contribute to the management of extra-intestinal infections as well as the prevention and control of drug resistance.

Antifungal susceptibility profiles and drug resistance mechanisms of clinical Candida duobushaemulonii isolates from China.

Candida duobushaemulonii, type II Candida haemulonii complex, is closely related to Candida auris and capable of causing invasive and non-invasive infections in humans. Eleven strains of C. duobushaemulonii were collected from China Hospital Invasive Fungal Surveillance Net (CHIF-NET) and identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF), VITEK 2 Yeast Identification Card (YST), and internal transcribed spacer (ITS) sequencing. Whole genome sequencing of C. duobushaemulonii was done to determine their genotypes. Furthermore, C. duobushaemulonii strains were tested by Sensititre YeastOne™ and Clinical and Laboratory Institute (CLSI) broth microdilution panel for antifungal susceptibility. Three C. duobushaemulonii could not be identified by VITEK 2. All 11 isolates had high minimum inhibitory concentrations (MICs) to amphotericin B more than 2 µg/ml. One isolate showed a high MIC value of ≥64 µg/ml to 5-flucytosine. All isolates were wild type (WT) for triazoles and echinocandins. FUR1 variation may result in C. duobushaemulonii with high MIC to 5-flucytosine. Candida duobushaemulonii mainly infects patients with weakened immunity, and the amphotericin B resistance of these isolates might represent a challenge to clinical treatment.

Effects of hCG on DA neuronal death of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, with the incidence in men being about twice as compared to women. Gender differences may provide clues for finding key targets that mediate the death of dopaminergic (DA) neurons in PD. Luteinizing hormone (LH), analog of human chorionic gonadotropin (hCG), and their receptor, luteinizing hormone/choriogonadotropin receptor (LHCGR), are associated with the pathogenesis of PD. Movement-related symptoms are partially improved by hCG in PD patients. However, the relationship between hCG and PD, as well as its roles in mediating DA neuronal death, has not been elucidated. In this study, we investigated the potential of hCG as a treatment during PD progression. After establishment of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse models, we found that hCG restored the decrease of LHCGR activity caused by down-regulation of LH in the substantia nigra. Furthermore, the reduction of LHCGR activity led to DA neuronal death through knocking down the LHCGR in DA neurons by AAV-mTH-shRNA. Treatment with hCG alleviated the DA neuronal death induced by MPTP. Finally, hCG exerted neuroprotective effects by inhibiting the activation of glycogen synthase kinase 3 beta (GSK3ß) in our MPTP-induced PD mouse and MPP+-treated SH-SY5Y cell models. Together, these results demonstrate that hCG exerts neuroprotective effects for PD through LHCGR, and the inhibition of GSK3ß activation is involved in this protective effect, suggesting that hCG can be taken as a potential therapeutic for the treatment of PD.

Continual Decline in Azole Susceptibility Rates in Candida tropicalis Over a 9-Year Period in China.

BACKGROUND: There have been reports of increasing azole resistance in Candida tropicalis, especially in the Asia-Pacific region. Here we report on the epidemiology and antifungal susceptibility of C. tropicalis causing invasive candidiasis in China, from a 9-year surveillance study. METHODS: From August 2009 to July 2018, C. tropicalis isolates (n = 3702) were collected from 87 hospitals across China. Species identification was carried out by mass spectrometry or rDNA sequencing. Antifungal susceptibility was determined by Clinical and Laboratory Standards Institute disk diffusion (CHIF-NET10-14, n = 1510) or Sensititre YeastOne (CHIF-NET15-18, n = 2192) methods. RESULTS: Overall, 22.2% (823/3702) of the isolates were resistant to fluconazole, with 90.4% (744/823) being cross-resistant to voriconazole. In addition, 16.9 (370/2192) and 71.7% (1572/2192) of the isolates were of non-wild-type phenotype to itraconazole and posaconazole, respectively. Over the 9 years of surveillance, the fluconazole resistance rate continued to increase, rising from 5.7 (7/122) to 31.8% (236/741), while that for voriconazole was almost the same, rising from 5.7 (7/122) to 29.1% (216/741), with no significant statistical differences across the geographic regions. However, significant difference in fluconazole resistance rate was noted between isolates cultured from blood (27.2%, 489/1799) and those from non-blood (17.6%, 334/1903) specimens (P-value < 0.05), and amongst isolates collected from medical wards (28.1%, 312/1110) versus intensive care units (19.6%, 214/1092) and surgical wards (17.9%, 194/1086) (Bonferroni adjusted P-value < 0.05). Although echinocandin resistance remained low (0.8%, 18/2192) during the surveillance period, it was observed in most administrative regions, and one-third (6/18) of these isolates were simultaneously resistant to fluconazole. CONCLUSION: The continual decrease in the rate of azole susceptibility among C. tropicalis strains has become a nationwide challenge in China, and the emergence of multi-drug resistance could pose further threats. These phenomena call for effective efforts in future interventions.

