Decreased mortality seen in rifampicin/multidrug-resistant tuberculous meningitis treated with linezolid in Shenzhen, China.

BACKGROUND: The morbidity of rifampicin/multidrug-resistant tuberculous meningitis (RR/MDR-TBM) has shown an increasing trend globally. Its mortality rate is significantly higher than that of non-rifampicin/multidrug-resistant tuberculous meningitis (NRR/MDR-TBM). This article aimed to explore risk factors related to RR/MDR-TBM, and compare therapeutic effects of linezolid (LZD)- and non-linezolid-containing regimen for RR/MDR-TB patients in Shenzhen city. Furthermore, we aimed to find a better therapy for pathogen-negative TBM with RR/MDR-TBM related risk factors. METHODS: We conducted a retrospective study enrolling 137 hospitalized cases with confirmed TBM from June 2014 to March 2020. All patients were divided into RR/MDR-TBM group (12 cases) and NRR/MDR-TBM group (125 cases) based on GeneXpert MTB/RIF and (or) phenotypic drug susceptibility test results using cerebral spinal fluid (CSF). The risk factors related to RR/MDR-TBM were investigated through comparing clinical and examination features between the two groups. The mortality rate of RR/MDR-TBM patients treated with different regimens was analyzed to compare their respective therapeutic effects. A difference of P < 0.05 was considered statistically significant. RESULTS: Most patients (111/137, 81%) were from southern or southwestern China, and a large proportion (72/137, 52.55%) belonged to migrant workers. 12 cases were RR/MDR-TBM (12/137, 8.8%) while 125 cases were NRR/MDR-TBM (125/137, 91.2%). The proportion of patients having prior TB treatment history in the RR/MDR-TBM group was significantly higher than that of the NRR/MDR-TBM group (6/12 vs. 12/125, 50% vs. 10.5%, P < 0.01). No significant difference was observed on other clinical and examination features between the two groups. Mortality was significantly lower in RR/MDR-TBM patients on linezolid-containing treatment regimen than those who were not (0/7 versus 3/5, 0% versus 60%, P = 0.045). CONCLUSIONS: The main related risk factor of RR/MDR-TBM is the history of anti-tuberculosis treatment. Linezolid-containing regimen appears to lower mortality rate of RR/MDR-TBM significantly in our study. We think Linezolid should be evaluated prospectively in the treatment of RR/MDR-TBM.

Expression and Clinical Significance of Golgi Phosphoprotein 3 (GOLPH3) in Papillary Thyroid Carcinoma.

This study aimed to explore the correlation of Golgi phosphoprotein 3 (GOLPH3) levels in papillary thyroid carcinoma (PTC) and papillary thyroid microcarcinoma (PTMC) with clinicopathologic features. GOLPH3 expression was determined by western blotting in solid tumors and the adjacent normal thyroid tissues. Mammalian target of rapamycin (mTOR) and Ki-67 were examined by immunohistochemical staining. Significantly higher levels of GOLPH3 protein were observed in PTC and PTMC compared with the adjacent normal thyroid tissues ( P <0.001). GOLPH3 level was positively associated with lymph node metastasis and clinical stage in PTC ( P <0.05) and utterly related to the clinical stage in PTMC ( P =0.012). No correlation was observed between GOLPH3 level and other clinicopathologic parameters such as sex, local invasion, tumor number, and tumor size. The expression level of GOLPH3 protein in mTOR-positive PTC was significantly higher than in mTOR-negative PTC ( P =0.002 in PTC, P =0.022 in PTMC) and positively correlated with Ki-67 proliferation index in PTC via Pearson correlation analysis ( r =0.353, P =0.007 in PTC; r =0.583, P <0.001 in PTMC). In conclusion, the relative expression level of GOLPH3 protein was significantly higher in PTC and PTMC than in normal thyroid tissues and increased with cancer severity. It may provide adjunctive information for diagnosing and predicting prognosis in patients with PTC or PTMC.

Self-standing boron nitride bulks enabled by liquid metals for thermal management.

