This study is aimed to identify and assess the methodological quality of community-acquired pneumonia (CAP) clinical practice guidelines (CPG) in China by using AGREE Ⅱ tool. CNKI, SinoMed, Wanfang, and VIP Chinese databases from database establishment to March 2017 were searched by manual retrieval to collect all the clinical practice guidelines prepared by various associations or organizations, then AGREE Ⅱtool was used to assess them. Data in each CPG were analyzed in terms of six domains, including scope and purpose, participants, rigor, clarity and readability, applicability and editorial independence. A total of 4 CPGs were included. The results showed that the scope and purpose scored 45.8%; the clarity of expression scored 44.75%; the participants scored 31.9%; the rigor scored 18.98%; the applicability scored 7%; and finally the editorial independence scored 1%. It is concluded that the quality of applicability and the editorial independence should attained paid more attention in future development or updating of the guidelines. In addition to strengthening the compliance with international general principles, we should also pay attention to the characteristics of traditional Chinese medicine treatment, especially the related evidences as complementary and alternative treatment for western intervention measures.

An 8-year-old girl who had experienced intermittent cough and fever over a 3 year period, was admitted after experiencing a recurrence for one month. One year ago the patient experienced a recurrent oral mucosal ulcer. Physical examination showed vitiligo in the skin of the upper right back. Routine blood tests and immune function tests performed in other hospitals had shown normal results. Multiple lung CT scans showed pulmonary infection. The patient had recurrent fever and cough and persistent presence of some lesions after anti-infective therapy. The antitubercular therapy was ineffective. Routine blood tests after admission showed agranulocytosis. Gene detection was performed and she was diagnosed with dyskeratosis congenita caused by homozygous mutation in RTEL1. Patients with dyskeratosis congenita with RTEL1 gene mutation tend to develop pulmonary complications. Since RTEL1 gene sequence is highly variable with many mutation sites and patterns and can be inherited via autosomal dominant or recessive inheritance, this disease often has various clinical manifestations, which may lead to missed diagnosis or misdiagnosis. For children with unexplained recurrent pulmonary infection, examinations of the oral cavity, skin, and nails and toes should be taken and routine blood tests should be performed to exclude dyskeratosis congenita. There are no specific therapies for dyskeratosis congenita at present, and when bone marrow failure and pulmonary failure occur, hematopoietic stem cell transplantation and lung transplantation are the only therapies. Androgen and its derivatives are effective in some patients. Drugs targeting the telomere may be promising for patients with dyskeratosis congenita.
Child ; Dyskeratosis Congenita ; complications ; therapy ; Female ; Humans ; Mouth Diseases ; etiology ; Mouth Mucosa ; pathology ; Recurrence ; Respiratory Tract Infections ; etiology ; Telomere ; drug effects ; Ulcer ; etiology

BACKGROUNDSepsis is the leading cause of death among critically ill patients. Herein, we conducted a national survey to provide data on epidemiology and treatment of sepsis in the clinical practice in China, which has no detailed epidemiological data available on sepsis.

METHODSThis was a prospective cross-sectional survey from December 1, 2015 to January 31, 2016 in all provinces/municipalities of the mainland of China. The primary outcome of this study was the incidence of sepsis, and the secondary outcome was its etiology in China. Patients with sepsis admitted to the Intensive Care Units were included in this study. The demographic, physiological, bacteriological, and therapeutic data of these patients were recorded. The incidence of sepsis was estimated using the data from the sixth census in China, reported by the Chinese National Health and Family Planning Commission and the National Bureau of Statistics as the standard population. The independent risk factors for increased mortality from sepsis were calculated.

CONCLUSIONSThis study indicated the incidence and outcome of sepsis in China. It also showed the most common etiology of different sites and types of infection, which could guide empiric antibiotic therapy. Moreover, it provided information on the independent risk factors for increased mortality due to sepsis. The findings provide evidence to guide clinical management and may help improve the outcome in septic patients.

TRIAL REGISTRATIONClinicalTrials.gov, NCT02448472; https://clinicaltrials.gov/show/NCT02448472.

China ; epidemiology ; Cross-Sectional Studies ; Epidemiologic Studies ; Female ; Humans ; Incidence ; Intensive Care Units ; statistics & numerical data ; Male ; Prospective Studies ; Sepsis ; epidemiology ; etiology

OBJECTIVETo find and identify HLA-A*0201 restricted cytotoxic T lymphocyte (CTL) epitopes from epidermal growth factor pathway substrate number 8 (Eps8) for specific immunotherapy based on Eps8-derived epitopes in clinic.

