Study on the relationship between peripheral nerve fiber types and levodopa usage in Parkinson's disease.

Background and purpose:

The aim of this study is to comprehensively determine the types of affected fibers in Parkinson’s disease (PD) patients by employing nerve conduction studies (NCS), sympathetic skin response (SSR) examinations, and current perception threshold (CPT) testing and to analyze the correlation between levodopa use and nerve involvement.

This retrospective study included 36 clinically diagnosed PD patients who were recruited between January 2018 and April 2019. All patients underwent NCS, SSR testing, and CPT sensory examinations. Additionally, the PD patients were assessed for disease staging using the Hoehn and Yahr (H-Y) scale. 

Fifteen patients were included in the tremor-dominant subtype, ten patients in the rigid-dominant subtype, and eleven patients in the mixed subtype. Eleven patients were using levodopa, while twenty-five patients had never used any anti-Parkinson’s medication. Ten patients (28%) showed abnormal sympathetic skin responses (SSR). The CPT examination revealed sensory abnormalities in twenty-four patients (67%), with eighteen patients (75%) experiencing sensory hypersensitivity and six patients (25%) experiencing sensory hypoesthesia. Twelve patients (33%) had normal CPT results. Among the patients with abnormal CPT findings, seven cases (29%) involved large myelinated fiber damage, twenty-two cases (92%) involved small myelinated fiber damage, and nineteen cases (79%) involved unmyelinated fiber damage. The rate of sensory abnormalities was 64% (7/11) in the levodopa group and 68% (17/25) in the non-levodopa group, with no statistically significant difference between the two groups. 

The incidence of abnormal CPT findings in PD patients was higher than that of abnormal SSR responses, suggesting that nerve fiber damage primarily affects small fiber nerves (SFN).

Optofluidic SERS based on Ag nanocubes with high sensitivity for detecting a prevalent water pollutant.

To enhance the integration and practical applicability of the Raman detection system, silver nanocubes (Ag NCs) were synthesized using a polyol method. A liquid-liquid interface approach was employed to transfer a monolayer of Ag NCs "film" onto a SiO2 substrate, resulting in the fabrication of a highly sensitive and uniform surface-enhanced Raman scattering (SERS) substrate denoted as "Ag NCs@SiO2." The electromagnetic field distribution of various dimers on the Ag NCs@SiO2 was analyzed using finite difference time domain (FDTD) software. The results reveal that the electromagnetic enhancement effect is most pronounced in cube-cube dimers, indicating that Ag NCs exhibit superior localized surface plasmon resonance (LSPR) response due to their well-defined geometric regularity and sharp geometric angles. For Rhodamine 6G (R6G) probe molecules, the Ag NCs@SiO2 shows ultrahigh sensitivity, with a limit of detection (LOD) of 10-12 mol/L, and the enhancement factor (EF) can reach 1.4 × 1010. The relative standard deviation (RSD) at the main characteristic peaks is below 10%, demonstrating good consistency in substrate performance. In addition, the Ag NCs@SiO2 modified with hexanethiol exhibits high sensitivity, uniformity, and repeatability in detecting for pyrene, with the LOD of 10-8 mol/L and a minimum RSD of 6.09% at the main characteristic peak, and effective recognition capabilities for pyrene and anthracene in mixed solutions. Finally, chemisorption and physisorption strategies were prepared in optofluidic channels and experimentally compared, enabling real-time detection of the pyrene solution. This method can achieve a rapid detection and precise differentiation of polycyclic aromatic hydrocarbons in a water pollutant.

Stability and integrity of self-assembled bovine parvovirus virus­like particles (BPV­VLPs) of VP2 and combination of VP1VP2 assisted by baculovirus-insect cell expression: a potential logistical platform for vaccine deployment.

