Fear memories are temporarily suppressed after repeated retrieval, a phenomenon known as memory extinction.How to reduce or even eliminate fear memory is the key to the treatment of fear related diseases such as post-traumatic stress disorder(PTSD). A single extinction training based on Pavlov's fear regulation task could only inhibit the expression of conditioned fear memory traces, but it could not eliminate the acquired conditioned fear memory. However, according to the reconsolidation theory based on memory, the retrieval-extinction paradigm has a more lasting effect on the erasure and rewriting of fear memory, and can effectively prevent the return of fear memory. Studies have shown that extraction-regression is closely related to a variety of neurotransmitter receptors such as glutamate receptor(GluR), dopamine receptor(DAR), L-type voltage-gated calcium channels(LVGCs) and cannabinoid. Moreover, its effect is closely related with factors such as retrieval-extinction memory stage. At present, most of the researches on extracted boundary conditions only stay at the level of behavior, with little understanding and exploration on the level of molecular mechanism. From the perspective of molecular neurobiology, with different stages of memory and different types of receptors and molecular mechanisms, this research reviewed the mechanisms of retrieval-extinction in recent years.It provided valuable signaling pathways, molecular targets and research directions for the treatment of fear-related diseases such as PTSD.

Chemokine CXC ligand 12 (CXCL12)-chemokine receptor 4 (CXCR4) signal axis is involved in the regulation of liver injury repair and the occurrence and development of liver fibrosis. In case of acute and chronic liver injury, the expression of CXCL12 is up-regulated to collect CXCR4-positive immune cells to migrate to the liver. The CXCL12-CXCR4 pathway participates in the occurrence of liver fibrosis by promoting the activation and proliferation of hepatic stellate cells. The emergence of small molecule inhibitors of CXCR4 makes this receptor an attractive target for anti-fibrosis therapy. At present, CXCR4 has been tried as an anti-fibrosis treatment targets for fibrosis of various organs, including pulmonary fibrosis and chronic pancreatitis. However, some studies have shown that simply blocking the CXCL12/CXCR4 axis cannot improve liver fibrosis and even aggravate liver injury. In recent years, with the discovery and understanding of CXCR7, another receptor of CXCR12, the counteracting role of CXCR4-promoting fibrosis pathway and CXCR7-promoting regeneration pathway in liver regeneration and liver fibrosis has been interpreted. Therefore, a full understanding of the regulatory mechanism of CXCL12-CXCR4/CXCR7 pathway, the development of corresponding targeted therapy research for liver disease, and the rebalancing of CXCR4 and CXCR7 are expected to become a new strategy for the liver fibrosis therapy.

Objective To compare the clinical efficacy between a direct aspiration first-pass technique(ADAPT)and stent-retriever thrombectomy(SRT)in the treatment for acute ischemic stroke(AIS)caused by intracranial atherosclerotic stenosis related large vessel occlusion(ICAS-LVO).Methods We retrospectively included patients with AIS caused by ICAS-LVO who received endovascular treatment in The First Affiliated Hospital of Xi'an Jiaotong University or The Second Affiliated Hospital of Shaanxi University of Chinese Medicine between January 2020 and January 2023.They were divided into ADAPT group and SRT group according to the first-selected device for thrombectomy.We compared the baseline data,test and examination results,operation process,clinical prognosis and follow-up data of the two groups.Results A total of 117 patients were recruited,including 48 patients in the ADAPT group and 69 patients in the SRT group.There was no significant difference in the baseline data between the two groups.The success rate of both the first-time thrombectomy(P=0.014)and the first-selected device of thrombectomy(P＜0.001)was significantly higher in the SRT group than in the ADAPT group.Meanwhile,the incidence of iatrogenic dissection(P＜0.001)and vasospasm(P=0.003)was significantly lower in the SRT group than in the ADAPT group.The proportion of patients for whom the device of thrombectomy was changed for remedial treatment in the ADAPT group was significantly higher than that in the SRT group(P＜0.001).However,the two groups did not differ significantly in the rate of successful vascular recanalization,incidence of symptomatic/asymptomatic intracranial hemorrhage or the rate of 90-day favorable prognosis.Conclusion For patients with AIS caused by ICAS-LVO of MCA,SRT has a higher rate of immediate successful vascular recanalization with a lower rate of secondary vascular injury compared with ADAPT,but the two techniques have similar efficacy on the 90-day prognosis.

