Objective To evaluate the clinical value of a modified Cancer and Aging Research Group(CARG)model in guiding anticancer drug dose adjustments for elderly cancer patients in China.Methods This prospective study enrolled patients aged≥65 years with solid tumors at the Department of Oncology,Peking Union Medical College Hospital from September 1,2022 to October 29,2023.All patients underwent comprehensive geriatric assessment(CGA)and CARG risk scoring,and were stratified into low-,intermediate-,and high-risk groups.Anti-cancer drug doses(including chemotherapy,targeted therapy or immunotherapy)were reduced proportionally based on CARG risk stratification and treatment intent(curative vs.palliative).Treatment outcomes and adverse events(AEs)were recorded regularly.Fisher's Exact Test compared AE incidence between the CARG-guided dose adjust-ment group(experimental)and the physician-experience-guided dose adjustment group(control).Receiver operating characteristic(ROC)curve analysis was used to assess the predictive value of the CARG model for severe toxicity.Results Among 166 enrolled patients(median age:71 years[range:65-90];78.3%were male;68.7%had gastro-intestinal cancers;69.3%had stageⅣ),95 were assigned to the experimental group(CARG low-risk:24[25.3%],intermediate-risk:51[53.7%],high-risk:20[21.0%])and 71 were included into the control group.By December 31,2024,81 patients experienced disease progression and 10 patients died.Overall AE rates was 92.6%in the ex-perimental group and 94.4%in the control group,while grade≥3 AEs were recorded in 45.3%vs.43.7%,respec-tively(both P＞0.05).Conclusions The modified CARG model-guided dose adjustment strategy achieved comparable safety to empirical dose adjustment,which is in line with the individualized treatment paradigm for elderly cancer pa-tients,representing a structured framework for optimizing therapeutic decision-making in geriatric oncology.

Objective:To characterize the brain structure of Chinese children with autism spectrum disorder (ASD) using artificial intelligence automatic brain segmentation technique, and to analyze the correlation between the characteristics of the brain structure and the degree of brain development.Methods:A case-control study.The data of 52 children who were diagnosed with ASD according to the diagnostic criteria for ASD in the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition of the United States at the Department of Psychology of Qingdao University Affiliated Women and Children′s Hospital from January 2023 to April 2024 were prospectively analyzed.Meanwhile, 48 gender- and age-matched typically developing (TD) children in Qingdao were also included.The three-dimensional T1 weighted imaging sequences of all patients were obtained using a GE 3.0T magnetic resonance imaging scanner.Automated brain segmentation techniques were used to obtain the standardized volumes of each brain structure (the ratio of the absolute volume of the brain structure to the whole brain volume).Two-independent-samples t and Mann-Whitney U tests were used to compare the standardized volumes of different brain regions between the 2 groups.Pearson and Spearman correlation analyses were used to depict the correlations between volume data of brain areas with significant differences and Gesell Developmental Scale scores. Results:Compared with those in the TD group, the volumes of the left grey matter[25.45%(0.70%) vs.25.16%(1.05%)], the right grey matter [(25.89±0.71)% vs.(25.51±0.73)%], the right lateral orbitofrontal cortex [(0.62±0.03)% vs.(0.59±0.05)%], the right medial orbitofrontal cortex[(0.48±0.04)% vs.(0.46±0.04)%], the right pars triangularis [(0.38±0.07)% vs.(0.35±0.05)%], the left hippocampus [0.22%(0.04%) vs.0.20%(0.02%)], the right hippocampus [0.23%(0.04%) vs.0.22%(0.02%)], the left parahippocampal gyrus [0.15%(0.03%) vs.0.14%(0.02%)], the right parahippocampal gyrus [(0.15±0.02)% vs.(0.14±0.02)%], the left fusiform gyrus [(0.82±0.08)% vs.(0.78±0.08)%], the right superior temporal gyrus [(0.96±0.10)% vs.(0.90±0.09)%], the left insular lobe [(0.54±0.03)% vs.(0.53±0.04)%], the right insular lobe [(0.55±0.03)% vs.(0.53±0.04)%], the right inferior parietal cortex [(1.40±0.16)% vs.(1.33±0.12)%], the right precuneus cortex [(0.99±0.09)% vs.(0.94±0.09)%], the right putamen [(0.37±0.04)% vs.(0.35±0.03)%], the left pallidum [(0.14±0.01)% vs.(0.13±0.01)%], the right pallidum [0.14%(0.02%) vs.0.13%(0.01%)], and the right thalamus [(0.51±0.04)% vs.(0.49±0.03)%] were significantly increased in the ASD group (all P<0.05).Nonetheless, the volumes of the left pericalcarine cortex [(0.19±0.04)% vs.(0.20±0.04)%] and the corpus callosum posterior region [0.05%(0.01%) vs.0.06%(0.01%)] in the ASD group were considerably smaller than those in the TD group (all P<0.05).Correlation analysis showed that the right thalamus volume was negatively correlated with the Gesell-adaptation development quotient in children with ASD ( r=-0.276, P=0.048).The volumes of the left fusiform gyrus and left pericalcarine cortex were negatively correlated with the Gesell-fine motor development quotient in children with ASD ( r=-0.290, P=0.037; r=-0.368, P=0.007). The right precuneus cortex volume was negatively correlated with the Gesell-personal and social competence development quotient in children with ASD ( r=-0.396, P=0.007). Conclusions:Children with ASD show abnormalities in the volumes of multiple brain regions, and some brain regions are related to the degree of brain development.Automatic brain segmentation technology based on artificial intelligence can rapidly and directly measure and display the volume of brain structures in both ASD and TD children.

