Objective:To explore the effect of exercise on the memory of rats modeling vascular cognitive impairment (VCI) and also its effects on the hippocampal Sema3G/neuropilin-2 (Nrp2)/PlexinA4 signaling pathway.Methods:Eighteen male Sprague-Dawley rats were randomly divided into a sham-operated group, a model group, and an exercise group, each of 6. The model and exercise groups underwent VCI modeling via bilateral common carotid artery occlusion, while the sham-operated group received the same surgical procedure without vessel ligation or transection. Beginning forty-eight hours after the surgery, the exercise group carried out daily 30-minute treadmill training sessions, 5 days a week, for a total of 4 weeks, while the other two groups were placed on the same treadmill with it not in operation. After the intervention, cognitive functioning was assessed using the novel object recognition (NOR) test and a Y-maze test. Western blotting was employed to evaluate the expression of Sema3G, Nrp2, PlexinA4, and Rac1 in the hippocampus. Immunofluorescence staining was used to observe the distribution of Nrp2 and PlexinA4 in the hippocampus.Results:Compared with the model group, the exercise group exhibited significantly higher NOR indices during both the short-term and long-term memory testing phases after the intervention. Those rats also tended to have significantly longer total exploration times in the novel arm of the Y-maze test. The western blotting revealed that the expression levels of Sema3G, PlexinA4, and Rac1 in the hippocampus were significantly higher in the exercise group compared to the model group, on average. Immunofluorescence showed significantly increased PlexinA4 fluorescence intensity in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus, and significantly elevated Nrp2 fluorescence intensity in the CA3 region in the exercise group compared to the model group. The Pearson correlation coefficients for Nrp2/PlexinA4 co-localization in the CA1, CA3 and DG regions were significantly higher in the exercise group than in the model group.Conclusions:Exercise training significantly improves memory function in rats with VCI, and this effect may be associated with activation of the hippocampal Sema3G/Nrp2/PlexinA4 signaling pathway.

Objective:To explore the application effects of the blended teaching methodology of "teaching-selection-investigation-analysis-presentation-discussion" in Medical Immunology. Methods:Eight-year program clinical medical students who were enrolled at Peking Union Medical College in 2016, 2017, and 2018 were selected as the research subjects. An anonymous questionnaire survey was used to analyze students' multidimensional evaluations of the new teaching methodology. The percentage of frontier hotspot topics in the "Immunology Forum" was used to analyze the students' mastery of cutting-edge knowledge in immunology. The number of "Immunology Forum" related "College Students Innovative Training Plan Program" from 2020 to 2023 was used to analyze the effectiveness of this new teaching method in cultivating students' scientific research and innovation abilities. Statistical analysis was conducted using SPSS 25.0 software, and the normality of all continuous variables was assessed using the Shapiro-Wilk test.Results:The questionnaire survey showed 100.00% satisfaction with the course and 95.90% recognition of the new teaching method. More than 90% of students agreed that the new teaching method improved their learning ability, research ability, innovation ability, internal drive, and academic communication ability. The average proportion of hotspot topics in the "Immunology Forum" was 90.37%±7.12%, which was significantly higher than the proportion of non-hotspot topics (5.67%±3.12%). The average number of topics related to "Immunology Forum" in the "College Students Innovative Training Plan Program" was 17.67±1.15 per session, which was significantly higher than the number of topics not related to "Immunology Forum" (8.00±1.73).Conclusions:The blended teaching methodology of "teaching-selection-investigation-analysis-presentation-discussion" can help students timely grasp the cutting-edge knowledge of immunology, cultivate their learning ability, internal drive, academic communication ability, innovation ability, and research ability, and lay a foundation for students to further explore their scientific research and innovation activities.

