Myopia Control Effect of Repeated Low-Level Red-Light Therapy Combined with Orthokeratology: A Multicenter Randomized Controlled Trial.

PURPOSE: To investigate the efficacy and safety of repeated low-level red-light(RLRL) therapy combined with orthokeratology(Ortho-k) among the children who, despite undergoing Ortho-k treatment, exhibited an axial elongation of at least 0.50mm over 1 year. DESIGN: Multicenter, randomized, parallel-group, single-blind clinical trial (ClinicaTrials.gov,NCT04722874). PARTICIPANTS: Eligible children were aged 8-13 years with a cycloplegic spherical equivalent refraction of -1.00 to -5.00 diopters in the initial Ortho-k fitting examination and had annual axial length (AL) elongation ≥ 0.50 mm despite undergoing Ortho-k for 1 year. A total of 48 children were enrolled from March 2021 to January 2022, and the final follow-up was completed in March 2023. METHODS: Children were randomly assigned to the RLRL combined with Ortho-k(RCO) or the Ortho-k group in a 2:1 ratio. The Ortho-k group wore Ortho-k at least 8 hours per night, while the RCO group received daily RLRL therapy twice a day for 3 minutes in addition to Ortho-k wearing. MAIN OUTCOME MEASURES: The primary outcome was AL change measured at 12 months relative to baseline. The primary analysis was conducted in children who received the assigned intervention and completed at least 1 post-randomization follow-up using the modified intention-to-treat principle. RESULTS: A total of 47(97.9%) children were included in the analysis (30 in the RCO group and 17 in the Ortho-k group). The mean axial elongation rate before the trial was 0.60mm/year in the RCO group and 0.61mm/year in the Ortho-k group. After 12 months following the intended intervention, the adjusted mean AL changes were -0.02mm(95% CI, -0.08 to +0.03 mm) in the RCO group and 0.27mm(0.19-0.34 mm) in the Ortho-k group. The adjusted mean difference in AL change was -0.29mm(-0.44 to -0.14mm) between the RCO and Ortho-k groups. The percentage of children achieving an uncorrected visual acuity greater than 20/25 was similar in the RCO (64.3%) and Ortho-k (65.5%) groups (Chi2 test, P=0.937). CONCLUSIONS: Combining RLRL therapy with Ortho-k may offer a promising approach to optimize axial elongation control among myopic children. This approach also potentially allows children to achieve satisfactory visual acuity, reducing the daytime dependence on corrective eyewear.

Effect of artificial natural light on the development of myopia among primary school-age children in China: a three-year longitudinal study.

AIM: To assess the efficacy of artificial natural light in preventing incident myopia in primary school-age children. METHODS: This is a prospective, randomized control, intervention study. A total of 1840 students from 39 classes in 4 primary schools in Foshan participated in this study. The whole randomization method was adopted to include classes as a group according to 1:1 randomized control. Classrooms in the control group were illuminated by usual light, and classrooms in the intervention group were illuminated by artificial natural light. All students received uncorrected visual acuity and best-corrected visual acuity measurement, non-cycloplegic autorefraction, ocular biometric examination, slit lamp and strabismus examination. Three-year follow-up, the students underwent same procedures. Myopia was defined as spherical equivalent refraction ≤ -0.50 D and uncorrected visual acuity <20/20. RESULTS: There were 894 students in the control group and 946 students in the intervention group with a mean±SD age of 7.50±0.53y. The three-year cumulative incidence rate of myopia was 26.4% (207 incident cases among 784 eligible participants at baseline) in the control group and 21.2% (164 incident cases among 774 eligible participants at baseline) in the intervention group [difference of 5.2% (95%CI, 3.7% to 10.1%); P=0.035]. There was also a significant difference in the three-year change in spherical equivalent refraction for the control group (-0.81 D) compared with the intervention group [-0.63 D; difference of 0.18 D (95%CI, 0.08 to 0.28 D); P<0.001]. Elongation of axial length was significantly different between in the control group (0.77 mm) and the intervention group [0.72 mm; difference of 0.05 mm (95%CI, 0.01 to 0.09 mm); P=0.003]. CONCLUSION: Artificial natural light in the classroom of primary schools can result in reducing incidence rate of myopia during a period of three years.

Reproductive outcomes in patients with high levels of sperm DNA fragmentation using testicular sperm for intracytoplasmic injection: a retrospective analysis.

