Objective:To analyze the research status of scleral lenses by bibliometric method based on the relevant collection of scleral lenses in the Web of Science database.Methods:Using the scleral lens-related literature collected in the Web of Science Core Collection database in the past 10 years (January 2013 to December 2022) as the object of analysis, bibliometric method and CiteSpace tools were used to conduct visual analysis of the literature.A comprehensive analysis of the volume of literature published, the distribution of countries and institutions, the information of core authors, the distribution of journals, and keyword clustering was performed.Results:A total of 340 articles were retrieved, which were published in 54 journals, with an average of 6.3 articles per journal, involving 301 authors.Research in this area covered 35 countries or regions, and 256 research institutions were involved.Discipline development was mainly in the United States, India, Spain and Australia.The main focus was on scleral lens (scleral contact lens), ocular surface disease, corneal edema, miniature scleral lens, etc.In the past 10 years, the trend of research hot topics in scleral lenses had shifted from the initial study of combining scleral contact lenses with ocular surface diseases to the subsequent study of prosthetic replacement of the ocular surface ecosystem, and the exploration of corneal clearance and shape.From 2013 to 2021, the main focuses were ocular surface diseases, scleral contact lenses, and corneal edema.After 2021, research on ocular surface diseases and keratoplasty declined.From January 2013 to December 2022, emergent keywords related to scleral lens mainly included scleral contact lens, transplantation, anti-host disease, prosthetic device in the first stage, artificial replacement of ocular surface ecosystem and irregular cornea in the second stage, and the research on corneal gap and characteristic shape in the third stage.Optical coherence tomography and corneal topography were commonly used examinations for scleral lens research and fitting.Conclusions:At present, the scleral lens is mainly used for dry eye, corneal diseases, corneal ectasia, keratitis, and corneal transplantation, especially after penetrating keratoplasty and refractive errors.Prosthetic replacement of the ocular surface ecosystem, and the exploration of corneal clearance and shape are the research hotspots in scleral lenses.

ObjectiveTo explore the possible mechanism of Changweiqing （肠胃清） in the treatment of colorectal cancer. MethodsHCT 116 cancer cells were used to prepare intestinal cancer cells with silenced polypyrimidine region binding protein 3 （PTBP3） gene and stably transfected cells with overexpressed PTBP3 gene. Stably transfected cells with silenced PTBP3， stably transfected cells with overexpressed PTBP3 and untransfected cancer cells were injected into the armpit of 72 nude mice to construct three different subcutaneous transplanted tumor models of colorectal cancer cells， including the silenced model， the overexpressed model and the control model， with 24 mice per model. Mice of each transplanted tumor modelwere randomly divided into Changweiqing （CWQ） group， oxaliplatin （OXA） group and normal saline （NS） group， with 8 mice in each group. The CWQ groups were given intragastric administration of 35.9625 g/kg of Changweiqing oral liquid and were intraperitoneally injected with 0.2ml of normal saline； the NS groups were given 0.5ml of normal saline by gavage， and intraperitoneal injection of 0.2ml of normal saline； the OXA groups were intraperitoneally injected with 5 mg/kg （0.2 ml） of oxaliplatin and given 0.5ml of normal saline by gavage. Each group was given intragastric administration once a day and intraperitoneal injection three times a week. After 31 days， the weight of subcutaneous tumors in each group was measured， and the tumor inhibition rate of the groups in each model were measured. Immunohistochemistry and other methods were used to detect the expression level of cell proliferation cell nuclear antigen Ki67 and apoptosis index. Real-time PCR and Western Blot were used to detect mRNA and protein expressions of PTBP3， signal transducer and activator of transcription 3 （STAT3） splicing isoform α （STAT3α）， STAT3 splicing isoform β （STAT3β）， B-cell lymphoma/leukemia-2 （Bcl-2） splicing isoform α （Bcl-2α）， and Bcl-2 splicing isoform β （Bcl-2β） in subcutaneous tumor cells in each group. ResultsFor all three transplanted tumor models， the weight of the subcutaneous tumors and Ki67 expression level of subcutaneous tumor tissue in all CWQ groups and OXA groups were lower than those of the corresponding NS groups， while the apoptosis level were higher （P＜0.05 or P＜0.01）. The mRNA and protein expressions of PTBP3， STAT3α， and Bcl-2α in the subcutaneous tumor tissues of the silenced model CWQ group and the overexpressed model CWQ group were lower than those of the corresponding NS groups， while the mRNA and protein expression levels of STAT3β and Bcl-2β were higher （P＜0.05 or P＜0.01）. All there groups of silenced model had lower subcutaneous tumor weight， Ki67 expression level， and mRNA and protein expression levels of PTBP3， STAT3α， and Bcl-2α in subcutaneous tumor tissue， as well as higher apoptosis level and mRNA and protein expression levels of STAT3β and Bcl-2β than those in all groups of control model； all groups of overexpressed model had higher subcutaneous tumor weight， Ki67 expression level， and mRNA and protein expression levels of PTBP3， STAT3α， and Bcl-2α ， while lower apoptosis level and mRNA and protein expression levels of STAT3β and Bcl-2β than those in all control model groups （P＜0.05 or P＜0.01）. In the control model， compared with the NS group， The tumor inhibition rate of all OXA groups was higher than that of corresponding CWQ groups， respectively. Compared to that of each control model group， the tumor inhibition rate was positive value of each silenced model group， and negative value of each overexpressed model group. ConclusionPTBP3 can promote the proliferation and inhibit apoptosis of intestinal cancer cells， upregulate the expression of STAT3α and Bcl-2α， and downregulate the expression of STAT3β and Bcl-2β in intestinal cancer cells. The meachnism of action of Changweiqing in the treatment of colorectal cancer maybe related to the inhibition of PTBP3， and regulation of the expression of STAT3α， STAT3β， Bcl-2α， and Bcl-2β.

