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 investigate the correlation of serum growth differentiation factor-15(GDF-15)with coronary slow flow phenomenon(CSFP)and coronary atherosclerosis(AS).Meth-ods A total of 190 patients undergoing first-time coronary angiography in our hospital from January 2019 to June 2022 were recruited,and then according to definite diagnosis,divided into CSFP group(n=60),AS group(n=70)and NC group(normal coronary flow,n=60).Their gen-eral data,risk factors for coronary heart disease,clinical biochemical indexes and electrocardio-gram were collected.The serum GDF15 level was measured by ELISA.Results Age(OR=1.065,95％CI:1.014-1.119,P=0.021),smoking history(OR=0.330,95％CI:0.132-0.823,P=0.001)and GDF-15(OR=1.006,95％CI:1.003-1.009,P=0.018)were independent influencing factors of AS.Age(OR=0.956,95％CI:0.926-0.988,P=0.024)and GDF-15(OR=1.003,95％CI:1.000-1.006,P=0.031)were independent influencing factors of CSFP.The GDF-15 level was significantly higher in the moderate or severe AS group than the CSFP group and the mild AS group(867.02±222.82 ng/L vs 568.21±163.03 ng/L and 635.41±214.95 ng/L,P＜0.01).Serum GDF-15 level was positively correlated with hs-CRP level(r=0.228,P=0.014).Conclusion GDF-15 is highly expressed in the patients with CSFP and with AS.With the increase of GDF-15 level,the severe the degree of AS gradually.GDF-15 is highly correlated with hs-CRP.

Objective: To explore the influence of two voluntary counseling and testing(VCT) services on young students acquired immune deficiency syndrome(AIDS) related knowledge and behaviour, so as to provide a new idea for further improvement and promotion of VCT services. Methods: From April 2017 to December 2018, the sample size,selected from 12 patrol and fixed monitoring sites in colleges in Guangzhou, was calculated by non inferiority trial, and the students who received services at the same period were 1∶1 matched. A total of 113 students received conventional VCT and 186 recerived peer VCT services. The Chi square test was used to analyse the difference of AIDS related knowledge and behavior before and after intervention, and a survey was conducted on satisfaction. Results: After young students received conventional VCT services, the overall awareness rate of AIDS basic knowledge increased from 80.53% to 93.75%, and the frequency of condom use every time during heterosexual sexual activity in the past year increased by 29.17 percentage points ( χ 2=4.49,4.10, P <0.05). After young students received peer VCT services, the awareness rate of the Four Frees and One Care Policy increased from 34.95% to 58.26%, the rates of homosexual anal sex and more than or equal to 2 sexual partners in the past half a year decreased by 14.84 and 29.43 percentage points, respectively( χ 2=15.69, 4.82, 10.97, P <0.05). Conclusion After young students receive two modes of VCT services respectively, the AIDS related knowledge and behavior have been improved, and the influence of the two VCT services has different advantages. The combination of conventional VCT and peer education might be a more effective way of AIDS intervention.

Objective:To analyze the clinical characteristics of severe adenovirus pneumonia with bacterial infection in children, so as to provide clinical evidences for early diagnosis and reliable treatment.Methods:A total of 72 pediatric cases with severe adenovirus pneumonia admitted to Pediatric Intensive Care Unit at the First People′s Hospital of Chenzhou from January 2018 to August 2019 were included.The clinical features, laboratory and imaging data, efficacy of the treatments and prognosis were investigated retrospectively.Patients were divided into with bacterial infection group and without bacterial infection group.The clinical characteristics were analyzed.Results:Among the 72 children, there were 54 males and 18 females, aging from 3 months to 5 years, including 37cases with bacterial infection and 35 cases without bacterial infection.Compared with the group without bacterial infection, the group with bacterial infection had longer heat duration and hospital stay [12.0 (10.0, 18.5) days vs.10.0 (9.0, 12.0) days; 6.0(4.0, 7.0) days vs.11.0(6.5, 16.0) days, P<0.05], the incidences of diarrhea and hepatomegaly were higher[35.1% (13/37) vs.14.3%(5/35); 45.9%(17/37)vs.8.6%(3/35), P<0.05], the proportion of five lobes involved in lung imaging was higher [91.8% (34/37) vs. 57.1%(20/35), P<0.05]. The incidences of complications with respiratory failure, hemophagocytic lymphohistiocytosis, and bronchiolitis obliterans in the group with bacterial infection were significantly higher than those of without bacterial infection group ( P<0.05). Conclusion:For children under 2 years old age with severe adenovirus pneumonia, there are prolonged high fever and extensive pulmonary lesions.We should be highly alert to the combination of bacterial infection and timely anti-infection therapy.Children with severe adenovirus pneumonia with bacterial infection have severe clinical manifestations and many complications with respiratory failure, hemophagocytic lymphohistiocytosis, and bronchiolitis obliterans.

