OBJECTIVE: To explore the genotype-phenotype correlation in a Chinese family with structural brain abnormalities due to variant of the TUBB gene. METHODS: A family undergoing prenatal diagnosis at Beijing Obstetrics and Gynecology Hospital in October 2024 was selected as the study subject. Clinical data were collected. Amniotic fluid sample was subjected to chromosomal copy number variation sequencing (CNV-seq). Trio whole-exome sequencing (Trio-WES) was carried out on the amniotic fluid and parental blood samples, and candidate variant was verified by Sanger sequencing. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2023-KY-076-01). RESULTS: Both prenatal ultrasound and fetal MRI showed deviation of brain midline, unilateral lateral ventriculomegaly, and bilateral gyral asymmetry. Trio-WES revealed that the fetus has harbored a maternally derived heterozygous missense variant of the TUBB gene [NM_178014.4: c.155A>G (p.N52S)]. Sanger sequencing confirmed that the woman and a previously terminated fetus both harbored the same variant. Both the proband and two fetuses exhibited similar neuroimaging abnormalities including midline deviation and asymmetrical gyri. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_Supporting+PS2_Moderate+PS3). CONCLUSION The heterozygous c.155A>G (p.N52S) variant was the TUBB gene probably underlay the pathogenesis of the structural brain abnormalities in this family. Above findings have expanded the phenotypic spectrum associated with the variant and facilitated the prenatal diagnosis for this family.
Humans ; Female ; Pregnancy ; Prenatal Diagnosis ; Tubulin/genetics* ; Adult ; Brain/diagnostic imaging* ; Male ; Pedigree ; DNA Copy Number Variations/genetics* ; Exome Sequencing ; Genetic Association Studies ; Magnetic Resonance Imaging

Diabetic retinopathy(DR), the most common microvascular complication of diabetes, has become a leading cause of visual impairment and blindness across all age groups. The early diagnosis and severity assessment of DR rely on the precise evaluation of retinal microvascular alterations. The periarterial capillary-free zone(paCFZ), a physiological avascular region surrounding retinal arteries, has recently been recognized as an important biomarker reflecting the status of retinal microcirculation. Advances in optical coherence tomography angiography(OCTA)have enabled noninvasive, high-resolution quantification of the paCFZ, offering a novel approach for the early detection and stratification of DR. This review systematically summarizes the definition and developmental mechanism of the paCFZ, as well as its morphological characteristics across different stages of DR, with a particular focus on the advantages of OCTA in visualizing and quantifying the paCFZ. We further discuss the differential manifestations of the paCFZ in nonproliferative DR and proliferative DR, and its associations with retinal ischemia and oxygenation status. In addition, the potential clinical value of paCFZ in evaluating responses to anti-vascular endothelial growth factor(VEGF)therapy and predicting disease progression is summarized. Finally, the challenges in clinical translation and future research directions are addressed, aiming to provide theoretical support and new perspectives for early screening, risk stratification, and personalized management of DR.

