Immediate versus delayed sequential bilateral ICL implantation: A retrospective comparison of vault height and visual outcomes.

PURPOSE: To compare the visual outcomes and risks of suboptimal vault-related complications between immediate sequential bilateral ICL surgery (ISBICLS) and delayed sequential bilateral ICL surgery (DSBICLS). DESIGN: A retrospective cohort study. METHODS: Patients who underwent bilateral ICL implantation between November 2014 and December 2021 at the Eye and ENT Hospital of Fudan University (Shanghai, China) were included and divided into two groups: (1) ISBICLS: both eye surgeries performed on the same day, and (2) DSBICLS: second eye surgery performed < 7 days following the first one. Propensity score matching (PSM) was performed to compare the visual outcomes. Multivariable logistic regression models were used to estimate the odds ratios (ORs) of the suboptimal vaults. RESULTS: Finally, 10,985 eyes were included. After PSM, 204 first surgery eyes and 162 s surgery eyes with complete postoperative data were matched. The safety and efficacy indices did not statistically differ between groups (all > 1.00), except that ISBICLS first surgery eyes achieved better efficacy index than DSBICLS group (1.03 ± 0.26 vs. 1.08 ± 0.23, P = 0.034). Excessive vault was observed in eight (4.06 %) ISBICLS first eyes, one (0.50 %) DSBICLS first eye, and none in the second surgery eye in either group. An insufficient vault was observed in one second eye and one DSBICLS second eye. We found no evidence of differences in the rate of excessive vault (OR = 0.831, 95 % CI: 0.426-1.622, P = 0.588) or insufficient vault (OR = 0.609, 95 % CI:0.062-5.850, P = 0.668). CONCLUSION: ISBICLS provided safety, efficacy, and refraction predictability comparable to DSBICLS without increasing the risk of suboptimal vault-related complications.

Capsaicin reduces blood glucose and prevents prostate growth by regulating androgen, RAGE/IGF-1/Akt, TGF-ß/Smad signalling pathway and reversing epithelial-mesenchymal transition in streptozotocin-induced diabetic mice.

Type 2 diabetes mellitus (T2DM) is a metabolic disease. Diabetes increases the risk of benign prostatic hyperplasia (BPH). Capsaicin is extracted from chili peppers and possesses many pharmacological properties, including anti-diabetic, pain-relieving, and anti-cancer properties. This study aimed to investigate the effects of capsaicin on glucose metabolism and prostate growth in T2DM mice and uncover the related mechanisms. Mice model of diabetes was established by administering a high-fat diet and streptozotocin. Oral administration of capsaicin for 2 weeks inhibited prostate growth in testosterone propionate (TP)-treated mice. Furthermore, oral administration of capsaicin (5 mg/kg) for 2 weeks decreased fasting blood glucose, prostate weight, and prostate index in diabetic and TP-DM mice. Histopathological alterations were measured using hematoxylin & eosin (H&E) staining. The protein expression of 5α-reductase type II, androgen receptor (AR), and prostate-specific antigen (PSA) were upregulated in diabetic and TP-DM mice, but capsaicin reversed these effects. Capsaicin decreased the protein expression of p-AKT, insulin-like growth factor-1 (IGF-1), IGF-1R, and the receptor for advanced glycation end products (RAGE) in diabetic and TP-DM mice. Capsaicin also regulated epithelial-mesenchymal transition (EMT) and modulated the expression of fibrosis-related proteins, including E-cadherin, N-cadherin, vimentin, fibronectin, α-SMA, TGFBR2, TGF-ß1, and p-Smad in TP-DM mice. In this study, capsaicin alleviated diabetic prostate growth by attenuating EMT. Mechanistically, capsaicin affected EMT by regulating RAGE/IGF-1/AKT, AR, and TGF-ß/Smad signalling pathways. These results provide with new therapeutic approach for treating T2DM or T2DM-induced prostate growth.

Effects of Decentration of Implantable Collamer Lens V4c on Visual Quality With the OPD-Scan III Aberrometer.