METHODSOnline biological softwares involved C-proteasomal cleavage, MHC class I binding affinity and TAP transport efficiency were used for prediction of HLA-A*0201 restricted epitopes from Eps8. Then, T2-binding assays and peptide/MHC complex stability tests were used to further verify the predicted epitopes. Specific secretion of IFN-γ from human CTL was assayed using the IFN-γ ELISPOT kit, and cytolytic activity was measured by a 4-h lactate dehydrogenase (LDH) release assay. Finally, the functional effects in vivo were measured in HLA-A*0201/Kb transgenic (Tg) mice.

RESULTSFour natural epitopes were designed through online biological softwares. Of the four epitopes selected, p360-368 was found to have the high binding affinity to HLA-A*0201, while p101-109 and p276-284 showed moderate affinities. DC50 of peptide/MHC complexes of the natural epitopes mentioned were all longer than 8 h. In functional assays with human PBMNC in vitro and in HLA-A*0201/Kb transgenic mice in vivo, CTLs primed by each epitope (p101-109, p276-284 and p360-368) secreted IFN-γ and were toxic to cancer cells from a variety of tissue types in an HLA-A*0201-restricted and Eps8-specific manner.

CONCLUSIONNatural epitopes (p101-109, p276-284 and p360-368) may be the HLA-A*0201 restricted epitope derived from Eps8.

Adaptor Proteins, Signal Transducing ; immunology ; Animals ; Epitopes, T-Lymphocyte ; metabolism ; HLA-A2 Antigen ; metabolism ; Humans ; Mice ; Mice, Transgenic ; T-Lymphocytes, Cytotoxic

BACKGROUNDThe efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for immunoglobulin A nephropathy (IgAN) are unclear. This study was designed to evaluate the efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for IgAN.

METHODSIt is a multicenter, prospective, double-dummy randomized controlled trial. Primary IgAN patients were recruited in 13 renal units across Beijing, China, from July 2010 to June 2012. After a 4-week telmisartan (80 mg/d) wash-in, 400 patients continuing on 80 mg/d telmisartan were randomly assigned to additionally receive placebo (Group A), 50 mg/d clopidogrel (Group B), 20 mg/d leflunomide (Group C), or 50 mg/d clopidogrel and 20 mg/d leflunomide (Group D). The 24-week intervention was completed by 360 patients. The primary endpoint was change in 24-h proteinuria at 24 weeks. A linear mixed-effect model was used to analyze the changes at 4, 12, and 24 weeks. Generalized estimating equations were used to evaluate changes in hematuria grade. This trial was registered at the Chinese Clinical Trial Registry.

RESULTSThe effects of telmisartan combined with leflunomide on changes in proteinuria (0.36 [95% confidence interval (CI) 0.18-0.55] g/d, P < 0.001), in serum uric acid (76.96 [95% CI 57.44-96.49] μmol/L, P < 0.001), in serum creatinine (9.49 [95% CI 6.54-12.44] μmol/L, P < 0.001), and in estimated glomerular filtration rate (-6.72 [95% CI-9.46 to -3.98] ml·min-1·1.73 m-2, P < 0.001) were statistically significant, whereas they were not statistically significant on changes in systolic and diastolic blood pressure and weight (P > 0.05). Telmisartan combined with clopidogrel had no statistical effect on any outcome, and there was no interaction between the interventions. No obvious adverse reactions were observed.

CONCLUSIONSTelmisartan combined with leflunomide, not clopidogrel, is safe and effective for decreasing proteinuria in certain IgAN patients.

TRIAL REGISTRATIONchictr.org.cn, ChiCTR-TRC-10000776; http://www.chictr.org.cn/showproj.aspx?proj=8760.

