1.Design, synthesis, and biological activity evaluation of photocaged cyclin-dependent kinase 2 inhibitors
Qingxiao WANG ; Xiaoyuan SUN ; Chunlei TANG ; Yan ZHANG
Journal of China Pharmaceutical University 2026;57(3):304-313
This study aimed to design and synthesize a series of novel photocaged compounds based on the precise binding mode of cyclin-dependent kinase 2 (CDK2) inhibitor AT7519 with its target, to achieve precise optical control over molecular activity. Using AT7519 as the structural foundation, different types of photoremovable protecting groups were introduced at its key interaction sites (the NH of the pyrazole ring and the NH of the piperidine ring), resulting in the synthesis of eight dual-photocaged compounds. Their structures were confirmed by NMR and mass spectrometry, and their photochemical properties—including photolysis wavelength, photolysis time, and photolysis efficiency—were systematically evaluated. The optically controlled inhibitory effects of the compounds on HCT116 cell proliferation were assessed using MTT assay. The photoresponsive characteristics of the photocaged compounds were significantly influenced by the type of photoremovable protecting group and its introduction site. Among them, compounds 1a, 1b, and 2d exhibited excellent photolysis efficiency, each achieving a rate exceeding 90%. Particularly, compounds 1b and 2d demonstrated excellent optically controlled activity: under dark conditions, their half maximal inhibitory concentration (IC50) values were both greater than 150 µmol/L, indicating negligible cell proliferation inhibitory activity; however, upon irradiation, their cell proliferation inhibitory activity significantly increased, with IC50 values comparable to those of the positive control AT7519. The obtained compounds 1b and 2d possess excellent optically controlled properties, and can be further investigated as potential candidates for optically controlled CDK2 inhibitors.
2.Clinical application value of intracavitary PRP infusion combined with IVF-FET in patients with chronic endometritis
Xiaotong ZHANG ; Xiaoyuan HAO ; Rui FANG ; Shuyao HU ; Linkun MA ; Yaqi ZHAO ; Wei HAN
Chinese Journal of Blood Transfusion 2025;38(3):382-387
[Objective] To evaluate the clinical application value of intrauterine perfusion with platelet-rich plasma (PRP) combined with in vitro fertilization-frozen-thawed embryo transfer (IVF-FET) in patients with chronic endometritis (CE). [Methods] A randomized controlled trial (RCT) was conducted, enrolling 60 CE patients undergoing artificial cycle frozen embryo transfer at our hospital from January 2022 to January 2024. Participants were randomly divided into three groups: Group A (routine frozen embryo transfer, n=20), Group B (routine frozen embryo transfer + one PRP intrauterine perfusion, n=20), and Group C (routine frozen embryo transfer + two PRP intrauterine perfusions, n=20). Endometrial thickness during the transformation and transplantation phases, uterine artery pulsatility index (PI), resistance index (RI), systolic peak velocity/end-diastolic velocity (S/D) ratio during transplantation, serum levels of IL-2, IL-4, IL-6, IL-10, and TNF-α during transplantation, as well as biochemical pregnancy rate, clinical pregnancy rate, live birth rate, and early miscarriage rate were compared across groups. [Results] No significant differences in endometrial thickness were observed among the three groups during the transformation phase (P>0.05). During the transplantation phase, endometrial thickness in Groups C and B was significantly higher than in Group A[9.54 (8.96-10.22) and 8.90 (8.34-9.72) vs 8.37 (7.89-8.75) mm, P<0.05], with Group C showing greater thickness than Group B (Z=3.733, P<0.05). Endometrial thickness in Groups C and B during transplantation was significantly increased compared to their respective transformation phases (Z=2.191, 2.462; P<0.05). Groups C and B exhibited lower PI, RI, and S/D values than Group A[PI:1.87 (1.77-1.97), 1.94 (1.88-2.15) vs 2.43 (2.35-2.49); RI:0.75 (0.73-0.77), 0.78 (0.75-0.81) vs 0.84 (0.83-0.86); S/D:2.61 (2.33-3.42), 3.01 (2.20-3.93) vs 3.72 (3.06-4.49); P<0.05]. Group C demonstrated lower PI and RI than Group B (P<0.05). IL-2 levels in Groups C and B were higher than in Group A[3.88 (2.71-5.01), 3.59 (2.73-4.38) vs 3.16 (2.11-3.25) ng/L, P<0.05], while IL-4, IL-6, IL-10, and TNF-α levels were significantly lower (IL-4: Z=1.428, 2.421; IL-6: Z=1.754, 2.435; IL-10: Z=1.754, 2.854; TNF-α: Z=1.961, 1.765; P<0.05). Group C had lower IL-6 levels than Group B (Z=3.976, P<0.05). Biochemical pregnancy rate, clinical pregnancy rate, and live birth rate in Group C were significantly higher than in Group A (75% vs 40%, 70% vs 35%, 60% vs 20%, P<0.05). No significant differences in early miscarriage rates were observed among the groups (χ2=3.750, P>0.05). [Conclusion] Intrauterine autologous PRP perfusion in CE patients enhances pregnancy and live birth rates, improves pregnancy outcomes post-FET, and demonstrates superior efficacy in endometrial repair and receptivity with two PRP perfusions compared to a single perfusion. This provides a safe and effective therapeutic option for optimizing outcomes in CE patients with prior implantation failure.
