Objective: To evaluate the clinical value of the MeltPro MTB assays in the diagnosis of drug-resistant tuberculosis. Methods: A cross-sectional study design was used to retrospectively collect all 4 551 patients with confirmed tuberculosis between January 2018 and December 2019 at Beijing Chest Hospital, Capital Medical University. Phenotypic drug sensitivity test and GeneXpert MTB/RIF (hereafter referred to as "Xpert") assay were used as gold standards to analyze the accuracy of the probe melting curve method. The clinical value of this technique was also evaluated as a complementary method to conventional assays of drug resistance to increase the detective rate of drug-resistant tuberculosis. Results: By taking the phenotypic drug susceptibility test as the gold standard, the sensitivity of the MeltPro MTB assays to detect resistance to rifampicin, isoniazid, ethambutol and fluoroquinolone was 14/15, 95.7%(22/23), 2/4 and 8/9,respectively; and the specificity was 92.0%(115/125), 93.2%(109/117), 90.4%(123/136) and 93.9%(123/131),respectively; the overall concordance rate was 92.1%(95%CI:89.6%-94.1%),and the Kappa value of the consistency test was 0.63(95%CI:0.55-0.72).By taking the Xpert test results as the reference, the sensitivity of this technology to the detection of rifampicin resistance was 93.6%(44/47), the specificity was100%(310/310), the concordance rate was 99.2%(95%CI:97.6%-99.7%), and the Kappa value of the consistency test was 0.96(95%CI:0.93-0.99). The MeltPro MTB assays had been used in 4 551 confirmed patients; the proportion of patients who obtained effective drug resistance results increased from 83.3% to 87.8%(P<0.01); and detection rate of rifampicin, isoniazid, ethambutol, fluoroquinolone resistance, multidrug and pre-extensive drug resistance cases were increased by 3.2%, 14.7%, 22.2%, 13.7%, 11.2% and 12.5%, respectively. Conclusion: The MeltPro MTB assays show satisfactory accuracy in the diagnosis of drug-resistant tuberculosis. This molecular pathological test is an effective complementary method in improving test positivity of drug-resistant tuberculosis.
Humans ; Rifampin/therapeutic use* ; Antibiotics, Antitubercular/therapeutic use* ; Mycobacterium tuberculosis ; Ethambutol/pharmacology* ; Isoniazid/pharmacology* ; Paraffin Embedding ; Retrospective Studies ; Cross-Sectional Studies ; Drug Resistance, Bacterial ; Sensitivity and Specificity ; Tuberculosis, Multidrug-Resistant/drug therapy*

With the increasing availability of genetic tests, more doctors are offering and ordering such tests for their patients. Ordering a genetic test appears to be a simple process of filling in paperwork, drawing 3 mL of blood in an ethylenediaminetetraacetic acid tube and receiving a test report. This is identical to sending off a full blood count. However, it is far more complex than that. There are many potential pitfalls, as shown by the increasing number of complaints and lawsuits filed against doctors and allied health staff. Furthermore, clinical genetics involves more than just ordering tests; in fact, focusing on genetic tests alone is a potential pitfall. In this review, we discuss the common pitfalls in clinical genetics and how doctors can avoid these pitfalls to ensure patient safety and to safeguard their practice.
Humans ; Edetic Acid ; Fenbendazole ; Patient Safety ; Physicians