Adolescent ; Adult ; Benzimidazoles ; adverse effects ; therapeutic use ; Benzoates ; adverse effects ; therapeutic use ; Blood Pressure ; drug effects ; China ; Creatinine ; blood ; Female ; Glomerular Filtration Rate ; drug effects ; Glomerulonephritis, IGA ; blood ; drug therapy ; Humans ; Isoxazoles ; adverse effects ; therapeutic use ; Kidney Function Tests ; Male ; Middle Aged ; Prospective Studies ; Ticlopidine ; adverse effects ; analogs & derivatives ; therapeutic use ; Treatment Outcome ; Uric Acid ; blood ; Young Adult

BACKGROUNDDuring craniotomies using the transpetrosal-presigmoid approach, exposure of the sigmoid sinus remains an essential but hazardous step. In such procedures, accurate localization of the anterosuperior point of the transverse-sigmoid sinus junction (ASTS) is very important for reducing surgical morbidity. This study aimed to create an accurate and practical method for identifying the ASTS.

METHODSOn the lateral surfaces of 40 adult skulls (19 male skulls and 21 female skulls), a rectangular coordinate system was defined to measure the x and y coordinates of two points: the ASTS and the squamosal-parietomastoid suture junction (SP). With the coordinate system, the distribution characteristics of the ASTS were statistically analyzed and the differences between the ASTS and SP were investigated.

RESULTSFor ASTS-x, significant differences were found in different sides (P = 0.020); the ASTS-x in male skulls was significantly higher on the right side (P = 0.017); there was no significant difference between the sides in female skulls. There were no significant differences in gender or interaction of gender and side for ASTS-x, and for ASTS-y, there were no significant differences in side, gender, or interaction of gender and side. For both sides combined, the mean ASTS-x was significantly higher than the mean SP-x (P = 0.003) and the mean ASTS-y was significantly higher than the mean SP-y (P = 0.011).

CONCLUSIONSThis reference coordinate system may be an accurate and practical method for identifying the ASTS during presigmoid craniotomy. The SP might be difficult to find during presigmoid craniotomy and, therefore, it is not always a reliable landmark for defining the ASTS.

Adult ; Cranial Sinuses ; anatomy & histology ; Craniotomy ; Female ; Humans ; Male ; Middle Aged ; Skull ; anatomy & histology ; Transverse Sinuses ; anatomy & histology

BACKGROUNDThe diagnostic value of current prostate-specific antigen (PSA) tests is challenged by the poor detection rate of prostate cancer (PCa) in repeat prostate biopsy. In this study, we proposed a novel PSA-related parameter named PSA density variation rate (PSADVR) and designed a clinical trial to evaluate its potential diagnostic value for detecting PCa on a second prostate biopsy.

METHODSData from 184 males who underwent second ultrasound-guided prostate biopsy 6 months after the first biopsy were included in the study. The subjects were divided into PCa and non-PCa groups according to the second biopsy pathological results. Prostate volume, PSA density (PSAD), free-total PSA ratio, and PSADVR were calculated according to corresponding formulas at the second biopsy. These parameters were compared using t-test or Mann-Whitney U-test between PCa and non-PCa groups, and receiver operating characteristic analysis were used to evaluate their predictability on PCa detection.

RESULTSPCa was detected in 24 patients on the second biopsy. Mean values of PSA, PSAD, and PSADVR were greater in the PCa group than in the non-PCa group (8.39 μg/L vs. 7.16 μg/L, 0.20 vs. 0.16, 14.15% vs. -1.36%, respectively). PSADVR had the largest area under the curve, with 0.667 sensitivity and 0.824 specificity when the cutoff was 10%. The PCa detection rate was significantly greater in subjects with PSADVR >10% than PSADVR ≤10% (28.6% vs. 6.5%, P< 0.001). In addition, PSADVR was the only parameter in this study that showed a significant correlation with mid-to-high-risk PCa (r = 0.63, P = 0.03).

CONCLUSIONSOur results demonstrated that PSADVR improved the PCa detection rate on second biopsies, especially for mid-to-high-risk cancers requiring prompt treatment.

Aged ; Biopsy ; methods ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Prospective Studies ; Prostate ; metabolism ; pathology ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; blood ; diagnosis ; ROC Curve

OBJECTIVETo investigate the potential value of combined examinations of peripheral blood smear, bone marrow smear, bone marrow biopsy, chromosome banding analysis and flow cytometry (FCM) in the diagnoisis of myelodysplastic syndromes.

