Objective To explore the predictive model and its value of irAEs based on peripheral blood markers.Methods The baseline clinical data,laboratory tests,and irAEs follow-up results of 825 malignant tumor patients treated with PD-1/PD-L1 antibodies in the First Affiliated Hospital of Kunming Medical University were retrospectively collected from December 2020 to December 2023.The patients were divided into irAEs group and non-irAEs group according to the presence or absence of irAEs.The differences between and within groups were analyzed by t-test,rank-sum test,chi-square test and Fisher exact probability method.LASSO,Ridge and Elastic-net logistic regressions were used to screen the predictors and establish the risk prediction models for irAEs.Results 136 patients experienced 178 irAEs,of which endocrine toxicity accounted for 42.64％,hepatitis 35.29％,pneumonia 20.58％,grade≥G3 accounted for 19.07％,involving more than two organs accounted for 24.26％of the total number of irAEs.Univariate analysis showed that baseline CD4+T cell count,IL-6,IL-17,TSH,GLB and ALB were associated with irAEs.GLB,ALB,IL-17 and TSH were selected as the important risk factors by Ridge,LASSO and Elastic-Net logistic regression.The results showed that the AUC of the three algorithms were over 0.800.The AUC of internal validation set by LASSO-Logistic was 0.800(95％CI 0.739～0.862).The AUC of external validation set was 0.800(95％CI 0.739～0.861)and the DCA curve results indicated the highest net return for this predictive model.Conclusion GLB,ALB,IL-17 and TSH are independent predictors of irAEs,and the predictive model of irAEs based on them is effective.

Objective::To investigate the morphological and ultrastructural alterations in placentas from pregnancies with gestational diabetes mellitus (GDM)-induced macrosomia, term nondiabetic macrosomia, and normal pregnancies.Methods::Sixty full-term placentas were collected, and clinical data along with informed consent were obtained from pregnant women who underwent regular visit checks and delivered their newborns in Northwest Women’s and Children’s Hospital between May and December 2022. Placentas were divided into three equal groups: normal pregnancy (control group), nondiabetic macrosomia group, and macrosomia complicated with GDM (diabetic macrosomia) group. Gross morphological data of placentas were recorded, and placental samples were processed for examination of ultrastructural and stereological changes using transmission electron microscopy. Analysis of variance and chi-squared test were used to examine the differences among the three groups for continuous and categorical variables, respectively.Results::The baseline characteristics of mothers and neonates did not differ across the three groups, except for a significantly higher birth weight in the diabetic macrosomia group (4172.00 ± 151.20 g vs. 3192.00 ± 328.70 g, P < 0.001) and nondiabetic macrosomia group (4138.00 ± 115.20 g vs. 3192.00 ± 328.70 g, P < 0.001) compared with control group. Examination of the placentas revealed that placental weight was also highest in the diabetic macrosomia group compared with control group (810.00 ± 15.81 g vs. 490.00 ± 51.48 g, P < 0.001) and nondiabetic macrosomia group (810.00 ± 15.81 g vs. 684.00 ± 62.69 g, P < 0.001), but the ratio of neonatal birth weight to placental weight (BW/PW) was significantly lower in the diabetic macrosomia group compared with that in the control group (5.15 ± 0.19 vs. 6.54 ± 0.63, P < 0.001) and nondiabetic macrosomia group (5.15 ± 0.19 vs. 6.09 ± 0.52, P < 0.001) group. In contrast, the BW/PW ratio in nondiabetic macrosomia did not differ significantly from that in the control group. Distinct ultrastructural changes in terminal villi and stereological alterations in microvilli were observed in the diabetic macrosomia group, including changes in the appearance of cytoplasmic organelles and the fetal capillary endothelium and thickness of the vasculo-syncytial membrane and basal membrane. Conclusion::Significant ultrastructural and stereological alterations were discovered in the placentas from pregnant women with macrosomia induced by GDM. These alterations may be the response of the placenta to the hyperglycemia condition encountered during pregnancies complicated with GDM.

