Chinese guidelines for the diagnosis and treatment of hand, foot and mouth disease (2018 edition).

BACKGROUND: Hand, foot, and mouth disease (HFMD) is a common infectious disease in childhood caused by an enterovirus (EV), and which is principally seen in children under 5 years of age. To promote diagnostic awareness and effective treatments, to further standardize and strengthen the clinical management and to reduce the mortality of HFMD, the guidelines for diagnosis and treatment have been developed. METHODS: National Health Commission of China assembled an expert committee for a revision of the guidelines. The committee included 33 members who are specialized in diagnosis and treatment of HFMD. RESULTS: Early recognition of severe cases is utmost important in diagnosis and treatment of patients with HFMD. The key to diagnosis and treatment of severe cases lies in the timely and accurate recognition of stages 2 and 3 of HFMD, in order to stop progression to stage 4. Clinicians should particularly pay attention to those EV-A71 cases in children aged less than 3 years, and those with disease duration less than 3 days. The following indicators should alert the clinician of possible deterioration and impending critical disease: (1) persistent hyperthermia; (2) involvement of nervous system; (3) worsening respiratory rate and rhythm; (4) circulatory dysfunction; (5) elevated peripheral WBC count; (6) elevated blood glucose and (7) elevated blood lactic acid. For treatment, most mild cases can be treated as outpatients. Patients should be isolated to avoid cross-infection. Intense treatment modalities should be given for those severe cases. CONCLUSION: The guidelines can provide systematic guidance on the diagnosis and management of HFMD.

Analysis of the miRNA-mRNA networks in malignant transformation BEAS-2B cells induced by alpha-particles.

The aim of this study was to determine the toxicity induced by irradiation with alpha-particles on malignant transformation of immortalized human bronchial epithelial cells (BEAS-2B) using miRNA-mRNA networks. The expression of BEAS-2B cells was determined by measuring colony formation, mtDNA, mitochondrial membrane potential (MMP), and ROS levels. Changes in BEAS-2B cell gene expression were observed and quantified using microarrays that included an increase in 157 mRNA and 20 miRNA expression and a decrease in 77 mRNA and 48 miRNA. Bioinformatic software was used to analyze these different mRNA and miRNA, which indicated that miR-107 and miR-494 play an important role in alpha-particles-mediated cellular malignant transformation processes. The pathways related to systemic lupus erythematosus, cytokine-cytokine receptor interaction, MAPK signaling pathway, regulation of actin cytoskeleton, and cell adhesion molecules (CAMs) were stimulated, while those of ribosome, transforming growth factor (TGF)-beta signaling pathway, and metabolic pathways were inhibited. Data suggest that miRNA and mRNA play a crucial role in alpha-particles-mediated malignant transformation processes. It is worth noting that three target genes associated with lung cancer were identified and upregulated PEG 10 (paternally expressed gene 10), ARHGAP26, and IRS1.

Co-circulation of multiple hemorrhagic fever diseases with distinct clinical characteristics in Dandong, China.

Hemorrhagic fevers (HF) caused by viruses and bacteria are a major public health problem in China and characterized by variable clinical manifestations, such that it is often difficult to achieve accurate diagnosis and treatment. The causes of HF in 85 patients admitted to Dandong hospital, China, between 2011-2012 were determined by serological and PCR tests. Of these, 34 patients were diagnosed with Huaiyangshan hemorrhagic fever (HYSHF), 34 with Hemorrhagic Fever with Renal Syndrome (HFRS), one with murine typhus, and one with scrub typhus. Etiologic agents could not be determined in the 15 remaining patients. Phylogenetic analyses of recovered bacterial and viral sequences revealed that the causative infectious agents were closely related to those described in other geographical regions. As these diseases have no distinctive clinical features in their early stage, only 13 patients were initially accurately diagnosed. The distinctive clinical features of HFRS and HYSHF developed during disease progression. Enlarged lymph nodes, cough, sputum, and diarrhea were more common in HYSHF patients, while more HFRS cases presented with headache, sore throat, oliguria, percussion pain kidney area, and petechiae. Additionally, HYSHF patients displayed significantly lower levels of white blood cells (WBC), higher levels of creations kinase (CK) and alanine aminotransferase (ALT), while HFRS patients presented with an elevation of blood urea nitrogen (BUN) and creatinine (CREA). These clinical features will assist in the accurate diagnosis of both HYSHF and HFRS. Overall, our data reveal the complexity of pathogens causing HFs in a single Chinese hospital, and highlight the need for accurate early diagnosis and a better understanding of their distinctive clinical features.