Objective:To investigate the correlation between fat distribution and the composite indices of femoral neck strength in obese postmenopausal women.Methods:A total of 293 postmenopausal women with non-low body weight were selected, laboratory tests, body composition analyzer test and double-energy X-ray absorptiometry scan were performed. Based on the body mass index(BMI), they were divided into three groups, the normal BMI group(18.5 kg/m 2≤BMI<24.0 kg/m 2, n=91), the overweight group(24.0 kg/m 2≤BMI<28.0 kg/m 2, n=115), and the obese group(BMI≥28.0 kg/m 2, n=87). The measurement results were analyzed. Results:In the obese group, bone mineral density(BMD) of all sites was higher than that in the normal BMI group and overweight group( P<0.005), compression strength index(CSI), bending strength index(BSI), and impact strength index(ISI) were significantly lower than those in the normal BMI group( P<0.001, P=0.008, P=0.001). In the obese group, waist circumference, waist-hip ratio, total fat mass, appendicular fat mass, and trunk fat mass were risk factors for CSI, BSI and ISI independent of age, fasting blood glucose, and BMI( P<0.05). Visceral fat grade and Chinese visceral adiposity fat index were the risk factors for CSI, BSI, and ISI( P<0.05). Conclusion:The composite indices of femoral neck strength decreased in obese postmenopausal women, and both subcutaneous fat and visceral fat were negatively associated with the composite indices of femoral neck strength.

