Publications by authors named "Zhifang Xu"

97 Publications

The clinical characteristics and prognosis of Chinese acute myeloid leukemia patients with CSF3R mutations.

Int J Lab Hematol 2021 Nov 24. Epub 2021 Nov 24.

Shanxi Medical University, Taiyuan, China.

Introduction: The colony-stimulating factor 3 receptor (CSF3R) controls the proliferation of myeloid progenitors and differentiation into neutrophils. However, the clinical features and prognostic significance of CSF3R mutations in primary acute myeloid leukemia (AML) patients are still unclear.

Methods: 158 newly diagnosed AML patients were retrospectively evaluated in our study. Amplicon-based next-generation sequencing (NGS) and multiplex-nested reverse-transcription polymerase chain reaction (RT-PCR) were used to investigate the 34 genes and 43 fusion genes associated with leukemia. In addition, clinical features, mutation incidence, and survival outcomes were compared between patients with CSF3R mutation and patients with wild-type CSF3R.

Results: In our study, CSF3R mutations were found in 7.6% (12/158) cases. The membrane-proximal amino acid substitution T618I (58.3%) was the most frequent mutation. CSF3R mutations were associated with higher WBC counts (P = .035). CEBPA mutation, TET2 mutation, and RUNX1-RUNX1T1 translocation were the most common co-mutations of CSF3R. The CSF3R gene was mutually exclusive with signal transduction genes (P = .029), while positively associated with TET2 mutations (P = .014). CSF3R mutations had no effect on CR1 (P = .935), R (P = .625) and OS (P = .1172). Patients with CSF3R mutations had a worse DFS (P = .0352) than those with wild-type CSF3R. Multivariate survival analysis showed that CSF3R mutation was an independent risk factor for DFS of primary AML patients (HR=2.048, 95%CI: 1.006-4.170, P = .048).

Conclusion: AML patients with CSF3R mutations had unique clinical features and gene co-mutation spectrum. CSF3R mutation was an independent risk factor for DFS and could be a potential prognostic marker and therapeutic target for Chinese primary AML patients.
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http://dx.doi.org/10.1111/ijlh.13762DOI Listing
November 2021

PAC1 Receptor Mediates Electroacupuncture-Induced Neuro and Immune Protection During Cisplatin Chemotherapy.

Front Immunol 2021 6;12:714244. Epub 2021 Sep 6.

Center for Perioperative Organ Protection, Department of Anesthesiology, Duke University, Durham, NC, United States.

Platinum-based chemotherapy is an effective treatment used in multiple tumor treatments, but produces severe side effects including neurotoxicity, anemia, and immunosuppression, which limits its anti-tumor efficacy and increases the risk of infections. Electroacupuncture (EA) is often used to ameliorate these side effects, but its mechanism is unknown. Here, we report that EA on ST36 and SP6 prevents cisplatin-induced neurotoxicity and immunosuppression. EA induces neuroprotection, prevents pain-related neurotoxicity, preserves bone marrow (BM) hematopoiesis, and peripheral levels of leukocytes. EA activates sympathetic BM terminals to release pituitary adenylate cyclase activating polypeptide (PACAP). PACAP-receptor PAC1-antagonists abrogate the effects of EA, whereas PAC1-agonists mimic EA, prevent neurotoxicity, immunosuppression, and preserve BM hematopoiesis during cisplatin chemotherapy. Our results indicate that PAC1-agonists may provide therapeutic advantages during chemotherapy to treat patients with advanced neurotoxicity or neuropathies limiting EA efficacy.
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http://dx.doi.org/10.3389/fimmu.2021.714244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450570PMC
September 2021

Role of Neuroimmune Crosstalk in Mediating the Anti-inflammatory and Analgesic Effects of Acupuncture on Inflammatory Pain.

Front Neurosci 2021 2;15:695670. Epub 2021 Aug 2.

Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Inflammatory pain is caused by peripheral tissue injury and inflammation. Inflammation leads to peripheral sensitization, which may further cause central sensitization, resulting in chronic pain and progressive functional disability. Neuroimmune crosstalk plays an essential role in the development and maintenance of inflammatory pain. Studies in recent years have shown that acupuncture can exert anti-inflammatory and analgesic effects by regulating peripheral (i.e., involving local acupoints and inflamed regions) and central neuroimmune interactions. At the local acupoints, acupuncture can activate the TRPV1 and TRPV2 channels of mast cells, thereby promoting degranulation and the release of histamine, adenosine, and other immune mediators, which interact with receptors on nerve endings and initiate neuroimmune regulation. At sites of inflammation, acupuncture enables the recruitment of immune cells, causing the release of opioid peptides, while also exerting direct analgesic effects via nerve endings. Furthermore, acupuncture promotes the balance of immune cells and regulates the release of inflammatory factors, thereby reducing the stimulation of nociceptive receptors in peripheral organs. Acupuncture also alleviates peripheral neurogenic inflammation by inhibiting the release of substance P (SP) and calcitonin gene-related peptide from the dorsal root ganglia. At the central nervous system level, acupuncture inhibits the crosstalk between glial cells and neurons by inhibiting the p38 MAPK, ERK, and JNK signaling pathways and regulating the release of inflammatory mediators. It also reduces the excitability of the pain pathway by reducing the release of excitatory neurotransmitters and promoting the release of inhibitory neurotransmitters from neurons and glial cells. In conclusion, the regulation of neuroimmune crosstalk at the peripheral and central levels mediates the anti-inflammatory and analgesic effects of acupuncture on inflammatory pain in an integrated manner. These findings provide novel insights enabling the clinical application of acupuncture in the treatment of inflammatory diseases.
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http://dx.doi.org/10.3389/fnins.2021.695670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366064PMC
August 2021

GATA2 rs2335052 and GATA2 rs78245253 single-nucleotide polymorphisms in Chinese patients with acute myelocytic leukemia.