Objective:To characterize the brain structure of Chinese children with autism spectrum disorder (ASD) using artificial intelligence automatic brain segmentation technique, and to analyze the correlation between the characteristics of the brain structure and the degree of brain development.Methods:A case-control study.The data of 52 children who were diagnosed with ASD according to the diagnostic criteria for ASD in the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition of the United States at the Department of Psychology of Qingdao University Affiliated Women and Children′s Hospital from January 2023 to April 2024 were prospectively analyzed.Meanwhile, 48 gender- and age-matched typically developing (TD) children in Qingdao were also included.The three-dimensional T1 weighted imaging sequences of all patients were obtained using a GE 3.0T magnetic resonance imaging scanner.Automated brain segmentation techniques were used to obtain the standardized volumes of each brain structure (the ratio of the absolute volume of the brain structure to the whole brain volume).Two-independent-samples t and Mann-Whitney U tests were used to compare the standardized volumes of different brain regions between the 2 groups.Pearson and Spearman correlation analyses were used to depict the correlations between volume data of brain areas with significant differences and Gesell Developmental Scale scores. Results:Compared with those in the TD group, the volumes of the left grey matter[25.45%(0.70%) vs.25.16%(1.05%)], the right grey matter [(25.89±0.71)% vs.(25.51±0.73)%], the right lateral orbitofrontal cortex [(0.62±0.03)% vs.(0.59±0.05)%], the right medial orbitofrontal cortex[(0.48±0.04)% vs.(0.46±0.04)%], the right pars triangularis [(0.38±0.07)% vs.(0.35±0.05)%], the left hippocampus [0.22%(0.04%) vs.0.20%(0.02%)], the right hippocampus [0.23%(0.04%) vs.0.22%(0.02%)], the left parahippocampal gyrus [0.15%(0.03%) vs.0.14%(0.02%)], the right parahippocampal gyrus [(0.15±0.02)% vs.(0.14±0.02)%], the left fusiform gyrus [(0.82±0.08)% vs.(0.78±0.08)%], the right superior temporal gyrus [(0.96±0.10)% vs.(0.90±0.09)%], the left insular lobe [(0.54±0.03)% vs.(0.53±0.04)%], the right insular lobe [(0.55±0.03)% vs.(0.53±0.04)%], the right inferior parietal cortex [(1.40±0.16)% vs.(1.33±0.12)%], the right precuneus cortex [(0.99±0.09)% vs.(0.94±0.09)%], the right putamen [(0.37±0.04)% vs.(0.35±0.03)%], the left pallidum [(0.14±0.01)% vs.(0.13±0.01)%], the right pallidum [0.14%(0.02%) vs.0.13%(0.01%)], and the right thalamus [(0.51±0.04)% vs.(0.49±0.03)%] were significantly increased in the ASD group (all P<0.05).Nonetheless, the volumes of the left pericalcarine cortex [(0.19±0.04)% vs.(0.20±0.04)%] and the corpus callosum posterior region [0.05%(0.01%) vs.0.06%(0.01%)] in the ASD group were considerably smaller than those in the TD group (all P<0.05).Correlation analysis showed that the right thalamus volume was negatively correlated with the Gesell-adaptation development quotient in children with ASD ( r=-0.276, P=0.048).The volumes of the left fusiform gyrus and left pericalcarine cortex were negatively correlated with the Gesell-fine motor development quotient in children with ASD ( r=-0.290, P=0.037; r=-0.368, P=0.007). The right precuneus cortex volume was negatively correlated with the Gesell-personal and social competence development quotient in children with ASD ( r=-0.396, P=0.007). Conclusions:Children with ASD show abnormalities in the volumes of multiple brain regions, and some brain regions are related to the degree of brain development.Automatic brain segmentation technology based on artificial intelligence can rapidly and directly measure and display the volume of brain structures in both ASD and TD children.