BACKGROUND: Bovine parvovirus (BPV) is an autonomous DNA virus with a smaller molecular size and subtle differences in its structural proteins, unlike other animal parvoviruses. More importantly, this virus has the potential to produce visible to silent economic catastrophes in the livestock business, despite receiving very little attention. Parvoviral virus-like particles (VLPs) as vaccines and as logistical platforms for vaccine deployment are well studied. However, no single experimental report on the role of VP1 in the assembly and stability of BPV-VLPs is available. Furthermore, the self-assembly, integrity and stability of the VLPs of recombinant BPV VP2 in comparison to VP1 VP2 Cap proteins using any expression method has not been studied previously. In this study, we experimentally evaluated the self-assembling ability with which BPV virus-like particles (VLPs) could be synthesized from a single structural protein (VP2) and by integrating both VP2 and VP1 amino acid sequences. METHODS: In silico and experimental cloning methods were carried out. His-tagged and without-His-tag VP2 and V1VP2-encoding amino acid sequences were cloned and inserted into pFastbacdual, and insect cell-generated recombinant protein was evaluated by SDS‒PAGE and western blot. Period of infectivity and expression level were determined by IFA. The integrity and stability of the BPV VLPs were evaluated by transmission electron microscopy. The secondary structure of the BPV VLPs from both VP2 and V1VP2 was analyzed by circular dichroism. RESULTS: Our findings show that VP2 alone was equally expressed and purified into detectable proteins, and the stability at different temperatures and pH values was not appreciably different between the two kinds of VLPs. Furthermore, BPV-VP2 VLPs were praised for their greater purity and integrity than BPV-VP1VP2 VLPs, as indicated by SDS‒PAGE. Therefore, our research demonstrates that the function of VP1 has no bearing on the stability or integrity of BPV-VLPs. CONCLUSIONS: In summary, incredible physiochemically stable BPV VP2-derived VLPs have been found to be promising candidates for the development of multivalent vaccines and immunodiagnostic kits against enteric viruses and to carry heterogeneous epitopes for various economically important livestock diseases.

U-Shaped relationship of insulin-like growth factor I and incidence of nonalcoholic fatty liver in patients with pituitary neuroendocrine tumors: a cohort study.

Context: Although the role of insulin-like growth factor I (IGF-1) in nonalcoholic fatty liver disease (NAFLD) has garnered attention in recent years, few studies have examined both reduced and elevated levels of IGF-1. Objective: The aim of this study was to examine the potential relationship between IGF-1 levels and the risk of new-onset NAFLD in patients with pituitary neuroendocrine tumors (PitNET). Methods: We employed multivariable Cox regression models and two-piecewise regression models to assess the association between IGF-1 and new-onset NAFLD. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated to quantify this association. Furthermore, a dose-response correlation between lgIGF-1 and the development of NAFLD was plotted. Additionally, we also performed subgroup analysis and a series sensitivity analysis. Results: A total of 3,291 PitNET patients were enrolled in the present study, and the median duration of follow-up was 65 months. Patients with either reduced or elevated levels of IGF-1 at baseline were found to be at a higher risk of NAFLD compared to PitNET patients with normal IGF-1(log-rank test, P < 0.001). In the adjusted Cox regression analysis model (model IV), compared with participants with normal IGF-1, the HRs of those with elevated and reduced IGF-1 were 2.33 (95% CI 1.75, 3.11) and 2.2 (95% CI 1.78, 2.7). Furthermore, in non-adjusted or adjusted models, our study revealed a U-shaped relationship between lgIGF-1 and the risk of NAFLD. Moreover, the results from subgroup and sensitivity analyses were consistent with the main results. Conclusions: There was a U-shaped trend between IGF-1 and new-onset NAFLD in patients with PitNET. Further evaluation of our discoveries is warranted.

Efficacy of electroacupuncture on myocardial protection and postoperative rehabilitation in patients undergoing cardiac surgery with cardiopulmonary bypass: a systematic review and Meta-analysis.

