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 characteristics of human papillomavirus (HPV) prevalence and genotype distribution of 18 535 cases in Yuncheng . Methods A sample of 18535 residents who underwent HPV testing in our hospital from August 2020 to September 2023 were enrolled, and HPV genotyping was done to all samples. Then the rate of HPV infection, age distribution, genotype distribution, and multiple infections were statistically analyzed. Results Of the 18,535 subjects included, a total of 4,639 tested positive for HPV, demonstrating a positive rate of 25.03%. The positive rate of HPV infection varied among different age groups (χ²=29.587, P<0.05), with higher rates found in <25 years old group (29.61%) and >60 years old group (25.89%). Overall, 23 genotypes, covering 5315 viruses, were detected. There were 5 low-risk genotypes with the highest percentage of HPV42 (9.29%), and there were 18 high-risk genotypes with HPV52, HPV58, HPV66 and HPV53, subtypes as the most frequent subtypes, accounting for 13.64%, 8.97%, 7.41% and 7.04%, respectively. The type of HPV infection was predominantly single infections, with an overall single infection rate of 21.62% (4008/18535), which accounted for 86.40% (4 008/4 639) of all positive cases, and a multiple genotype infections rate of 3.40% (631/18535). The 25-34 year old group accounted for the largest proportion of single infections (25.12%), while the <25 year old group accounted for the largest proportion of multiple genotype infections (30.74%). Conclusion The prevalence rate of HPV infection in Yuncheng is 25.03%, with a higher positive rate in the <25 years age group and the >60 years age group. A total of 23 HPV genotypes are detected, of which the main genotypes are HPV42, HPV58, HPV66 and HPV53, and the type of infection is dominated by single infections.

Objective To investigate the liver histopathological features of chronic hepatitis B(CHB)patients with normal alanine aminotransferase(ALT)and their correlation with serological markers.Methods Clinical data were collected from 137 patients with normal ALT who were treated in Wuxi Fifth People's Hospital from April 2018 to June 2021,and the differences in liver histopathology and serological markers were analyzed,as well as the correlation between liver histopathology and serological markers.The chi-square test was used for comparison of categorical data between groups,and the Kruskal-Wallis H test was used for comparison of data between multiple groups.A Spearman rank correlation test was performed,and logistic regression was used to perform the multivariate analysis.Results In the ALT≤20 U/L,20—29 U/L,and 30—40 U/L groups,the patients with significant inflammatory necrosis(≥G2)accounted for 57.4%,53.4%,and 75%,respectively,and the patients with significant fibrosis(≥S2)accounted for 63.8%,62.1%,and 75%,respectively.There was a significant difference in the degree of inflammatory necrosis between the patients with positive or negative HBeAg,the patients with different levels of serum HBV DNA,and the patients with different levels of serum HBV RNA(χ2=10.008,6.911,and 7.946,all P<0.05),and there was a significant difference in fibrosis stage between the patients with positive or negative HBeAg and the patients with different levels of serum HBV RNA(χ2=7.996 and 10.874,both P<0.05).The degree of liver inflammation and fibrosis stage were not significantly correlated with serum HBV DNA(rs=0.024,P=0.785;rs=0.039,P=0.652),while they were significantly correlated with serum HBV RNA(rs=0.222,P=0.009;rs=0.187,P=0.029).The multivariate analysis showed that in CHB patients,positive HBeAg was an independent risk factor for inflammatory necrosis(odds ratio[OR]=-0.302,95%confidence interval[CI]:-1.160 to 0.386,P=0.002)and fibrosis(OR=-0.387,95%CI:-1.160 to 0.386,P=0.011).Conclusion There are varying degrees of inflammatory necrosis and fibrosis in the liver of CHB patients with normal ALT,and positive HBeAg is independent risk factor for significant inflammatory necrosis and fibrosis in liver tissue of these patients.

