[Progress on microneedle drug delivery systems for the treatment of corneal diseases].

Corneal diseases are prevalent eye conditions in China, and the lack of effective treatment in the short term can lead to blindness. However, delivering drugs to the cornea safely and effectively poses a significant challenge due to the presence of ocular barriers and clearance mechanisms. Conventional drug delivery methods exhibit low bioavailability, making it difficult to achieve therapeutic effects. Microneedles, with their ability to penetrate ocular surface barriers effectively, offer a low-invasive and highly promising drug delivery technology. This article introduces the main delivery barriers on the ocular surface, classifies microneedles, and highlights the latest developments in the treatment of corneal diseases. Finally, the potential challenges of applying microneedle delivery systems to the ocular surface are analyzed, aiming to provide insights for the clinical application of microneedles in corneal diseases.

Adjustable rotation of multiple vortices produced by diode-pumped Nd:YVO4 lasers using intracavity second harmonic generation.

The criteria for achieving adjustable rotation of optical vortices are analyzed and used to design a diode-pumped solid-state laser that incorporates intracavity second harmonic generation within a concave-flat cavity to produce frequency-doubled Hermite-Gaussian (FDHG) modes. These FDHG modes are subsequently employed to generate various structured lights containing 2, 4, and 6 nested vortices using an external cylindrical mode converter. Through theoretical exploration, we propose that increasing the radius of curvature of the concave mirror and extending the cavity length can enhance the rotational angles of multiple vortices by expanding the adjustable range of phase shift for FDHG modes. Moreover, theoretical analyses assess vortex rotation concerning the positions of a nonlinear medium, successfully validating the experimental observations and elucidating the phase structures of the transformed beams.

[A rational analysis of the commonly used renal tumor scoring systems in predicting surgical outcomes of cystic renal masses].

Objective: To explore the predictive effect of the renal tumor scoring system on the surgical outcomes of cystic renal masses (CRM). Methods: A retrospective analysis was performed on the data of 234 patients who received robotic-assisted partial nephrectomy (RAPN) treatment in the First Affiliated Hospital of Xi'an Jiaotong University from January 2018 to June 2020. And 31 cases had CRM and 203 cases had solid renal masses (SRM). The propensity score of patients was calculated by logistic regression model, and 1∶2 matching was performed by the nearest neighbor method. The changes in perioperative indexes and long-term estimated glomerular filtration rate (eGFR) in CRM group and SRM group were compared. The CRM group and SRM group were stratified according to the complexity grading of R.E.N.A.L. score and PADUA score, respectively, to compare the difference in the achievement rate of ideal surgical outcome between the two groups, and analyze the predictive factors affected. The CRM diameter was stratified with 4 cm as the cut-off value (CRM1 group with a diameter<4 cm, CRM2 group with a diameter≥4 cm), and the surgical results were compared with the matched SRM1 group and SRM2 group. Results: In the matching cohort, the CRM group comprised 29 patients with a mean age of (48.7±10.8) years, of which 22 (75.9%) were males. The SRM group included 58 patients with a mean age of (50.4±10.2) years, of which 41 (70.7%) were males, with no statistically significant difference (all P>0.05). The warm ischemia time (WIT) [M (Q1,Q3)] in the CRM group was longer than that in the SRM group [23(18, 25) vs 19(17, 25) min, P=0.040]. The operation time (OT) [M (Q1,Q3)] in the CRM group was also longer than that of the SRM group [130(100, 150) vs 108(86, 120) min, P=0.006]. The change in serum creatinine before and after the operation [M (Q1,Q3)] was higher in the CRM group than in the SRM group [15(10, 23) vs 12(6, 17) µmol/L, P=0.030]. The ideal surgical outcomes were achieved in 7 patients (24.1%) in the CRM group and 36 patients (62.1%) in the SRM group. The number of patients achieving ideal surgical outcomes in R.E.N.A.L. intermediate complex surgery and PADUA advanced complex surgery in the SRM group were 24 (58.5%) and 15 (51.7%), respectively, which were higher than those in the CRM group 6 (27.3%) and 1 (5.9%) respectively (P<0.05). Preoperative eGFR (OR=0.758, 95%CI: 0.719-0.799) and the nature of the tumor (CRM as reference, OR=4.883, 95%CI: 1.550-15.378) were influencing factors for achieving the ideal surgical outcome. Subgroup analysis showed that eGFR changes before and after surgery and the estimated blood loss (EBL) in the CRM2 group were higher than those in the SRM2 group, and WIT and OT were longer than those in the SRM2 group (all P<0.05). The EBL and WIT of the CRM1 group were shorter than those of the CRM2 group (P<0.05). Conclusion: The surgical risk of RAPN in complex CRMs with a maximum diameter of≥4 cm is higher than the risk of RAPN in SRM with equivalent R.E.N.A.L. and PADUA scores.