A hyperuricemic rat model induced by adenine and ethambutol was established to investigate the anti-hyperuricemia activity and its mechanism of the flavonoid extract from saffron floral bio-residues. Sixty-seven SD rats were randomly divided into control group, model group, positive control group, and flavonoid extract groups(with 3 doses), respectively, and each group contained 11 or 12 rats. The hyperuricemic model was established by continuous oral administration of adenine(100 mg·kg~(-1)) and ethambutol(250 mg·kg~(-1)) for 7 days. At the same time, the positive control group was given allopurinol(20 mg·kg~(-1) per day) and the flavonoid extract groups were given the flavonoid extract at doses of 340, 170 and 85 mg·kg~(-1) per day, respectively. On day 8, rat serum, liver, kidney, and intestinal tissues were collected, and the levels of uric acid in serum and tissue, the xanthine oxidase activities and antioxi-dant activities in serum and liver were evaluated, and the kidney histopathology was explored. In addition, an untargeted serum metabolomics study was performed. According to the results, the flavonoid extract effectively reduced the uric acid levels in serum, kidney and ileum and inhibited the xanthine oxidase activities and elevated the antioxidant activities of serum and liver in hyperuricemic rat. At the same time, it reduced the levels of inflammation factors in kidney and protected renal function. Moreover, 68 differential metabolites of hyperuricemic rats were screened and most of which were lipids and amino acids. The flavonoid extract significantly retrieved the levels of differential metabolites in hyperuricemic rats, such as SM(d18:1/20:0), PC[18:0/18:2(92,12Z)], palmitic acid and citrulline, possibly through the following three pathways, i.e., arginine biosynthesis, glycine, serine and threonine metabolism, and histidine metabolism. To sum up, the flavonoid extract of saffron floral bio-residues lowered the uric acid level, increased the antioxidant activity, and alleviated inflammatory symptoms of hyperuricemic rats, which may be related to its inhibition of xanthine oxidase activity and regulation of serum lipids and amino acids metabolism.
Rats ; Animals ; Flavonoids/pharmacology* ; Uric Acid ; Crocus ; Xanthine Oxidase ; Ethambutol/adverse effects* ; Rats, Sprague-Dawley ; Hyperuricemia/drug therapy* ; Kidney ; Antioxidants/pharmacology* ; Plant Extracts/adverse effects* ; Amino Acids ; Adenine/adverse effects* ; Lipids

OBJECTIVE: To investigate the clinical effect of Shenfu injection combined with glucocorticoid in the treatment of acute left heart failure complicated with bronchospasm. METHODS: A prospective study was conducted.Ninety patients with acute left heart failure complicated with bronchospasm admitted to Huai'an Second People's Hospital from January 2021 to July 2022 were selected and divided into conventional treatment group, hormone therapy group and combined treatment group according to random number table method, with 30 cases in each group. All patients in the 3 groups received basic Western medicine treatment. On this basis, the conventional treatment group was given 0.25-0.50 g aminophylline injection plus 5% glucose injection or 0.9% sodium chloride injection (diabetes patients) 100 mL slow intravenous infusion, 1-2 times a day. In the hormone treatment group, 1 mg of budesonide suspension for inhalation was diluted to 2 mL by 0.9% sodium chloride injection, twice a day, and applied until 48 hours after the pulmonary wheezing disappeared. The combined treatment group was given glucocorticoid combined with Shenfu injection 80 mL plus 5% glucose injection or 0.9% sodium chloride injection (diabetes patients) 250 mL intravenously, once a day. All treated for 1 week. The general data, traditional Chinese medicine (TCM) syndrome score, TCM syndrone efficacy index, acute left heart failure efficacy, bronchospasm efficacy, systolic blood pressure (SBP), mean arterial pressure (MAP), serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level and safety of the 3 groups were compared. The patients were followed up for 6 months, and the mortality and re-hospitalization rate of the 3 groups were recorded. RESULTS: Among the 90 patients, a total of 83 patients completed the study, excluding the cases dropped due to death and other reasons. There were 29 cases in the combined treatment group, 25 cases in the hormone therapy group and 29 cases in the conventional treatment group. There were no significant differences in age, gender, course of disease, and previous history (history of diabetes, history of hypertension, history of hyperlipidemia) among the 3 groups. Therefore, they were comparable. The difference of TCM syndrome score before and after treatment, TCM syndrome efficacy index of combined treatment group and hormone therapy group were higher than those of conventional treatment group [difference of TCM syndrome score: 15.14±5.74, 13.24±5.75 vs. 10.62±5.87, TCM syndrome efficacy index: (67.84±14.31)%, (59.94±14.26)% vs. (48.92±16.74)%, all P < 0.05], and the difference of TCM syndrome score and TCM syndrome efficacy index of combined treatment group were higher than those of hormone treatment group (both P < 0.05). The total effective rate of acute left heart failure and bronchospasm in the combined treatment group was significantly higher than that in the conventional treatment group (total effective rate of acute left heart failure: 96.55% vs. 75.86%, total effective rate of bronchospasm: 93.10% vs. 65.52%, both P < 0.05). The difference of serum NT-proBNP before and after treatment in combination therapy group and hormone therapy group was significantly higher than that in conventional treatment group (ng/L: 7 922.86±5 220.31, 7 314.92±4 450.28 vs. 4 644.79±3 388.23, all P < 0.05), and the difference of serum NT-proBNP before and after treatment in the combined treatment group was significantly higher than that in the hormone treatment group (P < 0.05). There were no significant differences in SBP difference, MAP difference, mortality and re-hospitalization rate among the 3 groups. No adverse reactions occurred in the 3 groups during treatment. CONCLUSIONS Shenfu injection combined with glucocorticoid is effective in the treatment of patients with acute left heart failure complicated with bronchospasm. It is superior to glucocorticoid and aminophylline in relieving bronchospasm, reducing NT-proBNP level and improving total effective rate, and has good prognosis and safety.
Humans ; Glucocorticoids/therapeutic use* ; Bronchial Spasm ; Prospective Studies ; Aminophylline/therapeutic use* ; Sodium Chloride/therapeutic use* ; Natriuretic Peptide, Brain ; Peptide Fragments ; Heart Failure/drug therapy* ; Diabetes Mellitus ; Glucose