This study aims to compare the embryological and clinical parameters of intracytoplasmic sperm injection (ICSI) cycles using testicular versus ejaculated sperm in male patients with elevated sperm DNA fragmentation (SDF). A total of 73 ICSI cycles were examined in couples where the male partner exhibited high levels of SDF. ICSI was performed using either ejaculated or testicular sperm. The primary outcomes were rates of blastocyst formation, high-quality embryo development, and clinical pregnancy. The DNA fragmentation index (DFI) for testicular sperm (16.81 ± 17.51) was significantly lower than that of ejaculated sperm (56.96 ± 17.56). While the blastocyst formation rate was significantly higher in the testicular sperm group compared to the ejaculated sperm group, no statistically significant differences were noted in fertilization rate (72.15% vs. 77.23%), rate of high-quality embryo formation (47.17% vs. 46.53%), clinical pregnancy (50% vs. 56.52%), Cumulative pregnancy (70.2% vs. 55.6%), or live birth rate (43.75% vs.43.48%). Testicular spermatozoa have no additional advantage over ejaculated spermatozoa except for blastocyst quality in patients with high SDF, the use of testicular spermatozoa for the first ICSI cycle in male infertility patients with high SDF should be undertaken after much consideration at present.

Distribution and determinants of choroidal vascularity index in healthy eyes from deep-learning choroidal analysis: a population-based SS-OCT study.

AIMS: To quantify the profiles of choroidal vascularity index (CVI) using fully artificial intelligence (AI)-based algorithm applied to swept-source optical coherence tomography (SS-OCT) images and evaluate the determinants of CVI in a population-based study. METHODS: This cross-sectional study included adults aged ≥35 years residing in the Yuexiu District of Guangzhou, China, a follow-up population-based study. All participants (n=646) underwent comprehensive ophthalmic examinations, including SS-OCT for quantifying choroidal parameters. The CVI and subfoveal choroidal thickness (SFCT) were measured by a novel AI-based system. RESULTS: A total of 556 participants were included, with a mean age of 56.4±9.9 years and 44.96% women. The average CVI and SFCT of the overall population were 69.7% (95% CI 69.2 to 70.3) and 263.0 µm (95% CI 257.2 to 268.8), respectively. After adjusting for other factors, older age and longer AL were significantly associated with a lower CVI. The CVI decreased by -0.13% (-0.19 to -0.06, p<0.001) with each 1-year increase in age, -2.10% (-3.29 to -0.92, p=0.001) with each 1 mm increase in AL. Furthermore, significantly positive correlation between CVI and SFCT has been observed, with coefficient of 0.059 (0.052 to 0.065, p<0.001). CONCLUSION: Using new AI-based choroidal segmentation software, we provided a fast, reliable and objective CVI profile for large-scale samples. Older age and longer AL were independent correlates of choroidal thinning and CVI decline. These factors should be considered when interpreting SS-OCT-based choroidal measurements.

The role of hepatitis B virus surface protein in inducing Sertoli cell ferroptosis.

BACKGROUNDS: Hepatitis B virus infection could result in male infertility with sperm defects and dysfunction. Sertoli cells are essential for testis function and play a crucial role in spermatogenesis. Sertoli cell death contributes to spermatogenesis impairment, leading to poor sperm quality. Ferroptosis has been implicated as a mechanism of Sertoli cell death. The issue in studying the relationship between hepatitis B virus and Sertoli cell ferroptosis has not yet been addressed. OBJECTIVES: To explore the mechanisms underlying ferroptosis in hepatitis B virus-exposed Sertoli cells. MATERIALS AND METHODS: Human Sertoli cells were treated in vitro with levels of 25, 50, and 100 µg/mL of hepatitis B virus surface protein (HBs). Cell viability and levels of glutathione, malondialdehyde, cellular ferrous ion (Fe2+ ), lipid peroxidation, and N6-methyladenosine in Sertoli cells were detected. The level of glutathione peroxidase 4, transferrin receptor 1, ferritin heavy chain, tripartite motif (TRIM) 37, methyltransferase like 3, and insulin-like growth factor 2 mRNA binding protein 2 was examined. Cell transfection was carried out to alter expression of ferroptosis-related proteins. qPCR and immunoblotting were performed to measure protein expression level. Immunoprecipitation was applied to determine the protein and protein-RNA interaction. Luminescence analysis was performed to identify the target of methyltransferase like 3. RESULTS: HBs exposure triggered ferroptosis featured with increased intracellular Fe2+ ion, reduced cell viability and expression of glutathione peroxidase 4 in Sertoli cells. HBs treatment significantly increased TRIM37 expression, which suppressed glutathione peroxidase 4 expression through ubiquitination. TRIM37 silencing attenuated the effect of HBs exposure-regulated cell viability and ferroptosis. HBs upregulated N6-methyladenosine modification in TRIM37 3'-UTR by increasing methyltransferase like 3 expression. The binding of N6-methyladenosine reader insulin-like growth factor 2 mRNA binding protein 2 and TRIM37 3'-UTR enhanced the stability of TRIM37 mRNA. CONCLUSION: HBs can decrease human Sertoli cell viability by promoting ferroptosis induced by the loss of glutathione peroxidase 4 activity through TRIM37-mediated ubiquitination of glutathione peroxidase 4. The findings highlight the role of TRIM37/glutathione peroxidase 4 signaling responsible for ferroptosis regulation in hepatitis B virus-infected Sertoli cells.

