TEAD4 Activates PCSK9 to Promote Stomach Adenocarcinoma Cell Stemness through Fatty Acid Metabolism.

INTRODUCTION: This study attempted to investigate how proprotein convertase subtilisin/kexin type 9 (PCSK9) influences the stemness of stomach adenocarcinoma (STAD) cells. METHODS: CCK-8 and sphere-formation assays were used to detect cell viability and stemness. qRT-PCR and Western blot were used to detect PCSK9 and TEAD4 expression. The binding relationship was verified by dual-luciferase and chromatin immunoprecipitation assays. The effect of TEAD4 activating PCSK9 on the stemness of STAD cells was detected by bioinformatics, BODIPY 493/503, Oil red O, Western blot, and kits. In vivo experiments verified the role of the TEAD4/PCSK9 axis in tumor formation in nude mice. RESULTS: PCSK9 and TEAD4 were highly expressed in STAD. PCSK9 was enriched in the fatty acid metabolism (FAM) pathway. PCSK9 activated the fatty acid metabolism and promoted the proliferation and stemness of STAD cells. TEAD4 as a transcription factor upstream of PCSK9, cell experiments revealed that knockdown of PCSK9 inhibited STAD cell stemness, whereas further addition of fatty acid inhibitors could attenuate the promoting effect on STAD cell stemness brought by STAD overexpression. Rescue experiments showed overexpressed PCSK9 exerted an inhibitory effect on the stemness of STAD cells brought by TEAD4 knockdown. The hypothesis that TEAD4/PCSK9 axis can promote STAD cell growth was confirmed by in vivo experiments. CONCLUSION: Transcription factor TEAD4 could activate PCSK9 to promote the stemness of STAD cells through FAM. These results added weight to the assumption that TEAD4/PCSK9 axis has the potential to be the therapeutic target that inhibits cancer stem cell in STAD.

A snap-shot of orthokeratology lens rinsing habits: An online survey in a major eye hospital in Shanghai.

PURPOSE: A hospital-based survey to explore lens rinsing habits of orthokeratology (ortho-k) patients, including the solution used for rinsing. METHODS: An anonymous survey, via an online questionnaire, was administered to ortho-k lens wearers or their parents when they attended Fudan University Eye and ENT Hospital for routine follow-up visits. Three major issues were investigated: basic demographics, lens rinsing solution used, and specific rinsing habits. Relationships between demographics and rinsing solution used and rinsing behaviours were explored. RESULTS: Of the total of 541 online questionnaires delivered, 296 were completed and returned. The respondents were the person responsible for lens care, either the ortho-k users themselves, or their parents. The median age of the lens wearers was 12.0 years (range: 8-22 years), and the median period of ortho-k lens wear was 18.0 months (range: 1-109 months). The most common rinsing solutions reported were a particular brand of multidose preserved saline (28.4%), cooled boiled water (23.3%), and non-preserved multidose saline (16.2%). Overall, the main reason for choice of rinsing solution was recommendation of eye care practitioners (90.2%). The respondents with a longer lens wear history tended to use commercially available bottled water, drinking water, or cooled boiled water rather than non-preserved saline (unidose or multidose) (p ≤ 0.009) and were more likely to use the rinsing solution to soak their lenses (p = 0.009). Lens wearers who rinsed the lenses themselves tended to use tap water compared to those whose lenses were handled by parents (p = 0.040). CONCLUSION: Inappropriate choice and usage of rinsing solution appeared to be a common issue among ortho-k lens wearers in Shanghai, China. The problem was more pronounced in long-term wearers and in those who performed rinsing themselves.

Chinese Parents' Perspective on Myopia: A Cross-Sectional Survey Study.

INTRODUCTION: The prevalence of myopia in young generations has dramatically increased over the years, especially in China. This study aims to understand Chinese parents' perspectives on myopia for further improvement of treatment compliance and informing future health planning and policy. METHODS: This was a prospective cross-sectional survey study. A self-administrated, internet-based questionnaire was distributed to 2545 parents in China. Detailed information about the demographics, the awareness of myopia, related complications, and practices of myopia prevention and control of the respondents were collected. The distribution of answers was compared among different groups of children's age, children's refractions, and parents' residential locations. Relationships between parental cognition and behavior were also analyzed. RESULTS: Eligible responses were returned by 2500 parents. A total of 55.1% of the respondents considered myopia as a disease and more than 70% of respondents did not realize pathological changes related to myopia. Most parents thought myopia could be prevented (82.0%) and controlled (75.2%), and these parents were more likely to take measures than the parents who did not think so (P < 0.001). The most common myopia control modality was spectacles (87.0%), among which single-vision spectacles are the most used (63.7%). CONCLUSIONS: Knowledge about health risks related to myopia was lacking in Chinese parents and their practices of myopia control mainly involved single-vision glasses. Nationwide education for parents about myopia is needed to further advance outcomes of myopia prevention and control.

