Distinct roles of excitatory and inhibitory neurons in the medial prefrontal cortex in the expression and reconsolidation of methamphetamine-associated memory in male mice.

Methamphetamine, a commonly abused drug, is known for its high relapse rate. The persistence of addictive memories associated with methamphetamine poses a significant challenge in preventing relapse. Memory retrieval and subsequent reconsolidation provide an opportunity to disrupt addictive memories. However, the key node in the brain network involved in methamphetamine-associated memory retrieval has not been clearly defined. In this study, using the conditioned place preference in male mice, whole brain c-FOS mapping and functional connectivity analysis, together with chemogenetic manipulations of neural circuits, we identified the medial prefrontal cortex (mPFC) as a critical hub that integrates inputs from the retrosplenial cortex and the ventral tegmental area to support both the expression and reconsolidation of methamphetamine-associated memory during its retrieval. Surprisingly, with further cell-type specific analysis and manipulation, we also observed that methamphetamine-associated memory retrieval activated inhibitory neurons in the mPFC to facilitate memory reconsolidation, while suppressing excitatory neurons to aid memory expression. These findings provide novel insights into the neural circuits and cellular mechanisms involved in the retrieval process of addictive memories. They suggest that targeting the balance between excitation and inhibition in the mPFC during memory retrieval could be a promising treatment strategy to prevent relapse in methamphetamine addiction.

Genes and pathways associated with fear discrimination identified by genome-wide DNA methylation and RNA-seq analyses in nucleus accumbens in mice.

Fear memory is critical for individual survival. However, the maladaptive fear response is one of the hallmarks of fear-related disorders, which is characterized by the failure to discriminate threatening signals from neutral or safe cues. The biological mechanisms of fear discrimination remain to be clarified. In this study, we found that the nucleus accumbens (NAc) was indispensable for the formation of cued fear memory in mice, during which the expression of DNA methyltransferase 3a gene (DNMT3a) increased. Injection of Zebularine, a nonspecific DNMT inhibitor, into NAc immediately after conditioning induced a maladaptive fear response to neutral cue (CS-). Using whole-genome bisulfite sequencing (WGBS), differentially methylated sites and methylated regions (DMRs) were investigated. 16,226 DMRs in the genenome were identified, in which, 214 genes with significant differences in their methylation levels and mRNA expression profiles were identified through correlation analysis. Notably, 15 genes were synaptic function-related and 8 genes were enriched in the cGMP-PKG signaling pathway. Moreover, inhibition of PKG impaired fear discrimination. Together, our results revealed the profile and role of genome-wide DNA methylation in NAc in the regulation of fear discrimination.

[Effect of Tiaoshen Qianyang acupuncture on blood pressure and sleep quality in patients with stroke-related sleep disorders complicated with hypertension].

OBJECTIVE: To observe the effect of Tiaoshen Qianyang acupuncture on morning blood pressure, sleep quality and post-stroke nerve function recovery in patients with stroke-related sleep disorders (SSD) complicated with hypertension. METHODS: A total of 120 patients were randomized into an observation group (60 cases) and a control group (60 cases, 1 case dropped off). Both groups were treated with Xingnao Kaiqiao acupuncture (Neiguan [PC 6], Shuigou [GV 26], Sanyinjiao [SP 6], Jiquan [HT 1], Chize [LU 5] and Weizhong [BL 40]). In addition, Tiaoshen Qianyang acupuncture was applied in the observation group, deep needling at Baihui (GV 20) and Sishencong (EX-HN 1) for 5 h. Once a day, 5 times a week, 30 times in total. The morning blood pressure was measured during treatment in the two groups, the Pittsburgh sleep quality index (PSQI) and National Institute of Health stroke scale (NIHSS) scores before and after treatment were observed in the two groups. RESULTS: Compared before treatment, the morning systolic blood pressure (SBP) after treatment were decreased in the two groups (P<0.05), and the morning diastolic blood pressure (DBP) after treatment was decreased in the observation group (P<0.05). The levels of SBP and DBP after treatment in the observation group were lower than the control group (P<0.05). Compared before treatment, the total score of PSQI and NIHSS score after treatment in the observation group were decreased (P<0.01, P<0.05), which were lower than the control group (P<0.01, P<0.05), the decreasing rate of NIHSS score in the observation group was higher than the control group (P<0.05). CONCLUSION: On the basis of Xingnao Kaiqiao acupuncture, Tiaoshen Qianyang acupuncture could improve morning blood pressure and sleep quality for patients with SSD complicated with hypertension, promote the recovery of nerve function.

[Professor WU Lian-zhong's clinical experience for treating post-stroke distal limb dyskinesia].

Professor WU Lian-zhong's experience for treating post-stroke distal limb dyskinesia is introduced from the aspects of syndrome differentiation principles, clinical acupoint selection and acupuncture manipulation. Professor WU proposes the original syndrome differentiation system of "ten factors" for stroke, and emphasizes the importance of spirit differentiation and syndrome differentiation. The syndrome differentiation focus on the three yang meridians and kidney meridian, as such, Quchi (LI 11), Shousanli (LI 10), Waiguan (TE 5), Hegu (LI 4), Zhongzhu (TE 3), Sidu (TE 9), Zusanli (ST 36), Fenglong (ST 40), Tengyue point, Taichong (LR 3), Xiangu (ST 43), Zulinqi (GB 41), Dazhong (KI 4), Genjian point, Zhaohai (KI 6), Fuliu (KI 7) and Taixi (KI 3) are selected. In addition, professor WU develops clear quantitative standards for acupuncture manipulation.

Manual Acupuncture or Combination with Vitamin B to Treat Diabetic Peripheral Neuropathy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

METHODS: Randomized controlled trials on manual acupuncture treatment of DPN were retrieved from the Medline, Web of Science, PubMed, Cochrane Library, EMBASE, CNKI, WanFang, and VIP databases. Extracted research data were summarized in the tables, and methodological assessment was performed using the risk-of-bias assessment tool of Cochrane. Meta-analysis was performed by Revman 5.3, Stata 14.0, and TSA 0.9.5.10 Beta software. RESULTS: A total of 18 randomized clinical trials (RCTs) were recruited: (1) 11 RCTs were acupuncture alone compared with vitamin B; (2) 7 RCTs were acupuncture combined with vitamin B compared with vitamin B, involving 1200 participants. Acupuncture alone improved clinical efficacy (P < 0.05) and nerve conduction velocity of the four peripheral nerves: peroneal nerve, tibial nerve, median nerve, and ulnar nerve (P < 0.05), but there was no significant difference between the group of acupuncture alone and the group of vitamin B (P = 0.36 > 0.05) in improving median nerve SCV (sensory nerve conduction velocity). Acupuncture combined with vitamin B improved clinical efficacy and nerve conduction velocity of the three peripheral nerves, peroneal nerve, tibial nerve, and median nerve (P < 0.05), and decreased the scores of the Toronto clinical scoring system (TCSS) (P < 0.05). CONCLUSION: Acupuncture alone and vitamin B combined with acupuncture are more effective in treating DPN compared to vitamin B. However, more high-quality RCTs on vitamin B combined with acupuncture are required to confirm our results.