Objective To investigate the population distribution of non-alcoholic fatty liver disease before and after renaming and the association between the types of metabolic risk factors(MRF)for metabolic dysfunction-associated steatotic liver disease(MASLD)and advanced liver fibrosis.Methods This study was conducted among 515 patients who were admitted to The Affiliated Hospital of Xuzhou Medical University and Wuxi Fifth People's Hospital from January 2019 to January 2022 and had hepatocyte steatosis≥5%by liver biopsy.Among these patients,2 patients did not meet the diagnostic criteria for nonalcoholic fatty liver disease(NAFLD)and metabolic associated fatty liver disease(MAFLD),respectively,and were classified as steatotic liver disease(SLD)with other specific causes,and the other 513 patients were divided into MASLD group with 275 patients,comorbid group with 216 patients(MASLD comorbid with other liver diseases),and cryptogenic SLD group with 22 patients.The above groups were compared in terms of clinical features,laboratory markers,and advanced liver fibrosis.The MASLD patients with different types of MRF were compared in terms of clinical features,laboratory markers,and advanced liver fibrosis,and the risk factors for advanced liver fibrosis in patients with MASLD were analyzed.The Kruskal-Wallis H test was used for comparison of continuous data with skewed distribution between multiple groups and further comparison between two groups;the chi-square test was used for comparison of categorical data between multiple groups,and Bonferroni correction was used for further comparison between two groups.The logistic regression analysis was used to identify the risk factors for liver fibrosis.Results Among the 515 patients with SLD,297 patients(57.7%)met the diagnostic criteria for NAFLD,among whom 22 were classified as cryptogenic SLD and 275 met the diagnostic criteria for MASLD,and 467(90.7%)were diagnosed with MAFLD.There were significant differences between the three groups in sex,body mass index(BMI),gamma-glutamyl transpeptidase,triglyceride,cholesterol,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,fasting plasma glucose,NAFLD fibrosis score(NFS),fibrosis-4(FIB-4),and F3-4(all P＜0.05).Compared with the MASLD group and the cryptogenic SLD group,the comorbid group had the highest proportion of patients with advanced liver fibrosis(P＜0.001).With the increase in the type of MRF,the patients tended to have an older age,a significantly higher proportion of female patients,a higher possibility of hypertension and diabetes,and higher levels of metabolic parameters including BMI,blood lipids,and blood glucose(all P＜0.05).With the increase in the types of MRF in MASLD patients,they tended to have significantly higher noninvasive fibrosis scores(NFS and FIB-4)and a significantly higher proportion of patients with advanced liver fibrosis(P＜0.05).The multivariate logistic regression analysis showed that age≥50 years(odds ratio[OR]=2.622,95%confidence interval[CI]:1.091-6.300,P=0.031)and the increase in the type of MRF(OR=1.876,95%CI:1.194-2.947,P=0.006)were independent risk factors for MASLD with severe liver fibrosis.Conclusion The new definition of MASLD is based on the positive identification of MRF,and the reclassified population of MASLD is smaller than that of MAFLD,with little difference from that of NAFLD.In addition,age≥50 years and the increase in the type of MRF are independent risk factors for MASLD with advanced liver fibrosis.

The clinical data of 5 patients with occupational contact dermatitis caused by methyl chlorobutyrate treated in the Affiliated Hospital of Jining Medical College and Mamiao Township Hospital of Jinxiang County from September to October 2021 were retrospectively analyzed. Patients were all males aged 33-47 years with a history of exposure to methyl chlorobutyrate 1 to 4 d before the onset of symptoms. Three patients were hospitalized and 2 patients were treated in outpatient clinic. The clinical manifestations were erythema on the trunk or extremities of varying degrees, scattered with blisters and bullae of different sizes, with thin and clear blisters, local ulceration and exudation; no erosion or ulceration was found in the oral cavity and vulva. All 5 patients had elevated white blood cell counts, and 2 patients had abnormal liver function. All patients received symptomatic treatment with topical drugs. Three hospitalized patients were given methylprednisolone and loratadine; in addition, 1 case also received human immunoglobulin and moxifloxacin hydrochloride injection and 2 cases received hepatoprotective drugs. Two outpatients were given prednisone acetate and loratadine for treatment. Three hospitalized patients were all improved and discharged after 14-30 d of treatment. The rash of 2 outpatients subsided after 14 d of treatment, and there was no recurrence after 1-month follow-up. The occupational contact dermatitis caused by methyl chlorobutyrate is primary irritant contact dermatitis, often manifested as erythema and blisters on the trunk or limbs, and timely anti-allergic treatment can effectively control the disease.