The proton conduction behavior of two 1D open-framework metal phosphates with similar crystal structures and different hydrogen bond networks.

Two open-framework zinc phosphates [C3N2H12][Zn(HPO4)2] (1) and [C6N4H22]0.5[Zn(HPO4)2] (2) were synthesized via hydrothermal reaction and characterized by powder X-ray diffraction, thermogravimetric analysis and scanning electron microscopy. Both compounds have a similar crystal structure and macroscopic morphology. However, the difference in equilibrium cations, in which the propylene diamine is for 1 and the triethylenetetramine is for 2, results in a significant distinction in the dense hydrogen grid. The diprotonated propylene diamine molecule in 1 is more favorable for forming a hydrogen-bond network in three dimensions than in 2, in which the twisted triethylenetetramine forms a hydrogen bond grid with the inorganic framework only in two dimensions owing to its large steric effect. This distinction further leads to a disparity in the proton conductivity of both compounds. The proton conductivity of 1 can reach 1.00 × 10-3 S cm-1 under ambient conditions (303 K and 75% RH) and then increase to 1.11 × 10-2 S cm-1 at 333 K and 99% RH, which is the highest value among the open-framework metal phosphate proton conductors operated in the same conduction. In contrast, the proton conductivity of 2 is four orders of magnitude smaller than 1 at 303 K and 75% RH and two orders smaller than 1 at 333 K and 99% RH.

An miR156-regulated nucleobase-ascorbate transporter 2 confers cadmium tolerance via enhanced anti-oxidative capacity in barley.

INTRODUCTION: Cadmium (Cd) is one of the most detrimental heavy metal pollutants, seriously affecting crop production and human health. Nucleobase-ascorbic acid transporters (NAT) are widely present in many living organisms including plants, animals and microbes; however, the role of NAT in plant Cd tolerance remains unknown. OBJECTIVES: To identify Cd-induced miRNAs that target HvNAT2 and to determine the role of this gene and its product in Cd tolerance. METHODS: High-throughput-sequencing was used to identify the miRNA expression profile of barley roots in response to Cd stress. Overexpression (OX) and RNAi lines were then constructed for HvNAT2 and comparative transcriptomic analysis was performed to determine the function of this transporter examining its effects on traits such as Cd uptake/flux and translocation, morphology and antioxidant capacity in relation to Cd tolerance. In addition, phylogenetic analysis was performed to obtain insights into the evolution of HvNAT2. RESULTS: Cd stress-induced genome-wide expression profiles of miRNAs identified a Cd-induced miRNA, miR156g-3p_3, that had HvNAT2 as its target. HvNAT2 was negatively regulated in the high-Cd-accumulating and Cd-tolerant genotype Zhenong8. Evolutionary analysis indicated that orthologues of the plasma membrane localized, HvNAT2, can be traced back to the sister group of land plants, the streptophyte algae. Overexpression of HvNAT2 increases Cd tolerance with higher tissue Cd accumulation but less oxidative damage in transgenic barley plants. RNAi of HvNAT2 leads to a significant reduction of Cd tolerance. The higher Cd accumulation in roots of the OX3 line was also demonstrated by confocal microscopy and electrophysiology. Transcriptome analysis showed that the enhancement of antioxidant capacity by HvNAT2 was related to stress signaling pathways. Furthermore, oxidative stress tolerance in HvNAT2-OX plants was regulated by the synthesis of phytochelatins and the glutathione metabolism cycle. CONCLUSION: Our study reveals a key molecular mechanism of NAT in Cd tolerance in plants that is useful for sustainable agricultural production and management of hazardous this heavy metal for better environment management and ecosystem function.

Long-Term Observation of Higher-Order Aberrations and Microdistortions in Bowman's Layer After Small Incision Lenticule Extraction for the Correcting Myopia With Spherical Equivalent Higher Than -9.0 Diopters.

