Alzheimer disease(AD)is a neurological disease characterized by cognitive decline.AD continuum refers to the dynamic development progression from early pathological changes to obvious clinical symptoms,covering the continuous spectrum of subjective cognition decline(SCD)stage,mild cognitive impairment(MCI)stage and dementia stage.As one of the key brain regions involved in early stage,hippocampus(HP)in AD continuum is closely related to the progression of disease.MRI has been widely used in the study of HP in the AD continuum.The progresses in structural and functional MRI research of HP changes in AD continuum were reviewed in this article.

Alzheimer disease(AD)is a neurological disease characterized by cognitive decline.AD continuum refers to the dynamic development progression from early pathological changes to obvious clinical symptoms,covering the continuous spectrum of subjective cognition decline(SCD)stage,mild cognitive impairment(MCI)stage and dementia stage.As one of the key brain regions involved in early stage,hippocampus(HP)in AD continuum is closely related to the progression of disease.MRI has been widely used in the study of HP in the AD continuum.The progresses in structural and functional MRI research of HP changes in AD continuum were reviewed in this article.

Objective:To observe and assess the clinical value of electrophysiology of ocular surface in the diagnosis and treatment of blepharospasm in Meige syndrome (MS).Methods:A single-center, cross-sectional study. A total of 413 patients diagnosed with MS and undergoing surgical treatment at the Henan Provincial Meige Syndrome Diagnosis and Treatment Center of the Henan Provincial Third People′s Hospital from May 2022 to December 2023 were included as the MS group. A total of 110 age- and gender-matched spouses of patients and community volunteers were selected as the control group. The bioelectricity detection program of the electrooculogram was used; the frequency bandwidth was set at 0.3 to 300.0 Hz. Surface electrodes were employed to record the surface electrophysiological manifestations of the corrugator supercilii muscle and the lower orbicularis oculi muscle, as well as the conditions and temporal characteristics of spasm waves. Based on the amplitude and waveform of the electrophysiology of ocular surface signals, it can be classified into 0-4 grades. The blepharospasm was divided into conditionally induced type, spastic type, reverse spastic type, and oro-ocular elicited type. All patients were treated with neural circuit occlusion, and the postoperative follow-up time was 4.1 (0.5-19.0) months. The distribution of different grades of electrophysiology of ocular surface in the MS and control group at baseline were observed, as well as within the MS group at the last follow-up visit. Additionally, the blepharospasm grades in the MS group were also assessed. The comparison of the distribution of the number of eyes with different grades of electrophysiology of ocular surface between groups was conducted using the Mann-Whitney U test. Results:At baseline, in the MS group, the number of cases with corrugator supercilii muscle amplitudes and morphologies graded from 0 to 4 were as follows: 15 (3.60%, 15/413) for grade 0, 95 (23.00%, 95/413) for grade 1, 142 (34.38%, 142/413) for grade 2, 127 (30.75%, 127/413) for grade 3, and 34 (8.24%, 34/413) for grade 4. In the control group, the corresponding numbers of individuals were 82 (74.54%, 82/110) for grade 0, 24 (21.82%, 24/110) for grade 1, 4 (3.64%, 4/110) for grade 2, 0 (0.00%, 0/110) for grade 3, and 0 (0.00%, 0/110) for grade 4. For the orbicularis oculi muscle, there were 35 cases (8.47%) in grade 0, 124 cases (30.03%) in grade 1, 150 cases (36.32%) in grade 2, 90 cases (21.79%) in grade 3, and 14 cases (3.39%) in grade 4 in the MS group. In the control group, there were 86 cases (78.18%) in grade 0, 24 cases (21.82%) in grade 1, and 0 cases in grades 2, 3, and 4. There were statistically significant differences in the distribution of the number of eyes with different electrophysiology of ocular surface grading of the corrugator supercilii muscle and the orbicularis oculi muscle between the MS and control group ( Z=-14.51, -13.86; P<0.001). Meanwhile, there were statistically significant differences in the distribution of the number of eyes with different electrophysiology of ocular surface grading of the corrugator supercilii muscle and the orbicularis oculi muscle between preoperation and at the last follow-up in the MS group ( Z=-16.52, -17.36; P<0.001). In the MS group, there were 61 (14.77%, 61/413), 306 (74.09%, 306/413), 27 (6.54%, 27/413) and 19 (4.60%, 19/413) cases of blepharospasm conditionally induced type, spasm type, reverse spasm type and oro-ocular elicited type, respectively. Conclusion:The electrophysiology of the ocular surface can objectively reflect the activity of periocular neuromuscular.