Deep Learner System Based on Focal Color Retinal Fundus Images to Assist in Diagnosis.

Retinal diseases are a serious and widespread ophthalmic disease that seriously affects patients' vision and quality of life. With the aging of the population and the change in lifestyle, the incidence rate of retinal diseases has increased year by year. However, traditional diagnostic methods often require experienced doctors to analyze and judge fundus images, which carries the risk of subjectivity and misdiagnosis. This paper will analyze an intelligent medical system based on focal retinal image-aided diagnosis and use a convolutional neural network (CNN) to recognize, classify, and detect hard exudates (HEs) in fundus images (FIs). The research results indicate that under the same other conditions, the accuracy, recall, and precision of the system in diagnosing five types of patients with pathological changes under color retinal FIs range from 86.4% to 98.6%. Under conventional retinopathy FIs, the accuracy, recall, and accuracy of the system in diagnosing five types of patients ranged from 70.1% to 85%. The results show that the application of focus color retinal FIs in the intelligent medical system has high accuracy and reliability for the early detection and diagnosis of diabetic retinopathy and has important clinical applications.

Segmentation Errors and Off-Center Artifacts in SS-OCT: Insight from a Population-Based Imaging Study.

PURPOSE: To evaluate the frequency and associated factors of artifacts in swept-source optical coherence tomography (SS-OCT) imaging. METHODS: This was a population-based cross-sectional study. Individuals aged 35 years or older, residing in the Yuexiu district of Guangzhou, China, were recruited by random cluster sampling. Nearly half of the participants were randomly selected for SS-OCT imaging centered on the optic nerve head. Six types of artifacts in the peripapillary choroidal layer and retinal nerve fiber layer (RNFL) were graded and identified. Univariate and multivariate logistic regression analyses were used to investigate the association between the presence of artifacts and clinical characteristics. RESULTS: Out of the 616 eligible individuals who underwent SS-OCT imaging, 18.3% and 13.6% of subjects exhibited at least one artifact in peripapillary RNFL (pRNFL) and peripapillary choroidal thickness (pCT) measurements, respectively, with posterior segmentation error and off-center artifact ranked as the most common artifacts. The presence of artifacts was significantly associated with age (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.06; p = .003), refractive error (OR, 0.80; 95% CI, 0.71-0.89; p < .001), and signal strength (OR, 0.95; 95% CI, 0.90-0.997; p = .039) in pRNFL thickness measurement. Similarly, the presence of artifacts in pCT measurement was significantly associated with age (OR, 1.05; 95% CI, 1.03-1.08; p < .001), and refractive error (OR, 0.76; 95% CI, 0.68-0.86; p < .001). CONCLUSION: Nearly one-fifth of the eyes were noted with at least one artifact in the population-scale SS-OCT study. Age was a risk factor for the presence of artifacts and should be considered in clinical settings.

Axial Shortening in Myopic Children after Repeated Low-Level Red-Light Therapy: Post Hoc Analysis of a Randomized Trial.