Cardiovascular magnetic resonance myocardial feature tracking for the determination of left atrial strain in hypertensive left ventricular hypertrophy and hypertrophic cardiomyopathy.

AIM: To measure the left atrial (LA) function in patients with hypertrophic cardiomyopathy (HCM; with [OHCM] and without obstruction [NOHCM]) and hypertension-related left ventricular hypertrophy (H-LVH) using cardiovascular magnetic resonance imaging feature tracking (CMR-FT). MATERIALS AND METHODS: Patients who met the criteria for HCM (n=68), H-LVH (n=46), and 30 healthy controls participated. Left atrial strain was analysed using CMR-FT in cine images with two and four chambers. RESULTS: The strain rate and LA strain measurements showed that patients with HCM, and H-LVH had impaired conduit and reservoir functions (versus controls). These capacities were more severely impaired in OHCM than those seen in NOHCM and H-LVH. The LA volume parameters (LAVIpac, LAVImin and LAVImax) from the OHCM group were higher than both the NOHCM and H-LVH groups (all p<0.05). There were differences between the OHCM and H-LVH groups in terms of the parameters for LA reservoir function (εs), booster pump function (SRa), and conduit function (SRe, LA passive EF, εe; p<0.05). The strongest correlations included the associations between LA total EF and εs, εe and LA passive EF, and SRe and LA passive EF. CONCLUSION: CMR-FT can reliably identify LA dysfunction and deformation in the early stages of HCM and H-LVH.

Extraction of heterocyclic amines and polycyclic aromatic hydrocarbons from pork jerky and the effect of flavoring on formation and inhibition.

Heterocyclic amines (HAs) and polycyclic aromatic hydrocarbons (PAHs)are widely distributed in foods.This study aims to extract PAHs and HAs from pork jerky simultaneously by QuEChERS for analysis by GC-MS/MS and UPLC-MS/MS, respectively. Also,the effects of flavoring materials and processing temperature on the formation of PAHs and HAswere studied. Acetonitrile containing 1% acetic acid possessed the highest extraction efficiency, with high accuracy and precision being attained forHAs and PAHs. Pork jerky roasted at 220℃ generated a higherPAHs content than180℃, but unaffected the HAs formation.Addition of sugarreduced formation ofboth HAs and PAHs during roasting, while soy sauce reduced somePAHs and promotedHAs formation. Incorporation of 0.5% curcumaorcinnamon powderinhibited HA formation with amore pronounced effect being shown by the latter,but neither inhibitedPAH formation. The correlation between HA and PAH formation was assessed by principle component analysis.

[The regulatory function of tumor-infiltrating Th9 cells to anti-tumor activity of CD8(+) T cells in patients with gastric cancer].

