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*

This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both Na_V1.7, Na_V1.8, and Na_V1.9 and K_V7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited Na_V1.7, Na_V1.8, and Na_V1.9 channels with a particularly low half maximal inhibitory concentration (IC₅₀) for Na_V1.9 by promoting sodium channel inactivation, and also effectively increased K_V7.2/7.3, K_V7.2, and K_V7.5 channels, excluding K_V7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

OBJECTIVES: This study aimed to investigate the correlation between clinical symptoms and unilateral chewing habits in patients with temporomandibular disorder (TMD) accompanied by tinnitus. METHODS: A total of 285 patients diagnosed with TMD at the Department of Stomatology of the First Medical Center of Chinese People's Liberation Army General Hospital between December 2020 and May 2024 were included and divided into two groups: tinnitus group and non-tinnitus group. Analysis was conducted on the proportion of patients with unilateral chewing habits in both groups, the correlation between the side of tinnitus and the side of unilateral chewing, and the correlation of tinnitus with TMD clinical symptoms (joint clicking, joint pain, and limited mouth opening) and unilateral chewing habits. The correlation of the type of disc displacement with unilateral chewing and tinnitus was also examined. RESULTS: In the tinnitus group, the proportions of patients with and without unilateral chewing habits were 90.70% (39/43) and 9.30% (4/43), respectively. In the non-tinnitus group, the proportions of patients with and without unilateral chewing habits were 76.03% (184/242) and 23.97% (58/242), respectively. The proportion of patients with unilateral chewing habits in the tinnitus group was significantly higher than in the non-tinnitus group (χ²=4.613, P<0.05). Correlation analysis showed a positive correlation between tinnitus and unilateral chewing habits (P<0.05). In the left-sided tinnitus group, the proportion of left-sided unilateral chewers [54.55% (12/22)] was higher than that of right-sided unilateral chewers [45.45% (10/22)]. In the right-sided tinnitus group, the proportion of right-sided unilateral chewers [81.82% (9/11)] was higher than that of left-sided unilateral chewers [18.18% (2/11)]. The difference was statistically significant (χ²=7.282, P<0.05). A positive correlation was also found between the side of tinnitus and the side of unilateral chewing habits (P<0.05). The proportion of patients with pain was significantly higher in the tinnitus group than in the non-tinnitus group (P<0.05). No significant difference in the proportion of joint clicking or limited mouth opening and disc displacement (no disc displacement, unilateral disc displacement, bilateral disc displacement, reducible disc displacement, or irreducible disc displacement) was found between the tinnitus and non-tinnitus groups (P>0.05). CONCLUSIONS TMD with unilateral chewing habits may be a contributing factor to unexplained tinnitus. Unexplained tinnitus is correlated with joint pain in patients with TMD.
Humans ; Tinnitus/physiopathology* ; Temporomandibular Joint Disorders/physiopathology* ; Mastication ; Male ; Adult ; Female ; Middle Aged ; Habits

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.

Objective:To analyze the correlation between drug-induced sleep endoscopy (DISE), results, polysomnography (PSG) indicators, and clinical parameters in patients with obstructive sleep apnea (OSA), and to establish and validate a predictive model for tongue base plane obstruction.Methods:This retrospective study analyzed 117 OSA patients diagnosed via PSG and treated at the Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, between October 2014 and March 2022. The cohort comprised of 114 males and 3 females, with an age range of 20 to 54 years (mean age 38.1±8.4 years). Data on DISE results, PSG results, and clinical indicators were collected for all 117 patients. Logistic regression analysis was performed to identify relevant indicators, and a predictive model for tongue base plane obstruction was constructed and internally validated using the R programming language.Results:Univariate logistic regression analysis identified four independent risk factors for predicting tongue root plane obstruction: tonsil grading, N2, N3, and rapid eye movement sleep(REM) stage [ OR:0.412(0.260~0.652),1.045(1.012~1.079),0.943(0.903~0.984),0.961(0.925~0.998), P <0.05]. Multivariate logistic regression analysis confirmed tonsil grading and N3 sleep stage (12.48±12.22%) as significant predictors. A nomogram model incorporating these factors demonstrated good predictive performance, with an area under curve(AUC) of 0.82 (95% CI: 0.548-1.000), an optimal cutoff of 0.519, a specificity of 80.0%, and a sensitivity of 86.7%. Internal validation of the model in the validation cohort yielded an AUC of 0.751 (95% CI: 0.625-0.876). Conclusions:Tongue base plane obstruction observed during DISE in OSA patients is associated with tonsil grading and N3 sleep stage duration. The predictive model developed for tongue base plane obstruction based on DISE demonstrates good efficacy, as evidenced by its internal validation.

