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 summarize the clinical manifestations, pathological characteristics, treatment options and prognosis of the world's first case of prostate ductal adenocarcinoma (PDA) complicated with prostate mucinous adenocarcinoma (PMA). [Methods] The clinical and follow-up data of a patient with PDA and PMA treated in Zhongnan Hospital of Wuhan University were retrospectively analyzed, and relevant literature in PubMed and CNKI databases was retrieved. [Results] The patient sought medical attention due to dysuria, frequent urination, urinary urgency and urinary pain for more than half a year, and was admitted to hospital 3 times in total.The initial diagnosis upon the first admission was benign prostatic hyperplasia complicated with prostatic abscess.After 2 months, the patient was readmitted due to worsening symptoms, received transurethral bladder neck incision+ cystoscopy+ transurethral plasma resection of the prostate, and postoperative diagnosis confirmed PDA with local PMA.Three months after surgery, the patient had bleeding.After auxiliary examinations revealed extensive metastasis, he received hormonal therapy.After 9 months, the patient died due to multiple lung metastases. [Conclusion] Early diagnosis has a significant impact on the treatment and prognosis, but there have been no previous reports of PDA combined with PMA, so the lack of specific biomarkers in the early stage has led to missed diagnosis or misdiagnoses.There is no specific treatment for PDA with PMA. Radical prostatectomy was not satisfactory in the treatment of this case.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To compare the application value of ultrasound-guided lumbar plexus block (LPB) and continuous adductor canal nerve block (ACNB) in total hip arthroplasty (THA), and to explore the anesthesia scheme of THA.Methods:A prospective randomized controlled trial was used. Ninety patients who received THA admitted to in Lishui People′s Hospital from March 2019 to February 2022 were selected as the study subjects. According to the random number table method, 90 patients were divided into the test group and the control group, with 45 patients in each. The control group received LPB + general anesthesia, and the test group received ACNB + general anesthesia. By evaluating the hemodynamic parameters heart rate (HR) and mean arterial pressure (MAP) at the time of entry (T 1), osteotomy (T 2), prosthesis implantation (T 3) and immediately after surgery (T 4); the pain degree visual analogue score (VAS) at 6 h (S 1), 12 h (S 2), 24 h (S 3), 48 h (S 4) after awakening; the dosage of anesthetic drugs, the anesthetic effects of LPB and ACNB in THA were compared. Results:From T 2 to T 4, HR of patients in the two groups had a trend of increase: (85.24 ± 4.26) times/min vs. (86.13 ± 4.86) times/min, (83.82 ± 5.11) times/min vs. (85.16 ± 3.56) times/min and (81.64 ± 4.32) times/min vs. (82.24 ± 4.62) times/min, while MAP was in a downward trend: (86.54 ± 4.25) mmHg (1 mmHg = 0.133 kPa) vs. (85.35 ± 4.66) mmHg, (86.15 ± 3.92) mmHg vs. (84.86 ± 4.13) mmHg and (90.65 ± 5.25) mmHg vs. (92.12 ± 4.62) mmHg. The difference at different time points was statistically significant ( P<0.05). There was no statistically significant difference in HR, MAP and change trend between the two groups at different time ( P>0.05). The VAS score of the two groups increased from S 2 time point, and the difference between different time points was statistically significant ( P<0.05). The rising trend of VAS score in the test group was lower than that in the control group, and the VAS score at different time points was lower than that in the control group ( P<0.05). The dosage of sufentanil used in the test group was less than that in the control group: (114.37 ± 16.61) μg vs. (131.36 ± 18.31) μg, and the number of press of analgesia pump was less than that in the control group: 6.00 (5.00, 6.50) times vs. 8.00 (7.00, 9.00) times ( P<0.05). Conclusions:Ultrasound-guided LPB and ACNB could maintain hemodynamic stability in THA. Especially, ACNB could play an analgesic role within 48 h after THA and reduce the dosage of analgesic drugs.