BACKGROUND:Studies have shown that vision recovery with thinner grafts is faster and the risk of rejection is lower.In China,there is a lack of clinical efficacy analysis of different graftthicknesses after endothelial transplantation.Therefore,determining the optimal graftthickness is crucial for improving surgical efficacy. OBJECTIVE:To evaluate the effects of different graftthickness on vision recovery and other prognostic indexes after simple Descemet's stripping endothelial keratoplasty. METHODS:A total of 72 patients(72 eyes)with corneal endothelial decompensation who received simple Descemet's stripping endothelial keratoplasty at the General Hospital of Northern Theater Command from January 2013 to February 2023 were selected.There were 32 cases(32 eyes)in the thin graftgroup(＜100 μm)and 40 cases(40 eyes)in the thick graftgroup(≥100 μm).The best corrected visual acuity,corneal endothelial cell count,corneal graft transparency,postoperative complications and graftsurvival were observed in both groups before and 1,3,6,and 12 months after surgery. RESULTS AND CONCLUSION:The visual acuity after surgery was significantly improved in both groups,and the best corrected visual acuity 3 months after surgery in the thin graftgroup was better than that in the thick graftgroup(P＜0.05).There was no significant difference in the number of corneal endothelial cells and grafttransparency between the two groups 1 year after surgery(P＞0.05).There was no significant difference in the incidence of postoperative complications such as secondary glaucoma,graftimmune rejection and graftdisplacement between the two groups(P＞0.05).There was no significant difference in the 1-year survival rate of grafts between the two groups(93.8%vs.92.3%,P＞0.05).To conclude,simple Descemet's stripping endothelial keratoplasty is a safe and effective surgical method for corneal endothelial transplantation,and its postoperative efficacy is similar to that of traditional Descemet's stripping endothelial keratoplasty,and the graftimplantation method is simpler.Thinner grafts can provide optimal corrected vision earlier and complete corneal remodeling sooner.Therefore,in the treatment of corneal endothelial decompensation,thinner grafts are preferred to improve recovery time.

Objective:To explore the application effects of the blended teaching methodology of "teaching-selection-investigation-analysis-presentation-discussion" in Medical Immunology. Methods:Eight-year program clinical medical students who were enrolled at Peking Union Medical College in 2016, 2017, and 2018 were selected as the research subjects. An anonymous questionnaire survey was used to analyze students' multidimensional evaluations of the new teaching methodology. The percentage of frontier hotspot topics in the "Immunology Forum" was used to analyze the students' mastery of cutting-edge knowledge in immunology. The number of "Immunology Forum" related "College Students Innovative Training Plan Program" from 2020 to 2023 was used to analyze the effectiveness of this new teaching method in cultivating students' scientific research and innovation abilities. Statistical analysis was conducted using SPSS 25.0 software, and the normality of all continuous variables was assessed using the Shapiro-Wilk test.Results:The questionnaire survey showed 100.00% satisfaction with the course and 95.90% recognition of the new teaching method. More than 90% of students agreed that the new teaching method improved their learning ability, research ability, innovation ability, internal drive, and academic communication ability. The average proportion of hotspot topics in the "Immunology Forum" was 90.37%±7.12%, which was significantly higher than the proportion of non-hotspot topics (5.67%±3.12%). The average number of topics related to "Immunology Forum" in the "College Students Innovative Training Plan Program" was 17.67±1.15 per session, which was significantly higher than the number of topics not related to "Immunology Forum" (8.00±1.73).Conclusions:The blended teaching methodology of "teaching-selection-investigation-analysis-presentation-discussion" can help students timely grasp the cutting-edge knowledge of immunology, cultivate their learning ability, internal drive, academic communication ability, innovation ability, and research ability, and lay a foundation for students to further explore their scientific research and innovation activities.

