Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

Objective To understand phenotype conversion in patients with first-episode depression over a 7-year period,to explore the longitudinal disease characteristics and functional outcomes of transitions and non-transitions,and to further analyse the relevant factors affecting transitions.Methods A total of 346 patients with Hamilton depression scale-17(HAMD-17)score≥18,aged 18-60 years and a single episode of major depressive disorder were included in the study.They were follow-up for 7 years to assess their natural history including demographic data,disease characteristics,whether transitions to manic occurred,treatment status.At the end of the 7-year follow-up,treatment emergent symptom scale(TESS),medication adherence rating scale(MARS),and global assessment function(GAF)were used to evaluate adverse reactions,compliance to medication,and patient's overall functional level.Patients were divided into two groups based on the occurrence of mania or hypomania episodes during the 7-year period:the conversion group(those who developed episodes)and the non-conversion group(those who did not).Results A total of 138 patients were followed up for 7 years,including 54 patients(39.1%)in the conversion group and 84 patients(60.9%)in the non-conversion group.When the first episode was enrolled at baseline,the age of first episode was earlier in the conversion group than in the non-conversion group[(27.63±9.63)years vs.(41.20±11.92)years],and there were differences in marital status(unmarried 40.7%vs.7.1%,first marriage 53.7%vs.85.7%,remarriage 3.7%vs.2.4%,separated/divorced 0.0%vs.2.4%,widowed 1.9%vs.2.4%).The proportion of patients with precipitating factors was lower in the conversion group(29.6%vs.48.8%)and shorter duration of untreated psychosis(DUP)[60(15,90)d vs.90(30,180)d].The treatment method in the conversion group had lower only used antidepressant drugs(61.1%vs.81.0%)and more antidepressant combined with mood stabilizers(31.5%vs.16.7%)(all P<0.05).In the 7 years,total number of episodes in the conversion group was more than in the non-conversion group(4.33±1.21 vs.2.70±1.25,P<0.05).By the end of 7 years,the GAF score was lower in conversion group than in the non-conversion group(66.57±8.22 vs.69.21±7.20,P<0.05).Dichotomous unconditional logistic regression analyses revealed that age at first episode(OR=1.109,95%CI:1.058-1.161,P<0.001),DUP(d)(OR=1.005,95%CI:1.001-1.009,P=0.017),was an independent influencing factor on conversion over a 7-year period in patients with first-episode depressive disorders.Conclusion The rate of conversion over 7 years in patients with first-episode depressive disorder is 39.1%in the present cohort and converted patients had relatively earlier age of onset,more pre-onset without inducement,shorter DUP(d),more recurrence,higher the rate of combined treatment and worse overall functional outcome.

Objective To understand phenotype conversion in patients with first-episode depression over a 7-year period,to explore the longitudinal disease characteristics and functional outcomes of transitions and non-transitions,and to further analyse the relevant factors affecting transitions.Methods A total of 346 patients with Hamilton depression scale-17(HAMD-17)score≥18,aged 18-60 years and a single episode of major depressive disorder were included in the study.They were follow-up for 7 years to assess their natural history including demographic data,disease characteristics,whether transitions to manic occurred,treatment status.At the end of the 7-year follow-up,treatment emergent symptom scale(TESS),medication adherence rating scale(MARS),and global assessment function(GAF)were used to evaluate adverse reactions,compliance to medication,and patient's overall functional level.Patients were divided into two groups based on the occurrence of mania or hypomania episodes during the 7-year period:the conversion group(those who developed episodes)and the non-conversion group(those who did not).Results A total of 138 patients were followed up for 7 years,including 54 patients(39.1%)in the conversion group and 84 patients(60.9%)in the non-conversion group.When the first episode was enrolled at baseline,the age of first episode was earlier in the conversion group than in the non-conversion group[(27.63±9.63)years vs.(41.20±11.92)years],and there were differences in marital status(unmarried 40.7%vs.7.1%,first marriage 53.7%vs.85.7%,remarriage 3.7%vs.2.4%,separated/divorced 0.0%vs.2.4%,widowed 1.9%vs.2.4%).The proportion of patients with precipitating factors was lower in the conversion group(29.6%vs.48.8%)and shorter duration of untreated psychosis(DUP)[60(15,90)d vs.90(30,180)d].The treatment method in the conversion group had lower only used antidepressant drugs(61.1%vs.81.0%)and more antidepressant combined with mood stabilizers(31.5%vs.16.7%)(all P<0.05).In the 7 years,total number of episodes in the conversion group was more than in the non-conversion group(4.33±1.21 vs.2.70±1.25,P<0.05).By the end of 7 years,the GAF score was lower in conversion group than in the non-conversion group(66.57±8.22 vs.69.21±7.20,P<0.05).Dichotomous unconditional logistic regression analyses revealed that age at first episode(OR=1.109,95%CI:1.058-1.161,P<0.001),DUP(d)(OR=1.005,95%CI:1.001-1.009,P=0.017),was an independent influencing factor on conversion over a 7-year period in patients with first-episode depressive disorders.Conclusion The rate of conversion over 7 years in patients with first-episode depressive disorder is 39.1%in the present cohort and converted patients had relatively earlier age of onset,more pre-onset without inducement,shorter DUP(d),more recurrence,higher the rate of combined treatment and worse overall functional outcome.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

