Hydromassage of macular hole edges for large and persistent full-thickness macular holes.

AIM: To introduce the macular hole (MH) hydromassage technique as a potentially beneficial approach for the treatment of large or persistent MH. METHODS: This retrospective observational case series comprised 16 consecutive patients (17 eyes) diagnosed with MH. Inclusion criteria involved a hole aperture diameter larger than 600 µm or the presence of an unclosed MH larger than 600 µm following the previous vitrectomy. Standard MH repair procedures were administered in all cases, involving the manipulation and aspiration of the hole margin through the application of water flow with a soft-tip flute needle. A comprehensive assessment was conducted for each case before and after surgery, and optical coherence tomography (OCT) images were captured at every follow-up point. RESULTS: The mean preoperative aperture diameter was 747±156 µm (range 611-1180 µm), with a mean base diameter of 1390±435 µm (range 578-2220 µm). Following surgery, all cases achieved complete anatomical closure of MH, with 13 cases (76.5%) exhibiting type 1 closure and 4 cases (23.5%) demonstrating type 2 closure. No significant differences were observed in the preoperative OCT variables between the two closure types. Eyes with type 1 closure showed a significantly improved visual acuity (0.70±0.10, range 0.50-0.80) compared to those with type 2 closure (0.90±0.12, range 0.80-1.00, P=0.014). CONCLUSION: The MH hydromassage technique demonstrates promising results, achieving acceptable closure rates in cases of large or persistent MH. This technique may serve as an effective adjunctive maneuver during challenging MH surgery.

Phase 1 study of safety and preliminary efficacy of intranasal transplantation of human neural stem cells (ANGE-S003) in Parkinson's disease.

BACKGROUND: Intranasal transplantation of ANGE-S003 human neural stem cells showed therapeutic effects and were safe in preclinical models of Parkinson's disease (PD). We investigated the safety and tolerability of this treatment in patients with PD and whether these effects would be apparent in a clinical trial. METHODS: This was a 12-month, single-centre, open-label, dose-escalation phase 1 study of 18 patients with advanced PD assigned to four-time intranasal transplantation of 1 of 3 doses: 1.5 million, 5 million or 15 million of ANGE-S003 human neural stem cells to evaluate their safety and efficacy. RESULTS: 7 patients experienced a total of 14 adverse events in the 12 months of follow-up after treatment. There were no serious adverse events related to ANGE-S003. Safety testing disclosed no safety concerns. Brain MRI revealed no mass formation. In 16 patients who had 12-month Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) data, significant improvement of MDS-UPDRS total score was observed at all time points (p<0.001), starting with month 3 and sustained till month 12. The most substantial improvement was seen at month 6 with a mean reduction of 19.9 points (95% CI, 9.6 to 30.3; p<0.001). There was no association between improvement in clinical outcome measures and cell dose levels. CONCLUSIONS: Treatment with ANGE-S003 is feasible, generally safe and well tolerated, associated with functional improvement in clinical outcomes with peak efficacy achieved at month 6. Intranasal transplantation of neural stem cells represents a new avenue for the treatment of PD, and a larger, longer-term, randomised, controlled phase 2 trial is warranted for further investigation.

Causal relationship between gut microbiota and differentiated thyroid cancer: a two-sample Mendelian randomization study.

Background: The gut microbiota has been significantly associated with differentiated thyroid cancer (DTC). However, the causal relationship between the gut microbiota and DTC remains unexplored. Methods: Genome-wide association study (GWAS) summary databases were utilized to select exposures and outcomes. The Mendelian randomization (MR) method was employed to investigate the causal relationship between the gut microbiota and DTC. A sensitivity analysis was performed to assess the reliability of the findings. Results: Four bacterial traits were associated with the risk of DTC: Class Mollicutes [odds ratio (OR) = 10.953, 95% confidence interval (95% CI): 2.333-51.428, p = 0.002], Phylum Tenericutes (OR = 10.953, 95% CI: 2.333-51.428, p = 0.002), Genus Eggerthella (OR = 3.219, 95% CI: 1.033-10.024, p = 0.044), and Order Rhodospirillales (OR = 2.829, 95% CI: 1.096-7.299, p = 0.032). The large 95% CI range for the Class Mollicutes and the Phylum Tenericutes may be attributed to the small sample size. Additionally, four other bacterial traits were negatively associated with DTC: Genus Eubacterium fissicatena group (OR = 0.381, 95% CI: 0.148-0.979, p = 0.045), Genus Lachnospiraceae UCG008 (OR = 0.317, 95% CI: 0.125-0.801, p = 0.015), Genus Christensenellaceae R-7 group (OR = 0.134, 95% CI: 0.020-0.886, p = 0.037), and Genus Escherichia Shigella (OR = 0.170, 95% CI: 0.037-0.769, p = 0.021). Conclusion: These findings contribute to our understanding of the pathological mechanisms underlying DTC and provide novel insights for the clinical treatment of DTC.