Purpose: To evaluate the outcomes in corneal higher-order aberrations (HOAs) and microdistortions in the Bowman's layer after femtosecond laser small incision lenticule extraction (SMILE) for correcting extremely high myopia. Methods: This prospective study included patients with myopia with spherical equivalent ≥ -9.0 Diopters (D). SMILE was performed in forty eyes of 40 patients. Pentacam was used to evaluate HOAs before and at 1 day, 3 months, 6 months, and 2 years after surgery. Fourier-domain optical coherence tomography was used to evaluate microdistortions at 2 years postoperatively. Thirty-two eyes of 32 patients receiving femtosecond laser-assisted in situ keratomileusis (FS-LASIK) were enrolled as the control group. HOAs were measured before, at 1 day and at least 1 year postoperatively. Results: After SMILE, the long-term safety and effectiveness index was 1.25 and 0.85, respectively. Microdistortions were observed in 73.5% of the eyes at 2 years, with an average number of 1.20 ± 1.22 microdistortions and an average width of 287.37 ± 259.00 µm. We detected more microdistortions in the horizontal meridian than in the vertical meridian (p = 0.035). The average number and width of microdistortions were both higher in the central region (≤4 mm) than in the peripheral region (4-8 mm) (both p < 0.001). With the exception of horizontal trefoil in the SMILE group and vertical trefoil in the FS-LASIK group, significant changes over time were observed in all other HOAs (all p < 0.05). Meanwhile, we detected significant increases in the total corneal HOA, spherical aberration (SA), and coma at all time-points after both surgeries (all p < 0.01). Compared with FS-LASIK, SMILE induced less SA (p < 0.001) and more horizontal coma (p = 0.036). In the SMILE group, the HOA, SA, and trefoil were more in the small optical zone (≤6.0 mm) than in the large optical zone (>6.0 mm) (all p < 0.05). The increase in SA and most trefoil correlated with the mean number of central microdistortions number (all p < 0.05). Conclusion: For myopia over -9.0D, the microdistortions in the Bowman's layer were still detectable in most eyes long-term after SMILE. Both SMILE and FS-LASIK induced more HOAs, mainly HOA, SA, and coma. The small optical zone and microdistortions may affect postoperative aberrations.

Enhanced Recovery Care vs. Traditional Care in Laparoscopic Hepatectomy: A Systematic Review and Meta-Analysis.

Background: Enhanced recovery care could alleviate surgical stress and accelerate the recovery rates of patients. Previous studies showed the benefits of enhanced recovery after surgery program in liver surgery, but the exact role in laparoscopic hepatectomy is still unclear. Aim: We aimed to perform a meta-analysis to evaluate the safety and efficacy of enhanced recovery after a surgery program in laparoscopic hepatectomy. Methods: The relative studies from a specific search of PUBMED, EMBASE, OVID, and Cochrane database from June 2008 to February 2022 were selected and included in this meta-analysis. The primary outcomes included length of hospital stay, duration to functional recovery, and overall postoperative complication rate. The secondary outcomes included operative time, intraoperative blood loss, cost of hospitalization, readmission rate, Grade I complication rate, and Grade II-V complication rate. Results: A total of six studies with 643 patients [enhanced recovery care (n = 274) vs. traditional care (n = 369)] were eligible for analysis. These comprised three randomized controlled trials and three retrospective studies. Enhanced recovery care group was associated with decreased hospital stay [standard mean difference (SMD) = -0.56, 95% confidence interval (CI) = -0.83~-0.28, p < 0.0001], shorter duration to functional recovery (SMD = -1.14, 95% CI = -1.92~-0.37, p = 0.004), and lower cost of hospitalization Mean Difference (MD) = -1,539.62, 95% CI = -1992.85~-1086.39, p < 0.00001). Moreover, a lower overall postoperative complication rate was observed in enhanced recovery care group [Risk ratio (RR) = 0.64, 95% CI = 0.51~0.80, p < 0.0001] as well as lower Grade II-V complication rate (RR = 0.55, 95% CI = 0.38~0.80, p = 0.002), while there was no significant difference in intraoperative blood loss (MD = -65.75, 95% CI = -158.47~26.97, p = 0.16), operative time (MD = -5.44, 95% CI = -43.46~32.58, p = 0.78), intraoperative blood transfusion rate [Odds ratio (OR) = 0.71, 95% CI = 0.41~1.22, p = 0.22], and Grade I complication rate (RR = 0.73, 95% CI = 0.53~1.03, p = 0.07). Conclusion: Enhanced recovery care in laparoscopic hepatectomy should be recommended, because it is not only safe and effective, but also can accelerate the postoperative recovery and lighten the financial burden of patients.