BACKGROUND:Accurate reduction of ankle fractures under direct vision has become a common understanding among foot and ankle surgeons.How to fully expose free or compressed fragments of the posterior ankle remains one of the most challenging problems. OBJECTIVE:To explore the clinical efficiency of the para-Achilles tendon approach in exposing and repositioning the posterior malleolus sandwich fracture. METHODS:A retrospective study was made for 26 patients with posterior malleolus sandwich fracture treated with open reduction and internal fixation via para-Achilles tendon approach from January to December 2020 in The Second People's Hospital of Dalian.21 of 26 cases were managed with the lateral approach of Achilles tendon and 5 cases were managed with the medial approach of Achilles tendon.There were 19 males and 7 females,with the age of 24-69 years,averagely 38.6 years.The operation time and postoperative complications were recorded.The fracture reduction condition was evaluated by Burwell-Charnley imaging standard.Before operation,3 months after operation and last follow-up,visual analog scale score,ankle plantar flexion and dorsiflexion and American Orthopedic Foot&Ankle Society Ankle Hind Score were used to evaluate the treatment effect. RESULTS AND CONCLUSION:(1)All 26 patients were followed up for an average of 14.6 months(range 13-18 months).The operation time was 52-85 minutes(average 64.2 minutes).(2)Part of the skin edge of the lateral malleolus incision was necrotic in one patient and healed completely after a dressing change.Incision healing of the other patients was in one stage.(3)Through Burwell-Charnley imaging standard,anatomical reductions were obtained in 24 of 26,and good reductions were in 2 of 26,with an excellent and good rate of 100%.(4)At the last follow-up,the visual analog scale score(1.19±0.40)was significantly lower than the preoperative score(6.81±0.80)(P<0.01).Ankle plantar flexion(33.5±5.02)° and ankle plantar back stretch(17.23±0.99)° were significantly increased compared with preoperative data(14.58±2.50)° and(5.81±1.02)°(P<0.01).American Orthopedic Foot&Ankle Society Ankle Hind Score was improved to(89.31±3.62)points compared to preoperative(46.00±5.45)points(P<0.01).The results were excellent in 23 patients and good in 3 patients,with an excellent and good rate of 100%.(5)It is concluded that the open reduction and internal fixation via the para-Achilles tendon approach for the treatment of posterior malleolus sandwich fracture were efficient with decreased operation time,satisfying fracture reduction,fewer complications,satisfactory motion range,and functional recovery.