INTRODUCTION: Axial length (AL) elongation in myopia is considered irreversible. We aimed to systemically report unexpected AL shortening observed in a randomized clinical trial (RCT) after repeated low-level red-light (RLRL) therapy. METHODS: This is a post hoc analysis of a multicenter, single-masked RCT. Two hundred sixty-four myopic children aged 8-13 years allocated to RLRL treatment (intervention group) or a single vision spectacle (SVS, control group) were included. AL was measured using an IOL-master 500 at baseline, 1-, 3-, 6-, and 12-month follow-up visits. AL shortening was defined as AL reduction from baseline to follow-up visits at three cutoffs: > 0.05 mm, > 0.10 mm, and > 0.20 mm. Frequency of AL shortening at different cutoffs was calculated. Analysis was done with intent to treat (ITT). RESULTS: At 12-months follow up, frequency of AL shortening > 0.05 mm was 26/119 (21.85%) and 2/145 (1.38%) for the RLRL group versus the control group, respectively. The frequency was 18/119 (15.13%) versus 0/145 (0%) for AL shortening > 0.10 mm, and 7/119 (5.88%) versus 0/145 (0%), for AL shortening > 0.20 mm, respectively (p < 0.001). Mean AL shortening after 12 months (SD) was -0.156 (0.086) mm in the RLRL group and -0.06 mm in the control group. Age was significantly associated with AL shortening in the multivariable analysis. For the RLRL group that exhibited AL shortening (n = 56), choroidal thickness (ChT) thickening (0.056 mm) could only explain 28.3% of AL shortening (-0.20 mm). CONCLUSION: Nearly a quarter of children had > 0.05 mm AL shortening following 12 months of RLRL therapy, whereas AL shortening rarely occurred among controls. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04073238).

MicroRNA profiling reveals the role of miR-133b-3p in promoting apoptosis and inhibiting cell proliferation and testosterone synthesis in mouse TM3 cells.

Late-onset hypogonadism (LOH) is an age-related clinical and biological syndrome in which serum testosterone deficiency is an important characteristic and diagnostic indicator. In this study, we firstly analyzed the difference in the expression level of three miR-133 s (including miR-133a-3p, miR-133a-5p, and miR-133b-3p) in rat testis samples, blood samples from mice before and 1 wk after testis removal, and mouse TM3 cells. Secondly, the mimics and inhibitors corresponding to the three miR-133 s of mouse were transfected into TM3 cells separately to determine the correlation between the three miRNAs. Finally, using mouse TM3 cells to analyze the effect of miR-133b overexpression or inhibition on the proliferation and apoptosis of mouse testicular Leydig cells, the effect on genes related to testosterone synthesis, and the effect on the level of testosterone in the culture medium. We found that, compared with the testis tissue of newborn rats, miR-133a-5p was increased in adult rats, and miR-133a-3p and miR-133b-3p were decreased. In addition, 1 wk after the testis was removed, the expression levels of these three miRNAs in the blood of adult mice decreased. The correlation of the three miRNAs was summarized, and it was found that miR-133b-3p played an important role in it. In TM3 cells, overexpression of miR-133b-3p suppressed the proliferation and promotes apoptosis of cells, suppressed the expression level of most genes related to cell proliferation and testosterone synthesis, and the concentration of testosterone in the culture medium decreased while these phenomena can be reversed by the inhibition of miR-133b-3p expression. It was found that miR-133b-3p can regulate testosterone production in TM3 cells at least by targeting FSCN1. The above results suggest that miR-133b-3p plays an important role in regulating testosterone synthesis. These findings also provide new candidate diagnostic indicators for late-onset hypogonadism in men and provide new clues for the further study of pathogenesis.

The efficacy and safety of low-intensity extracorporeal shock wave treatment combined with or without medications in Chronic prostatitis/chronic pelvic pain syndrome: a systematic review and meta-analysis.

BACKGROUND: We performed this systematic review and meta-analysis to investigate the efficacy and safety of Li-ESWT combined with or without medications for patients with Chronic prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS). METHODS: A comprehensive search was conducted of PUBMED, Cochrane Library, and Web of Science databases from inception to February 2022 for randomized controlled trials (RCTs) assessing the efficacy and safety of Li-ESWT with or without the combination of medications compared with the control group. The National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), Visual Analogue Scale/Score (VAS), International Index of Erectile Function (IIEF), and International prostate symptom score (IPSS) were used to assess the improvements of symptoms in CP/CPPS patients. RESULTS: 651 patients from 12 randomized controlled studies were included in this study. The total NIH-CPSI scores, pain domain scores, and quality of life (QOL) scores were significantly lower in the Li-ESWT group than those in the control group at the termination of treatment, and 1, 4, 12, and 24 weeks after treatment. And these scores were significantly reduced in the Li-ESWT group than in baselines. In the subgroup analysis, reductions of these scores lasted longer and were greater in Li-ESWT combined with medications than in Li-ESWT alone. In the Li-ESWT group, the VAS score; IIEF score; and IPSS score were significant improvements than those in control group at the termination of treatment, and 1, 4, and 12 weeks after treatment; 4, 12, and 24 weeks after treatment; and 1, 4, and 12 weeks after treatment, respectively. CONCLUSIONS: Li-ESWT is a safe, non-invasive, and effective option for patients with CP/CPPS, whether combined with medications or not, should be recommended for widespread use in clinical practice.

