Pressure-Gradient Counterwork of Dual-Fuel Driven Nanocarriers in Abnormal Interstitial Fluids for Enhancing Drug Delivery Efficiency.

The abnormal pressure in tumor tissue is a significant limitation on the drug delivery efficiency of tumor therapy. This work reports a gradient-driven nanomotor as drug nanocarrier with the pressure-counterworking function. The dual-fuel nanomotors are formed by co-electrospinning of the photosensitive polymers with calcium peroxide (CaO2 ) and catalase (CAT), followed by ultraviolet (UV) irradiation and bovine serum albumin (BSA) incubation. The UV-responsive cleavage nanomotors can effectively release O2 molecules at the fractures as a driving force to increase the delivery speed and escape the phagocytosis of macrophage system in normal tissues. Furthermore, CAT catalyzes H2 O2 produced by CaO2 and the tumor interstitial fluids to provide stronger power for the nanomotors. Additionally, according to the analysis of directional motions of the nanomotors, the functional relationship between the rotational diffusion coefficient (DR ) and the physiological viscosity is constructed. The dual-fuel nanocarriers enable up to 13.25% of the injected dose (ID)/per gram tissue and significantly improve the penetration in deep tumor. It is of vital importance to design and obtain the adaptive pressure-gradient counterworking nanomotors, which can effectively improve the drug delivery efficiency in vitro and in vivo.

The lymphocyte-to-monocyte ratio predicts intracranial atherosclerotic stenosis plaque instability.

Background and purpose: Gadolinium enhancement on high-resolution vessel wall imaging (HR-VWI) is an imaging marker of intracranial atherosclerotic stenosis (ICAS) plaque instability. This study aimed to evaluate the relationships between hematological inflammatory indicators and the enhancement of ICAS plaques and to search for hematological indicators that can predict ICAS plaque instability. Methods: Consecutive adult patients diagnosed with ICAS from April 2018 to December 2021 were recruited retrospectively, and every patient underwent HR-VWI. Plaque enhancement was measured qualitatively and quantitatively. The plaque-to-pituitary stalk contrast ratio (CR) indicated the degree of plaque enhancement. Clinical and laboratory data, including the lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and systemic immune inflammation index (SII), were recorded. The hematological inflammatory indicators were compared between ICAS patients with and without plaque enhancement and between patients with and without symptomatic plaque. The hematological inflammatory indicators and the CR were compared using linear regression. Furthermore, receiver operating characteristic curve analysis was performed to assess the discriminative abilities of the inflammatory indicators to predict plaque instability. Results: Fifty-nine patients were included. The NLR, SII and LMR were significantly correlated with plaque enhancement. The LMR was independently associated with plaque enhancement, and a linear negative correlation was observed between the LMR and CR (R = 0.716, P < 0.001). The NLR, LMR, plaque enhancement and CR were significantly associated with symptomatic ICAS, and the LMR and plaque enhancement were independent risk factors for symptomatic ICAS. The optimal cutoff value of the admission LMR to distinguish symptomatic plaque from asymptomatic plaque was 4.0 (80.0% sensitivity and 70.6% specificity). Conclusion: The LMR was independently associated with ICAS plaque enhancement and showed a linear negative correlation with CR. The LMR and plaque enhancement were independent risk factors for symptomatic ICAS. An LMR ≤ 4.0 may predict ICAS plaque instability.

Ecological Effect of Ecological Engineering Projects on Low-Temperature Forest Cover in Great Khingan Mountain, China.