Species Distribution and Antifungal Susceptibility of Invasive Candidiasis: A 2016-2017 Multicenter Surveillance Study in Beijing, China.

OBJECTIVE: Invasive candidiasis (IC), a life-threatening fungal infection prevalent among hospitalized patients, has highly variable regional epidemiology. We conducted a multicenter surveillance study to investigate recent trends in species distribution and antifungal susceptibility patterns among IC-associated Candida spp. in Beijing, China, from 2016 to 2017. MATERIALS AND METHODS: A total of 1496 non-duplicate Candida isolates, recovered from blood and other sterile body fluids of IC patients, were identified using matrix-assisted laser desorption/ionization time of flight mass spectrometry combined with ribosomal DNA internal transcribed spacer (ITS) region sequencing. Broth microdilution-based susceptibility testing using six antifungal agents was also conducted. RESULTS: Candida albicans was the most frequently isolated species (49.9%), followed by Candida tropicalis (15.5%), Candida glabrata (14.7%) and Candida parapsilosis (14.2%). No significant differences in species distribution were observed when compared with a 2012-2013 dataset. Overall, the rates of susceptibility to fluconazole and voriconazole were high among C. albicans (98% and 97.2%, respectively) and C. parapsilosis species complex (91.1% and 92%, respectively) isolates but low among C. tropicalis (81.5% and 81.1%, respectively) isolates. In addition, the rate of azole resistance among C. tropicalis isolates increased significantly (1.8-fold, P<0.05) compared with that observed in 2012-2013, while micafungin resistance rates were <5% for all tested Candida species. CONCLUSION: Our results suggest that species distribution has remained stable among IC-associated Candida isolates in Beijing. Resistance to micafungin was rare, but increased azole resistance among C. tropicalis isolates was noted. Our study provides information on local epidemiology that will be important for the selection of empirical antifungal agents and contributes to global assessments of antifungal resistance.

Chinese clinical practice guidelines for acute infectious diarrhea in children.

BACKGROUND: The guidelines addressed the evidence-based indications for the management of children with acute infectious diarrhea in Chinese pediatric population. DATA SOURCES: The experts group of evidence development put forward clinical problems, collects evidence, forms preliminary recommendations, and then uses open-ended discussions to form recommendations. The literature review was done for developing this guideline in databases including PubMed, Cochrane, EMBASE, China Biomedical Database, and Chinese Journal Full-text Database up to June 2013. Search the topic "acute diarrhea" or "enteritis" and "adolescent" or "child" or "Pediatric patient" or "Baby" or "Infant". RESULTS: For the treatment of mild, moderate dehydration, hypotonic oral rehydration solutions (ORS) are strongly recommended. Intravenous (IV) rehydration is recommended for severe dehydration, with a mixture of alkali-containing dextrose sodium solution. Nasogastric feeding tube rehydration is used for children with severe dehydration without IV infusion conditions with ORS solution. Regular feeding should resume as soon as possible after oral rehydration or IV rehydration. The lactose-free diet can shorten the diarrhea duration. Zinc supplements are recommended in children with acute infectious diarrhea. Saccharomyces boulardii and Lactobacillus Rhamnus are recommended to be used in acute watery diarrhea. Saccharomyces boulardii is recommended in children with antibiotic-associated diarrhea as well. Montmorillonite and Racecadotril (acetorphan) can improve the symptoms of diarrhea or shorten the course of acute watery diarrhea. Antibiotics are recommended with dysenteric-like diarrhea, suspected cholera with severe dehydration, immunodeficiency, and premature delivery children with chronic underlying disease; otherwise, antibiotics are not recommended. CONCLUSION: The principles of the most controversial treatments with of acute infectious disease are reaching to a consensus in China.