Fusobacterium nucleatum (F. nucleatum) is an early pathogenic colonizer in periodontitis, but the host response to infection with this pathogen remains unclear. In this study, we built an F. nucleatum infectious model with human periodontal ligament stem cells (PDLSCs) and showed that F. nucleatum could inhibit proliferation, and facilitate apoptosis, ferroptosis, and inflammatory cytokine production in a dose-dependent manner. The F. nucleatum adhesin FadA acted as a proinflammatory virulence factor and increased the expression of interleukin(IL)-1β, IL-6 and IL-8. Further study showed that FadA could bind with PEBP1 to activate the Raf1-MAPK and IKK-NF-κB signaling pathways. Time-course RNA-sequencing analyses showed the cascade of gene activation process in PDLSCs with increasing durations of F. nucleatum infection. NFκB1 and NFκB2 upregulated after 3 h of F. nucleatum-infection, and the inflammatory-related genes in the NF-κB signaling pathway were serially elevated with time. Using computational drug repositioning analysis, we predicted and validated that two potential drugs (piperlongumine and fisetin) could attenuate the negative effects of F. nucleatum-infection. Collectively, this study unveils the potential pathogenic mechanisms of F. nucleatum and the host inflammatory response at the early stage of F. nucleatum infection.
Humans ; Fusobacterium nucleatum/metabolism* ; NF-kappa B/metabolism* ; Periodontal Ligament/metabolism* ; Signal Transduction ; Fusobacterium Infections/pathology* ; Stem Cells/metabolism*

【Objective】 To observe the effects of paternal age on the pregnancy outcomes in frozen embryo transfer (FET) cycles. 【Methods】 The clinical data of two groups after propensity score matching (PSM) were retrospectively analyzed, including 738 cycles in the <40 year group and 387 cycles in the 40-60 year group. The differences in general information and pregnancy outcomes were compared between the two groups, and logistic regression analysis of pregnancy outcomes were conducted. 【Results】 There were no statistical differences in age, duration of infertility, female body mass index (BMI), infertility factors, fertilization method, endometrial preparation methods, endometrial thickness on the day of transformation, stage of embryo transfer, number of embryos transferred, and number of high-quality embryos between the two groups after PSM (P>0.05). The clinical pregnancy rate (52.2%vs. 67.2%) and live birth rate (41.1% vs. 57.2%) decreased in the 40-60 year group compared with those in the <40 year group (P<0.001), but there was no statistical difference in abortion rate (19.8% vs. 13.7%) (P>0.05). 【Conclusion】 Advanced paternal age decreases clinical pregnancy rate and live birth rate.

Objective:To evaluate the new model of group screening combined with opportunistic screening for the diagnosis and treatment of gastric cancer.Methods:Group screening combined with opportunistic screening was used for gastric cancer screening. (1) Group screening. Cluster sampling was used to screen gastric cancer by endoscopy in high-risk population (aged 40-<70 years) of rural residents in Weihai from July 2017 to December 2020, and biopsy was obtained for histopathology if necessary. Main collection parameters included the detection rate of advanced gastric cancer, early gastric cancer and high-grade intraepithelial neoplasia (HGIN). (2) Opportunistic screening. The changes of the detection rates of early gastric cancer in opportunistic screening in 2 hospitals in Weihai area were observed during the same period of time.Results:(1) In group screening, from July 2017 to December 2020, the first batch of 8 000 cases of gastric cancer screening were completed. The cases of advanced gastric cancer, early gastric cancer and HGIN were 36, 28, and 62, respectively. The detection rates of gastric cancer and early gastric cancer were 0.80% (64/8 000) and 43.75% (28/64), respectively. The proportion of early gastric cancer+HGIN who received endoscopic submucosal dissection (ESD) was 77.78% (70/90), and the rate of curative resection was 100.00%(70/70). (2) Opportunistic screening: from July 2017 to December 2020, the annual early gastric cancer detection rates in opportunistic screening in Wendeng District Traditional Chinese and Western Medicine Hospital were 16.67% (1/6), 20.00% (3/15), 23.53% (4/17), and 33.33% (6/18) in the consecutive 4 years, respectively. The annual detection rates of early gastric cancer in opportunistic screening in Ru Shan Peoples Hospital were 14.74% (14/95), 23.80% (60/252), 25.49% (65/255), and 24.04% (50/208), respectively. The detection rates of opportunistic screening for early gastric cancer in hospitals in Weihai city increased year by year.Conclusion:In areas with high incidence of gastric cancer, a certain scale of group screening can lead to a wider range of opportunistic screening, resulting in the increase of the detection rate of early gastric cancer. The new model of diagnosis and treatment of gastric cancer is worth recommendation.

