AIM: To conduct whole exome sequencing(WES)analysis on three pedigrees with blepharophimosis-ptosis-epicanthus inversus syndrome(BPES)to identify the pathogenic gene loci, uncover novel mutations, and expand the mutation spectrum of the disease-associated genes.METHODS:Retrospective study. A total of 3 pedigrees and 30 patients with BPES(with criteria of bilateral blepharophimosis, ptosis, epicanthus inversus and wider inner canthal distance at birth)treated in the Ophthalmology Department of the Second People's Hospital of Yunnan Province were collected from January 2021 to August 2021, including 8 patients and 22 unaffected family members. Peripheral blood samples were collected from patients and related family members, and genomic DNA was extracted for whole exome sequencing. The sequencing results were screened to identify potential pathogenic gene loci, and candidate mutations were validated using Sanger sequencing.RESULTS:WES analysis identified pathogenic gene mutations in 3 BPES pedigrees: pedigree 1(6 members, 3 affected individuals, with a history of disease across three generations)harbored a novel heterozygous mutation in the PIEZO2 gene(located 36 bp upstream of exon 11, G>C). Sanger sequencing confirmed that this mutation was present in all affected individuals and absent in normal family members, and it represents the first report of this mutation. Pedigree 2(14 members, 2 affected individuals)and pedigree 3(10 members, 3 affected individuals)carried known heterozygous mutations in the FOXL2 gene, namely the missense mutation c.313A>C(p.N105H)and the in-frame mutation c.672_701dupAGCGGCTGCAGCAGCTGCGGCTGCAGCCGC(p.A225_A234dupAAAAAAAAAA), respectively.CONCLUSION:WES successfully identified the pathogenesis of familial congenital BPES in two families, including a known FOXL2 gene mutation and a newly discovered PIEZO2 gene mutation. These findings provide a theoretical basis for genetic counseling and reproductive guidance. Notably, the PIEZO2 gene mutation(located 36 bp upstream of exon 11, G>C)discovered in the pedigree 1 is reported for the first time and plays a critical role in the onset of the disease in this family. Further investigation of this new mutation could not only expand the mutation spectrum of BPES, but also enhance our understanding of its pathogenic mechanisms.

Oral frailty and cognitive impairment are the common geriatric syndromes.There may be similar correlation mechanism between them,which are related with polypharmacy,malnutrition,inflammato-ry responses and psychosocial factors.The occurrence of oral frailty could potentially increase the risk of cog-nitive impairments,in which tooth loss,reduced chewing function,swallowing difficulties,low tongue pres-sure,and diminished oral motor function are closely correlated with cognitive impairments.Understanding the correlation between the two is conducive to prevent and interfere the healthy status in elderly people,thus in-crease their quality of life and health level.

Hydroxychloroquine is widely used in the treatment of autoimmune diseases and skin diseases, mainly for the treatment of diseases such as systemic lupus erythematosus, rheumatoid arthritis and other diseases. Hydroxychloroquine has many benefits to patients, but long-term use of the drug may lead to retinal chronic toxicity changes, seriously affect the patient’s vision and quality of their lives. However, there are few studies on retinal toxicity of hydroxychloroquine in the world, easy to miss diagnosis and misdiagnosis clinically. ophthalmologists should increase the knowledge with the etiology and pathology of hydroxychloroquine retinal toxicity, through relevant auxiliary check early detection of the drug to the retina and timely suggest patients to stop. This can effectively reduce the risk of vision loss caused by retinal toxicity, and reduce the adverse effects of hydroxychloroquine on the retina while patients get a good treatment effect.

Background:Ulcerative colitis(UC)is a chronic non-specific disease with potential for disability,and clinical treatment mainly relies on drugs.Currently,small molecule drugs(SMDs)have shown good application prospects.Aims:To evaluate the efficacy and safety of SMDs in the treatment of UC.Methods:Randomized controlled trials(RCTs)of SMDs in treatment of moderate-to-severe UC from CNKI,Wanfang Data,VIP,China Biomedical Literature Database,PubMed,Cochrane Library and Embase were searched from the establishment of the database to March 2024.References were screened and data extracted according to inclusion and exclusion criteria,and meta-analysis was performed using RevMan 5.3 software.Results:A total of 16 literatures involving 22 RCTs were finally included.Meta-analysis results suggested that SMDs had better efficacy indicators than placebo,such as clinical response rate(RR=1.86,95%CI:1.60-2.16,P<0.000 01),clinical remission rate(RR=3.01,95%CI:2.17-4.16,P<0.000 01),mucosal healing rate(RR=2.93,95%CI:2.27-3.79,P<0.000 01)and maintained response rate(RR=3.87,95%CI:3.11-4.81,P<0.000 01)were improved,and there was a statistical difference between them.And in terms of safety,SMDs compared to placebos,The incidence of adverse reactions(RR=1.02,95%CI:0.96-1.08,P=0.55),the incidence of serious adverse reactions(RR=0.77,95%CI:0.59-1.00,P=0.05),and the incidence of adverse reactions leading to drug withdrawal(RR=0.78,95%CI:0.59-1.02,P=0.07)were not statistically significant.Conclusions:SMDs are effective and safe in UC patients,which provides a new idea for the treatment of UC.

