A study of serum proteome expression in patients with severe hand-foot-mouth disease.

OBJECTIVE: Although numerous studies have been conducted on hand-foot-mouth disease (HFMD), the diagnosis of severe HFMD has not been fully clarified. Hence, it is important to further clarify the diagnosis of severe HFMD. In this study, we conducted a clinical biomarker discovery in patients with severe HFMD. PATIENTS AND METHODS: In this study, serum samples were isolated from severe HFMD, HFMD, and healthy controls. Each group consisted of 32 cases. Isobaric tagging for relative and absolute quantitation (iTRAQ) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to detect proteome expression in the serum samples. Then, candidate proteins were screened and verified by ELISA. Protein expressions were significantly different between the HFMD group, severe HFMD group, and healthy control group. RESULTS: Comparison of the proteins between the three groups showed that serum amyloid A-1 protein (P0DJ18), C-reactive protein (P02741), fibronectin (P02751), plasminogen (P00747) and apolipoprotein A (P08519) were different, so they were selected as candidate proteins. However, the results of ELISA showed that the expression levels of serum amyloid A-1 protein, C-reactive protein, fibronectin, and apolipoprotein a in the severe HFMD group were significantly different from those in the other two groups (p<0.05). CONCLUSIONS: In conclusion, the results showed that serum amyloid A-1, C-reactive protein, fibronectin, and apolipoprotein A may be potential biomarkers for clinical diagnosis of severe HFMD.

Coagulation parameters and Apgar score are associated with severity in preterm infants.

OBJECTIVE: Coagulation parameters are used to diagnose hematological diseases. The correlation between the coagulation parameters and Apgar score at 5 min is yet to be elucidated. The present study aimed at describing the neonatal coagulation parameters in preterm infants with a low Apgar score at 5 min. PATIENTS AND METHODS: In this case-control study, 32 serious preterm infants were compared with 20 preterm infants, according to the Apgar score at 5 min. The prothrombin time (PT), thrombin time (TT), fibrinogen (Fbg), activated partial thromboplastin time (APTT), calculated international normalized ratio (INR), D-dimer (D2), fructose diphosphate sodium (FDP), and procalcitonin (PCT) values were recorded. The linear correlation between coagulation parameters and Apgar score at 5 min was analyzed by linear regression. The two groups were compared using GraphPad Prism 8 (LaJolla, CA, USA). RESULTS: In the study, the mean coagulation parameters were significantly higher in the serious preterm infants with low the Apgar score at 5 min compared to the preterm infants with normal Agar scores at 5 min (p<0.05). The correlation between coagulation parameters and Apgar score at 5 min was recorded (PT: R=0.3984; APTT: R=0.3165; INR: R=0.4139). CONCLUSIONS: The coagulation parameters were significantly higher in serious preterm infants with a low Apgar score at 5 min. Also, the coagulation parameters and Apgar score at 5 min are associated with severity in preterm infants.

[Effects of hepatitis B virus on Th17, Treg and Th17/Treg ratio in different alanine aminetransferase stages].

OBJECTIVE: To evaluate the effects of hepatitis B virus (HBV) on helper T lymphocytes 17 (Th17), regulatory T lymphocyte (Treg) and Th17/Treg ratio in chronic hepatitis B patients in different alanine aminetransferase (ALT) stages. METHODS: In the study, 336 chronic hepatitis B patients in the first hospital of Lanzhou University were analyzed. The hepatitis B antigen antibody parameters were measured by chemiluminescence immunoassay analyzer, the liver function parameters were measured by automatic biochemical analyzer, the HBV loads were measured by quantitative PCR, Th17, Treg and Th17/Treg ratios were detected by flow cytometry. Among them, 111 cases (ALT < 40 U/L) of ALT were normal hepatitis B, 108 cases of chronic hepatitis B with ALT above normal upper limit and < 2 times higher (40 U/L≤ALT < 80 U/L), and 117 cases of chronic hepatitis B with ALT above 2 times normal upper limit (80 U/L≤ALT). According to the viral load, they were divided into low replication group with HBV DNA < 4.0 lg copies/mL, medium replication group with 4.0 lg copies/mL≤HBV DNA < 6.0 lg copies/mL and high replication group with HBV DNA ≥ 6.0 lg copies / mL. Dunnett T3 variance analysis were used to analyze the effects of HBV on Th17, Treg and Th17/Treg ratio in the chronic hepatitis B patients in different ALT stages. The changes of virological and immunological indexes before and after treatment were observed for 24 weeks of antiviral therapy in the hepatitis B patients with ALT≥double upper limit of normal group. RESULTS: In the ALT normal group, different virus load HBV had minor effects on Th17, Treg and Th17/Treg ratio. In the ALT≥2 times upper limit of normal group, with the virus load increased, Th17 (3.18%±0.79% in low replication group, 3.78%±0.92% in medium replication group and 4.57%±1.15% in high replication group), Treg cells (5.52%±1.58% in low replication group, 5.89%±1.84% in medium replication group and 6.37%±2.35% in high replication group) and their ratio Th17/Treg (0.57±0.25 in low replication group, 0.65±0.29 in medium replication group and 0.73±0.36 in high replication group) were significantly increased (P < 0.05). After entecavir treatment 24 weeks, the patient' s HBV-DNA decreased significantly, Th17 (3.89%±1.02% vs. 2.06%±0.46%), Treg (6.02%±2.03% vs. 5.06%±1.25%), Th17/Treg ratio (0.65±0.28 vs. 0.41±0.14) decreased significantly (P < 0.05). CONCLUSION: Investigation on the effects of HBV on Th17 and Treg cells and their ratios in different ALT states can clarify the effects of HBV on the body from the immunological perspective and can further understand the ALT grouping for antiviral treatment theoretical significance, which is helpful for clinical treatment.