3.Analysis of Research Hotspots on"One Hospital with Multiple Campuses"Construction of Public Hospi-tals in China Based on CiteSpace
Xinwen XU ; Nan WEI ; Wenli WANG ; Chaobin WANG ; Xiaoyuan QU ; Yanli ZHANG
Chinese Hospital Management 2025;45(8):1-5
Objective It analyzes the current research status of the"one hospital with multiple campuses"construc-tion in public hospitals in China,focuses on research hotspots and evolution trends,and provides references for the research on"one hospital with multiple campuses"in public hospitals.Methods Using CiteSpace 6.3.R1 software,a visual analysis was conducted on 323 academic journal articles related to"one hospital with multiple campuses"in public hospitals from CNKI from 2014 to 2024.Results Over the past decade,the number of publications in this field has shown an overall upward trend;a core author group has initially formed but the density of the collaboration net-work is low;the institutions with the highest number of publications are mainly healthcare institutions and universi-ties;High-frequency keywords include public hospitals,homogenization,financial management,etc;research hot-spots generally show a trend from foundational construction to system integration,from extensive expansion to re-fined internal management,and from single-factor optimization to technology empowerment and multidimensional integration.Conclusion The research on the"one hospital with multiple campuses"construction of public hospitals in our country is clearly driven by policy,with research efforts distributed in a dual-core structure of"medical institu-tions-universities".However,interdisciplinary collaboration needs to be strengthened.Future research can focus on areas such as healthcare professionals,medical quality,the integration of business and finance systems,and inno-vation in emergency management mechanisms,providing support for the high-quality development of public hospi-tals with"one hospital with multiple campuses".
4.Analysis of the Development Path of"One Hospital With Multiple Campuses"in Public Hospitals in China from the Perspective of csQCA
Chaobin WANG ; Nan WEI ; Wenli WANG ; Xinwen XU ; Xiaoyuan QU ; Yanli ZHANG
Chinese Hospital Management 2025;45(8):6-9,14
Objective To explore the development path of"one hospital with multiple campuses"in public hospitals in China,and provide a reference for promoting the healthy and high-level construction of"one hospital with multiple campuses".Methods Based on the SPO theory,an analytical framework for studying the development path of"one hospital with multiple campuses"in public hospitals in China was constructed.Taking 41 tertiary public hospitals in 20 provinces that participated in the performance assessment and carried out the construction of"one hospital with multiple campuses"as the analysis objects,the hospital performance assessment data and the development data of"one hospital with multiple campuses"were collected.Crisp-Set Qualitative Comparative Analysis was used to explore different conditional configurations for the development of"one hospital with multiple campuses"in public hospitals in China,and to reveal the development path of"one hospital with multiple campuses"in public hospitals.Results The high-quality development path of"one hospital with multiple campuses"is the result of the combined action of multiple factors.The management structure path,support and promotion path,quality and safety path,and operation performance pathare the four configurations that promote the high-quality development of"one hospital with multiple campuses"in public hospitals.Among them,quality and safety are the necessary conditions for the high-quality development of"one hospital with multiple campuses".Conclusion There are multiple paths for the high-quality development of"one hospital with multiple campuses"in public hospitals.Hospitals need to select appropriate development strategies according to their own situations,ensure the homogenization of medical quality among different hospital districts,and form a joint force for the development of multiple hospital districts.