Comparison of Corneal Biomechanics in Post-SMILE, Post-LASEK, and Keratoconic Eyes.

Significance: Our study found that SP-A1 (stiffness parameter at time of first applanation) was statistically different between post-laser-assisted subepithelial keratomileusis (LASEK) and post-small incision lenticule extraction (SMILE) eyes. The stiffness of keratoconus was lower than that of post-refractive surgery corneas. Purpose: To compare corneal biomechanics among post-SMILE, post-LASEK, and keratoconic eyes. Methods: In this retrospective study, 36 eyes of 36 patients after SMILE, 36 eyes of 36 patients after LASEK, and 36 eyes of 36 patients with keratoconus with matching (±5 µm) central corneal thickness (CCT) were examined using Scheimpflug corneal topography (Pentacam HR) and dynamic Scheimpflug analyzer (CorVis ST). Mixed linear model analysis with Bonferroni-adjusted post-hoc comparisons was performed to compare the differences in corneal biomechanics and topographic parameters among the three groups with the CCT and the bIOP (intraocular pressure with biomechanical correction) as the random factor. Results: All groups had comparable CCT at baseline. The bIOPs between the three groups were comparable. The mean values of the Belin/Ambrósio Deviation (BAD-D) in the keratoconus group were significantly higher than those of the SMILE (post hoc p < 0.001) and LASEK groups (post hoc p < 0.001). The SP-A1 in the keratoconus group was the lowest when compared with those of the SMILE (post hoc p = 0.003) and LASEK groups (post hoc p < 0.001). The SMILE group SP-A1 values were slightly lower than those of the LASEK group (post hoc p = 0.044). Conclusions: Keratoconus eyes were significantly softer when compared to post-refractive surgery corneas with comparable corneal thickness in terms of SP-A1 and BAD-D values, while the LASEK group may have the greatest stiffness. Post-SMILE and post-LASEK corneas showed significant differences in SP-A1.

Effects of warm compress on tear film, blink pattern and Meibomian gland function in dry eyes after corneal refractive surgery.

BACKGROUND: To assess the effects of warm compress (WC) on tear film lipid layer, blink pattern and Meibomian gland function in patients with dry eye following femtosecond laser small incision lenticule extraction (SMILE) and laser-assisted subepithelial keratomileusis (LASEK). METHODS: We enrolled 37 eyes of 37 participants, each with dry eye for more than 2 years following SMILE (25 eyes) or LASEK (12 eyes). WC was performed using a spontaneously heating eye mask. Tear film break-up time (TBUT), tear film lipid layer thickness (TFLLT), blink pattern, Meibomian secretory function scores (MGS), visual acuity, spherical equivalent (SE), keratometry, central corneal thickness (CCT) and aberration were assessed before and after WC. RESULTS: After WC, the following mean values all increased relative to baselines: CCT, SE, minimum (Min-), maximum (Max-) and average (Ave-) TFLLT, TBUT, total MGS (TMGS), number of glands secreting any liquid (MGL), and complete blink rate (CBR) (p values ranging from < 0.001 to 0.042). Partial blink frequency (PBF) and partial blink rate (PBR) decreased (p = 0.002 in both cases). The decrease of PBF was higher in SMILE subgroup than in LASEK (p = 0.030). TBUT variation was positively correlated with that of Ave-TFLLT and TMGS (p = 0.046, 0.028, respectively). Max-TFLLT variation was correlated with that of TMGS (p = 0.020). CONCLUSIONS: WC may temporarily increase tear film thickness and stability, decrease partial blink, and partly augment Meibomian gland function in dry eye patients after corneal refractive surgeries. Future studies are required to investigate long term clinical efficacy and safety.

miR-504 Promoted Gastric Cancer Cell Proliferation and Inhibited Cell Apoptosis by Targeting RBM4.

