Clinical efficacy and potential mechanism of ginseng polysaccharides in the treatment of non-small cell lung cancer based on meta-analysis associated with network pharmacology.

Background: The ginseng polysaccharide injection is a well-known traditional Chinese medicine often employed as a supplementary treatment for cancer. This treatment can not only alleviate the adverse effects caused by tumor radiotherapy and chemotherapy but also enhance the immune system of individuals diagnosed with lung cancer. It is important to acknowledge the efficacy of ginseng polysaccharide injection in the treatment of non-small cell lung cancer (NSCLC). However, these small-sample studies may have certain biases, and the underlying mechanisms of ginseng polysaccharides therapy for NSCLC are still unclear. Methods: The present study involved a systematic review of the literature on randomized controlled trials (RCTs) focusing on using ginseng polysaccharide injection as a therapeutic approach for NSCLC. Seven databases were searched for eligible studies published before April 2023. Two researchers independently managed data extraction, risk of bias assessment, and data analyses using RevMan 5.3 software. In network pharmacology, we thoroughly searched the relevant literature on ginseng polysaccharides (GPs) and the PubChem database. This search aimed to identify the main active ingredients and targets associated with ginseng polysaccharides. Subsequently, we compared these targets with those of NSCLC and utilized bioinformatics techniques to analyze and explore their potential interactions. Results: A total of 11 RCTs involving 845 patients with NSCLC were included in the meta-analysis. The meta-analysis revealed that ginseng polysaccharide injection combined significantly improved the objective response rate [RR = 1.45, 95% CI (1.26, 1.67), P < 0.00001]. Furthermore, it was observed that ginseng polysaccharide injection increased the serum levels of CD4+ T-lymphocytes (CD4+ T) [MD = 8.98, 95% CI (5.18, 12.78), P < 0.00001], and decreased the serum levels of CD8+ T-lymphocytes (CD8+ T) [MD = -2.68, 95% CI (-4.66, -0.70), P = 0.008]. Through network pharmacology analysis, a total of 211 target genes of GPs and 81 common targets were identified. GAPDH, EGFR, VEGFA, JUN, SRC, CASP3, STAT3, CCND1, HSP90AA1, and MMP9 were identified as the core target proteins. Additionally, KEGG enrichment analysis revealed 122 relevant signaling pathways, including Pathways in cancer, PD-L1 expression and PD-1 checkpoint pathway in cancer, and Proteoglycans in cancer. Conclusion: Ginseng polysaccharide injection can improve the ORR of patients with NSCLC, increase the serum levels of CD4+ T, and decrease the serum levels of CD8+ T. The potential mechanism may be associated with the PD-1/PD-L1 signaling pathway.

Dietary nitrate supplementation to enhance exercise capacity in patients with COPD: Evidence from a meta-analysis of randomized controlled trials and a network pharmacological analysis.

OBJECTIVE: The potential effects of nitrate in patients with chronic obstructive pulmonary disease (COPD) have attracted increased research interest. However, previous clinical trials have reported inconsistent results, and consecutive meta-analyses have failed to reach a consensus. Since some randomized controlled trials have recently been conducted that can provide more evidence, we performed an updated meta-analysis. METHODS: A comprehensive literature search was conducted using PubMed, the Cochrane Library, Embase, and Web of Science databases to identify trials that assessed the efficacy and safety of nitrate in patients with COPD. The Revman 5.3 software was used for data analysis. Mean difference (MD) or standardized mean difference (SMD) with 95 % confidence interval (CI) was used as the effect measure, and forest plots were used to display individual and pooled results. Network pharmacology analysis was conducted to investigate the potential mechanisms of nitrate action in COPD. RESULTS: Eleven studies involving 287 patients were included in this meta-analysis. The results indicated that dietary nitrate supplementation increased plasma nitrate and nitrite concentrations and fractional exhaled nitric oxide in patients with COPD. Nitrate improved exercise capacity [SMD = 0.38, 95 % CI = 0.04-0.72] and endothelial function [MD = 9.41, 95 % CI = 5.30-13.52], and relieved dyspnea in patients with COPD. Network pharmacology identified AKT1, IL1B, MAPK3, and CASP3 as key treatment targets. CONCLUSION: Dietary nitrate supplementation could be used as a potential treatment for patients with COPD, especially to increase their exercise capacity. The underlying mechanisms may be related to AKT1, IL1B, MAPK3, and CASP3.