5.Prediction model for mortality of patients with femoral neck fracture in hospital
Lin TUO ; Dazhi ZHANG ; Deyong HUANG ; Xiaoyuan BAO
Chinese Journal of Orthopaedics 2025;45(5):280-287
Objective:To analyze the risk factors of in-hospital mortality in patients with femoral neck fracture and establish a prediction model for in-hospital mortality.Methods:From 2014 to 2023, a total of 4,028,102 hospitalized patients from six directly affiliated hospitals and two co-constructed affiliated hospitals of Peking University were retrospectively analyzed. Among them, 4,744 patients were hospitalized with femoral neck fractures, including 1,486 males and 3,258 females, aged 74±13.3 years (range, 19-103 years). Gender, age, length of hospital stay, hospitalization costs, preoperative comorbidities, treatment methods, anesthesia methods, and in-hospital mortality were extracted from the medical records. According to the presence or absence of in-hospital death, the patients were divided into death group and survival group. The differences in general data and clinical indicators between the two groups were compared, and the indicators with statistically significant differences were included in binary logistic regression analysis to screen the risk factors for in-hospital death in patients with femoral neck fracture. The receiver operating characteristic (ROC) curve for predicting in-hospital mortality of femoral neck fracture was drawn, and the area under the curve (AUC) was calculated.Results:There were 30 cases in the death group and 4,714 cases in the survival group, with a mortality rate of 0.63%. Among the dead patients, 20 had undergone hip replacement, and 10 had received non-surgical treatment. In the death group, age ( t=7.524, P<0.001), length of hospital stay ( t=3.802, P<0.001), hospitalisation cost ( t=3.961, P<0.001), rate of non-surgical treatment ( P<0.001), anaesthesia modality ( P=0.002), dementia ( P=0.045), malignant tumour ( P<0.001), renal insufficiency (χ 2=27.901, P<0.001), hypertension (χ 2=4.155, P=0.042), cerebral infarction (χ 2=8.271, P=0.004), urinary infections ( P=0.043), electrolyte disorders (χ 2=16.660, P<0.001), post-cholecystectomy ( P=0.070), abnormal liver function ( P=0.015), schizophrenia ( P=0.062), myocardial infarction (χ 2=19.057, P<0.001), diabetes mellitus with end-organ damage ( P=0.036), congestive heart failure (χ 2=93.122, P<0.001), and chronic obstructive pulmonary disease (χ 2=27.714, P<0.001) were greater than in the survival group, and the differences were statistically significance ( P<0.10). Bicategory logistic regression analysis showed age ( OR=1.08, P=0.008), non-surgical treatment ( OR=2.87, P=0.017), combined malignancy ( OR=9.35, P<0.001), renal insufficiency ( OR=4.07, P=0.004), hypertension ( OR=4.45, P=0.007), cerebral infarction ( OR=2.42, P=0.040), electrolyte disorders ( OR=4.29, P=0.009), schizophrenia ( OR=41.23, P=0.002), chronic obstructive pulmonary disease ( OR=3.84, P=0.002), and congestive heart failure ( OR=7.08, P<0.001) were the independent risk factors for in-hospital mortality of femoral neck fracture. The AUC and its 95% confidence interval (CI) for the predictive model were 0.908(0.84, 0.97), indicating excellent predictive value. Conclusion:Elderly, non-surgical treatment, malignant tumor, renal insufficiency, hypertension, cerebral infarction, electrolyte disturbance, schizophrenia, chronic obstructive pulmonary disease, congestive heart failure are associated with higher in-hospital mortality in patients with femoral neck fracture.
6.Evaluation of early outcomes and discussion of revisions of total hip arthroplasty in treatment for Kashin-Beck disease with hip problem
Haotian WU ; Xiaoyuan ZHANG ; Hui LI ; Yan KE ; Kai WANG ; Dan XING ; Zhichang LI ; Jianhao LIN
Chinese Journal of Orthopaedics 2025;45(6):335-342
Objective:To evaluate the early outcomes of total hip arthroplasty (THA) and discuss the revisions post THA in the treatment for Kashin-Beck disease (KBD) with severe hip problems.Methods:This retrospective cohort study enrolled 50 patients (64 hips) with a mean age of 52.4±8.7 years, including 25 male patients and 25 female patients (36 left hips and 28 right hips), who were diagnosed as KBD with hip problems and received THA at Arthritis Clinical and Research Centre, Peking University People's Hospital from October 2019 to January 2024. The leg length discrepancy (LLD), femoral offset (FO), abduction angle and anteversion angle were calculated preoperatively and one week post-operation. The postoperative radiological indexes and the functional outcomes in the last follow-up were compared with the preoperative assessment.Results:The surgical duration was 105(80, 120) min and the bleeding amount was 300(200, 400) ml. All the cases were followed up for an average of 37 months (ranging from 21 to 44 months). Significant differences were found on postoperative radiological images, with LLD improving to 0.50±0.78 cm from a preoperative value of -1.36±0.79 cm, and FO increasing to 3.28±1.01 cm from 2.72±0.83 cm ( P<0.05). The mean postoperative abduction angle and anteversion angle were 42.5°±7.7° and 15.1°±5.9°, respectively. A total of 71.8% and 95.3% hips fell within the Lewinnek safe zones of abduction angle and anteversion angle, respectively. In terms of functional outcomes, the average range of motion improved significantly to 185°(173°, 210°) from a preoperative value of 99°(76°, 123°), and the Harris Hip Score increased from 35(26, 43) preoperatively to 70(63, 80) postoperatively ( P<0.05). During the follow-up, there were complications for two cases of femoral stem loosening, one case of periprosthetic femoral fracture, one case of hip dislocation, and one case of acetabular component loosening with hip subluxation. Additionally, seven patients exhibited Trendelenburg gait. A total of five hips required revision surgery due to severe complications, including two cases of femoral stem loosening, one case of periprosthetic femoral fracture, one case of hip dislocation, and one case of acetabular component loosening with subluxation. Conclusions:Patients with KBD demonstrated significant early improvements in both radiological and functional outcomes following THA.
