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

Purpose To explore the value of contrast-enhanced ultrasound(CEUS)in the differential diagnosis of gallbladder polypoid lesions(GPLs)(diameter≥10 mm).Materials and Methods A prospective enrollment of 229 patients with GPLs who underwent cholecystectomy in 17 hospitals from December 1 2021 to June 30 2024 was conducted to analyze the relationship between general data,conventional ultrasound,CEUS characteristics and the nature of GPLs.Multivariate Logistic regression was employed to identify independent risk factors for neoplastic polyps,the differential diagnostic value of different indicators was compared.Results Among 229 patients with GPLs,there were 108 cases of cholesterol polyps,102 cases of adenoma and 19 cases of gallbladder cancer.Age(Z=-4.476,P<0.001),polyp number(χ2=15.561,P<0.001),diameter(Z=-8.149,P<0.001),echogenicity(χ2=9.241,P=0.010),vascularity(χ2=23.107,P<0.001),enhancement intensity(χ2=47.610,P<0.001),enhancement pattern(χ2=6.468,P=0.011),vascular type(χ2=84.470,P<0.001),integrity of gallbladder wall(χ2=7.662,P=0.006)and stalk width(Z=-9.831,P<0.001)between cholesterol polyps and neoplastic polyps were statistically significant.Age,location,diameter,echogenicity,enhancement pattern,vascular type and stalk width between adenoma and gallbladder cancer were statistically significant(Z=-4.333,-3.902,-5.042,all P<0.05).Multivariate Logistic regression analysis showed that hyper-enhancement,branched vascular type and stalk width were independent risk factors for neoplastic polyps(OR=4.563,5.770,3.075,all P<0.001).The combination of independent risk factors was better than single factor and diameter in the differential diagnosis of cholesterol polyps and neoplastic polyps(all P<0.01).Conclusion CEUS can effectively identify the nature of GPLs and provide a valuable imaging reference for the selection of treatment methods.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To establish an ideal modeling method for diarrhea predominant irritable bowel syndrome(IBS-D)with anxiely and depression in rats,and to provide a basis for the clinical study of IBS-D.Methods 60 rats were used in this study.(1)At first,20 rats were randomly divided into blank,3%acetic acid enema,4%acetic acid enema,and 5%acetic acid enema groups.After the modeling and observation period,the diarrhea status and the degree of colon injury caused by different modeling concentrations were observed by diarrhea related index and colon histopathology.(2)After the optimal modeling concentration was assessed,40 rats were randomly divided into control(a),acetic acid enema(b),acetic acid+binding(c),and acetic acid+binding+tail clip(d)groups and correspondingly treated for 8 days.After the treatments,the general condition,diarrhea-related index,open field test(OFT)score,and colonic histopathology of rats were evaluated.Results(1)Compared with the blank group,the fecal trait score of 4%acetic acid enema group was increased on days 1 to 3 after intervention(P＜0.001),and gradually decreased on days 4 to 7 after intervention.After 1 week,there was no significant difference between the fecal trait score and that of the blank group(P＞0.05).Body weight was lower(P＜0.01),fecal water content was higher(P＜0.001).Compared with blank group,body weight of the 5%acetic acid enema group was decreased(P＜0.001),the fecal trait score and diarrhea index were increased(P＜0.01).No significant difference was found between 3%acetic acid enema and blank groups.The pathological colon tissue showed that,compared with the blank group,the mucosal structure of the 4%acetic acid enema group was complete with a small amount of inflammatory cell infiltration,and the pathological tissue score showed no significant difference(P＞0.05),whereas the 5%acetic acid enema had a medium to large amount of inflammatory cell infiltration,and the pathological tissue score was increased(P＜0.01).(2)Compared with group a,group b had lower body weight(P＜0.001),and higher fecal trait score,fecal water content and diarrhea index(P＜0.01).Compared with a and b groups,the body weight of c and d groups was lower(P＜0.001),the fecal traits score,fecal water content,and diarrhea index were increased(P＜0.01),and the colon running time was decreased(P＜0.01).Compared with group c,Fecal water content in group D was higher(P＜0.001).In the OFT score,compared with a and b groups,the OFT distance,standing times,and upright times in c and d groups were lower(P＜0.05).Compared with c,the OFT distance,standing times,and upright times in d group were lower(P＜0.05).The pathological tissue of colon showed that the mucosal structure of the four groups was complete,and there were different degrees of inflammatory cell infiltration.The pathological tissue scores of groups c and d were higher than those of groups a and b(P＜0.05).Conclusions The 4%acetic acid concentration is appropriate for IBS-D modeling.After superposition and binding,the IBS-D diarrhea and internal hypersensitivity characteristic state can be better simulated.After superposition of a tail clip,the IBS-D model of liver stagnation and spleen deficiency can be established successfully.