Effect of Cinobufacini plus platinum-based chemotherapy regimen on the immune function of patients with non-small-cell lung cancer: A meta-analysis.

Background: Cinobufacini is a Chinese medicinal preparation extracted from the traditional Chinese medicine toad skin and is commonly used clinically as an adjuvant treatment for malignant tumours. Purpose: To systematically evaluate the effects of Cinobufacini combined with a first-line platinum-based chemotherapy regimen in patients with non-small-cell lung cancer (NSCLC), especially in terms of immune function. Materials and methods: Eight electronic databases were searched for randomised controlled trials (RCTs) investigating Cinobufacini in conjunction with platinum-based chemotherapy for NSCLC (stage III-IV) published from 2012 to the present. GRADE Pro GDT was used to assess RCT quality and meta-analysis was performed mainly using Review Manager version 5.4, with the assistance of Stata version 16.0 (StataCorp LLC, College Station, TX, USA), and trial sequential analysis software. Results: A total of 35 studies were included. Meta-analysis revealed that the combination therapy group exhibited a better disease control rate (DCR) [OR = 2.63, 95%CI (2.15, 3.21), P < 0.00001], with a higher one-year [OR = 2.41,95% CI (1.75,3.33), P < 0.00001], and two-year [OR = 2.28, 95% CI (1.56,3.33), P < 0.00001] survival rate, plus lower leukocyte toxicity [OR = 0.40, 95%CI (0.33,0.49), P < 0.00001]. For immune function, the combination of chemotherapy with Cinobufacini effectively increased the proportion of CD3+ [SMD = 1.15, 95% CI (0.89,1.42), P < 0.00001], CD4+ [SMD = 1.60, 95%CI (1.26,1.94), P < 0.00001] and the CD4+/CD8+ ratio [SMD = 2.15, 95% CI (1.45,2.86), P < 0.00001] in peripheral blood. Conclusion: The addition of Cinobufacini to platinum-based chemotherapies for advanced NSCLC significantly improved clinical efficacy, enhanced immune function, and reduced chemotherapeutic toxicity, irrespective of administration and treatment duration.

[Effects of electroacupuncture on the expression of serum exosomes and pro-inflammatory factors in spinal cord of rats with spinal cord injury].

OBJECTIVE: To investigate the effect of electroacupuncture (EA) on the morphology and microstructure of spinal cord tissue, the expression of serum exosomes, and the pro-inflammatory factors interleukin (IL)-1ß and IL-6 in spinal cord of rats with spinal cord injury (SCI), so as to explore the underlying mechanism of EA in the treatment of SCI. METHODS: Twenty-four female Wistar rats were randomly divided into sham operation group, model group, EA group, EA+GW4869 group, with 6 rats in each group. The SCI model was established by impinging spinal cord at T10 with a hammer, while the vertebral lamina was only opened without impingement for rats in sham operation group. Rats in EA group received EA intervention at "Jiaji"(EX-B7) acupoints at bilateral T9 and T10 (0.4-0.6 mA, 100 Hz), 3 h after modeling, once a day, for 7 concecutive days. Besides the treatment as EA group, rats in the EA+GW4869 group received injection of exosome inhibitor GW4869(200 µL, 300 µg/mL) once every 2 days from the day before modeling. Motor function of hind limbs of rats was evaluated using BBB scores. The histopathological changes of spinal cord were observed under light mircoscope after H.E. staining. Microstructure of spinal cord was observed and extracted serum exosomes were identified by using transmission electron microscopy. The expression of exosome marker proteins in serum exosomes, the levels of IL-1ß and IL-6 in spinal cord were detected by Western blot. RESULTS: H.E. stanining showed severe tissue looseness, inflammatory cell infiltration, cellular hydropic degeneration in spinal cord of the model group, which were relatively milder in the EA and EA+GW4869 groups. Under transmission electron microscopy, there were nerve fiber disintegration, myelin sheath structure dispersion, axonal atrophy with submembrane edema and widened space, and mitochondrial swelling in spinal cord of rats in the model group, with the lesions in EA group milder than EA+GW4869 group, which were both moderate. Typical exosomes were detected by transmission electron microscope in the extracted serum of rats in each group after ultracentrifugation. Compared with the sham operation group, the motor function scores was significantly decreased (P<0.01), the expression of IL-6 and IL-1ß in the spinal cord was significantly increased (P<0.01), while the expression of serum exosome marker protein CD81 was slightly increased in rats of the model group. Compared with the model group, the motor function scores was significantly increased (P<0.01), the expression of IL-6 and IL-1ß in the spinal cord was significantly decreased (P<0.01) in rats of the EA and EA+GW4869 group, while the expression of serum CD81 protein was slightly increased in rats of the EA group. Compared with the EA+GW4869 group, the expression of IL-6 and IL-1ß in the spinal cord was significantly decreased (P<0.01), while the expression of serum CD81 protein was slightly increased in rats of the EA group. However, there was no significance in expression of CD81 between each group mentioned above. CONCLUSION: EA can promote the secretion of serum exosomes and inhibit the expression of pro-inflammatory cytokines IL-6 and IL-1ß, so as to improve the microenvironment of injured spinal cord and SCI.