7.Screening of high risk children for lysosomal storage diseases and analysis of disease spectrum
Xueying SU ; Xiaoyuan ZHAO ; Yonglan HUANG ; Xi YIN ; Yanna CAI ; Li LIU ; Wen ZHANG
Chinese Journal of Pediatrics 2025;63(6):620-624
Objective:To screen high risk children for lysosomal storage diseases (LSD) in southern China and analyze the spectrum characteristics of LSD in this region.Methods:A cross-sectional study was conducted. A total of 7 435 children at high risk of LSD were screened at Guangzhou Women and Children′s Medical Center, Guangzhou Medical University from January 2009 to December 2024. The activities of 22 lysosomal enzymes from peripheral blood leukocytes or plasma were measured by fluorescence or colorimetric assays with synthetic substrates to screen for 24 LSD subtypes.Results:Among the 7 435 high risk children, 759 children were diagnosed with LSD (10.2%). The diagnosed cases included 506 males and 253 females, with an age at diagnosis of 3.0 (2.5, 5.5) years. The common disease types were mucopolysaccharidosis (MPS) (390 cases (51.4%)), sphingolipidoses (269 cases (35.4%)), glycogen storage disease (62 cases (8.2%)), and mucolipidosis types Ⅱ and Ⅲ (29 cases (3.8%)). Among the positive cases, 21 disease subtypes were identified. The 5 frequent subtypes, in descending order, were MPS type Ⅱ (197 cases (26.0%)), Gaucher disease (111 cases (14.6%)), MPS type ⅣA (87 cases (11.5%)), glycogen storage disease type Ⅱ (62 cases (8.2%)), and metachromatic leukodystrophy (MLD) (49 cases (6.5%)). The rarest subtypes were mannosidosis, multiple sulfatase deficiency and Wolman disease, each with 1 case (0.1%).Conclusions:Enzyme activity screening is essential for diagnosing high risk children with LSD. In Southern China, the most common LSD subtypes are MPS Ⅱ, Gaucher disease, MPS ⅣA, glycogen storage disease type Ⅱ, and MLD, while mannosidosis, multiple sulfatase deficiency and Wolman disease are the rarest.
8.Effects of family delivery room service combined with staged psychological intervention on labor progress and comfort in primiparas undergoing painless delivery
Xiaoyuan LI ; Yan MIAO ; Xin ZHANG ; Jing MENG
Journal of Navy Medicine 2025;46(2):205-209
Objective To explore the effects of family delivery room service combined with staged psychological intervention on labor progress and comfort in primiparas undergoing painless delivery.Methods A total of 200 primiparas with a gestational age of above 36 weeks who were admitted to Cangzhou People's Hospital between January 2020 and January 2024 were enrolled in this study.Their mean age was(28.94±4.38)years(range,20-38 years),and mean body weight was(69.31±6.83)kg(range,60-80 kg).They were divided into control group(100 cases,routine nursing)and observation group(100 cases,family delivery room service combined with staged psychological intervention).The progress of labor(the first,second and third stages of labor)was compared between the two groups.The comfort(general comfort questionnaire[GCQ]),pain(visual analogue scale[VAS]),psychological health(childbirth attitude questionnaire[CAQ],pregnancy-related anxiety questionnaire[PAQ],Edinburgh postnatal depression scale[EPDS])and nursing satisfaction were evaluated.Results The first and second stages of labor in the observation group were shorter than those in the control group([7.14±1.05]h vs[8.18±1.12]h,[1.05±0.14]h vs[1.22±0.16]h,P<0.05),but there was no significant difference in the third stage of labor between the two groups(P>0.05).After intervention,GCQ scores in the observation group were higher than those in control group,while VAS,CAQ,PAQ and EPDS scores in the observation group were lower than those in control group(P<0.05).The nursing satisfaction rate in the observation group was higher than that in the control group(86.00%vs 75.00%,P<0.05).Conclusion Family delivery room service combined with staged psychological intervention can alleviate negative emotions and pain during delivery,accelerate labor progress and improve comfort level in primiparas undergoing painless delivery.