BACKGROUND: Abnormal type I collagen (COL1) expression is associated with the development of many cardiovascular diseases. The TGF-beta/Smad signaling pathway and circRNAs have been shown to regulate COL1 gene expression, but the underlying molecular mechanisms are still not fully understood. METHODS: Gain- and loss-of-function experiments were prformed to study the effect of circZBTB46 on the expression of alpha 2 chain of type I collagen (COL1A2). Co-immunoprecipitation assay was performed to observe the interaction between two proteins. RNA immunoprecipitation assay and biotin pull-down assay were performed to observe the interaction of circZBTB46 with PDLIM5. RESULTS: In this study, we investigated the role of circZBTB46 in regulating COL1A2 expression in human vascular smooth muscle cells (VSMCs). We found that circZBTB46 is expressed in VSMCs and that TGF-beta inhibits circZBTB46 formation by downregulating KLF4 expression through activation of the Smad signaling pathway. CircZBTB46 inhibits the expression of COL1A2 induced by TGF-beta. Mechanistically, circZBTB46 mediates the interaction between Smad2 and PDLIM5, resulting in the inhibition of Smad signaling and the subsequent downregulation of COL1A2 expression. Furthermore, we found that the expression of TGF-beta and COL1A2 is decreased, while circZBTB46 expression is increased in human abdominal aortic aneurysm tissues, indicating that circZBTB46-mediated regulation of TGF-beta/Smad signaling and COL1A2 synthesis in VSMCs plays a crucial role in vascular homeostasis and aneurysm development. CONCLUSIONS CircZBTB46 was identified as a novel inhibitor of COL1 synthesis in VSMCs, highlighting the importance of circZBTB46 and PDLIM5 in regulating TGF-beta/Smad signaling and COL1A2 expression.

Bosworth fracture and dislocation is relatively rare, accounting for about 1% of ankle fractures. It is characterized by the proximal fibula fracture embedded in the posterolateral distal tibia. Due to an insufficient understanding of this fracture, it is easy to cause missed diagnosis and misdiagnosis in clinical practice. Due to the insertion of the fracture, it is challenging to perform closed reduction, and improper treatment is easy to cause complications. Surgical treatment is recommended for this type of fracture. In order to improve the understanding of orthopedic surgeons about Bosworth fracture and dislocation, this paper reports the diagnosis and treatment of 2 cases of Bosworth fracture and dislocation, and reviews the literature on Bosworth fracture's mechanism, diagnosis, classification, complications, and treatment options in recent years.
Humans ; Ankle Fractures/surgery* ; Joint Dislocations/surgery* ; Fracture Fixation, Internal ; Fibula ; Tibia

Aim To develop a ultra-high performance liquid chromatography electrospray-ionization tandem mass spectrometry ( UPLC-MS/MS ) method for the simultaneous determination of salidroside derivative pOBz in rat plasma and brain tissue, and to study the pharmacokinetic profile and penetration of the blood-brain barrier in rats after a single dose intravenous administration of pOBz. Methods SD rats were administered pOBz at a dose of 50 mg • kg

Aim To investigate the neuroprotective effect of prophylactic administration of salidroside (Sal) on MCAO rats. Methods A total of 52 SD adult male rats were randomly divided into sham operation group (Sham), model group (MCAO) and salidroside pre-administration group (MCAO + Sal). The dose of Sal was 50 mg·kg

