As a member of class I histone deacetylase (HDACs), HDAC8 is an important anticancer drug target. Based on our previously developed pharmacophore model for the HDAC8 inhibitor, we designed and synthesized 13 quinoline acid derivatives as new HDAC8 inhibitors. Among them, the compound SDFZ-E2 and SDFZ-E3 exhibited good HDAC8 inhibitory activities and isoform selectivity. In cell experiments, the target compounds SDFZ-E2 and SDFZ-E3 showed better antiproliferation activities than the known HDAC8 selective inhibitor PCI-34051. In addition, the proposed binding mode of SDFZ-E2 was investigated using molecular docking and molecular dynamics simulation. This work is a new attempt to develop HDAC8 selective inhibitor using quinoline as the scaffold, and the active compounds could serve as lead compounds for further structural optimization.

Objective:To analyze retinal vascular parameters and distribution characteristics in Chinese population via the fully automated quantitative measurement of retinal vascular morphological parameters based on artificial intelligence technology.Methods:A cross-sectional study was performed.A total of 1 842 patients without fundus diseases who visited Beijing Tongren Hospital from January 2011 to December 2021 were included.Standardized questionnaires, blood draws and ophthalmologic examinations of enrolled subjects were conducted.Color fundus photographs centered on the optic disk of one eye of patients were collected, and a deep learning-based semantic segmentation network ResNet101-Unet was used to construct a vascular segmentation model for fully automated quantitative measurement of retinal vascular parameters.The main measurement indexes included retinal vascular branching angle, vascular fractal dimension, average vascular caliber, and average vascular tortuosity.To compare different retinal parameters between sexes, the correlation between the above parameters and ocular factors such as best corrected visual acuity, intraocular pressure, and axial length, as well as systemic factors such as sex, age, hypertension, diabetes mellitus, and cardiovascular disease was analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Beijing Tongren Hospital, Capital Medical University (No.20001220). Written informed consent was obtained from each subject.Results:The model established in this study achieved an accuracy over 0.95 for both vascular and optic disk segmentation.The vascular branching angle, vascular fractal dimension, average vascular caliber, and average vascular tortuosity were (51.023±11.623)°, 1.573(1.542, 1.592), 64.124(60.814, 69.053)μm, (0.001 062±0.000 165)°, respectively.Compared with females, males had larger vascular branching angle, smaller average vascular caliber and smaller vascular tortuosity, and the differences were statistically significant (all at P<0.05). The average vascular caliber increased by 1.142 μm in people with cardiovascular disease compared to people without cardiovascular disease ( B=1.142, P=0.029, 95% CI: 0.116-2.167). The average vascular tortuosity was positively correlated with hypertension ( B=3.053×10 -5, P=0.002, 95% CI: 1.167×10 -5-4.934×10 -5) and alcohol consumption ( B=1.036×10 -5, P=0.014, 95% CI: 0.211×10 -5-1.860×10 -5) and negatively correlated with hyperlipidemia ( B=-2.422×10 -5, P=0.015, 95% CI: -4.382×10 -5-0.462×10 -5). For each 1-mm increase in axial length, there was a decrease of 0.004 in vessel fractal dimension ( B=-0.004, P<0.001, 95% CI: -0.006--0.002), a decrease of 0.266 μm in the average vessel caliber ( B=-0.266, P=0.037, 95% CI: -0.516--0.016), and a decrease of -2.45×10 -5° in the average vessel tortuosity ( B=-2.45×10 -5, P<0.001, 95% CI: -0.313×10 -5--0.177×10 -5). For each 1.0 increase in BCVA, there was an increase of 3.992° in the vascular branch angle ( B=3.992, P=0.004, 95% CI: 1.283-6.702), an increase of 0.090 in vascular fractal dimension ( B=0.090, P<0.001, 95% CI: 0.078-0.102) and a decrease of 14.813 μm in the average vascular diameter ( B=-14.813, P<0.001, 95% CI: -16.474--13.153). Conclusions:A model for retinal vascular segmentation is successfully constructed.Retinal vessel parameters are associated with sex, age, systemic diseases, and ocular factors.

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Objective To study the population genetic structure and phylogenetic relationships by combining Y-STR haplotype genetic information from the Han population in Dalian with 32 domestic and foreign groups.Methods Blood samples of 958 Han male volunteers from Dalian were collected.Genetic typing of 42 genetic loci was completed using Y-STR fluorescent reagent kits and capillary electrophoresis.Related forensic parameters were calculated.Nei's standard genetic distances among 33 populations based on 17 Y-STR loci were computed,in order to create a principal coordinate analysis as well as construct a phylogenetic tree.Results The analysis of genetic polymorphisms at 42 Y-STR loci revealed 30 unconventional alleles at 10 loci.Genetic analysis of the population based on 17 Y-STR loci confirmed that Dalian's Han population had the closest genetic distance to the Anshan's Han population,followed by populations from Henan,Heilongjiang,Jilin,Shandong,and Chongqing.Furthermore,the genetic distances between the Han population in Dalian and the Qiang population in Beichuan or the Miao population in Guizhou were relatively closer than that to the Manchu population living in Liaoning.Conclusion The genetic distance between the Han population in Dalian and other groups is not entirely proportional to ethnicities and geographical proximity.Both population migration and ethnic assimilation or isolation may have influence on it.