Objective:To explore the relationship between Metabolic Score of Visceral Fat(METS-VF)and new-onset stroke in Chinese middle-aged and elderly individuals aged ≥45 years.Methods:This study is a prospective cohort study that included 3 311 participants from the China Health and Retirement Longitudinal Study(CHARLS)database, with new-onset stroke as the primary endpoint.The association between METS-VF and new-onset stroke was evaluated by Cox proportional hazards model, subgroup analysis and restricted cubic spline(RCS)analysis.Additionally, mediation analysis was used to assess the mediating effect of remnant cholesterol(RC)on the association between METS-VF and stroke.Results:During the 9-year follow-up period, 138(4.2%)middle-aged and elderly individuals experienced stroke.Compared with the lowest quartile group of METS-VF, the fully adjusted HR and 95% CI of new-onset stroke in the second, third and fourth quartiles were 1.78(1.03-3.08), 1.96(1.12-3.44)and 2.19(1.17-4.10), respectively with a statistically significant trend( P for trend<0.05). Mediation analysis indicated that the indirect effect mediated by RC accounted for 13.51% of the association between METS-VF and new-onset stroke( P=0.03), and RCS analysis revealed a linear dose-response relationship between METS-VF and stroke( P for overall=0.022, P for non-linearity=0.198); The results of the subgroup analyses were consistent with the main analyses( P interaction>0.05). Conclusions:METS-VF may serve as a potential biomarker in risk stratification of stroke, with RC partially mediating this association.

Objective:To explore the relationship between Metabolic Score of Visceral Fat(METS-VF)and new-onset stroke in Chinese middle-aged and elderly individuals aged ≥45 years.Methods:This study is a prospective cohort study that included 3 311 participants from the China Health and Retirement Longitudinal Study(CHARLS)database, with new-onset stroke as the primary endpoint.The association between METS-VF and new-onset stroke was evaluated by Cox proportional hazards model, subgroup analysis and restricted cubic spline(RCS)analysis.Additionally, mediation analysis was used to assess the mediating effect of remnant cholesterol(RC)on the association between METS-VF and stroke.Results:During the 9-year follow-up period, 138(4.2%)middle-aged and elderly individuals experienced stroke.Compared with the lowest quartile group of METS-VF, the fully adjusted HR and 95% CI of new-onset stroke in the second, third and fourth quartiles were 1.78(1.03-3.08), 1.96(1.12-3.44)and 2.19(1.17-4.10), respectively with a statistically significant trend( P for trend<0.05). Mediation analysis indicated that the indirect effect mediated by RC accounted for 13.51% of the association between METS-VF and new-onset stroke( P=0.03), and RCS analysis revealed a linear dose-response relationship between METS-VF and stroke( P for overall=0.022, P for non-linearity=0.198); The results of the subgroup analyses were consistent with the main analyses( P interaction>0.05). Conclusions:METS-VF may serve as a potential biomarker in risk stratification of stroke, with RC partially mediating this association.