BACKGROUND: The purpose of this study was to explore the role and underlying mechanism of miR-504 and RBM4 in gastric cancer. METHODS: The qRT-PCR or Western blot was performed to determine the expressions of miR-504 and RBM4 in the gastric cancer tissues and normal tissues. Human SGC-7901 cells were transfected with miR-504 mimic/inhibitor or pcDNA-RBM4. Cell proliferation and cell apoptosis were assessed by colony formation assay and flow cytometry, respectively. Luciferase reporter gene assays were used to investigate interactions between miR-504 and RBM4 in SGC-7901 cells. RESULTS: The relative expression of miR-504 was significantly upregulated in the gastric cancer group (n = 25) than in the paired normal group (n = 25), but the relative RBM4 expression was remarkably downregulated in the gastric tumor group, compared with the normal group. Additionally, miR-504 overexpression increased the viability of gastric cancer cells. Moreover, RBM4 is a functional target of miR-504 in gastric cancer cells. miR-504 was further confirmed to promote SGC-7901 cell proliferation and inhibit cell apoptosis by downregulation RBM4 in vitro. CONCLUSIONS: miR-504 promotes gastric cancer cell proliferation and inhibits cell apoptosis by targeting RBM4, and this provides a potential diagnostic biomarker and treatment for patients with gastric cancer.

Comparison of posterior corneal elevation after SMILE and FS-LASIK in correcting myopia over -9.0 diopters.

BACKGROUND: To compare the changes in posterior corneal elevation after small incision lenticule extraction (SMILE) and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) in correcting myopia over -9 diopters (D). METHODS: In this prospective comparative study, 82 eyes of 82 patients scheduled for refractive correction were recruited. Eyes were randomly assigned to the SMILE group (45 eyes, -10.43±0.92 D) or FS-LASIK group (37 eyes, -10.97±1.37 D). The posterior corneal surface was measured using a Scheimpflug camera (Pentacam, Oculus, Germany) preoperatively and at 1 day, 1 month, and 6 months after surgery. Posterior corneal elevation in the central point and central 4-mm area, and in various optical zones above the best-fit sphere, was analyzed. A P value of less than 0.05 was considered statistically significant. RESULTS: All surgeries were completed successfully. The safety index and efficacy index were 1.20 and 1.00, respectively, in the SMILE group, and was 1.10 and 0.90, respectively, in the FS-LASIK group. No significant difference existed in all analyzed data before and at 6 months after surgery in both the SMILE group and the FS-LASIK group. Changes in posterior corneal elevation after FS-LASIK were greater than after SMILE, with no statistical significance (P≥0.07). In the SMILE group, residual bed thickness was found to be moderately negatively correlated with changes in the elevation in the central area (P≤0.045); whereas it was positively correlated in the peripheral area (P=0.002). CONCLUSIONS: SMILE and FS-LASIK presented stable posterior corneal surface in correction of myopia over -9.0 D at the follow-up visit of 6 months.

Seven-year observation of posterior corneal elevation after small-incision lenticule extraction in patients with moderate and high myopia.

PURPOSE: To investigate the long-term changes in posterior corneal elevation in moderate and high myopia after small-incision lenticule extraction (SMILE). SETTING: Eye & ENT Hospital, Fudan University, Shanghai, China. DESIGN: Prospective case series. METHODS: 33 eyes of 20 patients (30.1 ± 9.5 years, 7 men and 13 women, spherical equivalent [SE] range -4.00 to -8.75 D, mean SE -6.25 ± 1.29 D) who underwent SMILE were included. Changes in the posterior corneal elevation at central points (PCE), the thinnest point (PTE), the maximal point (PME), and an additional 20 points within the 4 mm area of the best-fit sphere were evaluated with a Pentacam (Oculus Optikgeräte GmbH) during a 7-year follow-up period. Mixed linear models were used to evaluate changes with P values less than 0.05. Correlations of elevation changes and residual bed thickness (RBT) were also evaluated. RESULTS: No ectasia was observed among the 33 eyes studied. The safety index was 1.08, and the efficacy index was 1.03. The mean change in PCE at 1 year, 3 years, 5 years, and 7 years was -1.42 ± 0.95 µm, -2.67 ± 0.98 µm, -2.44 ± 1.06 µm, and -1.91 ± 0.92 µm, respectively. Statistically significant differences were found at 3 years, 5 years, and 7 years (P = .007, .023, and .040, respectively). PTE reduced significantly at each time point compared with baseline. The mean change was -2.82 ± 1.19 µm, -3.55 ± 1.22 µm, -3.47 ± 1.32 µm, and -2.39 ± 1.15 µm, respectively (P = .019, .004, .010, and .039, respectively). PME changed in 2.45 ± 1.02 µm at 7 years compared with baseline (P = .017). The changes in PCE and PME negatively correlated with the RBT. CONCLUSIONS: Long-term posterior corneal elevation was stable in moderate and high myopia after SMILE.

Four-Year Outcomes of Small Incision Lenticule Extraction for Extreme High Myopia and Myopic Astigmatism.