Objective:To investigate the efficacy and safety of plasma exchange(PE) in the treatment of autoimmune hemolytic anemia in children.Methods:The data from 8 hospitals in China during November 2014 to April 2017 were collected, and the clinical characteristics of PE in children with AHA were analyzed retrospectively.Results:A total of 21 children with AHA were included in the study, including 17 cases from PICU and 4 cases from pediatric kidney ward, with 11 boys and 10 girls, and the median age was 3.64(0.25, 11.10)years old, and median hospital stay was 12(4, 45)days.There were 15 cases(71.4%) with infection, 2 cases(9.5%)with autoimmune diseases, 4 cases(19.0%) with unknown.Consciousness disturbance occurred in 4 patients before replacement and recovered to normal after PE.The volume of blood decreased in two cases(9.5%) and completely relieved.There were 20 cases of anemia (95.2%), 15 cases were normal after PE, and 5 cases were improved.Jaundice occurred in 18 cases (85.7%), 12 cases were normal after PE, 6 cases were improved.Hepatosplenomegaly was found in 11 cases, 10 cases were normal after PE, 1 case was improved.After PE, the hemoglobin and red blood cell count increased, while the total bilirubin, indirect bilirubin, urea nitrogen and lactate dehydrogenase decreased, there were significant differences between pre-and post-replacement ( P<0.05). Only 1 case had allergic reaction, which was improved after symptomatic treatment, and PE was continued.After PE, 2 cases (9.5%) had complete remission, 16 cases (76.2%) had partial remission and 3 cases (14.3%) had been discharged. Conclusion:PE therapy can obviously improve the clinical symptoms and laboratory indexes of children with AHA who have failed to respond to conservative treatment.It can be used as a treatment measure for children with severe AHA and has a good safety.

Objectives:To evaluate the role of pancreas multidisciplinary team(MDT) clinic in the diagnosis of pancreatic diseases,patient compliance with MDT advice,and the impact of MDT on the postoperative survival of patients with pancreatic cancer.Methods:The study included 927 patients(554 males,373 females,aged (58.1±13.3)years (range: 15 to 89 years)) that had visited the pancreas MDT clinic of Zhongshan Hospital from May 2015 to December 2021,and 677 patients(396 males, 281 females, aged (63.6±8.9)years(range: 32 to 95 years)) who underwent radical surgery and with pathologically confirmed pancreatic adenocarcinoma from January 2012 to December 2020,of whom 79 patients had attended the pancreas MDT. The clinical and pathological data were collected and analyzed retrospectively. Diseases were classified in accordance with 2010 WHO classification of tumors of the digestive system and usual clinical practices. The Kaplan-Meier method was used for drawing the survival curve and calculating the survival rate. The univariate analysis was done by Log-rank test and the multivariate analysis was done by COX proportional hazards model. Survival rates were compared using χ 2 test. Results:Among the 927 patients that had visited the MDT clinic,233 patients(25.1%) were referred due to undetermined diagnosis. A direct diagnosis was made in 109 cases (46.8%,109/233) by the MDT clinic, of which 98 were consistent with the final diagnosis,resulting in an accuracy of 89.9%(98/109). The direct diagnosis rate in the recent years(36.6%(41/112),from June 2019 to December 2021) decreased compared to that in the previous years(56.2%(68/121),from May 2015 to May 2019),yet the accuracy in the recent years(90.2%,37/41) was basically the same as before (89.7%,61/68). The rate of compliance of the entire cohort was 71.5%(663/927), with the compliance rate in the recent two and a half years(81.4%,338/415) remarkably higher than that in the previous four years(63.4%,325/512). Patients with pancreatic cancer that attended the MDT exhibited a trend toward longer median postoperative survival than patients that did not attend the MDT,but the difference was not statistically significant(35.2 months vs.30.2 months, P>0.05). The 1-year and 3-year survival rates of patients that attended the MDT were significanly higher than patients that did not attend the MDT(88.6% vs. 78.4%, P<0.05;32.9% vs. 21.9%, P<0.05,respectively),but the 5-year survival rate was not statistically different(7.6% vs. 4.8%, P>0.05). Conclusions:The pancreas MDT clinic is an accurate and convenient way to diagnose intractable pancreatic diseases,and in the recent years the patients′ compliance rate with MDT advice has increased. Pancreatic cancer patients that have attended the MDT have higher 1-year and 3-year postoperative survival rates,but the long-term survival benefits of MDT still needs to be proved by clinical studies on a larger scale.