OBJECTIVE: To evaluate the efficacy of electroacupuncture (EA) intervention on myocardial protection and postoperative rehabilitation in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). METHODS: Eight databases, including PubMed, Embase, the Cochrane Library, Web of Science, Chinese BioMedical Literature Database, China National Knowledge Infrastructure Database, Wanfang Data, China Science and Technology Journal Database, and two clinical trial registries, were searched. All randomized controlled trials (RCTs) related to EA intervention in cardiac surgery with CPB were collected. Based on the inclusion and exclusion criteria, two researchers independently screened articles and extracted data. After the quality evaluation, RevMan 5.3 software was used for analysis. RESULTS: Fourteen RCTs involving 836 patients were included. Compared with the control treatment, EA significantly increased the incidence of cardiac automatic rebeat after aortic unclamping [relative risk (RR) = 1.15, 95% confidence interval (CI) (1.01, 1.31), P < 0.05; moderate]. Twenty-four hours after aortic unclamping, EA significantly increased the superoxide dismutase [standardized mean difference (SMD) = 0.96, 95% CI(0.32, 1.61), P < 0.05; low], and interleukin (IL)-2 [SMD = 1.33, 95% CI(0.19, 2.47), P < 0.05; very low] expression levels and decreased the malondialdehyde [SMD =－1.62, 95% CI(－2.15, －1.09), P < 0.05; moderate], tumour necrosis factor-α [SMD = －1.28, 95% CI(－2.37, －0.19), P < 0.05; moderate], and cardiac troponin I [SMD = －1.09, 95% CI(－1.85, －0.32), P < 0.05; low] expression levels as well as the inotrope scores [SMD = －0.77, 95% CI(－1.22, －0.31), P < 0.05; high]. There was no difference in IL-6 and IL-10 expression levels. The amount of intraoperative sedative [SMD = -0.31, 95% CI(－0.54, －0.09), P < 0.05; moderate] and opioid analgesic [SMD = -0.96, 95% CI(－1.53, －0.38), P < 0.05; low] medication was significantly lower in the EA group than in the control group. Moreover, the postoperative tracheal intubation time [SMD = －0.92, 95% CI(－1.40, －0.45), P < 0.05; low] and intensive care unit stay [SMD = －1.71, 95% CI(－3.06, －0.36), P < 0.05; low] were significantly shorter in the EA group than in the control group. There were no differences in the time to get out of bed for the first time, total days of antibiotic use after surgery, or postoperative hospital stay. No adverse reactions related to EA were reported in any of the included studies. CONCLUSIONS: In cardiac surgery with CPB, EA may be a safe and effective strategy to reduce myocardial ischaemia-reperfusion injury and speed up the recovery of patients after surgery. These findings must be interpreted with caution, as most of the evidence was of low or moderate quality. More RCTs with larger sample sizes and higher quality are needed to provide more convincing evidence.

Inhibitory effect of berberine on morphine tolerance and hyperalgesia in mice.

OBJECTIVE: To evaluate the effect of berberine on morphine analgesia, tolerance, and hyperalgesia. METHODS: Morphine-induced acute tolerance model: mice received intraperitoneal berberine at doses of 2.5, 5.0, and 10 mg/kg; 30 min later, subcutaneous morphine 10 mg/kg was injected every hour for nine continuous h. Morphine 10 mg/kg alone was administered at 24 and 48 h. Morphine-induced chronic tolerance model: mice received intraperitoneal berberine 2.5, 5.0, and 10 mg/kg; 30 min later, 10 mg/kg morphine was injected subcutaneously for eight consecutive days. On the ninth day, morphine 10 mg/kg was given alone. Morphine-induced established tolerance model: mice were injected subcutaneously with morphine 10 mg/kg once a day for eight consecutive days. Berberine 2.5 mg/kg was administered on day one, four, and seven and morphine 10 mg/kg alone on day nine. The baseline latency (T0) and post-treatment latency (T1) were determined by the hot plate test, and the maximum possible analgesic effect (MPAE) was calculated. Nitric oxide synthase (NOS) activity and nitric oxide (NO) content in the spinal cord were measured by spectrophotometer. Verification of berberine analgesic effect by blocking N-methyl-D-aspartate (NMDA) receptor: HT-22 and HEK-293 cells transfected with NMDA plasmid were randomly divided into five groups: control group, NMDA group, berberine low-dose, medium-dose, and high-dose groups (5, 10, 20 µmol/L, respectively). Except for the control group, cells were treated with NMDA (HT-22 cells: 20 mmol/L; HEK-293 cells: 50 µmol/L). After 24 h, cell viability was detected by cell counting kit-8. The molecular mechanism between berberine and the NMDA receptor was studied by molecular docking. RESULTS: Berberine 2.5 and 5.0 mg/kg could prolong the analgesic time of morphine. In acute and chronic morphine tolerance models, berberine could inhibit the decrease of MPAE and baseline latency (0.05). In the established tolerance model, berberine could rapidly reverse the decreased MPAE (0.05). The combination of berberine and morphine on day one could effectively inhibit the morphine-induced increase of NOS activity and NO content in the spinal cord (0.05). Berberine significantly increased the cell viability of NMDA-induced nerve injury in HT-22 and HEK-293 cells (0.05). Molecular docking showed that berberine binds to the receptor pocket of NMDA. CONCLUSIONS: Berberine could effectively enhance and prolong the duration of morphine analgesia and inhibit the development of morphine-induced tolerance and hyperalgesia. Furthermore, berberine has a certain neuroprotective effect, which may be related to the inhibition of NMDA activity.