Background:Ulcerative colitis(UC)is a chronic non-specific disease with potential for disability,and clinical treatment mainly relies on drugs.Currently,small molecule drugs(SMDs)have shown good application prospects.Aims:To evaluate the efficacy and safety of SMDs in the treatment of UC.Methods:Randomized controlled trials(RCTs)of SMDs in treatment of moderate-to-severe UC from CNKI,Wanfang Data,VIP,China Biomedical Literature Database,PubMed,Cochrane Library and Embase were searched from the establishment of the database to March 2024.References were screened and data extracted according to inclusion and exclusion criteria,and meta-analysis was performed using RevMan 5.3 software.Results:A total of 16 literatures involving 22 RCTs were finally included.Meta-analysis results suggested that SMDs had better efficacy indicators than placebo,such as clinical response rate(RR=1.86,95%CI:1.60-2.16,P<0.000 01),clinical remission rate(RR=3.01,95%CI:2.17-4.16,P<0.000 01),mucosal healing rate(RR=2.93,95%CI:2.27-3.79,P<0.000 01)and maintained response rate(RR=3.87,95%CI:3.11-4.81,P<0.000 01)were improved,and there was a statistical difference between them.And in terms of safety,SMDs compared to placebos,The incidence of adverse reactions(RR=1.02,95%CI:0.96-1.08,P=0.55),the incidence of serious adverse reactions(RR=0.77,95%CI:0.59-1.00,P=0.05),and the incidence of adverse reactions leading to drug withdrawal(RR=0.78,95%CI:0.59-1.02,P=0.07)were not statistically significant.Conclusions:SMDs are effective and safe in UC patients,which provides a new idea for the treatment of UC.

Hydroxychloroquine is widely used in the treatment of autoimmune diseases and skin diseases, mainly for the treatment of diseases such as systemic lupus erythematosus, rheumatoid arthritis and other diseases. Hydroxychloroquine has many benefits to patients, but long-term use of the drug may lead to retinal chronic toxicity changes, seriously affect the patient’s vision and quality of their lives. However, there are few studies on retinal toxicity of hydroxychloroquine in the world, easy to miss diagnosis and misdiagnosis clinically. ophthalmologists should increase the knowledge with the etiology and pathology of hydroxychloroquine retinal toxicity, through relevant auxiliary check early detection of the drug to the retina and timely suggest patients to stop. This can effectively reduce the risk of vision loss caused by retinal toxicity, and reduce the adverse effects of hydroxychloroquine on the retina while patients get a good treatment effect.

[摘 要] 目的：探讨橙花叔醇通过Wnt-β-catenin通路抑制黑色素瘤A-375和WM-115细胞恶性生物学行为的分子机制。方法: 体外培养黑色素瘤细胞A-375和WM-115，用不同浓度的橙花叔醇处理，采用SRB法和克隆形成实验、FCM术、Transwell实验和细胞划痕实验、DCFH-DA染色法、qPCR和WB法分别检测橙花叔醇对A-375和WM-115细胞的增殖能力、细胞周期和凋亡、迁移能力、活性氧（ROS）水平和Wnt-β-catenin通路及其下游相关基因和相关蛋白表达的影响。利用ULCAN和GEPIA2数据库分析黑色素瘤中Wnt-β-catenin通路的激活与患者预后的关系。结果：与对照组比较，橙花叔醇处理组A-375和WM-115细胞的增殖能力受明显抑制（均P<0.01）、细胞周期阻滞于G2/M期（P<0.05或P<0.01）、细胞凋亡率增加（均P<0.01）、迁移能力降低（P<0.05或P<0.01）、ROS水平升高（均P<0.01）、Wnt-β-catenin通路被抑制而其下游基因和蛋白表达明显上调（均P<0.01）。数据库数据分析显示，WNT1基因高表达患者OS低于低表达患者（P<0.01）。结论：橙花叔醇通过上调A-375和WM-115细胞中ROS水平影响Wnt-β-catenin通路，从而抑制其恶性生物学行为；Wnt-β-catenin通路可能是黑色素瘤治疗的潜在靶点。

Background: Inflammatory bowel disease (IBD) is a chronic recurrent inflammatory disease of gastrointestinal tract including ulcerative colitis (UC) and Crohn's disease (CD). It is unclear whether there is a causal association between unsaturated fatty acids and IBD. Aims: A two⁃sample Mendelian randomization analysis was used to explore the causal association between unsaturated fatty acids and IBD. Methods: The data of the genome⁃wide association study (GWAS) of unsaturated fatty acids and IBD were obtained from web⁃based public databases. Two⁃sample Mendelian randomization analysis was performed by using inverse⁃variance weighted analysis, and weight median estimator and MR⁃Egger regression were conducted to validate the association of the causal effect. The causality of unsaturated fatty acids on the risk of IBD was evaluated by OR and 95% CI. Results: No direct causal association was found between ω⁃6 fatty acids and CD, and a direct causal association was found with UC. Inverse⁃variance weighted analysis showed a 16% increase in the risk of UC for each standard deviation increase in ω⁃6 fatty acid gene levels (OR=1.16, 95% CI: 1.00⁃1.36, P=0.04). However, no causal association was found between ω⁃3 fatty acids, monounsaturated fatty acids and IBD. Conclusions: ω⁃6 fatty acids may be only causally associated with UC, and no causal association is found between ω⁃3 fatty acids, monounsaturated fatty acids and IBD.