AIM: To explore the effects of preoperative anterior segment parameters on the rotational stability of Toric intraocular lens(Toric IOL).METHODS:Prospective study. A total of 41 cataract patients(54 eyes)with combined corneal regular astigmatism from March to December 2023 were included and treated with cataract phacoemulsification combined with plate loop Toric IOL implantation in the Department of Ophthalmology of the First Affiliated Hospital of Zhengzhou University. The rotation degree of Toric IOL and uncorrected distance visual acuity(UCDVA)were evaluated at 1 d, 2 wk, and 1 mo postoperatively, the corrected distance visual acuity(CDVA)was evaluated at 2 wk and 1 mo after surgery, and the decentration and tilt of the Toric IOL were assessed at 2 wk postoperatively.RESULTS:A total of 33 patients(40 eyes)were included in this study. The UCDVA(LogMAR)of 1 d, 2 wk and 1 mo postoperatively were 0.10(0.10, 0.30), 0.05(0, 0.10)and 0(0, 0.10), respectively, which was improved compared with the preoperative levels of [0.80(0.49, 1.00)](P<0.001). The CDVA(LogMAR)of 2 wk and 1 mo postoperatively were 0.05(0, 0.15)and 0(0, 0.138), respectively, which was improved compared with preoperative levels of [0.52(0.40, 0.80)](P<0.001). The residual astigmatism of 2 wk and 1 mo postoperatively were 0.625(0.25, 0.75)D and 0.50(0.25, 0.75)D, respectively, which was significantly reduced compared with preoperative astigmatism of [1.82(1.31, 2.59)D](P<0.001). The preoperative anterior segment length(ASL), and lens thickness(LT)were positively correlated with Toric IOL rotation degree at 1 d(rs=0.463, P=0.003; rs=0.340, P=0.032)and 2 wk(rs=0.520, P=0.001; rs=0.409, P=0.009)postoperatively. At 1 mo postoperatively, only ASL was positively correlated with Toric IOL rotation degree(rs=0.463, P=0.003). The results of linear regression analysis showed that preoperative ASL was a predictor of rotation degree at 1 d, 2 wk and 1 mo after surgery(F1 d=10.098, P1 d=0.003; F2 wk=16.915, P2 wk<0.001; F1 mo=10.957, P1 mo=0.002). The rotation degree of Toric IOL was positively correlated with lens decentration(rs=0.360, P=0.043).CONCLUSION:The early postoperative rotation of Toric IOL is positively correlated with ASL, and the rotation is also positively correlated with lens decentration.

BACKGROUND:Wolff's law points out that the lack of mechanical stress in the body will lead to the degradation of the microstructure of bone tissue,mass loss,and metabolic disorders,and eventually lead to osteoporosis,which suggests that mechanical stress plays an important role in the growth,reconstruction,and formation of bone tissue.At present,the relevant studies concerning mechanical stress on osteoblasts mainly focus on fluid shear force,but it is difficult to intervene in vivo.Meanwhile,some studies have found that compressive stress can also play a similar role in fluid shear force to a certain extent.Exploring the mode of action and influence of compressive stress on cells in vitro experiments can enrich the interaction relationship between mechanical stress and cells.It helps provide a theoretical basis for studies of metabolic bone diseases,including osteoporosis,and other diseases.OBJECTIVE:To review in vitro experiments,the application of compressive stress to cells,different biological behaviors caused by cells,the possible signaling pathways,and possible future applications.METHODS:We searched PubMed,Web of Science,CNKI,and WanFang databases from January 2000 to March 2024 to include all articles related to compressive stress on cells,including basic research and microscopic mechanism studies,using search terms"compressive stress,mechanical stress,hydrostatic pressure,cell"in Chinese and English.Finally,the 63 included articles were reviewed.RESULTS AND CONCLUSION:(1)There are various ways to apply compressive stress,and different experimental equipment has different ways of pressurizing cells,so it is necessary to further standardize the experimental equipment,standardize the pressurization unit,reduce the confounding factors,and make the reference and comparability between different experimental groups.(2)Compressive stress can cause changes in cell proliferation,differentiation,autophagy,apoptosis,migration,etc.,and the effect of compressive stress is time-or dose-dependent in most cases.(3)At present,most in vitro experimental studies have shown that compressive stress may mainly act on osteoblasts through MAPK signaling pathway and Wnt/β-catenin signaling pathway,causing osteoblasts to produce different responses.(4)The effect of compressive stress on different cells is not the same,and its possible biological effects need to be studied.(5)Further research on compressive stress is helpful to provide a theoretical basis for treatment in orthopedics,stomatology,tumors and other fields,and gentle disinfection using hydrostatic pressure is a promising disinfection method.