Microfluidic integrated D-shaped optical fiber SERS probe with high sensitivity and ability of multi-molecule detection.

In order to enhance the sensitivity, integration, and practical application capability of Raman detection systems, we propose a multi-channel microfluidic integrated D-shaped optical fiber SERS (Surface-enhanced Raman scattering) probe structure. Firstly, a microfluidic polydimethylsiloxane (PDMS) channel was fabricated using a self-designed multi-channel microfluidic template. Secondly, a uniform layer of silver nanoparticles was deposited on the D-shaped optical fiber using the liquid-liquid interface method. Finally, the D-shaped optical fiber was plasma-bonded to the multi-channel microfluidic channel and a cover glass, resulting in a microfluidic integrated D-shaped optical fiber SERS probe. The prepared sample exhibited excellent detection performance for R6G (rhodamine 6 G) with a detection limit as low as 10-11 mol/L and an enhancement factor of 1.14 × 109. Moreover, the multi-channel configuration enables simultaneous detection of multiple molecules, demonstrating excellent multi-channel multiplexing capability.

Plasmonic volcano-like fiber-optic probe for Raman enhancement.

Light-matter interaction is a fascinating topic extensively studied from classical theory, based on Maxwell's equations, to quantum optics. In this study, we introduce a novel, to the best of our knowledge, silver volcano-like fiber-optic probe (sensor 1) for surface-enhanced Raman scattering (SERS). We employ the emerging quasi-normal mode (QNM) method to rigorously calculate the Purcell factor for lossy open system responses, characterized by complex frequencies. This calculation quantifies the modification of the radiation rate from the excited state e to ground state g. Furthermore, we use and extend a quantum mechanical description of the Raman process, based on the Lindblad master equation, to calculate the SERS spectrum for the plasmonic structure. A common and well-established SERS probe, modified by a monolayer silver nanoparticle array, serves as a reference sensor (sensor 2) for quantitatively predicting the SERS performance of sensor 1 using quantum formalism. The predictions show excellent consistency with experimental results. In addition, we employ the FDTD (finite-difference time-domain) solver for a rough estimate of the all-fiber Raman response of both sensors, revealing a reasonable range of SERS performance differences compared to experimental results. This research suggests potential applications in real-time, remote detection of biological species and in vivo diagnostics. Simultaneously, the developed FDTD and quantum optics models pave the way for analyzing the response of emitters near arbitrarily shaped plasmonic structures.

Treatment of Liver Fibrosis after Hepatitis B with TCM Combined with NAs Evaluated by Noninvasive Diagnostic Methods: A Retrospective Study.

Objective. Chronic hepatitis B liver fibrosis is an important intermediate link in the development of liver cirrhosis. A retrospective cohort study was conducted in Longhua Hospital affiliated to the Shanghai University of Traditional Chinese Medicine in order to prove whether integrated traditional Chinese and Western medicine could improve the incidence of CHB complications and clinical prognosis. There are 130 patients with hepatitis B liver fibrosis (being treated from 2011-2021) included in the study, and the patients were divided into 64 TCM users (NAs combined with TCM) and 66 TCM nonusers (NAs antiviral therapy). The serum noninvasive diagnostic model (APRI, FIB-4) and LSM value were used to classify the stages of fibrosis. The results showed that the LSM value was decreased significantly in TCM users compared with TCM nonusers (40.63% versus 28.79%). Indicators of FIB-4 and APRI of TCM users have improved significantly compared with that of TCM nonusers (32.81% versus 10.61% and 35.94% versus 24.24%). The AST, TBIL, and HBsAg levels in TCM users were lower than those in TCM nonusers, and the HBsAg level was inversely correlated with the CD3+, CD4+, and CD8+ in TCM users. The PLT and spleen thickness of TCM users also were improved considerably. The incidence rate of end-point events (decompensated cirrhosis/liver cancer) in TCM nonusers was higher than that of TCM users (16.67% versus 1.56%). The long course of the disease and a family history of hepatitis B were the risk factors for disease progression, and long-term oral administration of TCM was the protective factor. As a result, the serum noninvasive fibrosis index and imaging parameters in TCM users were lower than those of TCM nonusers. Patients in the treatment of NAs combined with TCM had better prognoses such as a lower HBsAg level, a more stable lymphocyte function, and a lower incidence of end-point events. The present findings suggest the effect of TCM combined with NAs in the treatment of chronic hepatitis B liver fibrosis is better than that of single drug treatment.