Int J Lab Hematol 2021 Dec 9;43(6):1491-1500. Epub 2021 Aug 9.

Institute of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan, China.

Introduction: GATA binding protein 2 (GATA2) gene, involved in progression of hematologic malignancies and various solid tumors, is a susceptibility gene for inherited acute myeloid leukemia (AML). However, the influence of its single-nucleotide polymorphisms (SNPs) on AML remains unknown.

Methods: We used allele-specific PCR to genotype GATA2 rs2335052 and rs78245253 in 159 newly diagnosed AML (non-M3) patients and 300 healthy volunteers, and all of participants came from China. And 34 common hematological tumor gene mutations in 159 AML patients were detected by next-generation sequencing. Kaplan-Meier survival analysis and Cox proportional hazard regression were used to analyze the association between the two SNPs and the prognosis of AML.

Results: We found GATA2 rs2335052 C/T genotype, rs2335052 T/T genotype and rs78245253 G/C genotype in 51.6%, 13.8% and 11.3% AML patients. Our results demonstrated that GATA2 rs2335052 and rs78245253 were associated with certain laboratory features in AML patients, which had no effect on the pathogeny, chemotherapy response and recurrence of patients. Nevertheless, Kaplan-Meier survival analysis showed that, compared with rs78245253 G/G genotype, rs78245253 G/C genotype was significantly related to a decrease in overall survival (OS) (P = .020). Additionally, multivariate cox regression analysis showed that GATA2 rs78245253 was an independent risk factor for OS of AML patients in China.

Conclusion: GATA2 rs78245253 was an independent predictor for prognosis of AML patients in China and may be used as a potential indicator to predict the survival of AML patients in China. Further studies are needed to validate these findings and clarify the underlying mechanism.
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http://dx.doi.org/10.1111/ijlh.13649DOI Listing
December 2021

Multiple isotopic tracing for sulfate and base cation sources of precipitation in Hangzhou city, Southeast China: Insights for rainwater acidification mechanism.

Environ Pollut 2021 Nov 9;288:117770. Epub 2021 Jul 9.

State Key Laboratory of Geological Processes and Mineral Resources, China University of Geosciences, Wuhan, 430074, China.

Acid deposition has been regarded as a serious factor in the deteriorative water environment and ecosystems. Despite the powerful acid emission control measures have been implemented by the Chinese government, many areas (especially Southeast China) are still suffering from acid deposition. The chemical and isotopic (δS and Sr/Sr) compositions of rainwater in Hangzhou, a typical megacity in Southeast China with serious acid rain problem, for one year were studied with the aim to better constrain potential sources and explore the causes of rainwater acidification. Most rainwater samples were acidic, with a VWM pH value of 4.65. SO was the dominant anion and the main acid ion in rainwater. Sulfur isotope and the quantity equilibrium model revealed that sea salt, crustal, biogenic, and anthropogenic sulfur represented 2.3%, 0.1%, 16.7%, and 80.8% of the SO source in rainwater, respectively. The back trajectory and strontium isotopes indicated that the base cations (BCs) in rainwater originated mainly from anthropogenic sources. The relatively low neutralizing capacity caused by limited BCs input and emission control measures undermines some efforts to reduce rainwater acidity. This case study demonstrated that a valuable tool to probe the source of acid rain and unravel the mechanism of rainwater acidification can be provided by multiple lines of evidence, including rainwater chemical compositions, stable sulfur isotopes, and stable strontium isotopes.
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http://dx.doi.org/10.1016/j.envpol.2021.117770DOI Listing
November 2021

The role of macrophage polarization and associated mechanisms in regulating the anti-inflammatory action of acupuncture: a literature review and perspectives.

Chin Med 2021 Jul 19;16(1):56. Epub 2021 Jul 19.

Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, No.10 Poyang Lake Road, Tuanbo New Town, Jinghai District, Tianjin, 301617, People's Republic of China.

Acupuncture is used in the treatment of a variety of inflammatory conditions and diseases. However, the mechanisms of its anti-inflammatory action are complex and have not been systematically investigated. Macrophages are key components of the innate immune system, thus, balancing the M1/M2 macrophage ratio and modulating cytokine levels in the inflammatory environment may be desirable therapeutic goals. Evidence has shown that acupuncture has anti-inflammatory actions that affect multiple body systems, including the immune, locomotory, endocrine, nervous, digestive, and respiratory systems, by downregulating pro-inflammatory M1 and upregulating anti-inflammatory M2 macrophages, as well as by modulating associated cytokine secretion. Macrophage polarization is controlled by the interlocking pathways of extrinsic factors, the local tissue microenvironment, and the neural-endocrine-immune systems. It has been suggested that polarization of T lymphocytes and cytokine secretions resulting in modulation of the autonomic nervous system and the hypothalamic-pituitary-adrenal axis, may be upstream mechanisms of acupuncture-induced macrophage polarization. We further propose that macrophage polarization could be the principal pathway involved in acupuncture immune regulation and provide the scientific basis for the clinical application of acupuncture in inflammatory conditions.
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http://dx.doi.org/10.1186/s13020-021-00466-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287695PMC
July 2021

Control of phytoplankton by oysters and the consequent impact on nitrogen cycling in a Subtropical Bay.

Sci Total Environ 2021 Nov 13;796:149007. Epub 2021 Jul 13.