Objective: To investigate the levels of Th9 cells and interleukin-9 (IL-9), and to assess the regulatory activity of Th9/IL-9 to anti-tumor immune response in patients with gastric cancer. Methods: Thirty-four patients with gastric cancer who received operation in the First Affiliated Hospital of Xinxiang Medical University between October 2018 and August 2019 were included. Twenty individuals who received physical examination in the same period were also enrolled. Peripheral blood was collected, and then plasma and peripheral blood mononuclear cells (PBMCs) were isolated. Tumor-infiltrating lymphocytes (TILs) and autologous gastric cancer cells were isolated from resected gastric cancer tissues. CD4(+) T cells, CD8(+) T cells, and CD4(+) CCR4(-)CCR6(-)CXCR3(-) cells were purified from PBMCs and TILs. Plasma IL-9 level was measured by enzyme linked immunosorbent assay (ELISA). The percentage of CD3(+) CD4(+) IL-9(+) Th9 cells in PBMCs and TILSs was assessed by flow cytometry. The mRNA levels of IL-9 and transcriptional factors purine-rich nucleic acid binding protein 1 (PU.1) were semi-quantified by real-time quantitative polymerase chain reaction (RT-qPCR). PBMCs and TILs from gastric cancer patients were stimulated with recombinant human IL-9. Cellular proliferation was measured by cell counting kit-8. The phosphorylation levels of signal transducer and activator of transcription 3 (STAT3) and STAT6 were investigated by western blot. Cytokine production was measured by ELISA. Purified CD8(+) T cells from TILs of gastric cancer patients were stimulated with recombinant human IL-9. CD8(+) T cells and autologous gastric cancer cells were cocultured in direct contact and indirect contact manner. The percentage of target cell death was calculated by measuring the lactate dehydrogenase (LDH) level. These cretion of γ-Interferon (γ-IFN) and tumor necrosis factor-α (TNF-α) was measured by ELISA. CD4(+) CCR4(-)CCR6(-)CXCR3(-)cells, CD8(+) T cells, and autologous gastric cancer cells were directly cocultured, and anti-IL-9 neutralizing antibody was added. The target cell death was measured. Results: The percentages of CD3(+) CD4(+) IL-9(+) Th9 cells in PBMCs of control group and PBMCs of gastric cancer group were (1.21±0.25)% and (1.14±0.19)%, respectively. The difference was not statistically significant (P=0.280). The percentage of CD3(+) CD4(+) IL-9(+) Th9 cells in TILs of gastric cancer group was (2.30±0.55)%, which was higher than those in PBMCs of control group and PBMCs of gastric cancer group (P<0.001). The plasma IL-9 level in control group and gastric cancer group were (5.04±1.51) and (4.93±1.25) ng/ml. The difference was not statistically significant (P=0.787). The relative levels of IL-9 mRNA in PBMCs of control group and PBMCs of gastric cancer group were 1.33±0.39 and 1.36±0.27. The difference was not statistically significant (P=0.691). The relative level of IL-9 mRNA in TILs of gastric cancer group was 2.90±0.75, which was higher than those in PBMCs of control group (P<0.001) and PBMCs of gastric cancer group (P<0.001). The relative levels of PU.1 mRNA in PBMCs of control group and PBMCs of gastric cancer group were 1.21±0.12 and 1.20±0.11. The difference was not statistically significant (t=0.21, P=0.833). PU.1 mRNA relative level in TILs of gastric cancer group was 2.81±0.65, which was higher than those in PBMCs of control group (P<0.001) and PBMCs of gastric cancer group (P<0.001). Recombinant human IL-9 stimulation did not affect the proliferation of PBMCs and TILs of gastric cancer patients (P>0.05), but elevated the phosphorylation level of STAT6 and induced the secretions of γ-IFN, IL-17, and IL-22 by TILs (P<0.05). In direct contact culture system, IL-9 stimulation promoted tumor-infiltrating CD8(+) T cells-induced autologous gastric cancer cell death [(20.62±2.27)% vs. (16.08±2.61)%, P<0.01)]. In indirect contact culture system, IL-9 stimulation did not increase CD8(+) T cell-induced autologous gastric cancer cell death [(5.21±0.70)% vs. (5.31±1.22)%, P=0.998)]. However, the secretion levels of γ-IFN were elevated in response to IL-9 stimulation in both culture systems [direct contact culture system: (100.40±12.05) pg/ml vs. (76.45±8.56) pg/ml; indirect contact culture system: (78.00±9.98) pg/ml vs. (42.09±10.71) pg/ml; P<0.01]. The TNF-α secretion level did not significantly changed (P>0.05). In direct contact culture system, the percentage of target cells was (22.01±3.05) % and γ-IFN secretion level was (104.5±12.84) pg/ml in CD4(+) CCR4(-)CCR6(-)CXCR3(-) cells+ CD8(+) T cells+ gastric cancer cells group, which was higher than (16.08±2.61)% and (76.45±8.56) pg/ml in CD8(+) T cells+ gastric cancer cells group (P<0.01). However, the percentage of target cells was (14.47±3.14)% and γ-IFN secretion level was (70.45±19.43) pg/ml in CD4(+) CCR4(-)CCR6(-)CXCR3(-) cells+ CD8(+) T cells+ gastric cancer cells+ anti-IL-9 neutralizing antibody group, which were lower than those in CD4(+) CCR4(-)CCR6(-)CXCR3(-) cells+ CD8(+) T cells+ gastric cancer cells group (P<0.01). Conclusion: Tumor-infiltrating Th9 cells and the secreting IL-9 promote the activity of CD8(+) T cells in gastric cancer patients, and enhance anti-tumor immune response.