The evaluation of ecological restoration projects can provide support for further strengthening the efforts of ecological restoration work and implementing the strategic objectives of the ecological region. Considering the current problem of the single evaluation index, this study evaluated the implementation effect of ecological projects from different temporal and spatial dimensions. Based on the MODIS vegetation index time series data, this study first computed the Sustainable Development Goal (SDG) indicator 15.3.1 of Great Khingan Mountain (GKM) to evaluate the impact of ecological engineering on land use change and land productivity. As a common indicator, the Normalized Difference Vegetation Index (NDVI) values showed a trend of a decrease and then gradual increase after the start of the Natural Forest Protection Project (NFPP) II, which was related to the land use changes from the forest to the grassland during the implementation of the NFPP. However, land productivity maintained a steady trend because of the transition between the forest and grassland. Meanwhile, to detect changes in vegetation at a smaller scale, the LandTrendr algorithm was used to identify the magnitude of forest disturbance, the years when it occurred, and the year of restoration. After implementing the ecological project, the forests in the GKM region were only partially disturbed, and most of the forests in most areas maintained a stable trend. Our study highlighted the varying effectiveness of different indexes for NFPP and evaluated the ecological impact of ecological projects from multiple perspectives.

Transcriptome analysis reveals possible antitumor mechanism of Chlorella exopolysaccharide.

Microalgae, one of the most important classes of biomass producers, can produce exopolysaccharides similar to bacteria. The exopolysaccharide from Chlorella (CEPS) displays remarkable anticancer activity the mechanism of which remains to be elucidated. In this study, we analyzed the inhibitory effect of CEPS on the growth of HeLa cells. The results showed that CEPS inhibited the proliferation, decreased the viability, and changed the morphology of HeLa cells. Transcriptome analysis showed that 1894 genes were differentially expressed in the CEPS-treated group compared with the control group, including 1076 genes that were upregulated and 818 genes that were downregulated. The results of gene function enrichment analysis showed that the differentially expressed genes (DEGs) were significantly enriched in apoptosis and tumor-related biological processes and participated in several cancer and apoptosisrelated signaling pathways, including the MAPK signaling pathway, TNF signaling pathway, and the PI3K-Akt signaling pathway. The protein-protein interaction network identified 13 DEGs including PTPN11, RSAD2, ISG15, IFIT1, MX2, IFIT2, OASL, OAS1, JUN, OAS2, XAF1, ISG20, and IRF9 as hub genes. Our results suggest that CEPS is a promising therapeutic drug for the follow-up interventional therapy of cancer.

EZH2 is a potential prognostic predictor of glioma.

The enhancer of zeste homologue 2 (EZH2) is a histone H3 lysine 27 methyltransferase that promotes tumorigenesis in a variety of human malignancies by altering the expression of tumour suppressor genes. To evaluate the prognostic value of EZH2 in glioma, we analysed gene expression data and corresponding clinicopathological information from the Chinese Glioma Genome Atlas, the Cancer Genome Atlas and GTEx. Increased expression of EZH2 was significantly associated with clinicopathologic characteristics and overall survival as evaluated by univariate and multivariate Cox regression. Gene Set Enrichment Analysis revealed an association of EZH2 expression with the cell cycle, DNA replication, mismatch repair, p53 signalling and pyrimidine metabolism. We constructed a nomogram for prognosis prediction with EZH2, clinicopathologic variables and significantly correlated genes. EZH2 was demonstrated to be significantly associated with several immune checkpoints and tumour-infiltrating lymphocytes. Furthermore, the ESTIMATE and Timer Database scores indicated correlation of EZH2 expression with a more immunosuppressive microenvironment for glioblastoma than for low grade glioma. Overall, our study demonstrates that expression of EZH2 is a potential prognostic molecular marker of poor survival in glioma and identifies signalling pathways and immune checkpoints regulated by EHZ2, suggesting a direction for future application of immune therapy in glioma.

Anlotinib or platinum-pemetrexed as second-line therapy in EGFR T790M-negative lung cancer.