Objective:To investigate the agreement of ultrasound derived fat fraction (UDFF) with magnetic resonance imaging proton density fat fraction (MRI PDFF) on evaluating hepatic steatosis, and the performance of UDFF on diagnosing metabolic dysfunction associated steatotic liver disease (MASLD).Methods:One hundred and twenty-five volunteers and one hundred and seven inpatients who underwent abdominal ultrasound examination in Zhongda Hospital Southeast University from November 2023 to February 2024 were prospectively enrolled.UDFF and MRI PDFF were applied to evaluate hepatic steatosis. Spearman correlation test and Bland-Altman plot were applied to analyze the agreement of UDFF and MRI PDFF. Receiver operating characteristic curve (ROC) was applied to calculate the performance of UDFF on diagnosing MASLD.Results:In our participants, compared to individuals without hepatic steatosis, patients with MASLD had higher body mass index (BMI), waist-to-hip ratio, prevalence of diabetes mellitus, levels of alanine transaminase (ALT), aspertate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), triglyceride, and UDFF (all P<0.05). The percentage of hepatic steatosis measured by UDFF and MRI PDFF was strongly correlated[ρ=0.873(95% CI=0.837-0.901), P<0.001]. UDFF performed excellent for diagnosing MASLD with an area under the curve (AUC) of 0.983(95% CI=0.956-0.995, P<0.001), and was better than semi-quantitative assessment based on two-dimensional ultrasound as well as ultrasound attenuation parameter. The optimal cut off value of UDFF to diagnose MASLD was ≥6%. Conclusions:The percentage of hepatic steatosis measured by UDFF and MRI PDFF agrees with each other, and UDFF obtains an excellent performance on diagnosing MASLD, so that UDFF should be considered a reliable imaging technique for quantitively evaluating hepatic steatosis and diagnosing MASLD.

Objective: To analyze the using of pre-hospital emergency resources and treatment characteristics of acute alcoholism patients in Guangzhou. Methods: The pre-hospital emergency data of the emergency department of the Second Affiliated Hospital of Guangzhou Medical University from January 1st in 2009 to December 31st in 2018 were obtained from the database of the Guangzhou Emergency Medical Command Center. The related data of patients with acute alcoholism were collected, including gender, age, poisoning severity, treatment results, caller type, number of empty vehicles (empty vehicle was defined as the empty vehicle return caused by the ambulance who did not receive or refused to come to the hospital after the ambulance leaved), departure time (from the ambulance to the completion time), on-site time (from the ambulance to the patient boarding time) and the distribution of pre-hospital emergency time in 24 hours on weekdays and weekends. The relationship between acute alcoholism patients and the peak of in-hospital emergency treatment was analyzed. Results: A total of 2 408 acute alcoholism patients were recorded, among whom 2 109 patients (87.58%) with acute alcoholism, 126 (5.23%) with drug poisoning, 67 (2.78%) with chemical poisoning, 3 (0.13%) with pesticide poisoning, and 103 (4.28%) with other poisoning. Acute alcoholism patients were mainly male, with a total of 1 862 cases (88.29%), and the ratio between males and females was 7.54∶1. In 2 109 patients with acute alcoholism, 93.41% were in the age range of 18-59 years old. The number of mild patients was 1 717 (81.41%), 1 178 (55.86%) needed further treatment, and no patient died. For the occupation of pre-hospital emergency resources, 43.24% (912/2 109) of acute alcoholism called 120 through 110 with empty vehicles of 36.79% (776/2 109), which were significantly higher than the acute cerebrovascular disease [3.83% (362/9 461), 5.80% (549/9 461), both P < 0.01], acute trauma [24.29% (1 708/7 033), 7.96% (560/7 033), both P < 0.01], acute circulation system disease [2.44% (90/3 694), 2.87% (106/3 694), both P < 0.01], and acute respiratory system disease [0.86% (31/3 606), 1.58% (57/3 606), both P < 0.01]. Furthermore, empty vehicles were more likely to happen through 110 with empty vehicles rate of 51.75% (472/912), which was significantly higher than that through the witness [40.82% (60/147), P < 0.01] and relatives and friends [23.24% (244/1 050), P < 0.01]. The driving time and on-site time of acute alcoholism were significantly shorter than those of acute cerebrovascular disease, acute circulation system disease, and acute respiratory system disease [driving time (minutes): 26 (20, 34) vs. 34 (26, 45), 38 (29, 49), 38 (29, 50); on-site time (minutes): 6 (4, 10) vs. 10 (7, 14), 10 (7, 15), 10 (8, 15), all P < 0.01], but there was no statistical difference as compared with acute trauma [driving time (minutes): 26 (20, 34) vs. 29 (20, 42), on-site time (minutes): 6 (4, 10) vs. 7 (4, 11), both P > 0.05]. The regularity of variation in number of critically acute alcoholism patients was distinctive, which peaked in the period of 21:00-00:00 and bottomed out in the period of 09:00-13:00, which overlapped with the peak flow in the hospital emergency department (17:00-22:00). Conclusions Acute alcoholism patients occupy excessive pre-hospital emergency resources, and overlap with the hospital emergency treatment peak. It is necessary to strengthen the public propaganda and education on the rational usage of 120 emergency resources and reduce waste.

