AIM: To analyze the changes in binocular visual function before and after small incision lenticule extraction(SMILE)in patients with different degrees of myopia.METHODS:A prospective non-randomized controlled study was conducted. A total of 94 patients(188 eyes)who visited the refractive outpatient department of the ophthalmology department of the General Hospital of the PLA from June 2022 to June 2023 and voluntarily chose SMILE were consecutively included. They were grouped according to the degree of myopia, including 24 cases(48 eyes)in the low myopia group(-3.00 D

Objective To describe the characteristics and registration status of clinical trials of new drugs for nonalcoholic steatohepatitis (NASH), and to provide a reference for the design and implementation of clinical trials of new drugs for NASH. Methods The U.S. Clinical Trials Database, China Clinical Trial Registry, and Center for Drug Evaluation, National Medical Products Administration, were searched for clinical trials of new drug registration and interventional studies with NASH as the indication published up to August 6, 2021, using NASH in English and Chinese characters as the keywords, and liver cirrhosis was excluded. Two researchers independently searched and screened the articles to extract relevant information. Results A total of 196 clinical trials of new drug registration or interventional studies for NASH were included, among which there were 174 trials registered abroad and 22 trials registered in China, and the number of registrations tended to increase year by year. The numbers of phase Ⅰ, phase Ⅰ/Ⅱ(including Ⅰb/Ⅱa), phase Ⅱ, phase Ⅱ/Ⅲ, and phase Ⅲ clinical trials were 45(23.0%), 8(4.1%), 112(57.1%), 4(2.0%), and 19(9.7%), respectively. The main drug types included farnesoid X receptors, fibroblast growth factors, peroxisome proliferator-activated receptor agonists, and glucagon-like peptide-1, with numbers of 16(8.16%), 14(7.14%), 11(5.61%), and 13(6.63%), respectively. The clinical trials of innovative drugs for NASH initiated by the sponsors in European and American regions accounted for the highest proportion, and there was a gradual increase in the number of clinical trials of innovative drugs in China in recent years, with a similar distribution of single-center and multicenter clinical trials. As for the trials with NASH patients as subjects, the numbers of trials with pathology, imaging, and clinical diagnosis as the main inclusion criteria were 125, 66, and 42, respectively. Phase Ⅰ clinical trials used safety, tolerability, and pharmacokinetic parameters as the main assessment indices, while phase Ⅱ and phase Ⅲ clinical trials often used safety and efficacy as the main assessment indices. The number of clinical trials for the registration of innovative drugs for NASH was relatively low but kept increasing in China, and there were fewer clinical trials of innovative traditional Chinese medicine drugs compared with innovative chemical drugs. Conclusion There is a significant increase in the registration of international clinical trials of innovative drugs for NASH, and most of these trials are in the early phases, with large differences in inclusion criteria and assessment indices, a lack of unified evaluation indices, and relatively few trials with new designs. There are fewer clinical trials of innovative drugs for NASH in China than in European and American countries, and the number of such trials is gradually increasing in China.