Objective::To investigate the morphological and ultrastructural alterations in placentas from pregnancies with gestational diabetes mellitus (GDM)-induced macrosomia, term nondiabetic macrosomia, and normal pregnancies.Methods::Sixty full-term placentas were collected, and clinical data along with informed consent were obtained from pregnant women who underwent regular visit checks and delivered their newborns in Northwest Women’s and Children’s Hospital between May and December 2022. Placentas were divided into three equal groups: normal pregnancy (control group), nondiabetic macrosomia group, and macrosomia complicated with GDM (diabetic macrosomia) group. Gross morphological data of placentas were recorded, and placental samples were processed for examination of ultrastructural and stereological changes using transmission electron microscopy. Analysis of variance and chi-squared test were used to examine the differences among the three groups for continuous and categorical variables, respectively.Results::The baseline characteristics of mothers and neonates did not differ across the three groups, except for a significantly higher birth weight in the diabetic macrosomia group (4172.00 ± 151.20 g vs. 3192.00 ± 328.70 g, P < 0.001) and nondiabetic macrosomia group (4138.00 ± 115.20 g vs. 3192.00 ± 328.70 g, P < 0.001) compared with control group. Examination of the placentas revealed that placental weight was also highest in the diabetic macrosomia group compared with control group (810.00 ± 15.81 g vs. 490.00 ± 51.48 g, P < 0.001) and nondiabetic macrosomia group (810.00 ± 15.81 g vs. 684.00 ± 62.69 g, P < 0.001), but the ratio of neonatal birth weight to placental weight (BW/PW) was significantly lower in the diabetic macrosomia group compared with that in the control group (5.15 ± 0.19 vs. 6.54 ± 0.63, P < 0.001) and nondiabetic macrosomia group (5.15 ± 0.19 vs. 6.09 ± 0.52, P < 0.001) group. In contrast, the BW/PW ratio in nondiabetic macrosomia did not differ significantly from that in the control group. Distinct ultrastructural changes in terminal villi and stereological alterations in microvilli were observed in the diabetic macrosomia group, including changes in the appearance of cytoplasmic organelles and the fetal capillary endothelium and thickness of the vasculo-syncytial membrane and basal membrane. Conclusion::Significant ultrastructural and stereological alterations were discovered in the placentas from pregnant women with macrosomia induced by GDM. These alterations may be the response of the placenta to the hyperglycemia condition encountered during pregnancies complicated with GDM.

Humans ; Aortic Valve/surgery* ; Retrospective Studies ; Transcatheter Aortic Valve Replacement ; Sex Factors ; Heart Valve Prosthesis Implantation ; Treatment Outcome ; China ; Aortic Valve Stenosis/surgery* ; Risk Factors ; Risk Assessment

Humans ; Retrospective Studies ; Transcatheter Aortic Valve Replacement/adverse effects* ; Risk Assessment ; China ; Prognosis ; Aortic Valve Stenosis/surgery* ; Treatment Outcome ; Risk Factors ; Aortic Valve

Ferroptosis is defined as an iron-dependent, non-apoptotic cell death pathway, with specific morphological phenotypes and biochemical changes. There is a growing realization that ferroptosis has significant implications for several neurodegenerative diseases. Even though ferroptosis is different from other forms of programmed death such as apoptosis and autophagic death, they involve a number of common protein molecules. This review focuses on current research on ferroptosis and summarizes the cross-talk among ferroptosis, apoptosis, and autophagy that are implicated in neurodegenerative diseases. We hope that this information provides new ideas for understanding the mechanisms and searching for potential therapeutic approaches and prevention of neurodegenerative diseases.
Apoptosis ; Autophagy ; Cell Death ; Ferroptosis ; Humans ; Neurodegenerative Diseases

【Objective】 To establish and evaluate a nephelometric assay for the determination of immunoglobulin A (IgA) residues in human intravenous immunoglobulin(IVIG). 【Methods】 BN ProSpec^© automatic protein analyzer and its supporting immunoglobulin A determination kit (nephelometry) produced by German Siemens and the national standard of human IgA were used to establish the nephelometric assay to determine IgA residue in test products and verify the methodology. The test products include IVIG (pH4) prepared by low-temperature ethanol protein separation process and a novel IVIG prepared by chromatography. 【Results】 The average deviation of three calibration curves for IgA residues determination by the nephelometric assay were 1.08%, 0.95% and 1.54%,, and the three deviations of the quality control were 4.00%, -2.30% and -0.20%, respectively, which indicated good calibration and quality control. In the specificity test, the average recovery rates of IgA for reference substance 1 containing 100g/L maltose and reference substance 2 containing 20g/L glycine were 102.7% and 105.8%, respectively. The relative standard deviation (RSD) values of the repeatability tests of the two test products were 3.9% and 1.9%, and the RSD values of the intermediate precision test were 3.6% and 2.3%, respectively.The difference values at each time point in the durability test of test products′ storage time were all less than 10%, and the RSD values of the two test products in the durability test of kits of different batches were 2.8% and 2.2%, respectively. In the accuracy test, the average recovery rates of IVIG (pH4) added to the standard were 94.2%, 101.7% and 96.2%, respectively, and the average recovery rates of the novel IVIG added to the standard were 102.8%, 106.3% and 99.7%, respectively. The average recovery rate of the limit quantification test was 101.0%, and the RSD was 4.0%. 【Conclusion】 Nephelometric assay has the advantages of strong specificity, high precision and accuracy, good repeatability, simple and rapid operation, and automation, and can be used for the determination of IgA residue in IVIG (pH4) and novel IVIG products.

