ObjectiveTo explore the potential mechanism of acupuncture with the method of soothing the liver and regulating the mind in improving depressive disorder. MethodsEighteen C57BL/6J mice were randomly divided into blank group， model group， and acupuncture group， with 6 mice in each group. The model group and the acupuncture group were subjected to depression induction by intraperitoneal injection of lipopolysaccharide （LPS）， while the blank group received an equal volume of normal saline once daily for seven consecutive days. Concurrently， the acupuncture group received "soothing the liver and regulating the mind" acupuncture intervention starting from the first day of modeling， once daily for 14 days； whereas the blank group and the model group were only restrained without acupuncture. The sucrose preference test was used to assess sucrose preference rate， the open-field test to measure center stay time and total travel distance， and the forced swim test to evaluate immobility time. Hematoxylin-eosin （HE） staining was performed to observe hippocampal morphological changes. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in hippocampal tissue. Western blot analysis was conducted to examine the protein expression levels of Toll-like receptor 4 （TLR4） and nuclear factor-κB （NF-κB） in the hippocampus. ResultsCompared to the blank group， the model group showed a significant reduction in sucrose preference rate， center stay time， and total travel distance， along with a significant increase in immobility time in the forced swim test， hippocampal IL-1β， IL-6， and TNF-α levels， as well as TLR4 and NF-κB protein expression （P＜0.01）， and the histological examination revealed blurred hippocampal neuronal boundaries， loose arrangement， and some neurons exhibiting nuclear pyknosis and deep staining. Compared to the model group， the acupuncture group demonstrated a significant increase in sucrose preference rate， center stay time， and total travel distance， along with a significant reduction in immobility time in the forced swim test， hippocampal IL-1β， IL-6， and TNF-α levels， and TLR4 and NF-κB protein expression （P＜0.01）， and the histological analysis showed that hippocampal neurons in the acupuncture group were more tightly arranged， with reduced nuclear pyknosis and deep staining. ConclusionAcupuncture with the "soothing the liver and regulating the mind" method can significantly improve depression-like behavior， potentially by inhibiting the hippocampal TLR4/NF-κB signaling pathway and alleviating inflammatory responses.

Objective: To investigate the effects of "liver-smoothing and spirit-regulating" acupuncture on the intestinal flora, lipopolysaccharide (LPS) and the hippocampal toll-like receptor 4 (TLR4)/ transcription factor (NF)-κB signaling pathway in depressive disorder mouse model, and to explore its underlying mechanisms. Methods: Eighteen male SPF-grade C57BL/6J mice were randomly assigned to the control, model, and acupuncture groups using a random number method, with six mice in each group. The depression disorder model was induced in mice from both the acupuncture and model groups using CUMS. The mice in the acupuncture group were treated with acupuncture at the acupoints of "Baihui" (DU20), "Yintang" (DU29), "Hegu" (LI4), and "Taichong" (LR3) on the 15th day of modeling, with a duration of 20 min per session, once per day, for 2 consecutive weeks. Behavioral differences were assessed using the sucrose preference test, open field test, and forced swim test. Hematoxylin-eosin staining was used to observe pathological changes in the hippocampus and colon. The levels of the inflammatory factors interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and LPS in the hippocampus and colon were measured using Enzyme-linked Immunosorbent Assay. Western blotting was used to detect the expression of TLR4 and NF-κB protein in the hippocampus. Changes in gut microbiota structure and abundance were analyzed by 16 S rDNA sequencing. Results: Compared to the control group, the model group showed reduced sucrose preference rate, time in the center area, and total distance, with an increase in immobility time (P<0.01). Inflammatory pathological changes were observed in the hippocampal CA1 region and colon. The contents of IL-1β, IL-6, TNF-α, and LPS in the hippocampus and colon increased (P<0.01). The protein expression levels of hippocampal TLR4 and NF-κB were increased (P<0.01). The Chao1 index was increased (P<0.01). The relative abundances of Pseudomonadales, Acinetobacter, Moraxellaceae, Solibacillus, Escherichia_shigella, Enterobacteriaceae, Enterobacterales, Dubosiella, and Erysipelottichales were decreased, while the relative abundances of Alloprevotella and gram_negative_bacteriurh_cTPY_13 were increased (P<0.05). The pathways of lipopolysaccharide biosynthesis and pathogenic Escherichia coli infection were upregulated, and the pathway of terpenoid backbone biosynthesis was downregulated (P<0.01). Compared to the model group, the acupuncture group showed increased sucrose preference, time in the center area, and total distance, with a decrease in immobility time (P<0.01). The inflammatory pathological changes in the hippocampal CA1 region and colon were alleviated. The contents of IL-1β, IL-6, TNF-α, and LPS in the hippocampus and colon were reduced(P<0.01). The protein expression levels of hippocampal TLR4 and NF-κB were reduced (P<0.01). The Chao1 index was decreased (P<0.05), and the relative abundances of Dubosiella and Erysipelotrichaceae were increased, while the relative abundance of Rikenellaceae, Alloprevotella, and gram_negative_bacteriuch_cTPY_13 were decreased(P<0.05). The pathways of lipopolysaccharide biosynthesis and pathogenic Escherichia coli infection were significantly downregulated, and the pathway of terpenoid backbone biosynthesis was upregulated (P<0.01). Conclusion " Liver-smoothing and spirit-regulating" acupuncture can improve depressive symptoms in depressive disorder mice, potentially through regulating the LPS and TLR4/NF-κB signaling pathway mediated by intestinal flora, reducing the inflammatory response of the hippocampus, and improving the pathological injury of the hippocampus.