Objective:To investigate the effect of transcatheter arterial chemoembolization (TACE) combined with ultrasound-guided radiofrequency ablation (RFA) on the efficacy and immune function in patients with primary liver cancer.Methods:The clinical data of 152 patients with primary liver cancer from February 2019 to February 2021 in the Second Affiliated Hospital of Xi′an Jiaotong University were retrospectively analyzed. Among them, 76 patients were treated with TACE combined with RFA (combined group), and 76 patients were treated with TACE (control group). The efficacy was compared; the α-L fucosidase, T lymphocyte subsets (CD 3, CD 4, CD 8 and CD 4/CD 8), B lymphocyte subsets (CD 19) and tumor markers (alpha-fetoprotein, AFP; carcinoembryonic antigen, CEA; carbohydrate antigen 125, CA125) before treatment and 1 month after treatment were detected. Results:The total clinical effective rate in combined group was significantly higher than that in control group: 81.58% (62/76) vs. 52.63% (40/76), and there was statistical difference ( χ2 = 4.54, P<0.05). There were no statistical difference in all indexes before treatment between 2 groups ( P>0.05); the α-L fucosidase, AFP and CD 8 1 month after treatment in combined group were significantly lower than those in control group: (18.06 ± 5.33) U/L vs. (26.58 ± 7.75) U/L, (87.93 ± 22.55) μg/L vs. (146.83 ± 21.85) μg/L and 0.295 ± 0.052 vs. 0.367 ± 0.064, the CD 3, CD 4 and CD 4/CD 8 were significantly higher than those in control group (0.489 ± 0.054 vs. 0.462 ± 0.063, 0.363 ± 0.059 vs. 0.303 ± 0.075 and 1.43 ± 0.27 vs. 0.89 ± 0.14), and there were statistical differences ( P<0.01 or<0.05); there was no statistical difference in CEA, CA125 and CD 19 1 month after treatment between 2 groups ( P>0.05). Conclusions:TACE combined with RFA in the treatment of primary liver cancer patients can not only improve the total clinical effective rate, but also significantly improve the immune function, and help to reduce level of the liver tumor marker of AFP.

OBJECTIVE: To explore the clinical characteristics and prognostic values of TP53 gene variant in patients with acute leukemia(AL). METHODS: The clinical data of 44 newly diagnosed AL patients with TP53 variant detected by next generation sequencing (NGS) were analyzed retrospectively. Targeted sequencing technique containing 108 leukemia-related genes was used for variant analysis, and conventional R-banding technique was used for karyotype analysis. The clinical features, cytogenetics, gene variant, curative effect and survival of AL patients with TP53 gene variant were analyzed. RESULTS: The median age of AML patients with TP53 gene variant (46 years) was higher than that of ALL patients (17.5 years), and the median number of bone marrow blasts (40.5%) was lower than the latter (89.2%), the differences were statistically significant (P< 0.01). A total of 28 cases of abnormal karyotype were detected, of which 25 cases were complex karyotype, 16 cases were monomeric karyotype, 14 cases had -17/17p-. The detection rates of TP53 in complex karyotype, monomeric karyotype and -17/17p- were 59.5%, 38.1% and 33.3%, respectively. Subgroup analysis showed that the detection rate of TP53 gene abnormalities in AML and ALL complex karyotypes was 73.1% and 40% respectively, the difference was statistically significant. A total of 41 TP53 gene variant types were found, and the median variant frequency was 43.58%. 75.6% variant was located in the DNA binding domain. The concomitant variant genes were mainly TET2 and IKZF1. Among 18 AML and 17 ALL patients who could be evaluated the curative effect, the CR rate of one course of treatment was 22.2% and 94.12% respectively, and the difference was statistically significant. The median RFS of 4 cases of AML with CR and 16 cases of ALL with CR were 174 and 246 days respectively, the difference was statistically insignificant. The median OS of AML and ALL was 20 and 375 days respectively, the difference was statistically significant. CONCLUSION The TP53 gene variant is associated with the complex karyotype of AML, but has no significant effect on ALL. The variant site of TP53 gene was mainly distributed in the DNA binding domain. The remission rate of AML with TP53 gene variant was lower than that of ALL. The prognosis of AL patients with TP53 gene variant is poor, so allogeneic hematopoietic stem cell transplantation should be performed as soon as possible to prolong the survival of the patients.
Acute Disease ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Mutation ; Retrospective Studies ; Tumor Suppressor Protein p53/genetics*