[P.F. von Siebold and his destiny with Chinese materia medica (Ben Cao)].

P. F. von Siebold (1796-1866) was a physician at the Dutch Business Centre (Shang Wu Hui Guan) located at Nagasaki, Japan, in the Edo period. He collected a great amount of botanical and mineral specimens, books, and living wares when he stayed in Japan. He brought these materials to Europe and kept some of them at the Japan Museum Siebold Huis in Leiden in Netherlands. This collection showed the role of Siebold in connecting scientific and cultural exchanges between East and West and provided references in the research of the transmission of traditional Chinese medicine worldwide in the 19th century.

[Effects of cortical bone trajectory screw in adjacent-segment disease after posterior lumbar interbody fusion].

Objective: To investigate the effect of the cortical bone trajectory (CBT) screw fixation combined with midline lumbar fusion (MIDLF) for adjacent spondylopathy after posterior lumbar interbody fusion. Methods: A retrospective analysis was conducted in 16 patients, including 9 males and 7 females, with a mean age of (68±6) years, who underwent revision surgery for adjacent spondylopathy after posterior lumbar fusion surgery using CBT combined with MIDLF technology in Sir Run Run Shaw Hospital, Zhejiang University from May 2013 to August 2019. The reasons for revision were radiculalgia in 4 cases, intermittent claudication in 10 cases and protrusive dissociate in 2 cases. Eleven cases had 1 segment fused in the first operation, while the other 5 cases received fusion in 2 segments. The average interval time between the first operation and the revision operation was (7.5±2.0) years. For the levels underwent revision, 1 case was L2/3, 6 cases were L3/4, 7 cases were L4/5 and 2 cases were L5/S1. Before the operation, all the patients took X-rays scans of the thoracic and lumbar spine. CT and MRI scans were also performed. The operation time, intraoperative bleeding, surgical complications, visual analog scale (VAS) of low back and leg pain before the operation and at each follow-up were all recorded. Oswestry disability index (ODI) questionnaire was used to evaluate the functional improvement of patients after the operation. Results: All operations were completed successfully. The operation time was 120-240 (170±30) mins, intraoperative bleeding was 100-280 (220±45) ml. One case had a slight split in the isthmus, and the screw was inserted smoothly after adjusting the insertion point. In one case, the cerebrospinal fluid leaked during the operation and was successfully treated with conservative methods including no pillow supine treatment and strengthened anti-infection. The average follow-up time was of (19.5±1.3) months. The VAS of low back pain was 2.9±1.7 before the operation and it was 1.8±0.5 at the last follow-up, and the difference was statistically significant (P<0.01). The VAS of leg pain was 5.9±1.5 before the operation and it was 1.5±0.4 at the last the follow-up (P<0.01). The ODI score was 34.5±3.2 preoperatively and it decreased to 12.6±4.2 at the last follow-up, the difference was statistically significant (P<0.01). Conclusion: CBT technique combined with MIDLF for the adjacent-segment disease after posterior lumbar interbody fusion is minimally invasive and convenient, with good clinical effects. This technique can be used as an option for the revision of adjacent spondylopathy.

Texture analysis applied in T1 maps and extracellular volume obtained using cardiac MRI in the diagnosis of hypertrophic cardiomyopathy and hypertensive heart disease compared with normal controls.

AIM: To assess the potential of texture analysis (TA) applied in T1 maps and extracellular volume (ECV) obtained using cardiac magnetic resonance (CMR) in the diagnosis of hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HHD) compared with normal controls (NC). Strain parameters were analysed to compare with final TA models. MATERIALS AND METHODS: This retrospective study included 66 HCM patients, 39 HHD patients, and 41 NC. Step-wise dimension reduction and feature selection were performed by reproducibility, machine learning, collinearity, and multivariable regression analysis to select the texture features that enable diagnosis of and differentiation between HCM and HHD. Strain parameters were calculated by short-axis and three long-axis cine sequences. RESULTS: Independent features in T1 maps and ECV analysis allowed for the differentiation between patients (HCM and HHD) and NC. Of the best-calculated model, the areas under the receiver operating curve (AUCs) were as follows: 0.969 for T1 map and 0.964 for ECV. To distinguish HCM from HHD, two independent features were screened out for both T1 and ECV maps. The AUCs were as follows: 0.793 for T1 map and 0.894 for ECV. Radial, circumferential, and longitudinal strain parameters could differentiate patients from NC, but only longitudinal strain parameters was significantly different between HCM and HHD. CONCLUSIONS: Texture analysis of T1 maps and ECV shows high accuracy in differentiating hypertrophic myocardium from NC, and HCM from HHD. Strain parameters are able to demonstrate the difference between patients and NC, but were less impressive in differentiating HCM and HHD.

