AIM:To explore the effectiveness of predictive models based on quantitative characteristics of multimodal fundus images in assessing the risk of progression of non-proliferative diabetic retinopathy(NPDR).METHODS:A single-center retrospective cohort study was conducted. Patients diagnosed with moderate to severe NPDR between January 2021 and December 2023 in Wuhan Ninth Hospital were selected. Baseline color fundus photography(CFP), optical coherence tomography(OCT), and fundus autofluorescence(FAF)images were collected. Microaneurysm count, hard exudate area, central retinal thickness, retinal nerve fiber layer thickness, and total area of hyperautofluorescent spots were extracted and quantified. All patients were followed up regularly. The primary endpoint was the progression to treatment-requiring proliferative diabetic retinopathy(PDR)or clinically significant diabetic macular edema(DME)during the follow-up period. According to the occurrence of endpoint events during follow-up, the patients were divided into the progression group and the non-progression group. Combined with clinical significance and inter-group comparison results, candidate quantitative imaging parameters were included in the multivariate logistic regression analysis to construct a prediction model. The model was visualized using a Nomogram. The discriminative ability and calibration degree of the model were evaluated via receiver operating characteristic(ROC)curves and calibration curves.RESULTS:A total of 300 patients(300 eyes)completed follow-up, with 93 in the progression group, including 47 males and 46 females, with an average age of 59.02±8.21 y. There were 207 cases in the non-progression group, including 105 males and 102 females, with an average age of 58.01±8.10 y. Multivariate logistic regression showed that the total area of FAF hyperautofluorescent spots(OR=1.580, 95%CI: 1.061-1.718, P=0.002),OCT retinal nerve fiber layer thickness(OR=1.520, 95%CI: 1.307-6.212, P=0.013), and CFP microaneurysm count(OR=1.459, 95%CI: 1.089-2.095, P=0.015)were risk factors for DR progression. The AUC of the Nomogram for predicting progression risk during the follow-up period was 0.889(95%CI: 0.826-0.952), and the calibration curve showed good consistency between predicted probability and actual risk.CONCLUSION: The prediction model integrating quantitative imaging features of CFP, OCT and FAF can effectively identify NPDR patients with high progression risk and exhibits good predictive efficacy, which can serve as a quantitative tool for individualized clinical risk management.

Depression is a psychological disorder that imposes a tremendous social burden, with a high prevalence in China. In recent years, the number of diagnosed cases of depression in China has steadily increased, yet the recognition rate of the disease remains low. Depression demostrates a clear familial aggregation pattern. To improve its recognition, numberous studies have utilized the polygenic risk score for major depressive disorder (MDD-PRS) as a potential genetic marker to identify high-risk populations. This article reviews the latest progress and research on the use of MDD-PRS in depression, aiming to clarify its capacity to capture genetic variations associated with depression, its interaction with environmental factors, and their relationship to the onset of the disorder. Additionally, this review evaluates the predictive performance of existing risk models for depression and proposes potential directions for future research.

Depression is a psychological disorder that imposes a tremendous social burden, with a high prevalence in China. In recent years, the number of diagnosed cases of depression in China has steadily increased, yet the recognition rate of the disease remains low. Depression demostrates a clear familial aggregation pattern. To improve its recognition, numberous studies have utilized the polygenic risk score for major depressive disorder (MDD-PRS) as a potential genetic marker to identify high-risk populations. This article reviews the latest progress and research on the use of MDD-PRS in depression, aiming to clarify its capacity to capture genetic variations associated with depression, its interaction with environmental factors, and their relationship to the onset of the disorder. Additionally, this review evaluates the predictive performance of existing risk models for depression and proposes potential directions for future research.