Objective:To investigate the clinical features, molecular etiology, and treatment of a family with Treacher Collins Syndrome 2 (TCS2).Methods:Information of the proband (female, 8 years old) including medical history and family history was collected. Physical examination and examinations concerning laboratory, audiology, and radiology were performed on the proband. Physical examination was also performed on the family members. Genomic DNA of proband was extracted for whole exome sequencing, and then the genomic DNA of family members was extracted for Sanger sequencing. POLR1D and TCS2 related literatures published before August 31,2023 were searched and sifted in PubMed and CKNI databases. The clinical characteristics of TCS2 were summarized. Results:The proband had poor hearing since childhood, with pure tone audiometry indicating conductive hearing loss. She had a smaller jaw, bilateral preauricular fistulas and cup-shaped ear deformities. Temporal bone CT scan revealed deformities in the left external ear canal, bilateral middle ear and inner ear. A bone-conduction hearing aid device was surgically implanted, resulting in restoration of almost normal hearing levels. The proband′s mother also had a slightly smaller jaw. Genetic analysis revealed a novel heterozygous variant NM_015972.4:c.38_47del in the POLR1D gene in the proband, which was inherited from her mother. A review of the literature revealed no clear evidence of genotype-phenotype correlation in TCS2. Conclusions:Molecular diagnosis plays a vital role in the diagnosis of TCS2. Patients with normal facial phenotype may be carriers of pathogenic variants in the POLR1D gene and have the risk of passing it to the offsprings with complete penetrance. Proper bone conductive hearing devices can improve the quality of life of TCS2 patients.

ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan（RYZBW）in the treatment of initial and early knee osteoarthritis （KOA） through a prospective multicenter，randomized，double-blind，and placebo-parallel controlled trial. MethodFrom October 13^th， 2021 to December 25^th， 2021， 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital， Chinese Academy of Chinese Medical Sciences， and they were randomly divided into observation group and control group， with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education， and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks， and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score （WOMAC score）， and the secondary outcome measures were the response rate of visual scale （VAS） pain score， WOMAC sub item scores （joint pain， joint stiffness， and joint function）， quality of life （SF-12） score， and traditional Chinese medicine （TCM） syndrome score. Result（1） Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW， and the difference was statistically significant （P<0.05）. There was no significant difference between the two groups in improving VAS score response rate， WOMAC function score， WOMAC stiffness score， SF12-PCS （quality of life-physical health） score， SF12-MCS （quality of life-mental health） score， and TCM syndrome score. （2） Subgroup analysis. ① In terms of VAS score response rate， the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of （4， 5］， and the difference was statistically significant （P<0.05）. ② In terms of TCM syndrome score， for subjects aged ［56， 60］ and ［61， 65］， the decrease in total TCM syndrome score in the observation group was better than that in the control group， and the difference was statistically significant （P<0.05）. ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score， VAS score response rate， WOMAC pain score， WOMAC function score， and TCM syndrome score for patients with initial and early KOA， which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.

Objective To study the causes of two Chinese families with Branchio-oto syndrome.Methods The clinical data of two families were collected,and the pathogenic genes and variants of Branchio-oto syndrome were screened and verified by whole exome sequencing and Sanger sequencing.Results Two proband patients were diagnosed with Branchio-oto syndrome.Proband 1 presented with preauricular and anterior cervical fistulas,as well as congenital severe sensorineural hearing loss.On the other hand,proband 2 displayed a preauricular fistula and an anterior cervical cyst.At the age of 5,progressive deterioration of binaural hearing was observed,leadingtothe cur-rent diagnosis of severe mixed deafness.Genetic analysis showed that proband 1 and 2 carried nonsense variants of EYA1 gene:NM_000503.6:c.1408G＞T(p.Glu470Ter),and c.889C＞T(p.Arg297Ter).According to the guide-lines of the American College of Medical Genetics and Genomics(ACMG),the above variants were rated as patho-genic variants.After reviewing the literature,the c.1408G＞T variant had not been previously reported,and the c.889C＞T is a known variant.Conclusion The variants c.1408G＞T(p.Glu470Ter)and c.889C＞T(p.Arg297Ter)of EYA1 gene are the cause of these two families with Branchio-oto syndrome.The first report of c.1408G＞T broadens the mutational spectrum of EYA1 gene and provids a clinical reference for the diagnosis of Branchio-oto syndrome.

