Persistent and maladaptive drug-related memories represent a key component in drug addiction. Converging evidence from both preclinical and clinical studies has demonstrated the potential efficacy of the memory reconsolidation updating procedure (MRUP), a non-pharmacological strategy intertwining two distinct memory processes: reconsolidation and extinction-alternatively termed "the memory retrieval-extinction procedure". This procedure presents a promising approach to attenuate, if not erase, entrenched drug memories and prevent relapse. The present review delineates the applications, molecular underpinnings, and operational boundaries of MRUP in the context of various forms of substance dependence. Furthermore, we critically examine the methodological limitations of MRUP, postulating potential refinement to optimize its therapeutic efficacy. In addition, we also look at the potential integration of MRUP and neurostimulation treatments in the domain of substance addiction. Overall, existing studies underscore the significant potential of MRUP, suggesting that interventions predicated on it could herald a promising avenue to enhance clinical outcomes in substance addiction therapy.
Humans ; Substance-Related Disorders/psychology* ; Memory Consolidation/physiology* ; Animals ; Extinction, Psychological/physiology*

Mesangial cell proliferation is an early pathological indicator of diabetic nephropathy (DN). Growing evidence highlights the pivotal role of paired-related homeobox 1 (Prrx1), a key regulator of cellular proliferation and tissue differentiation, in various disease pathogenesis. Notably, Prrx1 is highly expressed in mesangial cells under DN conditions. Both in vitro and in vivo studies have demonstrated that Prrx1 overexpression promotes mesangial cell proliferation and contributes to renal fibrosis in db/m mice. Conversely, Prrx1 knockdown markedly suppresses hyperglycemia-induced mesangial cell proliferation and mitigates renal fibrosis in db/db mice. Mechanistically, Prrx1 directly interacts with the Yes-associated protein 1 (YAP) promoter, leading to the upregulation of YAP expression. This upregulation promotes mesangial cell proliferation and exacerbates renal fibrosis. These findings emphasize the crucial role of Prrx1 upregulation in high glucose-induced mesangial cell proliferation, ultimately leading to renal fibrosis in DN. Therefore, targeting Prrx1 to downregulate its expression presents a promising therapeutic strategy for treating renal fibrosis associated with DN.

Objective To discuss the effectiveness and safety of transarterial chemoembolization(TACE)combined with regorafenib and programmed death receptor-1(PD-1)in the second-line sequential treatment of advanced hepatocellular carcinoma(HCC).Methods The clinical data of a total of 83 patients with advanced HCC,who received TACE combined with regorafenib and PD-1(triple-therapy group)or TACE combined with regorafenib(dual-therapy group)at the Affiliated Hospital of Nantong University and Nantong Municipal Third People's Hospital of China between October 2020 and May 2022,were retrospectively analyzed.The clinical data were collected and evaluated.Modified response evaluation criteria in solid tumors(mRECIST)was used to evaluate the curative effect.The progression-free survival(PFS),overall survival(OS)and treatment-related adverse events(TRAEs)were compared between the two groups.The Kaplan-Meier method was used to draw PFS and OS curves,the Log-rank test was used to compare the relevant data between the two groups,and the COX regression model was drawn to determine the factors influencing PFS and OS.Results There were no statistically significant differences in the baseline data between the two groups(P≥0.05).In the triple-therapy group and the dual-therapy group,the objective response rate(ORR)was 31.1％and 18.4％respectively(P=0.024),and the disease control rate(DCR)was 77.8％and 57.8％respectively(P=0.038).The OS and PFS in the triple-therapy group were higher than those in the dual-therapy group(16.80 months vs 13.20 months,and 9.10 months vs.7.40 months,respectively).No statistically significant difference in the incidence of adverse drug reactions existed between the two groups(P 0.05).Conclusion In the second-line sequential treatment of advanced HCC,TACE combined with regorafenib and PD-1 is more effective than TACE combined with regorafenib,therefore,it can be used as a preferred second-line treatment for advanced HCC.

Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs prolifer-ation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

Experiential teaching is a practical, reflective, and situational teaching method. Based on the systematic review of literature published worldwide, this paper summarizes the characteristics and organizational forms of experiential teaching, with a focus on its current application and existing problems in teaching geriatric nursing. This review provides suggestions for the reform of teaching methods of geriatric nursing in China.

