WGCNA reveals a biomarker for cancer-associated fibroblasts to predict prognosis in cervical cancer.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are crucial components of the cervical cancer tumor microenvironment, playing a significant role in cervical cancer progression, treatment resistance, and immune evasion, but whether the expression of CAF-related genes can predict clinical outcomes in cervical cancer is still unknown. In this study, we sought to analyze genes associated with CAFs through weighted gene co-expression network analysis (WGCNA) and to create a predictive model for CAFs in cervical cancer. METHODS: We acquired transcriptome sequencing data and clinical information on cervical cancer patients from the TCGA and GEO databases. Weighted gene co-expression network analysis was conducted to identify genes related to CAFs. We developed a prognostic model based on CAF genes in cervical cancer using LASSO Cox regression analysis. Single-cell sequencing data analysis and in vivo experiments for validation of hub genes in CAFs. RESULTS: A prognostic model for cervical cancer was developed based on CAF genes including COL4A1, LAMC1, RAMP3, POSTN, and SERPINF1. Cervical cancer patients were divided into low and high risk groups based on the optimal cutoff value. Patients in the high risk group had significantly worse prognosis. Single-cell RNA sequencing data revealed that hub genes in the CAFs risk model were expressed mainly in fibroblasts. The real-time fluorescence quantitative PCR results revealed a significant difference in the expression levels of COL4A1, LAMC1, POSTN, and SERPINF1 between the cancer group and the normal group (p < 0.05). Consistently, the results of the immunohistochemical tests exhibited notable variations in COL4A1, LAMC1, RAMP3, POSTN, and SERPINF1 expression between the cancer and normal groups (p < 0.001). CONCLUSION: The CAF risk model for cervical cancer constructed in this study can be used to predict prognosis, while the CAF hub genes can be utilized as crucial markers for cervical cancer prognosis.

The impact of eco-preneurship and green technology on greenhouse gas emissions - An analysis of East Asian economies.

The pressing need to address the effects of rising greenhouse gas emissions on the environment has become a global concern. Policymakers, governments, and stakeholders advocate a sustainable clean environment. Therefore, green technology and eco-entrepreneurship initiatives are being implemented to reduce these emissions. Despite their efforts in sustainable environments, there is insufficient research on how these initiatives impact economies. This study explores the impact of eco-entrepreneurship and green technology on reducing greenhouse gas emissions in East Asia. Using China and Japan, ranked the first and fifth highest greenhouse gas emitters globally, as case studies, the study employed ARDL and NARDL models for empirical analysis. The findings show that short-run linear estimates of eco-entrepreneurship are significant only in China, while nonlinear short-run estimates are significant for both China and Japan. Comparably, short-run linear estimates of green technology are significant for both China and Japan, while nonlinear coefficient estimates are significant only in Japan. The linear estimate of eco-entrepreneurship was significant and negative in both countries. The coefficient estimates for green technology are significant and negative for both countries. In the nonlinear model, the positive shock coefficient estimates for eco-entrepreneurship are negative and significant in China and Japan. These initiatives are vital for reducing greenhouse gas emissions and improving East Asian economies.

Efficacy and adverse events of immune checkpoint inhibitors in esophageal cancer patients: Challenges and perspectives for immunotherapy.

Esophageal cancer (EC) is the seventh most common cancer worldwide. Patients with EC have a generally poor prognosis mainly due to the lack of effective treatments. Cancer immunotherapy is a promising novel treatment option for EC. This literature review investigated the clinical efficacy of immunotherapy either alone or in combination with chemotherapy or targeted therapy. In addition, we analyzed the adverse events associated with immune checkpoint inhibitors (ICIs). In conclusion, ICIs increase the efficacy of EC treatments, thereby improving the outcomes of EC patients. The findings of this study may help enhance the response to immunotherapy, diminish toxicity, and thus eventually improve medical care for patients with EC.

Alleviation effect of GR24, a strigolactone analogue, on low-nitrogen stress in Malus baccata seedlings.