【Objective】 To investigate the correlation between perioperative zero red blood cell(RBC) transfusion and the prognosis of patients with acute Stanford type A aortic dissection. 【Methods】 A retrospective analysis was made on 96 patients who underwent one-stop Hybrid surgery for acute Stanford type A aortic dissection in our hospital from May 2021 to May 2022. The patients were divided into two groups according to whether they received perioperative RBC transfusion: zero RBC transfusion group (group A, n=26) and RBC transfusion group (group B, n=70). The preoperative general data and laboratory indexes were recorded and the propensity score matching method was used to screen the patients with the same preoperative baseline data, with comparison of operation-related indicators, intraoperative and postoperative blood component dosage and prognostic indicators. 【Results】 With BMI index, hemoglobin, platelet count, and troponin T as co variables, 48 patients were included in the study after matching according to 1∶1 propensity score: Group A (n=24) and Group B (n=24). Compared with group A, hemoglobin and hematocrit in group B decreased significantly at the end of operation and 24 h after operation, with a statistically significant difference (P<0.05). There was no significant difference between the two groups in operation-related indicators, intraoperative and postoperative blood component dosage, in-hospital mortality, continuous renal replacement therapy, incidence of infection and cerebral infarction (P>0.05). 【Conclusion】 The perioperative hemoglobin of patients with acute Stanford type A aortic dissection with zero RBC transfusion did not significantly decrease, and the postoperative complications and mortality did not increase.

Cardiomyopathy, Dilated/metabolism* ; Humans ; Microfilament Proteins/metabolism* ; Models, Cardiovascular ; Mutation ; Myocytes, Cardiac ; Pluripotent Stem Cells/metabolism* ; Transcription Factors/metabolism* ; Troponin T/metabolism*

Multi-modal therapeutics are emerging for simultaneous diagnosis and treatment of cancer. Polymeric carriers are often employed for loading multiple drugs due to their versatility and controlled release of these drugs in response to a tumor specific microenvironment. A theranostic nanomedicine was designed and prepared by complexing a small gadolinium chelate, conjugating a chemotherapeutic drug PTX through a cathepsin B-responsive linker and covalently bonding a fluorescent probe pheophorbide a (Ppa) with a branched glycopolymer. The branched prodrug-based nanosystem was degradable in the tumor microenvironment with overexpressed cathepsin B, and PTX was simultaneously released to exert its therapeutic effect. The theranostic nanomedicine, branched glycopolymer-PTX-DOTA-Gd, had an extended circulation time, enhanced accumulation in tumors, and excellent biocompatibility with significantly reduced gadolinium ion (Gd