OBJECTIVES: To explore the effect of acupuncture and moxibustion on intestinal flora in the rats with diarrhea-predominant irritable bowel syndrome (IBS-D) based on 16S rDNA technique. METHODS: Ten rats were randomized from 58 SPF-grade male SD rats to be the blank group. The remained 48 rats were prepared to be IBS-D models by the modified method of acetic acid enema combined with binding tail-clip stress. Forty successfully-modeled rats were randomly divided into a model group, an acupuncture group, a moxibustion group and a western medication group, with 10 rats in each one. In the acupuncture group, the needle was inserted at bilateral "Zusanli" (ST 36) and remained for 15 min in each rat. In the moxibustion group, the suspending moxibustion was delivered at bilateral "Zusanli" (ST 36) for 15 min. The rats in the western medication group were given pinaverium bromide suspension (10 mL/kg) by intragastric administration. The above interventions were performed once daily for consecutive 14 days. The body mass and the score of fecal trait were compared before and after modeling, as well as after intervention in each group. Fecal water content, diarrhea index and colon transit time (CTT) were measured after modeling and intervention in the rats of each group separately. After intervention, the colonic morphology of rats in each group was observed, and using 16S rDNA technique, the intestinal flora was detected. RESULTS: After modeling, compared with the blank group, the body mass and CTT were reduced (P<0.01); fecal trait scores, fecal water contents and diarrhea index increased (P<0.01) in the other 4 groups. After intervention, the body mass and CTT of the rats decreased (P<0.01), and fecal trait score, fecal water content and diarrhea index increased (P<0.01) in the model group compared with those in the blank group. In the acupuncture group, the moxibustion group and the western medication group, when compared with the model group, the body mass and CTT were elevated (P<0.01), while fecal trait scores, fecal water contents and diarrhea index declined (P<0.01). Compared with the western medication group, fecal water content decreased in the acupuncture group and the moxibustion group (P<0.05), while CTT increased in the acupuncture group (P<0.01), the body mass increased and fecal trait score was dropped in the moxibustion group (P<0.05). The colonic mucosa structure was clear and complete, and there was no obvious inflammatory cell infiltration in the blank group. The mild interstitial edema of intestinal mucosa was presented with the infiltration of few inflammatory cells in the model group. There was the infiltration of few inflammatory cells in the mucosa of the acupuncture group, the moxibustion group and the western medication group. Compared with the blank group, the indexes of Richness, Chao1, ACE and Shannon decreased in the model group (P<0.05). Indexes of Richness, Chao1 and ACE increased in the acupuncture group and the moxibustion group (P<0.05), and the Richness index in the western medication group increased (P<0.05) when compared with those in the model group. The relative abundance of Bacteroidetes, Proteobacteria and Prevotella increased (P<0.05), and that of Firmicutes and Muribaculaceae decreased (P<0.05) in the model group compared with those in the blank group. When compared with the model group, the relative abundance of Bacteroidetes, Proteobacteria and Prevotella was reduced (P<0.05), while that of Firmicutes and Muribaculaceae increased (P<0.05) in the acupuncture group, the moxibustion group and the western medication group; and that of Actinobacteria and Bifidobacterium increased in the acupuncture group and the moxibustion group (P<0.05). Compared with the blank group, the relative abundance of lipopolysaccharide (LPS) biosynthesis was elevated (P<0.05), and that of folate biosynthesis, lipoic acid metabolism, zeatin biosynthesis, ubiquinone and other terpenoid quinone biosynthesis decreased (P<0.05) in the model group. The relative abundance of LPS biosynthesis was dropped (P<0.05), and that of folate biosynthesis, lipoic acid metabolism, zeatin biosynthesis, ubiquinone and other terpenoid quinone biosynthesis increased (P<0.05) in the acupuncture group, the moxibustion group and the western medication group compared with those of the model group. CONCLUSIONS Either acupuncture or moxibustion can relieve the symptoms of IBS-D and protect intestinal mucosa, which may be associated with regulating the structure of intestinal flora and promoting nutrient metabolism and biosynthesis.
Rats ; Male ; Animals ; Irritable Bowel Syndrome/therapy* ; Moxibustion/methods* ; Rats, Sprague-Dawley ; Gastrointestinal Microbiome ; Lipopolysaccharides ; Thioctic Acid ; Ubiquinone ; Zeatin ; Acupuncture Therapy ; Diarrhea/therapy* ; Terpenes ; Water ; Folic Acid ; Acupuncture Points