To investigate the efficacy of foliar application of GR24, a strigolactone analogue, in alleviating low-nitrogen stress in Malus baccata, we applied GR24 with different concentrations (0, 1, 5, 10, and 20 µmol·L-1) to leaves of plants under low nitrogen stress. We evaluated the changes in photosynthetic characteristics of leaves, reactive oxygen metabolism, and nitrogen assimilation in roots. The results showed that shoot biomass of seedling significantly decreased and root-shoot ratio increased under low-nitrogen stress. The chlorophyll contents decreased, the carotenoid content increased, and the photosynthetic activity decreased. The activities of superoxide dismutase and catalase enzymes in roots changed little, while the activities of peroxidase and ascorbic acid peroxidase enzymes, along with the levels of soluble sugar, free proline, and reactive oxygen species showed a significant increase, and the soluble protein content decreased. The NO3- content in roots decreased, the NH4+ content increased, while activities of nitrate reductase and glutamine synthase decreased. Compared to the control group without GR24 application, foliar sprays of 10 and 20 µmol·L-1 GR24 under both normal and low-nitrogen increased biomass and root-shoot ratio to varying degrees. Additionally, GR24 application increased chlorophyll content, photosynthesis indices (net photosynthetic rate, transpiration rate and stomatal conductance), and fluorescence (maximum photochemical efficiency of PSⅡ and quantum yield of electron transfer per unit area) performance parameters, as well as the contents of osmotic regulation substances (soluble protein, soluble sugar, and free proline) and glutamine synthase activity. Application of 10 and 20 µmol·L-1 GR24 under low-nitrogen stress decreased carotenoid, reactive oxygen species, and NH4+ contents, while increased the activities of antioxidases and key enzymes in nitrogen metabolism (nitrate reductase and glutamine synthase) and NO3- content. The 10 µmol·L-1 GR24 treatment was the most effective in alleviating low nitrogen stress, which has potential for application in apple orchards with low nitrogen soil.

Covalent netting restrains dissolution enabling stable high-loading and high-rate iron difluoride cathodes.

Metal fluoride conversion cathodes are promising for the production of cheap, sustainable, and high-energy lithium-ion batteries. Yet, such systems are plagued by active material dissolution that causes capacity fade and hinders commercialization. Here, a covalent netting strategy is proposed to overcome this hurdle. In a proof-of-concept design, polydopamine derived carbon-mediated covalent binding inhibited the dissolution, while the pyrolyzed bacterial cellulose netting structure furnished fast electronic and ionic transport pathways. We demonstrate high-capacity, high-rate and long-lasting stability attained at practical loading levels. Our investigations suggest that the covalent netting-enabled formation of a robust and efficient blocking layer, highly competent in suppressing the leaching, is key for a stable performance. The successful stabilization of metal difluorides in the absence of electrolyte engineering opens an avenue for their practical deployment in future higher-level but lower-cost batteries, and provides a solution to similar challenges encountered by other dissolving energy electrode materials.

Mini-invasive Therapy for Primary Chronic Canaliculitis without Damaging Lacrimal Punctum.

This study aimed to introduce a mini-invasive surgical approach without damaging lacrimal punctum for treating primary chronic canaliculitis (PCC). A retrospective analysis of 35 patients (35 eyes) suffering from PCC were recruited in the study. The surgery method is described briefly below: After making a conjunctival incision about 3-mm in length along the horizontal canaliculus at about 3-mm to the nasal of punctum, a curette of 2-mm diameter was used to evacuate the concretions through the incision of canaliculus. After evacuating all concretions, a silicon tube was inserted into the lacrimal duct through canaliculus to nasal cavity. With a follow-up of 12 months, all patients had resolution of symptoms of inflammation and no recurrent case was found. The anatomical success was achieved in 34 cases (97.1%). The functional success was achieved in 32 cases (91.4%). Key Words: Primary chronic canaliculitis, Mini-invasive, Silicone tube.

Effect of Flexible Half-Dose Gonadotropin-Releasing Hormone Antagonist Protocol on in vitro Fertilization Outcome in Predicted Normal Responder: A Study Protocol for a Multicentered, Randomized, Non-Inferiority, Parallel Controlled Trial.