Objective To establish a neural network model based on enhanced CT for distinguishing ISUP grade of clear cell renal cell carcinoma (ccRCC). Methods We collected 131 cases of ccRCC, with 92 cases of low ISUP grade and 39 cases of high ISUP grade. Patients were divided into training set and validation set according to 5:5 stratified sampling. The enhanced CT images of each ccRCC patient were evaluated by the radiologist. Recursive feature elimination (RFE) was used to reduce the dimension of patients' general features and enhanced CT features, which was used for neural network modeling and validation. Results Patients' general features and enhanced CT features were verified by RFE method and then reduced to 14 features. The top 5 features were growth pattern, necrosis, enlargement of lymph nodes, tumor size and capsule. The AUC of the neural network model based on these 5 features in training set was 0.8844 (95%CI: 0.8062-0.9626), sensitivity was 89.47% and specificity was 82.61%; and those in validation set were 0.7924 (95%CI: 0.6567-0.9280), 75.00% and 86.96%, respectively. Conclusion The neural network model of ccRCC ISUP grade based on enhanced CT has relatively high diagnostic efficiency.

Objective:To describe the current status of registration and design characteristics of clinical trials of new drugs for curing hepatitis B through domestic and foreign websites, so as to provide references for the follow-up clinical trials of new hepatitis B drugs.Methods:A search was conducted on the US Clinical Trials Database and the Chinese Clinical Trial Registry Center. The search date was from the establishment of the database to May 26, 2020, and the registration trials of new drugs for curing hepatitis B at home and abroad were included. Two researchers independently searched and screened the literature and extracted the data.Results:A total of 106 registered clinical trials of new drugs for curing hepatitis B were included (94 English registration websites and 12 Chinese registration websites), and the number of registrations had increased year by year. Among them, the proportion of therapeutic vaccines and core protein inhibitors were the highest, accounting for 27.4% ( n = 29) and 22.6% ( n = 24), respectively. The vast majority of clinical trials ( n = 96, 90.6%) were in the early stages (Phase I and II). The subjects in phase I clinical trial were mainly healthy people and treated CHB patients, while the subjects in phase II clinical trial were mainly CHB patients who had achieved viral suppression after initial or post-treatment. The main evaluation indicators of Phase I clinical trials were the safety and tolerability of new drugs. The main evaluation indicators in about half of Phase II clinical trials were HBsAg negative conversion/quantitative decline. Overall, the number of clinical trials with the new design was small, accounting for 3.8% (4 / 106). There were relatively few trials of new drugs for curing hepatitis B on domestic registration websites, and the information provided was incomplete. Conclusion:The number of clinical trials of new hepatitis B drugs at home and abroad is increasing year by year, but most of them are in phase I and II, with few adopting new designs. In addition, the information integrity of the domestic website registration center needs to be improved.

The research and development of chronic hepatitis B (CHB) therapeutic drugs has been undergoing rapid development in recent years in order to achieve the World Health Organization's goal of eliminating viral hepatitis as a major public health threat by 2030. The focus of early stage clinical trials (including the first human trial) is the selection of subjects, study design, dose selection, administration method, dose escalation, monitoring, observation and reporting procedures for adverse events/reactions (tolerability evaluation), and criteria for subjects to continue and discontinue administration. Therefore, quantitative pharmacology knowledge is required to analyze the relationship between in vivo drug exposure, efficacy and adverse reactions, and the inclusion of exploratory indicators such as HBV RNA, hepatitis B virus core-related antigen (HBcrAg), etc., to analyze the mechanism and target of innovative drugs and the efficacy of cccDNA in anti-hepatocytes. On the other hand, Phase II-III clinical trials prioritize the optimal dose, efficacy and safety indicators to verify the efficacy and safety of new drugs in a wider range of subjects. This paper refers to the relevant domestic and foreign literature, combined with the author's practical experience in early clinical research, and then briefly introduces the clinical issues that should be paid attention to in the design of clinical trials of CHB innovative drugs.