Novel molecular typing reveals the risk of recurrence in patients with early-stage papillary thyroid cancer.

BACKGROUND: Papillary thyroid cancer (PTC) is an indolent disease with a favorable prognosis but characterized by a high recurrence rate. We aimed to improve precise stratification of recurrence risk in PTC patients with early stage using multi-gene signatures. PATIENTS AND METHODS: The present study was performed using data from The Cancer Genome Atlas (TCGA) and multi-center datasets. Unsupervised consensus clustering was used to obtain the optimal molecular subtypes and least absolute shrinkage and selection operator (LASSO) analysis was performed to identify potential genes for the construction of recurrence signature. Kaplan-Meier survival analysis and the log-rank test was used to detect survival differences. Harrells concordance index (C-index) was used to assess the performance of the DNA damage repair (DDR) recurrence signature. RESULTS: Through screening 8 candidate gene sets, the entire cohort was successfully stratified into two recurrence-related molecular subtypes based on DDR genes: DDR-high subtype and DDR-low subtype. The recurrence rate of DDR-high subtype was significantly lower than DDR-low subtype [HR = 0.288 (95%CI, 0.084-0.986), P = 0.047]. Further, a two-gene DDR recurrence signature was constructed, including PER1 and EME2. The high-risk group showed a significantly worse recurrence-free survival (RFS) than the low-risk group [HR = 10.647 (95%CI, 1.363-83.197), P = 0.024]. The multi-center data demonstrated that proportion of patients with low expression of PER1 and EME2 was higher in the recurrence group than those in the non-recurrence group. CONCLUSIONS: These findings could help accurately and reliably identify PTC patients with high risk of recurrence so that they could receive more radical and aggressive treatment strategies and more rigorous surveillance practices.

Cornuside inhibits glucose-induced proliferation and inflammatory response of mesangial cells.

Cornuside is a secoiridoid glucoside compound extracted from the fruits of Cornus officinalis. Cornuside has immunomodulatory and anti-inflammatory properties; however, its potential therapeutic effects on diabetic nephropathy (DN) have not been completely explored. In this study, we established an in vitro model of DN through treating mesangial cells (MMCs) with glucose. MMCs were then treated with different concentrations of cornuside (0, 5, 10, and 30 µM). Cell viability was determined using cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays. Levels of proinflammatory cytokines, including interleukin (IL)-6, tumor necrosis factor-α, and IL-1ß were examined using enzyme-linked immunosorbent assay. Reverse transcription quantitative real-time polymerase chain reaction and Western blotting were performed to detect the expression of AKT and nuclear factor-kappa B (NF-κB)-associated genes. We found that cornuside treatment significantly reduced glucose-induced increase in MMC viability and expression of pro-inflammatory cytokines. Moreover, cornuside inhibited glucose-induced phosphorylation of AKT and NF-κB inhibitor alpha, decreased the expression of proliferating cell nuclear antigen and cyclin D1, and increased the expression of p21. Our study indicates that the anti-inflammatory properties of cornuside in DN are due to AKT and NF-κB inactivation in MMCs.

Intraoperative slow-release dexamethasone intravitreal implant (Ozurdex) in epiretinal membrane peeling surgery: a prospective randomized controlled trial.