Epigenetic regulation of IPF fibroblast phenotype by glutaminolysis.

OBJECTIVE: Excessive extra-cellular-matrix production and uncontrolled proliferation of the fibroblasts are characteristics of many fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). The fibroblasts have enhanced glutaminolysis with up-regulated glutaminase, GLS1, which converts glutamine to glutamate. Here, we investigated the role of glutaminolysis and glutaminolysis-derived metabolite α-ketoglutarate (α-KG) on IPF fibroblast phenotype and gene expression. METHODS: Reduced glutamine conditions were carried out either using glutamine-free culture medium or silencing the expression of GLS1 with siRNA, with or without α-KG compensation. Cell phenotype has been characterized under these different conditions, and gene expression profile was examined by RNA-Seq. Specific profibrotic genes (Col3A1 and PLK1) expression were examined by real-time PCR and western blots. The levels of repressive histone H3K27me3, which demethylase activity is affected by glutaminolysis, were examined and H3K27me3 association with promoter region of Col3A1 and PLK1 were checked by ChIP assays. Effects of reduced glutaminolysis on fibrosis markers were checked in an animal model of lung fibrosis. RESULTS: The lack of glutamine in the culture medium alters the profibrotic phenotype of activated fibroblasts. The addition of exogenous and glutaminolysis-derived metabolite α-KG to glutamine-free media barely restores the pro-fibrotic phenotype of activated fibroblasts. Many genes are down-regulated in glutamine-free medium, α-KG supplementation only rescues a limited number of genes. As α-KG is a cofactor for histone demethylases of H3K27me3, the reduced glutaminolysis alters H3K27me3 levels, and enriches H3K27me3 association with Col3A1 and PLK1 promoter region. Adding α-KG in glutamine-free medium depleted H3K27me3 association with Col3A1 promoter region but not that of PLK1. In a murine model of lung fibrosis, mice with reduced glutaminolysis showed markedly reduced fibrotic markers. CONCLUSIONS: This study indicates that glutamine is critical for supporting pro-fibrotic fibroblast phenotype in lung fibrosis, partially through α-KG-dependent and -independent mechanisms, and supports targeting fibroblast metabolism as a therapeutic method for fibrotic diseases.

[Protective effect and mechanism of Maiwei Yangfei Decoction on pulmonary fibrosis mice based on Nrf2 regulation of oxidative stress].