PURPOSE: This study aimed to analyze the relationship between visual quality and implantable collamer lenses (ICL) decentration. DESIGN: Prospective treatment evaluation clinical study METHODS: This prospective study included 119 eyes with ICL implantation. Refractive parameters and ocular aberrations were examined pre- and postoperatively. ICL decentration and higher-order aberrations (HOAs) were evaluated using the OPD-Scan III aberrometer. RESULTS: At the 1-month follow-up, the mean values for decentration were 0.38 ± 0.19 mm (0.02-0.78). Regarding the position of decentration in right and left eyes, 22.8% and 17.7% were located in the superior nasal section, 0% and 6.5% in the inferior nasal section, 50.9% and 53.2% in the superior temporal section, and 26.3% and 22.6% in the inferior temporal section, respectively. The root mean square values of whole-eye total HOAs, coma, and trefoil had significantly increased. Decentration had a significant negative correlation with variation in the pre- and postoperative trefoils of the whole eye. CONCLUSIONS: ICL decentration had a slightly negative correlation with trefoil and slightly affected visual quality.

Effect of vault on predicting postoperative refractive error for posterior chamber phakic intraocular lens based on a machine learning model.

PURPOSE: To investigate how vault and other biometric variations affect postoperative refractive error of implantable collamer lenses (ICLs) by integrating artificial intelligence and modified vergence formula. SETTING: Eye and ENT Hospital of Fudan University, Shanghai, China. DESIGN: Artificial intelligence and big data-based prediction model. METHODS: 2845 eyes that underwent uneventful spherical ICL or toric ICL implantation and with manifest refraction results 1 month postoperatively were included. 1 eye of each patient was randomly included. Random forest was used to calculate the postoperative sphere, cylinder, and spherical equivalent by inputting variable ocular parameters. The influence of predicted vault and modified Holladay formula on predicting postoperative refractive error was analyzed. Subgroup analysis of ideal vault (0.25 to 0.75 mm) and extreme vault (<0.25 mm or >0.75 mm) was performed. RESULTS: In the test set of both ICLs, all the random forest-based models significantly improved the accuracy of predicting postoperative sphere compared with the Online Calculation & Ordering System calculator ( P < .001). For ideal vault, the combination of modified Holladay formula in spherical ICL exhibited highest accuracy ( R = 0.606). For extreme vault, the combination of predicted vault in spherical ICL enhanced R values ( R = 0.864). The combination of predicted vault and modified Holladay formula was most optimal for toric ICL in all ranges of vault (ideal vault: R = 0.516, extreme vault: R = 0.334). CONCLUSIONS: The random forest-based calculator, considering vault and variable ocular parameters, illustrated superiority over the existing calculator on the study datasets. Choosing an appropriate lens size to control the vault within the ideal range was helpful to avoid refractive surprises.

Predicting Vault and Size of Posterior Chamber Phakic Intraocular Lens Using Sulcus to Sulcus-Optimized Artificial Intelligence Technology.

PURPOSE: To investigate the accuracy of posterior chamber phakic intraocular lens (PIOL) vault and size prediction models based on sulcus to sulcus (STS) optimized artificial intelligence and big data analysis technology. DESIGN: Big data and artificial intelligence prediction model. METHODS: We included 5873 eyes with posterior chamber PIOL implantation, and the postoperative vault was measured using an anterior segment analyzer (Pentacam AXL) 1 month postoperatively. A random forest regression model and classification model were used to predict the postoperative vault and PIOL size. The postoperative vault and PIOL size were set as output features; other vault-related eye parameters were set as input features. The influence of white to white (WTW), horizontal sulcus to sulcus (STS), and vertical STS on predicting postoperative vault and PIOL size was analyzed and compared. RESULTS: The mean preoperative WTW diameter was 11.64 ± 0.37 mm, the mean horizontal STS diameter was 11.85 ± 0.47 mm, and the mean vertical STS diameter was 12.39 ± 0.52 mm. In the regression model for numerical prediction of the vault, the combination of WTW, horizontal STS, and vertical STS was the most optimal for vault prediction (R2 = 0.3091, root mean square error [RMSE] = 0.1705); solely relying on WTW was the least optimal (R2 = 0.2849, RMSE = 0.1735). Among the models for classification prediction of the vault, the combination of WTW, horizontal STS, and vertical STS was the most accurate (accuracy, 0.6302; mean area under the curve, 0.8008; and mean precision recall rate, 0.6940). Moreover, the combination of WTW, horizontal STS, and vertical STS exhibited the highest accuracy for classification prediction of PIOL size (accuracy, 0.8170; mean area under the curve, 0.9540; and mean precision recall rate, 0.8864). Whether in the regression prediction models of vault values or in the classification prediction models of vault and PIOL size, the accuracy of STS optimized model was significantly improved compared with the traditional WTW model (P < .001). CONCLUSION: Artificial intelligence combined with STS optimization contributes to the accuracy of PIOL size and vault prediction models. The random forest machine-learning model optimized by STS is superior to the traditional WTW model.