Background: Gonadotropin-releasing hormone antagonists (GnRH-ant) are widely used in current in vitro fertilization-embryo transfer (IVF-ET), however, whether the lowest daily dose of GnRH-ant is individualized remains unknown. Due to the negative effect of GnRH-ant on endometrial receptivity, lessening the amount of GnRH-antagonists used during controlled ovarian stimulation may be helpful for embryo implantation. As such, a randomized controlled study is essential to validate the feasibility and efficacy of daily GnRH-ant dose reduction to 0.125 mg geared towards providing scientific evidence for guidance in clinical practice. Methods: In total, 620 infertile women undergoing in vitro fertilization will be enrolled in the multicentered, randomized, parallel controlled trial. Based on a computer-generated random list, they will be randomly and equally subdivided into half-dose GnRH-ant group or conventional-dose GnRH-ant group. The primary outcome is ongoing pregnancy ie, intrauterine pregnancy diagnosed by pelvic ultrasonography at more than 12 weeks of gestation accompanied by normal fetal heartbeats. Secondary outcomes include cycle cancellation, premature luteinizing hormone surge, positive pregnancy, embryo implantation rate, clinical pregnancy, early spontaneous abortion, and live birth. The intention-to-treat and per protocol analyses will be used to initially analyze the difference in ongoing pregnancy rate between the two groups, while the multiple imputation method was used to handle missing values in the data. Discussion: At present, no randomized controlled trials (RCTs) have been performed on the use of the half-dose GnRH-ant protocol (0.125mg/d) to improve reproductive outcomes of IVF-ET in predicted normal responder, compared to conventional-dose GnRH-ant protocol (0.25mg/d). Half-dose GnRH-ant protocol might provide a suitable clinical solution for predicted normal responder undergoing IVF treatment. Thus, it is critical to conduct a well-designed RCT to evaluate the impact of a half-dose GnRH-ant protocol on the reproductive outcomes of IVF-ET in predicted normal responder. Trial Registration: This study was registered in the Chinese Clinical Trials Registry Platform on August 29, 2020. (chictr.org.cn; identifier: ChiCTR2000037629). This trial is version 1.3.

Mechanism of Guilu Erxian ointment based on targeted metabolomics in intervening in vitro fertilization and embryo transfer outcome in older patients with poor ovarian response of kidney-qi deficiency type.

Objective: To study the effect of Guilu Erxian ointment on the outcome of IVF-ET in older patients with poor ovarian response infertility of kidney-qi deficiency type, and to verify and analyze the mechanism of action of traditional Chinese medicine on improving older patients with poor ovarian response infertility of kidney-qi deficiency type from the perspective of metabolomics using targeted metabolomics technology, identify the related metabolic pathways, and provide metabolic biomarker basis and clinical treatment ideas for improving older patients with poor ovarian response infertility. Methods: This study was a double-blind, randomized, placebo-controlled trial, and a total of 119 infertile patients who underwent IVF-ET at Shandong Center for Reproduction and Genetics of Integrated Traditional Chinese and Western Medicine were selected. Eighty older patients with infertility undergoing IVF were randomly divided into older treatment group and older placebo group, and another 39 young healthy women who underwent IVF-ET or ICSI due to male factors were selected as the normal control group. Flexible GnRH antagonist protocol was used for ovulation induction in all three groups, and Guilu Erxian ointment and placebo groups started taking Guilu Erxian ointment and placebo from the third day of menstruation until IVF surgery. And ultra-high performance liquid chromatography-triple quadrupole mass spectrometer (UHPLC-QTRAP MS) was used to detect metabolites in the three groups of samples. Results: Compared with the placebo group, the number of oocytes retrieved, 2PN fertilization, high-quality embryos, total number of available embryos and estrogen on HCG day were increased in the treatment group, and the differences were statistically significant (P > 0.05), but the clinical pregnancy rate of fresh embryos and frozen embryos were not statistically significant (P > 0.05). The results of targeted metabolomics analysis showed that follicular fluid in the treatment group clustered with the normal young group and deviated from the placebo group. A total of 55 significant differential metabolites were found in the follicular fluid of older patients with poor ovarian response of kidney-qi deficiency type and patients in the normal young group, after Guilu Erxian ointment intervention, Metabolites such as L-Aspartic acid, Glycine, L-Serine, Palmitoleic Acid, Palmitelaidic acid, L-Alanine, Gamma-Linolenic acid, Alpha-Linolenic Acid, and N-acetyltryptophan were down-regulated, mainly involving amino acid metabolism and fatty acid metabolism. Conclusion: Guilu Erxian ointment can effectively improve the clinical symptoms and IVF outcomes of older patients with poor ovarian response of kidney-qi deficiency type. There were differences in follicular fluid metabolites between older patients with poor ovarian response of kidney-qi deficiency type and normal women. L-Aspartic acid, L-Alanine, Aminoadipic acid, L-Asparagine, L-Arginine, L-Serine, Gamma- Linolenic acid, Pentadecanoic acid and Alpha-Linolenic Acid are closely related to older patients with poor ovarian response due to deficiency of kidney-qi and may be inferred as biomarkers. The mechanism of Guilu Erxian ointment intervention may be mainly through amino acid metabolism and fatty acid metabolism regulation.