25-Gauge pars plana vitrectomy combined with air tamponade for primary rhegmatogenous retinal detachment.

OBJECTIVE: This study was performed to evaluate the outcomes of 25-gauge (25-G) pars plana vitrectomy (PPV) with air tamponade for primary rhegmatogenous retinal detachment (RRD). METHODS: This retrospective consecutive case series included 126 eyes of 125 patients with primary RRD who underwent 25-G PPV with air tamponade. The patients were followed up for at least 6 months following surgery. The main outcome measures were the primary and final anatomical success rates and postoperative complications. RESULTS: The mean age of the 125 patients (80 men and 45 women) was 53.7 ± 10.0 years. The mean follow-up period was 8.3 ± 2.2 months (range, 6-18 months). Twenty-four eyes (19.0%) presented with high myopia, and 13 eyes (10.3%) were pseudophakic. Of the 126 eyes, 37 (29.4%) had inferior breaks, 2 (1.6%) had choroidal detachment, and 86 (68.3%) had macular detachment. The single- and final-operation success rates were 96.0% and 100%, respectively. Postoperative complications included macular hole formation in two eyes. During follow-up, secondary cataract surgery was performed in 27 (23.9%) of the 113 phakic eyes. CONCLUSION: 25-G PPV with air tamponade is effective and safe in treating selected patients with primary RRD with a high anatomical success rate.

Sustained and rebound effect of repeated low-level red-light therapy on myopia control: A 2-year post-trial follow-up study.

BACKGROUND: To evaluate the long-term efficacy and safety of continued repeated low-level red-light (RLRL) therapy on myopia control over 2 years, and the potential rebound effect after treatment cessation. METHODS: The Chinese myopic children who originally completed the one-year randomised controlled trial were enrolled. Children continued RLRL-therapy were defined as RLRL-RLRL group, while those who stopped and switched to single-vision spectacle (SVS) in the second year were RLRL-SVS group. Likewise, those who continued to merely wear SVS or received additional RLRL-therapy were SVS-SVS and SVS-RLRL groups, respectively. RLRL-therapy was provided by an at-home desktop light device emitting red-light of 650 nm and was administered for 3 min at a time, twice a day and 5 days per week. Changes in axial length (AL) and cycloplegic spherical equivalence refraction (SER) were measured. RESULTS: Among the 199 children who were eligible, 138 (69.3%) children attended the examination and 114 (57.3%) were analysed (SVS-SVS: n = 41; SVS-RLRL: n = 10; RLRL-SVS: n = 52; RLRL-RLRL: n = 11). The baseline characteristics were balanced among four groups. In the second year, the mean changes in AL were 0.28 ± 0.14 mm, 0.05 ± 0.24 mm, 0.42 ± 0.20 mm and 0.12 ± 0.16 mm in SVS-SVS, SVS-RLRL, RLRL-SVS and RLRL-RLRL group, respectively (p < 0.001). The respective mean SER changes were -0.54 ± 0.39D, -0.09 ± 0.55D, -0.91 ± 0.48D, and -0.20 ± 0.56D (p < 0.001). Over the 2-year period, axial elongation and SER progression were smallest in RLRL-RLRL group (AL: 0.16 ± 0.37 mm; SER: -0.31 ± 0.79D), followed by SVS-RLRL (AL: 0.44 ± 0.37 mm; SER: -0.96 ± 0.70D), RLRL-SVS (AL: 0.50 ± 0.28 mm; SER: -1.07 ± 0.69D) and SVS-SVS group (AL: 0.64 ± 0.29 mm; SER: -1.24 ± 0.63D). No self-reported adverse events, functional or structural damages were noted. CONCLUSIONS: Continued RLRL therapy sustained promising efficacy and safety in slowing myopia progression over 2 years. A modest rebound effect was noted after treatment cessation.

Air Tamponade for Rhegmatogenous Retinal Detachment With Inferior Breaks After 25-Gauge Pars Plana Vitrectomy: Technique and Outcome.