Objective:To explore the efficient construction of HSF1 gene knockout mouse model using CRISPR/Cas9 gene editing technology, and to establish the early basis for the mouse model of primary osteosarcoma.Methods:According to exon 9 of HSF1 gene structure, the corresponding GRNA (guideRNA) was selected and screened. Then the transcription template of sgRNA (small guide RNA) was amplified by PCR, and four up stream primers were obtained. Subsequently, sgRNA was transcribed in vitro and screened by Tube Screen platform to screen the sgRNA with effective cutting, and the sgRNA with the highest cutting efficiency was selected from the screening results for subsequent experiments. The transcription template of SPCas9mRNA was amplified by PCR, and then Cas9mRNA was transcribed in vitro. The sgRNA transcribed in vitro and Cas9mRNA were injected into the fertilized eggs of healthy C57BL/6 mice, and the tissue was extracted from the tail of the born mice and identified by PCR sequencing. Heterozygous female mice of F0 generation were selected to mate with wild-type male mice too btain F1 generation off spring. The mutation of gene bases of F1 generation mice was detected by AGAR gel electrophoresis and gene sequencing. The heterozygous male mice of the F1 generation and female mice of the F0 generation were back crossed to obtain the F2 generation daughter mice. The tail tissues were cut and sequenced to obtain the F2 generation homozygous knockout mice. PCR was used to observe the cutting efficiency of sgRNA and the sequencing of rat tail tissue, and SNAPGene software was used for gene sequence alignment to determine the deletion of base fragments.Results:The up stream primers sgRNA-1 Primer-f, sgRNA-2 Primer-f, sgRNA-3 Primer-f, sgRNA-4 Primer-f and down stream primers sgRNA-4 Primer -r were obtained by PCR amplification. After in vitro tran scription and screening of sgrRNA, sgrRNA-1, sgrRNA-2 and sgrRNA-4 had high cleavage efficiency and were selected for subsequent experiments. T7 promoter was added to the 5 'end of Cas9 mRNA, and Cas9 mRNA was obtained by PCR and in vitro transcription kit. Mixed Cas9-sgRNA solution was injected into the fertilized eggs of mice and cultured. The cultured two-cell fertilized eggs were injected into the ampulla of the pseudo pregnant female mice, and the F0 generation mice were obtained successfully. A total of 8 heterozygous mice of F0 generation were obtained by Agar gel electrophoresis. Three heterozygous knockout mice of F1 generation were obtained by breeding the female heterozygous mice of F0 generation with healthy wild-type male mice and PCR and sequencing. Three heterozygous male mice of F1 generation were back crossed with female mice of F0 generation 3 to obtain F2 generation mice. Through the observation of electrophoresis and sequencing results of F2 generation mice, it was confirmed that 7 mice were missing HSF1 base sequence, and the electrophoresis results showed mutant bands and no wild-type bands, which were identified as homozygous. The F2 generation homozygous mice were able to breed stably. As eries of results proved that the HSF1 gene knockout mouse model was successfully established in this experiment.Conclusion:CRISPR/Cas9 technology was successfully used to construct HSF1 gene knockout mouse model, with strong stability and high reproducibility, which laida foundation for further study of HSF1 gene expression products and establishment of mouse model of primary osteosarcoma.

Objective:To evaluate alterations of periventricular pseudocysts (PVPC) on MRI before and after birth, and to assess the prognosis.Methods:We retrospectively analyzed the data of 67 cases that were diagnosed with PVPC on prenatal MRI, of which 24 cases were lost to follow-up, 2 died after birth. A total of 41 surviving fetuses were included in this prognosis study. The gestational ages in this group were between 23 and 39 weeks, with an average of (33±3) weeks.All the subjects underwent brain MRI examinations and Gesell Developmental Scale (GDS) testing between 0-3 years of age. According to the location of cysts and with or without other intracranial and extracranial malformations (dilated ventricles orcerebella medulla, hypoxic-ischemic encephalopathy, TORCH virus infection, corporal hypoplasia, chromosomal malformations and nodular sclerosis) , the patients were divided into four groups: isolated connatal cysts, connatal cysts with additional findings,isolated subependymal pseudocysts, and subependymal pseudocysts with additional findings.The MR images were independently reviewed by two radiologists blinded to the clinical information. Intraclass correlation efficient (ICC) was used to analyze the consistency between the two reviewers.Chi-square test was used to compare the location of cysts (single/bilateral), the number of cyst cavities (single/multi-chamber), and other abnormalities in the connatal cyst group and subependymal cyst group. The mean anteroposterior diameter and mean height of cysts between the connatal cyst group and subependymal cyst group were compared by independent sample t-test.The ANOVA test was used to compare the differences in GDS outcomes among the groups. Multiple comparisons were conducted using the LSD test. Results:Inter-observer agreements between the two radiologists were good for the collected data (all ICC>0.75). Eleven isolated connatal cysts and 7 connatal cysts with additional findings became smaller or disappeared, and all had good prognosis. Of the 14 isolated subependymal cysts, 12 became smaller or disappeared, 2 had no change in size, and 13 had good prognosis. The subependymal cysts with additional findings group included 9 cases: 6 became smaller or disappeared, only 3 showed no apparent changes, and 7 had an abnormal outcome. Subependymal cysts with additional findings were significantly reduced and patients demonstrated significant differences compared with the those with isolated subependymal cysts in the development quotients (DQ) of adaptability, large movements, fine movements, personal social interaction, and language DQ ( P all<0.05). DQ between patients with isolated connatal cysts and isolated subependymal cysts was comparable ( P all>0.05). When associated with additional findings, connatal cysts and subependymal cysts could induce significant different DQ outcome ( P all<0.05). Conclusions:Isolated PVPC usually become smaller or disappeared and have a benign presentation after birth, whereas patients with subependymal cysts with additional findings usually have a poor prognosis. Connatal cysts usually have a good prognosis.