Purpose: To evaluate the long-term safety, efficacy, predictability, and stability of small incision lenticule extraction (SMILE) for the treatment of high myopia and myopic astigmatism >-10.0 D. Methods: This was a prospective study that incorporated 35 consecutive patients (35 eyes) undergoing SMILE from September 2015 to March 2016. These patients had a mean preoperative spherical equivalent refraction of -10.06 ± 0.64 D. Patients were followed over a 4-year period and assessed for outcomes including uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refraction, and corneal topography. Results: At 4 years post-SMILE, respective efficacy and safety indices were 1.01 ± 0.19 and 1.07 ± 0.15. In total, 97% of operated eyes achieved an UDVA of 20/25 or better. ≥1 line was gained for 9 eyes (26%), with 25 eyes (71%) remaining stable. Twenty-four (69%) and 33 (94%) eyes, respectively, were within ±0.50 D and ±1.0 D of target refraction. From 3 months to 4 years postoperatively, a mean refractive regression of -0.22 D (-0.06 D per year) was detected, whereas no significant changes in mean corneal back curvature or posterior central elevation were detected (P = 0.617 and 0.754, respectively). We detected significant increases in higher-order aberrations (HOAs) of the anterior and total cornea (all P < 0.001), with spherical aberrations and vertical coma being particularly common, whereas posterior corneal HOA remained fairly stable (all P < 0.05). Conclusion: SMILE is a safe, effective, predictable, and stable means of correcting high myopia and myopic astigmatism over a 4-year postoperative period.

Impact of ablation ratio on 5-year postoperative posterior corneal stability after refractive surgery: SMILE and FS-LASIK.

BACKGROUND: To investigate the impact of the ablation ratio on 5-year postoperative posterior corneal stability in myopic eyes after small incision lenticule extraction (SMILE) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK) surgery. METHODS: A prospective, nonrandomized, cohort study: 80 eyes of 43 patients underwent SMILE surgery and 63 eyes of 32 patients underwent FS-LASIK surgery at the EYE & ENT Hospital, Fudan University. Ablation ratio was defined as lenticule thickness (SMILE cases) or ablation depth (FS-LASIK cases) divided by central corneal thickness (CCT). Posterior corneal elevation changes were recorded as posterior central elevation (PCE), posterior corneal surface at thinnest point (PTE) and posterior corneal mean elevation (PME). Patients were followed up at 6-month and 5-year interval to investigate the impact of the ablation ratio on posterior corneal elevation after SMILE and FS-LASIK surgery. RESULTS: PCE dropped at the 6-month follow-up for both SMILE (decreased by -1.11 ± 2.93 µm, P < 0.05) and FS-LASIK groups (decreased by -0.46 ± 3.72 µm, P < 0.05). PTE also dropped in SMILE (reduced by -2.04 ± 3.02 µm, P < 0.05) and FS-LASIK group (reduced by -1.28 ± 4.21 µm, P < 0.05) at the 6-month follow-up. Stable PCE (elevation change: SMILE -0.28 ± 4.03 µm; FS-LASIK 0.79 ± 4.13 µm, P > 0.05) and PTE (elevation change: SMILE -0.08 ± 4.28 µm; FS-LASIK 1.42 ± 3.85 µm, P > 0.05) for both groups were recorded at the 5-year follow-up compared to the 6-month visit. Ablation ratio was strongly correlated with 5-year postoperative PCE (ß = 2.68 ± 1.05, P < 0.01) and PTE (ß = 2.35 ± 1.17, P < 0.05). Cut-off value for 5-year postoperative raised PCE and PTE was 27.3 and 27.1%, respectively. CONCLUSIONS: Ablation ratio was strongly correlated with postoperative posterior corneal elevation in a 5-year follow-up in both SMILE and FS-LASIK groups. PCE and PTE underwent slight backward displacement 6-month postoperatively and remain stable at the 5-year follow-up. Threshold of the ablation ratio for resisting forward displacement of posterior corneal surface was 27.3 and 27.1% for SMILE and FS-LASIK groups, respectively.

Identification of Potential Metabolite Markers for Middle-Aged Patients with Post-Stroke Depression Using Urine Metabolomics.