Objective To analyze the efficacy of hepatic arterial infusion chemotherapy(HAIC)sequential drug-eluting beads transcatheter arterial chemoembolization(DEB-TACE)in the treatment of liver metastases from colorectal cancer.Methods 86 patients with colorectal cancer liver metastasis admitted to multiple centers from September 2022 to September 2023 were selected and divided into a control group(43 cases)and an experimental group(43 cases)according to the random number table method.The control group was treated with HAIC,and the experimental group was treated with HAIC sequential DEB-TACE.The clinical data and the changes of tumor markers and liver function indexes before and after treatment were compared between the two groups,and the short-term and long-term efficacy was evaluated,and the adverse reactions were recorded.Results After treatment,the levels of carcinoembryonic antigen,carbohydrate antigen 125,carbohydrate antigen 199,carbohydrate antigen 242,aspartate aminotransferase,alanine aminotransferase,alkaline phosphatase and γ-glutamyl transpeptidase in the two groups decreased(P<0.05),and those in the experimental group were lower than the control group(P<0.05).The proportion of repeated treatment in the experimental group was lower than that in the control group(P<0.05).The objective remission rate and disease control rate in the experimental group were 60.00%and 82.50%respectively,which were higher than 30.95%and 61.90%in the control group(P<0.05).There was no significant difference in the incidence of adverse reactions between the control group and the experimental group(P>0.05).The results of Kaplan-Meier survival curve showed that the overall survival rate and progression-free survival rate of the experimental group were higher than those of the control group(P<0.05).Conclusions HAIC sequential DEB-TACE can effectively remove tumor cells and improve liver function in patients with colorectal can-cer liver metastasis,and it has good clinical efficacy and can prolong the survival time of patients.

Objective:To compare the mydriatic effects of a combination of 1% tropicamide and 2.5% phenylephrine with a 0.5% tropicamide and 0.5% phenylephrine combination in patients with type 2 diabetes.Methods:A randomized, double-blind, controlled trial was conducted.Ninety Chinese patients (90 eyes) with dark irises and type 2 diabetes who needed mydriasis examination at the Fundus Disease Clinic of Tianjin Medical University Eye Hospital from June to September 2024 were included.The subjects were divided into control group (30 patients 30 eyes), high concentration group (30 patients 30 eyes) and half-dilution group (30 patients 30 eyes) using the random number table method, which received 2 drops of a mixture of 0.5% tropicamide and 0.5% phenylephrine, 2 drops of a mixture of 1% tropicamide and 2.5% phenylephrine, 1 drop of a mixture of 1% tropicamide and 2.5% phenylephrine+ 1 drop of saline respectively.The pupil diameter of the patients was measured with a pupillometer 40 minutes before and after instillation.The study adhered to the Declaration of Helsinki and the study protocol was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (No.2024KY-16).Written informed consent was obtained from all participants.Results:The proportions of patients whose pupil diameters reached 7 mm 40 minutes after the initial administration in the control group, high-concentration group, and half-dilution group were 56.7%(17/30), 86.7%(26/30) and 66.7%(20/30), respectively, with a statistically significant overall difference ( χ2=6.667, P=0.036).The proportion of patients in the high-concentration group whose pupil diameter reached 7 mm 40 minutes after the initial administration was higher than that in the control group, and the difference was statistically significant ( P<0.05).The pupil diameters 40 minutes after the initial administration in the control group, the high-concentration group and the half-dilution group were (7.01±0.86), (7.64±0.61) and (7.49±1.15)mm, respectively, with a statistically significant overall difference ( F=4.019, P=0.021), and the pupil diameter of the high-concentration group was significantly higher than that of the control group ( P=0.024).Changes in pupil diameter 40 minutes after the initial administration in the control group, high-concentration group and half-dilution group were (3.23±0.81), (3.82±0.60) and (3.62±0.75)mm, respectively, with a statistically significant overall difference ( F=5.121, P=0.008), and the change in pupil diameter in the high-concentration group was higher than that in the control group ( P=0.007). Conclusions:The combination of 1% tropicamide and 2.5% phenylephrine has better pupil dilation than the combination of 0.5% tropicamide and 0.5% phenylephrine.It is recommended that pupil dilation be performed with a high-concentration mydriatic drug prior to outpatient fundus examination for diabetic patients.