Effect of long-term rotation on astigmatism following EVO-toric intraocular collamer lens implantation.

Objective: To evaluate the effect of long-term rotation on astigmatism following Evolution-toric intraocular collamer lens (EVO-TICL) implantation. Methods: Forty eyes of 22 patients were enrolled in this prospective study. Visual acuity, refractive parameters, and axial position of the EVO-TICL by OPD-Scan III aberrometer were measured preoperatively, 1 month and 3 years postoperatively. Results: Last visit, the safety index was 1.32 ± 0.15 and the efficacy index was 1.01 ± 0.23. The best-fitting curve of the attempted versus achieved correction was y = 0.9751x + 0.001. The mean spherical equivalent (SE) decreased from -8.94 ± 2.72D preoperatively to 0.06 ± 0.24D and - 0.36 ± 0.46D 1 month and 3 years postoperatively, respectively. The mean target and surgical induced astigmatism were 1.55 ± 0.61D and 1.67 ± 0.94D 3 years postoperatively. The average expected axis of the TICL was-1.15 ± 9.07 (-21-19°). One month and 3 years postoperatively, the average actual axis was -0.70 ± 9.86 (-20-20°) and - 0.35 ± 11.72 (-25-30°), respectively. The absolute rotation of the TICL was 3.70 ± 4.42 (0-22°) and 6.00 ± 6.70 (0-32°) 1 month and 3 years postoperatively, respectively (p < 0.001). The expected astigmatism was -0.10 ± 0.12D, and the mean actual astigmatism was -0.21 ± 0.30D and - 0.44 ± 0.45D 1 month and 3 years postoperatively, respectively. The mean absolute rotation without postoperative astigmatism was 3.73 ± 2.69 (0-9°) and 1.67 ± 1.66 (0-5°) for low (<2D) and high (≥2D) astigmatic TICL, respectively (p < 0.05). Conclusion: EVO-TICL implantation is safe and effective, with good predictability and stability. OPD-Scan is a fast device to detect the axial position of the TICL without mydriasis, and the axial position is relatively stable in the long term postoperatively. A slight rotation of low-astigmatic TICL may not cause postoperative astigmatism, whereas rotation of the high-astigmatic TICL may cause it.

Neferine attenuates development of testosterone-induced benign prostatic hyperplasia in mice by regulating androgen and TGF-ß/Smad signaling pathways.

Benign prostatic hyperplasia (BPH) is a common urinary disease among the elderly, characterized by abnormal prostatic cell proliferation. Neferine is a dibenzyl isoquinoline alkaloid extracted from Nelumbo nucifera and has antioxidant, anti-inflammatory and anti-prostate cancer effects. The beneficial therapeutic effects and mechanism of action of neferine in BPH remain unclear. A mouse model of BPH was generated by subcutaneous injection of 7.5 mg/kg testosterone propionate (TP) and 2 or 5 mg/kg neferine was given orally for 14 or 28 days. Pathological and morphological characteristics were evaluated. Prostate weight, prostate index (prostate/body weight ratio), expression of type Ⅱ 5α-reductase, androgen receptor (AR) and prostate specific antigen were all decreased in prostate tissue of BPH mice after administration of neferine. Neferine also downregulated the expression of pro-caspase-3, uncleaved PARP, TGF-ß1, TGF-ß receptor Ⅱ (TGFBR2), p-Smad2/3, N-cadherin and vimentin. Expression of E-cadherin, cleaved PARP and cleaved caspase-3 was increased by neferine treatment. 1-100 µM neferine with 1 µM testosterone or 10 nM TGF-ß1 were added to the culture medium of the normal human prostate stroma cell line, WPMY-1, for 24 h or 48 h. Neferine inhibited cell growth and production of reactive oxygen species (ROS) in testosterone-treated WPMY-1 cells and regulated the expression of androgen signaling pathway proteins and those related to epithelial-mesenchymal transition (EMT). Moreover, TGF-ß1, TGFBR2 and p-Smad2/3, N-cadherin and vimentin expression were increased but E-cadherin was decreased after 24 h TGF-ß1 treatment in WPMY-1 cells. Neferine reversed the effects of TGF-ß1 treatment in WPMY-1 cells. Neferine appeared to suppress prostate growth by regulating the EMT, AR and TGF-ß/Smad signaling pathways in the prostate and is suggested as a potential agent for BPH treatment.