Adiponectin improves isoflurane-induced cognitive dysfunction in elderly rats via inhibiting p38-MAPK signal pathway in hippocampus.

OBJECTIVE:   To investigate the intervention of exogenous adiponectin in the elderly rats with cognitive dysfunction induced by isoflurane through mitogen-activated protein kinase (MAPK) signaling pathway in hippocampus. MATERIALS AND METHODS: A total of 60 healthy elder Sprague Dawley (SD) rats aged 15-20 months and weighing 400-500 g were selected. These rats were randomly divided into four groups, i.e., the control group, the anesthetic group, adiponectin intervention group, and p38-MAPK antagonist group, in which the rats in the control group were treated through inhalation of pure oxygen for 4 h at a rate of 4 L/min, while the rats in the other 3 groups were treated through inhalation of isoflurane for 4 h. During the inhalation of isoflurane, the concentration of isoflurane was 3.5% at the beginning and decreased to 2.2% at 1 h, and 1.7% between 2 h and 4 h. Then, the intraperitoneal injection of 0.5 mL normal saline was performed for the rats in the control group and the anesthetic group, while adiponectin (300 mg/kg) was injected into the rats in the adiponectin intervention group and p38-MAPK antagonist group. Simultaneously, the antagonist (20 mg/kg) diluted to 0.5 mL was given to the rats in the p38-MAPK antagonist group, once/day for 3 days. Morris water maze test was carried out respectively in the 1st, 3rd, and 7th day, and 5 rats participated in the test at each time point, during which we recorded the escape latency, as well as the length of the swimming route of rats. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting were employed to detect the mRNA and protein expressions of p38 in the hippocampus. RESULTS: The escape latency and the length of the swimming route at any time point after the intervention in the anesthetic group were significantly longer than those in the control group (p<0.05), and they were significantly shorter in the adiponectin intervention group than those in the anesthetic group (p<0.05), but there were no differences between the p38-MAPK antagonist group and the anesthetic group (p>0.05). The mRNA and protein expressions of p38 at any time point after intervention in the anesthetic group were higher than those in the control group (p<0.05), and they were significantly lower in the adiponectin intervention group than those in the anesthetic group (p<0.05), but there were no differences between the p38-MAPK antagonist group and the anesthetic group (p>0.05). CONCLUSIONS: Exogenous adiponectin can improve the cognitive dysfunction of the elderly rats after anesthesia using isoflurane, possibly by inhibiting the p38-MAPK signal pathway in hippocampus.

[(68)Ga-exendin-4 PET-CT for the localization of occult insulinomas: a prospective cohort study].

