PGC-1α regulate critical period plasticity via gene × environment interaction in the developmental trajectory to schizophrenia.

Genes and environmental conditions are thought to interact in the development of postnatal brain in schizophrenia (SZ). Genome wide association studies have identified that PPARGC1A being one of the top candidate genes for SZ. We previously reported GABAergic neuron-specific PGC-1α knockout mice (Dlx5/6-Cre:PGC-1αfl/fl) presented some characteristic features of SZ. However, there is a fundamental gap of the molecular mechanism by which PGC-1α gene involved in the developmental trajectory to SZ. To explore whether PGC-1α regulates environmental factors interacting with genetic susceptibility to trigger symptom onset and disease progression, PGC-1α deficient mice were utilized to model genetic effect and an additional oxidative stress was induced by GBR injection. We confirm that PGC-1α gene deletion prolongs critical period (CP) timing, as revealed by delaying maturation of PV interneurons (PVIs), including their perineuronal nets (PNNs). Further, we confirm that gene × environment (G × E) influences CP plasticity synergistically and the interaction varies as a function of age, with the most sensitive period being at preweaning stage, and the least sensitive one at early adult age in PGC-1α deficient mice. Along this line, we find that the synergic action of G × E is available in ChABC-infusion PGC-1α KO mice, even though during the adulthood, and the neuroplasticity seems to remain open to fluctuate. Altogether, these results refine the observations made in the PGC-1α deficient mice, a potential mouse model of SZ, and illustrate how PGC-1α regulates CP plasticity via G × E interaction in the developmental trajectory to SZ.

Mice Lacking the Transcriptional Coactivator PGC-1α Exhibit Hyperactivity.

Significant evidence from various sources suggests that structural alterations in mitochondrial function may play a role in both the pathogenesis of mood disorders and the therapeutic effects of available treatments. PGC-1α is a distinct transcriptional regulator designed to mediate the synchronous release of neurotransmitter in the brain and thereby to coordinate a number of gene expression pathways to promote mitochondrial biogenesis and oxidative phosphorylation. The role of PGC-1α in the context of affective disorder phenotypes and treatments has been suggested but not studied in depth. To further investigate the possible involvement of PGC-1α in affective disorders, we generated conditional PGC-1α null mice through transgenic expression of cre recombinase under the control of a Dlx5/6 promoter; cre-mediated excision events were limited to γ-amino-butyric-acid (GABA)-ergic specific neurons. We tested these mice in a battery of behavioral tests related to affective change including spontaneous activity, elevated plus maze, forced swim test, and tail suspension test. Results demonstrated that mice lacking PGC-1α in GABAergic neurons exhibited increased activity across tests that might be related to a mania-like phenotype. These results suggest possible relevance of PGC-1α to affective change, which corresponds with data connecting mitochondrial function and affective disorders and their treatment.