Purpose: This study aimed to determine the efficacy of the dexamethasone (DEX) intravitreal implant for the regression of macular edema and the improvement of best-corrected visual acuity (BCVA) after the removal of idiopathic epiretinal membrane (ERM). Methods: This prospective randomized controlled trial recruited 81 patients with idiopathic ERM. These patients all underwent 25-gauge pars plana vitrectomy combined with ERM and internal limiting membrane peeling surgery. Among them, 41 eyes in the DEX group received additional DEX implants and 40 in the non-DEX group did not. Outcomes including central retinal thickness (CRT), BCVA, and intraocular pressure were measured 1 and 3 months after surgery. Results: The DEX group had thinner CRTs compared to the non-DEX group at 1 month postoperatively (p <0.05), but did not differ significantly at the 1-week and 3-month follow-up visits (p = 0.109 and p = 0.417, respectively). There were no statistical differences with respect to BCVA (p = 0.499, 0.309, 0.246, and 0.517, respectively) and intraocular pressure (p = 0.556, 0.639, 0.741, and 0.517, respectively) between the two groups at each point of follow-up visits. Conclusion: DEX accelerated the reduction of CRT at 1 month after surgery. However, no evidence of further anatomical (CRT) or functional (BCVA) benefits using DEX was observed at 3 months. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT05416827.

Sulfur dioxide-releasing polymeric micelles based on modified hyaluronic acid for combined cancer therapy.

In this study, an amphiphilic polymer mPEG-HA(SA)-DNs was designed and synthesized to fabricate a multifunctional micellar system to enhance the therapeutic efficacy and reduce the toxic effect of paclitaxel (PTX). The polymer was prepared by introducing mPEG, stearic acid (SA) and 2,4-dinitrobenzenesulfonic acid (DNs) to the backbone of hyaluronic acid (HA). With above modifications, the fabricated micelles could encapsulate PTX in the core with high drug loading. The optimized PTX-loaded micelles had a mean size of 158.3 nm. Upon the effect of mPEG, the mPEG-HA(SA)-DNs micelles reduced the non-specific protein adsorption. In vitro drug release study revealed the excellent glutathione (GSH)-triggered PTX release behavior of the micelles. Moreover, GSH could trigger the detachment of DNs segment from mPEG-HA(SA)-DNs, and result in the release of SO2. In vitro and in vivo antitumor efficacy studies demonstrated that the PTX-loaded mPEG-HA(SA)-DNs micelles exhibited outstanding tumor suppression effect. The micelles would be potential carriers for combination cancer therapy by SO2 and PTX.

Functions and mechanisms of protein lysine butyrylation (Kbu): Therapeutic implications in human diseases.

Post-translational modifications (PTM) are covalent modifications of proteins or peptides caused by proteolytic cleavage or the attachment of moieties to one or more amino acids. PTMs play essential roles in biological function and regulation and have been linked with several diseases. Modifications of protein acylation (Kac), a type of PTM, are known to induce epigenetic regulatory processes that promote various diseases. Thus, an increasing number of studies focusing on acylation modifications are being undertaken. Butyrylation (Kbu) is a new acylation process found in animals and plants. Kbu has been recently linked to the onset and progression of several diseases, such as cancer, cardiovascular diseases, diabetes, and vascular dementia. Moreover, the mode of action of certain drugs used in the treatment of lymphoma and colon cancer is based on the regulation of butyrylation levels, suggesting that butyrylation may play a therapeutic role in these diseases. In addition, butyrylation is also commonly involved in rice gene expression and thus plays an important role in the growth, development, and metabolism of rice. The tools and analytical methods that could be utilized for the prediction and detection of lysine butyrylation have also been investigated. This study reviews the potential role of histone Kbu, as well as the mechanisms underlying this process. It also summarizes various enzymes and analytical methods associated with Kbu, with the goal of providing new insights into the role of Kbu in gene regulation and diseases.

Variants in the SOX9 transactivation middle domain induce axial skeleton dysplasia and scoliosis.