Retrograde adeno-associated viruses (AAVs) are capable of infecting the axons of projection neurons and serve as a powerful tool for the anatomical and functional characterization of neural networks. However, few retrograde AAV capsids have been shown to offer access to cortical projection neurons across different species and enable the manipulation of neural function in non-human primates (NHPs). Here, we report the development of a novel retrograde AAV capsid, AAV-DJ8R, which efficiently labeled cortical projection neurons after local administration into the striatum of mice and macaques. In addition, intrastriatally injected AAV-DJ8R mediated opsin expression in the mouse motor cortex and induced robust behavioral alterations. Moreover, AAV-DJ8R markedly increased motor cortical neuron firing upon optogenetic light stimulation after viral delivery into the macaque putamen. These data demonstrate the usefulness of AAV-DJ8R as an efficient retrograde tracer for cortical projection neurons in rodents and NHPs and indicate its suitability for use in conducting functional interrogations.
Animals ; Haplorhini ; Axons ; Motor Neurons ; Interneurons ; Macaca ; Dependovirus/genetics* ; Genetic Vectors

【Objective】 To study the effects of platelets donation frequency on iron, copper, zinc content and superoxide dismutase(SOD) activity in plasma of blood donors. 【Methods】 128 apheresis platelet donors from August 25, 2020 to August 25, 2021 in our center were divided into 4 groups according to the frequency of platelet donation: first-time donors(n=30) were enrolled as group 1, and donors with 2 to 7 donations(n=23), 8 to 14 donations(n=29), 15 to 24 donations(n=46) within the previous period were group 2, group 3 and group 4. All these donors were males, with the average age of 42 ± 8.3, and had not donated whole blood in the past two years. Inductively coupled plasma mass spectrometry(ICP-MS) was used to detect the content of copper, iron and zinc in plasma of different groups of platelet donors. The SOD activity was detected by WST colorimetric kit. All data were statistically analyzed by SPSS 19.0 software. 【Results】 Significant differences in the content of iron and copper, but no in zinc, were noticed in donors of different groups(P<0.05). Multiple comparison showed that first-time blood donors presented significantly higher iron content but significantly lower copper content than those of donors with 15 to 24 blood donations per year(P<0.05), and no significant difference was found in iron and copper content among other groups(P>0.05). There was no significant difference in zinc content between every two groups(P>0.05). The SOD inhibition rate of blood donors in different groups was not significantly different. 【Conclusion】 The content of plasma iron, copper, and zinc and the SOD activity were not significantly affected if platelet donations were less than 15 times within a year. For those donated platelets more than 15 times within a year, the content of iron was found to decrease and copper to increase. It is suggested that platelet donations more than 15 times is correlated with the content of iron and copper in plasma of blood donors. Therefore, the proportion of iron-rich food should be appropriately increased in the daily diet for high-frequency(≥15 times per year) apheresis platelet donors after blood donation.