Objectives:To evaluate the role of pancreas multidisciplinary team(MDT) clinic in the diagnosis of pancreatic diseases,patient compliance with MDT advice,and the impact of MDT on the postoperative survival of patients with pancreatic cancer.Methods:The study included 927 patients(554 males,373 females,aged (58.1±13.3)years (range: 15 to 89 years)) that had visited the pancreas MDT clinic of Zhongshan Hospital from May 2015 to December 2021,and 677 patients(396 males, 281 females, aged (63.6±8.9)years(range: 32 to 95 years)) who underwent radical surgery and with pathologically confirmed pancreatic adenocarcinoma from January 2012 to December 2020,of whom 79 patients had attended the pancreas MDT. The clinical and pathological data were collected and analyzed retrospectively. Diseases were classified in accordance with 2010 WHO classification of tumors of the digestive system and usual clinical practices. The Kaplan-Meier method was used for drawing the survival curve and calculating the survival rate. The univariate analysis was done by Log-rank test and the multivariate analysis was done by COX proportional hazards model. Survival rates were compared using χ 2 test. Results:Among the 927 patients that had visited the MDT clinic,233 patients(25.1%) were referred due to undetermined diagnosis. A direct diagnosis was made in 109 cases (46.8%,109/233) by the MDT clinic, of which 98 were consistent with the final diagnosis,resulting in an accuracy of 89.9%(98/109). The direct diagnosis rate in the recent years(36.6%(41/112),from June 2019 to December 2021) decreased compared to that in the previous years(56.2%(68/121),from May 2015 to May 2019),yet the accuracy in the recent years(90.2%,37/41) was basically the same as before (89.7%,61/68). The rate of compliance of the entire cohort was 71.5%(663/927), with the compliance rate in the recent two and a half years(81.4%,338/415) remarkably higher than that in the previous four years(63.4%,325/512). Patients with pancreatic cancer that attended the MDT exhibited a trend toward longer median postoperative survival than patients that did not attend the MDT,but the difference was not statistically significant(35.2 months vs.30.2 months, P>0.05). The 1-year and 3-year survival rates of patients that attended the MDT were significanly higher than patients that did not attend the MDT(88.6% vs. 78.4%, P<0.05;32.9% vs. 21.9%, P<0.05,respectively),but the 5-year survival rate was not statistically different(7.6% vs. 4.8%, P>0.05). Conclusions:The pancreas MDT clinic is an accurate and convenient way to diagnose intractable pancreatic diseases,and in the recent years the patients′ compliance rate with MDT advice has increased. Pancreatic cancer patients that have attended the MDT have higher 1-year and 3-year postoperative survival rates,but the long-term survival benefits of MDT still needs to be proved by clinical studies on a larger scale.

Objective:To explore the consistency of peripheral whole blood and venous serum procalcitonin (PCT) levels, and the value of peripheral whole blood PCT in evaluating pediatric bacterial infection.Methods:This multicenter cross-sectional parallel control study was conducted in 11 children′s hospital. All the 1 898 patients older than 28 days admitted to these hospitals from March 2018 to February 2019 had their peripheral whole blood and venous serum PCT detected simultaneously with unified equipment, reagent and method. According to the venous serum PCT level, the patients were stratified to subgroups. Analysis of variance and chi-square test were used to compare the demographic characteristics among groups. And the correlation between the peripheral blood and venous serum PCT level was investigated by quantitative Pearson correlation analysis.The PCT resultes were also converted into ranked data to further test the consistency between the two sampling methods by Spearman′s rank correlation test. Furthermore, the ranked data were converted into binary data to evaluate the consistency and investigate the best cut-off of peripheral blood PCT level in predicting bacterial infection.Results:A total of 1 898 valid samples were included (1 098 males, 800 females),age 27.4(12.2,56.7) months. There was a good correlation between PCT values of peripheral whole blood and venous serum ( r=0.97 , P<0.01). The linear regression equation was PCT?venous serum=0.135+0.929×PCT peripheral whole blood. However, when stratified to 5 levels, PCT results showed diverse and unsatisfied consistency between the two sampling methods ( r=0.51-0.92, all P<0.01). But after PCT was converted to ordinal categorical variables, the stratified analysis showed that the coincidence rate of the measured values by the two sampling methods in each boundary area was 84.9%-97.1%. The dichotomous variables also showed a good consistency (coincidence rate 96.8%-99.3%, Youden index 0.82-0.89). According to the severity of disease, the serum PCT value was classified into 4 intervals（<0.5、0.5-<2.0、2.0-<10.0、≥10.0 μg/L）, and the peripheral blood PCT value also showed a good predictive value (AUC value was 0.991 2-0.997 9). The optimal cut points of peripheral whole blood PCT value 0.5、1.0、2.0、10.0 μg/L corresponding to venous serum PCT values were 0.395, 0.595, 1.175 and 3.545 μg/L, respectively. Conclusions:There is a good correlation between peripheral whole blood PCT value and the venous serum PCT value, which means that the peripheral whole blood PCT could facilitate the identification of infection and clinical severity. Besides, the sampling of peripheral whole blood is simple and easy to repeat.