[Randomized controlled study of integrated treatment of traditional Chinese medicine and western medicine on AIDS with pulmonary inflammation patients].

OBJECTIVE: To compare effects of integrated treatment traditional Chinese medicine and Western medicine (TCM-WM) and simple western medicine on TCM clincal symptoms in the patient of AIDS with pulmonary inflammation. METHOD: A multicenter randomized controlled trials of 164 subjects evaluated the effects of clinical symptoms of AIDS with pulmonary inflammation of TWO regimens: the TCM-WM group (n = 111) and western medicine treatment group (n = 53), while incidence of TCM symptoms in different time points in two groups were analyzed. RESULT: Twenty eight days after treatment, the cured and markedly effective rate of TCM symptoms in the TCM-WM group significantly exceeding that in the western medicine treatment group (cured and markedly effective rate significant efficiency 44.55% vs 20.00%), while the incidence rate for the TCM symptoms of fever and headache in the TCM-WM group was significantly lower than that in western medicine group. CONCLUSION: The integrated treatment of traditional Chinese medicine and Western medicine helps to alleviate the TCM clinical symptoms of AIDS with pulmonary inflammation.

Oxidative damage in various tissues of rats exposed to radon.

Oxidative damage can be induced by many environmental stressors. 8-Hydroxydeoxyguanosine (8-OHdG) has been used as a biomarker of oxidative DNA damage in both in vitro and in vivo studies. In the present study, Wistar rats were exposed to radon gas at a concentration of 100,000Bq/m(3) for 12 h/d for 30, 60, and 120 d, equivalent to cumulative doses of 60, 120, and 240 working level months (WLM), respectively. Changes in levels of 8-OHdG, reactive oxygen species (ROS), and total antioxidant (T-AOC), as well as expressions of some DNA repair enzymes such as 8-oxoguanine DNA glycosylase (OGG1) and MutT homolog 1 (oxidized purine nucleoside triphosphatase, MTH1), were determined in rat urine, peripheral blood lymphocytes, and lung after exposure to radon. The results revealed an increase in 8-OHdG and ROS levels, a decrease in T-AOC levels, and reduced OGG1 and MTH1 expression levels. The elevated amount of 8-OHdG in urine or lymphocytes was positively correlated with the cumulative exposure dose, whereas OGG1 and MHT1 expression levels in lung were inversely correlated with cumulative exposure dose. These findings indicate that oxidative damage induced by radon may be involved in radon-induced carcinogenesis.

Evolution of viral RNA in a Chinese patient to interferon/ribavirin therapy for hepatitis C.

OBJECTIVE: The combination of interferon (IFN) and ribavirin (RBV) is the standard therapy for hepatitis C virus (HCV) infection. HCV genotype 2a has proved more amenable to the therapy, but its efficacy is yet limited. This study aimed to investigate the mechanism of the poor response in a case of HCV genotype 2a infection. METHODS: We analyzed dynamic change of HCV RNA from a patient, infected with HCV genotype 2a, showing a poor virological response to IFN/RBV as judged 12 weeks after initiation of the therapy by HCV clone sequencing. Then we constructed subgenomic Japanese fulminant hepatitis-1 (JFH1) replicon and different chimeric replicons with humanized Gaussia luciferase gene. The chimeric replicons were derived from subgenomic JFH1 replicon, in which the NS5A region was replaced by the patient's sequence from the pre/post-treatment, and the chimeric replicons' susceptibility to IFN were evaluated by relative Gausia Luciferase activity. RESULTS: The pretreatment HCV sequences appeared almost uniform, and the quasispecies variation was further more simplified after 12 weeks of therapy. Besides, the quasispecies variation seemed to be more diversified in the NS5A, relatively, a region crucial for IFN response, and each of chimeric replicons exhibited distinct response to IFN. CONCLUSIONS: During the course of the chronic infection, HCV population seems to be adapted to the patient's immunological system, and further to be selected by combination of IFN/RBV therapy, indicating quasispecies may completely eliminated by addition of other drugs with targets different from those of IFN. In addition, each different response of chimeric replicon to IFN is most likely related to amino acid changes in or near the IFN-sensitivity determining region (ISDR) of NS5A during chronic infection and IFN/RBV therapy.