Key Laboratory of Aquatic Botany and Watershed Ecology, Wuhan Botanical Garden, Chinese Academy of Sciences, Wuhan 430074, China; Center of Plant Ecology, Core Botanical Gardens, Chinese Academy of Sciences, Wuhan 430074, China. Electronic address:

Although there has been growing interest in using oysters to remediate estuarine eutrophication since the 1980s, the role of oysters in remediation remains controversial. In this study, we took advantage of the intensive oyster farming in a nutrient-enriched estuary to evaluate the control of phytoplankton blooms by oysters. Observing the phytoplankton density variations in March and October, we found that despite doubled nutrient levels in March, oysters kept the phytoplankton density low. This is the first estuary-scale evidence that oysters can effectively suppress phytoplankton blooms. Measuring the isotopic signals in seawater revealed the significant impact of pelagic nitrogen cycling in the estuary. In March, oysters facilitated NO removal in the water column by enhancing the coupled phytoplankton assimilation-oyster filtration and denitrification in the sediments. While in October, the oysters-related nitrification could outcompete the removal processes, adding a significant amount of NO to the water column. Our study illustrates the influence of massive oysters on pelagic nitrogen cycling in an "oyster-remediated" estuary, providing implications for restoring oyster reefs to mitigate the symptoms of estuarine eutrophication.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149007DOI Listing
November 2021

Acupuncture for Parkinson's Disease: Efficacy Evaluation and Mechanisms in the Dopaminergic Neural Circuit.

Neural Plast 2021 15;2021:9926445. Epub 2021 Jun 15.

Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.

Parkinson's disease (PD) is a chronic and progressive neurodegenerative disease caused by degeneration of dopaminergic neurons in the substantia nigra. Existing pharmaceutical treatments offer alleviation of symptoms but cannot delay disease progression and are often associated with significant side effects. Clinical studies have demonstrated that acupuncture may be beneficial for PD treatment, particularly in terms of ameliorating PD symptoms when combined with anti-PD medication, reducing the required dose of medication and associated side effects. During early stages of PD, acupuncture may even be used to replace medication. It has also been found that acupuncture can protect dopaminergic neurons from degeneration via antioxidative stress, anti-inflammatory, and antiapoptotic pathways as well as modulating the neurotransmitter balance in the basal ganglia circuit. Here, we review current studies and reflect on the potential of acupuncture as a novel and effective treatment strategy for PD. We found that particularly during the early stages, acupuncture may reduce neurodegeneration of dopaminergic neurons and regulate the balance of the dopaminergic circuit, thus delaying the progression of the disease. The benefits of acupuncture will need to be further verified through basic and clinical studies.
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http://dx.doi.org/10.1155/2021/9926445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221898PMC
June 2021

The clinical characteristics and prognosis of cytogenetically normal AML with single mutations of CEBPA.

Int J Lab Hematol 2021 Dec 3;43(6):1424-1431. Epub 2021 Jul 3.

Institute of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, China.

Introduction: CEBPA mutation is a common mutation in normal karyotype AML. CEBPAdm AML has been recognized as a separate entity, but there is still controversy to the prognosis of CEBPAsm patients.

Methods: A total of 151 newly diagnosed cytogenetically normal AML patients treated at the Second Hospital Center of Shanxi Medical University from February 2017 to December 2019 were the subjects of the study. According to the number of mutations in the CEBPA gene, the patients were divided into three groups, CEBPAsm, CEBPAdm, and CEBPAwt patients. The clinical characteristics, gene mutations, response, and prognosis were retrospectively compared among the three groups.

Results: CEBPAsm patients had lower hemoglobin values compared to CEBPAdm (P = .049). There was no statistical difference between the CEBPAsm cases and the CEBPAdm cases in the mutation types and the distribution of mutation regions (P > .050). Compared with CEBPAdm, cases with CEBPAsm were more likely associated with multiple other gene mutations (P = .023). Patients with CEBPAdm had a higher CR, ORR, and OS than those CEBPAwt (P < .050). CEBPAsm patients had a similar OS with CEBPAdm and CEBPAwt patients (P = .281). These CEBPAsm patients with VAF<30% had lower OS than the patients with VAF≥30%. FLT3-ITD mutations could reduce CEBPAsm patients' OS (P = .019).

Conclusion: Our data first highlighted the impact of CEBPAsm VAF on OS, and the results showed the lower the VAF was, the shorter the OS tended to. The VAF of CEBPAsm could provide specific significance in some extent for the prognosis of patients.
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http://dx.doi.org/10.1111/ijlh.13612DOI Listing
December 2021

Peripheral and Central Pathological Mechanisms of Chronic Low Back Pain: A Narrative Review.

J Pain Res 2021 27;14:1483-1494. Epub 2021 May 27.

Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China.

Chronic low back pain (CLBP), lasting >3 months, is the end result of multiple pathogenic factors. Unfortunately, little is known about CLBP pathogenesis, which limits its advancements in clinical therapy and disease management. This paper summarizes the known pathological axes of CLBP, involving both peripheral and central systems. In particular, this paper details injurious nerve stimulation, inflammation-induced peripheral pathway, and central sensitization. Lumbar components, such as intervertebral disc (IVD), facet joints, muscles, fascia, ligaments, and joint capsules, contain pain receptors called nociceptors. Degeneration of the aforementioned lumbar components activates inflammatory pathways, which can directly damage nerves, lower nociceptor threshold to fire action potentials (AP), and cause pain. Additionally, damaged lumbar IVDs and endplates can also lead to the pathologic invasion of nerve growth and innervation, followed by the compression of herniated IVDs on nerve roots, thereby causing traumatic neuropathic pain. The central mechanism of CLBP involves alteration of the sensory processing of the brain and malfunction of the descending pain modulatory system, which facilitates pain amplification in the center nervous system (CNS). Lastly, abnormalities in the brain biochemical metabolism, activation of glial cells, and subsequent inflammation also play important roles in CLBP development. Taken together, inflammation plays an important role in both peripheral and central sensitization of CLBP. Due to the heterogeneity of CLBP, its pathological mechanism remains complex and difficult to understand. Therefore, it is a worthy field for future research into the subcomponents of CLBP pathogenesis, in order to distinguish the specific form of the disease, identify its origins, and develop corresponding highly effective comprehensive therapy against CLBP.
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http://dx.doi.org/10.2147/JPR.S306280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166276PMC
May 2021