BACKGROUND:If not detected and treated in a timely manner,immune-associated peripheral ulcerative keratitis can lead to corneal thinning,ulcers and even perforation,thereby causing visual loss and affecting the patient's quality of life.OBJECTIVE:To discuss the pathogenesis of immune-associated peripheral ulcerative keratitis and summarize the diagnosis and treatment ideas and the latest treatment methods for this disease.METHODS:Search terms were"peripheral ulcerative keratitis,immunity,immune system disease,pathogenesis,immunomodulatory therapy,surgical treatment,keratoplasty"in English and Chinese.Relevant literature on peripheral ulcerative keratitis published from database inception to October 2024 was searched by computer in CNKI,WanFang,PubMed,and El databases.A total of 68 papers were ultimately selected to comprehensively describe the new research progress in the research on immune-associated peripheral ulcerative keratitis.RESULTS AND CONCLUSION:Immune-associated peripheral ulcerative keratitis includes Mooren's ulcer,blepharokeratoconjunctivitis,superior limbic keratoconjunctivitis,and autoimmune related peripheral ulcerative keratitis.Due to the physiology of the corneal limbus,peripheral ulcerative keratitis is usually associated with an immune response,and the pathophysiologic mechanism is usually related to the deposition of immune complexes in the blood vessels at the limbus and the production of microangiitis.Systemic immunomodulatory therapy should be used whether or not an autoimmune disease is diagnosed prior to the onset of immune-associated peripheral ulcerative keratitis,which can help to reduce ocular complications associated with systemic inflammation.Nonsurgical treatment,such as immunomodulatory therapy,is beneficial for relieving ocular symptoms,but when nonsurgical treatment is ineffective or the lesion infiltrates the Descemet membrane,it can cause corneal perforation.Combined surgical treatment can help maintain the structural integrity of the eyeball.However,there is no clear evidence for the combination of immunomodulatory therapy and surgical treatment in the development of immune-associated Peripheral ulcerative keratitis.This article reviews the literature on the diagnosis and treatment of immune-associated peripheral ulcerative keratitiss.

Objective:To investigate the clinicopathological characteristics of solid, endometrial-like and transitional (SET) cell growth subtype in high-grade serous ovarian carcinoma (HGSC).Methods:Clinical data of 25 cases of HGSC-SET were collected from January 2020 to March 2024 at the Affiliated Suzhou Hospital of Nanjing Medical University, and their histological features were analyzed. Immunohistochemical stains were used to analyze the expression of ER, PR, PAX8, WT-1, p16, p53 and Ki-67. Next generation sequencing method was used to detect breast cancer susceptibility (BRCA1/2) gene mutation, homologous recombination deficiency (HRD) status, and other homologous recombination repair (HRR) genes. The difference of HRD status between HGSC-SET and typical HGSC patients was further compared.Results:The age of HGSC-SET patients ranged from 41 to 81 years, with an average age of 59 years and a median age of 57 years. Four cases were premenopausal and 21 were postmenopausal. There were 12 cases of bilateral ovarian masses and 13 cases of unilateral ovarian masses. Serum CA125 was elevated in 21 patients and CA19-9 in 2 patients. Lymph node involvement was found in 9 cases, and distant dissemination or metastasis was found in 15 cases. Tumor cells were found in ascites of 10 cases. All the cases were of mixed type, with both typical components (papillae, micropapillae, and glands) and SET components. The total proportion of SET components was>25%. There were 15 cases with comedo/map-like necrosis. Most of the SET form showed pushing pattern of invasion, while the classic form showed infiltrative pattern of invasion. All 25 cases of HGSC-SET showed mutant type staining of p53, of which 20 cases indicated missense mutation and 5 cases indicated nonsense mutation. The positive rates of PAX8, WT-1 and p16 were 100% (25/25), 84% (21/25) and 92% (23/25), respectively. The positive rate of ER was 80% (20/25) in the SET morphological region and 68% (17/25) in the classic morphological region. The positive rate of PR was 16% (4/25) in the SET morphological region and 32% (8/25) in the classic morphological region. The proliferative index of Ki-67 was 60%-95% in the SET region and 20%-90% in the classic region. BRCA1/2 gene mutation was detected in 36% (9/25) of HGSC-SET patients. Among them, 2 cases had BRCA1 gene mutation, 6 cases had BRCA2 gene mutation, and 1 case had gene mutation both in BRCA1 and BRCA2. HRD was positive in 84% (21/25) of patients and negative in 16% (4/25) of patients. The positive rate of HRD in BRCA1/2 wild-type cases was 12/16. A total of 21 patients had HRR-related gene alterations other than BRCA1/2. The mutation rate of BRCA1/2 gene in HGSC-classic patients was 4/20, and the positive rate of HRD was 11/20.Conclusions:Histologically, HGSC-SET presents as a mixed pattern, with comedo/map-like necrosis in most cases. The mutation rate of BRCA1/2 and the positive rate of HRD are higher in HGSC-SET than in HGSC-classic type. BRCA1/2 wild-type HGSC-SET also has a higher HRD positive rate. Besides BRCA1/2, other HRR related gene mutations should not be ignored to avoid missing patients who may benefit from PARP inhibitor treatment.