9.Effect of exercise on the function and size of the liver in adolescents
Liyuan ZHANG ; Xiaoyuan GUO ; Hanze DU ; Shi CHEN ; Bo BAN ; Mei ZHANG ; Hui PAN
Basic & Clinical Medicine 2025;45(4):517-521
Objective To evaluate the effects of physical exercise on liver function and size in adolescents.Methods A total of 361 adolescent subjects from Jining,Shandong Province were selected and divided into low,moderate,and high-intensity exercise groups according to the frequency of moderate intensity exercise.Physical ex-amination tests were conducted including morphological indicators,blood biochemical indicator measurements,liver size and the presence of non-alcoholic fatty liver disease.Independent sample t-tests and variance analysis were per-formed using SPSS 26.0,and correlation analysis was conducted using Spearman correlation analysis and multivari-ate linear regression analysis.Results Compared with the moderate and low-intensity exercise groups,the high-intensity exercise group had significantly lower diastolic blood pressure,homeostatic model assessment of insulin resistance(HOMA-IR),and triglycerides(TG),as well as significantly higher height,maximum oblique diameter of the right liver lobe,and direct bilirubin(DBIL).Correlation analysis showed that as exercise intensity in-creased,aspartate aminotransferase/alanine aminotransferase,DBIL,and the maximum oblique diameter of the right liver lobe increased significantly(P<0.05).The results of the cumulative effect of exercise type and intensity indicate that exercise type does not influence the effect of exercise intensity on liver function and size.Conclusions Regular exercise in adolescents can not only shape body,but also improve glucose and lipid metabolism and en-hance liver function.
10.Association of tumor circumferential involvement range with neoadjuvant therapy efficacy and long-term outcomes in locally advanced rectal cancer
Ganbin LI ; Xiaoyuan QIU ; Xiao ZHANG ; Lai XU ; Beizhan NIU ; Guannan ZHANG ; Junyang LU ; Bin WU ; Yi XIAO ; Guole LIN
Chinese Journal of Oncology 2025;47(8):750-755
Objective:To detect the association of tumor circumferential involvement range (CIR) with neoadjuvant chemoradiotherapy (NCRT) efficacy and long-term survival outcomes in locally advanced rectal cancer (LARC) patients.Methods:Clinical data of 451 patients admitted to our hospital from January, 2018 to January, 2022 were retrospectively collected. According to the CIRs as determined by rectal magnetic resonance imaging, patients were divided into the High group (≥2/3 cycle, 270 patients) and the Low group (<2/3 cycle, 181 patients). The primary outcome was three-year disease-free survival. The baseline characteristics, pathological features, and survival outcomes were compared.Results:Compared to patients in the Low group, patients in the High group exhibited significantly larger tumor vertical diameters [(4.7±1.7) vs. (3.6±1.4)cm, P<0.001], higher rates of mrT4 stage (37.8% vs. 13.2%, P<0.001), and higher rates of positive mesorectal fascia (54.1% vs. 29.8%, P<0.001) and extramural vascular invasion (55.6% vs. 38.1%, P<0.001). Patients in the High group were mainly pT3-4 stages (46.7% vs. 30.9%, P=0.002), with significantly lower rates of pathological complete response (22.2% vs. 33.1%, P=0.010) , poorer tumor regression grades (48.9% vs. 60.8%, P=0.013), and higher rates of positive peripheral nerve invasion (11.5% vs. 5.5%, P=0.031), as compared to patients in the Low group. The median follow-up time was 40 months. About 11 (2.4%) and 48 patients (10.6%) experienced tumor local recurrence and distant metastasis, respectively. The recurrence rates were 2.2% and 2.6%, and the distant metastasis rates were 7.7% and 12.6%, respectively, in the Low group and the High group, with no statistical significance ( P=0.957, P=0.096). The three-year disease-free survival in the High group was significantly lower than that in the Low group (84.4% vs. 92.4%, P=0.014). Conclusions:The CIR is closely related to tumor burden, which can judge tumor response to NCRT, and is negatively related to survival prognosis. For patients who have more than a 2/3 cycle of CIR, intensified or consolidated treatments may be required to improve survival outcomes.

Result Analysis
Print
Save
E-mail