Nanophthalmos (NNO) is a hereditary, congenital, ocular developmental disorder characterized by shortening of the entire eyeball.It has a low incidence worldwide and is considered a rare disease.Genetic modes of nanophthalmos include autosomal dominant and recessive inheritance, and sporadic cases have also been reported.Currently, at least six genes, including PRSS56, MFRP, TMEM98, MYRF, CRB1 and BEST1, have been reported to be associated with the onset of this disease.Common pathological phenotypes include short axial length, high hyperopia, and a high tendency to be complicated by angle-closure glaucoma and uveal effusion syndrome, etc.Different NNO genotypes show significant differences in clinical phenotypes.Studies on the correlation between NNO genotypes and phenotypes have provided an important basis for early clinical intervention.However, due to the limitated sample size of rare diseases, existing studies mainly focus on exploring the variant sites of different genotypes and the clinical phenotypes of patients.It is difficult to form a discussion on the overall correlation between the phenotypes and genotypes of NNO.This article collects and sorts out the research reports on NNO from 2010 to 2024, aiming to review the research progress on the correlation between genotypes and phenotypes of NNO from aspects such as gene mutation types and regional populations, in order to improve the understanding of NNO and provide more ideas and theoretical basis for studying its occurrence and development as well as gene therapy.

Nanophthalmos (NNO) is a hereditary, congenital, ocular developmental disorder characterized by shortening of the entire eyeball.It has a low incidence worldwide and is considered a rare disease.Genetic modes of nanophthalmos include autosomal dominant and recessive inheritance, and sporadic cases have also been reported.Currently, at least six genes, including PRSS56, MFRP, TMEM98, MYRF, CRB1 and BEST1, have been reported to be associated with the onset of this disease.Common pathological phenotypes include short axial length, high hyperopia, and a high tendency to be complicated by angle-closure glaucoma and uveal effusion syndrome, etc.Different NNO genotypes show significant differences in clinical phenotypes.Studies on the correlation between NNO genotypes and phenotypes have provided an important basis for early clinical intervention.However, due to the limitated sample size of rare diseases, existing studies mainly focus on exploring the variant sites of different genotypes and the clinical phenotypes of patients.It is difficult to form a discussion on the overall correlation between the phenotypes and genotypes of NNO.This article collects and sorts out the research reports on NNO from 2010 to 2024, aiming to review the research progress on the correlation between genotypes and phenotypes of NNO from aspects such as gene mutation types and regional populations, in order to improve the understanding of NNO and provide more ideas and theoretical basis for studying its occurrence and development as well as gene therapy.

Immunotherapy,represented by immune checkpoint inhibitors(ICIs),has significantly changed the treatment status of most patients with malignant tumors.In order to regulate and guide the immunotherapy of cancer patients in China,the Chinese Society of Clinical Oncology(CSCO)has updated the Immune Checkpoint Inhibitor Clinical Practice Guidelines every year since 2020,which has been widely praised.The Version 2024 released this year has been significantly updated in terms of content,which can be summarized in five keywords as:"addition","deletion","upgrade","downgrade"and"definiteness",with the characteristic of a large overall update range,the continuous advancement of immunotherapy,continuous enrichment of combination strategies,more first-line treatment options,and excellent performance of several drugs.This article provides a point-to-point interpretation of major updates in the new guideline.