BACKGROUND: Post-stroke depression (PSD) is one of the most common complications in stroke survivors. But, there are still no objective methods to diagnose PSD. This study aims to identify potential biomarkers for diagnosing PSD in middle-aged stroke survivors. METHODS: Middle-aged subjects aged 30 to 59 years (92 PSD patients and 89 stroke survivors without depression) were included in this study. Urinary metabolites were detected by gas chromatography-mass spectrometry (GC-MS). Differential urinary metabolites and potential biomarkers were screened by applying statistical analysis. RESULTS: The different urinary metabolic phenotypes between PSD patients and stroke survivors without depression were identified. A total of 12 differential urinary metabolites were accurately identified by using orthogonal partial least-squares-discriminant analysis. After analyzing those 12 differential urinary metabolites by step-wise logistic regression analysis, only seven metabolites (palmitic acid, hydroxylamine, myristic acid, glyceric acid, lactic acid, tyrosine and azelaic acid) were finally selected as potential biomarkers for diagnosing PSD in middle-aged stroke survivors. A panel consisting of these potential biomarkers could effectively diagnose middle-aged PSD patients. CONCLUSION: Urinary metabolic profiles were different between middle-aged PSD patients and stroke survivors without depression. Our results would be helpful in future for developing an objective method to diagnose PSD in middle-aged stroke survivors.

MiR-34a suppresses the proliferation and invasion of gastric cancer by modulating PDL1 in the immune microenvironment.

OBJECTIVES: As one of the most serious malignant carcinomas that threaten the life of sufferers constantly, gastric cancer has attracted a lot of interest among researchers. miR-34a, a member of hundreds of microRNAs (miRNAs), has been elucidated to exert a suppressive role in gastric cancer tumorgenesis based on previous extensive studies. Our study was performed with the aim to explore the functional effects of miR-34a and its predictive target programmed death ligand 1 (PDL1) in gastric cancer development. METHODS: We employed reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western Blot analysis to investigate the regulatory effect of miR-34a on PDL1 mRNA and the corresponding protein expression. The CCK-8 and colony formation assays were used to validate the influence of the combination of miR-34a and PDL1 on the proliferation of gastric tumor cells. Meanwhile, the migration and invasion of gastric tumor cells were measured using Transwell assay. RESULTS: PDL1 was targeted and negatively modulated by miR-34a. In addition, the re-expression of miR-34a suppressed the proliferation as well as the migration and invasion of gastric tumor cells, whereas PDL1 reduced the aforementioned inhibitory effect. CONCLUSIONS: PDL1 is the downstream gene of miR-34a, which can act as an anti-oncogene in gastric cancer. The miR-34a/PDL1 axis might provide a promising anticancer therapeutic approach for the clinical diagnosis, treatment, and prognosis of gastric cancer.

Naringin inhibits colorectal cancer cell growth by repressing the PI3K/AKT/mTOR signaling pathway.

In recent years, the incidence of colorectal cancer (CRC) has increased and research into new treatment methods for CRC has become a hot topic. Naringin has an inhibitory effect on the PI3k/AKT/mTOR signaling pathway in various tumor cell types and the effect of naringin is closely related to the occurrence and proliferation of tumor cells. The aim of this present study was to investigate whether naringin could inhibit the proliferation of CRC cells by inhibiting the PI3K/AKT/mTOR signaling pathway. This could provide a more mechanism-based treatment for CRC. MTT assays were used to detect the proliferation of CRC cells treated with various concentrations of naringin. The degree of apoptosis and the expression of apoptosis-related proteins (Bcl-2 and Bax) in CRC cells stimulated by naringin was detected using flow cytometry and western blot assays, respectively. The expression levels of PI3K/AKT/mTOR-related proteins [PI3K, AKT, mTOR, phosphorylated (p)-PI3K, p-AKT and p-mTOR] after naringin stimulation in CRC cells were detected using western blot assays. Naringin inhibited the proliferation of CRC cells in a dose-dependent manner. Naringin promoted the apoptosis of CRC cells and inhibited the activation of the PI3K/AKT/mTOR signaling pathway in a dose-dependent manner. The results demonstrated that naringin may be a promising therapeutic agent for the treatment of CRC, which may inhibit the proliferation of CRC cells and induce apoptosis by inhibiting the PI3K/AKT/mTOR signaling pathway.

Refractive outcomes comparing small-incision lenticule extraction and femtosecond laser-assisted laser in situ keratomileusis for high myopia.