Objective Early evaluate the feasibility and reproducibility of sorafenib-targeted therapy for hepatocellular carcinoma by RECIST1.1, mRECIST and three-dimensional volume measurement. Methods Seventy patients with pathology or typical imaging findings confirmed as hepatocellular carcinoma along with the sorafenib-targeted treatment for more than 2 months between October 2004 to April 2017 in the Fifth Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed. Patients underwent chest, abdominal and pelvic CT scans and enhanced scans before and after 2 weeks of sorafenib treatment. Two physicians used RECIST 1.1, mRECIST, and volume measurement criteria to evaluate the efficacy of treatment. According to their averaged results, the patients were divided into two groups (control group and non-control group). Kaplan-Meier survival analysis was used to compare the prognostic values between different response evaluation criterias for early predicting the efficacy of sorafenib-targeted therapy in advanced hepatocellular carcinoma. Kappa test was used to assess the efficacy response consistency in intra-group and inter-group. Results Based on mRECIST and RECIST 1.1 measurements, the control group included 34 cases, and the non-control group included 36 cases. Based on semi-automatic volume measurement, the control group included 38 cases, and the non-control group included 32 cases. Before the treatment with sorafenib, the RECIST 1.1 and mRECIST methods were used. There was a high degree of consistency between the two doctors (Kappa values were 0.79 and 0.71, respectively), and the semi-automatic volume measurement method was extremely consistent (Kappa value was 0.90); the consistency in intra-observer by three different methods was extremely high (Kappa values were 0.91, 0.85, 0.97, respectively). After the treatment with sorafenib, the consistency between the two radiologists using RECIST 1.1 measurement was high (Kappa value was 0.65), the consistency of mRECIST measurement was moderate (Kappa value was 0.52), and the consistency of tumor volume measurement was extremely high (Kappa The value was 0.83), the consistency in intra-observer using the above three methods was high or very high (Kappa values were 0.86, 0.74, 0.90, respectively). The RECIST 1.1 and mRECIST measurements were less sensitive in early evaluation of sorafenib-targeted treatment, and there was no significant difference between the control group and the non-control group (P=0.578 and 0.613) while the semi-automatic volumetric measurement was sensitive (P=0.004). Conclusion Semi-automated three-dimensional volume measurement which has better intra-and inter-group consistency and reproducibility can reflect the efficacy of sorafenib-targeted therapy for hepatocellular carcinoma in early stage.

OBJECTIVE To identify potential mutations in five infants with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). METHODS The SLC25A13 gene was analyzed by next-generation sequencing. Suspected mutations were confirmed by PCR and Sanger sequencing in the probands and their parents. Impact of novel mutations was predicted with PolyPhen-2 software. RESULTS All neonates have harbored mutations of the SLC25A13 gene. Eight mutations were discovered, which included two novel mutations (c.1357A>G and c.1663dup23). All parents were found to be carriers of the mutations. CONCLUSION Mutations of the SLC25A13 gene probably underlie the NICCD among the five patients, among which 851del4 and 1638-1660dup were the most common ones. This has enriched the spectrum of SLC25A13 mutation in association with NICCD.

Objective To analyze the gonadal hormone and seminal plasma of patients with abnormal semen liquefaction and investigate the influence mechanism in order to provide guidance for the diagnosis and treatment. Methods 152 men of childbearing age were divided into two groups according to the liquefaction time (cut?off point: 60 minutes). Routine semen parameters,gonadal hormone and seminal plasma were tested and compared between the above groups. T?test was applied to compare individual gland function (pH value,neutralα?glycosidase,fructopyranose,seminal plasma zinc and citric acid) and gonadal hormone (FSH,LH,PRL,T and E2). Logistic regression analysis was adopted to probe the influencing factors for abnormal semen liquefaction. Results Seminal pH value (7.47 ± 0.13 vs. 7.32 ± 0.18),citric acid(51.12 ± 12.95 vs. 83.11 ± 33.46)and FSH (4.40 ± 1.03 vs. 4.85 ± 1.50)levels were significant different between the two groups (P < 0.05),but the other indexes showed no significant difference. Correlation regression analysis showed that semen liquefaction capacity has correlative relationship with seminal plasma fructose (OR=2.644),citric acid (OR=0.922),serum T (OR=1.029) and E2,while no correlative relationship with other indexes. Conclusions Correlation between two glands (seminal vesicle and prostate) and balance in the two hormones (T and E2) influence the liquefaction time. Specific causes should be distinguished before diagnosis.