Objective: To explore the accuracy in localizing occult insulinomas with Glucagon-like peptide-1 receptor(GLP-1R) PET-CT with (68)Ga-exendin-4. Methods: In this prospective cohort study, patients with biochemically proven endogenous hyperinsulinemic hypoglycemia and negative contrast-enhanced CT with pancreatic perfusion scans were enrolled consecutively at Department of Nuclear Medicine, Peking Union Medical College Hospital from February 2014 to June 2018.There were 37 males and 32 females, with age of (43.2±17.9)years. (68)Ga-exendin-4 PET-CT, MRI and endoscopic ultrasound(EUS) were done before elective surgery. Sensitivity, specificity, accuracy, positive predictive value(PPV) and negative predictive value(NPV) of the above imaging modalities were calculated. Results: A total of 69 patients were recruited. Thirty-two patients were diagnosed with insulinomas at histology. Four patients with positive (68)Ga-exendin-4 PET-CT findings did not undergo surgery so far. Twenty-eight patients were proven to be noninsulinoma induced hyperinsulinemic hypoglycemia. Five patients were unknown of etiology of hypoglycemia. The sensitivity, specificity, accuracy, PPV and NPV of (68)Ga-exendin-4 in localizing occult insulinomas were 96.9%(31/32), 100%(30/30), 98.3%(59/60), 100%(29/29), 96.8%(30/31), respectively.The sensitivity, specificity, accuracy, PPV and NPV of MRI were 74.1%(20/27), 9/11, 76.3%(29/38), 90.9%(20/22), 9/16, respectively. The sensitivity, specificity, accuracy, PPV and NPV of EUS were 75.0% (15/20), 2/2, 77.3%(17/22), 15/15, and 2/7. Conclusion: (68)Ga-exendin-4 PET-CT has a high sensitivity, specificity and accuracy for detection of occult insulinoma, which shows superiority to MRI and EUS.

[Analysis of antimicrobial resistance and risk factors of community-onset methicillin-resistant staphylococcus aureus infection].

Objective: To analyze risk factors and drug resistance of community-onset methicillin-resistant staphylococcus aureus (CO-MRSA) infection through the investigation of patients infected with CO-MRSA. Methods: The clinical data of 97 cases infected with community-onset staphylococcus aureus (COSA) was collected in this hospital from July 2016 to June 2017. Epidemiological survey method and the variables were determined according to expert consultation, literature and practical work experience. Results: Among 97 patients infected with COSA, the diagnosis rate of CO-MRSA was 21.65%(21/97). The drug sensitivity results showed that: CO-MRSA was high resistant to erythromycin, tetracycline and clindamycin, and the drug resistance rate exceeded 50%. Multiple variables were analyzed by Logistic regression. The usage of antimicrobial agents in the past three months and the history of hospitalization within one year were the independent risk factors. The MRSA infection rate was 57.89%(11/19) of the persons who had taken antibacterial agents in the recent three months.The MRSA infection rate was 48.28%(14/29) of the persons who had been hospitalized in the past one year. OR value of two risk factors was respectively 10.006(95%CI: 2.200-45.519, P=0.030) and 11.519(95%CI: 2.405-55.177, P=0.002). Conclusions: Most COSA is sensitive to methicillin, but CO-MRSA is multidrug resistant and has more risk factors. The clinicians should reasonably use the antibacterial agents according to the drug sensitivity in order to prevent the occurrence of multidrug resistant MRSA.

[The 462nd case: chronic watery diarrhea and acute kidney injury].

A 60-year-old man presented with severe watery diarrhea for 2 months complicated with weight loss and acute kidney injury. He did not respond well to antidiarrheal medicines, empirical antibiotics and dietary exclusion of gluten or even complete bowel rest. The final diagnosis of autoimmune enteropathy (AIE) was made based on histopathologic findings of endoscopic biopsy from duodenal mucosa after excluding neoplastic disease, inflammatory bowel disease, and infectious diarrhea, etc. Chronic diarrhea and oliguria alleviated after the administration of corticosteroids.

An in vitro bioassay for the quantitative evaluation of mosquito repellents against Stegomyia aegypti (=Aedes aegypti) mosquitoes using a novel cocktail meal.

To assess the efficacy of new insect repellents, an efficient and safe in vitro bioassay system using a multiple-membrane blood-feeding device and a cocktail meal was developed. The multiple-membrane blood-feeding device facilitates the identification of new insect repellents by the high-throughput screening of candidate chemicals. A cocktail meal was developed as a replacement for blood for feeding females of Stegomyia aegypti (=Aedes aegypti) (L.) (Diptera: Culicidae). The cocktail meal consisted of a mixture of salt, albumin and dextrose, to which adenosine triphosphate was added to induce engorging. Feeding rates of St. aegypti on the cocktail meal and pig blood, respectively, did not differ significantly, but were significantly higher than the feeding rate on citrate phosphate dextrose-adenine 1 (CPDA-1) solutions, which had been used to replace bloodmeals in previous repellent assays. Dose-dependent biting inhibition rates were analysed using probit analysis. The RD(50) (the dose producing 50% repellence of mosquito feeding) values of DEET, citronella, carvacrol, geraniol, eugenol and thymol were 1.62, 14.40, 22.51, 23.29, 23.83 and 68.05 µg/cm(2), respectively.