BACKGROUND: Clinical management of T790M-negative patients after first-line epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) treatment failure is controversial. Anlotinib is a novel multi-target TKI for tumor angiogenesis and tumor cell proliferation, and it has been approved as a thirdline or beyond treatment for advanced non-small cell lung cancer (NSCLC). The impact of anlotinib as a second-line therapy compared with platinum-pemetrexed chemotherapy in T790M-negative patients after first-line EGFR-TKIs failed remains unclear. METHODS: In this retrospective cohort study, we reviewed 20 patients who were given anlotinib and 42 patients who received platinum-pemetrexed chemotherapy as a control after first-line EGFR-TKIs therapy progression. All the patients were confirmed to be T790M-negative using the cobas EGFR Mutation Test. The primary end point included progression-free survival (PFS) time, objective response rate (ORR) and disease control rate. RESULTS: The duration of PFS was significantly longer in the platinum-pemetrexed group than in the anlotinib group (median, 4.5 vs. 3.0 months; HR, 1.972; 95% CI, 1.078 to 3.607; P=0.021). The response rate was significantly better in the platinum-pemetrexed group (30.9%) than that in the anlotinib group (15%), and disease control rate (DCR) of both groups was 70% and 83%, respectively. All the adverse events in anlotinib group appeared to be manageable. CONCLUSIONS: Anlotinib was less effective than platinum-pemetrexed chemotherapy in T790M-negative NSCLC patients after disease progression with first-line EGFR-TKIs therapy failure.

[Efficacy comparision of lumbar disc herniation treated with acupuncture at different time intervals].

OBJECTIVE: To observe the effect of lumbar disc herniation treated with acupuncture at different time intervals. METHODS: A total of 180 patients of lumbar disc herniation were randomized into an observation group 1, an observation group 2 and an observation group 3, 60 cases in each one. All patients were treated with acupuncture at Jiaji L3-L5 (EX-B 2), Huantiao (GB 30), Weizhong (BL 40), etc. And then KWD-808 electroacupuncture instrument was connected, time intervals of acupuncture were once every day, once every 2 days and once every 3 days, 3 weeks were provided. At 1-week, 2-week and 3-week treatment, the visual analogous scale (VAS) and Japanese Orthopedics Association (JOA) scale were observated, and the effects were evaluated. RESULTS: The effective rates in the observation group 1 and the observation group 2 were 96.7% (58/60) and 95.0% (57/60), there was no significant different between the two groups (P>0.05), which were superior to 88.3% (53/60) in the observation group 3 (both P<0.01). The VAS score in each group decreased to different degrees at 1-week, 2-week and 3-week treatment compared with those before treatment (all P<0.01), there was no significant different between the observation group 1 and the observation group 2 (all P>0.05) at 1-week, 2-week and 3-week treatment, however, they were significantly reduced compared with the observation group 3 (all P<0.05). The JOA score in each group increased to different degrees at 1-week, 2-week and 3-week treatment compared with those before treatment (all P<0.01), there was no significant different between the observation group 1 and the observation group 2 (all P>0.05) at 1-week, 2-week and 3-week treatment, however, they were significantly increased compared with the observation group 3 at 3-week treatment (both P<0.05). CONCLUSION: Acupuncture once every day and once every 2 days in the treatment of lumbar disc herniation is equally effective, better than once every 3 days.

Bone marrow mesenchymal stem cells could reduce the toxic effects of hexavalent chromium on the liver by decreasing endoplasmic reticulum stress-mediated apoptosis via SIRT1/HIF-1α signaling pathway in rats.

This study focused on the effect of bone marrow mesenchymal stem cells (BMSCs) on the repair of rat liver injury induced by Cr (VI). Twenty-four Wistar rats were randomly divided into the control, model and cell therapy group, with 8 rats in each group. Potassium dichromate solution containing 0, 0.4 and 0.4 mg/kg·bw Cr (VI) was administered 5 times a week for 30 days. At the end of treatment, rats in the cell therapy group were administered 1 × 107 BMSCs. Two weeks later, serum alanine and aspartate aminotransferase levels in the cell therapy group were significantly improved compared with those in the model group, CM-Dil-labeled BMSCs were localized in rat livers. Compared with the model group, in the cell therapy group the number of apoptotic hepatocytes by TUNEL assay, MDA content, the expression of HIF-1α, endoplasmic reticulum (ER) stress-mediated apoptosis-related proteins including Grp78, CHOP, Cleaved-Caspase-12, ATF6, and Bax was significantly lower, and SOD activity, the expression of SIRT1 and Bcl-2 was significantly higher. It is suggested that BMSCs are localized in livers and reduce the toxic effects of Cr (VI) on the liver, and the possible mechanism may be related to the mechanisms of BMSCs decreasing ER stress-mediated hepatocyte apoptosis via the SIRT1/HIF-1α signaling pathway.