Predictive value of procalcitonin for excluding bloodstream infection: results of a retrospective study and utility of a rapid, quantitative test for procalcitonin.

OBJECTIVES: To assess retrospectively the diagnostic value of procalcitonin (PCT) in excluding suspected bloodstream infection, establish cut-off values for PCT levels, and compare PCT with other clinical markers. METHODS: The predictive accuracy of different continuous parameters was estimated by univariate analysis of the area under the receiver operating characteristic curve. Optimized cut-off points for the parameters were selected according to the maximum Youden index values, which in turn were used to define positive and negative predictive values of different parameters in diagnosing bloodstream infection. RESULTS: The PCT level yielded a statistically significant area under the receiver operating characteristic curve of 0.765, with a best cut-off value of 0.80 ng/ml (83% sensitivity; 65% specificity, Youden index, J = 0.48). Positive and negative predictive values at this cut-off value were 38% and 94%, respectively. Mann-Whitney U-test revealed significantly higher values for PCT, C-reactive protein and percentage of neutrophils, but not for white blood cell count, in patients with bloodstream infection. CONCLUSIONS: The serum PCT level can potentially be used as surrogate marker to exclude bacteraemia and to inform critical management decisions regarding antibiotic usage, in patients admitted with suspected bloodstream infection.

[Mutations in NPHS2 in familial steroid-resistant nephrotic syndrome in Southern Chinese Han ethnic group].

OBJECTIVE: Mutations in NPHS2 mapped to 1q25-q31 and encoding podocin, which is exclusively expressed in glomerular podocytes, are responsible for autosomal recessive familial steroid-resistant nephrotic syndrome (SRNS) with minor glomerular abnormalities or focal segmental glomerulosclerosis. Different groups from European and North American countries have screened NPHS2 mutations in familial SRNS with recessive inheritance, documenting a mutation detection rate of 45% - 55% in families. This study aimed to examine mutations in the NPHS2 gene in Southern Chinese Han ethnic group patients with familial SRNS. METHODS: Genomic DNA from 3 probands from Southern Chinese Han families with autosomal recessive SRNS, and their siblings and parents was isolated and analyzed for all eight exons, exon-intron boundaries and promoter of NPHS2 using the polymerase chain reaction and direct sequencing. RESULTS: No mutation of NPHS2 in all eight exons and exon-intron boundaries was identified in the 3 probands. However, a polymorphism of 954T > C in exon 8 was detected in all the 3 probands and some controls, and 5 variants of NPHS2 promoter, -1709G > A, -1000A > T, -670C > T, -116C > T and -51G > T, were identified in some patients and controls, indicating that these variants are polymorphisms. One heterozygous variant of NPHS2 promoter, -1715A > G, was also identified in one proband and her mother whose urinalyses were normal, whereas it was not found in any of the 50 controls. There was no significant difference in the allelic frequencies of -1709G > A, -1000A > T, -670C > T, -116C > T and -51G > T polymorphisms between the patients and controls. CONCLUSION: NPHS2 mutations are not a major cause of familial steroid-resistant nephrotic syndrome in Southern Chinese Han ethnic group included in the study.

[Neuroprotective effects of topiramate and folic acid on young rats with kindling-induced epilepsy].