A prospective study comparing mini-invasive and conventional canaliculotomy of punctum-sparing canaliculotomy for primary canaliculitis treatment.

PURPOSE: To compare outcomes of mini-invasive canaliculotomy with those of conventional canaliculotomy conducted using the punctum-sparing approach for the treatment of primary canaliculitis. METHODS: A prospective, comparative, and interventional case series study was conducted on 118 individuals with unilateral inferior primary canaliculitis. These patients were randomly divided into two groups, each with 59 cases. Group A underwent mini-invasive canaliculotomy (minor incision ~3 mm), whereas group B received conventional canaliculotomy (long incision ~6-8 mm). Punctum-sparing and canaliculus-reconstructing procedure was used to treat all patients. Both groups had silicone tube intubations and were retained in the lacrimal passages for one month. Both groups' surgical success rates and postoperative complications were measured at the last follow-up of 12 months after surgery. RESULTS: A total of 108 patients were finally included in the study, 53 in group A and 55 in group B. There were 79 females and 29 males with a median age of 57 ± 13.4 years. The anatomical success rates for groups A and B were 96.2% and 92.7% (P = 0.679), respectively. Functional success rate was accomplished by considerably more patients in group A (50/53, 94.3%) compared to group B (45/55, 81.8%) (P = 0.046). No recurrences were seen during follow-up visits in any of the participants. CONCLUSIONS: The two procedures employed in this study to treat primary canaliculitis achieves excellent clinical effects with no incidence of recurrence. The mini-invasive canaliculotomy is worthy to be recommended for its higher functional success rate with mini-invasion of canaliculus and intact lacrimal punctum.

Soluble dietary fiber from tea residues with inhibitory effects against acrylamide and 5-hydroxymethylfurfural formation in biscuits: The role of bound polyphenols.

This study investigated the impact of soluble dietary fiber (SDF) from untreated (U-SDF), fermented (F-SDF) and high temperature cooked (H-SDF) from tea residues on formation of acrylamide (AA) and 5-hydroxymethylfurfural (5-HMF) in biscuits. Both 3% F-SDF and 2% H-SDF can simultaneously inhibit AA and 5-HMF and SDFs increased the types of volatile compounds in biscuits. After the determination of the bound polyphenol compositions in SDFs by LC-QTOF-MS/MS, six polyphenols with different structural characteristics were selected to explore their contributions on the inhibitory effect of SDFs and structure-inhibitory capacity relationships in the "glucose-asparagine-linoleic acid" model system. It showed that the inhibitory activities of those polyphenols were greatly affected by the number of hydroxyl groups and methoxy groups on the benzene ring. Almost all polyphenols were also found to scavenge hydroxyl radicals generated in reactions. Thus, this study suggests that the bound polyphenols of SDFs play a key role in the inhibition of AA and 5-HMF.

Application Value of the Diagnosis during Early Carcinoma of Upper Digestive Tract Based on Optical Enhanced Endoscopic Technique.