To evaluate the outcomes of 25-guage (G) pars plana vitrectomy (PPV) with air tamponade for rhegmatogenous retinal detachment (RRD) with inferior breaks. This retrospective consecutive case series included fifty-two eyes of fifty-two RRD patients with inferior breaks who underwent 25-G PPV with air tamponade. These patients were followed up for at least 6 months following surgery. Primary and final anatomical success rates and postoperative complications were the main outcome measures. The mean age of the patients (39 men and 13 women) was 51.8 ± 11.8 years. There were 49 primary RRDs (94.2%) and three recurrent RRDs (5.8%). The mean follow-up period was 8.2 ± 1.6 months (range: 6-13 months). Sixteen eyes (30.8%) presented with high myopia, and six eyes (11.5%) were pseudophakic. Proliferative vitreous retinopathy grade was C1 in four eyes (7.7%). Of the 52 eyes, two (3.8%) were complicated with choroidal detachment, and forty (76.9%) had the macula detached. The single- and final-operation success rates were 96.2% and 100%, respectively. During follow-up, secondary cataract surgery was performed in eight eyes (17.4%) of the 46 phakic eyes. 25-G PPV with air tamponade is effective in treating selected RRD patients with inferior breaks. Patients can benefit from early visual recovery and less complications.

LncRNA HOTAIR promotes proliferation and suppresses apoptosis of mouse spermatogonium GC-1 cells by sponging miR-761 to modulate NANOS2 expression.

LncRNA HOX antisense intergenic RNA (HOTAIR) can regulate cancer-related gene expression and promote stem cell and tumor cell proliferation via mechanisms including the competing endogenous RNA (ceRNA) mechanism. HOTAIR is abundantly expressed in the genital tubercle of E11.5, E12.5, and E13.5 embryos, whereas it became barely detectable at E13.5 and expressed again in adult mouse testis. However, the underlying function and mechanism of HOTAIR in spermatogenesis have not been elucidated. Interestingly, other researchers reported that the function of gene Nanos C2HC-Type Zinc Finger 2 (nanos2) includes the maintenance of both the primordial germ cells (PGCs) and germline stem cells, and Nanos2 protein and transcripts (NANOS2) were detected only in PGCs from day E11.5 and undifferentiated spermatogonia in spermatogenesis. We therefore investigated the relationship between HOTAIR and NANOS2 in maintaining spermatogonial stem cell population. We found that, compared to the adult mouse, the expression levels of HOTAIR and NANOS2 in embryo mouse were significantly higher and miR-761expression level was lower. In mouse GC-1 spermatogonia cells, overexpression of miRNA-761 significantly inhibited the expression of NANOS2 and HOTAIR, suppressed the proliferation, and promotes apoptosis of cells. Knock down and overexpression of HOTAIR indicated that HOTAIR expression was positively correlated with NANOS2 expression; overexpressed HOTAIR could promote proliferation and suppresses apoptosis of GC-1 cells. By a rescue experiment and dual luciferase reporter assay, miR-761 was identified as a direct target of HOTAIR, and NANOS2 was identified as the direct target of miR-761. The above results indicate that HOTAIR promotes proliferation and suppresses apoptosis of mouse spermatogonium GC-1 cells by sponging miR-761 to modulate NANOS2 expression. Our findings elucidate one of possible mechanisms and importance of HOTAIR in maintaining spermatogonial stem cell population, and provide new candidate genes and possible pathogenesis for male infertility.

Multi-stage screening cell-free seminal mRNAs to diagnose completion of meiosis and predict testicular sperm retrieval in men with non-obstructive azoospermia.