Artificial intelligence-based refractive error prediction and EVO-implantable collamer lens power calculation for myopia correction.

BACKGROUND: Implantable collamer lens (ICL) has been widely accepted for its excellent visual outcomes for myopia correction. It is a new challenge in phakic IOL power calculation, especially for those with low and moderate myopia. This study aimed to establish a novel stacking machine learning (ML) model for predicting postoperative refraction errors and calculating EVO-ICL lens power. METHODS: We enrolled 2767 eyes of 1678 patients (age: 27.5 ± 6.33 years, 18-54 years) who underwent non-toric (NT)-ICL or toric-ICL (TICL) implantation during 2014 to 2021. The postoperative spherical equivalent (SE) and sphere were predicted using stacking ML models [support vector regression (SVR), LASSO, random forest, and XGBoost] and training based on ocular dimensional parameters from NT-ICL and TICL cases, respectively. The accuracy of the stacking ML models was compared with that of the modified vergence formula (MVF) based on the mean absolute error (MAE), median absolute error (MedAE), and percentages of eyes within ± 0.25, ± 0.50, and ± 0.75 diopters (D) and Bland-Altman analyses. In addition, the recommended spheric lens power was calculated with 0.25 D intervals and targeting emmetropia. RESULTS: After NT-ICL implantation, the random forest model demonstrated the lowest MAE (0.339 D) for predicting SE. Contrarily, the SVR model showed the lowest MAE (0.386 D) for predicting the sphere. After TICL implantation, the XGBoost model showed the lowest MAE for predicting both SE (0.325 D) and sphere (0.308 D). Compared with MVF, ML models had numerically lower values of standard deviation, MAE, and MedAE and comparable percentages of eyes within ± 0.25 D, ± 0.50 D, and ± 0.75 D prediction errors. The difference between MVF and ML models was larger in eyes with low-to-moderate myopia (preoperative SE > - 6.00 D). Our final optimal stacking ML models showed strong agreement between the predictive values of MVF by Bland-Altman plots. CONCLUSION: With various ocular dimensional parameters, ML models demonstrate comparable accuracy than existing MVF models and potential advantages in low-to-moderate myopia, and thus provide a novel nomogram for postoperative refractive error prediction and lens power calculation.

Matrine-induced nephrotoxicity via GSK-3ß/nrf2-mediated mitochondria-dependent apoptosis.

INTRODUCTION: Matrine (MT), an ingredient extracted from the Chinese herb Sophora flavescens, can result in nephrotoxicity because of long-term exposure. However, the underlying mechanism by which MT leads to kidney injury remains unclear. This study aimed to investigate the roles of oxidative stress and mitochondria in MT-induced kidney toxicity both in vitro and in vivo. METHODS: Mice were exposed to MT for 20 days, and NRK-52E cells were exposed to MT with or without LiCl (a GSK-3ß inhibitor), tert-Butylhydroquinone (t-BHQ, an Nrf2 activator), or small interfering RNA. RESULTS: The results showed that MT caused nephrotoxicity accompanied by an increase in reactive oxygen species (ROS) accumulation and mitochondrial dysfunction. Meanwhile, MT significantly upregulated glycogen synthase kinase-3ß (GSK-3ß) activity, released cytochrome c (Cyt C) and cleaved caspase-3, decreased the activity of nuclear factor-erythroid 2-related Factor 2 (Nrf2), and reduced the expression of heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1), which led to the inactivation of antioxidant enzymes and the activation of apoptosis. In addition, GSK-3ß inhibition by LiCl or small interfering RNA pretreatment or Nrf2 activation by t-BHQ pretreatment attenuated the toxic effects of MT in NRK-52E cells. CONCLUSIONS: Taken together, these results revealed that MT-induced apoptosis triggered kidney toxicity and that GSK-3ß or Nrf2 might serve as a promising nephroprotective target for MT-induced kidney injury.

Clinical Evaluation Of a 0.05 D-step Binocular Wavefront Optometer in Young Adults in China.