Effects of body mass and temperature on routine metabolic rate of juvenile largemouth bronze gudgeon Coreius guichenoti.

The effects of body mass (M) and temperature (T) on routine metabolic rate (m(R) ) were assessed in the largemouth bronze gudgeon Coreius guichenoti, from Three Gorges Reservoir, Yangtze River, China. The m(R) increased with increasing M by factors (b-value in the equation m(R) = aM(b) ) of 0·843, 0·800, 0·767, 0·788 and 0·822 at 10, 15, 20, 25 and 30° C, respectively. A significant interaction between M and T on m(R) was observed. The variation in the b-value at different T suggests that the b-values were not consistent with the universal allometric exponent 0·75. After controlling for M, the relationship between the normalized standard metabolic rate (m(S), mg O(2) kg(-1) h(-1)) and T was described by an exponential equation: m(S) = 9·89e((0·093T)) . The results indicate that the effects of M on m(R) depend on T. The increased water temperature induced by dam construction on the Yangtze River may cause a marked increase in energy demand by this species, with potential ecological consequences.

The role of proto-oncogene Fra-1 in remodeling the tumor microenvironment in support of breast tumor cell invasion and progression.

A growing body of evidence indicates that interactions between neoplastic cells and tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) are crucial in promoting tumor cell invasion and progression. Macrophages have an ambiguous role in these processes as this M1 phenotype correlates with tumoricidal capacity, whereas TAMs of M2 phenotype exert tumor-promoting effects. In this study, we provide evidence that interactions between mouse breast tumor cells and TAMs remodel the TME, leading to the upregulation of Fra-1, a member of the FOS family of transcription factor. In turn, this proto-oncogene initiates activation of the IL-6/JAK/Stat3 signaling pathway. This creates a malignant switch in breast tumor cells, leading to increased release of proangiogenic factors MMP-9, vascular endothelial growth factor and transforming growth factor-beta from tumor cells and intensified invasion and progression of breast cancer. Proof of the concept for the crucial role played by transcription factor Fra-1 in regulating these processes was established by specific knockdown of Fra-1 with small interfering RNA, which resulted in a marked suppression of tumor cell invasion, angiogenesis and metastasis in a mouse breast cancer model. Such a strategy could eventually lead to future efficacious treatments of metastatic breast cancer.

Heavy metal concentrations in soils and plant accumulation in a restored manganese mineland in Guangxi, South China.

Heavy metal contamination of metal-mined soils is a widespread problem in China. In the restored (over 20 years) Lipu manganese mineland, 36 plant species from 22 families were found colonizing, some of which were planted agronomic ones. Heavy metal concentrations in tailings were very high. Minesoils were basically unpolluted, but soils in the remaining mining area and in the vicinity of tailings dumps were polluted by Cd and Mn. Measurements of metal contents in dominant plants showed they were close to those of other mineland plants. Plants tended to have a higher Cd accumulation (as reflected by Biological Accumulation Coefficient) from soil, but have a higher Mn translocation (as indicated by Biological Transfer Coefficient) to aboveground parts. The Chinese chestnut and sugarcane cultivated on the reclaimed mineland were not safe for human consumption, and this agricultural restoration pattern should be carefully reconsidered.

[Tumor necrosis factor and interleukin 6 in acute leukemia].

In order to clarify the role of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF alpha) in the pathogenesis of acute leukemia, IL-6 and TNF alpha level was determined in patients with various types of acute leukemia. In comparison with normal subjects, IL-6 activity was significantly elevated in patients with ALL and ANLL (P < 0.01) and TNF alpha level increased in patients with ANLL (P < 0.05). The effect of IL-6 and TNF alpha on leukemia cell in vitro was also observed. The results indicated that IL-6 can promote the proliferation of leukemia cells, while TNF alpha can inhibit proliferation of leukemia cell in vitro. It is suggested that abnormal level of TNF alpha and IL-6 in patients with acute leukemia is probably related to the pathogenesis of acute leukemia.