BACKGROUND: Differential diagnosis of men with subtypes of non-obstructive azoospermia (NOA) is important for their treatment. Many genes are transcripted during meiosis. We hypothesized that some of these genes can be detected in cell-free seminal message RNA (mRNAs) (cfs-mRNA) and be developed as non-invasive biomarkers for diagnosing NOA subtypes. OBJECTIVE: To screen cfs-mRNA to diagnose the completion of meiosis and predict successful sperm retrieval (SR) in men with NOA. MATERIALS AND METHODS: NOA patients who visited our institutes from September 2018 to December 2020 for testicular histopathological diagnosis (n = 109) or testicular SR (n = 92) were screened for participation in the study. Microarray and real-time quantitative polymerase chain reaction were used in five stages to obtain candidate cfs-mRNAs for comparisons between patients with early maturation arrest (eMA, meiosis not completed) and late MA or hypospermatogenesis (meiosis completed) and between NOA patients with successful SR and SR failure. RESULTS: Twelve cfs-mRNAs were selected based on this comparison between men with eMA and hypospermatogenesis and their gene expression and function information. Of these, AKAP1, BOLL, TCP11 and SETX predominantly derived from testes and germ cells were proposed as candidate cfs-mRNAs. Further quantification in men with NOA demonstrated significantly higher levels of BOLL cfs-mRNA (p < 0.0001) in men with late MA or hypospermatogenesis (n = 23), compared with men with eMA (n = 51); and significantly higher levels (p < 0.0001) in patients with successful SR (n = 44) when compared with patients with SR failure (n = 37). Interestingly, with a similar cutoff value, BOLL cfs-mRNA showed high sensitivity and specificity in diagnosing late MA and hypospermatogenesis (>404 copies/ml) and predicting successful SR (>415 copies/ml). Correlation of BOLL mRNA levels was observed in paired semen and testicular tissues. DISCUSSION AND CONCLUSIONS: We propose that BOLL cfs-mRNA is a promising non-invasive marker for diagnosing the completion of meiosis and predicting successful testicular SR in men with NOA.

Identification of novel susceptibility factors related to CP/CPPS-like symptoms: Evidence from a multicenter case-control study.

BACKGROUND: We aimed to systematically identify novel susceptible factors related to the occurrence and development of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)-like symptoms that were not limited to lifestyles or dietary habits in Chinese population. METHODS: We recruited participants from three centers (Shanghai [northeast], Hefei [east], and Lanzhou [northwest]) from August 2020 to June 2021. Demographics, lifestyles, dietary habits, past medical history, and national institutes of health-chronic prostatitis symptom index (NIH-CPSI) were collected from the individuals via optimized questionnaires. Logistic regression analysis and multivariate adjustment models were used to calculate the odds ratio (OR) and 95% confidence interval (95% CI) to assess the association between these variables and CP/CPPS-like symptoms. RESULTS: A total of 1851 participants were enrolled in this study (764 cases and 1087 controls). Age distributions differed between groups (median, range: 32, 18-74 vs. 29, 18-70, p < 0.001). After adjustment, physicochemical occupational hazards were identified significantly related to CP/CPPS-like symptom occurrence and development (ORoccurrence : 1.389, 95% CI: 1.031-1.870, p < 0.001; ORdevelopment : 2.222, 95% CI: 1.464-3.372, p < 0.001); besides, greater than or equal to four ejaculations per week significantly increased the likelihood of CP/CPPS-like symptoms compared with one ejaculation per week (ORoccurrence : 3.051, 95% CI: 1.598-5.827, p = 0.001). For these patients, who were easily felt gastrointestinal discomfort caused by spicy food intake, they had a higher incidence to affect with CP/CPPS-like symptoms (ORoccurrence : 2.258, 95% CI: 1.858-2.745, p < 0.001). In addition, history of drug allergy and genitourinary infections were identified as independent susceptible factors for the occurrence of CP/CPPS-like symptoms (ORoccurrence : 1.689, 95% CI: 1.007-2.834, p = 0.047; ORoccurrence : 3.442, 95% CI: 2.202-5.382, p < 0.001, respectively), while the history of rheumatic immune diseases was found tightly associated with the development of CP/CPPS-like symptoms (ORdevelopment : 2.002, 95% CI: 1.008-4.058, p = 0.048). CONCLUSION: Infection/inflammatory/immune-related disorders, novel dietary habits, and lifestyles associated with the susceptibility of CP/CPPS-like symptoms' occurrence and development are identified. Altering these irregular conditions serves as potential strategies for the treatment of patients with CP/CPPS-like symptoms.

[Human microbiome and chronic prostatitis / chronic pelvic pain syndrome: An update].

The significance of symbiotic microorganisms in the human body was recognized with the advancing of the concept of human microbiome and the development of related studies and technologies. These microorganisms play important roles in metabolism, immune regulation, the maintenance of health, and the development and progression of diseases in the human body. Recent studies show that chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS) is related with human microbiome, mainly involving the urogenital tract, intestinal canal, and oral cavity. This review summarizes the studies on the relationship between the human microbiome and CP/CPPS in recent years.

Efficacy and safety evaluation of low-intensity extracorporeal shock wave therapy on prostatitis-like symptoms: An open-label, single-arm trial.