CLINICAL RELEVANCE: Myopia has become a public health priority as its prevalence increases worldwide, and in clinical practice, the precise evaluation of refraction errors is necessary. BACKGROUND: This study aimed to compare objective and subjective refraction measured by a binocular wavefront optometer (BWFOM) in adults with conventional objective and subjective refractions measured by an optometrist. METHODS: This cross-sectional study included 119 eyes of 119 participants (34 men and 85 women; mean age:27.5 ± 6.3 years). Refractive errors were measured using BWFOM and conventional methods, with and without cycloplegia. The mean outcome measures were spherical power, cylindrical power, and spherical equivalence (SE). The agreement test was assessed using a two-tailed paired t-test and Bland - Altman plots. RESULTS: Under noncycloplegic conditions, there were no significant differences in the objective SE between BWFOM and Nidek. Significant differences in subjective SE were observed between BWFOM and conventional subjective refraction (-5.79 ± 1.86 vs -5.65 ± 1.75 D, P < 0.01). Under cycloplegic conditions, the mean objective SE was significantly different between BWFOM and Nidek (-5.70 ± 1.76 vs -5.50 ± 1.83 D, P < 0.001); the mean subjective SE was significantly different between BWFOM and conventional subjective refractions (-5.52 ± 1.77 vs -5.62 ± 1.79 D, P < 0.001). The Bland - Altman plots revealed mean percentages of 95.38% and 95.17% for the points within the limits of agreement between BWFOM and conventional measurements and those between noncycloplegic and cycloplegic refractions, respectively. CONCLUSION: The BWFOM is a new device that measures both objective and subjective refraction. It is more convenient and faster to obtain a proper prescription at a 0.05-D interval. The subjective refraction results of the BWFOM and the conventional subjective refraction were in good agreement.

Long-Term Vault Changes in Different Levels and Factors Affecting Vault Change After Implantation of Implantable Collamer Lens with a Central Hole.

INTRODUCTION: This study evaluated vault changes in eyes implanted with an implantable Collamer lens (ICL) with a central hole (ICL V4c) for myopia and astigmatism correction as well as factors related to vault changes over time. METHODS: This retrospective study enrolled 169 myopic eyes from 169 patients (137 women and 32 men) who underwent ICL V4c implantation to correct myopia and astigmatism. Vault values were measured quantitatively using a rotating Scheimpflug camera. Each patient underwent at least four postoperative follow-up visits at 1 month, 6 months, 1 year, and more than 2 years. We compared postoperative values between groups and identified factors affecting vault changes over time. RESULTS: The mean vaults at 1 month (baseline), 6 months, 1 year, and the last follow-up time following ICL implantation were 540.83 ± 186.13, 520.00 ± 196.08, 503.79 ± 198.30, and 471.42 ± 211.35 µm, respectively. Eyes with baseline vaults of 250-750 and ≥ 750 µm exhibited a trend of vault decrease over time, and the differences were statistically significant (P < 0.05) at 6 months and 1 year postoperatively, respectively. The variables relevant to the value of vault decrease between baseline and last follow-up time were anterior chamber depth (ACD) and ICL power (adjusted R2 = 0.121, P < 0.001). CONCLUSIONS: We found a trend of decreased mean objective vault values over time, which was more obvious in eyes with higher baseline vault values. The vault value of the ICL decreased more in eyes with shallower ACDs, higher ICL power, or both. Moreover, the decrease in vault values became statistically significant earlier in eyes with higher baseline vaults or shallower ACDs.

Comparisons of objective and subjective refraction with and without cycloplegia using binocular wavefront optometer with autorefraction and retinoscopy in school-age children.