Objective To investigate the level of spirituality in cancer patients in a 3A grade hospital of Changsha and to analyze the influencing factors. Methods In this study, convenience sampling method was used to select 196 patients with cancer from three hospitals in a 3A grade hospital of Changsha from October 2016 to October 2017. The general situation questionnaire, the functional assessment of chronic illness therapy (FACIT-Sp-12), the social support scale and the post traumatic growth inventory were used to investigate the patient′s spiritual status and to analyze the influencing factors. Results The total spiritual score of cancer patients was 31.09 ± 8.89, the score of meaning dimension was 10.71±2.75, and the peace dimension was 9.84±3.19 and the belief dimension was 10.54± 2.98. The results of multiple regression analysis showed that age, cancer stage, education level, the subjective support of Social Support, relating to others and personal strength of The Posttraumatic Growth were the influencing factors for the spiritual status of cancer patients. Conclusions the spiritual status of cancer patients in a 3A grade hospital of Changsha is at medium level, and the spiritual status is closely related to age, education level, cancer stage, social support and post traumatic growth level. Medical staff should provide spiritual care for patients to improve their psychology and Mental Health and quality of life.

Objective To explore the differences of macrostructural and microstructural and their correlations in brain white matter (WM) between left-and right-handed adults.Methods Structural magnetic resonance imaging (sMRI) and diffusion tensor imaging (DTI) were performed on twenty-three left-handed (LH) and thirty-two right-handed (RH) healthy subjects.The WM volume,fractional anisotropy (FA) and mean diffusivity (MD) were mearsured and compared between the two groups by using the voxel-based morphometry (VBM) and voxel-based analysis (VBA) methods.Results (1) LH adults showed lower WM volume than RH adults in bilateral splenium of corpus callosum (SC) (Left:x=-15,y=-57,z =13.5,t=-5.160;Right:x=18,y=-42,z=12,t=-3.654;P＜0.001).Compared with the RH adults,the FA values in WM of the left postcentral gyrus (PoCG) (x =-24,y =-46,z =54) and the above left insula (INS) (x =-36,y =-12,z =20) increased (P＜ 0.001),as well as the average FA values,the average length and number of streamlines in WM tracts increased (P＜0.05) in LH adults.Compared with the RH adults,the MD values in the right HIP (x=24,y=-34,z=-2) decreased(P＜0.001),as well as the average MD values decreased,and the average length in WM tracts increased (P＜0.05) in LH adults.(2)There was positive correlation between FA and the volume of right splenium of corpus callosum in LH and RH adults (LH:r=0.716,RH:r=0.471,P＜0.05).There was negative correlation between FA and MD in the left PoCG (LH:r=-0.769,RH:r=-0.841),left INS (LH:r=-0.775,RH:r=-0.744) and right HIP (LH:r=-0.842,RH:r=-0.742) in LH and RH adults (all P＜0.05).Conclusion There are differences in both macrostructure and microstructure of white matter in several brain regions and WM tracts between left-handed and right-handed people,and correlations between these measures were also observed.

Objective To investigate the association between diabetic retinopathy ( DR) and atherosclerosis cardiovascular disease ( ASCVD) .Methods Clinical data of 654 patients with type 2 diabetic mellitus (T2DM) were collected from a cross sectional , population based survey on chronic diseases and risk factors which was conducted in Beijing Changping district from July 2010 to March 2011.Among 654 T2DM patients, there were 73 patients with ASCVD (ASCVD group) and 581 patients without ASCVD ( non-ASCVD group ) .The association between DR and ASCVD was analyzed .Results Patients with ASCVD had significantly older age [58.5(53.9,65.9) years], more female sex[52(71.2%)], higher proportion of ASCVD history [45(61.6%)], higher levels of PG 2 h[16.26(11.08,19.20) mmol/L], HbA1c[7.20(6.55,8.85)%], systolic pressure [151(133,165) mmHg(1 mmHg＝0.133 kPa)] and lower eGFR[87.2(75.0,103.0) ml· min-1· 1.73 m-2] than non-ASCVD patients[52.4(46.5,58.3) years, Z＝-5.86, P＝0.00; 307(52.8%),χ2＝-8.86, P＝0.00; 256(44.1%),χ2＝8.07, P＝0.01; 13.10(8.99,17.93) mmol/L, Z＝-2.35, P＝0.02; 6.70(6.00, 7.90)%, Z＝-3.33, P＝0.00; 143(131,158) mmHg, χ2＝-2.28, P＝0.02; 94.6(84.8,106.3) ml· min-1· 1.73 m-2, Z＝-3.47, P＝0.00].The trend to develop DR in ASCVD group was significantly higher than that in non-ASCVD group [19.2%(14/74) vs.8.3%(48/581), χ2＝9.01, P ＝0.00] .DR was an independent statistical indicator of the presence of ASCVD [ OR ( 95%CI ): 2.64 ( 1.37 -5.06 ), P ＝0.00 ] . Furthermore, when DR was divided into NPDR and PDR according to its severity , only PDR was significantly associated with incident ASCVD [OR(95%CI): 12.05 (2.63-55.12), P＝0.00].After adjusting for traditional ASCVD risk factors , such an association still existed , with the risk of having ASCVD increasing by 718%[ OR (95% CI): 8.18 ( 1.56 -42.81 ), P ＝0.01] .DR associates strongly with ASCVD in the Chinese population with T 2DM.Conclussion With the severity of DR increasing , the risk of ASCVD also grows.After adjustment for traditional risk factors , PDR is still associated with the risk of prevalent ASCVD.