Objective:To observe and assess the clinical value of electrophysiology of ocular surface in the diagnosis and treatment of blepharospasm in Meige syndrome (MS).Methods:A single-center, cross-sectional study. A total of 413 patients diagnosed with MS and undergoing surgical treatment at the Henan Provincial Meige Syndrome Diagnosis and Treatment Center of the Henan Provincial Third People′s Hospital from May 2022 to December 2023 were included as the MS group. A total of 110 age- and gender-matched spouses of patients and community volunteers were selected as the control group. The bioelectricity detection program of the electrooculogram was used; the frequency bandwidth was set at 0.3 to 300.0 Hz. Surface electrodes were employed to record the surface electrophysiological manifestations of the corrugator supercilii muscle and the lower orbicularis oculi muscle, as well as the conditions and temporal characteristics of spasm waves. Based on the amplitude and waveform of the electrophysiology of ocular surface signals, it can be classified into 0-4 grades. The blepharospasm was divided into conditionally induced type, spastic type, reverse spastic type, and oro-ocular elicited type. All patients were treated with neural circuit occlusion, and the postoperative follow-up time was 4.1 (0.5-19.0) months. The distribution of different grades of electrophysiology of ocular surface in the MS and control group at baseline were observed, as well as within the MS group at the last follow-up visit. Additionally, the blepharospasm grades in the MS group were also assessed. The comparison of the distribution of the number of eyes with different grades of electrophysiology of ocular surface between groups was conducted using the Mann-Whitney U test. Results:At baseline, in the MS group, the number of cases with corrugator supercilii muscle amplitudes and morphologies graded from 0 to 4 were as follows: 15 (3.60%, 15/413) for grade 0, 95 (23.00%, 95/413) for grade 1, 142 (34.38%, 142/413) for grade 2, 127 (30.75%, 127/413) for grade 3, and 34 (8.24%, 34/413) for grade 4. In the control group, the corresponding numbers of individuals were 82 (74.54%, 82/110) for grade 0, 24 (21.82%, 24/110) for grade 1, 4 (3.64%, 4/110) for grade 2, 0 (0.00%, 0/110) for grade 3, and 0 (0.00%, 0/110) for grade 4. For the orbicularis oculi muscle, there were 35 cases (8.47%) in grade 0, 124 cases (30.03%) in grade 1, 150 cases (36.32%) in grade 2, 90 cases (21.79%) in grade 3, and 14 cases (3.39%) in grade 4 in the MS group. In the control group, there were 86 cases (78.18%) in grade 0, 24 cases (21.82%) in grade 1, and 0 cases in grades 2, 3, and 4. There were statistically significant differences in the distribution of the number of eyes with different electrophysiology of ocular surface grading of the corrugator supercilii muscle and the orbicularis oculi muscle between the MS and control group ( Z=-14.51, -13.86; P<0.001). Meanwhile, there were statistically significant differences in the distribution of the number of eyes with different electrophysiology of ocular surface grading of the corrugator supercilii muscle and the orbicularis oculi muscle between preoperation and at the last follow-up in the MS group ( Z=-16.52, -17.36; P<0.001). In the MS group, there were 61 (14.77%, 61/413), 306 (74.09%, 306/413), 27 (6.54%, 27/413) and 19 (4.60%, 19/413) cases of blepharospasm conditionally induced type, spasm type, reverse spasm type and oro-ocular elicited type, respectively. Conclusion:The electrophysiology of the ocular surface can objectively reflect the activity of periocular neuromuscular.

BACKGROUND:Our previous experimental results have shown that hyaluronic acid hydrogel can act as a vehicle for bone marrow mesenchymal stem cell delivery to improve the cardiac function of rats with myocardial infarction. OBJECTIVE:To explore the molecular mechanism of bone marrow mesenchymal stem cells and hyaluronic acid hydrogel in promoting damaged heart repair. METHODS:Bone marrow mesenchymal stem cells from male Sprague-Dawley rats were isolated and cultured,and then hyaluronic acid-encapsulated bone marrow mesenchymal stem cells were cultured in vitro in a three-dimensional manner.A model of myocardial infarction was made by ligating the left anterior descending artery of female Sprague-Dawley rats.After 1 week,the model rats were screened by ultrasonic testing and then eligible ones were randomly divided into four groups:PBS group(n=12),hyaluronic acid group(n=12),bone marrow mesenchymal stem cell group(n=15),and hyaluronic acid-encapsulated bone marrow mesenchymal stem cell group(n=15).At 1 week after ligation,the model rats underwent the secondary thoracotomy followed by corresponding injections into the infarcted region and its marginal zone.The expression levels of matrix metalloproteinase-2,vascular endothelial growth factor,thymosin β4 and c-Kit were examined at post-injection day 1,week 1 and week 2 by western blot assay.At post-injection week 2,immunofluorescence staining was used to detect the differentiation of transplanted cells. RESULTS AND CONCLUSION:(1)The expression levels of matrix metalloproteinase-2 and vascular endothelial growth factor protein in the infarct zone in the bone marrow mesenchymal stem cell group were significantly up-regulated at week 1 compared with the other three groups(P<0.05).At week 2,the hyaluronic acid group had a lower expression of matrix metalloproteinase-2 and vascular endothelial growth factor protein than the other three groups(P<0.05).However,the expression of matrix metalloproteinase-2 and vascular endothelial growth factor protein in the hyaluronic acid+bone marrow mesenchymal stem cell group was not significantly different compared with the bone marrow mesenchymal stem cell group.This was primarily attributable to a prolonged paracrine effect via the controlled release of the hyaluronic acid hydrogel.This prolonged paracrine effect offsets the inhibitory effect induced by hyaluronic acid hydrogel at 2 weeks.(2)Compared with the PBS group,thymosin β4 and c-Kit expression levels in the hyaluronic acid group,bone marrow mesenchymal stem cell group and bone marrow mesenchymal stem cell+hyaluronic acid group were significantly increased(P<0.05).(3)No differentiation of transplanted cells into cardiomyocytes or blood vessels was detected 2 weeks after transplantation.(4)It is indicated that transplanted bone marrow mesenchymal stem cells promote myocardial repair through the paracrine effect,and hyaluronic acid hydrogel prolongs the paracrine effect of transplanted bone marrow mesenchymal stem cells.