Objective To explore the therapeutic effect of ethambutol tablets (EMB) on pulmonary tuberculosis (PTB) in rats and whether the action mechanism of EMB is related to Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway. Methods Sixty SD rats were assigned into a control group,a PTB group,a PTB+EMB group (30 mg/kg),and a PTB+EMB+Colivelin (JAK/STAT pathway activator) group (30 mg/kg+1 mg/kg) via the random number table method,with 15 rats in each group.The rats in other groups except the control group were injected with 0.2 ml of 5 mg/ml Mycobacterium tuberculosis suspension to establish the PTB model.After the modeling,the rats were administrated with corresponding drugs for 4 consecutive weeks (once a day).On days 1,14,and 28 of administration,the body weights of rats were measured and the Mycobacterium tuberculosis colonies were counted.Hematoxylin-eosin staining was carried out to detect the pathological changes in the lung tissue.Enzyme-linked immunosorbent assay was employed to measure the levels of interleukin(IL)-6,tumor necrosis factor-α (TNF-α),IL-1β,and interferon-γ (IFN-γ) in the serum.Flow cytometry was used to determine the levels of T lymphocyte subsets CD3+,CD4+,CD8+,and CD4+/CD8+.The 16S rRNA sequencing was performed to detect the relative abundance of the intestinal microorganisms.Western blotting was employed to determine the expression of the proteins in the JAK/STAT pathway. Results Compared with the control group,the modeling of PTB reduced the rat body weight (on days 14 and 28),increased Mycobacterium tuberculosis colonies,caused severe pathological changes in the lung tissue,and elevated the levels of IL-6,TNF-α,and IL-1β in serum and CD8+.Moreover,the modeling increased the relative abundance of Bacteroides,Peptococcus,Clostridium,Actinomyces,Lactobacillus,Verrucomicrobium,and Veillonella in the intestine,up-regulated the protein levels of phosphorylated JAK2 and phosphorylated STAT3 in the lung tissue,and lowered the levels of CD3+,CD4+,CD4+/CD8+,and IFN-γ levels (all P<0.001).Compared with the PTB group,PTB+EMB increased the rat body weight (on days 14 and 28),reduced Mycobacterium tuberculosis colonies,alleviated the pathological damage in lung tissue,lowered the levels of IL-6,TNF-α,and IL-1β in serum and CD8+.Moreover,the treatment decreased the relative abundance of Bacteroides,Peptococcus,Clostridium,Actinomyces,Lactobacillus,Verrucomicrobium,Veillonella in the intestine,down-regulated the protein levels of phosphorylated JAK2 and phosphorylated STAT3 in the lung tissue,and elevated the levels of CD3+,CD4+,CD4+/CD8+,and IFN-γ (all P<0.001).Colivelin weakened the alleviation effect of EMB on PTB (all P<0.001). Conclusion EMB can inhibit the JAK/STAT signaling pathway to alleviate the PTB in rat.
Animals ; Body Weight ; Ethambutol/pharmacology* ; Interferon-gamma/pharmacology* ; Interleukin-6/metabolism* ; Janus Kinases/pharmacology* ; Mycobacterium tuberculosis/metabolism* ; RNA, Ribosomal, 16S ; Rats ; Rats, Sprague-Dawley ; STAT Transcription Factors/pharmacology* ; Signal Transduction ; Tablets/pharmacology* ; Tuberculosis, Pulmonary/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*