Objective: The diagnostic value of optical enhanced endoscopy in early cancer of upper digestive tract was studied by comparing the disease accuracy, tumor type, invasion, and various surgical indicators between the two groups. Methods: 188 patients with early upper gastrointestinal cancer treated in our hospital from January 2020 to February 2021 were selected as the research objects. The patients were randomly divided into the observation group and control group with 94 cases in each group. Results: The accuracy of early detection of early carcinoma of upper digestive tract in the observation group was 94.68% and that in the control group was 76.60%. The accuracy of the observation group was significantly higher than that in the control group, with statistical significance (P < 0.05). In the observation group, 36 cases of early gastric cancer, 28 cases of early esophageal cancer, and 30 cases of early colorectal cancer were detected; 25 cases of early gastric cancer, 19 cases of early esophageal cancer, and 28 cases of early colorectal cancer were detected; 26 cases of early carcinoma of upper digestive tract infiltration were detected; and 68 cases were not detected, and the detection rate was 27.66%, which was higher than 9.57% in the control group, and the difference was statistically significant (P < 0.05). After different methods of treatment, no death occurred in all patients. Except for the operation time, the surgical indexes of the observation group were better than the control group, the difference was statistically significant (P < 0.05). Conclusion: Optical enhanced endoscopic technique had obvious effect in the diagnosis of patients with early cancer of upper digestive tract, it was helpful to improve the clinical detection rate of early carcinoma of upper digestive tract and had certain diagnostic ability for the invasion depth of early cancer of high upper gastrointestinal tract, which was conducive to the detection of clinical invasion lesions and had high clinical promotion and application value.

"An integrated clip-shaped costal cartilage carving approach for rhinoplasty".

BACKGROUND: Nasal tip management is considered to be one of the most complicated and challenging parts of rhinoplasty in East Asian patients. Within current rhinoplasty surgical practice, costal cartilage serves as an ideal source for grafting due to its ability to provide strong support to the nasal tip. METHODS: From March 2013 to December 2021, integrated clip-shaped costal cartilage grafts were applied to patients with primary (n = 12) or secondary (n = 3) short nose deformities. The costal cartilage was carved into an monobloc clip-shaped cartilage graft and then placed on the nasal septum and fixed with sutures. The nasal length index, projection index, and nasolabial angles were measured preoperatively and postoperatively. Postoperative evaluation at 8 months was performed using a grading scale. RESULTS: A total of 15 patients were included in this study with an average age of 23.7 ± 3.6 years. The mean follow-up period was 14.3 ± 5.3 months and ranged from 8 to 26 months. There were statistically significant differences between the preoperative and postoperative values in nose length index and projection index. Also, the nasolabial angle was significantly reduced. Postoperative evaluation, conducted at a minimum of 8 months following surgery, showed that 86.6% (13/15) of patients felt that their surgical results were good or excellent. No patients rated the results as "poor". CONCLUSION: The integrated clip-shaped costal cartilage carving approach has been shown to be a practical method of obtaining satisfactory esthetic outcomes in patients with nasal deformities.

Downregulation of ITGß3 in colon adenocarcinoma reveals poor prognosis by affecting genome stability, cell cycle, and the tumor immune microenvironment.

Introduction: Abnormal expression of integrin subunit beta 3 (ITGß3), a gene-encoding protein, is related to the occurrence and development of cancers; however, the biological role of ITGß3 in colon adenocarcinoma (COAD) remains unclear. Methods: We used the Cancer Genome Atlas database to obtain the clinical data of patients with COAD, analyzed the mRNA gene clusters related to ITGß3, and analyzed the interaction signal pathway and interaction protein network of the differentially expressed gene clusters. The results showed that ITGß3 expression in COAD tumor tissues was significantly downregulated compared with that in paracancerous tissues. Low ITGß3 expression in tumor tissues is associated with poor overall survival of patients with COAD. In multivariate analysis, stage IV and ITGß3 low expression were independent prognostic factors. Gene Ontology analysis showed that differentially expressed genes (DEGs) were significantly enriched in leukocyte migration, cell adhesion, and extracellular matrix (ECM) organization. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the DEGs were mainly enriched in ECM-receptor interactions, focal adhesion, and the PI3K-Akt signaling pathway. Protein-protein interaction network analysis revealed the hub and seed genes of the key modules related to ITGß3. Finally, we analyzed the correlation between TGß3 and immune-related genes and found that ITGß3 expression was significantly correlated with tumor purity and infiltration level of dominant immune cells. Discussion: These findings indicate that ITGß3 downregulation in COAD may profoundly affect genome stability and multiple steps of the cell cycle, alter the tumor immune microenvironment, and be related to the prognosis of patients with COAD.