Objective:To study the clinical characteristics and risk factors for hypertriglyceridemia-induced severe acute pancreatitis (HTG-SAP) complicated by acute kidney injury.Methods:The clinical data of HTG-SAP patients admitted to the Department of Critical Care Medicine of the Second Affiliated Hospital of Anhui Medical University from January 2014 to July 2022 were retrospectively collected, and divided into an AKI group and a non-AKI group according to whether AKI occurred. The general condition, laboratory data and clinical characteristics of the two groups were compared. Factors with statistically significant differences were screened for logistic regression analysis and a predictive model was constructed. We plotted the receiver operating characteristic curve and used the area under the curve (AUC) to evaluate the predictive ability of each predictor for HTG-SAP complicated with AKI.Results:A total of 91 patients were included, including 37 (40.7%) with AKI and 54 (59.3%) without AKI. The proportions of extrapancreatic infection, sepsis and multiple organ dysfunction syndrome, requiring mechanical ventilation, continuous renal replacement therapy (CRRT), retroperitoneal puncture, and surgical intervention were higher in the AKI group than in the non-AKI group (all P<0.05). The length of ICU stay, total length of hospitalization, and mortality rate in the AKI group were higher than those in the non-AKI group (all P<0.05). Multivariate logistic regression analysis showed that acute physiology and chronic health status scoreⅡ (APACHEⅡ) ( OR=2.069, 95% CI: 1.286-3.417, P=0.003), abdominal pressure ( OR=1.469, 95% CI: 1.108-1.958, P=0.007), and lactic acid ( OR=3.156, 95% CI: 1.013-9.831, P=0.047) were independent risk factors for AKI in HTG-SAP patients. The AUCs of the APACHEⅡ score, abdominal pressure, lactic acid level and combined prediction model were 0.951, 0.918, 0.837 and 0.986, respectively. Conclusions:Patients with HTG-SAP complicated with AKI were more likely to have complications related to extrapancreatic infection, sepsis and multiple organ dysfunction, and the proportion of mechanical ventilation, CRRT, retroperitoneal puncture and surgical intervention required during hospitalization was greater, the lengths of ICU stay and total hospital stay were longer, and the mortality rate was higher. APACHEⅡ score, abdominal pressure and lactic acid were independent risk factors for HTG-SAP concurrent AKI, and the prediction model established based on these three factors had higher value in predicting HGT-SAP concurrent AKI

Objective:To explore the relevance between secondary retroperitoneal infection, as well as the outcomes, and the approach of intensive care unit (ICU) admission for the patients suffered from acute pancreatitis.Methods:Patients with acute pancreatitis admitted to the ICU of the Second Affiliated Hospital of Anhui Medical University from January 2013 to July 2022 were retrospectively analyzed. According to ICU admission approaches, the patients were divided into the emergency group (first admission or transferred from the emergency department) and the delayed group (transferred from the general wards due to disease evolution). Patients were also divided into retroperitoneal infection group and non-retroperitoneal infection group according to whether retroperitoneal infection was accompanied. Patients' baseline data including gender, age, underlying diseases, laboratory test indicators, acute physiology and chronic health evaluationⅡ score (APACHEⅡ), sequential organ failure assessment (SOFA), computed tomography severity index (CTSI), bedside index of severity in acute pancreatitis (BISAP), and acute complications were collected. Univariate and multivariate logistic regression was used to analyze the risk factors of retroperitoneal infection in patients with acute pancreatitis.Results:A total of 271 patients with acute pancreatitis were enrolled, including 95 cases in the emergency group and 176 cases in the delayed group. The cohort included 71 cases with and 200 cases without retroperitoneal infection development. The incidence of retroperitoneal infection and the 30-day mortality of patients in the delayed group, which was observed with a significantly longer ICU stay (days), [(15.4±21.3) vs. (8.6±10.8), P<0.05], were significantly higher than those in the emergency group [retroperitoneal infection incidence rate: 31.82% (56/176) vs.15.79%(15/95), 30-day mortality: 13.64%(24/176) vs. 4.21%(4/95), both P<0.05]. Univariate Logistic analysis showed significant differences in diabetes, APACHEⅡ, SOFA, CTSI and BISAP score, urea nitrogen, creatinine, blood calcium, D-D dimer, peritoneal puncture catheter drainage and ICU transferred from general wards due to disease evolution between the retroperitoneal infection group and the non-retroperitoneal infection group. Multivariate Logistic regression analysis showed that diabetes, SOFA score, CTSI score, peritoneal puncture catheter drainage and transfered from general wards to ICU due to disease evolution were independent risk factor for retroperitoneal infection in acute pancreatitis patients[odds ratio were 3.379, 1.150, 1.358, 3.855, 2.285, respectively]. Conclusions:Acute pancreatitis patients in ICU transferred from general wards are more likely to develop retroperitoneal infection, and have a higher risk of mortality and a longer ICU stay. Delayed admission to ICU, diabetes, SOFA score, CTSI score and peritoneal puncture catheter drainage are independent risk factors for retroperitoneal infection in patients with acute pancreatitis.