[The analysis of the clinical features between survivors and non-survivors with the severe form of new influenza A (H1N1) viral infection].

OBJECTIVE: To understand the clinical features of critically ill patients with pandemic 2009 influenza A (H1N1) and investigate the risk factors associated with death cases. METHODS: The clinical features of 55 critically ill patients with pandemic 2009 influenza A (H1N1) viral infection hospitalized at Beijing Ditan Hospital from October 3 to December 15, 2009 were retrospectively analyzed, and a comparative analysis was performed on the manifestations of the survival and the death groups of patients. RESULTS: There were 31 males and 24 females. The age ranged from 10 months to 84 year old, and the mean (SD) was 38 (20) year old. The critically ill cases were more in patients under age 65 (48/55), with obesity (33/49), with underlying diseases (26/49), and pregnancy (6/24). Both the survivors and non-survivors of patients had high fever, cough, sputum (some sputum with blood), dyspnea, räles of both lungs fields, and all further developed severe pneumonia. The patients also showed respiratory failure (54/55) and ARDS (26/55). All of them received oseltamivir therapy, and 38 patients received mechanical ventilation and 30 were given steroid therapy. Secondary infection occurred in 27 cases, and ventilator-associated pneumonia happened in 10 patients. In the early stage of onset, C-reactive protein (CRP) increased [(131 ± 130) mg/L] and low counts of T lymphocytes were present [CD(4)(+), CD(8)(+) T was (217 ± 139)/µl and (162 ± 82)/µl]. With the progress of disease, the non-survival cases had persistently increased CRP and the counts of T lymphocytes did not recover, while the secondary fungal infection was significantly higher than in the survivor cases (P < 0.05). By using BMI, underlying diseases, ARDS, the day of Oseltamivir initiated, steroid therapy, following bacterial and fungal infection as variables through logistic regression analysis, it was shown that higher BMI and following fungal infection were associated with higher fatal risks (OR was 6.512, 19.631 respectively, both of P value was low than 0.05). There was no death case who received oseltamivir treatment within 48 hours of onset of disease. CONCLUSIONS: Critical illness in pandemic 2009 influenza A (H1N1) was associated with patients under age 65, with obesity, underlying diseases, and pregnancy. Persistently increased CRP and lower counts of T lymphocytes were associated with unfavorable prognosis. The patients with higher BMI and secondary fungal infection had higher fatal risks. Oseltamivir treatments at early stage would probably reduce mortality.

[A clinical analysis of 33 cases of H1N1 influenza A].

OBJECTIVE: To review the clinical characteristics of H1N1 influenza A, and suggest the clinical practices for the diagnosis and treatment of H1N1 influenza A in the future. METHODS: Thirty-three cases of H1N1 influenza A hospitalized in Beijing Ditan Hospital from May 15 to June 22, 2009 were studied and the clinical data were statistically analyzed with SPSS 11.0 for Windows. RESULTS: Twenty-five of the 33 patients had a history of travelling in America, Canada, Japan etc within a week; the latent period was between 1 and 6 days in 12 close contact patients. The main symptoms of H1N1 influenza A are fever (66.7%), dry cough (60.6%), cough with sputum (42.4%) and sore throat (36.4%). The laboratory tests in 24 cases (72.7%) were normal, while mild abnormal results were found in the remaining patients. All of the 33 cases were discharged according to the Standard of Diagnosis and Treatment of H1N1 Influenza A published by The Minister of Health, China. The period between 2-consecutive negative results in viral nucleic acid RT-PCR detection and the presenting symptom was 2 to 16 days and the period of hospitalization was 3 to 16 days. CONCLUSION: The new type of H1N1 influenza A is characterized by mild symptoms, short period of hospitalization and good prognosis. All the patients can be cured, if they do not suffer from other severe chronic disease.