Recent advances in one-stage conversion of lipid-based biomass-derived oils into fuel components - aromatics and isomerized alkanes.

Nowadays, production of biofuels is a rather hot topic due to depleting of conventional fossil fuel feedstocks and a number of other factors. Plant lipid-based feedstocks are very important for production of diesel-, kerosene-, and gasoline-like hydrocarbons. Usually, (hydro)deoxygenation processes are aimed at obtaining of linear hydrocarbons known to have poor fuel characteristics compared to the branched ones. Thus, further hydroisomerization is required to improve their properties as motor fuel components. This review article is focused on conversion of lipid-based feedstocks and model compounds into high-quality fuel components for a single step - direct cracking into aromatics and merged hydrodeoxygenation-hydroisomerization to obtain isoparaffins. The second process is quite novel and a number of the research articles presented in the literature is relatively low. As auxiliary subsections, hydroisomerization of straight hydrocarbons and techno-economic analysis of renewable diesel-like fuel production are briefly reviewed as well.

[Implications of EET in renal ischemia/reperfusion by regulating NLRP3 expression and pyroptosis].

Objective: To investigate the mechanism of epoxyeicosatrienoic acids (EET) on renal ischemia/reperfusion (I/R). Methods: Thirty 10-week male C57BL6 mice were randomly divided into five groups: sham goup, I/R group, I/R with EET group, I/R with toll-like receptor 4 (TLR4) inhibitor (TAK242) group, I/R with EET and TAK242 group. Blood urea nitrogen (BUN) and serum creatinine (Scr) as well as renal pathological changes were observed 24 h after reperfusion. The protein expression of NOD-like receptor pyrin domain containing 3 (NLRP3), cysteinyl aspartate specific proteinase 1 (caspase-1), interleukin-1ß (IL-1ß), TLR4 and myeloid differentiation factor 88 (MyD88) were evaluated using Western blot. Results: Severe renal tubular epithelial cell injury and decreased renal function [BUN:(10.37±0.53) vs (6.70±0.82)mmol/L, t=9.17, P<0.001; Scr: (83.67±3.88) vs (32.50±3.51)µmol/L, t=23.96, P<0.001] occurred in I/R group. Compared to the sham group, the relative expression of NLRP3 (1.54±0.10 vs 0.71±0.05, t=13.14, P<0.001), caspase-1 (2.35±0.05 vs 0.62±0.02, t=73.77, P<0.001), IL-1ß (3.11±0.11 vs 1.26±0.05, t=35.97, P<0.001), TLR4 (1.58±0.03 vs 0.39±0.01, t=86.00, P<0.001), MyD88 (0.94±0.02 vs 0.26±0.01, t=72.61, P<0.001) were significantly increased. Mice pretreated with EET analog featured lower kidney damage and diminished levels of above proteins than I/R group (all P<0.001). Besides, the co-administration of TAK242 and EET analog could even markedly reduced the expression levels of each proteins than those in I/R group and I/R with EET group (all P<0.001). Conclusion: EET exerts a protective effect on attenuating renal I/R injury possibly through inhibiting TLR4 pathway to regulate the activation of NLRP3-induced pyroptosis.

Biventricular tissue tracking demonstrating associations between left ventricular myocardial extracellular volume, pulmonary artery pressure, and reduced right ventricular ejection fraction in patients with systemic lupus erythematosus using cardiovascular MRI.

