Fu's subcutaneous needling (FSN) is an acupuncture technique for the treatment of soft tissue diseases. Knee osteoarthritis often involves lower limb muscles. This study aimed to observe and compare the clinical efficacy of Fu's subcutaneous acupuncture and electroacupuncture in the treatment of patients with knee osteoarthritis. 62 patients with early or medial stage of knee osteoarthritis were randomly divided into the FSN therapy group or the electroacupuncture(EA) therapy group (1:1). The Lysholm score, range of motion, and equilibrium function were observed over a 3-month follow-up period. A total of 60 participants completed the study. Over the 3 months of follow-up, both treatment regimens showed equally favorable results on all prognostic measures compared with their respective baseline data (P<0.05). Compared with the EA group, the FSN group had a significantly greater improvement in claudication, joint stability, swelling, pain, and ROM after treatment (P<0.05). At 3 months after treatment, the FSN group revealed better scores of claudication, joint stability, swelling, walking up stairs, squatting, pain, ROM, and equilibrium function (forward and backward movement speed, left and right movement speed, movement ellipse area, movement length) compared to the EA group (all P<0.05). This study showed that FSN can significantly improve the pain symptoms, joint stability, and joint function of patients with knee osteoarthritis, and the clinical efficacy can be maintained at least 3 months after treatment.

Schizophrenia (SZ) is a chronic, severe mental disorder with heterogeneous clinical manifestations and unknown etiology. Research on SZ has long been limited by the low reliability of and ambiguous pathogenesis in schizophrenia animal models. Phencyclidine (PCP), a noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist, rapidly induces both positive and negative symptoms of SZ as well as stable SZ-related cognitive impairment in rodents. However, the neural mechanism underlying PCP-induced SZ-like symptoms is not fully understood. Nondopaminergic pathophysiology, particularly excessive glutamate release induced by NMDAR hypofunction in the prefrontal cortex (PFC), may play a key role in the development of PCP-induced SZ-like symptoms. In this review, we summarize studies on the behavioral and metabolic effects of PCP and the cellular and circuitary targets of PCP in the PFC and hippocampus (HIP). PCP is thought to target the ventral HIP-PFC pathway more strongly than the PFC-VTA pathway and thalamocortical pathway. Systemic PCP administration might preferentially inhibit gamma-aminobutyric acid (GABA) neurons in the vHIP and in turn lead to hippocampal pyramidal cell disinhibition. Excitatory inputs from the HIP may trigger sustained, excessive and pathological PFC pyramidal neuron activation to mediate various SZ-like symptoms. In addition, astrocyte and microglial activation and oxidative stress in the cerebral cortex or hippocampus have been observed in PCP-induced models of SZ. These findings perfect the hypoglutamatergic hypothesis of schizophrenia. However, whether these effects direct the consequences of PCP administration and how about the relationships between these changes induced by PCP remain further elucidation through rigorous, causal and direct experimental evidence.

Objective: This study aimed to use network pharmacology to predict the therapeutic mechanism of oroxyli semen (OS) on triple-negative breast cancer (TNBC) and validate it through in vitro experiments. Methods: The active ingredients and target proteins of OS were retrieved from the Traditional Chinese Medicine Systems Pharmacology database, and the TNBC-related target genes were obtained from the GeneCards database. The overlapping genes were used to construct a protein–protein interaction (PPI) network via the String database. Furthermore, we employed an online bioinformatics analysis platform (https://www.bioinformatics.com.cn/) to perform gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses to evaluate biological processes, molecular functions, and cellular components and generate simulated signal pathways. Additionally, molecular docking was used to evaluate the binding ability of small molecule drugs and signaling pathway targets. CCK8 assay was conducted to detect the effect of small molecule drugs on TNBC cell viability, and Western Blot was utilized to verify the expression of AKT, VEGF, and hypoxia-inducible factor 1-alpha (HIF-1α) proteins. Results: Fifteen active ingredients and 166 therapeutic targets of OS were obtained from the Traditional Chinese Medicine Systems Pharmacology database. The Venn diagram revealed that 163 targets were related to TNBC. The protein–protein interaction network analysis identified AKT1, IL-6, JUN, vascular endothelial growth factor A (VEGFA), CASP3, and HIF-1α as potential core targets through which OS may treat TNBC. Furthermore, the molecular docking results indicated that the active ingredient chryseriol in OS had good binding ability with VEGFA, and HIF-1α. CCK8 assay results indicated that chryseriol inhibited the viability of MDA-MB-231 and BT-20 cells. Western Blot demonstrated that chryseriol intervention led to a decrease in VEGFA, and HIF-1α protein expression compared with the control group (P < .05), increased the cleaved PARP. Conclusion: OS may exert its therapeutic effects on TNBC through multiple cellular signaling pathways. Chryseriol, the active component of OS, can enhance the apoptosis of TNBC cells by targeting VEGFA/HIF-1α pathway. This study provided new insights into the potential therapeutic mechanism of OS for TNBC and may aid in the development of novel therapeutic approaches for TNBC.

Many studies in humans and rodents have shown that the anterior cingulate cortex (ACC) plays a critical role in the regulation of pain-related aversion and that the projection from the rostral ACC (rACC) to the ventral tegmental area (VTA) is implicated in this modulation process. The ACC is also reported to be involved in the regulation of itch-scratch behavior. However, it remains unclear whether the ACC is involved in the modulation of the negative emotions induced by acute itch sensation. In this study, we investigated the pruritogen-induced conditioned place aversion (CPA) and itch-scratching behavior in rats after pharmacogenetic inhibition of the activities of rACC-VTA pathway or the rACC neurons, respectively. Pharmacogenetic inhibition of glutamatergic neurons of rACC projecting to the VTA alleviated the CPA responses and itch-scratching behavior induced by the subcutaneous injection of 5-HT, a nonhistamine-dependent pruritogen. However, pharmacogenetic inhibition of rACC neurons did not change the CPA behavior associated with itch and, conversely, increased itch-scratching behavior. These results reveal that a specific subpopulation of rACC neurons projecting to the VTA positively regulates itch sensation and the negative emotion accompanying itch, whereas the global rACC negatively modulates acute non-histaminergic itch in rats. Postsynaptic GABAergic neurons in the VTA may mediate emotion modulation of the rACC-VTA pathway. The current findings contribute to a better understanding of the circuit mechanisms underlying the processing of different components of itch, such as sensation and emotion.