Objective: To investigate the expression of SMARCA4 (BRG1) and SMARCB1 (INI-1) protein in endometrial dedifferentiated carcinoma (DDC) and undifferentiated carcinoma (UDC), and their correlation with clinicopathologic features. Methods: Clinicopathological information was gathered for 26 cases of DDC and UDC and consulting hospitals from January, 2006 to December, 2018 in Fudan University Shanghai Cancer Center, including 10 cases of DDC and 16 cases of UDC. Morphologic features and diagnosis were reviewed by two pathologists. Immunohistochemistry for expression of BRG1 and INI1 protein was performed. The correlations with clinicopathologic features were analyzed. Results: BRG1 and INI1 loss were present in 14 of 26 cases of DDC/UDC, including 12 BRG1-deficient cases and 2 INI1-deficient cases, respectively. Six cases demonstrated variable amounts of rhabdoid cells in 14 BRG1/INI1-deficient cases, and only 1 case showed rhabdoid cells in the 12 intact expression cases. However, there was no significantly statistical difference (P=0.060). Age, invasive depth, lymph node status and FIGO stage were not associated with the expression of the BRG1 and INI1 (P=0.437, P=0.672, P=0.242, P=0.348). Remarkably, the BGR1/INI1-deficient patients had worse survival than those with intact expression (4.7 vs. 22.9, P=0.033). Conclusion BRG1/INI1-deficient is observed in approximately half of DDC and UDC. Identification of these tumors is clinically relevant due to their more aggressive behavior and poor prognosis. Hence, BRG1 and INI1 immunohistochemical stains should be performed for DDC and UDC in order to help the pathologists to distinguish these tumors from other carcinomas, and to predict the clinical prognosis.

Objective To investigate the expression of SMARCA4 (BRG1) and SMARCB1 (INI?1) protein in endometrial dedifferentiated carcinoma (DDC) and undifferentiated carcinoma (UDC), and their correlation with clinicopathologic features. Methods Clinicopathological information was gathered for 26 cases of DDC and UDC and consulting hospitals from January, 2006 to December, 2018 in Fudan University Shanghai Cancer Center, including 10 cases of DDC and 16 cases of UDC. Morphologic features and diagnosis were reviewed by two pathologists. Immunohistochemistry for expression of BRG1 and INI1 protein was performed. The correlations with clinicopathologic features were analyzed. Results BRG1 and INI1 loss were present in 14 of 26 cases of DDC/UDC, including 12 BRG1?deficient cases and 2 INI1?deficient cases, respectively. Six cases demonstrated variable amounts of rhabdoid cells in 14 BRG1/INI1?deficient cases, and only 1 case showed rhabdoid cells in the 12 intact expression cases. However, there was no significantly statistical difference (P=0.060). Age, invasive depth, lymph node status and FIGO stage were not associated with the expression of the BRG1 and INI1 (P=0.437,P=0.672,P=0.242,P=0.348). Remarkably, the BGR1/INI1?deficient patients had worse survival than those with intact expression (4.7 vs. 22.9, P=0.033). Conclusion BRG1/INI1?deficient is observed in approximately half of DDC and UDC. Identification of these tumors is clinically relevant due to their more aggressive behavior and poor prognosis. Hence, BRG1 and INI1 immunohistochemical stains should be performed for DDC and UDC in order to help the pathologists to distinguish these tumors from other carcinomas, and to predict the clinical prognosis.