Value of Magnifying Chromoendoscopy and Magnifying Optical Enhancement Technology in Classifying Colorectal Polyps: A Prospective Controlled Study.

BACKGROUND AND AIMS: Magnifying chromoendoscopy (ME-CE) through the observation of pit patterns is a productive way to distinguish between neoplastic and nonneoplastic polyps. Magnifying optical enhancement technology (ME-OE) is an emerging virtual chromoendoscopy imaging technology and appeared to be a promising approach. However, this information is currently not available. This study is aimed at comparing the differential diagnostic value of ME-CE and OE for neoplastic and nonneoplastic polyps. Patients and Methods. Consecutive patients undergoing colonoscopy were randomized (1 : 1) into examination by ME-OE or ME-CE. Histopathological findings were utilized as the reference standard. Accuracy, sensitivity, specificity, and positive and negative predictive values of two endoscopy methods were compared using ME-OE (were classified according to the JNET classification) and ME-CE (were classified according to the Kudo pit pattern classification), respectively, and the time to predict the histological polyp type was compared. And the agreements between the pathological and clinical diagnosis by ME-OE or ME-CE were analyzed. RESULTS: A total of 365 polyps were found in the 220 patients included (ME-OE: 185; ME-CE: 180.202 had nonneoplastic polyps, 163 had neoplastic polyps). The diagnostic accuracy of ME-OE was higher than that of ME-CE (93% vs. 92%, p > 0.05). The average diagnosis time was lower in ME-OE than ME-CE (83 ± 26.4 s vs. 194 ± 17.7 s, p < 0.001). The agreements between the pathological and clinical diagnosis were at least substantial in both groups. CONCLUSION: ME-OE was superlative to ME-CE in predicting the histology of polyps. OE devoted classification would possibly similarly enhance the endoscopist performance. The trial is registered with ChiCT2000032075.

Conjunctival flap with auricular cartilage grafting: a modified Hughes procedure for large full thickness upper and lower eyelid defect reconstruction.

AIM: To investigate the suitability of a modified Hughes procedure, which consists of conjunctival flap with auricular cartilage grafting in reconstructing large full thickness upper and lower eyelid defect. METHODS: Patients with full thickness eyelid carcinoma involving more than 50% margin length who underwent surgical resection were retrospectively reviewed in the study. The defects were reconstructed using conjunctival flap with auricular cartilage grafting, covered with myocutaneous flap above. Followed-up time ranged from 12 to 24mo. Outcomes were classified as "good", "fair", and "poor" by evaluating the margin appearance, eyelid appearance, and complications. RESULTS: A total of 42 patients were enrolled in the study (26 males, 16 females, mean age, 68.6±7.7y, range: 53 to 82y). The mean defect widths measured 23.2±2.9 mm (range, 17 to 28 mm). The mean posterior lamellar defect height was 5.5±1.3 mm (4 to 8 mm). Thirty-seven patients had a "good" outcome (88.1%), 5 patients had a "fair" outcome (11.9%), and no one had a "poor" outcome. CONCLUSION: Conjunctival flap with auricular cartilage grafting and myocutaneous flap grafting is an effective procedure in reconstructing large full thickness upper and lower eyelid defect. It can not only achieve satisfied reconstruction, but also preserve intact tarsal plate of the opposite eyelid, avoiding retraction or entropion.

Risk of Cardiac Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-Analysis.