Objective    To analyze the risk factors for acute kidney injury (AKI) after off-pump coronary artery bypass grafting (OPCABG). Methods     The PubMed, EMbase, The Cochrane Library, Web of Science, Wanfang data, CBM, VIP, CNKI were searched by computer for researches on risk factors associated with the development of AKI after OPCABG from the inception to March 2022. The meta-analysis was performed using RevMan 5.4 software. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of included studies. Results    A total of 18 researches were included, involving 9 risk factors. The NOS score of all included studies was≥6 points. Meta-analysis results showed that age [OR=1.03, 95%CI (1.01, 1.06), P=0.020], body mass index (BMI) [OR=1.10, 95%CI (1.05, 1.15), P<0.001], history of hypertension [OR=1.45, 95%CI (1.27, 1.66), P<0.001], history of diabetes [OR=1.50, 95%CI (1.33, 1.70), P<0.001], preoperative serum creatinine level [OR=2.05, 95%CI (1.27, 3.32), P=0.003], low left ventricular ejection fraction [OR=4.51, 95%CI (1.39, 14.65), P=0.010], preoperative coronary angiography within a short period of time [OR=2.10, 95%CI (1.52, 2.91), P<0.001], perioperative implantation of intra-aortic balloon pump [OR=3.42, 95%CI (2.26, 5.16),  P<0.001], perioperative blood transfusion [OR=2.00, 95%CI (1.51, 2.65), P<0.001] were risk factors for AKI after OPCABG. Conclusion    Age, BMI, history of hypertension, history of diabetes, preoperative serum creatinine level, low left ventricular ejection fraction, preoperative coronary angiography within a short period of time, perioperative implantation of intra-aortic balloon pump, perioperative blood transfusion are risk factors for AKI after OPCABG. Medical staff should focus on monitoring the above risk factors and early identifying, in order to prevent or delay the onset of postoperative AKI and promote early recovery of patients.

Objective:Due to the circumstances where people being required to home quarantine and eye hospitals being unable to receive patient normally, The application of internet plus technology is explored to build Remote Dedicated Doctor Platform of Ophthalmology (RDDPO) for online consultation, accessing to medication, medical services and advises orderly, and to help to further develop and apply the platform.Methods:In 2018, RDDPO was jointly developed.It has been modified and improved to the formulation of national medical policy and medical insurance policy and the outbreak of COVID-19 at the end of 2019, and it has been carried out comprehensive application verification during the prevention and control of COVID-19 epidemic.With a B/S structure, platform docks the official accounts of Wechat platform.On the server side, three J2EE frameworks of the integrated development, including Struts2, Spring and Hibernate are adopted; on the mobile client side, a combination of development tools including React-Native and Redux is used.Meanwhile, a micro-services Architecture (msA) of RESTful WebAPI is chosen at the business logic layer.The terminal data information is used to summarize the results of the platform's functional services for ophthalmic patients, such as remote diagnosis and treatment, online prescription, medicine delivery and health education, etc., and to make statistics on all kinds of data during the epidemic prevention and control period, so as to verify the operations management capabilities of the platform's functions.Results:During the period of COVID-19 epidemic prevention and control, the number of monthly visits of RDDPO increased from 1063 person times from September 1, 2019 to the end of September to 30 002 person times from February 1, 2020 to February 28, 2020.The proportion of diagnosis and treatment person times of this platform in the total number of diagnosis and treatment person times increased from 19.1% (203/1 063) to 92.3% (277/3 002), which can effectively avoid the risk of personal contact infection and meet the patients' medical needs.95.8% of the patients were very satisfied.95.8% of the patients were very satisfied.Conclusions:The RDDPO establishes a channel for doctor-patient communication during the epidemic, which can be considered as an important way to effectively address the needs of patients for medical treatment.

Objective: To investigate the influences of antibiotic-induced gut microbiota dysbiosis on Mycoplasma pneumoniae (Mp) airway infection. Methods: C57BL/6J mice were treated with vancomycin and gentamicin for 21 d by oral delivery and then intranasally infected with Mp. Quantitative real-time PCR (qPCR) was performed to detect five major phyla of gut microbiota in mouse fecal specimens before and after antibiotic treatment and the loads of Mp in lung tissues on 3 d and 7 d after infection. Pathological changes in lung tissues were evaluated with HE staining. IFN-γ and IL-4 secreted by spleen CD4⁺ T cells and CD8⁺ T cells were analyzed by flow cytometry. Mp-specific IgM and IgG in mouse serum samples were measured by indirect enzyme-linked immunosorbent assay (ELISA). Results: Vancomycin and gentamicin treatment significantly reduced the number of Bacteroidetes in mouse feces, but increased the amount of Firmicutes. Meanwhile, the numbers of δ, γ-Proteobacteria, Actinomycetes and Tenericutes also changed. These antibiotic-induced gut microbiota alterations in mice with Mp infection increased the loads of Mp in lung tissues and the pathological scores of lung tissue inflammation on 3 d and 7 d after infection, and reduced the number of IFN-γ-secreting spleen CD4⁺ T lymphocytes on 7 d. Conclusions Antibiotic-induced gut microbiota dysbiosis aggravated Mp airway infection.