Objective:To investigate the clinicopathological characteristics of solid, endometrial-like and transitional (SET) cell growth subtype in high-grade serous ovarian carcinoma (HGSC).Methods:Clinical data of 25 cases of HGSC-SET were collected from January 2020 to March 2024 at the Affiliated Suzhou Hospital of Nanjing Medical University, and their histological features were analyzed. Immunohistochemical stains were used to analyze the expression of ER, PR, PAX8, WT-1, p16, p53 and Ki-67. Next generation sequencing method was used to detect breast cancer susceptibility (BRCA1/2) gene mutation, homologous recombination deficiency (HRD) status, and other homologous recombination repair (HRR) genes. The difference of HRD status between HGSC-SET and typical HGSC patients was further compared.Results:The age of HGSC-SET patients ranged from 41 to 81 years, with an average age of 59 years and a median age of 57 years. Four cases were premenopausal and 21 were postmenopausal. There were 12 cases of bilateral ovarian masses and 13 cases of unilateral ovarian masses. Serum CA125 was elevated in 21 patients and CA19-9 in 2 patients. Lymph node involvement was found in 9 cases, and distant dissemination or metastasis was found in 15 cases. Tumor cells were found in ascites of 10 cases. All the cases were of mixed type, with both typical components (papillae, micropapillae, and glands) and SET components. The total proportion of SET components was>25%. There were 15 cases with comedo/map-like necrosis. Most of the SET form showed pushing pattern of invasion, while the classic form showed infiltrative pattern of invasion. All 25 cases of HGSC-SET showed mutant type staining of p53, of which 20 cases indicated missense mutation and 5 cases indicated nonsense mutation. The positive rates of PAX8, WT-1 and p16 were 100% (25/25), 84% (21/25) and 92% (23/25), respectively. The positive rate of ER was 80% (20/25) in the SET morphological region and 68% (17/25) in the classic morphological region. The positive rate of PR was 16% (4/25) in the SET morphological region and 32% (8/25) in the classic morphological region. The proliferative index of Ki-67 was 60%-95% in the SET region and 20%-90% in the classic region. BRCA1/2 gene mutation was detected in 36% (9/25) of HGSC-SET patients. Among them, 2 cases had BRCA1 gene mutation, 6 cases had BRCA2 gene mutation, and 1 case had gene mutation both in BRCA1 and BRCA2. HRD was positive in 84% (21/25) of patients and negative in 16% (4/25) of patients. The positive rate of HRD in BRCA1/2 wild-type cases was 12/16. A total of 21 patients had HRR-related gene alterations other than BRCA1/2. The mutation rate of BRCA1/2 gene in HGSC-classic patients was 4/20, and the positive rate of HRD was 11/20.Conclusions:Histologically, HGSC-SET presents as a mixed pattern, with comedo/map-like necrosis in most cases. The mutation rate of BRCA1/2 and the positive rate of HRD are higher in HGSC-SET than in HGSC-classic type. BRCA1/2 wild-type HGSC-SET also has a higher HRD positive rate. Besides BRCA1/2, other HRR related gene mutations should not be ignored to avoid missing patients who may benefit from PARP inhibitor treatment.

