Background: Metagenomic next-generation sequencing (mNGS) is an effective diagnostic method for infectious diseases, however, its clinical utility for tuberculosis (TB) diagnosis remains to be demonstrated. Methods: A total of 322 bronchoalveolar lavage fluid (BALF) samples were collected from 311 suspected and confirmed pulmonary TB patients and tested by mNGS, acid-fast bacillus (AFB) smear by microscopy, Xpert 1 MTB/RIF (Xpert), mycobacterium culture and bacterial/fungal culture. Diagnostic performance of mNGS was compared with conventional methods for detection of Mycobacterium tuberculosis complex (MTBC) and other pathogens in BALF. Underlying factors associated with positive detection in pulmonary TB patients were investigated. Results: mNGS, Xpert and culture presented a high proportion of complete matching for MTBC detection (244/322, 75.8%). In pulmonary TB patients pre-treatment the sensitivity of MTBC detection by mNGS, Xpert, culture and smear was 59.9% (85/142), 69.0% (98/142), 59.9% (85/142) and 24.6% (35/142), respectively, and 79.6% overall; MTBC was detected by mNGS in 33.2% (5/34) Xpert and culture negative samples. Positive MTBC detection by mNGS was affected by Vitamin D, erythrocyte sedimentation rate, TB initial treatment/ retreatment, and cavity in chest imaging (χ 2 = 37.42, P < 0.001), but not by prior anti-TB therapy within 3 months. mNGS was able to detect new potential pathogens in 8.7% (28/322) of samples. Conclusions: Combining mNGS with conventional detection methods could increase the detection rate for MTBC. Additionally, mNGS could identify pathogens in a non-targeted approach for better diagnosis of coinfection.

Purpose To investigate the influence of lycium barbarum polysaccharides (LBP), a functional derivative from lycium barbarum, on septic kidney injury. Methods The SD male rats were randomly divided into 8 groups. The concentration of IL-1β, IL-6, IL-8, TNF-α, NF-κB and ROS, in kidney cortex homogenates after 12 h treatments were determined by enzyme-linked immunosorbent assay and ROS test kit, respectively. Morphology observation of kidney tissue was conducted with HE staining. The mRNA and protein expression levels of Nrf2, HO-1, NQO1, NF-κB, and Keap1 in kidney tissues were determined by qRT-PCR and Western blot, respectively. Results LPS treatment significantly increased the oxidative stress. After LBP treatment, the ROS content reduced significantly in a dose-depend manner. However, the levels of HO-1, NQO1 and Nrf2 as molecular elements that respond to oxidative stress were further increased. Also, administration of LBP increased the levels of NF-κB and Keap1, and decreased the levels of Nrf2 in the Keap 1-Nrf2∕ARE signaling pathway. By administrating the brusatol, the inhibition of Nrf2 enhanced the expression of NF-κB, inhibits the antioxidant responses, and further reverse the protective effect of LBP on the LPS induced septic kidney injury. Conclusion Lycium barbarum polysaccharides can reduce inflammation and activate the antioxidant responses via regulating the level of pro-inflammatory cytokines and the Keap1-Nrf2/ARE signaling pathway.

The renoprotective effects of DEX-pretreatment which attenuates I/R-induced AKI were partly through inhibition of P38-MAPK activation and expression of TXINP in diabetic kidney.

Neuropathic pain is an intractable comorbidity of spinal cord injury. Increasing noncoding RNAs have been implicated in neuropathic pain development. lncRNAs have been recognized as significant regulators of neuropathic pain. lncRNA Small Nucleolar RNA Host Gene 4 (SNHG4) is associated with several tumors. However, the molecular mechanisms of SNHG4 in neuropathic pain remain barely documented. Here, we evaluated the function of SNHG4 in spinal nerve ligation (SNL) rat models. We observed that SNHG4 was significantly upregulated in SNL rat. Knockdown of SNHG4 was able to attenuate neuropathic pain progression via regulating behaviors of neuropathic pain including mechanical and thermal hyperalgesia. Moreover, knockdown of SNHG4 could repress the neuroinflammation via inhibiting IL-6, IL-12, and TNF-α while inducing IL-10 levels. Additionally, miR-423-5p was predicted as the target of SNHG4 by employing bioinformatics analysis. miR-423-5p has been reported to exert significantly poorer in several diseases. However, the role of miR-423-5p in the development of neuropathic pain is needed to be clarified. Here, in our investigation, RIP assay confirmed the correlation between miR-423-5p and SNHG4. Meanwhile, we found that miR-423-5p was significantly decreased in SNL rat models. SNHG4 regulated miR-423-5p expression negatively. As exhibited, the loss of miR-423-5p contributed to neuropathic pain progression, which was rescued by the silence of SNHG4. Therefore, our study indicated SNHG4 as a novel therapeutic target for neuropathic pain via sponging miR-423-5p.

PURPOSE:To determine whether Toll-like receptor 7 (TLR7) is the potential targets of prevention or progression in the renal ischemia/ reperfusion (I/R) injury of STZ-induced diabetic rats. METHODS:Thirty six Sprague-Dawley rats were randomly arranged to the nondiabetic (ND) or diabetic group (DM), with each group further divided into sham (no I/R injury), I/R (ischemia-reperfusion) and CD (given by Chloroquine) group. Preoperatively, Chloroquine (40 mg/kg, intraperitoneal injection.) was administrated 6 days for treatment group. I/R animals were subjected to 25 min of bilateral renal ischemia. Renal function, histology, apoptosis, cytokines, expression of TLR7, MyD88 and NF-κB were detected. RESULTS:The serum levels of blood urea nitrogen, creatinine, IL-6 and TNF-α, apoptotic tubular epithelial cells, expression of TLR7, MyD88 and NF-κB were significantly increased in DM+I/R group, compared with ND+I/R group (p<0.05). All these changes were further improved by TLR7 inhibition Chloroquine except Paller scores (p<0.05). CONCLUSION:Toll-like receptor 7 inhibition attenuates the acute renal ischemia/reperfusion injury of STZ-induced diabetic in SD rats.