Metabolomic analysis of human cerebrospinal fluid in patients with tuberculous meningitis using ultra high performance liquid chromatography tandem mass spectrometry / 中华检验医学杂志

Objective:To study the non-target metabolomics analysis and to analyze the metabolomic changesof cerebrospinal fluid (CSF) in patients with tuberculous meningitis.Methods:Case-control study. From July 2018 to July 2019, 20 cerebrospinal fluid specimens of diagnosed patients with tuberculous meningitis were collectedin the department of neurology from the first medical center of the PLA general hospital and the eighth medical center of the PLA general hospital and 20 CSF without tuberculous meningitis as the control. Among them, there were 12 males and 8 femalesin the tuberculous meningitis group, aged (37.9±16.1) years; there were 13 males and 7 femalesin the control group, aged (34.7±14.8) years. Using ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) technology with three different mode, namely reverse phase chromatography positive ion mode, reverse phase chromatography negative ion mode and hydrophilic chromatography positive ion mode,to detectthe metabolic fingerprints of patients′CSF and analyzed by SIMCA software for orthogonal partial least squares discriminant analysis (OPLS-DA). The variable importance projection value of OPLS-DA model (threshold value>1) plus the P value of t-test (P<0.05) was applied to find the differential metabolites in the cerebrospinal fluid of the two groups of patients.Results:Ten differential metabolites were found in CSF, including L-isoleucine, L-phenylalanine, L-kynurenine, L-methionine, L-tyrosine acid, dimethylglycine, L-alanine, L-threonine, L-histidine and L-lysine, and all of them were up-regulated in the tuberculous meningitis group.Conclusion:Changesof the amino acid metabolism found in the cerebrospinal fluid of tuberculous meningitis patients can provide basis for differential diagnosis and basic molecular research of tuberculous meningitis.

Efficacy and safety of high-dose fluconazole in the initial treatment of non-human immunodeficiency virus-related cryptococcal meningitis / 中华传染病杂志

Objective@#To evaluate the efficacy and safety of high-dose fluconazole alone or combined with flucytosine as initial therapy for cryptococcal meningitis (CM) in non-human immunodeficiency virus (HIV)-related patients.@*Methods@#Twenty-five non-HIV-infected patients with CM from June 2015 to September 2018 in Huashan Hospital, Fudan University, who were initially treated with high-dose fluconazole with or without flucytosine for at least seven days were retrospectively reviewed.Clinical features and antifungal (600-800 mg/d) regimens were recorded, clinical responses and drug-related adverse events were evaluated. Mann-Whitney test and Fisher′s exact probabilities test were applied to compare variables between groups.@*Results@#Of the 25 patients enrolled in this study, 15 had predisposing factors. Headache (25 cases), fever (21 cases), vomiting (13 cases) and neck stiffness (13 cases) were common manifestations. Abnormalities of cranial computed tomography (CT) scan and/or magnetic resonance imaging (MRI) were found in 22 cases.Nineteen patients were treated with high-dose fluconazole plus flucytosine for initial therapy, and six patients were treated with high-dose fluconazole alone. The course of initial regimens with high-dose fluconazole was 42 (29, 120) days. At the end of initial therapy, partial response in 20 patients, stable response in three patients and death in two patients were observed, and the overall effective rate was 80%(20/25). In treatment failure group of initial treatment, the proportion of patients with baseline cerebrospinal fluid opening pressure over 300 mmH2O (1 mmH2O=0.009 8 kPa) and with altered mental status were both significantly higher compared with those in treatment success group. Fluconazole related adverse drug events were observed including elevated transaminases (one case), gastrointestinal symptoms combined with hypokalemia (two cases), and systemic rash (three cases). Except for three patients with rash reduced the dosage of fluconazole, no other patients were given dosage adjustment.@*Conclusion@#High-dose fluconazole alone or combined with flucytosine is effective and safe for the initial therapy of non-HIV-related CM patients.