Ratiometric fluorescent probe based on pyrrole-modified rhodamine 6G hydrazone for the imaging of Cu2+ in lysosomes.

A novel rhodamine-based Schiff base derivative was obtained via the simple condensation of substituted formyl-1H-pyrrole and rhodamine 6G hydrazone. Fluorescence resonance energy transfer enabled the subsequent use of the derivative as a naked-eye colorimetric and ratiometric fluorescent sensor for Cu2+ in semi-aqueous solution, and the existence of the morpholine group enabled the further application of the sensor in imaging Cu2+ in the lysosomes of HeLa cells.

[Clinical research on fire filiform needle combined with mild moxibustion for postherpetic neuralgia].

OBJECTIVE: To compare efficacy differences between fire filiform needle combined with mild moxibustion and gabapentin combined with sham acupuncture for postherpetic neuralgia (PHN). METHODS: One hundred cases of PHN were randomly divided into a needle group and a medicine group, 50 cases in each one. In the needle group, pricking method of fire filiform needle was given at the Ashi points, and then mild moxibustion was applied for 15 min. In the medicine group, the oral administration of gabapentin capsule and sham acupuncture at non-acupoints in the distal end of lesions were applied. The treatment was required for 21 days in both groups. The visual analogue score (VAS) was recorded before treatment and on the 1st day, 2nd day, 3rd day, 6th day, 9th day and 12th day of treatment. The most severity of pain within last 24 h, preset severity of pain, immediate analgesia effect and starting time of pain relief were observed, also the efficacy was assessed and improvement of symptoms was observed in the follow-up visit. RESULTS: The total effective rate was 94.0% (47/50) in the fire filiform needle group, which was superior to 86.0% (43/50) in the medicine group (P < 0.05). Compared with medicine group, the VAS of the most severity of pain within last 24 h was obviously reduced after the 2nd treatment in the fire filiform needle group while that of present severity of pain was relieved after the 1st treatment (both P < 0.05). The immediate analgesia effect in the fire filiform needle group was obviously superior to that in the medicine group in the first three times of treatment (all P < 0.05). The average time of pain relief was (3.91 +/- 0.82) days in the fire filiform needle group, which was significantly earlier to (6.53 +/- 1.13) days in the medicine group (P < 0.05). 26 cases were cured in the fire filiform needle group in the follow-up visit, which was superior to 2 cases in the medicine group (P < 0.05). The improvement of VAS, pain range and sleep quality in the needle group were also superior to those in the medicine group (all P < 0.05). The direct medical cost in the fire filiform needle group was (232.32 +/- 48.108) yuan, which was significantly lower than (466.00 +/- 41.09) yuan in the medicine group (P < 0.05). There was only one case of adverse effect in the medicine group during the treatment. CONCLUSION: The fire filiform needle combined with mild moxibustion could obviously relieve the pain in PHN patients, which has superior immediate analgesia effect and pain relieving time compared with gabapentin, which also has less adverse effects and cheap cost.

[Endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of intrapulmonary lesions].