Thermally conductive materials (TCMs) are highly desirable for thermal management applications to tackle the "overheating" concerns in the electronics industry. Despite recent progress, the development of high performance TCMs integrated with an in-plane thermal conductivity (TC) higher than 50.0 W (m K)-1 and a through-plane TC greater than 10.0 W (m K)-1 is still challenging. Herein, self-standing liquid metal@boron nitride (LM@BN) bulks with ultrahigh in-plane TC and through-plane TC were reported for the first time. In the LM@BN bulks, LM could serve as a bonding and thermal linker among the oriented BN platelets, thus remarkably accelerating heat transfer across the whole system. Benefiting from the formation of a unique structure, the LM@BN bulk achieved an ultrahigh in-plane TC of 82.2 W (m K)-1 and a through-plane TC of 20.6 W (m K)-1, which were among the highest values ever reported for TCMs. Furthermore, the LM@BN bulks exhibited superior compressive and leakage-free performances, with a high compressive strength (5.2 MPa) and without any LM leakage even after being crushed. It was also demonstrated that the excellent TCs of the LM@BN bulks made them effectively cool high-power light emitting diode modules. This work opens up one promising pathway for the development of high-performance TCMs for thermal management in the electronics industry.

MicroRNA-145 exerts tumor-suppressive and chemo-resistance lowering effects by targeting CD44 in gastric cancer.

AIM: To determine the potential roles of CD4 and microRNA (miR)-145 in gastric cancer. METHODS: The levels of CD44 and miR-145 were determined in gastric cancer cells. Quantitative real-time polymerase chain reaction was used to measure to the level of CD44 mRNA. A luciferase reporter assay and western blotting were performed to examine the effect of miR-145 on CD44 expression. Tumor sphere and MTT assays were carried out to evaluate the self-renewal and chemo-resistance properties of gastric cancer cells. RESULTS: The expression of CD44 was greatly increased and miR-145 was decreased in gastric cancer cells that were highly enriched in cancer stem cells (CSCs). The results demonstrated that miR-145 regulated CD44 by targeting directly the CD44 3'-untranslated region (3'-UTR). In gastric cancer cells, overexpression of miR-145 repressed the activity of the CD44 3'-UTR, and disruption of miR-145/CD44 3'-UTR interactions abrogated the silencing effects. In addition, miR-145 inhibition stimulated CD44 3'-UTR activity and disruption of miR-145/CD44 3'-UTR interactions abrogated this stimulatory effect. Enforced CD44 expression greatly increased tumor sphere formation and chemo-resistance in gastric cancer cells. Furthermore, the inhibition of CSCs and the chemo-sensitivity of gastric cancer cells treated with miR-145 were significantly abrogated by overexpression of CD44. CONCLUSION: miR-145 targeting of CD44 plays critical roles in the regulation of tumor growth and chemo-resistance in gastric cancer.

Effects of morphine and sufentanil preconditioning against myocardial ischemic-reperfusion injury in rabbits.

OBJECTIVE: This study aims to explore the treatment method of myocardial ischemia-reperfusion injury. METHODS: Myocardial Ischemia-reperfusion rabbit model was established in this study. They were divided into four groups: sham operation (S) group, IRI control (I/R) group and IRI with morphine (MF) group and sufentanil (SF). Myocardial infarct size was compared with HE staining method. TUNEL assay was used to detect cell apoptosis. RESULTS: Myocardial infarct size of control group and morphine and sufetanil group was 36.0±3.6, 23.0±1.2 and 27.1±2.3, respectively. There were significant differences between them (P < 0.01). Apoptotic index of I/R, MF and SF groups was 26.9±2.2, 12.5±2.3, 15.8±2.0, with statistical significance (P < 0.05). The concentration of CK-MB in serum: there were no significant differences of CK-MB between each group at baseline. The concentration of CK-MB after reperfusion were higher than that of baseline, except for group S (P < 0.05); Compared with group S, after reperfusion, the CK-MB of other three groups were higher (P < 0.05); The concentration of CK-MB in group MF and SF were lower than group I/R (P < 0.05); In contrast to group MF, the concentration of CK-MB after reperfusion was higher in group SF (P < 0.05). CONCLUSION: Morphine and sufentanil can specifically protect the myocardial function.