OBJECTIVE: To investigate a new noninvasive diagnostic model for nonalcoholic fatty liver disease (NAFLD) based on features of tongue images. METHODS: Healthy controls and volunteers confirmed to have NAFLD by liver ultrasound were recruited from China-Japan Friendship Hospital between September 2018 and May 2019, then the anthropometric indexes and sampled tongue images were measured. The tongue images were labeled by features, based on a brief protocol, without knowing any other clinical data, after a series of corrections and data cleaning. The algorithm was trained on images using labels and several anthropometric indexes for inputs, utilizing machine learning technology. Finally, a logistic regression algorithm and a decision tree model were constructed as 2 diagnostic models for NAFLD. RESULTS: A total of 720 subjects were enrolled in this study, including 432 patients with NAFLD and 288 healthy volunteers. Of them, 482 were randomly allocated into the training set and 238 into the validation set. The diagnostic model based on logistic regression exhibited excellent performance: in validation set, it achieved an accuracy of 86.98%, sensitivity of 91.43%, and specificity of 80.61%; with an area under the curve (AUC) of 0.93 [95% confidence interval (CI) 0.68-0.98]. The decision tree model achieved an accuracy of 81.09%, sensitivity of 91.43%, and specificity of 66.33%; with an AUC of 0.89 (95% CI 0.66-0.92) in validation set. CONCLUSIONS The features of tongue images were associated with NAFLD. Both the 2 diagnostic models, which would be convenient, noninvasive, lightweight, rapid, and inexpensive technical references for early screening, can accurately distinguish NAFLD and are worth further study.
Humans ; Non-alcoholic Fatty Liver Disease/diagnostic imaging* ; Ultrasonography ; Anthropometry ; Algorithms ; China

Objective:To evaluate the efficacy and safety of CD30 antibody-drug conjugates (ADC) brentuximab vedotin (BV) combined with chemotherapy in children with refractory or relapsed classic Hodgkin′s lymphoma (R/R cHL).Methods:Clinical data (including age, gender, B symptoms, clinical stage, previous treatment, etc.) of the 10 R/R cHL children diagnosed and treated at Beijing Children′s Hospital Affiliated to Capital Medical University from October 2021 to August 2023 were analyzed retrospectively. According to the different intensity of chemotherapy drugs, the dose of BV applied in the same course of treatment was 1.8 mg/kg for BV applied once every 3 weeks, and 1.2 mg/kg for BV applied once every 2 weeks. All 10 patients received at least 2 cycles of BV combined with chemotherapy and were evaluated every 2 cycles. The patients were followed up until May 31, 2024. The infusion reactions and adverse reactions after treatment were recorded.Results:In all 10 patients, there were 7 males and 3 females, the age ranged from 5.3-16.9 years, and there were 6 cases of refractory and 4 cases of relapsed. There were 6 cases of nodular sclerosis type, 2 cases of mixed cell type, 1 case of lymphocyte-rich type, and 1 case of lymphodepletion type. There were 5 cases of stage Ⅳ and 5 cases of stage Ⅲ. Previous treatment was mainly chemotherapy, 4 cases received radiotherapy and 1 case received programmed cell death protein 1 (PD-1) antibody therapy. The follow-up time ranged from 9 to 27 months. A total of 43 courses with 49 doses of BV alone or combined with chemotherapy were recorded, and the number of courses was 2 to 10 times. All 10 children responded to the treatment, and 9 achieved complete remission. BV infusion was successfully completed in all cases. A total of 28 cases of grade 3 or above adverse events were recorded, mainly myelosuppression, all of which were related to chemotherapy and did not affect sequential treatment.Conclusion:Brentuximab vedotin has demonstrated efficacy and a tolerable safety profile in the treatment of refractory and relapsed CD30-positive Hodgkin′s lymphoma in children.

Following the reform of the professional title system for"Breaking Four One-sided Evaluation Criteria"—focu-sing on more than just papers,titles,academic qualifications,and awards-establishing a scientific,systematic,and comprehen-sive medical performance evaluation index system has become essential for developing medical talent teams and conducting profes-sional title assessments fundamentally.This study establishes a medical performance evaluation index system tailored for clinicians in various departments of a cancer hospital who are competing for senior professional titles.This system comprises six primary in-dicators and 18 secondary indicators,with results presented in a ranked format of medical performance.Additionally,we have al-so analyzed the corr-elation between clinicians'medical performance rankings and their professional title evaluation outcomes through practical application.The results indicate that clinicians with higher performance rankings have significantly higher suc-cess rates in evaluations(P＜0.05).This index system underscores clinical practice,enhances classification-based evaluations,and supports advanced information management and precision in hospital administration,thereby providing a solid foundation for strengthening the hospital's core competitiveness.