The paper reviews systematically Professor FU Wenbin's academic thinking and clinical experience of integrative acupuncture-moxibustion therapy for cranial tinnitus. Professor FU believes that cranial tinnitus refers to psychosomatic comorbidity. This disease is associated mainly with the brain and liver in terms of the disease location. In pathogenesis, the dysfunction of qi movement, disharmony of internal organs and unhealthy conditions of body and mind are involved. In treatment, based on psychosomatic medicine, from the perspective of the integration of body and mind, and in line with the mode of the integrative acupuncture-moxibustion therapy, holistic regimens are used, including acupuncture, moxibustion, auricular acupuncture, etc. to consolidate the therapeutic effect of "tranquilizing the mind and relieving tinnitus".
Humans ; Tinnitus/psychology* ; Acupuncture Therapy ; Moxibustion ; Psychosomatic Medicine

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

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Objective:To use pan-genomics and subtractive proteomics techniques to screen the new antibacterial targets from the Staphylococcus aureus genome,and to lay the foundation for the development of anti-Staphylococcus aureus drugs.Methods:The genome sequencing data of 50 strains with sequencing level Complete were collected by searching the whole genome sequencing data in the National Center for Biotechnology Information(NCBI)Database with Staphylococcus aureus as the keyword;BPGA tool was used to conduct the pan-genomics analysis on the genomic data to obtain the core genes of Staphylococcus aureus;subtractive proteomics technique was used to screen the potential antibacterial targets from the core genes.These potential antibacterial targets were used as the receptors;LibDock software was used to screen the potential anti-Staphylococcus aureus drugs from the US Food and Drug Administration(FDA)-approved drug library;molecular docking technology was used to analyze the binding abilities of the drugs and targets.Results:There were 14 379 gene families in the 50 Staphylococcus aureus genomes,of which 1 620 were the core genes.The subtractive proteomics analysis results showed that tyrosine autokinase 1335 was the potential anti-Staphylococcus aureus target.LibDock software screened out nine compounds,including balofloxacin,tenofovir disoproxil fumarate,and adefovir,that may exert anti-Staphylococcus aureus effects on this target protein.The molecular docking results showed there was good binding abilities between the targets and the compounds.Conclusion:Tyrosine autokinase may be the potential target for antii-Staphylococcus aureus.