OBJECTIVE: To investigate the value of ⁶⁸Ga-labeled prostate specific membrane antigen (PSMA) PET/CT for assessing tumor load in primary lesions for risk stratification and predicting metastasis of newly diagnosed prostate cancer (PCa). METHODS: We retrospectively analyzed the data of 36 patients (mean age 71.3 ± 8.6 years, range 56 to 89 years) with newly diagnosed PCa undergoing ⁶⁸Ga-PSMA-I&T PET/CT from June 2018 to July 2019. SUVmax and SUVmean of the primary lesions were measured, and the primary PSMA tumor volume (PSMA-TV) and total lesion PSMA (TL-PSMA) were automatically measured and calculated in all the patients. The correlations of primary SUVmax, PSMA-TV, and TL-PSMA with PSA and Gleason score (GS) were analyzed, and SUVmax, PSMA-TV and TL-PSMA of the primary lesions were compared among different PCa subgroups. RESULTS: SUVmax, PSMA-TV and TL-PSMA of the primary lesions were all correlated with PSA and GS (P < 0.05). PCa subgroup analysis showed that SUVmax, PSMA-TV and TL-PSMA were all significantly higher in patients with PSA >20 ng/mL than in those with PSA ≤20 ng/mL (P < 0.001), and were higher in patients with a GS ≥8 than in those with a GS ≤7 (P < 0.001). PSMA-TV and TL-PSMA were significantly higher in patients with tumor metastasis than in those without metastasis (P < 0.001), while SUVmax did not differ significantly with tumor metastasis. SUVmax (P=0.002), PSMA-TV (P < 0.001), and TL-PSMA (P < 0.001) were all significantly higher in high-risk group than in low-to moderate-risk group. CONCLUSION PSMA-TV and TL-PSMA of ⁶⁸Ga-PSMA-I&T PET/CT have potential value in predicting risk stratification and metastasis of newly diagnosed PCa.
Aged ; Aged, 80 and over ; Edetic Acid ; Gallium Isotopes ; Gallium Radioisotopes ; Humans ; Male ; Middle Aged ; Oligopeptides ; Positron Emission Tomography Computed Tomography ; Prostate-Specific Antigen ; Prostatic Neoplasms/pathology* ; Retrospective Studies ; Tumor Burden

OBJECTIVES: To investigate the clinical effect of Er:YAG laser combined with ethylenediamine tetra acetic acid (EDTA) on three-walled periodontal intrabony defects adjacent to implant sites. METHODS: A total of 30 patients with three-walled periodontal intrabony defects adjacent to implant sites were treated with the combination therapy. Patients with three-walled intrabony defects were divided into two groups according to the depth of the intrabony pocket between the implant and natural teeth. Evaluation of wound healing was performed 10 days after the operation, and bone augmentation was evaluated 6 months after the operation. RESULTS: Primary healing in group 1 was 92.31%, primary healing in group 2 was 82.35%. No significant difference was observed between the two groups ( CONCLUSIONS The effect of bone augmentation with combination therapy was more ideal in group 2 than in group 1. Implant placement with combination therapy may be a viable technique to reconstruct three-walled intrabony defects due to the space maintenance provided by implants and bone grafts and the good root surface biocompatibility provided by the Er:YAG laser and EDTA.
Acetic Acid ; Alveolar Bone Loss ; Dental Implants ; Ethylenediamines ; Follow-Up Studies ; Guided Tissue Regeneration, Periodontal ; Humans ; Lasers, Solid-State ; Periodontal Attachment Loss ; Treatment Outcome