Open nanocavity-assisted Ag@PDMS as a soft SERS substrate with ultra-sensitivity and high uniformity.

To achieve high sensitivity and uniformity simultaneously in a surface-enhanced Raman scattering (SERS) substrate, this paper presents the preparation of a flexible and transparent three-dimensional (3D) ordered hemispherical array polydimethylsiloxane (PDMS) film. This is achieved by self-assembling a single-layer polystyrene (PS) microsphere array on a silicon substrate. The liquid-liquid interface method is then used to transfer Ag nanoparticles onto the PDMS film, which includes open nanocavity arrays created by etching the PS microsphere array. An open nanocavity assistant soft SERS sample, "Ag@PDMS," is then prepared. For electromagnetic simulation of our sample, we utilized Comsol software. It has been experimentally confirmed that the Ag@PDMS substrate with silver particles of 50 nm in size is capable of achieving the largest localized electromagnetic hot spots in space. The optimal sample, Ag@PDMS, exhibits ultra-high sensitivity towards Rhodamine 6 G (R6G) probe molecules, with a limit of detection (LOD) of 10-15 mol/L, and an enhancement factor (EF) of ∼1012. Additionally, the substrate exhibits a highly uniform signal intensity for probe molecules, with a relative standard deviation (RSD) of approximately 6.86%. Moreover, it is capable of detecting multiple molecules and can perform real detection on non-flat surfaces.

Role of the heat shock protein family in chlorpromazine-induced cardiotoxicity.

Chlorpromazine (CPZ), a first-generation antipsychotic, is widely used in treating schizophrenia and other psychiatric disorders. However, CPZ is also associated with an increased likelihood of sudden cardiac death, and the underlying mechanisms remain unclear. In our study, we aimed to determine the CPZ-induced changes in some members of the heat shock protein family in rat hearts and further explore the possible mechanisms of CPZ-induced cardiotoxicity. Twenty-four Sprague Dawley rats were randomly divided into three groups (n = 8 per group): control, low dose (33.216 mg/kg) and high dose (94.211 mg/kg). CPZ administration induced hypothermia in rats. Pathological changes, including ischaemia and hypoxia, were observed in rat hearts. Furthermore, the serum levels of cardiac Troponin T (c-TN-T) and brain natriuretic peptide (BNP) were elevated in the CPZ-exposed groups. Meanwhile, the protein and gene expression of HSP70, HSP60, HSP27 and HSP10 significantly differed between the CPZ-exposed and control groups. We conclude that acute CPZ exposure could lead to myocardial injury in rats, in which HSPs might play a crucial role. Further investigations are required to elucidate the underlying mechanisms.

Amelioration of Cholesterol Rich diet-induced Impaired Cognition in AD Transgenic Mice by an LXR Agonist TO901317 Is Associated with the Activation of the LXR-ß-RXR-α-ABCA1 Transmembrane Transport System and Improving the Composition of Lipid Raft.