Objective:To study the expressions of heat shock protein (HSP) 90α and HSP90β in colorectal cancer and paracancer tissues, and to investigate the relationships between HSP90α, HSP90β and clinicopathological features of colorectal cancer patients, and to analyze their correlation.Methods:The tumor tissues and paracancer tissues of 117 patients with colorectal cancer were selected from the Department of Gastrointestinal Surgery, Third Affiliated Hospital of Shandong First Medical University from January 2016 to December 2020. The expression levels of HSP90α and HSP90β were detected by immunohistochemistry, and the relationships between the two proteins and clinicopathological features and the correlation of their expressions were analyzed.Results:The positive expression rates of HSP90α in colorectal cancer tissues and paracancer tissues were 74.4% (87/117) and 12.0% (14/117) , and there was a statistically significant difference ( χ2=92.83, P<0.001) . The positive expression rate of HSP90β in colorectal cancer tissues and paracancer tissues was 61.5% (72/117) and 10.3% (12/117) , and there was a statistically significant difference ( χ2=66.86, P<0.001) . The expression of HSP90α was correlated with tumor location ( χ2=8.67, P=0.003) , vascular invasion ( χ2=8.68, P=0.003) , lymph node metastasis ( χ2=8.52, P=0.004) , T stage ( χ2=21.07, P<0.001) , N stage ( χ2=11.94, P=0.003) , M stage ( χ2=5.37, P=0.020) , pathological stage ( χ2=25.64, P<0.001) . The expression of HSP90β was correlated with lymph node metastasis ( χ2=4.03, P=0.045) , T stage ( χ2=11.09, P=0.007) , N stage ( χ2=6.56, P=0.038) , M stage ( χ2=12.43, P<0.001) , pathological stage ( χ2=17.34, P=0.001) . There was a positive correlation between the expressions of the two proteins in colorectal cancer tissues ( r=0.42, P<0.001) . Conclusion:The expressions of HSP90α and HSP90β in colorectal cancer tissues are significantly higher than those in paracancer tissues, and they are related to lymph node metastasis and pathological stage. There is a positive correlation between the two proteins, which may be involved in the occurrence and development of colorectal cancer and are expected to become new tumor markers.

Objective:To explore the value of nursing checklist in posterior surgery for thoracolumbar fracture with general anesthesia under prone position.Methods:A retrospective case series study was conducted to analyze the clinical data of 106 patients with thoracolumbar fracture admitted to Sir Run Run Shaw Hospital，Zhejiang University School of Medicine from June 2018 to May 2020. There were 80 males and 26 females，with age range of 25-57 years［（48.6 ± 11.9）years］. Segments of injury were located at T 11 in 18 patients，at T 12 in 26，at L 1 in 21，at L 2 in 25 and at L 3 in 16. All patients were treated with thoracolumbar posterior screw fixation under general anesthesia. Of all，51 patients received conventional postural nursing from June 2018 to May 2019（control group），and 55 patients received prone position nursing scheme for general anesthesia on the basis of conventional postural nursing from June 2019 to May 2020（verification group）. The incidence of postoperative complications including stress injury，brachial plexus injury，ulnar nerve injury and ocular discomfort as well as length of hospital stay and patients’ satisfaction were compared between the two groups. Visual analogue scale（VAS）and Oswestry disability index（ODI）were also used to measures outcome at postoperative 3 months. Results:All patients were followed up for 8-12 months［（10.5±0.9）months］. Verification group and control group showed significant differences in the incidence of stress injury（4%∶29%），brachial plexus injury（4%∶16%）and ocular discomfort consisiting of tears（2%∶12%），foreign body sensation（0%∶4%）and dryness（4%∶16%）（ P < 0.05），not in ulnar nerve injury and blurred vision. Length of hospitalization in verification group was（7.0±1.3）days，significantly shorter than that in control group［（9.9±1.9）days］（ P < 0.05）. Satisfaction of patients in verification group and control group was 85%（47/55）and 69%（35/51），respectively（ P < 0.05）. At 3 months postoperatively，VAS in verification group［（1.9 ± 0.8）points］was significantly lower than that in control group［（3.5±1.1）points］（ P < 0.05），and ODI was similar between the two groups（ P > 0.05）. Conclusions For patients with thoracolumbar fracture treated by posterior surgery with general anaesthesia under prone position，nursing checklist helps reduce occurrence of the related complication，shorten length of hospital stay，improve patient satisfaction，reduce postoperative pain and promote rehabilitation.