Objective:To explore the optimal labeling conditions of 177Lu-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)- D-Phe1-Tyr3-Thr8-octreotide (TATE), and evaluate its biodistribution and imaging characteristics in mice. Methods:The reaction temperature, pH, reaction time and other labeling conditions were changed to realize the rapid labeling of NOTATATE by 177Lu. The optimal labeling conditions, radiochemical purity, in vitro stability, plasma protein binding rate, and lipid-water partition coefficient were determined. Twenty-four normal KM mice were divided into 6 groups by random number table method. After injected with 3.7 MBq 177Lu-NOTATATE through tail vein, they were sacrificed at 0.5, 1, 4, 24 h and 4, 6 d respectively to research the biological distribution (injection dose rate per gram of tissue percentage, %ID/g). Six normal mice were randomly divided into 2 groups and injected with 11.1 MBq 177Lu-NOTATATE and 177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)TATE, respectively. SPECT planar imaging was performed at 1, 2, 3 h after injection. Another 8 mice were divided into 4 groups, injected with 3.7, 7.4, 18.5 MBq 177Lu-NOTATATE and saline respectively for an acute toxicity test. Results:At pH 5 and reaction temperature between 95 ℃ and 100 ℃ for 15 min, the labeling rate could reach more than 98%. After being placed in human serum for 24 h, the radiochemical purity was still higher than 95%. The plasma protein binding rate of 177Lu-NOTATATE was (58.6±1.9)% and the lipid-water partition coefficient was 0.048±0.014. In normal mice, the concentration of radioactivity is mainly in the liver, kidney and spleen, especially in the kidney (up to (29.120±1.204) %ID/g after 0.5 h of injection), which is less distributed in the blood and excreted rapidly. Compared with 177Lu-DOTATATE, 177Lu-NOTATATE was excreted faster by the kidney. The toxicity study results revealed that no damage was observed in mice of each group, and no obvious damage or inflammatory changes were observed in organ tissue sections. Conclusions:The optimal labeling condition of 177Lu-NOTATATE were determined in this study. The physical, chemical, and biological properties of 177Lu-NOTATATE were proved to be good and safe, and it was excreted faster by the kidney than 177Lu-DOTATATE. The results of this study lay a foundation for further clinical transformation research.

Objective:To synthesize 177Lu-prostate-specific membrane antigen (PSMA)-617 with domestic 177Lu (made in China), and explore its optimal labeling condition, biodistribution, stability, and safety. Methods:177Lu-PSMA-617 was prepared with domestic 177Lu by a manual method. The optimal labeling condition, radiochemical purity, stability ( in vivo and in vitro), lipid-water partition coefficient, and plasma protein binding rate were determined. The uptake rate of 177Lu-PSMA-617 was evaluated by using 22RV1 cells. Biodistribution and SPECT/CT imaging were performed on normal mice with imported 177Lu-PSMA-617 as control group. The blood routine test was performed to evaluate the safety. Results:The best labeling result of domestic 177Lu-PSMA-617 can be obtained under the following conditions: pH=4.5, 100 ℃ for 30 min. And the radiochemical purity was ≥99%. The product was stable in vivo and in vitro, with the radiochemical purity >95% in 72 h. The plasma protein binding rate was (35.3±5.3)%, the lipid-water partition coefficient was -2.27±0.06, and the specific uptake rate of domestic 177Lu-PSMA-617 by 22RV1 cells reached the highest in 1 h ((7.58±0.84)%), which was slightly lower than the imported 177Lu-PSMA-617 ((7.86±0.96)%), but there was no significant difference between them ( t=-0.439, P>0.05). The distribution and SPECT/CT imaging of normal mice showed that domestic and imported 177Lu-PSMA-617 in blood were cleared quite fast, and both of them were excreted mainly through the kidneys. No obvious adverse reactions were found in the toxicity test of domestic and imported 177Lu-PSMA-617. There was no obvious abnormality in blood routine and liver and kidney metabolism. Conclusion:The domestic 177Lu-PSMA-617 has many advantages, such as qualified quality control, good biological properties and safety, which support its potential application value in diagnosis of prostatic neoplasms.

Objective To screen and verify the proteins interacting with phosphorylation cluster of DNA dependent protein kinase catalytic subunit((DNA-PKcs) by yeast two-hybrid assay.Methods To know the proteins interacting with DNA-PKcs phosphorylation cluster,yeast two-hybrid assay was applied to screen the cDNA library of human hepatic tissue with a previously constructed plasmid pGBKT7-DPC.The positive clones were further identified by PCR,rotary validation and sequence analysis.Then the eukaryotic expression vectors of the bait protein and screened positive clone proteins were constructed and transfected into human embryonic kidney 293T cells to detect whether the proteins could been expressed correctly.At last,the bait protein and screened positive clone proteins were co-transfected into 293T cells and protein interaction was detected with Co-Immunoprecipitation (Co-IP) assay.Results After two rounds of screening using the yeast two-hybrid assay,12 candidate clones were obtained.Then 7 clones with different insert fragments were identified by PCR,and 3 positive proteins interacted with DNA-PKcs phosphorylation cluster were further verified by rotary validation.Sequencing analysis demonstrated that these 3 proteins were MBNL1,SIK2 and YY1AP1,respectively.Accordingly,the eukaryotic expression vectors of bait protein and 3 positive clone proteins were constructed successfully and expressed correctly in 293T ceils.Finally,the Co-IP assay confirmed that these 3 positive clone proteins could interact with DNA-PKcs phosphorylation cluster.Conclusions Proteins interacting with DNA-PKcs phosphorylation cluster are successfully screened and identified.