OBJECTIVE: To analyze the using of pre-hospital emergency resources and treatment characteristics of acute alcoholism patients in Guangzhou. METHODS: The pre-hospital emergency data of the emergency department of the Second Affiliated Hospital of Guangzhou Medical University from January 1st in 2009 to December 31st in 2018 were obtained from the database of the Guangzhou Emergency Medical Command Center. The related data of patients with acute alcoholism were collected, including gender, age, poisoning severity, treatment results, caller type, number of empty vehicles (empty vehicle was defined as the empty vehicle return caused by the ambulance who did not receive or refused to come to the hospital after the ambulance leaved), departure time (from the ambulance to the completion time), on-site time (from the ambulance to the patient boarding time) and the distribution of pre-hospital emergency time in 24 hours on weekdays and weekends. The relationship between acute alcoholism patients and the peak of in-hospital emergency treatment was analyzed. RESULTS: A total of 2 408 acute alcoholism patients were recorded, among whom 2 109 patients (87.58%) with acute alcoholism,126 (5.23%) with drug poisoning, 67 (2.78%) with chemical poisoning, 3 (0.13%) with pesticide poisoning, and 103 (4.28%) with other poisoning. Acute alcoholism patients were mainly male, with a total of 1 862 cases (88.29%), and the ratio between males and females was 7.54:1. In 2 109 patients with acute alcoholism, 93.41% were in the age range of 18-59 years old. The number of mild patients was 1 717 (81.41%), 1 178 (55.86%) needed further treatment, and no patient died. For the occupation of pre-hospital emergency resources, 43.24% (912/2 109) of acute alcoholism called 120 through 110 with empty vehicles of 36.79% (776/2 109), which were significantly higher than the acute cerebrovascular disease [3.83% (362/9 461), 5.80% (549/9 461), both P < 0.01], acute trauma [24.29% (1 708/7 033), 7.96% (560/7 033), both P < 0.01], acute circulation system disease [2.44% (90/3 694), 2.87% (106/3 694), both P < 0.01], and acute respiratory system disease [0.86% (31/3 606), 1.58% (57/3 606), both P < 0.01]. Furthermore, empty vehicles were more likely to happen through 110 with empty vehicles rate of 51.75% (472/912), which was significantly higher than that through the witness [40.82% (60/147), P < 0.01] and relatives and friends [23.24% (244/1 050), P < 0.01]. The driving time and on-site time of acute alcoholism were significantly shorter than those of acute cerebrovascular disease, acute circulation system disease, and acute respiratory system disease [driving time (minutes): 26 (20, 34) vs. 34 (26, 45), 38 (29, 49), 38 (29, 50); on-site time (minutes): 6 (4, 10) vs. 10 (7, 14), 10 (7, 15), 10 (8, 15), all P < 0.01], but there was no statistical difference as compared with acute trauma [driving time (minutes): 26 (20, 34) vs. 29 (20, 42), on-site time (minutes): 6 (4, 10) vs. 7 (4, 11), both P > 0.05]. The regularity of variation in number of critically acute alcoholism patients was distinctive, which peaked in the period of 21:00-00:00 and bottomed out in the period of 09:00-13:00, which overlapped with the peak flow in the hospital emergency department (17:00-22:00). CONCLUSIONS Acute alcoholism patients occupy excessive pre-hospital emergency resources, and overlap with the hospital emergency treatment peak. It is necessary to strengthen the public propaganda and education on the rational usage of 120 emergency resources and reduce waste.
Acute Disease ; Adolescent ; Adult ; Alcoholism/epidemiology* ; China/epidemiology* ; Emergency Service, Hospital ; Female ; Humans ; Male ; Middle Aged ; Surveys and Questionnaires ; Young Adult