Objective:To evaluate the effect of emodin on liver injury in a mouse model of intestinal ischemia-reperfusion (I/R) and the role of heme oxygenase-1-mediated autophagy.Methods:Twenty-four SPF-grade healthy male C57BL/6 mice, aged 6-8 weeks, weighing 18-22 g, were divided into 4 groups ( n=6 each) using a random number table method: sham operation group (Sham group), I/R group, emodin group (E group) and emodin plus HO-1 inhibitor Zinc Protoporphyrin Ⅸ (ZnPP) group (ES group). The intestinal I/R injury model was established by clamping the superior mesenteric artery for 45 min followed by 120 min of reperfusion. Emodin 40 mg/kg dissolved in 5% methylcellulose sodium was given by gastric gavage once a day for 5 days before ischemia in E group. Emodin 40 mg/kg dissolved in 5% methylcellulose sodium was given by gastric gavage once a day for 5 days before intestinal I/R, and ZnPP 7.5 mg/kg was injected via the tail vein at 12 h before ischemia in ES group. Orbital venous blood samples were collected at the end of reperfusion for determination of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations. Then the mice were sacrificed, and liver tissues were obtained for microscopic examination of the pathological changes (after HE staining) and for determination of the activity of superoxide dismutase (SOD), content of malondialdehyde (MDA), expression of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) mRNA (by fluorescent quantitative polymerase chain reaction), the expression of HO-1, autophagy-related protein Beclin1 and microtubule-associated protein 1 light chain 3 (LC3) (by Western blot). The LC3-Ⅱ/Ⅰ ratio was calculated. Results:Compared with Sham group, the activity of SOD was significantly decreased, the content of MDA and serum ALT and AST concentrations were increased, the expression of IL-6 and TNF-α mRNA and HO-1 was up-regulated, the expression of Beclin1 was down-regulated, the LC3-Ⅱ/Ⅰ ratio was decreased ( P<0.05), and the pathological changes of liver tissues were found in I/R group. Compared with I/R group, the activity of SOD was significantly increased, the content of MDA and serum ALT and AST concentrations were decreased, the expression of IL-6 and TNF-α mRNA was down-regulated, the expression of HO-1 and Beclin1 was up-regulated, the LC3-Ⅱ/Ⅰ ratio was increased ( P<0.05), and the pathological changes of liver tissues were significantly attenuated in E group ( P<0.05). Compared with E group, the activity of SOD was significantly decreased, the content of MDA and serum ALT and AST concentrations were increased, the expression of IL-6 and TNF-α mRNA was up-regulated, the expression of HO-1 and Beclin1 was down-regulated, the LC3-Ⅱ/Ⅰ ratio was decreased ( P<0.05), and the pathological changes of liver tissues were aggravated in ES group. Conclusions:Emodin can alleviate liver injury induced by intestinal I/R in mice, and the mechanism may be related to the activation of HO-1-mediated autophagy.

The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer.Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis(YTE-17),attributing these effects to the regu-lation of multiple signaling pathways.However,knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited.In this study,we conducted isobaric tags for relative and absolute quantification(iTRAQ)analysis on intestinal epithelial cells(IECs)exposed YTE-17,both in vitro and in vivo,revealing a significant inhibition of the Wnt family member 5a(Wnt5a)/c-Jun N-terminal kinase(JNK)signaling pathway.Subsequently,we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment(TME),specifically focusing on macrophage-mediated T helper 17(Th17)cell induction in a colitis-associated cancer(CAC)model with Wnt5a deletion.Additionally,we performed the single-cell RNA sequencing(scRNA-seq)on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition,lineage,and functional status of immune mesenchymal cells during different stages of colorectal cancer(CRC)progression.Remarkably,our findings demon-strate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17,leading to the restoration of regulatory T(Treg)/Th17 cell balance in azoxymethane(AOM)/dextran sodium sulfate(DSS)model.Furthermore,we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages.Notably,our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical β-catenin oncogenic pathway in vivo.Specifically,we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with β-catenin activity within the TME,involving macrophages and T cells.In summary,our study undergoes the po-tential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment,thereby mitigating the risk of malignancies.