Objective To investigate the clinical characteristics,treatment methods,and prognosis of a-cute leukemia patients with extramedullary infiltration.Methods The clinical characteristics and treatment methods of 47 acute leukemia patients with extramedullary infiltration admitted to the Affiliated Hospital of Guizhou Medical University from April 2014 to April 2023 were retrospectively analyzed.Subgroup analysis was performed according to whether there was extramedullary infiltration before transplantation,and whether there was isolated extramedullary recurrence after transplantation.Based on this analysis,the patients were di-vided into the pre-transplantation radiotherapy group and pre-transplantation non-radiotherapy group,the post-transplantation radiotherapy group and post-transplantation non-radiotherapy group.According to the treatment methods of central nervous system leukemia(CNSL),the patients were divided into the intrathecal injection group(n=12)and combination of intrathecal injection and radiotherapy group(n=13).The local remission situation,survival duration,and toxic and side effects of radiotherapy and chemotherapy were com-pared.Results For acute leukemia patients with extramedullary infiltration,the overall survival time(OS)in the radiotherapy group was better than that in the non-radiotherapy group(median OS:706 d vs.151 d,P=0.015).Subgroup analysis showed that the OS of the pre-transplantation radiotherapy group was better than that of the pre-transplantation non-radiotherapy group(median OS:592 d vs.386 d,P=0.035).For CNSL,the combination of intrathecal injection and radiotherapy group had a better OS than the intrathecal injection group(median OS:547 d vs.388 d,P=0.045).The event-free survival time(EFS)of the radiotherapy group was better than that of the non-radiotherapy group(median EFS:175 d vs.50 d,P=0.005).The COX pro-portional-hazards model showed that treatment with or without radiotherapy had a significant impact on the OS of acute leukemia patients with extramedullary infiltration.The risk of death in the pre-transplantation non-radiotherapy group was 2.231 times higher than that in the pre-transplantation radiotherapy group(HR=3.231,95％CI:1.021-10.227,P=0.046).Compared with the non-radiotherapy group,the radiother-apy group had a higher local remission and a lower risk of haematological toxicity,infection,and haemorrhage.Conclusion Radiotherapy can rapidly alleviate the local symptoms of acute leukemia complicated with extr-amedullary infiltration,prolong the survival time of these patients,and reduce the risk of hematologic toxicity,infection,and haemorrhage.