A rapid analytical method for determination of paraquat and diquat in tea samples was established by improving the QuEChERS pre-treatment method combined with ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry(UPLC-MS/MS).Four kinds of tea powder were extracted by using acetonitrile-0.1％formic acid solution(3∶7,V/V)and ultrasonic treatment,and the supernatant was purified with 400 mg C18 and 400 mg PSA and separated on hydrophilic HILIC(100 mm×2.1 mm,1.8 μm)column by using 0.1％formic acid aqueous solution(Containing 5 mmol/L ammonium formate)and acetonitrile as mobile phases.In the electrospray ion source positive ion mode(ESI+),multiple reaction monitoring scanning technology(MRM)was used for determination,and the matrix-matched standard solution external standard method was used for quantitative analysis.The results showed that paraquat obtained good linear relationship in the content range of 0.18-200 μg/kg and diquat obtained good linear relationship in the content range of 0.36-200 μg/kg,and the correlation coefficients(R2)were 0.9939-0.9976 and 0.9959-0.9987,respectively.The limits of detection(LODs)were 0.06 and 0.12 μg/kg,and the limits of quantitation(LOQs)were 0.18 and 0.36 μg/kg,respectively.The average spiked recoveries for tea samples varied from 84.4％to 128.8％,with the relative standard deviations(RSDs)from 0.6％to 13.5％.The method was simple and efficient,with accurate quantification ability and low detection limit,which could realize efficient determination of paraquat and diquat in tea samples.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To compare the clinical effects of total hip arthroplasty(THA)with and without femoral osteotomy in Crowe Ⅳ developmental hip dislocation(DDH).Methods The data on 46 patients who underwent THA for unilateral Crowe ⅣDDH between 2012 and 2017 were analyzed retrospectively.They were divided into two groups according to the different surgical methods.There were 24 patients in the osteotomy group,3 males and 21 females,with an average age of(47.3±9.0)years old ranged from 34 to 57 years old;and 22 patients in the non-osteotomy group,2 males and 20 females,with an average age of(51.6±8.3)years old ranged from 40 to 61 years old.The operative time,bleed loss,postoperative drainage volume,postoperative com-plications,ROM of hip,Harris hip score,limb length discrepancy(LLD),and radiological data were recorded.The femoral dislo-cation height and the implantation depth of sleeve were measured.Results All patients were followed up.The mean follow-up time was(3.8±1.2)years ranged from 2 to 6 years in the osteotomy group and(3.2±0.9)years ranged from 1 to 5 years in the non-os-teotomy group.The operative time(136.8±18.9)min,bleed loss(709.8±89.4)ml,postoperative drainage volume(308.8±98.2)ml of osteotomy group were all significantly greater than those of non-osteotomy group(100.7±15.8)min,(516.5±103.3)ml,(245.3±79.3)ml(P＜0.05).The Harris score at the latest follow up was significantly increased compared with preoperative score in two groups(P＜0.05),but there was no significant difference between two groups(P＞0.05).The LLD at last follow up was sig-nificantly increased compared with preoperative LLD in two groups,the LLD in non-osteotomy group(0.7±0.2)cm showed signif-cant smaller than the two osteotomy group(1.2±0.4)cm.Between osteotomy and non-osteotomy groups,the preoperative range of motion of hip joint[(89.5±19.7)°vs(102.5±16.8)°],the preoperative height of dislocation of femoral head[(4.56±0.61)cm vs(3.10±0.73)cm],the proximal implant depth of S-ROM[(0.93±0.36)cm vs(1.67±0.28)cm]was significantly different(P＜0.05).Eleven patients in the osteotomy group still had claudication,and 4 patients in the non-osteotomy group had mild claudica-tion(P＜0.05).In non-osteotomy group,3 patients developed nerve injury(1 patient of sciatic nerve,2 patients of femoral nerve)and 1 case developed periprosthetic fracture.In osteotomy group,2 case of dislocation and 2 cases of periprosthetic fractures.Conclusion Whether osteotomy or not can achieve satisfactory results for treating Crowe type Ⅳ DDH and significantly improve LLD.However,osteotomy is more complex and time-consuming,limb length difference is greater,and the incidence of claudica-tion is higher.Furthermore,patients with smaller preoperative hip mobility,higher femoral dislocation,limb lengthening≥4 cm and severely narrow femoral proximal canals are prone to be peformed with subtrochanteric osteotomy.