OBJECTIVE: To study the neuroprotective effects of topiramate (TPM) alone or together with folic acid (FA) on young rats with kindling-induced epilepsy. METHODS: Rat models of epilepsy were prepared by pentylenetetrazol (PTZ)-induced kindling. Seventy-two 3-week-old male Wistar rats were randomly divided into 6 groups: four TPM-treated epilepsy groups (TPM 20, 40 or 80 mg/kg/d and TPM 40 mg/kg/d + FA 5 mg/kg/d), a positive control group (untreated epilepsy group) and a negative control group (normal control group). After two months of administration, behaviors of the rats were recorded; serum levels of neuron-specific enolase (NSE) were measured using ELISA; pathological changes in the hippocampus were observed. RESULTS: The frequency of convulsion seizures in the 20, 40 and 80 mg TPM treatment and TPM+FA groups was 44.7 +/- 2.9, 44.3 +/- 3.1, 42.7 +/- 3.2, and 40.8 +/- 3.7 respectively, which were significantly lower than that in the positive control group (48.4 +/- 3.7) (P <0.01). Twenty, forty and eighty mg TPM treatment and TPM+FA treatment significantly reduced NSE levels from 35.71 +/- 5.97 microg/L of the control group to 27.40+/- 6.40, 24.79 +/- 6.22, 21.47 +/- 6.87 and 22.55 +/- 7.02 microg/L respectively (P <0.05). Neuronal apoptosis in the CA3 and CA1 regions were alleviated in the four TPM treatment groups compared with positive control. The number of necrotic neurons was progressively reduced with the increased dose of TPM. The 40 mg TPM+FA treatment group showed less necrotic neurons in the CA3 and CA1 regions than the 40 mg TPM alone treatment group. CONCLUSIONS: TPM has protective effects against epilepsy-induced neuronal damage. The effect is dose-dependent. A combination of TPM and FA can produce a synergistic effect.

[Relationship between brain-derived neurotrophic factor and birth weight in neonates].

OBJECTIVE: Recent research has shown that brain-derived neurotrophic factor (BDNF) can improve obesity. This study aimed to explore the relationship between BDNF and birth weight by measuring BDNF levels in the umbilical cord blood of neonates. METHODS: Based on birth weight, 51 first-born full-term healthy neonates were classified into 3 groups: small for gestational age (SGA, n=8), appropriate for gestational age (AGA, n=31) and large for gestational age (LGA, n=12). Height and birth weight as well as umbilical concentrations of BDNF, leptin, insulin, total cholesterol and triglyceride were determined. RESULTS: BDNF level in the SGA group (19980.00 +/- 5470.54 pg/mL) was significantly higher than that in the AGA (10598.00 +/- 6295.71 pg/mL) and LGA (7508.57 +/- 3767.81 pg/mL) groups (P <0.05). There was no significant difference in the BDNF level between the AGA and LGA groups. Stepwise regression analysis showed that the value of BDNF was negatively correlated with birth weight and BMI of neonates, but had no correlation with leptin and insulin levels. Leptin levels showed positive correlations with birth weight and BMI of neonates. There were no significant differences in total cholesterol and triglyceride levels among the three groups. CONCLUSIONS: BDNF is closely correlated to birth weight but not correlated with leptin and insulin in neonates.

[An experimental study on hepatotoxicity of topiramate in young rats].