OBJECTIVE: To evaluate real-time endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the diagnosis of intrapulmonary lesions. METHODS: From October 2009 to November 2011, EBUS-TBNA was performed in 78 patients with parabrachial or parabronchial intrapulmonary lesions proved by CT scan. On-site cytological evaluation was not performed. Immunohistochemistry was applied to distinguish the type of malignant tumor when necessary. RESULTS: Sixty-five malignancies and 13 benign diseases were finally diagnosed in 78 intrapulmonary lesions, of which 62 malignancies and 13 benign diseases were distinguished by EBUS-TBNA, including 61 primary lung cancer (adenocarcinoma 36, squamous carcinoma 8, poorly-differentiated carcinoma 5, unknown type carcinoma 3, small cell carcinoma 9), one metastatic lung cancer, 7 pulmonary inflammation, 5 pulmonary tuberculosis and one fibrosis. There were 3 false negative cases which were diagnosed as pulmonary poorly-differentiated carcinoma, pulmonary sarcomatoid carcinoma and pulmonary lymphoma, respectively. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of EBUS-TBNA in distinguishing malignant from benign thoracic lesions was 95%, 100%, 81%, 100%, 96%, respectively. Immunohistochemistry was performed in 8 malignant tumors without definite type or origin, 5 primary lung cancer and one metastatic lung adenocarcinoma were further confirmed. Moderate bleeding from the puncture site during needle aspiration forming blood clot and obstructing the central airway was noted in 1 hypercoagulable subject. CONCLUSIONS: EBUS-TBNA is a minimally invasive, safe procedure with high sensitivity for distinguishing malignant from benign lesions. Immunohistochemistry can provide evidence for the definitive diagnosis of malignant lesions.

[Observation on therapeutic effect of acupuncture on spontaneous facial paralysis in acute stage].

OBJECTIVE: To observe the therapeutic effect and to explore the best opportunity of acupuncture on spontaneous facial paralysis in acute stage. METHODS: By prospective cohort study, 80 patients were divided into an observation group (n = 59) and a control group (n = 21). The course of disease was less than 5 days in the observation group and more than 7 days in the control group and had not received acupuncture treatment. They were all treated with acupuncture at Sibai (ST 2), Dicang (ST 4), Jiache (ST 6) and Cuanzhu (BL 2) etc. for 8 weeks. The facial nerve function grading (House-Brackmann, HB) and facial disable index (FDI) before treatment, 8 days after onset, 2, 4, 6, 8 weeks and 3 months after treatment were evaluated. RESULTS: Both two groups could decrease HB grading and increase FDI score (all P < 0.05), and the observation group was superior to the control group in improvement degree (all P < 0.05). The cured rate of 86.4% (51/59) in the observation group was superior to that of 76.2% (16/21) in the control group, with significant difference between the two groups (P < 0.05). Compared with the control group, the treatment time of cured patients in the observation group was shorter [(25.98 +/- 11.25) days vs (39.31 +/- 13.07) days, P < 0.01], and the incidence of sequelae of 5.1% (3/59) in the observation group was lower than that of 9.5% (2/21) in the control group (P < 0.05). CONCLUSION: Acupuncture can improve the therapeutic effect, shorten the treatment course and reduce the sequelae incidence of spontaneous facial paralysis in acute stage.

The value of tumor markers in evaluating chemotherapy response and prognosis in Chinese patients with advanced non-small cell lung cancer.

OBJECTIVE: The aim of this study was to assess the value of tumor markers in monitoring chemotherapy response and predicting prognosis in patients with advanced non-small cell lung cancer (NSCLC). METHODS: We studied carcinoembryonic antigen (CEA), CYFRA21-1 and neuron-specific enolase (NSE) of 111 untreated patients with advanced NSCLC before and after 2 cycles of chemotherapy, meanwhile evaluating the response according to the image, and analyzed the relationship between tumor markers and response rate, time to progression (TTP) and overall survival (OS). RESULTS: The mean percentages of CEA decrease of the 111 patients with advanced NSCLC whose image response was partial response, no response and progressive disease were 22.8, -5.5 and -59.8% (p = 0.002), 28.1, 1.8 and -70.8% for CYFRA21-1 (p = 0.001), and 17.5, -3.1 and -16.9% for NSE, respectively (p = 0.03). The median TTP for all patients was 6.7 months, while the median TTP for CEA decrease and CEA elevated or stable patients was 9.2 and 4.3 months, respectively (p < 0.001). Radiologic and CYFRA21-1 responses were significant predictive factors for TTP on multivariate analysis (p < 0.001 and p = 0.003, respectively). The median OS was 19.2 months for all patients, with a 1-year survival rate of 69.4%. Baseline CEA, baseline CYFRA21-1 and CEA response were significant predictive factors for OS on multivariate analysis (P = 0.004, P = 0.004 AND P < 0.001, respectively). CONCLUSION: CEA, CYFRA21-1 and NSE can be used in evaluating chemotherapy response, and CYFRA21-1 response was a significant predictive factor for TTP, while baseline CEA, baseline CYFRA21-1 and CEA response were significant predictive factors for OS in Chinese patients with advanced NSCLC.