A lineage switch from NPM1-mutant acute myeloid leukemia to acute T-cell lymphoblastic leukemia with KMT2D and ARID2 mutant.

Int J Lab Hematol 2021 08 21;43(4):O230-O233. Epub 2021 Apr 21.

The Haematology Department, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.

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http://dx.doi.org/10.1111/ijlh.13534DOI Listing
August 2021

ST36 Acupuncture Alleviates the Inflammation of Adjuvant-Induced Arthritic Rats by Targeting Monocyte/Macrophage Modulation.

Evid Based Complement Alternat Med 2021 27;2021:9430501. Epub 2021 Feb 27.

Acupuncture Research Center, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.

Background: Rheumatoid arthritis (RA) is a chronic systemic chronic autoimmune disease characterized by the aggregation of immune cells and secretion of cytokines in the joint synovium, causing hyperblastosis and even bone destruction. Acupuncture has been proven effective in RA treatment. This study aimed to investigate the anti-inflammatory action of acupuncture, specifically, in relation to immune cell interactions and key mediators.

Methods: Rats with adjuvant-induced arthritics (AIA) were treated with manual acupuncture (MA) at (ST36). Joint edema and paw withdrawal latency were monitored to observe the effects on inflammation. The levels of 24 cytokines, chemokines, and growth factors in ankle joints during the treatment (on days 1, 7, 15, and 21) were detected by multiplex immunoassay. A bioinformatics analysis based on a directed weighted mathematical model was used to construct cell communication network diagrams and identify the key cells through calculation. The monocyte/macrophage polarization in inflamed joints was investigated by detecting M1- and M2-phenotypic populations and their related cytokines.

Results: ST36 MA alleviated paw edema and upregulated the nociceptive threshold of AIA rats. Several innate and adaptive immune cytokines were dynamically regulated by MA, and MA-treated rats showed a significant improvement in symptoms compared with AIA rats by day 21. The immune cell-cell communication networks were intensified with the development of RA but were significantly reduced after treatment with MA. MA was found to specifically regulate monocytes/macrophages in inflamed ankle joints ST36 MA also inhibited M1-phenotype macrophages accompanied by decreased levels of IL-1.

Conclusions: ST36 MA showed anti-inflammatory and analgesic effects as well as inhibition of immune cell communication networks in inflamed joints of AIA rats. Inhibiting the polarization of macrophages to the M1-phenotype in inflamed joints may be one of the key mechanisms of MA anti-inflammatory action. This research highlighted a systematic research paradigm for investigating mechanisms of acupuncture action.
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http://dx.doi.org/10.1155/2021/9430501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936911PMC
February 2021

A study on the characteristics of cognitive function in patients with multiple system atrophy in China.

Sci Rep 2021 03 2;11(1):4995. Epub 2021 Mar 2.

Department of Neurology, Dongfang Hospital, Beijing University of Chinese Medicine, Fengtai District, Beijing, 100078, China.

Nonmotor symptoms in patients with multiple system atrophy (MSA) have received an increasing amount of attention in recent years, but no research on MSA patients' cognitive characteristics has been conducted in China. To evaluate the cognitive function of MSA patients in China. Using a case-control study design, 256 MSA patients and 64 controls were evaluated by the Montreal cognitive assessment (MoCA) scale to characterize their cognitive function. Like the controls, 60.5% of the patients with MSA had cognitive impairment, but the characteristics of cognitive impairment between the two groups were different. The cognitive impairment in MSA patients was prominent in the cognitive domains of visuospatial/executive functions, naming, attention, and orientation; particularly, the visuospatial/executive functions were the most significantly impaired, while impairment in language function was mainly seen in the controls. Besides, impairments in visuospatial/executive functions, attention, language, and orientation were more prominent in MSA-P (MSA with predominant Parkinsonism) patients than in MSA-C (MSA with predominant cerebellar ataxia). The cognitive impairments were more severe in patients with probable MSA than in patients with possible MSA. In addition, the results showed that the level of cognitive function was negatively correlated with the severity of MSA. This study, which characterized the cognitive function of MSA patients with the largest sample size known so far in China, found that patients with MSA do have cognitive impairment and display specific characteristics. Therefore, the cognitive impairment of MSA should be paid more attention.The study has been registered in the Chinese Clinical Trial Registry (ChiCTR) (Registration No: ChiCTR1900022462).
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http://dx.doi.org/10.1038/s41598-021-84393-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925668PMC
March 2021

The Role of Neuroglial Crosstalk and Synaptic Plasticity-Mediated Central Sensitization in Acupuncture Analgesia.

Neural Plast 2021 18;2021:8881557. Epub 2021 Jan 18.

Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.