OBJECTIVE: Topiramate (TPM) has an evident efficacy in the treatment of childhood epilepsy for multiple pharmacologic properties. However it was reported that it may cause adverse effects such as liver failure and hepatitis, which arouses the attention of the medical field. This study aimed to investigate the hepatotoxicity of low-dosage, high-dosage TPM or TPM along with valproate sodium (VPA) in aspects of biochemistry indexes, oxidative stress indexes and liver pathomorphology in young rats. METHODS: Sixty 3-week-old male Wistar rats were randomly assigned into five groups of 12 rats (Groups A-E). The rats in the experimental groups (Groups A-C) were administered intragastrically with TPM 40 mg/(kg.d), 80 mg/(kg.d) and TPM 40 mg/(kg.d) plus VPA 300 mg/(kg.d) respectively. The rats in the negative control group (Group D) were administered with the same volume of distilled water. The ones in the positive control group (Group E) were treated by injection of 10% carbon tetrachloride dissolved in olive oil subcutaneously at a dose of 5 mL/kg twice a week. After 3-month administration, the changes of body weight and liver pathomorphology were observed; biochemical markers in serum and indexes of oxidative stress in liver homogenate associated with hepatotoxicity were examined. RESULTS: The body weights of rats in the experimental groups were significantly lower than that of rats in the negative control group. The levels of serum alanine aminotransferase, alkaline phosphatase and the content of malondialdehyde, and the activity of superoxide dismutase in liver tissues did not change significantly in the experimental groups. The contents of glutathion in the high dosage of TPM group (29.85 +/- 1.62 mg/g prot) or in the TPM plus VPA group (29.63 +/- 4.47 mg/g prot) were significantly reduced compared with those of the negative control group (33.09 +/- 1.69 mg/g prot) and that of the low dosage of TPM group (32.43 +/- 2.11 mg/g prot) (both P < 0.05). In the histopathological examination, extensive steatosis and diffuse punctate necrosis of hepatocytes distributed in the portal area were found by microscopy in the positive control group. There were granular degeneration of some hepatocytes near the central veins of hepatic lobules in the low dosage of TPM group and punctate necrosis of some hepatocytes in the high dosage of TPM group. In the TPM plus VPA group, histological examination showed granular degeneration and fatty degeneration of partial liver cells and punctate necrosis of some hepatocytes. CONCLUSIONS: Long-term use of TPM can decrease antioxidant capacity of organism, resulting in slight pathological changes of liver tissues. High dosage of TPM or TPM along with VPA administration enhances the risk of the side effects.

[Treatment of hemolytic uremic syndrome after acute stage].

OBJECTIVE: Hemolytic uremic syndrome (HUS) is a common primary disease that can cause acute renal failure in childhood. Renal disease is the most important long-term complication in patients who survived the acute stage of HUS. Use of angiotensin-converting enzyme inhibitors (ACEI) and a restricted protein intake may be beneficial to the patients. However, it is not established whether such patients should be treated with steroids and immunosuppressors. The present study aimed to probe into the benefit of using steroid and immunosuppressor in patients after acute stage of HUS. METHODS: The subjects included 17 patients (aged 9 months to 15 years, 12 males, 5 females) with HUS. Thirteen patients recovered from the acute stage of HUS, and underwent continuative treatment and follow-up. All the patients were treated with ACEI and early restriction of protein intake. Additionally, 2 children manifested as glomerulonephritis, one was treated with triperygium glycosides. Other 11 children who manifested as nephrotic syndrome were treated with prednisone, among them 5 children had no response or had incomplete response to prednisone, for these children short-term high dose cyclophosphamide or methylprednisolone pulse treatment were added; in 3 of the children short-term high dose methylprednisolone treatment was applied additionally for membranoproliferative glomerulonephritis and/or focal segmental glomerulosclerosis and crescentic glomerulonephritis. RESULTS: After follow-up for 2 months to 8 years, 4 patients with milder disease recovered, their blood pressure, renal function and urinalysis became normal, but 1 patient had recurrence. Among 9 patients with severe disease, 6 maintained normal blood pressure, recovered renal function and urinalysis, the other 3 patients failed to comply with treatment protocol and died during the 3rd, 9th and 13th month. The remainder (4 cases) gave up therapy and died on the 27th to 48th days of the course. CONCLUSION: The treatment applied in this study could improve the prognosis of patients after acute phase of HUS evidently by using the steroid and immuno suppressor according to clinical classification and pathological findings. It is recommended that triperygium glycosides is beneficial to children with glomerulonephritis, proteinuria and hematuria after acute stage of HUS. Adjustment of therapeutic schedule based on pathological findings after renal biopsy is helpful. To the patients with progressive renal failure who have no response to the steroid and immunosuppressors, steroid and immunosuppressor should be discontinued and dialysis treatment should be applied. Protocol compliance is also an important factor.