BACKGROUND: We performed a systematic review and meta-analysis to evaluate the risks of cardiac adverse events in solid tumor patients treated with monotherapy of immune checkpoint inhibitors (ICIs) or combined therapy of ICIs plus chemotherapy. METHODS: Eligible studies were selected through the following databases: PubMed, Embase and clinical trials (https://clinicaltrials.gov.) and included phase III/IV randomized controlled trials (RCTs) involving patients with the solid tumor treated with ICIs. The data was analyzed by using Review Manager (version5.3), Stata (version 15.1). RESULTS: Among 2,551 studies, 25 clinical trials including 20,244 patients were qualified for the meta-analysis. Compared with PD-1 inhibitor (nivolumab) or CTLA-4 inhibitor (ipilimumab), PD-1 inhibitor (nivolumab) plus CTLA-4 inhibitor (ipilimumab) combined therapy showed significant increase in grade 5 arrhythmology (OR 3.90, 95% CI: 1.08-14.06, p = 0.603). PD-1 inhibitor plus chemotherapy show significant increase in grades 1-5 myocardial disease (OR 5.09, 95% CI: 1.11-23.32, p = 1.000). Compared with chemotherapy, PD-1 inhibitor (nivolumab) or CTLA-4 inhibitor (ipilimumab), PD-1 inhibitor (nivolumab) plus CTLA-4 inhibitor (ipilimumab) combined therapy show significant increase in grades 1-5 arrhythmology (OR 2.49, 95% CI: 1.30-4.78, p = 0.289). CONCLUSIONS: Our meta-analysis demonstrated that PD-1 inhibitor plus CTLA-4 inhibitor can result in a higher risk of grade 5 arrhythmology in comparison with PD-1/CTLA-4 inhibitor alone, and a higher risk of grade 5 arrhythmology in comparison with chemotherapy. PD-1 inhibitor plus chemotherapy treatment could increase the risk of all-grade myocardial disease compared with chemotherapy. However, in most cases, there was no significant increase of risks of cardiovascular toxicity in PD-1/PD-L1 inhibitor monotherapy or PD-1/PD-L1 inhibitor plus chemotherapy compared with chemotherapy alone.

Auricular cartilage versus donor sclera as a wrapping of hydroxyapatite orbital implants.

AIM: To retrospectively compare postoperative outcomes after primary enucleation and placement of a hydroxyapatite (HA) implant without wrapping, wrapped with auricular cartilage or donor sclera. METHODS: Medical records of patients presented as intraocular tumor or severe ocular injury were identified from the electronic medical record system. Cases underwent enucleation and HA orbital implantation were enrolled in this study and were divided into 3 groups according to the wrapping material of HA implant. Cases with autogenous cartilage caps were enrolled in group A (n=11), with donor sclera caps in group B (n=12), and without any wrapping material in group C (n=9). Follow-ups were set at 1, 2wk, 1, 3, 6, and 12mo after surgery. RESULTS: Altogether 32 cases finished the follow-up and were enrolled in this study. Three cases (27.27%) in group A, 4 cases (33.33%) in group B, and 4 cases (44.44%) in group C developed one complication each after surgery. In group A, no HA exposure occurred, but conjunctival inclusion cyst occurred in one and severe conjunctive chemosis in two cases. In group B, one HA exposure occurred, conjunctive inclusion cysts occurred in one, severe conjunctive chemosis occurred in one, and conjunctival granuloma occurred in one case. In group C, one HA exposure occurred, severe conjunctive chemosis occurred in two cases, and conjunctival granuloma occurred in one case. The case of exposure of none-wrapped implant was noted in the first 6mo after placement of the orbital implant. The case of exposure of donor sclera-wrapped implant was noted at the 12mo after placement of the orbital implant. Both exposure cases were treated successfully with conservative treatment. CONCLUSION: With low incidence of implant exposure and mild complications, auricular cartilage can be a good choice of alternative wrapping material of orbit implant with satisfied outcome.

Improved Eyelid Muscle Tension Balance With Refined Frontalis Muscle Flap Suspension in the Treatment of Severe Ptosis.