BACKGROUND: Long-term administration of ethambutol (EMB) for Mycobacterium avium complex lung disease (MAC-LD) sometimes leads to permanent discontinuation of EMB due to various adverse events. This study aimed to investigate treatment outcomes after discontinuation of EMB.METHODS: Among patients diagnosed with MAC-LD between January 2001 and December 2014, 508 patients whose treatment was initiated with standard regimen until May 2018 were enrolled at a tertiary referral center in Korea. Of these 508 patients, 60 (11.8%) discontinued EMB due to various adverse effects. Among these 60 patients, treatment outcomes were analyzed for 44 patients by comparing their outcomes with those of matched subjects who received the standard treatment regimen without EMB discontinuation.RESULTS: The mean age of the 60 patients who discontinued EMB was 64.4 years. Ocular toxicity was the most common cause of discontinuation of EMB (75.0%, 45/60). The mean duration of EMB administration before its discontinuation was 7.0 ± 4.6 months. The treatment failure rate of the 44 patients with EMB discontinuation analyzed for treatment outcome was 29.6%, which was higher than that of the matched patients who received the standard regimen (18.3%), although the difference was not significant (P = 0.095). Of these 44 patients, EMB was substituted with later-generation fluoroquinolone in 23 patients, and the treatment failure rate of these 23 patients was significantly higher than that of the matched patients who received the standard regimen (39.1% vs. 19.3%, P = 0.045).CONCLUSION: These findings suggest that treatment outcomes are unsatisfactory in patients with MAC-LD who discontinue EMB owing to adverse events. Notably, there was a statistically significant high failure rate in patients who were prescribed fluoroquinolone to replace EMB.
Ethambutol ; Fluoroquinolones ; Humans ; Korea ; Lung Diseases ; Mycobacterium avium Complex ; Mycobacterium avium ; Mycobacterium ; Tertiary Care Centers ; Treatment Failure ; Treatment Outcome

ethambutol (E) administered in patients with new sputum positive drug-susceptible pulmonary tuberculosis (TB) with tuberculous meningoencephalitis (TM) and human immunodeficiency virus (HIV) co-infection in the intensive phase of treatment.METHODS: Fifty-four patients with TB/TM and HIV co-infection were enrolled for this study. Group 1 comprised of 23 patients treated with E and H intravenously, while rifampicin and pyrazinamide were prescribed orally. Group 2 consisted of 31 patients treated with the first-line anti-TB drugs orally. The concentrations of H and E in blood serum were detected using a chromatographic method.RESULTS: A significant improvement in the clinical symptoms and X-ray signs in patients treated intravenously with H and E was observed and compared to group 2. The sputum Mycobacterium tuberculosis positivity was observed during the second month of the treatment in 25.0% of patients from group 1 and 76.1% of the patients from the control group (p=0.003). In addition, nine patients (39.1%) died up to 6 months when H and E were prescribed intravenously compared with 22 (70.9%) in group 2 (p=0.023).CONCLUSION: In TB/TM with HIV, the intravenous H and E treatment was more effective than oral H and E treatment at 2 months of intensive treatment in sputum conversion as well as in clinical improvement, accompanied by significantly higher mean serum concentrations. In addition, the mortality rate was lower in intravenous H and E treatment compared to oral treatment.]]>
Coinfection ; Ethambutol ; HIV Infections ; HIV ; Humans ; Isoniazid ; Meningoencephalitis ; Methods ; Mortality ; Mycobacterium tuberculosis ; Pyrazinamide ; Rifampin ; Serum ; Sputum ; Tuberculosis ; Tuberculosis, Meningeal ; Tuberculosis, Pulmonary

The aim of this study was to compare the efficiency of four final irrigation protocols in smear layer removal and bacterial inhibition in root canal systems. Thirty roots inoculated with Enterococcus faecalis were prepared with ProTaper Universal files. The teeth were disinfected by conventional needle irrigation, sonic agitation using the EndoActivator device, passive ultrasonic irrigation, or an M3 Max file. Teeth with no root canal preparation served as blank controls for the establishment of the infection baseline. Teeth with preparation but no final irrigation served as a post-instrumentation baseline. After the final irrigation, the teeth were sectioned in half. One half of each tooth was examined by scanning electron microscopy (SEM) to assess smear layer removal using a five-point scale. The other half was examined by confocal laser scanning microscopy (CLSM) using the LIVE/DEAD BackLight bacterial viability kit to evaluate the depth of bacterial survival in dentinal tubules. SEM analysis revealed no significant difference in smear layer removal throughout the whole canal among the EA, PUI, and M3 Max groups (P > 0.05). CLSM revealed that PUI achieved the greatest bacterial inhibition depth in the coronal ((174.27 ± 31.63) μm), middle ((160.94 ± 37.77) μm), and apical ((119.53 ± 28.49) μm) thirds of the canal (all P < 0.05 vs. other groups). According to this comprehensive SEM and CLSM evaluation, PUI appears to have the best infection control ability in root canal systems.
Dental Pulp Cavity ; Edetic Acid ; Humans ; Microscopy, Electron, Scanning ; Root Canal Irrigants ; Root Canal Preparation ; Smear Layer ; Sodium Hypochlorite