SOX9 is an essential transcriptional regulator of cartilage development and homeostasis. In humans, dysregulation of SOX9 is associated with a wide spectrum of skeletal disorders, including campomelic and acampomelic dysplasia, and scoliosis. The mechanism of how SOX9 variants contribute to the spectrum of axial skeletal disorders is not well understood. Here, we report four novel pathogenic variants of SOX9 identified in a large cohort of patients with congenital vertebral malformations. Three of these heterozygous variants are in the HMG and DIM domains, and for the first time, we report a pathogenic variant within the transactivation middle (TAM) domain of SOX9 . Probands with these variants exhibit variable skeletal dysplasia, ranging from isolated vertebral malformation to acampomelic dysplasia. We also generated a Sox9 hypomorphic mutant mouse model bearing a microdeletion within the TAM domain ( Sox9 Asp272del ). We demonstrated that disturbance of the TAM domain with missense mutation or microdeletion results in reduced protein stability but does not affect the transcriptional activity of SOX9. Homozygous Sox9 Asp272del mice exhibited axial skeletal dysplasia including kinked tails, ribcage anomalies, and scoliosis, recapitulating phenotypes observed in human, while heterozygous mutants display a milder phenotype. Analysis of primary chondrocytes and the intervertebral discs in Sox9 Asp272del mutant mice revealed dysregulation of a panel of genes with major contributions of the extracellular matrix, angiogenesis, and ossification-related processes. In summary, our work identified the first pathologic variant of SOX9 within the TAM domain and demonstrated that this variant is associated with reduced SOX9 protein stability. Our finding suggests that reduced SOX9 stability caused by variants in the TAM domain may be responsible for the milder forms of axial skeleton dysplasia in humans.

Chinese Guideline on the Management of Polypoidal Choroidal Vasculopathy (2022).

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

Synthesis and Antineoplastic Activity of a Dimer, Spiroindolinone Pyrrolidinecarboxamide.

The mutation or function loss of tumour suppressor p53 plays an important role in abnormal cell proliferation and cancer generation. Murine Double Minute 2 (MDM2) is one of the key negative regulators of p53. p53 reactivation by inhibiting MDM2-p53 interaction represents a promising therapeutic option in cancer treatment. Here, to develop more effective MDM2 inhibitors with lower off-target toxicities, we synthesized a dimer, spiroindolinone pyrrolidinecarboxamide XR-4, with potent MDM2-p53 inhibition activity. Western blotting and qRT-PCR were performed to detect the impact of XR-4 on MDM2 and p53 protein levels and p53 downstream target gene levels in different cancers. Cancer cell proliferation inhibition and clonogenic activity were also investigated via the CCK8 assay and colony formation assay. A subcutaneous 22Rv1-derived xenografts mice model was used to investigate the in vivo anti-tumour activity of XR-4. The results reveal that XR-4 can induce wild-type p53 accumulation in cancer cells, upregulate the levels of the p53 target genes p21 and PUMA levels, and then inhibit cancer cell proliferation and induce cell apoptosis. XR-4 can also act as a homo-PROTAC that induces MDM2 protein degradation. Meanwhile, the in vivo study results show that XR-4 possesses potent antitumour efficacy and a favourable safety property. In summary, XR-4 is an interesting spiroindolinone pyrrolidinecarboxamide-derivative dimer with effective p53 activation activity and a cancer inhibition ability.

Construction of Prognostic Nomogram in Patients with N3-Stage Nasopharyngeal Carcinoma.

INTRODUCTION: The aim of the study was to retrospectively identify the metastatic influence factors and predict the prognosis and develop an individualized prognostic prediction model for patients with N3-stage nasopharyngeal carcinoma (NPC). METHODS: The study collected 446 NPC patients with N3 stage from the Surveillance, Epidemiology, and End Results database between 2010 and 2015. The patients were classified into subgroups based on the histological types and metastatic status. Multivariable logistic, Cox regression, and Kaplan-Meier method with the log-rank test were performed. The nomogram model was created using the prognostic factors identified from Cox regression analysis. The predictive accuracy was determined based on the concordance index (c-index) and calibration curves. RESULTS: The 5-year overall survival (OS) of the NPC patients with N3 stage was 43.9%, and the prognosis of patients without any distant metastases was largely longer than that with metastases. No difference was observed between different pathological types in the entire cohort. However, patients with non-keratinized squamous cell carcinoma had a better OS than that of the patients with keratinized squamous cell carcinoma in a nonmetastatic subgroup. Using the Cox regression analysis results, the nomogram successfully classified these patients into low- and high-risk subgroups and presented the survival difference. The c-index of the nomogram for predicting the prognosis was satisfactory. CONCLUSION: This study identified metastatic risk factors and developed a convenient clinical tool for the prognosis of NPC patients. This tool can be used for individualized risk classification and decision-making regarding treatment of NPC patients with N3 stage.