This study explored the effect and mechanism of Maiwei Yangfei Decoction(MWYF) on pulmonary fibrosis(PF) mice. MWYF was prepared, and its main components were detected by ultra-high-performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-MS/MS). Male C57BL/6J mice were randomly divided into a control group, a model group, a pirfenidone(PFD) group, and low-, medium-, and high-dose MWYF groups, with 10 mice in each group. The PF model was induced in mice except for those in the control group by intratracheal instillation of bleomycin(BLM), and model mice were treated with saline or MWYF or PFD by gavage the next day. The water consumption, food intake, hair, and activity of mice were observed daily. The pathological changes in lung tissues were observed by hematoxylin-eosin(HE) staining, Masson staining, and CT scanning. The level of hydroxyproline(HYP) in lung tissues was detected by alkaline hydrolysis. Immunohistochemistry was used to observe the expression of collagen type Ⅲ(COL3) and fibronectin. The mRNA expression levels of α-smooth muscle actin(α-SMA), type Ⅰ collagen α1(COL1α1), COL3, and vimentin were detected by reverse transcription real-time fluorescence quantitative polymerase chain reaction(RT-qPCR). Superoxide dismutase(SOD) and malondialdehyde(MDA) kits were used to detect oxidative stress indicators in lung tissues and serum. The nuclear translocation of nuclear factor E2-related factor 2(Nrf2) protein was detected by immunofluorescence. The protein and mRNA expression levels of Nrf2, catalase(CAT), and heme oxygenase 1(HO-1) in lung tissues were detected by Western blot and RT-qPCR. Twelve chemical components were detected by UPLC-MS/MS. Animal experiments showed that MWYF could improve alveolar inflammation, collagen deposition, and fibrosis in PF mice, increase body weight of mice, and down-regulate the expression of fibrosis indexes such as HYP, α-SMA, COL1α1, COL3, fibronectin, and vimentin in lung tissues. In addition, MWYF could potentiate the activity of SOD in lung tissues and serum of PF mice, up-regulate the expression level of Nrf2, and promote its transfer to the nucleus, up-regulate the levels of downstream antioxidant target genes CAT and HO-1, and then reduce the accumulation of lipid metabolite MDA. In summary, MWYF can significantly improve the pathological damage and fibrosis of lung tissues in PF mice, and its mechanism may be related to the activation of the Nrf2 pathway to regulate oxidative stress.

[Consolidating the foundation, highlighting the practice and strengthening the training of clinical thinking of acupuncture and moxibustion: the thoughts of compiling the China national standardized training textbook Acupuncture and Moxibustion for residents of traditional Chinese medicine].

Based on the clinical needs and examination requirements of standardized training students, the China national standardized training textbook Acupuncture and Moxibustion for residents of traditional Chinese medicine has made innovations in the textbook content and form. In the part of meridians and acupoints, the classic original text is introduced and the main indications and operation methods of 200 commonly-used acupoints are summarized in the form of tables. In the part of acupuncture and moxibustion technique, the operating procedures are standardized and the core technical points of 20 commonly-used acupuncture and moxibustion techniques are summarized in the form of flow chart. In the part of acupuncture and moxibustion treatment, 48 typical diseases are introduced in the form of case discussion, highlighting the problem orientation and demonstrating the diagnosis and treatment procedures.

[Effects of electroacupuncture on BNDF/mTORC1 signaling pathway and synaptic plasticity in prefrontal cortex of rats exposed to chronic unpredictable mild stress].

