Biomarkers on patient T cells diagnose active tuberculosis and monitor treatment response

BACKGROUND. The identification and treatment of individuals with tuberculosis (TB) is a global public health priority. Accurate diagnosis of pulmonary active TB (ATB) disease remains challenging and relies on extensive medical evaluation and detection of Mycobacterium tuberculosis (Mtb) in the patient’s sputum. Further, the response to treatment is monitored by sputum culture conversion, which takes several weeks for results. Here, we sought to identify blood-based host biomarkers associated with ATB and hypothesized that immune activation markers on Mtb-specific CD4⁺ T cells would be associated with Mtb load in vivo and could thus provide a gauge of Mtb infection.METHODS. Using polychromatic flow cytometry, we evaluated the expression of immune activation markers on Mtb-specific CD4⁺ T cells from individuals with asymptomatic latent Mtb infection (LTBI) and ATB as well as from ATB patients undergoing anti-TB treatment.RESULTS. Frequencies of Mtb-specific IFN-γ⁺CD4⁺ T cells that expressed immune activation markers CD38 and HLA-DR as well as intracellular proliferation marker Ki-67 were substantially higher in subjects with ATB compared with those with LTBI. These markers accurately classified ATB and LTBI status, with cutoff values of 18%, 60%, and 5% for CD38⁺IFN-γ⁺, HLA-DR⁺IFN-γ⁺, and Ki-67⁺IFN-γ⁺, respectively, with 100% specificity and greater than 96% sensitivity. These markers also distinguished individuals with untreated ATB from those who had successfully completed anti-TB treatment and correlated with decreasing mycobacterial loads during treatment.CONCLUSION. We have identified host blood-based biomarkers on Mtb-specific CD4⁺ T cells that discriminate between ATB and LTBI and provide a set of tools for monitoring treatment response and cure.TRIAL REGISTRATION. Registration is not required for observational studies.FUNDING. This study was funded by Emory University, the NIH, and the Yerkes National Primate Center.     

Deferoxamine promotes recovery of traumatic spinal cord injury by inhibiting ferroptosis

Ferroptosis is an iron-dependent novel cell death pathway. Deferoxamine, a ferroptosis inhibitor, has been reported to promote spinal cord injury repair. It has yet to be clarified whether ferroptosis inhibition represents the mechanism of action of Deferoxamine on spinal cord injury recovery. A rat model of Deferoxamine at thoracic 10 segment was established using a modified Allen's method. Ninety 8-week-old female Wistar rats were used. Rats in the Deferoxamine group were intraperitoneally injected with 100 mg/kg Deferoxamine 30 minutes before injury. Simultaneously, the Sham and Deferoxamine groups served as controls. Drug administration was conducted for 7 consecutive days. The results were as follows:(1) Electron microscopy revealed shrunken mitochondria in the spinal cord injury group.(2) The Basso, Beattie and Bresnahan locomotor rating score showed that recovery of the hindlimb was remarkably better in the Deferoxamine group than in the spinal cord injury group.(3) The iron concentration was lower in the Deferoxamine group than in the spinal cord injury group after injury.(4) Western blot assay revealed that, compared with the spinal cord injury group, GPX4, xCT, and glutathione expression was markedly increased in the Deferoxamine group.(5) Real-time polymerase chain reaction revealed that, compared with the Deferoxamine group, mRNA levels of ferroptosis-related genes Acyl-CoA synthetase family member 2(ACSF2) and iron-responsive element-binding protein 2(IREB2) were up-regulated in the Deferoxamine group.(6) Deferoxamine increased survival of neurons and inhibited gliosis. These findings confirm that Deferoxamine can repair spinal cord injury by inhibiting ferroptosis. Targeting ferroptosis is therefore a promising therapeutic approach for spinal cord injury.     