Objective: To explore preoperative predictive markers for invasive malignancy in intraductal papillary mucinous neoplasm(IPMN). Methods: The retrospective case-controlled study was adopted.Seventy-nine patients who underwent surgery and with pathologically confirmed IPMN from January 2005 to December 2014 at Department of Pancreatic Surgery, Zhongshan Hospital Fudan University were enrolled.Forty-six patients were male and 33 were female,with an average age of (62.9±8.9)years (range:37-82 years).Tumor sites:56 tumors were located at the head of the pancreas,22 were located at the body and tail of the pancreas,and 1 was located across the whole pancreas.Surgical procedures: 51 patients underwent pancreaticoduodenectomy, 22 patients underwent distal pancreatectomy, 4 patients underwent segmental pancreatectomy and 2 patients underwent total pancreatectomy.IPMNs were classified into non-invasive lesions and invasive carcinomas according to the histopathological findings of the tumor.Thirty-two tumors were non-invasive lesions and 47 were invasive carcinomas.The preoperative findings were compared between patients with non-invasive IPMN and patients with invasive carcinoma by univariate analysis using t test and χ² test accordingly,and factors with statistically significance were subsequently submitted to multivariate analysis. Results: Univariate analysis showed that tumor size(P=0.022), carcinoembryonic antigen(P=0.012), CA19-9(P=0.011), lymphocytes(P=0.034), neutrophil-to-lymphocyte ratio(P=0.010)and platelet-to-lymphocyte ratio(PLR)(P=0.004)were predictive markers with statistical significance.Multivariate analysis showed that CA19-9(P=0.012)and PLR(P=0.025) were independent predictive markers for invasive malignancy in IPMN.The area under curve of the combination factor of CA19-9 and PLR(0.864) was larger than that of CA19-9(0.806) or PLR(0.685) alone, and all the authentic indicators of the combination factor were better than those of each alone. Conclusions CA19-9 and PLR are independent predictive markers for invasive malignancy in IPMN.The combination of CA19-9 and PLR has improved efficacy than each alone.

Objective: To analyze the characteristics of the "Interner Plus-based AIDS Comprehensive Prevention Service System" among MSM who frequently using the Internet in Guangzhou. Methods: An online survey was conducted among MSM who were recruited through gay-website portals between August and September, 2018 in Guangzhou, to collect information regarding the use of and attitudes on the "Interner Plus-based AIDS Comprehensive Prevention Service System" . Logistic regression was used to explore the association between the use of Internet intervention tools and related behavioral characteristics. Information on the awareness of AIDS, HIV testing, and condomless anal sex behavior were compared between the core or non-core services users. Results: A total of 777 Internet-based MSM were recruited as participants including 638 men (82.1%) as core service users. MSM were satisfied in using the the "Interner Plus-based AIDS Comprehensive Prevention Service System" while more than 80.0% of the users felt that the tools were helpful in: increasing the HIV awareness, promoting test uptake, and reducing those related risk behavior. Comparing with those who did not use the tools, the users showed higher rates in practising condomless anal intercourse (1.50-1.86 times), commercial sex with men (11.60-21.21 times), and unprotected vaginal intercourse (13.62-20.67 times), in the last 6 months. Proportions of core service users appeared as: [96.6% vs. 74.8%, aOR (95%CI): 8.80 (4.85-15.97)] on HIV testing, [56.4% vs. 22.3%, aOR (95%CI): 4.54 (2.94-7.02)] on regular HIV testing and [86.2% vs. 80.6%, aOR (95%CI): 1.75 (1.06-2.89)] on awareness of HIV knowledge respectively, which were all significantly higher than the non-core service users. Conclusions The frequent Internet using MSM in Guangzhou claimed to have had high acceptance and satisfaction on the local Internet HIV intervention service tools. The "Internet Plus-based AIDS Comprehensive Prevention Service System" had effectively reached the high-risk subgroups of MSM, increasing the awareness on related risk and promoting testing on HIV.