OBJECTIVE: To investigate the effects of electroacupuncture (EA) on the expression of related proteins in the brain-derived neurotrophic factor (BDNF)/mammalian target of rapamycin complex 1 (mTORC1) signaling pathway and synapse-associated proteins and the density of dendrite spines in the prefrontal cortex (PFC) of depression model rats, and to reveal the underlying mechanism by which EA regulates the synaptic plasticity to improve depressive symptoms. METHODS: Thirty-six healthy male Sprague-Dawley (SD) rats were randomly divided into normal group, model group, EA group, and scopolamine (SCOP) group, with 9 in each group. The depression model was established by exposing rats to chronic unpredictable mild stress (CUMS) combined with isolated feeding. Rats in the EA group were treated with EA (2 Hz/100 Hz, 1-1.2 mA) at "Baihui" (GV20), "Yintang" (EX-HN3), "Hegu" (LI4), and "Taichong" (LR3), 20 min each time, once per day, for 14 d, while those in the SCOP group treated with intraperitoneal injection of 25 µg/kg SCOP, once every 16 h, for 14 d. The sucrose preference and feeding latency of rats in each group were observed in the sucrose preference test (SPT) and novelty-suppressed feeding test. The expression levels of proteins in the BDNF/mTORC1 signaling pathway and synapse-associated proteins PSD95, Synapsin Ⅰ, and GluR1 were assayed by Western blot. Golgi-Cox staining was conducted for exploring the total density of dendritic spines on the apical dendrites of layer Ⅴ pyramidal neurons in PFC as well as the densities of mature, immature, and filopodial-like dendritic spines. RESULTS: Compared with the normal group, the model group exhibited significantly decreased sucrose preference (P<0.001), prolonged feeding latency (P<0.001), down-regulated BDNF, mTORC1, phosphorylated mTORC1 (p-mTORC1), PSD95, Synapsin Ⅰ, and GluR1 expression (P<0.001，P<0.01), and diminished total, mature, and immature spine dendritic densities (P<0.001). Compared with the model group, both EA and SCOP remarkably increased the sucrose preference (P<0.001), shortened the feeding latency (P<0.001), up-regulated the BDNF, mTORC1, p-mTORC1, PSD95, Synapsin Ⅰ, and GluR1 expression in PFC(P<0.05，P<0.01，P<0.001), and elevated the total and immature spine dendritic densities (P<0.001,P<0.01). The density of filopodial-like dendritic spine in the EA group was obviously enhanced (P<0.01), whereas the mature dendritic spine density in the SCOP group rose sharply (P<0.001). However, there were no significant differences between the EA group and SCOP group (P>0.05). CONCLUSION: EA alleviates the depressive symptoms of CUMS model rats possibly by up-regulating the expression of proteins in the BDNF/mTORC1 signaling pathway and synapse-asso-ciated proteins PSD95, Synapsin Ⅰ, and GluR1, increasing the dendritic spine density, and enhancing the synaptic plasticity in PFC.

Consolidating the foundation, highlighting the practice and strengthening the training of clinical thinking of acupuncture and moxibustion: the thoughts of compiling the China national standardized training textbook Acupuncture and Moxibustion for residents of traditional Chinese medicine / 中国针灸

Based on the clinical needs and examination requirements of standardized training students, the China national standardized training textbook Acupuncture and Moxibustion for residents of traditional Chinese medicine has made innovations in the textbook content and form. In the part of meridians and acupoints, the classic original text is introduced and the main indications and operation methods of 200 commonly-used acupoints are summarized in the form of tables. In the part of acupuncture and moxibustion technique, the operating procedures are standardized and the core technical points of 20 commonly-used acupuncture and moxibustion techniques are summarized in the form of flow chart. In the part of acupuncture and moxibustion treatment, 48 typical diseases are introduced in the form of case discussion, highlighting the problem orientation and demonstrating the diagnosis and treatment procedures.

[Professor FU Wen-bin's experience in treatment of mental disorder with acupuncture and moxibustion from perspective of "psychosomatic medicine"].

The paper summarizes the ideas and characteristics of acupoint selection in treatment of mental disorder with acupuncture and moxibustion by professor FU Wen-bin. Professor FU believes that mental disorder is manifested as the simultaneous illness of "heart" and "body". On the base of "holism" for the unity of body and mind, professor FU proposes the treating idea as "soothing the liver, regulating the mind and focusing on the heart and the gallbladder in treatment". In clinical practice, the acupoint prescription on specifically regulating and harmonizing yin and yang is composed to calm down the mind. The eight confluent points and back-shu points of five zang organs are selected to regulate zangfu functions. The "ghost" points, the points on the second line of bladder meridian and the acupoints with specific effect are used to tranquilize the mind, open the orifices and consolidate therapeutic effect. Meanwhile, the complicated symptoms are also considered in treatment. The integrative and holistic pattern of acupuncture and moxibustion therapy as "acupuncture at the top priority, followed by moxibustion, and consolidation at the end" achieves the co-regulation of qi and blood and tranquilization for both the mental and the physical.

Efficacy and Safety of Tripterygium Wilfordii Hook. F for Connective Tissue Disease-Associated Interstitial Lung Disease:A Systematic Review and Meta-Analysis.