The present work aims to evaluate the clinical efficacy and safety of low-intensity extracorporeal shock wave therapy (Li-ESWT) on patients with prostatitis-like symptoms (PLS). Patients with PLS were recruited and received four-week Li-ESWT (once per week), which was conducted at a frequency of 3 Hz with a preferred energy flow density of 0.25 mJ/mm2 . The scores of the National Institute of Health Chronic Prostatitis Symptoms Index (NIH-CPSI), International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF-5), and Visual Analogue Scale (VAS) were recorded to assess the remission of disease in the 0, 1st, 2nd, 3rd, 4th, 5th, 8th and 16th weeks. A decrease of the NIH-CPSI score ≥6 was regarded as the effectiveness standard of Li-ESWT. Among 91 enrolled patients, the scores of all validated questionnaires presented significant improvements in the 4th week (p < .05) compared with that in baseline, except for IIEF-5. The treatment effective rates in the 1st, 2nd, 3rd, 4th, 5th, 8th and 16th weeks were 28.57%, 38.46%, 47.25%, 51.65%, 57.30%, 68.18% and 69.44%, respectively. No pronounced undesirable side effect has occurred. Li-ESWT is effective and safe in treating PLS. The efficacy can be maintained within three months.

Effect of Repeated Low-Level Red-Light Therapy for Myopia Control in Children: A Multicenter Randomized Controlled Trial.

PURPOSE: To assess the efficacy and safety of repeated low-level red-light (RLRL) therapy in myopia control in children. DESIGN: Multicenter, randomized, parallel-group, single-blind clinical trial. PARTICIPANTS: Two hundred sixty-four eligible children 8 to 13 years of age with myopia of cycloplegic spherical equivalent refraction (SER) of -1.00 to -5.00 diopters (D), astigmatism of 2.50 D or less, anisometropia of 1.50 D or less, and best-corrected visual acuity (BCVA) of 0.0 logarithm of the minimum angle of resolution or more were enrolled in July and August 2019. Follow-up was completed in September 2020. METHODS: Children were assigned randomly to the intervention group (RLRL treatment plus single-vision spectacle [SVS]) and the control group (SVS). The RLRL treatment was provided by a desktop light therapy device that emits red light of 650-nm wavelength at an illuminance level of approximately 1600 lux and a power of 0.29 mW for a 4-mm pupil (class I classification) and was administered at home under supervision of parents for 3 minutes per session, twice daily with a minimum interval of 4 hours, 5 days per week. MAIN OUTCOME MEASURES: The primary outcome and a key secondary outcome were changes in axial length and SER measured at baseline and the 1-, 3-, 6-, and 12-month follow-up visits. Participants who had at least 1 postrandomization follow-up visit were analyzed for treatment efficacy based on a longitudinal mixed model. RESULTS: Among 264 randomized participants, 246 children (93.2%) were included in the analysis (117 in the RLRL group and 129 in the SVS group). Adjusted 12-month axial elongation and SER progression were 0.13 mm (95% confidence interval [CI], 0.09-0.17mm) and -0.20 D (95% CI, -0.29 to -0.11D) for RLRL treatment and 0.38 mm (95% CI, 0.34-0.42 mm) and -0.79 D (95% CI, -0.88 to -0.69 D) for SVS treatment. The differences in axial elongation and SER progression were 0.26 mm (95% CI, 0.20-0.31 mm) and -0.59D (95% CI, -0.72 to -0.46 D) between the RLRL and SVS groups. No severe adverse events (sudden vision loss ≥2 lines or scotoma), functional visual loss indicated by BCVA, or structural damage seen on OCT scans were observed. CONCLUSIONS: Repeated low-level red-light therapy is a promising alternative treatment for myopia control in children with good user acceptability and no documented functional or structural damage.

Epigenetic Modifications and Therapy in Uveitis.

Uveitis is a sight-threatening intraocular inflammation, and the exact pathogenesis of uveitis is not yet clear. Recent studies, including multiple genome-wide association studies (GWASs), have identified genetic variations associated with the onset and progression of different types of uveitis, such as Vogt-Koyanagi-Harada (VKH) disease and Behcet's disease (BD). However, epigenetic regulation has been shown to play key roles in the immunoregulation of uveitis, and epigenetic therapies are promising treatments for intraocular inflammation. In this review, we summarize recent advances in identifying epigenetic programs that cooperate with the physiology of intraocular immune responses and the pathology of intraocular inflammation. These attempts to understand the epigenetic mechanisms of uveitis may provide hope for the future development of epigenetic therapies for these devastating intraocular inflammatory conditions.