AIM: To investigate the feasibility and prognostic value of biventricular strain analysis for patients with systemic lupus erythematosus (SLE) and relationship to left ventricular (LV) myocardial fibrosis, pulmonary hypertension (PAH), and right ventricular (RV) ejection fraction (RVEF). MATERIALS AND METHODS: A total of 50 SLE patients (47 women; 34.4±12 years) and 15 controls (13 women; 32.9±8.6 years) were imaged via echocardiography and a 3 T magnetic resonance imaging (MRI). Pulmonary artery systolic pressure (sPAP) was assessed using echocardiography. Biventricular global circumferential strain (GCS), global longitudinal strain (GLS), global circumferential strain rate (GCSR), and global longitudinal strain rate (GLSR) as well as LV myocardial extracellular volume (ECV) were derived for each subject. RESULTS: Elevated LV ECV was significantly associated with LV GCS (beta -0.428, p=0.000), GLS (beta 0.404, p=0.000), GCSR (beta -0.350, p=0.006), GLSR (beta -0.445, p=0.000) and RV GCS (beta -0.373, p=0.000), and the presence of reduced RVEF was significantly associated with LV GCS (beta -0.338, p=0.002), GLS (beta -0.465, p=0.000) and RV GCS (beta -0.465, p=0.000). Raised sPAP was significantly associated with RV GLS (beta 0.445, p=0.000) and GCSR (beta -0.387, p=0.001). Moreover, there were significantly correlations between LV and RV strain and strain rate. CONCLUSIONS: Biventricular strain analysis may be a better prognostic tool for patients with SLE as it allows greater comprehensive analysis and more definitive treatment planning compared to separate assessment of LV or RV contractility.

Magnetic glassy state at low spin state of Co3+ in EuBaCo2O5+δ (δ = 0.47) cobaltite.

The magnetic glassy state is a fascinating phenomenon, which results from the kinetic arrest of the first order magnetic phase transition. Interesting properties, such as metastable magnetization and nonequilibrium magnetic phases, are naturally developed in the magnetic glassy state. Here, we report magnetic glass property in the low spin state of Co3+ in EuBaCo2O5+δ (δ = 0.47) cobaltite at low temperature (T < 60 K). The measurements of magnetization under the cooling and heating in unequal fields, magnetization relaxation and thermal cycling of magnetization show the kinetic arrest of low magnetization state below 60 K. The kinetically arrested low temperature magnetic phase is further supported through the study of isothermal magnetic entropy, which shows the significant entropy change. The present results will open a new window to search the microscopic relation between the spin state transitions and the kinetic arrest induced magnetic glassy phenomena in complex materials.

Efficient middle-infrared generation in LiGaS2by simultaneous spectral broadening and difference-frequency generation: erratum.

In this erratum, we correct the abstract and introduction of Opt. Lett.43, 1742 (2018)OPLEDP0146-959210.1364/OL.43.001742 to not include a wrong name for the crystal.

Efficient middle-infrared generation in LiGaS2 by simultaneous spectral broadening and difference-frequency generation.

We report a surprisingly broadband and efficient midinfrared pulse generation in LiGaS2 (Langasite, LGS) by invoking a simultaneous interplay of intrapulse difference-frequency generation, self-phase modulation, and dispersion. This cascaded mechanism expands the output bandwidth and output power at the same time. With 30-fs driving pulses centered at 1030-nm wavelength we obtain a broadband middle-infrared spectrum of 8-11 µm with an LGS crystal as thick as 4 mm, which is eight times longer than the walk-off length.

The effect of percutaneous endoscopic lumbar discectomy under different anesthesia on pain and immunity of patients with prolapse of lumbar intervertebral disc.

OBJECTIVE: To explore the effect of percutaneous transforaminal endoscopic discectomy under different anesthesia on pain and immunity of patients with lumbar disc herniation. PATIENTS AND METHODS: 92 cases of patients with lumbar disc herniation in the Affiliated Hospital of Qingdao University from February 2015 to January 2016 were collected. These patients were randomly divided into control group and observation group (n = 46). Patients in the control group underwent percutaneous transforaminal endoscopic discectomy with the use of local anesthesia, while patients in the observation group used continuous epidural anesthesia. Oswestry Disability Index (ODI) and Visual Analogue Scale of Pain (VAS) were used to compare the surgical effect and the degree of pain of patients in the two groups. Adverse reactions (nausea, vomiting, dizziness, drowsiness) of patients in two groups were compared. T lymphocytes subset level (CD4+, CD8+) and inflammatory cytokines (IL-2, TNF) in the immune system were compared on the 1st, 3rd, and 10th day post-operatively. RESULTS: The pain degree of patients in the two groups had no significant difference before their operations (p > 0.05). The intraoperative pain rate of patients in the observation group was significantly lower than the control group (p < 0.05). Patients in both groups achieved a remarkable decrease of pain intensity on month 1 and month 3 post-operatively (p < 0.05). There is no significant difference between the two groups (p > 0.05). ODI scores of patients in the two groups had no significant difference pre-operatively (p > 0.05). Patients in both groups achieved a remarkable decrease of ODI scores after surgery (p < 0.05), and there is no significant difference between the two groups (p > 0.05). The occurrence of adverse reactions in the observation group was significantly lower than the control group (p < 0.05). On day 1 and 3 post-operatively, CD4+ and CD8+ levels of patients in both groups were lower than before operation, and data in the control group decreased more than the observation group (p < 0.05). IL-2 and TNF-α levels of patients in the two groups were significantly higher than pre-operatively, and data in the control group was higher than the observation group (p < 0.05). On day 10 post-operatively, all the indexes returned to the preoperative level. CONCLUSIONS: Both continuous epidural anesthesia and local anesthesia can reduce or avoid perioperative pain, but continuous epidural anesthesia has more advantages than local anesthesia, and it can improve the immune function for patients undergoing PTED for LDH.