BACKGROUND:If not detected and treated in a timely manner,immune-associated peripheral ulcerative keratitis can lead to corneal thinning,ulcers and even perforation,thereby causing visual loss and affecting the patient's quality of life.OBJECTIVE:To discuss the pathogenesis of immune-associated peripheral ulcerative keratitis and summarize the diagnosis and treatment ideas and the latest treatment methods for this disease.METHODS:Search terms were"peripheral ulcerative keratitis,immunity,immune system disease,pathogenesis,immunomodulatory therapy,surgical treatment,keratoplasty"in English and Chinese.Relevant literature on peripheral ulcerative keratitis published from database inception to October 2024 was searched by computer in CNKI,WanFang,PubMed,and El databases.A total of 68 papers were ultimately selected to comprehensively describe the new research progress in the research on immune-associated peripheral ulcerative keratitis.RESULTS AND CONCLUSION:Immune-associated peripheral ulcerative keratitis includes Mooren's ulcer,blepharokeratoconjunctivitis,superior limbic keratoconjunctivitis,and autoimmune related peripheral ulcerative keratitis.Due to the physiology of the corneal limbus,peripheral ulcerative keratitis is usually associated with an immune response,and the pathophysiologic mechanism is usually related to the deposition of immune complexes in the blood vessels at the limbus and the production of microangiitis.Systemic immunomodulatory therapy should be used whether or not an autoimmune disease is diagnosed prior to the onset of immune-associated peripheral ulcerative keratitis,which can help to reduce ocular complications associated with systemic inflammation.Nonsurgical treatment,such as immunomodulatory therapy,is beneficial for relieving ocular symptoms,but when nonsurgical treatment is ineffective or the lesion infiltrates the Descemet membrane,it can cause corneal perforation.Combined surgical treatment can help maintain the structural integrity of the eyeball.However,there is no clear evidence for the combination of immunomodulatory therapy and surgical treatment in the development of immune-associated Peripheral ulcerative keratitis.This article reviews the literature on the diagnosis and treatment of immune-associated peripheral ulcerative keratitiss.

Objective:To explore the effect of exercise on the memory of rats modeling vascular cognitive impairment (VCI) and also its effects on the hippocampal Sema3G/neuropilin-2 (Nrp2)/PlexinA4 signaling pathway.Methods:Eighteen male Sprague-Dawley rats were randomly divided into a sham-operated group, a model group, and an exercise group, each of 6. The model and exercise groups underwent VCI modeling via bilateral common carotid artery occlusion, while the sham-operated group received the same surgical procedure without vessel ligation or transection. Beginning forty-eight hours after the surgery, the exercise group carried out daily 30-minute treadmill training sessions, 5 days a week, for a total of 4 weeks, while the other two groups were placed on the same treadmill with it not in operation. After the intervention, cognitive functioning was assessed using the novel object recognition (NOR) test and a Y-maze test. Western blotting was employed to evaluate the expression of Sema3G, Nrp2, PlexinA4, and Rac1 in the hippocampus. Immunofluorescence staining was used to observe the distribution of Nrp2 and PlexinA4 in the hippocampus.Results:Compared with the model group, the exercise group exhibited significantly higher NOR indices during both the short-term and long-term memory testing phases after the intervention. Those rats also tended to have significantly longer total exploration times in the novel arm of the Y-maze test. The western blotting revealed that the expression levels of Sema3G, PlexinA4, and Rac1 in the hippocampus were significantly higher in the exercise group compared to the model group, on average. Immunofluorescence showed significantly increased PlexinA4 fluorescence intensity in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus, and significantly elevated Nrp2 fluorescence intensity in the CA3 region in the exercise group compared to the model group. The Pearson correlation coefficients for Nrp2/PlexinA4 co-localization in the CA1, CA3 and DG regions were significantly higher in the exercise group than in the model group.Conclusions:Exercise training significantly improves memory function in rats with VCI, and this effect may be associated with activation of the hippocampal Sema3G/Nrp2/PlexinA4 signaling pathway.

Ferroptosis is a new programmed cell death dependent on iron ions.Ferroptosis can be induced by endogenous or exogenous pathways,and cells exhibit specific cell morphological signs and are regulated by a variety of molecular mechanisms.In recent years,more and more studies have shown that ferroptosis plays an important role in the treatment of cancer.This article summarizes the mechanism of ferroptosis in bladder cancer and the regulation of cancer cells,as well as the role of ferroptosis-related factors,non-coding RNA regulation,N6-methyladenosine(m6A),amino acid metabolism and autophagy dependent ferroptosis in the growth and proliferation of bladder cancer,with a view to provide new strategies for the treatment of bladder cancer.