BACKGROUND: It has been reported that LXR agonist can inhibit Aß generation and alleviate Aß-induced various adverse reactions in vivo and in vitro experiments, but the mechanisms have not been clarified. The study aimed to observe the effect of LXR agonist TO901317 on the cognitive function of AD transgenic mice fed with cholesterol-rich diet (CRD), and to explore the possible mechanism. Methods: 32 male 6-month-old double transgenic AD mice were enrolled and randomly divided into 4 groups: control (normal diet) group, CRD treatment group, TO901317 treatment group and GSK2033 treatment group. After 3 month, Morris water maze was for the changes of spatial exploration and memory ability; ELISA was for detecting the production of Aß42 in the brain; the concentration of total cholesterol (TC), low density lipoprotein (LDL) and high density lipoprotein (HDL) in serum were detected by cholesterol enzyme colorimetry; Finally, the expression of LXR-ß, RXR-α, ABCA1, caveolin-1, BACE1 and APP at protein level in the brains was measured by Western blotting. RESULTS: Compared with the control group, the learning, memory ability and spatial exploration ability of the mice were more significantly serious in the CRD group (P<0.05); The contents of TC and LDL in the serum and the production of Aß42 in the brains were significantly increased (P<0.05), but HDL was remarkably decreased (P<0.05); The protein levels of LXR-ß, RXR-α and ABCA1 were also significantly decreased (P<0.05); The expression of caveolin-1, APP and BACE1 were evidently increased (P<0.05). However, after treatment with TO901317, the impaired learning and memory and spatial exploration ability of the mice were significantly improved (P<0.05); The contents of TC and LDL in serum and the production of Aß42 in the brains were significantly decreased (P<0.05), but HLD was increased (P<0.05); The protein levels of LXR-ß, RXR-α, ABCA1were all significantly increased (P<0.05), while, the expression of caveolin-1, APP and BACE1 were all significantly decreased (P<0.05). All the changes were reversed by GSK2033 (P<0.05). CONCLUSIONS: TO901317 attenuated the more serious impairment of spatial exploration, learning and memory in transgenic AD mice induced by CRD, and the mechanism may be that TO901317 could activate the LXR-ß/RXR-α/ABCA1 transmembrane transport system, promote the cholesterol efflux, and decreased caveolin-1, APP and BACE1, further reduce Aß42 in the brains.

Cognitive and Brain Gray Matter Changes in Children with Obstructive Sleep Apnea: A Voxel-Based Morphological Study.

BACKGROUND: To explore the neural difference between children with obstructive sleep apnea (OSA) and healthy controls, together with the relation between this difference and clinical severity indicator of children with OSA. METHODS: Twenty-seven children with OSA (7.6 ± 2.5 years, apnea hypopnea index [AHI]: 9.7 ± 5.3 events/h) and 30 healthy controls (7.8 ± 2.6 years, AHI: 1.7 ± 1.2 events/h) were recruited and matched with age, gender, and handedness. All children underwent 3.0 T magnetic resonance imaging of the brain and cognitive testing evaluating. Volumetric segmentation of cortical and subcortical structures and voxel-based morphometry were performed. Pearson's correlation analysis was performed between these features of gray matter volume (GMV) and obstructive apnea index (OAI) among children with OSA. RESULTS: In the comparison of children's Wechsler test scores of full-scale intelligence quotient and verbal intelligence quotient, the OSA group was significantly lower than the control group (p < 0.05). Compared with the control group, the GMV of many brain regions in the OSA group was significantly decreased (p < 0.05). In the correlation analysis of GMV and OAI in OSA group, right inferior frontal gyrus volume was significantly negatively correlated with OAI (r = - 0.49, p = 0.02). CONCLUSION: Children with OSA presented abnormal neural activities in some brain regions and impaired cognitive functions. This finding suggests an association between the OSA and decreased GMV in children.

Effects of Cerebellar Transcranial Direct Current Stimulation in Patients with Stroke: a Systematic Review.