Rabies virus

Clinical data of 46 patients with trans-sphincter anal fistula treated by fistulectomy with external anal sphincter bareness in Department of Anorectal Surgery, Jiaxing TCM Hospital from July 2018 to July 2019 were retrospectively analyzed. All operations were performed successfully. There were no significant differences in Wexner incontinence scores (2.00±0.68 vs.1.99±0.70, P<0.05), mean anal resting pressure [(75.60±8.60) vs.(73.60±8.20)mmHg(1 mmHg=0.133 kPa), P<0.05] and maximum systolic pressure [(109.60±7.80) vs.(107.20±8.30)mmHg, P<0.05] before and 6 months after operation. There were 1 case with postoperative incision bleeding and 2 cases with postoperative infection. All patients were followed up for 6 months and there was no recurrence and changes in anal shape during the follow-up. Results indicate that the fistulectomy external anal sphincter bareness is safe, efficient with well preserved sphincter function for patients with trans-sphincter anal fistula.

Objective To investigate the influence of the concept of collaborative innovation on the construction of a scientific research system for regional liver pathology center from multiple perspectives, and to explore its application significance. Methods A total of 1246 liver biopsy specimens which were examined in Department of Pathology in Wuxi Second People's Hospital and Wuxi Fifth People's Hospital from January 2014 to September 2020 were collected, among which the specimens examined before the founding of the regional liver pathology center were collected as nI group, and those examined after the founding of the center were collected as nII group. According to the examination time of the first, second, or third year after founding, the nII group was further divided into nIIa group, nIIb group, and nIIc group. A multi-perspective analysis was performed based on five indices, i.e., number of liver biopsy specimens, growth rate of liver biopsy specimens, growth rate of internal collaborative departments, growth rate of external collaborative units, and evaluation of the collaborative and innovative scientific research system. Results The growth rate of liver biopsy specimens in the nI group was 15.51%; after the founding of the regional liver pathology center, the highest growth rate of 187.76% was observed in the nIIa group, and a relatively stable growth rate of 76.35% was observed in the nIIb group. There was a gradual increase in the number of specimens in internal collaborative departments, with a growth rate of 50% in the nIIa group and 83.33% in the nIIb group, while the number of external collaborative units increased steadily, with a growth rate of 100% in the nIIa group and 50% in the nIIb group. The nII group showed a diversified increasing trend in the evaluation indices of the scientific research system. Conclusion It is a new perspective for the construction of regional disciplinary scientific research system to grasp the opportunity of policy-supported development and innovate the effective cooperation mode between internal departments and external units under the concept of collaborative innovation.

RNAscope is a new generation of in situ hybridization technology and with the advantage of new probe design, it is now being gradually applied to a wide range of research fields, and its research scope is constantly expanding. Our country has large number of liver disease patients, so there is a great demand for histological testing and research evaluation based upon biological information. This technology has unique specificity and sensitivity in situ level, which makes up for the technical defects of immunohistochemistry and traditional in situ hybridization. Realizing the multiplicity and monomolecular level detection, the qualitative and quantitative analysis of nucleic acid level can be carried out in many aspects of the field of liver disease, and the visual evaluation can be achieved by combining it with tissue in situ to highlight the value of "gold standard". This article summarizes the recent year’s application of RNAscope technology carried out in liver histology field.

Objective: To explore drug utilizing regularity of traditional Chinese medicine(TCM) in treating and preventing asthenopia by analyzing the patent status of TCM in the field of asthenopia control for nearly 20 years. Method: Global patents about TCM in treating and preventing asthenopia were systematic searched in IncoPat platform.The application trend,legal status and categories of patents were analyzed.Meanwhile,the oral prescriptions and external prescriptions were performed correlation index analysis by IBM SPSS Modeler 18.0,respectively;the difference of compatibility rules between them was compared. Result: The number of global patents in treating and preventing asthenopia gradually increased,and the proportion of patents from China was more than 99%.The main patent applications were pharmaceutical composition,oral preparation,external eye patch and so on,but the ratio of licensed patents in total patents was low.In term of drug utilizing regularity,the oral prescriptions paid much attention to using TCM for nourishing the liver and kidney,while external prescriptions highlighted relieving sickness heat and detoxification. Conclusion: Patents of TCM in treating and preventing asthenopia has been kept increasing in recent years,but the authorization rate is low.Formulation based on TCM theory can be statistically summarized,which can be helpful for the development of anti-asthenopia products.