New Therapeutic Targets and Drugs for Schizophrenia Beyond Dopamine D2 Receptor Antagonists.

Schizophrenia is a disease with a complex pathological mechanism that is influenced by multiple genes. The study of its pathogenesis is dominated by the dopamine hypothesis, as well as other hypotheses such as the 5-hydroxytryptamine hypothesis, glutamate hypothesis, immune-inflammatory hypothesis, gene expression abnormality hypothesis, and neurodevelopmental abnormality hypothesis. The first generation of antipsychotics was developed based on dopaminergic receptor antagonism, which blocks dopamine D2 receptors in the brain to exert antipsychotic effects. The second generation of antipsychotics acts by dual blockade of 5-hydroxytryptamine and dopamine receptors. From the third generation of antipsychotics onwards, the therapeutic targets for antipsychotic schizophrenia expanded beyond D2 receptor blockade to explore D2 receptor partial agonism and the antipsychotic effects of new targets such as D3, 5-HT1A, 5-HT7, and mGlu2/3 receptors. The main advantages of the second and third generation antipsychotics over first-generation antipsychotics are the reduction of side effects and the improvement of negative symptoms, and even though third-generation antipsychotics do not directly block D2 receptors, the modulation of the dopamine transmitter system is still an important part of their antipsychotic process. According to recent research, several receptors, including 5-hydroxytryptamine, glutamate, γ-aminobutyric acid, acetylcholine receptors and norepinephrine, play a role in the development of schizophrenia. Therefore, the focus of developing new antipsychotic drugs has shifted towards agonism or inhibition of these receptors. Specifically, the development of NMDARs stimulants, GABA receptor agonists, mGlu receptor modulators, cholinergic receptor modulators, 5-HT2C receptor agonists and alpha-2 receptor modulators has become the main direction. Animal experiments have confirmed the antipsychotic effects of these drugs, but their pharmacokinetics and clinical applicability still require further exploration. Research on alternative targets for antipsychotic drugs, beyond the dopamine D2 receptor, has expanded the potential treatment options for schizophrenia and gives an important way to address the challenge of refractory schizophrenia. This article aims to provide a comprehensive overview of the research on therapeutic targets and medications for schizophrenia, offering valuable insights for both treatment and further research in this field.

Effectiveness and safety of Baduanjin for schizophrenia: A protocol for systematic review and meta-analysis.

BACKGROUND: The cause of schizophrenia is still unknown, the course of the disease is long and its onset is thought to be related to neurodevelopmental, genetic, and oxidative stress factors and so on. There is no means of cure. Typical drug therapy is effective in treating the acute stage of schizophrenia, while the impaired social and life functions of patients are often neglected. Baduanjin is a traditional Chinese physical and breathing exercise that not only strengthens the muscles, and moves the joints, but also exercises the will. Many studies have been reported in the study on the application of Baduanjin to schizophrenic patients to promote recovery, but no research systematically evaluates the therapeutic effects and safety of Baduanjin for schizophrenic patients. This study aims to systematically investigate the efficacy and safety of Baduanjin in the treatment of schizophrenic patients. METHODS: Reports of randomized controlled trials (RCTs) on Baduanjin for schizophrenia will be searched in the following data sources, including 3 English databases（PubMed, EMBASE, Cochrane Library）and 4 Chinese databases（China National Knowledge Infrastructure, Chinese Biomedical Literature, Wanfang, and China Clinical Trials Registry Database）, and their publication time is restricted from the establishment of the database to October 1, 2022. Two reviewers will independently perform study selection, data extraction, and quality assessment. RevMan V.5.4 software will be used for meta-analysis. The protocol will be performed according to preferred reporting items for systematic reviews and meta-analysis protocols (PRISMA-P) guidelines. RESULTS: The results will provide a systematic overview of the current evidence on the use of Baduanjin to treat schizophrenia. CONCLUSION: The conclusions of this study will help clarify whether Baduanjin is effective and safe for treating schizophrenia.

Effectiveness and safety of auricular acupuncture for psoriasis: A protocol for systematic review and meta-analysis.