BACKGROUND: The cerebellum is involved in regulating motor, affective, and cognitive processes. It is a promising target for transcranial direct current stimulation (tDCS) intervention in stroke. OBJECTIVES: To review the current evidence for cerebellar tDCS (ctDCS) in stroke, its problems, and its future directions. METHODS: We searched the Web of Science, MEDLINE, CINAHL, EMBASE, Cochrane Library, and PubMed databases. Eligible studies were identified after a systematic literature review of the effects of ctDCS in stroke patients. The changes in assessment scale scores and objective indicators after stimulation were reviewed. RESULTS: Eleven studies were included in the systematic review, comprising 169 stroke patients. Current evidence suggests that anode tDCS on the right cerebellar hemisphere does not appear to enhance language processing in stroke patients. Compared with the sham group, stroke patients showed a significant improvement in the verb generation task after cathodal ctDCS stimulation. However, with regard to naming, two studies came to the opposite conclusion. The contralesional anodal ctDCS is expected to improve standing balance but not motor learning in stroke patients. The bipolar bilateral ctDCS protocol to target dentate nuclei (PO10h and PO9h) had a positive effect on standing balance, goal-directed weight shifting, and postural control in stroke patients. CONCLUSIONS: ctDCS appears to improve poststroke language and motor dysfunction (particularly gait). However, the evidence for these results was insufficient, and the quality of the relevant studies was low. ctDCS stimulation parameters and individual factors of participants may affect the therapeutic effect of ctDCS. Researchers need to take a more regulated approach in the future to conduct studies with large sample sizes. Overall, ctDCS remains a promising stroke intervention technique that could be used in the future.

Hardware optical correlation method for dynamic detection of micrometer gaps with sub-nanometer resolution.

Surface plasmon lithography breaks through the diffraction limit with surface plasmon effect and achieves high-resolution imaging below sub-wavelengths. The dynamic detection and control of the working distance between the mask and the substrate is particularly important for the quality of the lithography samples. In this paper, the mask-substrate gap sensing mechanism is analyzed, and a mask-substrate gap absolute distance measurement model is established based on the principle of white light interference. We design a Fizeau interferometer demodulation system based on a hardware optical correlation method, and focus on analyzing the influence of the sub-nanometer surface profile of the optical wedge on the resolution. Finally, we propose a data processing method for extracting the dynamic gap value by SSA (singular spectrum analysis). The experimental results show that the system shows high performance with a gap detection range of 3.0∼6.0 µm, the stability of ±0.12 nm, and the resolution of better than 0.30 nm.

Antitumor Effects of 10058-F4 and Curcumin in Combination Therapy for Pancreatic Cancer In Vitro and In Vivo.

Background: Pancreatic cancer (PC) stands out as one of the most lethal cancers. Due to late diagnosis, only a fraction of patients can be resected. Although it still has significant adverse effects and poor results, the treatment is connected with better overall survival than the prior treatment. Thus, new alternative therapy for advanced PC is needed. Materials/Methods. The impact of 10058-F4 and curcumin combination therapy on apoptosis and cell growth in SW1990 pancreatic cancer cells were determined in vitro using the CCK-8 assay and flow cytometry of Annexin V-FITC/PI, and the in vivo antitumor effect was determined utilizing SW1990-bearing pancreatic tumor mouse models induced by subcutaneous implantation. Results: At concentrations of (10 mol/L+2 mol/L), 10058-F4+curcumin obtained the highest rate of SW1990 cell death, and they had a beneficial effect on SW1990 pancreatic tumor-bearing animals. Furthermore, c-Myc, Akt phosphorylation, and the expression of apoptosis-related molecular were reduced, and the combination therapy modified the expression of apoptosis-related molecular. Conclusions: In vitro and in vivo, the combination of 10058-F4 plus curcumin has antipancreatic cancer actions that are substantially effective.

Preoperative Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and CEA as the Potential Prognostic Biomarkers for Colorectal Cancer.

Background: This study was to evaluate the prognostic value of the preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and carcinoembryonic antigen (CEA) in colorectal cancer (CRC) patients and to identify the potential and easily accessible prognostic biomarkers for CRC. Methods: We retrospectively reviewed altogether the records of 330 CRC patients according to inclusion criteria. The clinical characteristics include age at diagnosis, body mass index (BMI), preoperative CEA level, neutrophil , lymphocyte, and platelet count, tumor primary site and size, clinical pathological TNM stage, and survival status were recorded through the review of medical records. The overall survival (OS) was calculated using the Kaplan-Meier method. The Cox proportional hazards model was used for the univariate and multivariate analysis to evaluate the prognostic factors of CRC. Results: A total of 330 patients were finally included in the current study. The mean follow-up duration was 32.8 ± 19.1 months (range, 0.1-67.7). Compared with the median OS, preoperative high NLR, PLR, and CEA, and low BMI had lower median OS. The NLR and PLR value rise indicates lower median OS in stage I-II CRC; however, the NLR value and CEA level rise indicates lower median OS in stage III-IV CRC. Preoperative high NLR, PLR, and CEA level and low BMI have poorer OS by univariate analysis. By multivariate analysis, the age, sex, N, M stage, and BMI demonstrated independently influence the OS of CRC. NLR was an independent predictor of stage I-II CRC, and the CEA level was an independent predictor of stage III-IV CRC. Conclusions: Our results show that preoperative high NLR, PLR, CEA, and low BMI had poorer OS, NLR was an independent predictor of stage I-II CRC, and the CEA level was an independent predictor of stage III-IV CRC.