PURPOSE: To compare school-age children's objective and subjective refraction using a binocular wavefront optometer (BWFOM) with autorefraction and retinoscopy before and after cycloplegia. METHODS: Eighty-six eyes from 86 children (6-15 years old) were enrolled in this cross-sectional study. BWFOM objective and subjective refractions were compared with autorefraction and retinoscopy under cycloplegia. BWFOM refraction was evaluated before and after cycloplegia. Measurements were compared using a paired t-test; agreement was assessed using Bland-Altman plots. RESULTS: Under cycloplegia, the sphere, spherical equivalence, and J45 were significantly more negative on BWFOM objective refraction than autorefraction (- 1.39 ± 2.20 D vs. - 1.28 ± 2.23 D, P = 0.003; - 1.84 ± 2.38 D vs. - 1.72 ± 2.43 D, P = 0.001; - 0.02 ± 0.17 D vs. 0.03 ± 0.21 D, P = 0.004). The subjective sphere of BWFOM was less myopic, and the cylinder and the J45 were more negative than those with retinoscopy (- 1.17 ± 2.09 D vs. - 1.25 ± 2.20 D, P = 0.02; - 0.91 ± 0.92 D vs. - 0.76 ± 0.92 D, P < 0.001; - 0.01 ± 0.15 D vs. 0.03 ± 0.21 D, P = 0.028). For both BWFOM objective and subjective refraction, sphere and spherical equivalence with noncycloplegia were more myopic than those with cycloplegia (objective: - 1.76 ± 2.10 D vs. - 1.39 ± 2.20 D, - 2.21 ± 2.30 D vs. - 1.84 ± 2.38 D, P < 0.001; subjective: - 1.57 ± 1.92 D vs. - 1.17 ± 2.09 D, - 2.01 ± 2.13 D vs. - 1.62 ± 2.27 D, P < 0.001). Bland-Altman plots showed good agreement in spherical equivalence between BWFOM objective refraction and autorefraction (mean difference = 0.12 D, 95% confidence interval [CI] - 0.52 to 0.76), subjective refraction with retinoscopy (mean difference = - 0.01 D, 95% CI - 0.65 to 0.64), and BWFOM refractions with or without cycloplegia (objective: mean difference = - 0.37 D, 95% CI - 1.31 to 0.57; subjective: mean difference = - 0.39 D, 95% CI - 1.30 to 0.51). The time cost by BWFOM was significantly less than the total time of autorefraction and retinoscopy (264.88 ± 90.67 s vs. 315.89 ± 95.31 s, P < 0.001). CONCLUSION: BWFOM is a new device that realizes both objective and subjective refraction. For children's refractive errors, it is more convenient and quicker to obtain the proper prescription at a 0.05-D interval, and it is more accurate than autorefraction and retinoscopy under cycloplegia.

Immediate or Delayed Sequential Bilateral ICL Surgery: a Survey of Chinese Ophthalmologists.

INTRODUCTION: In China, the demand for implantable collamer lens (ICL) surgery is booming. Immediate sequential bilateral ICL surgery (ISBICLS) benefits patients and clinics, but it remains controversial and lacks standardization. We aim to investigate the prevalence of, factors for, and surgeon attitudes toward ISBICLS. METHODS: In this cross-sectional survey study, an electronic questionnaire about the practice and attitudes toward performing ISBICLS or delayed sequential bilateral ICL surgery (DSBICLS) was distributed to 792 qualified ICL surgeons in Mainland China, between 4 April and 22 April 2022. RESULTS: A total of 531 surgeons (66.79%) from 30 provinces in Mainland China responded. Among them, 374 (67.23%) were currently performing ISBICLS. Fifty-two percent (277) of surgeons reported performing ISBICLS more than 50% of the time, while 85.05% of surgeons chose to perform the second eye surgery 1 day after the first eye surgery. Seventy percent (248) of surgeons performing ISBICLS chose to perform the second eye surgery less than 30 min after the first eye surgery. Surgeons who started ICL surgery earlier (before 2010, OR = 2.772, 95% CI = 1.290-5.957, P = 0.009; 2011-2013, OR = 2.479, 95% CI = 1.060-5.800, P = 0.036), completed one-eye ICL surgery faster (< 3 min, OR = 3.936, 95% CI = 1.505-10.293, P = 0.005) and modified the second eye ICL selection less frequently (1-25%, OR = 0.203, 95% CI = 0.054-0.771, P = 0.019; 26-50%, OR = 0.173, 95% CI = 0.041-0.726, P = 0.017; 51-75%, OR = 0.299, 95% CI = 0.041-0.726, P = 0.123; 76-100%, OR = 0.163, 95% CI = 0.039-0.688, P = 0.014) tended to perform ISBICLS. No significant association was found among clinical settings, preoperative measurement devices, and hospital policies with performing ISBICLS. Regarding their attitudes toward ISBICLS, 54.63% preferred ISBICLS and 45.37% preferred DSBICLS. The main supporting reasons were patient convenience (98.64%), faster vision rehabilitation (73.56%), and improved perioperative compliance (73.22%). The concerns regarding ISBICLS included the risk of endophthalmitis (62.22%), lack of recommendation in expert consensus (61.67%), and decreased vault predictability (60.93%). The most common desires for further adoption were expert consensus on surgical criteria and patient indicators for ISBICLS (82.3%). CONCLUSIONS: ISBICLS has been gradually adopted in Mainland China, but has not been widely accepted as a routine procedure. Surgeons' experience and skills mainly influence whether ISBICLS is performed. Further research is needed to explore standardized protocols to prevent endophthalmitis, the appropriate time interval of two eye surgery, and requisitions for surgeon skills.