BACKGROUND: Psoriasis is a chronic, immune-mediated, polygenic skin disease that is common in clinical practice and often develops on the extremities, back, and scalp of patients. In that psoriasis lesions are stubborn and prone to recurrence, it has a serious impact on patients' quality of life and is detrimental to their physical and psychological health. Auricular acupuncture is one of the traditional Chinese medical treatments, which has the advantages of low adverse effects and simple operation and has been widely used in clinical practice with good efficacy. However, there has been no systematic evaluation of auricular acupuncture in the treatment of psoriasis. This protocol aims to evaluate the effectiveness and safety of auricular acupuncture in patients with psoriasis. METHODS: We will search the following 8 databases including PubMed, MEDLINE, EMBASE, Cochrane Library, CNKI, Wan Fang, VIP, and CBM databases for randomized controlled trials of auricular acupuncture treated psoriasis from their inception to 10 October 2022. We will analyze the data meeting the inclusion criteria with the RevMan V.5.4 software. Two authors will assess the quality of the study with the Cochrane systematic evaluation tool. Treatment effectiveness and the psoriasis area and severity index are defined as the main outcomes, and the additional outcomes include itchy, dermatology life quality index, relapse rate, and adverse events. RESULTS: This study will review and evaluate the available evidence on the effectiveness and safety of auricular acupuncture for psoriasis. CONCLUSIONS: The results of this study will provide evidence for the effectiveness and safety of treating psoriasis, providing clinicians and patients with appropriate treatment options for this disease.

Scutellarin attenuates hypoxia/reoxygenation injury in hepatocytes by inhibiting apoptosis and oxidative stress through regulating Keap1/Nrf2/ARE signaling.

Scutellarin is a natural flavonoid that has been found to exhibit anti-ischemic effect. However, the effect of scutellarin on hepatic hypoxia/reoxygenation (ischemia-reperfusion (I/R)) injury remains unknown. The aim of the present study was to explore the protective effect of scutellarin on I/R-induced injury in hepatocytes. Our results showed that scutellarin improved cell viability in hepatocytes exposed to hypoxia/reoxygenation (H/R). Scutellarin treatment resulted in decreased levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and increased superoxide dismutase (SOD) activity in H/R-induced hepatocytes. In addition, scutellarin reduced cell apoptosis in H/R-stimulated hepatocytes, as proved by the decreased apoptotic rate. Moreover, scutellarin significantly up-regulated bcl-2 expression and down-regulated bax expression in hepatocytes exposed to H/R. Furthermore, scutellarin treatment caused significant decrease in Keap1 expression and increase in nuclear Nrf2 expression. Besides, scutellarin induced the mRNA expressions of heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1). Inhibition of Nrf2 significantly reversed the protective effects of scutellarin on H/R-stimulated hepatocytes. In conclusion, these findings demonstrated that scutellarin protected hepatocytes from H/R-induced oxidative injury through regulating the Keap1/Nrf2/ARE signaling pathway, indicating a potential relevance of scutellarin in attenuating hepatic I/R injury.

Clinical application of ventriculoperitoneal shunting in treating traumatic brain injury.

This study explored the clinical application of ventriculoperitoneal (VP) shunting in treating traumatic brain injury (TBI). A retrospective analysis was performed on 100 patients who had hydrocephalus due to TBI and were admitted to Shanxian Central Hospital from February 2012 to June 2016. Among these patients, 50 underwent VP shunting surgery and were assigned to the experimental group. The remaining 50 underwent lumboperitoneal (LP) shunting surgery and were assigned to the control group. Twenty days after surgery, all patients were evaluated for clinical outcomes, neurological deficit scores and complications. The results were compared between the two groups. Patients in the experimental group were further separated into three subgroups according to the severity of hydrocephalus, and clinical outcomes were compared among the subgroups. It was found that the effective rate in the experimental group was significantly higher than that in the control group, and the difference was statistically significant (P<0.05). The effective rate in the mild hydrocephalus subgroup was significantly higher than that in the severe hydrocephalus subgroup, with a statistically significant difference (P<0.05). The effective rate in the moderate hydrocephalus subgroup was significantly higher than that in the severe hydrocephalus subgroup, with a statistically significant difference (P<0.05). The incidence of complications in the control group was significantly higher than that in the experimental group, and the difference was statistically significant (P<0.05). The postoperative neurological deficit score in the experimental group was significantly lower than that in the control group, and the difference was statistically significant (P<0.05). In conclusion, patients with hydrocephalus due to TBI had better clinical outcome when treated with VP shunting than those treated with LP shunting. Moreover, a better outcome was observed when the patient had milder hydrocephalus. Therefore, the early diagnosis and timely treatment with VP shunting are of great importance for patients with hydrocephalus.