Background: Tripterygium wilfordii Hook. F (TwHF), a Chinese herbal medicine used to treat CTD-ILD patients in China, has been previously found to have immunoinhibitory, antifibrotic and anti inflammatory effects. It has also shown good results in treating autoimmune and inflammatory diseases. Objectives: This systematic review and meta-analysis aims to evaluate the efficacy and safety of TwHF for CTD-ILD. Methods: A systematic search was performed on PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, Scopus, CNKI, Wanfang, VIP, and CBM databases up to May 2021. Randomized controlled trials (RCTs) comparing TwHF plus conventional therapy versus conventional therapy alone were included. We followed the PRISMA checklist, and applied Cochrane handbook 5.1.0 and RevMan 5.3 for data analysis and quality evaluation of the included studies. Results: Based on Cochrane handbook 5.1.0, nine RCTs consisting 650 patients met the inclusion/exclusion criteria and were selected for further analysis. The obtained data showed significant improvement in lung function with TwHF plus conventional treatment compared with conventional treatment (post-treatment FVC% (MD= 8.68, 95%Cl (5.10, 12.26), p < 0.00001), FEV1% (MD = 11.24, 95%Cl (6.87, 15.61), p < 0.00001), TLC% (MD = 5.28, 95%Cl (0.69, 9.87), p = 0.02)], but no significant difference in the post-treatment DLCO% [(MD = 4.40, 95%Cl (-2.29, 11.09), p = 0.20)]. Moreover, the data showed that TwHF combined with conventional treatment significantly reduced the HRCT integral of patients [MD = -0.65, 95% (-1.01, -0.30), p = 0.0003], the level of erythrocyte sedimentation rate (MD = -9.52, 95%Cl (-11.55, -7.49), p < 0.00001), c-reactive protein (CRP) (MD = -8.42, 95%Cl (-12.47, -4.38), p < 0.0001), and rheumatoid factor (MD = -25.48, 95%Cl (-29.36, -21.60), p < 0.00001). Compared to conventional therapy, TwHF combined with conventional therapy significantly improved clinical effects (RR = 1.33, 95%Cl (1.17, 1.51), p < 0.0001), in five trials with 354 patients. In terms of improvement of symptoms and signs, the TwHF group showed a more significant improvement than the conventional treatment group (Cough (MD = -0.96, 95%Cl (-1.43, -0.50), p < 0.0001), velcro rales (MD = -0.32, 95%Cl (-0.44, -0.20), p < 0.00001), shortness of breath (MD = -1.11, 95%Cl (-1.67, -0.56), p < 0.0001)], but no statistical difference in dyspnea (MD = -0.66, 95%Cl (-1.35, 0.03), p = 0.06). There was no statistical significance in the incidence of adverse reactions. Conclusion: The performed meta-analysis indicated that TwHF combined with conventional treatment was more beneficial to patients for improving symptoms, lung function and laboratory indicators. As it included studies with relatively small sample size, the findings require confirmation by further rigorously well-designed RCTs.

The Role of Acupuncture in Hormonal Shock-Induced Cognitive-Related Symptoms in Perimenopausal Depression: A Randomized Clinical Controlled Trial.

Introduction: Perimenopausal depression is predominantly caused by hormone shock, but the underlying physical and psychological factors are still unclear. Objectives: To explore the constituent components of perimenopausal depression by dynamically depicting its influencing factors and interactive pathways from the perspective of embodied cognition. Methods: This is a randomized clinical controlled trial. In this study, electroacupuncture was compared with escitalopram. A total of 242 participants with mild to moderate perimenopausal depression were enrolled from 6 hospitals in China. Each participant had a 12-week intervention and a 12-week follow-up period. The primary outcome of this study is the Hamilton Depression Rating Scale (HAMD-17), and the secondary outcome is the menopause-specific quality of life scale (MENQOL), serum Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estrogen (E2) levels. Results: The structural equation model suggested that hormone levels were not directly associated with HAMD-17 (P = 0.852), while MENQOL was statistically correlated with HAMD-17 as an intermediary variable (P < 0.001). Electroacupuncture gradually showed positive impacts on MENQOL and HAMD-17 during the follow-up period (P < 0.05). Cognitive impairment is the dominant dimension of perimenopausal depression. Conclusions: Hormonal shock may affect clinical symptoms and poor quality of life to induce cognitive impairment leading perimenopausal depression, and this impact on cognition is embodied. Electroacupuncture has positive effect on perimenopausal depression and quality of life.

Professor / 中国针灸

The paper summarizes the ideas and characteristics of acupoint selection in treatment of mental disorder with acupuncture and moxibustion by professor