Protective effect and mechanism of ginsenoside Rg2 on atherosclerosis.

Background: Ginsenoside Rg2 (Rg2) has a variety of pharmacological activities and provides benefits during inflammation, cancer, and other diseases. However, there are no reports about the relationship between Rg2 and atherosclerosis. Methods: We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to detect the cell viability of Rg2 in vascular smooth muscle cells (VSMCs) and human umbilical vein endothelial cells (HUVECs). The expression of inflammatory factors in HUVECs and the expression of phenotypic transformation-related marker in VSMCs were detected at mRNA levels. Western blot method was used to detect the expression of inflammation pathways and the expression of phenotypic transformation at the protein levels. The rat carotid balloon injury model was performed to explore the effect of Rg2 on inflammation and phenotypic transformation in vivo. Results: Rg2 decreased the expression of inflammatory factors induced by lipopolysaccharide in HUVECs-without affecting cell viability. These events depend on the blocking regulation of NF-κB and p-ERK signaling pathway. In VSMCs, Rg2 can inhibit the proliferation, migration, and phenotypic transformation of VSMCs induced by platelet derived growth factor-BB (PDGF-BB)-which may contribute to its anti-atherosclerotic role. In rats with carotid balloon injury, Rg2 can reduce intimal proliferation after injury, regulate the inflammatory pathway to reduce inflammatory response, and also suppress the phenotypic transformation of VSMCs. Conclusion: These results suggest that Rg2 can exert its anti-atherosclerotic effect at the cellular level and animal level, which provides a more sufficient basis for ginseng as a functional dietary regulator.

Tumor tissue microorganisms are closely associated with tumor immune subtypes.

Studies have found that different immune subtypes are present in the same tumor. Different tumor subtypes have different tumor microenvironments (TME). This means that the efficacy of immunotherapy in actual applications will, therefore, have different results. Existing tumor immune subtype studies have mostly focused on immune cells, stromal cells, genes and molecules without considering the presence of microbes. Some studies have shown that microflora can strongly promote many gastrointestinal cancers. The microbiome has, therefore, become an important biomarker and regulatory factor of cancer progression and therapeutic responses. In addition, the presence of microflora can strongly regulate the host immune system, indirectly affecting tumor growth. Taken together, it is important to study the relationships that develop among tumor tissue microorganisms, tumor immune subtype, and the TME. In this study, correlations between microbial abundance, immune cell infiltration, immune gene expression and tumor immune subtype were studied. To accomplish this, tissue microorganisms and immune cell ratios with significant differences between the different cancers were obtained by comparing 203 gastric cancer and intestinal cancer samples. Two immune subtypes of intestinal samples were obtained by K-means clustering algorithm and tissue microorganisms, immune cell ratios and immune-related genes with significant differences between different immune subtypes were screened through Wilcoxon rank sum test. The results showed that Clostridioides difficile, Aspergillus fumigatus, Yarrowia lipolytica, and Fusarium pseudograminearum were all closely associated with the identified tumor immune subtypes. Our open-source software is freely available from GitHub at https://github.com/gutmicrobes/IMM-subtype.git.

CBL/CAP Is Essential for Mitochondria Respiration Complex I Assembly and Bioenergetics Efficiency in Muscle Cells.