Although pain is regarded as a global public health priority, analgesic therapy remains a significant challenge. Pain is a hypersensitivity state caused by peripheral and central sensitization, with the latter considered the culprit for chronic pain. This study summarizes the pathogenesis of central sensitization from the perspective of neuroglial crosstalk and synaptic plasticity and underlines the related analgesic mechanisms of acupuncture. Central sensitization is modulated by the neurotransmitters and neuropeptides involved in the ascending excitatory pathway and the descending pain modulatory system. Acupuncture analgesia is associated with downregulating glutamate in the ascending excitatory pathway and upregulating opioids, 𝛾-aminobutyric acid, norepinephrine, and 5-hydroxytryptamine in the descending pain modulatory system. Furthermore, it is increasingly appreciated that neurotransmitters, cytokines, and chemokines are implicated in neuroglial crosstalk and associated plasticity, thus contributing to central sensitization. Acupuncture produces its analgesic action by inhibiting cytokines, such as interleukin-1, interleukin-6, and tumor necrosis factor-, and upregulating interleukin-10, as well as modulating chemokines and their receptors such as CX3CL1/CX3CR1, CXCL12/CXCR4, CCL2/CCR2, and CXCL1/CXCR2. These factors are regulated by acupuncture through the activation of multiple signaling pathways, including mitogen-activated protein kinase signaling (e.g., the p38, extracellular signal-regulated kinases, and c-Jun-N-terminal kinase pathways), which contribute to the activation of nociceptive neurons. However, the responses of chemokines to acupuncture vary among the types of pain models, acupuncture methods, and stimulation parameters. Thus, the exact mechanisms require future clarification. Taken together, inhibition of central sensitization modulated by neuroglial plasticity is central in acupuncture analgesia, providing a novel insight for the clinical application of acupuncture analgesia.
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http://dx.doi.org/10.1155/2021/8881557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834789PMC
October 2021

P2RX7 in Dopaminergic Neurons of Ventral Periaqueductal Gray Mediates HTWP Acupuncture-Induced Consciousness in Traumatic Brain Injury.

Front Cell Neurosci 2020 13;14:598198. Epub 2021 Jan 13.

Acupuncture Research Center, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

The induction of a coma by traumatic brain injury (TBI) is a crucial factor for poor clinical prognoses. We report that acupuncture at the hand 12 -Well points (HTWP) improved consciousness and neurologic function in TBI rats. Gene chip analyses showed that HTWP acupuncture mostly activated genes modulating neuronal projections (, and ), protein secretion (, and ), and dopamine (DA) receptor D3 () in the ventral periaqueductal gray (vPAG), among which the expression rate of was the most obviously increased. Acupuncture also increased the expression and excitability of DA and P2RX7 neurons, and the DA neurons expressed P2RX7, P2RX3, and TRPV1 in the vPAG. Intracerebroventricular administration of P2RX7, P2RX3, or TRPV1 antagonists blocked acupuncture-induced consciousness, and the subsequent injection of a P2RX7 antagonist into the vPAG nucleus also inhibited this effect. Our findings provide evidence that acupuncture alleviates TBI-induced comas via DA neurons expressing P2RX7 in the vPAG, so as to reveal the cellular and molecular mechanisms of the improvement of TBI clinical outcomes by HTWP acupuncture.
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http://dx.doi.org/10.3389/fncel.2020.598198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838360PMC
January 2021

The Combinatorial Effect of Cisplatin and Moxibustion on Tumor Growth Inhibition with Special Reference to Modulation of the Immune Microenvironment in Lewis Lung Cancer Mice.

Evid Based Complement Alternat Med 2020 29;2020:3170803. Epub 2020 Dec 29.

Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.

Objective: As a first-line treatment for non-small cell lung cancer (NSCLC), the efficacy of chemotherapy is still unsatisfactory. Moxibustion has been shown to improve the side effects of radiotherapy and chemotherapy and regulate immune function. This study aimed to explore the antitumor effects and potential mechanisms of combinatorial cisplatin and moxibustion treatment for NSCLC by targeting the tumor microenvironment.

Methods: Lewis lung cancer (LLC)-bearing mice were induced and treated with cisplatin or/and moxibustion at ST36 (Zusanli), and the growth, weight, and area of the tumor were evaluated. The numbers of various T cell subsets and myeloid cells in the tumor were assessed by flow cytometry, and the gene expression of related markers and cytokines was detected with real-time quantitative polymerase chain reaction (RT-qPCR). In addition, the tumor vascular structure was investigated using CD31 and -smooth muscle actin (-SMA) immunofluorescence staining. The expression of the vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1 (HIF-1) was detected by immunohistochemical staining.

Results: Both cisplatin and moxibustion inhibited LLC tumor growth and reduced both the tumor area and weight, with the combinatorial therapy showing superior outcomes. Moxibustion upregulated the infiltration of CD4 T cells and Th1 cells in the tumor, and the combinatorial therapy increased the proportion of CD8 cytotoxic T cells (CTLs), CD4T cells, Th1, Th9 cells, and M1 macrophages, as well as the expression of , , and mRNA. The combinatorial therapy improved vascular normalization by increasing both the microvessel density (MVD) and pericyte coverage (-SMA area density) and inhibiting the expression of the VEGF.

Conclusions: Combinatorial cisplatin and moxibustion treatment inhibited the LLC tumor growth by mechanisms related to the improvement of the tumor immune microenvironment and vascular normalization, providing an effective combinatorial therapy beneficial for patients with NSCLC.
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http://dx.doi.org/10.1155/2020/3170803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785363PMC
December 2020

Geochemical Behaviors of Rare Earth Elements (REEs) in Karst Soils under Different Land-Use Types: A Case in Yinjiang Karst Catchment, Southwest China.

