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.

Objective To evaluate the value of serum E2 levels during COH in predicting IVF-ET outcome. Method Data from 311 IVF-ET cycles received long protocol were collected and analyzed according to E 2 levels 5 days after stimulation:Group A (E2≤500 pmol/L), Group B (500 2 000 pmol/L). Results In groups with E2>1 000 pmol/L, the conditions of oocyte and embryo are higher than E2<1 000 pmol/L. With the increase of E2 levels, period cancellation rate increases. When E2> 2 000 pmol/L, the pregnancy rate become lowest. Conclusion E2 levels among 1 000~1 500 pmol/L during early COH predicts a better pregnancy outcome.

Objective To investigate the classiifcation, and reasonable choice and curative effect of the surgical procedures for pancreatic duct stone. Methods Clinical data of 18 patients with pancreatic duct stone undergoing surgery in Sun Yat-sen Memorial Hospital, Sun Yat-sen University from January 2010 to December 2012 were retrospectively analyzed. There were 13 males and 5 females with the average age of (53±12) years. Fourteen cases suffered from abdominal pain, 5 complicated with pancreatic cancer, 6 with bile duct stone and 8 with mellitus diabetes. The informed consents of all patients were obtained and the local ethical committee approval was received. Classiifcation, surgical procedures and postoperative complications of the pancreatic duct stone patients during perioperative period and the curative effect during follow-up were observed. Results All patients received surgical treatment. Two cases with typeⅠ pancreatic duct stone underwent pancreaticoduodenectomy (Whipple operation), 8 with type Ⅱand 1 with typeⅢunderwent pancreatolithotomy+pancreato-jejunal Roux-en-Y anastomosis (Partington operation). Two with typeⅢunderwent distal pancreatectomy+splenectomy. Among 5 cases with typeⅣ,2 underwent Whipple operation and 3 underwent Partington operation. No patients died during perioperative period. Postoperative complications were observed in 5 cases, including 3 with pancreatic ifstula and 2 with ascites, and the patients were cured after symptomatic treatments. Abdominal pain disappeared after surgery in 12 cases and was signiifcantly alleviated in 2 cases. One case complicated with pancreatic cancer died 1 year after surgery. No recurrence of stones was observed in the remaining cases. Conclusions Based on the priciple of individualized treatment, reasonable surgical procedure should be choosed according to the classiifcation of pancreatic duct stone. Pancreatolithotomy and pancreatojejunostomy are the main surgical procedures.

Objective To compare the effect of kidney-tonifying blood-activating recipe (KBR) and Aescuven Forte Tablets ( AFT) in improving the sperm quality of varicocele-induced male sterility, thus to optimize the therapeutic therapy for varicocele-induced male sterility. Methods A total of 102 varicocele-induced male sterility with abnormal sperm parameters after conservative treatment were randomized into KBR group (N=53) and AFT group ( N=49) . KBR group was given KBR plus natural vitamin E and AFT group was given AFT plus natural vitamin E, and the treatment lasted for 8 continuous weeks. Before and after treatment, the quality of seminal fluid was analyzed, sperm quantization parameters such as total number of sperm (TNS) , total number of progressive motility sperm ( TNPS) , total number of normal form sperm ( TNNS) and total number of nor mal form and progressive motility sperm ( TNNPS) were observed, and the improvement rate of sperm quantization parameter was compared. Results (1) Before treatment, the differences of TNS, TNPS, TNNS and TNNPS were insignificant between the two groups ( P>0.05) . After treatment, TNNS was not improved in AFT group ( P>0.05) , but TNS, TNPS, TNNPS were much improved in both groups ( P<0.01 compared with those before treatment) . The improvement of KBR group was superior to that of AFT group ( P<0.05) . ( 2) The improvement rate for TNS, TNPS, TNNS, TNNPS was 90.57%, 79.25%, 67.92%, 77.36%in KBR group, and was 75.51%, 73.47%, 28.57%, 61.22% in AFT group respectively. The improvement rate for TNS and TNNS in KBR group was superior to that in AFT group ( P<0.05 or P<0.01) . Conclusion Varicocele-induced male sterility patients usually have the syndrome of kidney deficiency and blood stasis, so KBR, which has the function of tonifying kidney and activating blood, has synergistic action on the effect of AFT in improving sperm quality of varicocele-induced male sterility patients.

In this study,the current status for breast diseases in a region with high-incidence of cervical cancer were epidemiologically investigated.From March to August,2009,17618 women,from Wufeng area of Hubei province,China,were recruited to screen breast diseases by using breast infrared diagnostic apparatus.Other diagnostic methods,such as B-mode ultrasound,X-ray mammography,needle biopsy and pathological examination were,if necessary,used to further confirm the diagnosis.The screening showed that 5990 of 17618 cases (34.00％) had breast diseases,5843 (33.16％) had mammary gland hyperplasia,48 (0.27％) had breast fibroadenoma,ll (0.06％) had breast carcinoma,and 88 (0.50％) had other breast diseases.The peak morbidity of breast cancer was found in the women aged 50-0 ages.The morbidity of breast cancer was significantly increased in women elder than or equal to 50 years old (n=8,0.157％) in comparison with that in the subjects younger than 50 years old (n=3,0.024％) (u=2.327,P＜0.05).It was shown that the occurrence of breast diseases was concentrated in women aged 20-40 years,while the total morbidity reached its peak at the age of 30 years and then decreased sharply after age of 40.Compared with the patients elder than or equal to 40 years old (n=3289,27.46％),the morbidity rate of breast diseases was significantly increased in women less than 40 years old (2648 cases,47.18％; P＜0.001).However,there was no significant difference in the morbidity of breast diseases between the age group of 20-29 years and that of 30-39 years (P=0.453),and both of them were high.There was no significant association between the morbidity of breast diseases and cervical cancer.Since the morbidity of breast diseases was higher among young women,more attention should be paid to the screening of breast diseases among young women for early diagnosis.