[Clinical features and outcome of infection of type 2 Streptococcus suis in human].

OBJECTIVE: To analysis the clinical features and efficacy of treatment for patients with type 2 Streptococcus suis (S. suis 2) infection, and to inform better diagnosis and treatment of S. suis 2. METHODS: Clinical data of 68 patients with S. suis 2 infection were retrieved retrospectively. The diagnoses were confirmed by clinical symtom or/and isolation of S. suis 2 from the infected sites in Shichuan province in the summer of 2005. The patients ranged from general type (simple sepsis) to septic shock type; meningitis type and mixed type. RESULTS: The outbreak of S. suis 2 infection occurred in June to August in 2005. The common source of infection came from pigs. The people in great risks were farmers who exposed to sick or dead pigs with S. suis 2 infection. Most infection occurred on the people who slaughtered infected pigs, followed by those who dressed infected meats. The prominent symptoms included fever with sharp chills, dizziness, headache, malaise and myalgia. Some patients had abdominal pain and diarrhea. Septic shock and coma often occurred in severe cases. According to the clinical manifestations, patients were categorized into four different clinical types: general type, septic shock type, meningitis type, and mixed type. S. suis 2 isolated from the patients were susceptible to most antimicrobial agents, except for tetracycline. All of the patients were treated with beta-lactam antibiotics (penicillins or cephalosporins). Some were given combined antimicrobial agents. Seventy seven percent (52/68) of patients survived. All of the general patients recovered completely. Fifty eight percent (15/26) of patients with septic shock died. The artificial ventilation and persistent blood filtering treatment played an important role for treating patients with septic shock. Although most patients with meningitis (97.5%) survived, a decrease in hearing or even hearing loss occurred to some of the survivors. CONCLUSION: Purulent meningitis and septic shock are the major clinical manifestations for S. suis 2 infection in human. The treatment for patients with meningitis is more effective than that for patients with septic shock.

[Association of haplotype formed on HLA-DRB1 and HLA-DQA1 alleles with outcomes of hepatitis B virus infection].

OBJECTIVE: To assess the association of haplotype of HLA-DRB1 and HLA-DQA1 alleles with outcomes of hepatitis B virus infection in Han population of north China. METHODS: Two hundred and seven chronic hepatitis B (HB) patients, two hundred and twelve chronic asymptomatic hepatitis B virus (HBV) carriers (HBV carrier) and one hundred and forty-eight self-limited HBV infection were investigated for HLA-DRB1 and HLA-DQA1 alleles by sequence specific-polymerase chain reaction (PCR-SSP). RESULTS: The frequency of DRB1*04-DQA1*0301 haplotype was 10.03% in self-limited HBV infection subjects, significantly higher than that in chronic HB patients (3.66%) (P=0.0005)ûthe frequency of DRB1*15/*16-DQA1*0102 haplotype was 6.80% in self-limited HBV infection subjects, significantly higher than 1.94% in chronic HB patients (P=0.0012) and 1.65% in asymptomatic HBV carriers (P=0.0004)ûwhile the frequency of DRB1*04-DQA1*0302 haplotype was 3.10% in chronic HB patients, higher than that in self-limited HBV infection subjects (0.39%) (P=0.0077). CONCLUSION: Individuals with different haplotypes composed of HLA-DRB1 and HLA-DQA1 might have different outcomes of HBV infection.

[An outbreak of human Streptococcus suis serotype 2 infections presenting with toxic shock syndrome in Sichuan, China].