Effectiveness and safety of adjunctive non-drug measures in improving respiratory symptoms among patients with severe COVID-19: A multicenter randomized controlled trial.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) infection posed a huge threat and burden to public healthcare in late 2022. Non-drug measures of traditional Chinese medicine (TCM), such as acupuncture, cupping and moxibustion, are commonly used as adjuncts in China to help in severe cases, but their effects remain unclear. OBJECTIVES: To observe the clinical effect of TCM non-drug measures in improving respiratory function and symptoms among patients with severe COVID-19. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This study was designed as a multicenter, assessor-blind, randomized controlled trial. Hospitalized patients with COVID-19 were randomly assigned to the treatment or control group. The treatment group received individualized TCM non-drug measures in combination with prone position ventilation, while the control group received prone position ventilation only for 5 consecutive days. MAIN OUTCOME MEASURES: The primary outcome measures were the percentage of patients with improved oxygen saturation (SpO2) at the end of the 5-day intervention, as well as changes of patients' respiratory rates. The secondary outcome measures included changes in SpO2 and total score on the self-made respiratory symptom scale. The improvement rate, defined as a 3-day consecutive increase in SpO2, the duration of prone positioning, and adverse events were recorded as well. RESULTS: Among the 198 patients included in the intention-to-treat analysis, 159 (80.3%) completed all assessments on day 5, and 39 (19.7%) patients withdrew from the study. At the end of the intervention, 71 (91%) patients in the treatment group had SpO2 above 93%, while 61 (75.3%) in the control group reached this level. The proportion of participant with improved SpO2 was significantly greater in the intervention group (mean difference [MD] = 15.7; 95% confidence interval [CI]: 4.4, 27.1; P = 0.008). Compared to the baseline, with daily treatment there were significant daily decreases in respiratory rates in both groups, but no statistical differences between groups were found (all P ≥ 0.05). Compared to the control group, the respiratory-related symptoms score was lower among patients in the treatment group (MD = -1.7; 95%CI: -2.8, -0.5; P = 0.008) after day 3 of treatment. A gradual decrease in the total scores of both groups was also observed. Thirty-one adverse events occurred during the intervention, and 2 patients were transferred to the intensive care unit due to deterioration of their illness. CONCLUSION: TCM non-drug measures combined with prone positioning can effectively treat patients with severe COVID-19. The combined therapy significantly increased SpO2 and improved symptom scores compared to prone positioning alone, thus improving the patients' respiratory function to help them recover. However, the improvement rate did not differ between the two groups. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2300068319). Please cite this article as: Yin X, Jin Z, Li F, Huang L, Hu YM, Zhu BC, Wang ZQ, Li XY, Li JP, Lao LX, Mi YQ, Xu SF. Effectiveness and safety of adjunctive non-drug measures in improving respiratory symptoms among patients with severe COVID-19: A multicenter randomized controlled trial. J Integr Med. 2024; Epub ahead of print.

[Professor ZHANG Ren's experience of stage treatment for refractory facial paralysis].

To introduce professor ZHANG Ren's experience that different stages of refractory facial paralysis should be treated with different acupuncture methods.In early stage of facial paralysis,identifcation is important. Electroacupuncture is applied to connect Qianzheng (Extra) with Cuanzhu (BL 2), Sibai (ST 2) and Jiachengjiang (Extra), by observing the twitches of facial muscles, it is determined whether it is easy to develop into refractory facial paralysis, in order to actively take preventive treatment. In the recovery stage of refractory facial paralysis, comprehensive therapy including acupuncture, acupoint injection, quick cupping and auricular point pressure are adopted, and penetration needling is applied at three points of mouth, three points of cheek and three points of forehead.In the sequelae stage of refractory facial paralysis，on the basis of comprehensive therapy, targeted treatment is adopted according to different sequelae.

[Effects of enrofloxacin and Cu combined pollution on the activities of digestive enzymes of earthworm in soil.] / æ©è¯ºæ²™æ˜Ÿå’Œé“œå¤åˆæ±¡æŸ“å¯¹èš¯èš“æ¶ˆåŒ–é ¶æ´»æ€§çš„å½±å“.

The effects of single and combined pollution of enrofloxacin and Cu on the digestive enzymes of earthworms were studied, based on the actual pollution of caused by the application of livestock feces in farmland soil. Results showed that single enrofloxacin (0.1-4 mg·kg-1, 28 d) did not affect protease, but inhibited cellulase and alkaline phosphatase, with an induced effect on acid phosphatase. Single Cu pollution (20-200 mg·kg-1, 28 d) had inhibitory effects on the four digestive enzymes in earthworms. The effects of combined exposures on the digestive enzymes were mainly negative, showing a synergistic increasing character of toxicity in cellulase and acid phosphatase activities. The response dynamics of digestive enzymes to exposure duration was regulatory response (3 d)-intense response (7 d)-reaction recovery (14 d)-chronic exposure (28 d). Chronic exposure results showed that the combined treatments containing high-dose pollutant (200 mg·kg-1 Cu or 4 mg·kg-1 ENR) had more ecological risk.