Int J Environ Res Public Health 2021 01 9;18(2). Epub 2021 Jan 9.

Key Laboratory of Cenozoic Geology and Environment, Institute of Geology and Geophysics, Chinese Academy of Sciences, Beijing 100029, China.

The geochemical characteristics of rare earth elements (REEs) can be employed to identify the anthropogenic and natural influence on the distributions of REEs in soils. A total of 47 soil samples from the three soil profiles of the secondary forest land, abandoned cropland, and shrubland in the Yinjiang county of Guizhou province, southwest China, were collected to determine the contents and distribution of REEs in the soil environment. The total REEs (ΣREE) contents in different soil profiles are in the following sequence: secondary forest land (mean: 204.59 mg·kg) > abandoned cropland (mean: 186.67 mg·kg) > shrubland (mean: 139.50 mg·kg). The ratios of (La/Gd) and (Gd/Yb) ranged from 0.62 to 1.00 and 1.18 to 2.16, which indicated that the enrichment of the medium rare earth elements (MREEs) was more obvious than that of the light rare earth elements (LREEs) and the heavy rare earth elements (HREEs). The phenomenon could be attributed to the preferential absorption of MREEs by fine particles and the substitution of Ca by MREEs. Most soil samples were characterized by the negative Ce anomalies (anomalies values: 0.30-1.10) and positive Eu anomalies (anomalies values: 0.43-2.90). The contents of REEs in the profiles of secondary forest land and shrubland were mainly regulated by soil pH and Fe contents while clay content and agricultural activities were the main controlling factors in the soil profile of abandoned cropland. This study highlights the role of agricultural activities in affecting the distributions of REEs in karst soils, which could provide some insights for the protection of the soil environment.
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http://dx.doi.org/10.3390/ijerph18020502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826674PMC
January 2021

Multiple isotopic compositions reveal complex nitrogen cycling in a subtropical estuary.

Environ Pollut 2021 Mar 30;272:116410. Epub 2020 Dec 30.

Shenzhen Key Laboratory of Marine Microbiome Engineering, Institute for Advanced Study, Shenzhen University, Shenzhen, 518060, China. Electronic address:

Nitrogen (N) pollution and the resulting eutrophication can have deleterious consequences on estuaries, such as hypoxia, fish kills, and loss of biotic diversity. An understanding of N sources and cycling in estuaries is fundamental to determining how to effectively manage these ecologically and commercially important areas. We applied a multiple-isotopic approach to examine the transformations and sources of the N pools in the Pearl River Estuary (PRE) during winter. The surface water in the West PRE was characterized by low salinity and high NO, while that in the east had high salinity and low NO. The NO in the West PRE was largely regulated by a conservative mixing process. In contrast, assimilation and nitrification dominated in the East PRE, which was attributed to the long water-residence time. For the first time, the source contributions of NO and NH were estimated by isotope mixing models. Our results suggest that river discharge and nitrification contributed 81% and 12% to the NO pool, respectively. A major portion (68%) of the NH was from river discharge, with the remainder likely from sewage and the aquitard-aquifer system. Our study demonstrates that internal nitrification can potentially be of pivotal importance in determining the NO level in an estuary and its export to coastal waters.
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http://dx.doi.org/10.1016/j.envpol.2020.116410DOI Listing
March 2021

Climatic and anthropogenic driving forces of the nitrogen cycling in a subtropical river basin.

Environ Res 2021 03 7;194:110721. Epub 2021 Jan 7.

Key Laboratory of Cenozoic Geology and Environment, Institute of Geology and Geophysics, Chinese Academy of Sciences, Beijing, 100029, China; CAS Center for Excellence in Life and Paleoenvironment, Beijing, 100044, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

To date, basin-scale understanding of nitrogen (N) cycling is lacking, which undermines riverine N pollution control efforts. Applying a multiple-isotopic approach, this study provided insights into the impacts of climate and anthropogenic activities on the N cycling at a basin scale. The isotopic compositions of the river water were regulated by a simple mixing process in winter, while unconservative processes (nitrification and denitrification) occurred in warm seasons. Denitrification dominated the N transformations in summer, while coupled nitrification-denitrification in soils after fertilization was responsible for the isotopic fractionations in spring and autumn. While at least 58.7% of the nitrate (NO) was removed from the basin, the NO loadings in the river remained high, suggesting that the ecosystem services could not balance the anthropogenic pollution. After correcting the isotopic fractionations, the sources of the riverine NO were quantified by a Markov chain Monte Carlo isotope mixing model. The contributions of point sources versus non-point sources changed dynamically with the precipitation and fertilization patterns. In summer and autumn, the soil organic N and chemical fertilizer dominated the riverine NO, with total contributions of 75.9% and 74.6%, respectively. The contributions from sewage and manure significantly increased during spring (47.9%) and winter (50.2%). Overall, the annual NO fluxes were from SON (28.7%), CF (28.1%), DS (18.2%), MA (23.9%), and AP (1.1%). In addition, we presented the large uncertainties in source apportionment that arose from the ignorance of isotope fractionations, highlighting the importance of considering the effect of isotopic fractionations in N source apportionment studies.
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http://dx.doi.org/10.1016/j.envres.2021.110721DOI Listing
March 2021

Simultaneous Detection of Ascorbic Acid, Dopamine, and Uric Acid Using a Novel Electrochemical Sensor Based on Palladium Nanoparticles/Reduced Graphene Oxide Nanocomposite.

Int J Anal Chem 2020 16;2020:8812443. Epub 2020 Dec 16.

Research Center of Experimental Acupuncture Science, College of Acumox and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.