嵌顿痔不同治疗方法疗效分析

目的探讨嵌顿痔不同治疗方法的疗效。方法回顾性分析2009年8月至2012年8月迁西县人民医院确诊为嵌顿痔的160例患者的临床资料,其中采取外剥内扎法的80例患者作为A组,吻合器痔上黏膜环切术(PPH)结合外痔血栓剥除术的80例患者作为B组。对比分析两组患者的手术时间、住院时间、住院费用等指标及临床疗效,对比分析两组术后6个月并发症发生情况。结果B组患者的手术时间、住院时间显著少于A组[(15.4±1.1)min比(38.7±0.5)min,(5.3±0.6)d比(12.4±1.3)d,P<0.01];B组患者的有效率显著高于A组(88.8%比66.3%),而总体并发症发生率及复发率显著低于A组(17.5%比33.8%,5%比18.8%,P<0.05)。结论 PPH结合外痔血栓剥除术临床疗效显著。     

The Long-Term Effective Rate of Different Branches of Idiopathic Trigeminal Neuralgia After Single Radiofrequency Thermocoagulation: A Cohort Study

To evaluate the efficacy of computed tomography (CT) guided single radiofrequency thermocoagualtion (RFT) in 1137 patients with idiopathic trigeminal neuralgia after a follow-up period of 11 years, specially focused on duration of pain relief in different branches of trigeminal nerve, side effect, and complications.Retrospective study of patients with idiopathic trigeminal neuralgia treated with a single CT guided RFT procedure between January 2002 and December 2013.The mean follow-up time was 46.14 ± 30.91 months. Immediate postprocedure pain relief was 98.4%. V2 division obtained the best pain relief rate: 91%, 89%, 80%, 72%, 60%, and 54% at 1, 3, 5, 7, 9, and 11 years, respectively. No statistical difference pairwise comparison was in other groups. The complications included masseter muscle weakness, corneitis, diplopia, ptosis, hearing loss, limited mouth opening, and low pressure headache. Masticatory weakness mostly occurred in patients with V3 branch involvement, while Corneitis and Diplopia all in patients with V1 branch involvement. No mortalities observed during or after RFT.All different branches division of trigeminal neuralgia achieved comparable satisfactory curative effect; V2 obtained the best excellent pain relief, after RFT procedure. Facial numbness is inevitable after RFT, which patients who have pain in all 3 trigeminal divisions and patients who desire no facial numbness should be cautious. Masticatory weakness is mainly related with V3 injured, while Corneitis and Diplopia in patients with V1 injured by RFT.     

Comparison of Laparoscopic-Assisted Operations and Laparotomy Operations for the Treatment of Hirschsprung Disease: Evidence From a Meta-Analysis

The purpose of this meta-analysis is to compare the relative merits among laparoscopic-assisted operations and laparotomy operations for patients with Hirschsprung disease.PubMed, Web of Science, and Wanfang databases were searched for the related articles. We analyzed dichotomous variables by estimating odds ratios (ORs) with their 95% confidence intervals (CIs) and continuous variables using the weighted mean difference (WMD) with the 95% CI. The random-effects model (REM) was used to combine the results. The outcome measures included operating time (OT), estimated blood loss (EBL), length of hospital stay (LOHS), mean first bowel movement (MFBM), and number of complications.Sixteen articles were included in the meta-analysis. These studies involved a total of 774 patients, 396 of whom underwent laparoscopic-assisted operations and 378 of whom underwent laparotomy operations. The EBL (WMD = −1.48, 95% CI = −1.82, −1.13), LOHS (WMD = −0.67, 95% CI = −0.86, −0.49), MFBM (WMD = −0.83, 95% CI = −1.05, −0.61), and number of complications (OR = 0.60, 95% CI = 0.40, 0.89) were significantly lower in laparoscopic-assisted operations than in laparotomy operations. The OT (WMD = 0.12, 95% CI = −0.05, 0.28) showed no significant differences between laparoscopic-assisted operations and laparotomy operations.Compared with laparotomy operations, laparoscopic-assisted operations are generally safer and more reliable for patients with Hirschsprung disease.