6-Gingerol suppresses cell viability, migration and invasion via inhibiting EMT, and inducing autophagy and ferroptosis in LPS-stimulated and LPS-unstimulated prostate cancer cells.

6-Gingerol is a bioactive compound isolated from Zingiber officinale. 6-Gingerol has been shown to have anticancer effects in numerous types of cancer cell. The mechanisms underlying the anticancer effect of 6-Gingerol in prostate cancer requires investigation. In the present study, the effect on cell viability of 6-Gingerol on LNCaP, PC3 and DU145 prostate cancer cells were determined using the MTT and colony formation assays. 6-Gingerol significantly inhibited cell migration, adhesion and invasion in LPS-stimulated and LPS-unstimulated prostate cancer cells. Furthermore, these changes were accompanied by alterations in the protein expression levels of epithelial-mesenchymal transition biomarkers, including E-cadherin, N-cadherin, Vimentin and zonula occludens-1. 6-Gingerol also induced autophagy by significantly increasing LC3B-II and Beclin-1 protein expression levels in prostate cancer cells. Combining 6-Gingerol with LY294002, an autophagy inhibitor, significantly increased cell survival in DU145 cells. Furthermore, 6-Gingerol significantly decreased the protein expression levels of glutathione (GSH) peroxidase 4 and nuclear factor erythroid 2-related factor 2 in prostate cancer cells. Reactive oxygen species (ROS) levels were significantly increased but GSH levels were decreased following 6-Gingerol treatment in prostate cancer cells. Co-treatment with the ferroptosis inhibitor, ferrostatin-1, significantly increased cell viability and significantly decreased ROS levels in 6-Gingerol-treated cells. These results suggested that 6-Gingerol may have inhibited prostate cell cancer viability via the regulation of autophagy and ferroptosis. In addition, 6-Gingerol inhibited cell migration, adhesion and invasion via the regulation of EMT-related protein expression levels in LPS-stimulated and LPS-unstimulated prostate cancer cells. In conclusion, 6-Gingerol may induce protective autophagy, autophagic cell death and ferroptosis-mediated cell death in prostate cancer cells. These findings may provide a strategy for the treatment and prevention of prostate cancer.

The antiandrogenic effect of neferine, liensinine, and isoliensinine by inhibiting 5-α-reductase and androgen receptor expression via PI3K/AKT signaling pathway in prostate cancer.

Neferine, liensinine, and isoliensinine are bisbenzylisoquinoline alkaloids extracted from seed-embryos of Nelumbo nucifera Gaertn. In this study, we evaluated the anticancer activities and mechanism of action of these natural products in prostate cancer cells by MTT, wound healing, ELISA and Western blotting. Neferine, liensinine, and isoliensinine showed growth inhibition and displayed a significant anti-migration activity in prostate cancer cells. They induced apoptosis and autophagy by activating cleaved caspase-9, cleaved PAPR, Bax, LC3B-II, but decreased Bcl-2 and PARP protein expression in LNCaP cells 24 h after treatments. The apoptotic and cytotoxic effects of neferine, liensinine, and isoliensinine were significantly attenuated in the presence of the caspase inhibitor, Z-VAD-FMK. However, the effects were enhanced in the presence of Akt inhibitor (MK2206) and PI3K inhibitor (LY294002). Moreover, neferine, liensinine, and isoliensinine also downregulated the protein expression of androgen receptor, prostate-specific antigen, and type II 5-α-reductase. These results demonstrated that these bisbenzylisoquinoline alkaloids have the potential as promising therapeutics agents. They induced apoptosis via inactivation with the PI3K/AKT signal pathway.

Docosahexaenoic acid inhibits lipopolysaccharide-induced metastatic activities by decreasing inflammation on prostate cancer cell.

Docosahexaenoic acid (DHA) is rich in fish oil with many pharmacological impacts such as anti-inflammation and anti-cancer activities. In the present study, we aimed to investigate the inhibitory effects of DHA on the invasion and inflammation in prostate cancer cells. The cytotoxicity of DHA with or without lipopolysaccharides (LPS) treatment was evaluated by MTT assay. The invasion and wound healing assays were used to determine the roles of DHA in cell migration and invasion after LPS treatment. The expression levels of IL-6 and IL-8 were detected using ELISA assay. The protein expression was investigated by Western blotting. DHA exhibited significant cytotoxicity at the concentration of 100 µM in PC3 cells. Exposure to DHA (6, 12 and 25 µM) dose-dependently inhibited invasion and wound closure potential in PC3 cells after LPS treatment. DHA dose-dependently downregulated LPS-induced expression levels of IL-6 and IL-8. In addition, the LPS-induced protein levels of p-AKT and COX-2 were suppressed by DHA treatment. Our results indicate that low doses of DHA effectively inhibit metastasis by decreasing IL-6, IL-8, p-AKT and COX-2 expression levels after LPS treatment.