Objective To investigate the differences in the influencing factors for acute necrotizing pancreatitis (ANP) and infectious pancreatic necrosis (IPN) between Eastern and Western countries, and to provide a theoretical basis for the prediction and prevention of ANP. Methods Databases including PubMed, Embase, the Cochrane Library, and Web of Science were searched for articles on the influencing factors for ANP and IPN published up to January 21, 2021, and a Meta-analysis was performed. Results A total of 59 studies were included, with 22 studies from Eastern countries and 37 studies from Western countries.The Meta-analysis showed that in Eastern countries, male sex (odds ratio[ OR ]=1.51, 95% confidence interval[ CI ]: 1.18-1.91, P < 0.01), C-reactive protein (CRP)(standardized mean difference[ SMD ]=1.39, 95% CI : 1.06-1.71, P < 0.01), D-dimer ( SMD =0.44, 95% CI : 0.07-0.81, P =0.02), Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE-Ⅱ) score (mean difference[ MD ]=3.51, 95% CI : 1.38-5.64, P < 0.01), alcoholic etiology ( OR =3.57, 95% CI : 2.68-4.75, P < 0.01), and biliary etiology ( OR =0.60, 95% CI : 0.46-0.77, P < 0.01) were the influencing factors for ANP, and in Western countries, male sex ( OR =1.63, 95% CI : 1.30-2.05, P < 0.01), CRP ( SMD =2.09, 95% CI : 1.12-3.05, P < 0.01), APACHE-Ⅱ score ( MD =4.28, 95% CI : 2.73-5.83, P < 0.01), Ranson score ( MD =2.99, 95% CI : 2.50-3.47, P < 0.01), and organ failure ( OR =10.87, 95% CI : 2.62-45.04, P < 0.01) were the influencing factors for ANP.In Eastern countries, age ( MD =2.16, 95% CI : 0.43-3.89, P =0.01), body mass index (BMI)( MD =1.74, 95% CI : 1.23-2.25, P < 0.01), albumin level ( SMD =-0.43, 95% CI : -0.75 to-0.12, P < 0.01), CRP ( SMD =0.58, 95% CI : 0.04-1.11, P =0.03), procalcitonin ( SMD =0.80, 95% CI : 0.56-1.04, P < 0.01), D-dimer ( MD =0.23, 95% CI : 0.15-0.31, P < 0.01), APACHE-Ⅱ score ( MD =2.47, 95% CI : 0.73-4.22, P < 0.01), Ranson score ( MD =1.60, 95% CI : 1.46-1.73, P < 0.01), and extent of necrosis ≥30%( OR =2.52, 95% CI : 1.26-5.06, P < 0.01) were the influencing factors for IPN, while in Western countries, age ( MD =4.07, 95% CI : 1.82-6.31, P < 0.01), APACHE-Ⅱ score ( MD =3.28, 95% CI : 1.39-5.17, P < 0.01), Ranson score ( MD =2.18, 95% CI : 1.75-2.62, P < 0.01), SIRS score ( OR =3.88, 95% CI : 1.58-9.51, P < 0.01), alcoholic etiology ( OR =0.61, 95% CI : 0.42-0.87, P < 0.01), and organ failure ( OR =3.63, 95% CI : 1.11-11.92, P =0.03) were the influencing factors for IPN. Conclusion Current evidence shows that biliary etiology and alcoholic etiology are unique influencing factors for ANP in the Eastern population, while Ranson score is a unique influencing factor in the Western population.BMI and extent of necrosis ≥30% are unique influencing factors for IPN in the Eastern population, while alcoholic etiology is a unique influencing factor in the Western population.

Humans ; COVID-19 ; Brain/diagnostic imaging* ; Magnetic Resonance Imaging ; Longitudinal Studies

Objective:To evaluate the effect of preoperative cognitive behavioral therapy (CBT) on pain catastrophizing in the patients with orthopedic trauma.Methods:A total of 120 patients with lower extremity bone trauma, aged 18-64 yr, of American Society of Anesthesiologists physical status Ⅰor Ⅱ, with body mass index of 18-28 kg/m 2, with Pain Catastrophic Scale (PCS) score on admission >16, scheduled for surgical treatment, were enrolled.The patients were divided into 2 groups ( n=60 each) by the stratified randomization method based on the type of fracture: CBT group and routine group (group R). Group CBT received CBT for pain through the internet on the day of admission and one day before operation.The patients in both groups underwent reduction and internal fixation of lower extremity fractures under combined spinal-epidural anesthesia.The PCS scores were recorded immediately after admission and on the morning of the operation day.The effective pressing times of the patient-controlled analgesia pump, consumption of analgesics for rescue analgesia, and occurrence of nausea and vomiting within 48 h after operation were recorded.The visual analogue scale score of the surgical site during activity and occurrence of the score >3 at 3 months after operation and use of opioids within 3 months after operation were recorded. Results:Compared with group R, the PCS score was significantly decreased on the morning of the operation day, the pressing times of the patient-controlled analgesia pump, consumption of analgesics for rescue analgesia and incidence of nausea and vomiting within 48 h after operation were decreased, the requirement for opioids within 3 months after operation was decreased ( P<0.05), and no significant change was found in VAS score during activity and occurrence of the score >3 at 3 months after operation in group CBT ( P>0.05). Conclusions:Preoperative CBT can reduce the degree of pain catastrophizing and is helpful in increasing the quality of postoperative analgesia in the patients with orthopedic trauma.