Objective:To investigate the effect of transurethral green laser prostate enucleation (GreenLEP) in the treatment of benign prostate hyperplasia (BPH) with detrusor underactivity (DU).Methods:The clinical data of 157 BPH patients treated with GreenLEP at Zhejiang Provincial People's Hospital from June 2019 to June 2020 were retrospectively analysed. The average age of the patients was (73.2±7.9) years old, with disease duration of 4(2, 8) years. Prior to surgery, all patients underwent comprehensive urodynamic studies and prostate ultrasonography (or enhanced MRI). Preoperative prostate volume was 42.1(34.2, 59.4) ml, international prostate symptom score (IPSS) was (27.9±3.4), quality of life (QOL) score was (5.1±0.8), preoperative residual urine volume (PVR) was 40.0(20.0, 80.0) ml, and preoperative maximum urinary flow rate (Q max) was 4.0(2.0, 7.0) ml/s. Patients were stratified into DU and non-DU groups using a bladder contractility index (BCI) threshold of less than 100 to diagnose DU. The cohort comprised 76 individuals in the DU group and 81 in the non-DU group. At the three-month postoperative juncture, a follow-up assessment was conducted on the patients, focusing on the evolution of subjective metrics (IPSS, QOL) and objective parameters (PVR, Q max). This study defined successful treatment outcomes at the 3-month mark as achieving PVR<20 ml and Q max>10 ml/s. Cases not meeting these criteria were categorized as treatment failure. Based on treatment outcomes, receiver operator characteristic (ROC) curve were plotted to identify the optimal cutoff value of BCI for predicting treatment efficacy. Subsequently, DU patients were classified into mild and severe DU groups based on this optimal BCI threshold. The differences of subjective indicators (IPSS, QOL) and objective parameters (PVR, Q max) preoperatively among non-DU, mild DU, and severe DU groups, as well as changes in these indices three months postoperatively were analyzed. Results:All 157 surgeries were successfully completed, with a median hospital stay of 6(5, 8) days. At the 3-month postoperative follow-up, 78 patients were deemed treatment successes and 3 as failures in non-DU group, 64 were successful and 12 failed in DU group. Utilizing ROC curve analysis, the BCI was optimally set at 57.5. This stratification resulted in 56 cases classified as mild DU (57.5≤BCI<100) group and 20 cases as severe DU (BCI<57.5) group. A comparative analysis of the three patient cohorts, revealed no significant statistical variation in terms of age, disease duration, or prostate volume ( P>0.05). In the non-DU, mild DU, and severe DU groups, IPSS were (26.8±3.4), (28.6±3.0), and (30.6±2.4) respectively, QOL sores were (4.9±0.9), (5.2±0.7), and (5.7±0.5) respectively, PVR volumes were 50.0(20.0, 90.0), 20.0(10.0, 50.0), and 60.0(27.5, 165.0) ml respectively, Q max were 4.0(2.0, 7.0), 5.0(4.0, 6.0), and 0(0, 2.3) ml/s respectively. Preoperative IPSS and QOL were significantly lower in the non-DU group compared with mild and severe DU groups ( P<0.05). Mild DU group had lower preoperative IPSS and QOL than the severe DU group ( P<0.05). Preoperative PVR in the mild DU group was less than that in both non-DU and severe DU groups ( P<0.05), but there was no statistically significant difference in preoperative PVR between non-DU and severe DU groups ( P>0.05). Preoperative Q maxof non-DU and mild DU groups was significantly higher than that of severe DU group ( P<0.05), with no significant difference between non-DU and mild DU ( P>0.05). Three months after surgery, IPSS scores of non-DU group, mild DU group and severe DU group were (12.5±4.7), (14.9±3.6) and (18.8±4.1), respectively. QOL scores of the 3 groups improved to (1.1±0.4), (1.2±0.5) and (1.9±1.0), respectively. PVR was 0 in non-DU and mild DU, and 20.0 (19.5, 61.3) ml in severe DU. Q max of the 3 groups were improved to 22.0(18.0, 27.0), 17.0(14.0, 22.3), and 9.0(6.8, 13.0) ml/s, respectively. Significant improvements of subjective symptoms (IPSS, QOL) and objective parameters (PVR, Q max) were observed in non-DU and mild DU group compared with preoperative( P<0.05). Significant improvements of IPSS, QOL and Q max ( P<0.05) but not PVR ( P=0.14)were observed in severe DU group. Additionally, significant differences were noted in PVR and Q max changes among the three groups ( P<0.05), but not in IPSS and QOL changes ( P>0.05). The absolute value of PVR and Q max changes in the non-DU group were higher than those in the mild DU group and the severe DU group ( P<0.05). Additionally, the change of Q max in mild DU group was significantly higher than that in severe DU group ( P<0.05). Conclusions:BPH patients with different degrees of DU can benefit from GreenLEP surgery, but for BPH patients with severe DU (BCI < 57.5), the improvements in PVR and Q max are less than that in the non-DU group.

Leptomeningeal metastasis(LM)is a serious late complication in patients with solid tumors,which is common in patients with lung cancer,breast cancer and melanoma.In recent years,due to the progress of diagnosis,the diagnosis rate of LM has gradually increased.The main goal of the therapy is to maintain neurological function,improve the quality of life and the overall survival rate,and prolong the progression-free survival time of patients.Intrathecal therapy is one of the main treatments for LM,which can deliver drugs directly to the subarachnoid space.The traditional intrathecal drugs are methotrexate,cytarabine and thiotepa.With the development of new research,a variety of chemotherapeutic drugs,targeted drugs and immune checkpoint inhibitors have also been used in intrathecal therapy.In addition,different ways of intrathecal administration also bring new hope to patients.This article reviewed the clinical research progress of intrathecal therapy in the treatment of LM.