Objective To investigate the efficacy and safety of programmed death receptor-1 (PD-1) inhibitor combined with transarterial chemoembolization (TACE) and anti-angiogenic drug tyrosine kinase inhibitor (TKI) versus TACE combined with TKI in the treatment of advanced hepatocellular carcinoma (HCC) and related influencing factors for prognosis. Methods An analysis was performed for all patients who received TACE+TKI+PD-1 inhibitor and some patients who received TACE+TKI in The First Affiliated Hospital of Air Force Medical University from June 2018 to July 2021. Related clinical data were collected, and propensity score matching (PSM) was used to balance the baseline characteristics between groups. The chi-square test was used for comparison of categorical data between two groups; the Wilcoxon rank-sum test was used for comparison of the number of TACE procedures between two groups; the Kaplan-Meier method was used to analyze overall survival (OS), and univariate and multivariate Cox regression models were used to analyze the influencing factors for prognosis. Results A total of 181 patients with advanced HCC were screened out, among whom 50 patients were treated with TACE+TKI+PD-1 inhibitor; after PSM, 40 patients treated with TACE+TKI+PD-1 inhibitor were enrolled as observation group and 40 patients treated with TACE+TKI were enrolled as control group. At the end of follow-up, the median follow-up time was 28.6 (95% confidence interval [ CI ]: 22.1-35.1) months, and the median OS was 15.9 (95% CI : 7.5-24.2) months in the observation group and 11.2 (95% CI : 5.0-17.5) months in the control group. The Cox regression analysis showed that the application of PD-1 inhibitor (hazard ratio [ HR ]=0.42, 95% CI : 0.23-0.80, P =0.008), the number of TACE procedures ( HR =0.67, 95% CI : 0.46-0.99, P =0.043), Child-Pugh class ( HR =2.40, 95% CI : 1.15-5.00, P =0.019), and vascular invasion ( HR =3.42, 95% CI : 1.11-9.42, P =0.031) were independent influencing factors for prognosis. The incidence rate of grade > 2 adverse events was 40% for both the observation group and the control group, and there was no significant difference between the two groups ( P =0.818). Conclusion Compared with TACE+TKI, TACE+TKI+PD-1 inhibitor can significantly prolong the OS of patients in advanced HCC, with relatively controllable adverse events.

Genome-wide association studies (GWASs) are the most widely used method to identify genetic risk loci associated with orofacial clefts (OFC). However, despite the increasing size of cohort, GWASs are still insufficient to detect all the heritability, suggesting there are more associations under the current stringent statistical threshold. In this study, we obtained an integrated epigenomic dataset based on the chromatin conformation of a human oral epithelial cell line (HIOEC) using RNA-seq, ATAC-seq, H3K27ac ChIP-seq, and DLO Hi-C. Presumably, this epigenomic dataset could reveal the missing functional variants located in the oral epithelial cell active enhancers/promoters along with their risk target genes, despite relatively less-stringent statistical association with OFC. Taken a non-syndromic cleft palate only (NSCPO) GWAS data of the Chinese Han population as an example, 3664 SNPs that cannot reach the strict significance threshold were subjected to this functional identification pipeline. In total, 254 potential risk SNPs residing in active cis-regulatory elements interacting with 1 718 promoters of oral epithelium-expressed genes were screened. Gapped k-mer machine learning based on enhancers interacting with epithelium-expressed genes along with in vivo and in vitro reporter assays were employed as functional validation. Among all the potential SNPs, we chose and confirmed that the risk alleles of rs560789 and rs174570 reduced the epithelial-specific enhancer activity by preventing the binding of transcription factors related to epithelial development. In summary, we established chromatin conformation datasets of human oral epithelial cells and provided a framework for testing and understanding how regulatory variants impart risk for clefts.
Chromatin ; Cleft Lip/genetics* ; Cleft Palate/genetics* ; Epithelium ; Genome-Wide Association Study ; Humans