Objective:To evaluate the clinical outcomes of Chaput tuberosity osteotomy and lateral malleolus sagittal osteotomy in the treatment of talus osteochondral lesions with autologous osteochondral transplantation (AOT).Methods:From January 2017 to December 2019, Chaput tuberosity osteotomy and lateral malleolus sagittal osteotomy were performed in the AOT treatment of 11 patients with talus osteochondral lesions. They were 9 men 2 women, with a mean age of 32. 6 years (range, from 22 to 45 years). Their lesions were all Hepple type V. Their American Orthopaedic Foot and Ankle Society (AOFAS) score, visual analogue scale (VAS), International Knee Documentation Committee Knee Evaluation Form (IKDC) score, and imaging data were measured pre- and post-operatively for assessment of clinical outcomes.Results:All the patients were followed up for 13 to 24 months (average, 15.6 months). Their AOFAS (94.3±2.9) and VAS (1.2±0.4) scores at the final follow-up were significantly improved compared with the pre-operative values (49.5±6.6 and 5.7±1.2) ( P<0.05). There was no significant difference between their pre- and post-operative IKDC scores for the ipsilateral knee joint ( P>0.05). The imaging showed that the talus cystic change disappeared and the grafted bone was fully fused with the talus with no abnormal change in the joint space. Conclusion:In the AOT treatment of talus osteochondral lesions, Chaput tuberosity osteotomy and lateral malleolus sagittal osteotomy can obviously relieve ankle pain and improve ankle function.

Autism spectrum disorder (ASD), a representative disease of children's neurodevelopmental disorders, brings huge pressure and financial burden to families and society. It is of great significance to explore its etiology and pathogenesis. Therefore, we established an ASD Cohort based on the existing China National Birth Cohort (CNBC), which applied parallel design to recruit and follow up families who achieved pregnancy after receiving assisted reproductive technologies (ART) and families with spontaneous conception. The main aims of this study are to compare the incidence of ASD among children born after ART with those born under spontaneous pregnancy, and to evaluate the impact of ART on the neurobehavioral development of offspring. Additionally, with a variety of clinical and behavioral related information collected during pregnancy and at early life of offspring, we are able to investigate the risk factors associated with ASD comprehensively. This article briefly introduces the objectives, contents, preliminary progress, strength and limitations, as well as further prospects of the ASD cohort study, mainly focusing on the overall design and current progress.

Objective:To evaluate the retinal differentiation ability of human induced pluripotent stem cells (hiPSCs) from various somatic cell sources.Methods:The hiPSCs lines BC1- green fluorescent protein (GFP) and Gibco obtained by blood cell reprogramming and the hiPSCs line UE017 obtained by urine cell reprogramming were used to induce retinal differentiation.The morphogenesis and development of retina were recorded with an optical microscope, and the expression of specific molecular markers of various cell subclasses in the retina was detected by immunofluorescence, and the efficiency of retinal differentiation of different cell lines was analyzed and compared.Results:All three hiPSC lines derived from blood and urine cells were able to be induced into three-dimensional (3D) retinal organoids, including neuroretina and retinal pigment epithelial cells.Retinal organoids simulated the development process of retina in vivo and gradually differentiated into all cell subtypes of retina, including retinal ganglion cells, photoreceptor cells, amacrine cells, horizontal cells, bipolar cells, Müller cells, and even formed lamellar structures.However, in terms of the efficiency of acquiring retinal organoids, the hiPSCs derived from blood were more efficient than those derived from urine. Conclusions:hiPSCs from both blood and urine somatic cells can differentiate into 3D retinal organoids, including all subtypes of retinal cells.The differentiation efficiency among lines is different.