A fresh strategy based on two-step electrochemical reduction for the fabrication of palladium nanoparticles/reduced oxide nanocomposite-modified glass carbon electrode (PdNPs/rGO/GCE) was established in this study. Field emission scanning electron microscopy (FESEM) images showed that spherical PdNPs were evenly distributed on the surface of rGO-modified electrode (rGO/GCE), and the introduction of PdNPs has no effect on the morphology of rGO. Electrochemical impedance spectroscopy (EIS) studies revealed that the conductivity of PdNPs/rGO/GCE was higher than that of rGO/GCE and bare GCE. The electrochemical performances of PdNPs/rGO/GCE sensor were investigated by cyclic voltammetry (CV), differential pulse voltammetry (DPV), and chronoamperometry using ascorbic acid (AA), dopamine (DA), and uric acid (UA) as analytes. At the optimized conditions, wide linear ranges of 0.5-3.5 mM (  = 0.99), 3-15 M (  = 0.99) and 15-42 M (  = 0.99), and 0.3-1.4 mM (  = 0.99) towards AA, DA, and UA in ternary mixture were observed, respectively. In addition to superior anti-interference capability, fast response (≤5 s), excellent reproducibility, and good long-term stability were also given by this sensor. These results suggested that PdNPs/rGO/GCE is promising for the simultaneous detection of AA, DA, and UA in practical application.
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http://dx.doi.org/10.1155/2020/8812443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759412PMC
December 2020

Thujasutchins N and O, two new compounds from the stems and roots of .

Nat Prod Res 2020 Oct 23:1-7. Epub 2020 Oct 23.

Key Laboratory of Plant Resources Conservation and Sustainable Utilization, Guangdong Provincial Key Laboratory of Applied Botany, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou, People's Republic of China.

Two novel secondary metabolites, including one thujopsene-type sesquiterpene designated thujasutchin N () and one norlignan named thujasutchin O () were obtained from the ethanolic extract of the stems and roots of . Among them, thujasutchin O () represents the first example of lignan sharing a unique carbon-reduced skeleton with novel acetal functionality. Their structures were unambiguously determined by means of extensively spectroscopic analysis including UV, IR, HRESIMS, NMR, and single crystal X-ray diffraction. Both of the isolates were evaluated for their cytotoxic and antibacterial activities.
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http://dx.doi.org/10.1080/14786419.2020.1836627DOI Listing
October 2020

Effects and Mechanisms of Acupuncture Combined with Mesenchymal Stem Cell Transplantation on Neural Recovery after Spinal Cord Injury: Progress and Prospects.

Neural Plast 2020 25;2020:8890655. Epub 2020 Sep 25.

Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.

Spinal cord injury (SCI) is a structural event with devastating consequences worldwide. Due to the limited intrinsic regenerative capacity of the spinal cord in adults, the neural restoration after SCI is difficult. Acupuncture is effective for SCI-induced neurologic deficits, and the potential mechanisms responsible for its effects involve neural protection by the inhibition of inflammation, oxidation, and apoptosis. Moreover, acupuncture promotes neural regeneration and axon sprouting by activating multiple cellular signal transduction pathways, such as the Wnt, Notch, and Rho/Rho kinase (ROCK) pathways. Several studies have demonstrated that the efficacy of combining acupuncture with mesenchymal stem cells (MSCs) transplantation is superior to either procedure alone. The advantage of the combined treatment is dependent on the ability of acupuncture to enhance the survival of MSCs, promote their differentiation into neurons, and facilitate targeted migration of MSCs to the spinal cord. Additionally, the differentiation of MSCs into neurons overcomes the problem of the shortage of endogenous neural stem cells (NSCs) in the acupuncture-treated SCI patients. Therefore, the combination of acupuncture and MSCs transplantation could become a novel and effective strategy for the treatment of SCI. Such a possibility needs to be verified by basic and clinical research.
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http://dx.doi.org/10.1155/2020/8890655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533022PMC
September 2021

Isotopic Composition Reveals the Impact of Oyster Aquaculture on Pelagic Nitrogen Cycling in a Subtropical Estuary.

Water Res 2020 Dec 25;187:116431. Epub 2020 Sep 25.

Shenzhen Key Laboratory of Marine Microbiome Engineering, Institute for Advanced Study, Shenzhen University, Shenzhen, 518060, China. Electronic address:

To offset estuarine eutrophication, interest is increasing in restoring oyster reefs and expanding oyster aquaculture. However, ecosystem-scale evidence is lacking on oyster assemblages' impacts on estuarine pelagic nitrogen (N) cycling. Using a multiple-isotope approach and isotope-mixing model, we examined the sources, transformations, and influence of intensive oyster aquaculture on N pollution in a subtropical estuary. The salinity-dependent NO and NH concentrations and their correlations with isotopic signals (δN-NO, δO-NO, δN-NH) indicated the nutrient spatial distribution in low-salinity areas was largely regulated by mixing between freshwater and seawater. However, the intensive oyster aquaculture greatly increased nitrification in the estuary. In high-salinity areas where oyster assemblages were absent, the assimilation of NO by phytoplankton became dominant and sharply increased the δN-NO and δO-NO. Soil organic nitrogen and fertilizer, domestic sewage, and wastewater treatment plants were the major NO sources in the estuary, while internal nitrification contributed 20.6% to the NO pool. Oyster biodeposits comprised up to one-third of the particulate organic matter in the water column, and as much as 47.3% of the NH pool could be from the oysters. Our study shows that oysters significantly contribute to the pelagic nutrient pools and N transformations, adding an important dimension to our understanding of oyster assemblages' impacts on estuarine N cycling.
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http://dx.doi.org/10.1016/j.watres.2020.116431DOI Listing
December 2020

Berberine Exerts Anti-cancer Activity by Modulating Adenosine Monophosphate- Activated Protein Kinase (AMPK) and the Phosphatidylinositol 3-Kinase/ Protein Kinase B (PI3K/AKT) Signaling Pathways.