Objective To investigate the significance of miR-103 as noninvasive biomarker for diagnosis of nonalcoholic fatty liver disease (NAFLD).Methods The serum samples were collected from healthy subjects and NALFD patients to detect biochemical parameters.NucleoZOL method was used to isolate serum miRNA.SYBR Green qPCR was used for relatively quantitative analysis of miR103a-2.The correlations between miR-103a-2 and biochemical parameters were analyzed by Spearman method.Results Compared with healthy control group,the levels of total cholesterol (TC),triacylglyceride (TG),alanine aminotransferase (ALT) and glutamyl transpeptidase (γ-GGT) were all significantly increased in NAFLD group (P ＜ 0.01).Compared with the NAFLD group accompanying ortholiposis,the levels of TC,TG and low density lipoprotein-cholesterol (LDL-C) were all significantly increased in the NAFLD group accompanying dyslipidemia (P ＜0.01).Compared with the healthy control group,the level of serum miR-103a-2 increased in both NAFLD with ortholiposis group (P ＜ 0.05) and NAFLD with dyslipidemia group (P ＜ 0.01).The level of serum miR-103a-2 was positively correlated with serum TC (r =0.495,P =0.001).Conclusion Serum miR-103a-2 may be a more sensitive parameter for noninvasive screening of NAFLD than the parameters of blood lipid.

Objective To discuss the training effect driven by clinical demand in a cross-sectional research, and provide evidence for specialized nursing training.Methods One month before the survey, 46 nurses received various forms of comprehensive training, including multimedia lectures, workshop, case analysis, group discussion, clinical demonstration teaching of ostomy wound, research operations training, risk assessment training of pressure ulcer and incontinence associated dermatitis, etc. Then theory examinations, picture analysis examinations and operation examinations were conducted before and after training based on the unified papers and operating criteria. Results After training, the score of theoretical examination, operating examination and picture analysis examination of 46 nurses were higher than that before the training (P<0.05). 89.1% of nurses thought that the training content was very good;93.5% of nurses were satisfied with the training form, and 95. 7% of nurses thought that this training was significant for clinical work. Conclusions The comprehensive training method based on clinical demand can effectively improve the professional theory and skills of nurses, thus it can be used as a effective training and assessment methods before the survey of pressure ulcer and incontinence dermatitis in comprehensive hospitals.

Objective To screen specific human antibodies against Vibrio vulnificus hemolysin (VVH ) from natural single stranded large capacity phage antibody library and to perform initial identification of the antibodies,for the treatment of vibrio vulnificus infection.Methods The specific antibody against purified VVH was screened from large natural phage antibody library by 4 rounds of " adsorption-elution-amplification" screening process.Soluble ScFvs were prepared through infecting E coli.HB2151 and inducing expression with IPTG.The antigen binding activity and DNA sequence of the antibodies against VVH were identified by ELISA and DNA fingerprint analysis.Results After 4 rounds of panning,22 positive clones with specific binding ability to VVH were obtained,of which 8 obtained soluble expressions.DNA sequence analyses showed that the variable region genes of the clones belonged to different subgroups of immunoglobulin gene family.Conclusions The acquirement of human anti-VVH ScFv from large phage antibody library has laid a good foundation for the treatment of vibrio vulnificus infection.

Objective To screen specific human antibodies against Vibrio vulnificus hemolysin (VVH ) from natural single stranded large capacity phage antibody library and to perform initial identification of the antibodies,for the treatment of vibrio vulnificus infection.Methods The specific antibody against purified VVH was screened from large natural phage antibody library by 4 rounds of " adsorption-elution-amplification" screening process.Soluble ScFvs were prepared through infecting E coli.HB2151 and inducing expression with IPTG.The antigen binding activity and DNA sequence of the antibodies against VVH were identified by ELISA and DNA fingerprint analysis.Results After 4 rounds of panning,22 positive clones with specific binding ability to VVH were obtained,of which 8 obtained soluble expressions.DNA sequence analyses showed that the variable region genes of the clones belonged to different subgroups of immunoglobulin gene family.Conclusions The acquirement of human anti-VVH ScFv from large phage antibody library has laid a good foundation for the treatment of vibrio vulnificus infection.