BACKGROUND: Vernix caseosa (VC), which is known as a unique human substance, is a biofilm that covers the skin of most human newborns. VC has many biological functions including anti-infective, skin cleansing and skin barrier repair. OBJECTIVE: In the study, we purpose to investigate the novel effect of lipids extracted from VC on the regulation of filaggrin (FLG) expression and anti-inflammation in normal human epidermal keratinocyte (NHEK) cells. METHODS: The lipids were extracted by chloroform/methanol (Folch method) and the major properties of fatty acid methyl esters were determined with gas chromatography-mass spectrometer. The relative viability of NHEK cells was evaluated by Cell Counting Kit 8 assay. The related expression of skin barrier protein was accessed with real-time quantitative polymerase chain reaction, Western blot and Immunofluorescence in NHEK cells with or without poly (I:C). Meanwhile, the changes of thymic stromal lymphopoietin (TSLP) and tumor necrosis factor alpha (TNF-α) are analyzed by enzyme-linked immunosorbent assay. RESULTS: VC lipids mostly contained saturated and branched chains fatty acids. The expression of mRNA and protein of FLG were significantly increased after the supplement with lipid in NHEK cells. Meanwhile, lipids reversed the inhibition of poly (I:C) on FLG. Moreover, lipids suppressed the over secretion of TSLP and TNF-α induced by poly (I:C). CONCLUSION: These results indicate that lipids extracted from VC has positive effects on the expression of FLG and anti-inflammation, suggesting that lipids of VC may be used for a reference for novel therapeutic method in reducing and remedying skin disease like atopic disease.
Biofilms ; Blotting, Western ; Cell Count ; Enzyme-Linked Immunosorbent Assay ; Esters ; Fatty Acids ; Fluorescent Antibody Technique ; Humans ; Infant, Newborn ; Inflammation ; Keratinocytes ; Methods ; Polymerase Chain Reaction ; RNA, Messenger ; Skin ; Skin Diseases ; Tumor Necrosis Factor-alpha ; Vernix Caseosa

Objective To determine the expression of Caspase 8 and phospho-Akt(p-Akt)in condyloma acuminatum(CA)lesions, and to evaluate their significance. Methods Skin lesion samples were collected from 30 patients with CA, cancer tissue samples from 20 with cervical cancer, and normal skin samples from 20 healthy controls. All the samples were subjected to paraffin embedding. An immunohistochemical study was conducted to determine the expression and distribution of Caspase 8 and p-Akt in the above samples. Results The expression rate of Caspase 8 was significantly lower in CA lesions (23.33%)than in normal skin samples(90%, P < 0.01)and cervical cancer lesions(80%, P < 0.001). Moreover, the expression rate of p-Akt in CA lesions(93.33%)was significantly higher than that in the normal skin samples(90%, P<0.001), but lower than that in the cervical cancer lesions(95%, P<0.001). No significant correlations were observed between the expression of Caspase 8 and p-Akt in either CA lesions or normal skin samples. However, the expression of Caspase 8 was positively correlated with the expression of p-Akt in cervical cancer lesions(r=0.369, P<0.05). Conclusion Both suppressed apoptosis initiation of Caspase 8 and anti-apoptotic effect of p-Akt may be involved in the occurrence and development of CA.

Objective: To explore the advantage of radiofrequency catheter ablation under the three-dimensional mapping in the treatment of atrioventricular nodal reentrant tachycardia (AVNRT) in reducing the X-ray exposure dose of interventional doctors. Methods: 79 patients with AVNRT, in the first hospital of Shanxi Medical University from January 2015 to June 2016, performed to do radiofrequency catheter ablation treatment were selected, and according to the random number method were divided into two-dimensional mapping group and three-dimensional mapping group. The two-dimensional mapping group was mapped the ablation target at the X-ray, while the ablation target was mapped by CARTO 3 system in the three-dimensional mapping group. Compare the X-ray fluoroscopy time, success rate, complications rate and doctor’s X-ray exposure dose between the two groups. Results: Compared with the two-dimensional mapping group, acute success rate and complication rate of the three dimensional mapping group were not statistically significant (P>0.05) , while the X-ray fluoroscopy time and the X-ray dose of the three-dimensional mapping group decreased significantly, the difference was statistically significant (P<0.05) . Conclusion Three-dimensional mapping can significantly reduce the X-ray irradiation time and interventional doctor’s X-ray exposure dose in radiofrequency catheter ablation of AVNRT patients and the potential hazards of ionizing radiation on the human body.