PURPOSE: To compare the long-term refractive effects of small-incision lenticule extraction (SMILE) and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) on the correction of high myopia and astigmatism. SETTING: The Eye and ENT Hospital of Fudan University, Shanghai, China. DESIGN: Retrospective case series. METHODS: Patients had SMILE or FS-LASIK for high myopia. Subgroup analyses of high myopia (-6.00 to -8.75 diopters [D]) and extremely high myopia (≥-9.00 D) were performed. The main outcome measure was refractive predictability, compared between SMILE and FS-LASIK groups. Secondary outcomes included efficacy, safety, and residual astigmatism. RESULTS: This study included 121 patients (121 eyes: 75 in the SMILE group and 46 in the FS-LASIK group). No differences were found in terms of refractive predictability between SMILE and FS-LASIK in eyes with high myopia: 56% vs 58.7% achieved ± 0.50 D of attempted correction (P = .771) and 81.3% vs 76.1% achieved ± 1.00 D of attempted correction (P = .489). Efficacy indices of the SMILE and FS-LASIK groups were 1.02 ± 0.24 and 1.03 ± 0.24 (P = .742), respectively; safety indices were 1.23 ± 0.22 and 1.20 ± 0.24 (P = .324), respectively. Logarithm of the minimum angle of resolution uncorrected distance visual acuity and spherical equivalent in the high myopia subgroup were better than in the extremely high myopia subgroup after both SMILE and FS-LASIK (P < .01). CONCLUSIONS: SMILE and FS-LASIK were both effective in correcting high myopia and myopic astigmatism. However, both techniques may require further nomogram adjustments when treating eyes with extremely high myopia.

Two-year observation of posterior corneal elevations after small incision lenticule extraction (SMILE) for myopia higher than -10 dioptres.

AIM: To investigate the change in posterior corneal elevations (PCEs) of eyes with extremely high myopia 2 years after small incision lenticule extraction (SMILE). METHODS: We evaluated 39 eyes of 39 patients with spherical equivalent higher than -10.00 dioptres (D). Using a Scheimpflug camera (Pentacam), we measured change in PCEs at 1 day, 3 months, 6 months and 2 years after SMILE. Another 34 eyes of 34 patients who underwent femtosecond laser-assisted in situ keratomileusis (FS-LASIK) were examined before, at 1 day and long-term after surgery as the control group. For each eye, elevations at central, thinnest, maximal points and 24 other predetermined points were measured. RESULTS: No significant forward displacements of PCEs were observed in both surgeries. The maximal but not significant forward displacement occurred around 3-6 months following SMILE, and all returned to original levels 6 months postoperatively except superior area. The peripheral area tended to displace backward, while the central area tended forwardly. In both procedures, elevations along horizontal meridians, inferior and temporal hemispheres were significantly higher than those along vertical meridians, superior and nasal hemispheres, respectively (p<0.05). Elevation on the 4 mm, 6 mm diameters at 1 day and on the 6 mm diameter and temporal hemisphere at long-term follow-up postoperatively were significantly higher in FS-LASIK than SMILE (p<0.05). Change in elevations on the 6 mm diameter circle correlated with residual bed thickness (p=0.047). CONCLUSIONS: SMILE is a safe way to correct for myopia higher than -10 D, with PCEs remaining stable 2 years after surgery.

RNA-Binding Motif 4 (RBM4) Suppresses Tumor Growth and Metastasis in Human Gastric Cancer.

BACKGROUND Dysregulation of the splicing activator, RNA-binding motif 4 (RBM4), has recently been reported to be involved in the progression of several cancers. However, the mechanisms that underpin the activity of RBM4 in gastric cancer (GC) remain unknown. The purpose of our study was to explore how RBM4 affects the biological behavior of GC through in vivo and in vitro experiments. MATERIAL AND METHODS Western blot and flow cytometry analyses were used to investigate the RBM4 protein levels in normal gastric epithelial cells and 5 types of GC cells. Cell Counting Kit-8 assay, flow cytometry analysis, wound-healing, and migration and invasion assays were evaluated in vitro in BGC823 and MGC803 GC cells. A xenograft tumor model was used to assess whether RBM4 inhibits GC growth in vivo. Mitogen-activated protein kinase (MAPK) protein levels were determined using western blot analyses. RESULTS Our study revealed that RBM4 protein was downregulated in GC cells. Re-expression of RBM4 inhibited the proliferation, migration, and invasion of GC cells, while promoting apoptosis. Thus, the overexpression of RBM4 can inhibit tumor growth in GC mouse models. We also report that RBM4 was involved in the activation of MAPK-dependent signaling pathways in human GC. CONCLUSIONS It is hoped that these findings will improve our understanding of GC pathogenesis while also helping us to explore the feasibility of RBM4-targeted therapy for GC treatment.