Objective:This study aimed to evaluate the efficacy and safety of lenalidomide combined with bortezomib and dexamethasone (VRD) in the treatment of newly diagnosed multiple myeloma (MM) .Methods:A total of 150 newly diagnosed patients with MM diagnosed in The First Affiliated Hospital of Soochow University from November 2018 to February 2021 and received VRD as the induction regimen were included to evaluate the safety and efficacy of VRD induction therapy for newly diagnosed MM.Results:The median follow-up was 22 months, two patients (1.3%) died early after treatment, and 148 patients (98.7%) completed induction therapy. 116 patients (77.3%) were mobilized to collect autologous hematopoietic stem cells, 101 cases (87.1%) were qualified in the collection, of which 48 cases (41.4%) were excellent in the collection. The 3-year progression-free survival (PFS) rate was 59%, and the 3-year overall survival (OS) rate was 83%. After induction, complete remission (CR) /stringent CR rate was 54.4%, ≥ very good partial remission rate was 77.3%, overall response rate was 86.0%, and minimal residual disease negative rate was 46.0%. There was no statistically significant difference in the efficacy of cytogenetic high-risk patients compared with standard risk patients ( P=0.456) . The median PFS time of cytogenetic high-risk patients was shorter than that of standard risk patients (not reached vs 33 months, P=0.014) . There was no statistically significant difference in the median OS time (not reached vs not reached, P=0.072) . The highest incidence of hematological adverse events was thrombocytopenia (72%) , followed by neutropenia (42%) and anemia (20%) . The highest incidence of non-hematological adverse events was peripheral neuritis (56.7%) . The main digestive tract symptoms include constipation (30.0%) and diarrhea (17.3%) . Upper respiratory tract infection (23.3%) and lung infection (7.3%) are the main infections. The incidence of adverse thrombocytopenia (90.0% vs 63.7%, P=0.001) , neutropenia (54.2% vs 36.3%, P=0.038) , anemia (33.3% vs 13.7%, P=0.005) , diarrhea (27.1% vs 12.7%, P=0.030) , limb edema (20.8% vs 3.9%, P=0.030) , fever (20.8% vs 4.9%, P=0.006) , thrombosis (8.3% vs 0, P=0.016) , and renal function deterioration (20.8% vs 3.9%, P=0.030) in patients with renal insufficiency was higher than that in patients with normal renal function. Conclusion:The VRD regimen has a significant effect on newly diagnosed MM, does not affect the hematopoietic stem cell collection, and has controllable adverse events; however, the incidence of adverse events was higher in patients with renal insufficiency.