The identification, logic and enlightenments of intra-urban place communities in China.

Spatial agglomeration phenomena on the earth permeate in various fields of the natural and human world, yet their researches in human society are relatively few with the focus mainly on the economic concept of "industrial clusters". Precise quantitative descriptions, in-depth logical analyses and proper application approaches for urban planning are lacked in various intra-urban spatial agglomeration phenomena. By using over 10 million POIs in the mainland China, 18 grid network models with two varieties of spatial relationships (co-location/adjacent) are constructed in this article. 23 typical place communities are extracted based on complex network analysis, and four types of agglomeration driving forces are summarized. A comprehensive demonstration displaying the application process of co-location/adjacent place matrices in auxiliary decision of the implanted place types is carried out with the example of the revitalization project of Taoxichuan Area in the city of Jingdezhen.

A phase II study of bevacizumab in non-squamous, non-small-cell lung cancer patients with malignant pleural effusion.

Aim: To investigate the efficacy, safety and optimal dosage of bevacizumab in non-squamous, non-small-cell lung cancer (NSCLC) patients with malignant pleural effusion (MPE). Methods: 20 patients were enrolled and received intrapleural injection of bevacizumab (group A: 2.5 mg/kg d1, d8; group B: 5 mg/kg d1, d8; group C: 7.5 mg/kg d1, d8). Results: The objective response rate (ORR) of MPE was 50%. The median progression-free survival (PFS) of MPE was 7.0 months (95% CI 4.9-9.2). The ORR and PFS of MPE from group B were better than those of group A and group C. The most common adverse events (AEs) were hypertension (15%) and anemia (15%). Conclusion: Bevacizumab has certain efficacy in non-squamous NSCLC patients with MPE. Clinical Trial Registration: NCT02942043 (ClinicalTrials.gov).

Intratracheal Keratinocyte Growth Factor Enhances Surfactant Protein B Expression in Mechanically Ventilated Preterm Pigs.

Bronchopulmonary dysplasia (BPD) is a devastating disease of prematurity that is associated with mechanical ventilation and hyperoxia. We used preterm pigs delivered at gestational day 102 as a translational model for 26-28-week infants to test the hypothesis administering recombinant human keratinocyte growth factor (rhKGF) at initiation of mechanical ventilation will stimulate type II cell proliferation and surfactant production, mitigate ventilator induced lung injury, and reduce epithelial to mesenchymal transition considered as a precursor to BPD. Newborn preterm pigs were intubated and randomized to receive intratracheal rhKGF (20 µg/kg; n = 6) or saline (0.5 ml 0.9% saline; control; n = 6) before initiating 24 h of ventilation followed by extubation to nasal oxygen for 12 h before euthanasia and collection of lungs for histopathology and immunohistochemistry to assess expression of surfactant protein B and markers of epithelial to mesenchymal transition. rhKGF pigs required less oxygen during mechanical ventilation, had higher tidal volumes at similar peak pressures indicative of improved lung compliance, and survival was higher after extubation (83% vs. 16%). rhKGF increased surfactant protein B expression (p < 0.05) and reduced TGF-1ß (p < 0.05), that inhibits surfactant production and is a prominent marker for epithelial to mesenchymal transition. Our findings suggest intratracheal administration of rhKGF at initiation of mechanical ventilation enhances surfactant production, reduces ventilator induced lung injury, and attenuates epithelial-mesenchymal transition while improving pulmonary functions. rhKGF is a potential therapeutic strategy to mitigate pulmonary responses of preterm infants that require mechanical ventilation and thereby reduce the incidence and severity of bronchopulmonary dysplasia.