Efficacy and safety of high-dose fluconazole in the initial treatment of non-human immunodeficiency virus-related cryptococcal meningitis / 中华传染病杂志

Objective To evaluate the efficacy and safety of high-dose fluconazole alone or combined with flucytosine as initial therapy for cryptococcal meningitis(CM)in non-human immunodeficiency virus(HIV)-related patients.Methods Twenty-five non-HIV-infected patients with CM from June 2015 to September 20 18 in Huashan Hospital,Fudan University,who were initially treated with high-dose fluconazole with or without flucytosine for at least seven days were retrospectively reviewed.Clinical features and antifungal(600-800 mg/d)regimens were recorded,clinical responses and drug-related adverse events were evaluated.Mann-Whitney test and Fisher's exact probabilities test were applied to compare variables between groups.Results of the 25 patients enrolled in this study,15 had predisposing factors.Headache(25 cases),fever(21 cases),vomiting(13 cases)and neck stiffness(13 cases)were common manifestations.Abnormalities of cranial computed tomography(CT)scan and/or magnetic resonance imaging(MRI)were found in 22 cases.Nineteen patients were treated with high-dose fluconazole plus flucytosine for initial therapy,and six patients were treated with high-dose fluconazole alone.The course of initial regimens with high-dose fuconazole was 42(29,120)days.At the end of initial therapy,partial response in 20 patients,stable response in three patients and death in two patients were observed,and the overall effective rate was 80％(20/25).In treatment failure group of initial treatment,the proportion of patients with baseline cerebrospinal fuid opening pressure over 300 mmH2 O(1 mmH2O=0.009 8 kPa)and with altered mental status were both significantly higher compared with those in treatment Success group.Fluconazole related adverse drug events were observed including elevated transaminases(one case),gastrointestinal symptoms combined with hypokalemia(two cases),and systemic rash(three cases).Except for three patients with rash reduced the dosage of fluconazole.no other patients were given dosage adjustment.Conclusion High-dose fluconazole alone or combined with flucytosine is effective and safe for the initial therapy of non-HIV-related CM patients.

Exploration of the serum differential biomarkers for osteoarticular tuberculosis based on matrix-assisted laser desorption/ionization time of flight mass spectrometry / 中华检验医学杂志

Objective Toinvestigatestatistically significant peptide peaks as biomarkersto diagnose osteoarticular tuberculosis, matrix-assisted laser desorption/ ionization time of flight mass spectrometry (MALDI-TOF MS) was applied to identify the characteristic fingerprint among the serum of patients with osteoarticular tuberculosis, rheumatoid arthritis and healthy adults.Methods Clinical Study. Serum samples of untreatedpatients with osteoarticular tuberculosis and rheumatoid arthritis were collected from August 2018 to December 2018, and serum samples of healthy adults from physical examination were collected as control. After analysis with MALDI-TOF MS, the serum peptide fingerprint datawas imported into software, and protein polypeptide peaks with obvious differences were screened to establish diagnostic models.Results Established the diagnostic model of osteoarticular tuberculosis and healthy adults with m/z 2943.9, 5929.6, 7615.4 and 9033.8 as differential protein polypeptides, the diagnostic model of osteoarticular tuberculosis and rheumatoid arthritis with m/z 4195.6, 5847.6, 5929.6 and 7748.6 as differential protein polypeptides. To these two models, the sensitivity were 95.00％ and 97.50％, respectively. The specificity were 85.71％ and 88.46％, respectively. The accuracy rates were 89.58％ and 92.39％, respectively. The AUC value of ROC curves were 0.8859 and 0.8709, respectively. Conclusions By mass spectrometry and software analysis, the serum protein polypeptides with statistical difference were found successfully. The related diagnostic modelsarealso established, which has certain reference value for auxiliary diagnosis of osteoarticular tuberculosis.