[Effects of fractal structure on settling velocities of flocs].

Fractal structures of kaolin and humic flcos by the mass-size method based on the microbalance and free-settling method based on particle image velocimetry technique were investigated. The results showed that kaolin and humic flocs were characterized by fractal structure. The three-dimensional fractal dimensions of Fe flocs with more compact structure ranged from 2.14 to 2.28 are larger than those of alum flocs ranged from 1.75 to 1.83 by the mass-size method. The fractal dimensions of humic flocs are smaller than those of kaolin flocs. The fractal dimension has a close relationship with the settling velocity of flocs. The larger the fractal dimension, the higher the settling velocity. The fractal dimensions by the mass-size method are in good agreement with those by the free-settling method. The measured settling velocities of fractal aggregates do not follow with Stokes' law.

[Three-dimensional fluorescence fingerprint for source determination of dissolved organic matters in polluted river].

Fluorescence fingerprint technique was used to characterize dissolved organic matter (DOM) in river from different sources. The results showed that two types of DOM fluorescence signals were observed in river water: a humic-like fluorescence with three maxima at lambda(ex)/lambda(em) = 250/460 nm(A1), 220/400 nm(A2) and 325/420 nm(C); and a protein-like fluorescence with two maxima at lambda(ex)/lambda(em) = 230/360 nm(T2) and 285/357 nm(T1). The intensity of both of protein-like fluorescence distinctly increased because of the domestic wastewater drainage in the tributary stream. After the tributary converges into the main stream, the Fe3+ concentration in the main stream is 30 times as much as that of tributary stream, and the visible blue-shift of humic-like fluorescence occurred while the others didn't occur. The intensity of all types of fluorescence decreased from source to estuary resulting from different solute chemistry. However, the intensities of humic-like fluorescence C, A1 and protein-like fluorescence T2 at the longer excitation wavelength decreased significantly because of dilution from main river stream and complexation of humic-like with Fe3+, thus the peaks disappeared at the estuary while the fluorescence peaks at the shorter excitation wave-length were relatively stable on which the river solute chemistry had little effect. Therefore, the fluorophores at the shorter excitation wavelength of 220-230 nm area potential tool to determine the sources of DOM in polluted river.

Highly sensitive determination of the methylated p16 gene in cancer patients by microchip electrophoresis.

The p16 tumor suppressor gene is inactivated by promoter region hypermethylation in many types of tumor. Recent studies showed that aberrant methylation of the p16 gene is an early event in many tumors, especially in lung cancer, and may constitute a new biomarker for early detection and monitoring of prevention trials. We detected tumor-associated aberrant hypermethylation of the p16 gene in plasma and tissue DNA from 153 specimens using a modified semi-nested methylation-specific PCR (MSP) combining plastic microchip electrophoresis or slab gel electrophoresis, respectively. Specimens were from 79 lung cancer patients, 15 abdominal tumor patients, 30 positive controls and 30 negative controls. The results showed that the positive rate obtained by microchip electrophoresis was more than 26.6% higher and the same specificity was kept when compared with slab gel electrophoresis. The microchip electrophoresis can rapidly and accurately analyze the PCR products of methylated DNA and obviously improve the positive rate of diagnosis of cancer patients when compared with gel electrophoresis. This method with the high assay sensitivity might be used for detection of methylation of p16 gene and even to facilitate early diagnosis of cancer patients.