METHODSA total of 105 MDS patients who were admitted in our hospital from May 2013 to May 2015 and were diagnosed as MDS according to the criteria formulated by WHO were enrolled in this study. The accordance rate of diagnosis by the double test (peripheral blood smear plus bone marrow smear), triple test (above mentioned 2 tests plus bone marrow biopsy), quadruple test (above 3 tests plus chromosome banding analysis), and quintuple test (above 4 plus FCM) was amalyzed and compared.

RESULTSAmong the 105 MDS patients, the diagnosis accordance rate was 70.48% for double tests, while 83.81%, 84.76% and 93.33% for triple, quadruple and quintuplet tests, respectively which were significantly higher than that for double tests (peripheral blood smear plus bone marrow smear) (P < 0.05).

CONCLUSIONThe combined examination of the 5 methods can improve the accuracy of MDS diagnosis.

Biopsy ; Bone Marrow Examination ; Chromosome Banding ; Flow Cytometry ; Humans ; Myelodysplastic Syndromes ; diagnosis

To systematically review the incidence rate of adverse drug reaction/event by Qingkailing injection. Such databases as the PubMed, EMbase, the Cochrane library, CNKI, VIP WanFang data and CBM were searched by computer from foundation to July 30, 2015. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data and cross check data. Then, Meta-analysis was performed by using the R 3.2.0 software, subgroup sensitivity analysis was performed based on age, mode of medicine, observation time and research quality. Sixty-three studies involving 9,793 patients with Qingkailing injection were included, 367 cases of adverse reactions/events were reported in total. The incidence rate of adverse reaction in skin and mucosa group was 2% [95% CI (0.02; 0.03)]; the digestive system adverse reaction was 6% [95% CI(0.05; 0.07); the injection site adverse reaction was 4% [95% CI (0.02; 0.07)]. In the digestive system as the main types of adverse reactions/events, incidence of children and adults were 4.6% [0.021 1; 0.097 7] and 6.9% [0.053 5; 0.089 8], respectively. Adverse reactions to skin and mucous membrane damage as the main performance/event type, the observation time > 7 days and ≤ 7 days incidence of 3% [0.012 9; 0.068 3] and 1.9% [0.007 8; 0.046 1], respectively. Subgroup analysis showed that different types of adverse reactions, combination in the incidence of adverse reactions/events were higher than that of single drug, the difference was statistically significant (P < 0.05). This study suggested the influence factors of adverse reactions occur, and clinical rational drug use, such as combination, age and other fators, and the influence factors vary in different populations. Therefore, clinical doctors for children and the elderly use special care was required for a clear and open spirit injection, the implementation of individualized medication.
Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Drugs, Chinese Herbal ; adverse effects ; Female ; Humans ; Incidence ; Infant ; Infant, Newborn ; Injections ; Male ; Middle Aged

OBJECTIVETo investigate the protective effect of ulinastatin against the activation of tourniquet-induced platelet mitochondria apoptotic signaling.

METHOD44 patients with unilateral lower limb operation and tourniquet application were randomly divided into normal saline group and ulinastatin group, and were treated with normal saline and ulinastatin respectively. 12 patents with unilateral lower limb operation but without tourniquet application were enrolled in control group. Lipid hydroperoxide (LPO) in serum was detected by LPO assay kit, the content of ATP was examined by fluorescein-luciferase assay kit; the change of mitochondrial membrane potential (Δ ψm) was detected by JC-1 mitochondrial membrane potential kit; the content of cytoplasmic cytochrome C was examined by Cytochrome C ELISA kit; Caspase-3 activity was detected by Caspase-3 fluorometric assay kit.

RESULTSAs compared with control group, the patients in normal saline group exhibited significant platelet mitochondrial dysfunction which characterized by low ATP level and low mitochondrial membrane potential (Δ ψm) (P < 0.05). Tourniquet application resulted in the activation of the mitochondria apoptotic signaling in platelet, displaying increase in the serum LPO level, release of mitochondrial cytochrome C into the cytoplasm, and activation of caspase-3 (P < 0.05). These alterations above-mentioned were obviously improved by ulinastatin treatment (P < 0.05).

CONCLUSIONTourniquet induces platelet mitochondrial dysfunction and mitochondria-dependent apoptotic signaling activation, which can be improved by ulinastatin treatment.

Apoptosis ; Blood Platelets ; Caspase 3 ; Cytochromes c ; Glycoproteins ; Humans ; Membrane Potential, Mitochondrial ; Mitochondria ; Signal Transduction ; Tourniquets