CBL is rapidly phosphorylated upon insulin receptor activation. Mice whole body CBL depletion improved insulin sensitivity and glucose clearance; however, the precise mechanisms remain unknown. We depleted either CBL or its associated protein SORBS1/CAP independently in myocytes and assessed mitochondrial function and metabolism compared to control cells. CBL- and CAP-depleted cells showed increased mitochondrial mass with greater proton leak. Mitochondrial respiratory complex I activity and assembly into respirasomes were reduced. Proteome profiling revealed alterations in proteins involved in glycolysis and fatty acid degradation. Our findings demonstrate CBL/CAP pathway couples insulin signaling to efficient mitochondrial respiratory function and metabolism in muscle.

The mesenchymal circulating tumor cells as biomarker for prognosis prediction and supervision in hepatocellular carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of death worldwide. Accurate prognosis prediction tools are urgently needed. While the use of circulating tumor cells (CTCs) as prognostic prediction tool has a clear potential. METHODS: We established a comprehensive, negative enrichment-based strategy for CTCs analysis in patients with HCC, involving identification of epithelial CTCs (E-CTCs) and mesenchymal CTCs (M-CTCs) through specific biomarker. This strategy was performed in 127 HCC cases, 21 nonmalignant liver disease (NMLD) patients and 42 health control to analyze the relevance between CTCs and tumor recurrence. RESULTS: The total CTC number and M-CTC percent were positively correlated with tumor malignancy and high recurrence risk. Individually, preoperative total CTC number and M-CTC percent could robustly distinguish relapse cases from those with no relapse, with sensitivity of 80.95% and 90.48%, specificity of 74.12% and 84.71%, respectively. Levels of preoperative total CTC number and M-CTC percent can both be regarded as independent risk factors for HCC with early recurrence (P = 0.0053, P < 0.0001), and are both significantly correlated with worse recurrence-free survival (RFS) (log rank P < 0.0001; HR 7.78, 95% CI = 3.59-16.87; log rank P < 0.0001; HR 24.4, 95% CI = 8.67-68.77). The levels of total CTC number and M-CTC number had higher effectiveness than alpha fetal protein (AFP) in HCC longitudinal supervision (77.78% vs 88.89% vs 22.22%). CONCLUSION: Preoperative and postoperative CTCs with higher effectiveness than AFP in prognosis prediction and recurrence supervision, indicating that CTCs could work as the biomarker for HCC clinical management.

Analysis of Systemic and Serum Risk Factors in Patients with Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy.

INTRODUCTION: It remains controversial whether polypoidal choroidal vasculopathy (PCV) represents a subtype of neovascular age-related macular degeneration (nAMD) or is a distinct disease entity. This study aimed to compare and analyze systemic and serum risk factors for nAMD and PCV in an aging Chinese population. METHODS: A retrospective study was performed on 108 patients with nAMD, 131 patients with PCV, and 219 control subjects. Serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), apolipoprotein A1 (APOA1), apolipoprotein B (APOB), complement 3 (C3), and complement 4 (C4) together with data on systemic risk factors, including hyperlipidemia, hypertension, diabetes mellitus (DM), coronary artery disease (CAD), and asthma, were collected. Chi-square tests, independent-samples t tests, and binary logistic regression analyses were performed to evaluate the associations of risk factors with nAMD and PCV. RESULTS: Patients with PCV and those with nAMD were likely to have hyperlipidemia (P < 0.001). CAD (P = 0.020) and hypertension (P = 0.006) correlated significantly with nAMD and PCV, respectively. Although no association of age and asthma with PCV or nAMD was found (P > 0.05), DM was associated with PCV development (OR = 0.535, P = 0.044). Regarding serum risk factors, HDL, LDL, TG, APOB, and C3 were significantly associated with nAMD (OR < 0.001, P < 0.001; OR = 0.028, P < 0.001; OR = 0.175, P < 0.001; OR = 0.922, P = 0.022; OR < 0.001, P < 0.001) and PCV (OR = 0.001, P = 0.001; OR = 0.097, P = 0.003; OR = 0.410, P = 0.037; OR = 0.895, P = 0.001; OR = 0.001, P < 0.001). Compared with nAMD, higher levels of HDL (P = 0.003) and LDL (P = 0.016) and lower levels of TG (P = 0.039) were found in patients with PCV, but the association of systemic risk factors between the two diseases was not significant (P > 0.05). CONCLUSION: Our findings indicate that hyperlipidemia is significantly associated with both nAMD and PCV. Serum lipid and complement levels have an effect on the pathogenesis of nAMD and PCV, and consideration of the differences between systemic and serum risk factors should be taken into account in clinical management.