Objective:To study the correlation between anti-gp210 antibody, anti-sp100 antibody with clinical features and prognosis of patients with PBC.Methods:A total of 992 patients with PBC from 9 medical centers in Yunnan Province from January 1, 2015 to December 31, 2021 were included retrospectively. The demographic data, medical history, UDCA treatment, laboratory and imaging data were collected, and telephone follow-up was conducted. The positive rates of anti-gp210 antibody and anti-sp100 antibody in PBC patients with different clinical characteristics were compared, and the differences of laboratory parameters and prognosis between the anti-gp210 and anti-sp100 antibodies positive and negative groups were compared. T test, rank sum test, variance analysis were used for statistical analysis.Results:The positive rate of anti-gp210 antibody in Han patients was significantly higher than that in minority patients (21.5% vs 9.9%, χ2=6.88, P=0.009), but there was no significant difference in the positive rate of anti-sp100 antibody between the two groups (10.9% vs 6.6%, χ2=1.62, P=0.204).There were no significant differences in the positive rates of anti-gp210 antibody and anti-sp100 antibody among different genders ( χ2=0.50, P=0.478)( Z=-0.41, P=0.682)and ages( χ2=0.01, P=0.951)( Z=-0.60, P=0.549). There was no significant difference in the positive rate of anti-gp210 antibody between AMA M2 antibody positive and negative patients ( χ2=3.45, P=0.063), PBC patients with Sj?gren′s syndrome compared with those without Sj?gren′s syndrome (21.3% vs 20.4%, χ2=0.05, P=0.828), and PBC patients with viral hepatitis compared with those without viral hepatitis(19.6% vs 20.5%, χ2=0.02, P=0.877). The positive rate of anti-gp210 antibody was significantly increased in patients with PBC confirmed by liver biopsy with unknown diagnosis (25.6% vs 18.4%, χ2=6.52, P=0.011), patients with AIH (26.6% vs 18.9%, χ2=5.82, P=0.016), cirrhosis (23.3% vs 11.3%, χ2=16.00, P<0.001), decompensation of cirrhosis (23.9% vs 18.2%, χ2=4.66, P=0.031), jaundice (29.7% vs 17.1%, χ2=18.59, P<0.001) and hyperlipidemia (24.9% vs 18.1%, χ2=6.30, P=0.012). The positive rate of anti-sp100 antibody was significantly increased in patients with negative AMA M2 antibody PBC patients (20.9% vs 7.2%, χ2=36.54, P<0.001)and patients with PBC confirmed by liver biopsy with unknown diagnosis (17.9% vs 7.5%, χ2=23.40, P<0.001), while in patients with AIH (11.1% vs 10.3%, χ2=0.09, P=0.769), Sj?gren′s syndrome (15.7% vs 10.0%, χ2=2.87, P=0.090), viral hepatitis (4.3% vs 10.8%, χ2=1.94, P=0.164), cirrhosis(10.5% vs 10.5%, χ2<0.01, P=0.991), decompensated symptoms of cirrhosis (10.3% vs 10.6%, χ2=0.03, P=0.868), jaundice (12.5% vs 9.7%, χ2=1.62, P=0.203)and hyperlipidemia (8.7% vs 11.5%, χ2=1.86, P=0.172), the positive rate was not significantly increased. The levels of ALT [71.00(48.00, 111.00)U/L vs 58.00 (31.00,112.75)U/L, Z=-2.63, P=0.009], AST [92.00 (54.00, 133.00)U/L vs 76.00(42.00, 128.00)U/L, Z=-2.73, P=0.006], ALP[306.00(176.00, 528.00)U/L vs 204.00(126.25, 350.75)U/L, Z=-4.78, P<0.001], GGT[284.00(131.00, 524.00)U/L vs 165.00(53.63, 389.00)U/L, Z=-4.36, P<0.001], TBIL[33.60(16.60, 82.10)mmol/L vs 23.45 (14.80, 61.13)mmol/L, Z=-3.00, P=0.003], DBIL [20.30 (6.60, 66.40)mmol/L vs 11.60 (5.90, 45.00)mmol/L, Z=-3.13, P=0.002], bile acid[53.40(19.50, 148.00)mmol/L vs 39.30(11.70, 118.58)mmol/L, Z=-2.26, P=0.024], IgM[3.61(2.03,5.26)g/L vs 2.39(1.37, 3.67)g/L, Z=-5.38, P<0.001] and APTT[37.40(33.10, 41.30)s vs 35.70 (31.30, 41.30)s, Z=-3.28, P=0.001])were significantly increased in patients with positive anti-gp210 antibody compared patients with negative anti-gp210 antibody, while the IgG level was significantly increased in patients with positive anti-sp100 antibody compared with patients with negative anti-gp210 antibody( Z=-2.25, P=0.025), but no other indexes were significantly increased. The Mayo risk score[3.48(2.46, 5.01) vs 3.18 (2.20, 4.64), Z=-2.052, P=0.04] and mortality at the end of follow-up (24.6% vs 16.7%, χ2=6.57, P=0.0.038)in patients with positive anti-gp210 antibody were much higher than those in patients with negative anti-gp210 antibody, but there were no significant differences in Mayo risk score [3.16 (2.21, 4.53) vs 3.28 (2.23,4.71), Z=-0.86, P=0.392] and mortality at the end of follow-up (13.5% vs 18.9%, χ2=2.12, P=0.346) between anti-sp100 antibody positive and negative patients. Conclusion:PBC patients with positive anti-gp210 antibody may have more serious liver pathologic damage and extra-hepatic complications, more serious liver function impairment, more obvious cholestasis, and worse prognosis. Anti-sp100 antibody has been shown to have no significant correlation with disease severity and prognosis.