Norcantharidin regulates ERα signaling and tamoxifen resistance via targeting miR-873/CDK3 in breast cancer cells.

MiR-873/CDK3 has been shown to play a critical role in ERα signaling and tamoxifen resistance. Thus, targeting this pathway may be a potential therapeutic approach for the treatment of ER positive breast cancer especially tamoxifen resistant subtype. Here we report that Norcantharidin (NCTD), currently used clinically as an ani-cancer drug in China, regulates miR-873/CDK3 axis in breast cancer cells. NCTD decreases the transcriptional activity of ERα but not ERß through the modulation of miR-873/CDK3 axis. We also found that NCTD inhibits cell proliferation and tumor growth and miR-873/CDK3 axis mediates cell proliferation suppression of NCTD. More important, we found that NCTD sensitizes resistant cells to tamoxifen. NCTD inhibits tamoxifen induced the transcriptional activity as well ERα downstream gene expressions in tamoxifen resistant breast cancer cells. In addition, we found that NCTD restores tamoxifen induced recruitments of ERα co-repressors N-CoR and SMRT. Knockdown of miR-873 and overexpression of CDK3 diminish the effect of NCTD on tamoxifen resistance. Our data shows that NCTD regulates ERα signaling and tamoxifen resistance by targeting miR-873/CDK3 axis in breast cancer cells. This study may provide an alternative therapy strategy for tamoxifen resistant breast cancer.

Obacunone attenuates high glucose-induced oxidative damage in NRK-52E cells by inhibiting the activity of GSK-3ß.

Hyperglycemia-induced proximal tubule injury plays a critical role in the pathogenesis of diabetic nephropathy (DN). Attenuating high glucose (HG)-induced oxidative damage in renal tubular epithelial cells has been documented to ameliorate DN. Obacunone (OB), a natural bioactive compound isolated from the Rutaceae family, has been demonstrated to possess various pharmacological effects with low toxicity. However, the role of OB in DN has not yet been investigated. To explore the influence of OB on oxidative damage that is induced by HG and its potential mechanisms of action, we set up a high glucose model and induced oxidative damage in NRK-52E cells. OB could protect the NRK-52E cells from the HG-induced decrease of cell viability and the accumulation of ROS. The protective effects of OB were associated with its ability to increase the levels of antioxidants (SOD, GSH and CAT), inhibit the production of ROS, and stabilize the mitochondrial membrane potential. In addition, OB significantly downregulated the activity of GSK-3ß, enhanced the nuclear translocation of Nrf2 and increased the mRNA expression of the Nrf2-driven genes NQO-1 and HO-1 in HG-treated cells. OB also decreased the release of cytochrome c from the mitochondria to the cytosol and inhibited the activation of caspase-3 in HG-treated cells. Pretreatment with a GSK-3ß activator blocked the protective effects of OB, while pretreatment with a GSK-3ß inhibitor yielded opposite results. These findings indicate that the renoprotective effects of OB against HG-induced oxidative damage in NRK-52E cells may be mediated by its ability to inhibit oxidative stress and mitochondrial dysfunction through the GSK-3ß signaling pathway.

A survey of the venom of the spider Lycosa vittata by biochemical, pharmacological and transcriptomic analyses.

Lycosa vittata, mainly distributed in the southwest of China, is a medium-sized and venomous spider, whose venom remains unexplored so far. This study aims to present an overview of the venom. It mainly consisted of diverse peptides and exhibited inhibitory effects on voltage-gated ion channels in rat dorsal root ganglia neurons, with a strongest inhibition on tetrodotoxin-sensitive and tetrodotoxin-resistant voltage-gated Na(+) channels. Interestingly, it exerted cytotoxicity to cancer cells, with approximately 10-fold selectivity on PC-3 over others, implying the existence of selective anti-PC-3 agents in the venom. Moreover, 51 toxin-like peptides were deduced from the venom gland transcriptome. Bioinformatic analyses suggested their structures might have some distinguished properties and their predicted functions were consistent with the venom activities. This study suggests that the venom is an attractive source of neurotoxins with therapeutic significance, and provides references for the structure and function investigation of specific toxins in the future.