The comparison of two different strategies of intravitreal conbercept for polypoidal choroidal vasculopathy in Chinese patients results from a 48-week randomized phase 4 study: STAR study.

PURPOSE: To compare a treat-and-extend (TAE) strategy with a fixed dosing regimen of intravitreal conbercept (IVC) for the management of treatment-naïve polypoidal choroidal vasculopathy (PCV) patients. METHODS: 249 patients with treatment-naïve PCV were randomized 1:1 to fixed dosing regimen with injections every 12 weeks (3 + Q12W) group or treat-and-extend regimen(3 + TAE) group. Patients received 3 monthly intravitreal injections of 0.5 mg conbercept as loading dose in both groups. The 3 + Q12W patients were monitored monthly and received mandated injections every 12 weeks; the 3 + TAE patients were monitored and treated monthly until the resolution of exudative disease activity; the interval between visits was then individualized according to study protocol. Visual and anatomical outcomes were compared between the two groups. RESULTS: At 48 weeks, there was no significant difference between the 3 + Q12W group and 3 + TAE group in mean BCVA improvement (p = 0.421), mean changes in central retinal thickness (CRT) (p = 0.818), maximum retinal thickness (MRT) (p = 0.448), pigment epithelial detachment (PED) height (p = 0.221), PED volume (p = 0.076), branching vascular network (BVN) area (p = 0.615), polypoidal lesion number (p = 0.701), polypoidal lesion area (p = 0.424), rates of patients who avoided vision loss of ≥15 ETDRS letters (p = 0.397) or complete polypoidal lesion regression rate (43.8% vs. 41.8%, p = 0.814). The 3 + Q12W group had more decreased retinal haemorrhage area (p = 0.014) and fewer mean numbers of injections comparing with 3 + TAE group (6.6 vs. 9.4, p < 0.001). Mean maximum extension interval between injections after loading injections was 9.6 ± 2.0 weeks for 3 + TAE group, with 27.8% of patients achieving an extension interval of 12 weeks and 61.1% patients 8 weeks or more. CONCLUSIONS: Both 3 + Q12W and 3 + TAE regimens of IVC could result in improvement in visual and anatomical outcomes in PCV patients.

Efficacy and Safety of Polycaprolactone in Treating Nasolabial Folds: A Prospective, Multicenter, and Randomized Controlled Trial.

Nasolabial folds (NLFs) are the most pronounced sign of facial aging. This study explored the efficacy and safety of polycaprolactone gel in treating Chinese patients with moderate-to-severe NLFs. Patients with moderate-to-severe NLF who wished to be treated by dermal fillers were recruited from three centers between July 2017 and September 2019. The randomizing ratio was 1:1 in the polycaprolactone group (polycaprolactone injection) or control group (sodium hyaluronate gel injection). The primary endpoint was the effectiveness rate of Wrinkle Severity Rating Score (WSRS) scores at 12 months after injection. The full-analysis set (FAS) and safety sets had 80 patients in the polycaprolactone group and control group, respectively. In the FAS, the effectiveness rate at 12 months in the polycaprolactone group was 88.8% compared with 23.8% in controls (P < 0.001). The improvement in WSRS sustained during 12 months in the polycaprolactone group, while gradually vanished in the control group since 3 months after surgery. The global aesthetic improvement scale (GAIS) by investigator assessments was improved, much improved, or very much improved in all patients during follow-up, while the proportion of patients with a "no change" assessment gradually increased during follow-up after 6 months in the control group. The rates of injection-related adverse event (AE) and serve injection-related AE were 8.8 versus 11.3% and 0 versus 1.3% in the polycaprolactone group and control groups, respectively. Polycaprolactone gel injection is effective and safe to treat moderate-to-severe NLFs in Chinese patients.

Corrigendum: Lobectomy may be more appropriate for patients with early-stage medullary thyroid cancer older than 60 years old.

[This corrects the article DOI: 10.3389/fendo.2022.1015319.].