ObjectiveTo investigate the expression and clinical significance of OX40/OX40L (CD134/CD134L) in CD4+ T cells, CD8+ T cells, monocytes, and B lymphocytes in peripheral blood of patients with autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and their overlap syndrome before and after standardized treatment. MethodsA total of 74 patients with AIH, PBC, and their overlap syndrome who were diagnosed in Subei People’s Hospital of Jiangsu from August 2015 to August 2019 were enrolled, and according to related diagnostic criteria, they were divided into AIH group (group A) with 29 patients, PBC group (group P) with 26 patients, and overlap syndrome group (group C) with 19 patients. A healthy control group with 30 individuals was also established. Peripheral blood samples were collected before and after standardized treatment to measure the expression of OX40/OX40L on the surface of peripheral blood cells by immunofluorescence flow cytometry, and the expression of OX40/OX40L was compared before and after treatment and between the three groups and the healthy control group to investigate its clinical significance. A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups; the paired t-test was used for comparison of paired samples between two groups. ResultsThere were no significant differences in sex composition and age composition between the three groups (P＞0.05). Before treatment, the positive rate of OX40 in peripheral blood CD4+ T cells gradually increased in groups A, P, and C, and groups A, P, and C had a significantly higher positive rate of OX40 than the control group (14.80%±4.99%/17.11%±2.71%/25.18%±5.55% vs 6.67%±2.26%, F=14.823, P＜0.001); groups A, P, and C had a significantly higher positive rate of OX40 in CD8+ T cells than the control group (4.86%±1.54%/6.40%±1.88%/7.33%±2.12% vs 4.09%±2.69%, F=5.486, P＜0.001); the positive rate of OX40L in CD14+ monocytes was 19.84%±6.11% in group A, 21.17%±4.35% in group P, 29.13%±6.32% in group C, and 4.86%±2.34% in the control group, and there was a significant difference between groups (F=17004, P＜0.001); the positive rate of OX40L in CD19+ B cells was 17.62%±3.86% in group A, 14.75%±4.32% in group P, 1013%±2.56% in group C, and 4.50%±1.38% in the control group, showing a trend of gradual reduction, and groups A, P, and C had a significantly higher positive rate than the control group (F=12.221, P＜0.001). After treatment, the positive rate of OX40 in CD8+ T cells decreased significantly to a similar level as the control group, and there was no significant difference between groups (F=0731, P=0.538). For the other three types of cells, although there were varying degrees of reduction in the positive rate of OX40/OX40L after treatment, groups A, P, and C still had a significantly higher positive rate than the control group; in CD4+ T cells, the positive rate of OX40 was 11.00%±1.98% in group A, 13.72%±1.03% in group P, 19.72%±3.47% in group C, and 6.67%±2.26% in the control group, and groups A, P, and C had a significantly higher positive rate than the control group (F=11.365, P＜0.001); in CD14+ monocytes, the positive rate of OX40L was 11.82%±2.23% in group A, 15.19%±4.42% in group P, 24.51%±4.09% in group C, and 4.86%±2.34% in the control group, and groups A, P, and C had a significantly higher positive rate than the control group (F=13748, P＜0.001); in CD19+ B cells, the positive rate of OX40L was 9.09%±3.25% in group A, 6.81%±2.20% in group P, 748%±2.85% in group C, and 4.50%±1.38% in the control group, and groups A, P, and C had a significantly higher positive rate than the control group (F=8.052, P＜0.001). Groups A, P, and C had significant reductions in the expression of OX40/OX40L in peripheral blood CD4+ T cells, CD8+ T cells, CD14+ monocytes, and CD19+ B lymphocytes after treatment (all P＜0.05). ConclusionThe expression of OX40/OX40L in peripheral blood increases in patients with AIH, PBC, and their overlap syndrome and decreases after treatment, indicating that the OX40/OX40L pathway is involved in the pathogenesis of the above diseases, and the role of OX40 on the surface of CD8+ T cells may better reflect the treatment outcome.