Diabetic cardiomyopathy(DCM)is a metabolic disease and a leading cause of heart failure among people with diabetes.Mass spectrometry imaging(MSI)is a versatile technique capable of combining the molecular specificity of mass spectrometry(MS)with the spatial information of imaging.In this study,we used MSI to visualize metabolites in the rat heart with high spatial resolution and sensitivity.We optimized the air flow-assisted desorption electrospray ionization(AFADESI)-MSI platform to detect a wide range of metabolites,and then used matrix-assisted laser desorption ionization(MALDI)-MSI for increasing metabolic coverage and improving localization resolution.AFADESI-MSI detected 214 and 149 metabolites in positive and negative analyses of rat heart sections,respectively,while MALDI-MSI detected 61 metabolites in negative analysis.Our study revealed the heterogenous metabolic profile of the heart in a DCM model,with over 105 region-specific changes in the levels of a wide range of metabolite classes,including carbohydrates,amino acids,nucleotides,and their derivatives,fatty acids,glycerol phospholipids,carnitines,and metal ions.The repeated oral administration of ferulic acid during 20 weeks significantly improved most of the metabolic disorders in the DCM model.Our findings provide novel insights into the molecular mechanisms underlying DCM and the potential of ferulic acid as a therapeutic agent for treating this condition.

Objective:To study the risk factors for the failure of retroperitoneal percutaneous catheter drainage (PCD) for infected pancreatic necrosis (IPN).Methods:The clinical data of 68 patients with IPN treated with PCD in the Second Affiliated Hospital of Anhui Medical University from January 2019 to April 2023 were retrospectively analyzed, including 43 males and 25 females, aged (49.0±16.3) years old. Patients were divided into the PCD success group ( n=26) and PCD failure group ( n=42). The score of disease severity and laboratory indices before PCD and the vital organ function scores and enteral nutrition tolerance 48 hours after PCD were collected and accessed by univariate analysis, and factors with P<0.05 were included in the logistic multivariate regression analysis for the risk factors of PCD failure. Results:There were statistical significance in the acute physiological and chronic health status (APACHE Ⅱ) score within 24 hours of admission; the modified CT severity index (MCTSI) score, time of enhanced CT scan, acute kidney injury, acute respiratory distress syndrome (ARDS), and the total amount of noradrenaline before first PCD; the APACHE II score and sequential organ failure (SOFA) score within 48 hours after first PCD; and the culture results of drainage and start of enteral nutrition in the two groups (all P<0.05). Multifactorial logistic regression analysis showed that the occurrence of ARDS before first PCD ( OR=4.682, 95% CI: 1.010-21.692, P=0.048), the delayed start of enteral nutrition ( OR=1.286, 95% CI: 1.020-1.622, P=0.033), the high MCTSI score before first PCD ( OR=2.125, 95% CI: 1.198-3.767, P=0.010), and high SOFA score within 48 hours after first PCD ( OR=1.579, 95% CI: 1.142-2.183, P=0.006) were independent risk factors for the failure of PCD. Conclusion:Patients with ARDS before first PCD, high MCTSI score before first PCD, high SOFA score within 48 hours after first PCD, and the delayed start of enteral nutrition were risk factors for the failure of PCD for IPN.

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