Objective:To identify independent risk factors for early recurrence following curative resection of resectable pancreatic cancer and establish a nomogram prediction model.Methods:Clinical data from 405 patients with resectable pancreatic cancer treated at Renji Hospital, Shanghai Jiao Tong University School of Medicine from February 2010 to December 2020 were retrospectively reviewed. Patients were stratified into a training cohort (265 patients form February 2010 to December 2018) and a validation cohort (140 patients from January 2019 to December 2020) based on surgery dates. Optimal cutoff values for clinical variables were determined using X-tile software. Independent risk factors were identified through univariate and multivariate Cox proportional hazards regression analyses. Kaplan-Meier curves for recurrence-free survival (RFS) were generated across subgroups, and a nomogram was developed to predict early recurrence (within 1 year post-surgery). Time-dependent receiver operating characteristic (tROC) curves was drawn and area under the curve (AUC) metrics were utilized to evaluate predictive accuracy, while model reliability was assessed by calibration curves. Individualized risk scores derived from the nomogram were stratified into high- and low-risk groups using X-tile-derived cutoff values. Survival differences between groups were analyzed via log-rank tests. The clinical application value was judged by decision curve analysis (DCA) compared to TNM staging. Results:In the training cohort, 139 patients (52.45%) experienced early recurrence, with a median RFS of 11.1 months [interquartile range ( IQR): 6.0-26.0]. The validation cohort reported 70 early recurrences (50.00%) and a median RFS of 11.8 months ( IQR: 4.9-21.4). Univariate analysis revealed significant associations between early recurrence and tumor diameter, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), systemic immune-inflammation index (SⅡ), and prognostic nutritional index (PNI). Multivariate analysis identified tumor diameter ≥3.75 cm ( HR=1.718, 95% CI 1.223-2.412, P=0.002), CA19-9≥218 U/ml ( HR=1.567, 95% CI 1.107-2.220, P=0.011), CA125≥20.98 U/ml ( HR=2.501, 95% CI 1.768-3.539, P<0.001), SⅡ≥388.28 ( HR=1.708, 95% CI 1.096-2.662, P=0.018), and PNI<53.18 ( HR=0.596, 95% CI 0.404-0.879, P=0.009) as independent risk factors for early recurrence. The nomogram achieved AUC values of 0.771 and 0.708 in the training and validation cohorts, respectively. Calibration curves demonstrated strong agreement between predicted and observed survival probabilities. Kaplan-Meier analysis revealed significantly lower 1-year RFS rates in high-risk versus low-risk groups for both cohorts (training: HR=3.65, 95% CI 2.45-5.44, P<0.001; validation: HR=2.37, 95% CI 1.39-4.06, P=0.001). DCA indicated superior net benefit of the nomogram over TNM staging across threshold probabilities of 0.2-0.9. Conclusions:The proposed nomogram effectively integrates clinical and serological biomarkers to preoperatively assess early recurrence risk in resectable pancreatic cancer patients, offering enhanced precision for clinical decision-making.

Objective:To explore the protective effect and mechanism of irisin on liver injury and mitochondrial dysfunction of hepatocytes in mice with acute necrotizing pancreatitis (ANP).Methods:24 mice were randomly divided into the control group, the ANP group, the irisin group and the cilengitide group, with 6 mice in each group. The ANP group was prepared by intraperitoneal injection of 20% L-arginine. The irisin group was injected with 250 μg/kg of irisin intraperitoneally on the basis of the induction of ANP. The cilengitide group was injected with the integrin receptor αVβ3/5 inhibitor cilengitide at 20 mg/kg on the basis of the treatment of the irisin group. The control group was injected with 0.9% normal saline instead of L-arginine. Routine liver histopathological examination and scoring were performed; immunohistochemical staining was used to detect the level of neutrophil infiltration in liver tissue; the ultrastructure changes of mitochondria were observed under transmission electron microscopy; biochemistry was used to detect the ATP content in liver tissue to reflect the changes in mitochondrial function; the total antioxidant capacity of liver tissue was detected by the ferric reducing/antioxidant power (FRAP) method; the DHE fluorescence probe labeling method was used to detect the accumulation degree of oxygen free radicals in liver tissue.Results:The livers of the control group showed no obvious abnormalities. However, the ANP group, the irisin group and the cilengitide group all had liver tissue damage and infiltration of inflammatory cells in the mice. Compared with the ANP group, the liver pathological score, the number of neutrophil infiltration, and the DHE fluorescence staining density in the irisin group were significantly lower [(3.40±0.72) vs (7.26±1.01) points, (14.67±2.51) vs (33.33±3.51) cells, (16.33±5.03) vs (50.33±10.69) cells], while the above indicators in the cilengitide group were all increased [(7.06±1.55) points, (40.33±5.03) cells, (51.00±12.8) cells]; the ATP content [(296.04±64.6), (54.77±18.05), (109.50±56.61), (40.29±11.68) μmol/gprot], and the antioxidant capacity [(0.19±0.01), (0.10±0.01), (0.17±0.02), (0.11±0.01) mmol/g] in the control group, ANP group, irisin group and cilengitide group changed accordingly. The above differences were statistically significant (all P value <0.05). Transmission electron microscopy observation revealed that the abnormal mitophagy of liver cells in the irisin group restored to normal, while the mitophagy abnormality in the cilengitide group was exacerbated. Conclusions:Irisin could improve the disordered mitochondrial function and oxidative stress in liver cells by acting on integrin receptors αVβ3/5, thereby alleviating liver damage and inflammatory responses in ANP mice.