BACKGROUND: The tension balance of the upper eyelid following ptosis repair is crucial to a successful postoperative outcome. To improve on existing surgical techniques, the authors developed a new refined frontalis muscle flap suspension (FMFS) for severe ptosis repair and explored the balancing effect between the orbicularis muscle and frontalis muscle following surgery. METHODS: Forty-three patients (47 eyes) with a mean age of 6.07 ± 2.55 years old were diagnosed with severe congenital ptosis and underwent refined FMFS with complete orbicularis preservation between January 1, 2010 and December 31, 2017 in the Wenzhou Eye Hospital, Wenzhou, China. The outcomes measured include upper eyelid margin reflex distance (MRD1), degree of lagophthalmos, and cosmetic outcome (lash angle, eyelid contour, and crease). Surgical complications were also recorded. RESULTS: The preoperative mean MRD1 was -1.29 ± 0.88 mm and preoperative levator function was 1.87 ± 0.82 mm (ranged from 0 to 3.0 mm). Following surgery, lagophthalmos was observed in all cases in the first week with a mean palpebral fissure height of 1.68 ± 0.40 mm and diminished over 3 months. The MRD1 improved to +3.04 ± 0.68 mm at 6 months following surgery. All cases showed excellent cosmetic outcomes. There were no significant complications. CONCLUSION: The refined FMFS is a safe and reliable surgery in treating severe ptosis. The eye-closing power of the intact orbicularis muscle is sufficient at countering the lifting power of the frontalis muscle suspension, achieving a balanced blink mechanism and eyelid closure.

A New Preoperative Upright Design for Dermatochalasis Correction.

BACKGROUND: Conventional assessment of the height of upper eyelid skin excision in dermatochalasis correction is performed with patient's eyes closed in supine position. It is not able to consider the effects of gravity on the upper eyelid, thus may lead to asymmetric postoperative appearance. The authors herein report a novel preoperative upright design (PUD) that can accurately determine the amount of skin excision with patients' eyes open in dermatochalasis correction. METHODS: Patients with dermatochalasis underwent PUD during blepharoplasty were enrolled and were followed-up for 9 to 15 months. RESULTS: A total of 116 patients (mean age 55.1 ±â€Š6.1 years, range 46-78 years) successfully underwent the surgery. Using the PUD, the vertical height of skin excision was 8.2 ±â€Š2.4 mm (6-19 mm), the preoperative margin fold distance was -0.5 ±â€Š1.0 mm (-4 - 1 mm), which improved to 2.1 ±â€Š0.6 mm (1-3 mm, P < 0.05) at the last follow-up visit. A total of 107 of 116 patients (92.2%) were judged as "good" (natural double eyelid folds with symmetric margin fold distance), 9 patients (7.8%) were judged as "fair" (natural double eyelid folds with the differences of margin fold distance between fellow eyelids within 2 mm), and no one was judged as "poor" (unsmooth double eyelid folds or the differences of margin fold distance between fellow eyelids is more than 2 mm). CONCLUSION: Preoperative upright design is a simple and effective method to accurately determine the amount of skin excision in blepharoplasty, and help to achieve symmetric double eyelids.

The Effect of Omega-3 Polyunsaturated Fatty Acid Supplementations on anti-Tumor Drugs in Triple Negative Breast Cancer.

Triple-negative breast cancer (TNBC) comprises about 10-20% of all diagnosed breast cancers. Increasing evidence shows that the omega-3 polyunsaturated fatty acids (ω-3PUFAs), docosahexaenoic acid and eicosapentaenoic acid, can influence the development, progression, and prognosis of TNBC In Vivo and In Vitro; however, clinical evidence supporting the effect of ω-3PUFAs on TNBC is lacking. Research has demonstrated that ω-3PUFAs can induce apoptosis in breast cancer cells by inhibiting the PI3K/AKT signal transduction pathway, and that ω-3PUFAs can improve the effectiveness of chemotherapy drugs. Using ω-3PUFA supplementation in addition to pharmacotherapy in the treatment of breast cancer may result in enhanced anti-tumor effects that will be particularly applicable to difficult to treat phenotypes such as TNBC. The aim of the current review was to summarize the evidence-base supporting the antitumor effects of omega-3 PUFAs in TNBC.