Objective:To investigate and compare the effectiveness and safety of infrared bipolar radiofrequency (IR-RF) and nonablative fractional laser (NAFL) including 1 540 nm Er: glass and 1 927 nm thulium-doped laser, so as to choose a better pathway for clinical treatments on periorbital wrinkles.Methods:A prospective randomized self-controlled study was conducted in the Department of Laser and Aesthetic Medicine, Shanghai Ninth People’s Hospital. A total of 27 patients divided into 3 groups by random number table underwent split-face treatments between December 2019 and January 2021. Two of the three treatments were selected randomly for patients in each group: Group A, left side IR-RF vs. right side 1 540 nm NAFL; Group B, left side IR-RF vs. right side 1 927 nm NAFL; Group C, left side 1 540 nm NAFL vs. right side 1 927 nm NAFL. In total 3 sessions were given at 2 months interval. Therapeutic outcomes were evaluated by subjective (GAIS and Fitzpatrick wrinkle score) and objective (VISIA-CR) assessments. Side effects and pain visual evaluation (VAS) were also recorded. Wilcoxon signed-rank tests were used to evaluate the differences among the three therapeutic method , and relationships with VAS and patients’ age.Results:In total 30 patients (10 in each group) were recruited and finally 27 cases completed all treatments and follow-ups: Group A, 9 patients (male 3, female 6); Group B, 8 patients (male 3, female 5); Group C, 10 patients (male 4, female 6). The age distributions: Group A, 33-65 years, mean 36.9 years; Group B, 28-67 years, mean 38.6 years; Group C, 25-58 years, mean 37.8 years. GAIS comparisons: no statistical differences were found in each group between baseline and post-treatment ( P>0.05). Fitzpatrick wrinkle score: the overall analysis showed significant improvements were not found in IR-RF treated-side but were observed in 1 540 nm and 1 927 nm NAFL treated sides ( P<0.05). Furthermore, the 1 927 nm NAFL treated side showed more decreased scores than 1 540 nm NAFL treated side ( P<0.05). The VISIA analysis of feature counts of skin texture showed similar result. Besides, the patients over 50 years old showed significantly improvements compared with the ones under this age threshold in IR-RF treated sides ( P<0.05). The pain VAS in IR-RF treated side was significant lower than NAFL-treated side (2.2 vs. 5.8, P<0.05). Only one patient reported post-inflammatory hyperpigmentation (PIH) in 1540 nm NAFL treated side, which disappeared progressively in 4 months after last treatment. Conclusion:Nonablative fractional laser is effective and safe in improving periorbital wrinkles. Infrared bipolar radiofrequency might be more suitable for elderly patients especially with low pain level.

Objective:To investigate and compare the effectiveness and safety of infrared bipolar radiofrequency (IR-RF) and nonablative fractional laser (NAFL) including 1 540 nm Er: glass and 1 927 nm thulium-doped laser, so as to choose a better pathway for clinical treatments on periorbital wrinkles.Methods:A prospective randomized self-controlled study was conducted in the Department of Laser and Aesthetic Medicine, Shanghai Ninth People’s Hospital. A total of 27 patients divided into 3 groups by random number table underwent split-face treatments between December 2019 and January 2021. Two of the three treatments were selected randomly for patients in each group: Group A, left side IR-RF vs. right side 1 540 nm NAFL; Group B, left side IR-RF vs. right side 1 927 nm NAFL; Group C, left side 1 540 nm NAFL vs. right side 1 927 nm NAFL. In total 3 sessions were given at 2 months interval. Therapeutic outcomes were evaluated by subjective (GAIS and Fitzpatrick wrinkle score) and objective (VISIA-CR) assessments. Side effects and pain visual evaluation (VAS) were also recorded. Wilcoxon signed-rank tests were used to evaluate the differences among the three therapeutic method , and relationships with VAS and patients’ age.Results:In total 30 patients (10 in each group) were recruited and finally 27 cases completed all treatments and follow-ups: Group A, 9 patients (male 3, female 6); Group B, 8 patients (male 3, female 5); Group C, 10 patients (male 4, female 6). The age distributions: Group A, 33-65 years, mean 36.9 years; Group B, 28-67 years, mean 38.6 years; Group C, 25-58 years, mean 37.8 years. GAIS comparisons: no statistical differences were found in each group between baseline and post-treatment ( P>0.05). Fitzpatrick wrinkle score: the overall analysis showed significant improvements were not found in IR-RF treated-side but were observed in 1 540 nm and 1 927 nm NAFL treated sides ( P<0.05). Furthermore, the 1 927 nm NAFL treated side showed more decreased scores than 1 540 nm NAFL treated side ( P<0.05). The VISIA analysis of feature counts of skin texture showed similar result. Besides, the patients over 50 years old showed significantly improvements compared with the ones under this age threshold in IR-RF treated sides ( P<0.05). The pain VAS in IR-RF treated side was significant lower than NAFL-treated side (2.2 vs. 5.8, P<0.05). Only one patient reported post-inflammatory hyperpigmentation (PIH) in 1540 nm NAFL treated side, which disappeared progressively in 4 months after last treatment. Conclusion:Nonablative fractional laser is effective and safe in improving periorbital wrinkles. Infrared bipolar radiofrequency might be more suitable for elderly patients especially with low pain level.