Objective To investigate alterations in interhemispheric functional connectivity(FC)in the cerebral cortices connected via the corpus callosum in patients with Alzheimer's disease(AD),and to explore their relationships with cognitive function and activities of daily living.Methods Resting-state functional magnetic resonance imaging data were collected from 28 patients with Alzheimer's dementia(d-AD),47 patients with mild cognitive impairment(MCI),and 37 healthy controls(HC).Using a trancallosal tract template,32 pairs of homologous cortical brain regions directly connected to 32 subregions of the corpus callosum were selected as regions of interest for interhemispheric FC analysis.Further correlation analyses were performed between FC values in patient groups and their scores on the Montreal Cognitive Assessment-Basic(MoCA-B)Scale and the Activities of Daily Living(ADL)Scale.Results Compared with HC group,both MCI and d-AD groups exhibited hyperconnectivity(significantly increased FC)in interhemispheric non-homologous brain regions.Specifically,hyperconnectivity in the MCI group was scattered across the frontal,parietal,temporal,and occipital lobes,while in the d-AD group,it was concentrated within the precentral and postcentral gyri.Notably,hyperconnectivity involving the prefrontal and occipital lobes in the MCI group showed significant declines in the d-AD group.The interhemispheric homologous FC in the d-AD group reduced more significantly than the MCI group.Additionally,in the d-AD group,2 interhemispheric FC within the prefrontal lobe(between the bilateral orbital parts of the inferior frontal gyrus,and between the left medial frontal gyrus and the right middle frontal gyrus)were correlated with MoCA-B scores,and 2 FC(between the bilateral middle occipital gyri,and between the left inferior parietal lobule and the right middle frontal gyrus)were correlated with ADL scores.Conclusion MCI and d-AD exhibit distinct patterns of interhemispheric FC alterations,and the interhemispheric FC changes in AD patients are non-progressive.The close relationships between interhemispheric homologous/non-homologous FC and MoCA-B/ADL scores in d-AD patients provide an objective basis and reference for clinical neuromodulation.

Vasovagal syncope is the common type of unexplained syncope,and non-drug therapy is the primary method for its treatment.Till now,there are obvious limitations of western medicine treatment.Vasovagal syncope can be attributed to the category of"syncope syndrome"in the field of traditional Chinese medicine.Professor Wu Wei believes that the fundamental pathogenesis of vasovagal syncope is due to the failure of spleen yang in ascending,and the therapeutic method is to elevate and flourish spleen yang.Professor Wu established the basic formula for elevating spleen yang,which is maily composed of Astragali Radix,Atractylodis Macrocephalae Rhizoma,Codonopsis Radix,Fici Simplicissimae Radix,Citri Reticulatae Pericarpium,Bupleuri Radix,salt-prepared Eucommiae Cortex,wine-prepared Corni Fructus,Psoraleae Fructus,Aconiti Lateralis Radix Preparata,Paeoniae Radix Alba and Zingiberis Rhizoma Recens.The formula has the primary actions of elevating and flourishing spleen yang,and also has the auxiliary effect on nourishing heart,soothing liver and warming kidney.The treatment of vasovagal syncope using the method of elevating and flourishing spleen yang by Professor Wu Wei has achieved satisfactory efficacy,and his experience can provide a reference for the clinical treatment of vasovagal syncope with Chinese medicine.