OBJECTIVE: In mid-July 2005, five patients presented with septic shock to a hospital in Ziyang city in Sichuan, China, to identify the etiology of the unknown reason disease, an epidemiological, clinical, and laboratory study were conducted. METHODS: An enhanced surveillance program were established in Sichuan, the following activities were introduced: active case finding in Sichuan of (a) laboratory diagnosed Streptococcus suis infection and (b) clinically diagnosed probable cases with exposure history; supplemented by (c) monitoring reports on meningococcal meningitis. Streptococcus suis serotype 2 infection was confirmed by culture and biochemical reactions, followed by sequencing for specific genes for serotype and virulence factors. RESULTS: From June 10 to August 21, 2005, 68 laboratory confirmed cases of human Streptococcus suis infections were reported. All were villagers who gave a history of direct exposure to deceased or sick pigs in their backyards where slaughtering was performed. Twenty six (38%) presented with toxic shock syndrome of which 15 (58%) died. Other presentations were septicaemia or meningitis. All isolates were tested positive for genes for tuf, species-specific 16S rRNA, cps2J, mrp, ef and sly. There were 136 clinically diagnosed probable cases with similar exposure history but incomplete laboratory investigations. CONCLUSION: An outbreak of human Streptococcus suis serotype 2 infections occurred in villagers after direct exposure to deceased or sick pigs in Sichuan. Prohibition of slaughtering in backyards brought the outbreak to a halt. A virulent strain of the bacteria is speculated to be in circulation, and is responsible for the unusual presentation of toxic shock syndrome with high case fatality.

[Anlysis on features of dead cases with human Streptococcus suis infections].

OBJECTIVE: To describe the clinical and epidemiological features of dead cases with human Streptococcus suis infections, and to find the target population for preventing death and the related indicators. METHODS: Epidemiological investigation on human Streptococcus suis infections was implemented used unified questionnaires. Analysis on dead cases and survival cases (as contrast) was done. RESULTS: The population with highest fatality rate was in 40-49 age group. 97.37% of dead cases had toxic shock syndrome. The mean interval from onset to admission was 0.76 days, and the mean course was 2.11 days. The progression among dead cases was faster than that among survival cases. Chief clinical manifestations of dead cases that are more frequent than survival cases are purpura (73.68%), diarrhea (50.0%), dyspnea (21.05%), conjunctival congestion (34.21%), etc. Renal impairment and liver involvement in dead cases were more significant than that in survival cases. No significant difference between mean incubation period, exposure rates of main risk factors in dead cases and in survival cases was found. CONCLUSION: Preventing toxic shock syndrome might reduce the fatality rate. The target population for preventing death is aged > or = 40. Liver function and renal function testing might be indicators for monitoring the progression of human Streptococcus suis infections.

[Dynamics of peripheral blood B lymphocytes and natural killer cells in patients with severe acute respiratory syndrome].

OBJECTIVE: To study the dynamics of peripheral blood B lymphocytes and natural killer (NK) cells in patients with severe acute respiratory syndrome (SARS). METHODS: The absolute numbers of peripheral blood B lymphocytes and NK cells in 602 serial samples from 240 patients with SARS were counted, using flow cytometry, and compared with that of normal population. RESULTS: The absolute numbers of peripheral blood B lymphocytes and NK cells in SARS patients were significantly lower than that of the normal population (P < 0.001) and were much lower in SARS patients with severe or extremely severe types, as compared with that of moderate or mild type cases (P < 0.001). The amount of B lymphocytes in recovery SARS patients increased at the 2nd week after onset, and gradually becoming normal at the 5th week of the disease onset. The number of NK cells was in the low level at onset, and keep decreasing at the 2nd week. However, it was increasing with the recovery of the disease, but did not reach to normal level at the 5th week after onset. CONCLUSION: The absolute numbers of peripheral blood B lymphocytes and NK cells were associated with the severity of the disease, and detection of these two kinds of cells was useful for predicting the prognosis of SARS.