Efficacy and safety of high-dose caspofungin in the treatment of invasive pulmonary aspergillosis / 中华传染病杂志

Objective To investigate the clinical efficacy and safety of high-dose caspofungin (70 mg/d)as initial or salvage treatment for invasive pulmonary aspergillosis.Methods Twenty-one patients with proven or probable invasive pulmonary aspergillosis from June 2014 to October 2017 in Huashan Hospital,Fudan University were retrospectively reviewed.According to the anti-fungal treatment before high-dose caspofungin application,patients were divided into initial treatment group and salvage treatment group.Patients' clinical data and laboratory data were collected.The characteristics,clinical efficacy,adverse reactions,one-year survival rate and the overall effective rate were evaluated.The prognosis of the two groups was compared by Kaplan-Meier analysis.Results Twenty of the 21 patients opportunistic acquired invasive pulmonary aspergillosis during the treatment of underlying diseases.Five patients were initially treated with high-dose caspofungin for 68 (62) days.At week 12,one patient achieved complete response,3 patients achieved partial response,and the overall effective rate was 80％ (4/5).Sixteen patients received caspofungin as salvage therapy for 66.50 (58) days,of which one patient got complete response at week 12,10 had partial response,and the overall effective rate was 68.75％ (11/16).One-year follow-up showed that no patient died in the initial treatment group,and the one-year survival rate was 100％ (5/5).In salvage treatment group,3 patients died of pulmonary bacterial infections and the one-year survival rate was 81.25％ (13/16).During treatment,one patient had elevated total bilirubin,which was possibly associated with high-dose caspofungin.Conclusions High-dose caspofungin regimen has good efficacy and safety,both for initial treatment and salvage therapy in patients with invasive pulmonary aspergillosis.

Comparison of the therapeutic effects of dark plum mixture given by gastric gavage and oral spray on rats with radiation-induced xerostomia / 中国比较医学杂志

Objective To compare the therapeutic effect of dark plum mixture on rats with radiation-induced xerostomia, given by gastric gavage and oral spray. Methods Rat model of radiation-induced xerostomia were developed by electron linear accelerator. Wistar rats were randomly divided into spray group and gastric gavage group, and normal group, positive control group and normal control group were set up within these two groups. The dark plum mixture was administered for 14 days. After treated for 7 days and 14 days, saliva was collected and submandibular gland samples were collected. The salivary secretion, Sorgan index, component analysis and pathological changes of submaxillary glands between the groups were assessed. Results On the 7thday after irradiation, the saliva secretion and gland coefficient of the dark plum spray group were significantly higher than the positive control group and normal control group (P＜ 0. 05). The saliva secretion, gland coefficient and saliva amylase activity of the dark plum mixture spray group were significantly higher than the dark plum mixture gastric gavage group (P＜ 0. 05). On the 14th day after irradiation, the saliva secretion and gland coefficient of the oral spray group were significantly higher than the gastric gavage group (P ＜ 0. 05 ). The pathological examination of submandibular gland tissues showed that 7 days after irradiation, there were less interglandular space and inflammatory cell infiltration in the oral spray group than the gastric gavage group. On the 14th day after irradiation, the ductal damage and cell nuclear pyknosis in the oral spray group were milder than the gastric gavage group. Vacuolated necrosis and nuclear pyknosis of some glandular cells were visible in the gastric gavage group 7 and 14 days after irradiation. Conclusions Compared with gastric gavage, the oral spray of dark plum mixture increases more saliva and salivary α-amylase secretion, effectively promote the repair of submandibular glandular cells after salivary gland irradiation, and indicates a better therapeutic effect on radiation-induced xerostomia.

Clinical Study on Si-Zi Powder for Hot Compress To Improve Living Quality of Hemodialysis Patients / 世界科学技术-中医药现代化

This study was aimed to observe the clinical effect and quality of life (QOL) of Si-Zi (SZ) powder for hot compress to improve gastrointestinal functions of hemodialysis patients.A total of 60 hemodialysis patients were randomly divided into the treatment group and the control group.Gastrointestinal Symptom Rating Scale (GSRS) and QOL of both groups before and after the treatment of SZ powder were compared continuously.The results showed that after intervention,the total relieve rate was 96.7％ in treatment group,and 53.3％ in the control group.The effect of SZ powder group was to obviously improve the gastrointestinal symptoms and QOL (P ＜ 0.05).It was concluded that SZ powder for hot compress can improve gastrointestinal functions and increase QOL of hemodialysis patients.