Preparation of carotenoid extracts and nanoemulsions from Lycium barbarum L. and their effects on growth of HT-29 colon cancer cells.

Lycium barbarum L., a traditional Chinese herb widely used in Asian countries, has been demonstrated to be protective against chronic diseases such as age-related macular degeneration. The objectives of this study were to determine the carotenoid content in L. barbarum by high-performance liquid chromatography-mass spectrometry, followed by preparation of a carotenoid nanoemulsion to evaluate the mechanism of inhibition on HT-29 colon cancer cells. The highest extraction yield of carotenoids was attained by employing a solvent system of hexane-ethanol-acetone (1:1:1, v/v/v). Nine carotenoids, including neoxanthin (4.47 µg g-1), all-trans-zeaxanthin and its cis-isomers (1666.3 µg g-1), all-trans-ß-cryptoxanthin (51.69 µg g-1), all-trans-ß-carotene and its cis-isomers (20.11 µg g-1), were separated within 45 min and quantified using a YMC C30 column and a gradient mobile phase of methanol-water (9:1, v/v) (A) and methylene chloride (B). A highly stable carotenoid nanoemulsion composed of CapryolTM 90, Transcutol®HP, Tween 80 and deionized water was prepared with a mean particle size of 15.1 nm. Characterization of zeaxanthin standard, blank nanoemulsion, carotenoid extract and carotenoid nanoemulsion by differential scanning calorimetry curves and Fourier transform infrared spectra revealed a good dispersion of zeaxanthin-dominated carotenoid extract with no significant chemical change after incorporation into nanoemulsion. The in vitro release kinetic study showed a higher release profile at pH 5.2 than at physiological pH 7.4, suggesting a rapid release of carotenoids in the acidic environment (pH 4.5-6.5) characteristic of tumors. Both the carotenoid nanoemulsion and the extract were effective at inhibiting growth of HT-29 colon cancer cells, with an IC50 of 4.5 and 4.9 µg ml-1, respectively. Also, both treatments could up-regulate p53 and p21 expression and down-regulate CDK2, CDK1, cyclin A and cyclin B expression and arrest the cell cycle at G2/M. The study may form a basis for further exploration of L. barbarum nanoemulsion in cancer treatment.

TGFß promotes mesenchymal phenotype of pancreatic cancer cells, in part, through epigenetic activation of VAV1.

The highly homeostasis-resistant nature of cancer cells leads to their escape from treatment and to liver metastasis, which in turn makes pancreatic ductal adenocarcinoma (PDAC) difficult to treat, especially the squamous/epithelial-to-mesenchymal transition (EMT)-like subtype. As the molecular mechanisms underlying tumour heterogeneity remain elusive, we investigated whether epigenetic regulation might explain inter-individual differences in the progression of specific subtypes. DNA methylation profiling performed on cancer tissues prior to chemo/radiotherapy identified one hypermethylated CpG site (CpG6882469) in the VAV1 gene body that was correlated with demethylation of two promoter CpGs (CpG6772370/CpG6772811) in both PDAC and peripheral blood. Transforming growth factor ß treatment induced gene-body hypermethylation, dissociation of DNMT1 from the promoter, and VAV1 expression via SMAD4 and mutant KrasG12D. Pharmacological inhibition of TGFß-VAV1 signalling decreased the squamous/EMT-like cancer cells, promoted nuclear VAV1 localization, and enhanced the efficacy of gemcitabine in prolonging the survival of KPfl/flC mice. Together, the three VAV1 CpGs serve as biomarkers for prognosis and early detection, and the TGFß-VAV1 axis represents a therapeutic target.