ObjectiveTo investigate the inhibitory effects and mechanism of the compound Phyllanthus urinaria Ⅱ （CPU Ⅱ）on the growth of transplanted hepatocellular carcinoma Hep3B2.1-7 （Short for Hep3R） cells in nude mice. MethodAfter the establishment of a xenograft model of hepatocellular carcinoma Hep3B cells in mice， the model mice were randomly divided into a model group， a high-dose CPU Ⅱ group （57.5 g·kg^-1）， a low-dose CPU Ⅱ group （28.75 g·kg^-1）， and a 5-fluorouracil （5-FU） group （0.025 g·kg^-1）， with eight mice in each group. The mice in the high- and low-dose CPU Ⅱ groups were treated with drugs by gavage， once per day， and those in the model group were treated with the same volume of normal saline. The mice in the 5-FU group were treated by 5-FU by intraperitoneal injection， once every other day. After 28 days of administration， mice were sacrificed， and transplanted tumors were collected. Immunohistochemistry （IHC） was used to detect the expression of proliferating cell nuclear antigen （PCNA） of tumor tissues. Terminal-deoxynucleotidyl transferase-mediated nick end labeling （TUNEL） was used to detect cell apoptosis of tumor tissues. The mRNA expression of miR-122 and insulin-like growth factor 1 receptor （IGF-1R） in tumor tissues was detected by Real-time quantitative PCR （Real-time PCR）. The protein expression of CCAAT/enhancer-binding protein α （C/EBPα）， hepatocyte nuclear factor-4α （HNF-4α）， and IGF-1R in tumor tissues was detected by Western blot. ResultThe tumor suppression rates of the high- and low-dose CPU Ⅱ groups and the 5-FU group were 74.90%， 63.62%， and 64.15%， respectively. Compared with the model group， the CPU Ⅱ groups and the 5-FU group showed reduced weight （P<0.01） and volume of tumors （P<0.01）， decreased PCNA positive cells， shallow staining， increased apoptosis cells of transplanted tumor tissues （P<0.05， P<0.01）， increased expression of mRNA expression of miR-122 （P<0.01）， down-regulated mRNA expression of IGF-1R （P<0.01）， and up-regulated protein expression of C/EBPα and HNF-4α in nude mouse transplanted tumor tissues （P<0.01）. The expression of IGF-1R protein in the high-dose CPU Ⅱ group was down-regulated （P<0.05）. Compared with the low-dose CPU Ⅱ group， the high-dose CPU Ⅱ group showed increased apoptotic cells （P<0.01）， up-regulated mRNA expression of miR-122 （P<0.01）， and increased expression of C/EBPα and HNF-4α proteins （P<0.01）. ConclusionCPU Ⅱ has an obvious inhibitory effect on the growth of transplanted hepatocellular carcinoma Hep3B cells in nude mice. The mechanism of action is related to enhancing the expression of transcription factors HNF-4α and C/EBPα， thereby promoting the expression of miR-122 and inhibiting the expression of its target gene IGF-1R.

【Objective】 To investigate the relationship between ABO blood types and the risk of malignant tumors in Chaoshan area, Guangdong. 【Methods】 Chi-square test was used to analyze the distribution of ABO blood types between 45 890 patients with malignant tumors from the Cancer Hospital of Shantou University Medical College and 42 465 healthy blood donors from Shantou Central Blood Bank. 【Results】 Among the main types of malignant tumors, the distributions of ABO blood types in patients with esophageal cancer or head and neck cancer were significantly different from that in the normal population (χ²=11.16, P<0.05; χ²=74.36, P<0.05; respectively). People with type B were identified with high risk of esophageal cancer and head and neck cancer (OR=1.09, 95% CI=1.03-1.15, P<0.05; OR=1.46, 95% CI=1.34-1.60, P<0.05), whereas those with type A or O were identified with low risk of head and neck cancer (OR=0.87, 95% CI=0.79-0.96, P<0.05; OR=0.83, 95% CI=0.76-0.90, P<0.05). 【Conclusion】 ABO blood type distribution in patients with esophageal cancer or head and neck cancer in Chaoshan area may be different from that in normal population, suggesting that different ABO blood types may be associated with the risk of esophageal cancer and head and neck cancer.