Objective:To investigate the consistency of Velum, Oropharygneal, Tongue base, Epiglottis (VOTE) scores between two surgeons with similar clinical experience in obstructive sleep apnea hypopnea syndrome (OSAHS) patients with different degree of disease, and to analyze the influencing factors leading to the difference in score.Methods:This was a cross-sectional study. 64 preoperative drug-induced sleep endoscopy (DISE) videos of OSAHS patients during December 2014 to July 2018, from Nanfang Hospital, Southern Medical University were analyzed. The VOTE score was assessed single-blind by two similar experienced surgeons, and the Kappa value between the two scorers was calculated by the third researcher. According to the characteristics of the case, Fisher's exact test or chi-square test method was used to further explore the factors that influenced the consistency.Results:Sixty-four patients were divided into four groups according to the severity of the disease, including mild (7 cases), moderate (30 cases), severe(18 cases), and extremely severe (9 cases). The scores evaluated between two researchers were analysed for consistency. For mild patients, the two scorers were completely consistent in the configuration and degree of obstruction in the velum and epiglottis (Kappa=1). There was no agreement on whether obstruction or not, obstructed configuration, obstructed degree of the oropharynx and tongue base, and presence of velum and epiglottis obstruction. For moderate patients, the two scorers had a good consistency in the configuration and degree of the velum (0.61≤Kappa≤0.80), and there was no consistency in the evaluation of the degree of tongue base and epiglottis ( P>0.05). The consistency of the remaining obstructed conditions in the four planes was generally or moderate (0.21≤Kappa≤0.60). For patients with severe OSAHS, the two raters were completely consistent in the evaluation of palatopharyngeal and epiglottic planes for the presence of obstruction, but there was no consistency in the degree of obstruction. Although the degree of obstruction in the oropharyngeal plane can be assessed with good consistency, the consistency of whether the plane was blocked or not was generally not high. In the assessment of other obstructive conditions in the four planes of severe patients, the agreement between the two scorers was moderate or generally. For extremely severe patients, the two scorers were completely consistent in the evaluation of the velum obstruction, but there was no consistency in the degree of obstruction of the oropharynx and tongue base, and the obstruction configuration and degree of the epiglottis. The evaluation of other obstructed conditions in the four planes is good or moderate. Among the patients with severe OSAHS, the difference in the assessment of obstruction of the oropharynx was associated with tonsil size ( P<0.05). Conclusion:When physicians with similar clinical experience scored VOTE, the consistency of whether the velum and oropharyngeal planes are obstructed is related to the severity of the disease. Better consistency is observed among more severe OSAHS patients. The reason for the poor consistency of the oropharyngeal plane in severe OSAHS patients OSAHS is due to the difference of the tonsils size. For severe OSAHS patients with small tonsils, the assessment of whether the oropharynx is obstructed should be more cautious.

Objective To observe the effects of mild hypothermia on the myocardial mitochondrial injury induced by oxidative stress after restoration of spontaneous circulation (ROSC) in rat of cardiac arrest model.Methods Eighteen male Wistar rats were randomly (raudom number) divided into normal temperature group and mild hypothermia group after ROSC.Ultrasound was used to measure the left ventricular ejection fraction (EF),shortening fraction (FS) and stroke volume (SV).The levels of glutathione (GSH),malondialdehyde (MDA) and adenosine triphosphate (ATP) in myocardium were detected.The ultramicroscopic structure of myocardial mitochondria was observed under transmission electron microscope at 4 h after ROSC.Results There were no significant differences in basic life support (BLS) time,dosage of epinephrine and number of defibrillation attempt between two groups (P ＞ 0.05).The concentrations of GSH and ATP in myocardium of rats in hypothermia group were significantly higher than those in normal temperature group,while the level of MDA was significantly lower in hypothermia group than that in normal temperature group.Echocardiographic findings showed that hypothermia could significantly improve the EF,FS and SV after ROSC.The hypothermia decreased the myocardial mitochondria injury rather than normothermia [mitochondrial injury score:(0.21-±0.04) vs.(0.42 ±0.08),P ＜ 0.05].Conclusions In this model,mild hypothermia can decrease myocardial oxidative stress injury,improving the cardiac function after ROSC.