Curr Pharm Des 2021 ;27(4):565-574

Department of Massage and Physiotherapy, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing 100078, China.

Background: The antagonistic relationship between adenosine monophosphate-activated protein kinase (AMPK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling play a vital role in cancer development. The anti-cancer effects of berberine have been reported as a main component of the traditional Chinese medicine Rhizoma coptidis, although the roles of these signaling pathways in these effects have not been systematically reviewed.

Methods: We searched the PubMed database for studies with keywords including ["berberine"] and ["tumor" or "cancer"] and ["AMPK"] or ["AKT"] published between January 2010 and July 2020, to elucidate the roles of the AMPK and PI3K/AKT pathways and their upstream and downstream targets in the anti-cancer effects of berberine.

Results: The anti-cancer effects of berberine include inhibition of cancer cell proliferation, promotion of apoptosis and autophagy in cancer cells, and prevention of metastasis and angiogenesis. The mechanism of these effects involves multiple cell kinases and signaling pathways, including activation of AMPK and forkhead box transcription factor O3a (FOXO3a), accumulation of reactive oxygen species (ROS), and inhibition of the activity of PI3K/AKT, rapamycin (mTOR) and nuclear factor-κB (NF-κB). Most of these mechanisms converge on regulation of the balance of AMPK and PI3K/AKT signaling by berberine.

Conclusion: This evidence supports the possibility that berberine is a promising anti-cancer natural product, with pharmaceutical potential in inhibiting cancer growth, metastasis and angiogenesis via multiple pathways, particularly by regulating the balance of AMPK and PI3K/AKT signaling. However, systematic preclinical studies are still required to provide scientific evidence for further clinical studies.
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http://dx.doi.org/10.2174/1381612826666200928155728DOI Listing
April 2021

Identification of Two Novel Truncated Transcripts of Janus Kinase 2 Gene.

Ann Clin Lab Sci 2020 Jul;50(4):497-503

Institute of Hematology, the Second Hospital of Shanxi Medical University

Jak2 is a nonreceptor tyrosine kinase that plays a critical role in signal transduction through an abundance of receptors, such as erythropoietin receptor. In this paper, we report two previously unknown transcripts of Jak2 gene. One transcript deletes the 77nt of 3' end exon 10 of the Jak2 gene, resulting in a frameshift that introduces a stop codon in the downstream exon and produces a truncated protein of 421 amino acids if translated. The other transcript skips the entire exon 10, leading to a premature stop codon in the adjacent exon 11, producing a truncated protein of 414 amino acids if translated. Therefore, the physiological significance of the expression of two novel transcripts in healthy volunteers and patients with myeloproliferative neoplasms, acute leukemia, and chronic myeloid leukemia needs to be investigated further.
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July 2020

Applying Complex Network and Cell-Cell Communication Network Diagram Methods to Explore the Key Cytokines and Immune Cells in Local Acupoint Involved in Acupuncture Treating Inflammatory Pain.

Evid Based Complement Alternat Med 2020 29;2020:2585960. Epub 2020 Jul 29.

Tianjin Key Laboratory of Food Biotechnology, Faculty of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China.

Manual acupuncture (MA) can effectively treat a variety of diseases, but its specific mechanism remains unclear. The "acupoint network" activated by MA participates in MA signal transduction, in which immune-related cells and cytokines play an important role. However, which cells and cytokines in the acupoint have changed after MA? What is the network relationship between them? Which cells and cytokines may play the most important role in MA effect? These problems are unclear. In this study, on the basis of affirming the analgesic, detumescence, and anti-inflammatory effect of MA, the concentration of 24 cytokines in ST36 acupoint in rats with inflammatory pain after MA treatment was detected by multiplex immunoassay technology. Then, using statistical and complex network and cell-cell communication (CCC) network diagram method to analyze the detected data depicts the network relationship between the cytokines and related cells objectively and establishes cytokine connection network and CCC network, respectively. The results showed that MA reinforced communication intensity between cells while reducing the overall correlation intensity. On this basis, the key cytokines and key cells at three MA time-points were screened out, cytokines IL-6, MCP-1, fibroblasts cell, and monocyte macrophage screened by the three methods at three MA time-points might be the key cytokines or key cells. After that, we detected the macrophages in ST36 acupoint by flow cytometry and immunofluorescence and found that the relative amount of macrophages increased significantly after MA, especially the macrophage of the dermis of skin. This study provided a basis for revealing the initiated mechanism of MA effect.
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http://dx.doi.org/10.1155/2020/2585960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411476PMC
July 2020

The Prevalence of Smartphones and WeChat Use Among Older Adults With Chronic Disease in a Western China.

Comput Inform Nurs 2020 Jul 8;39(1):42-47. Epub 2020 Jul 8.

Author Affiliations: School of Nursing, Youjiang Medical University for Nationalities, Baise (Dr Zhang and Ms Wei); Nursing Department, Taizhou Polytechnical College, Taizhou (Ms Xu); and Nursing Department (Ms Huang) and Neurology Department (Dr Liu), The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.

Telemedicine is a promising way to deliver patient education and health services, but access to information technology among potential patients is a prerequisite. This study surveyed the prevalence of smartphone use and the use of the Chinese social networking platform WeChat and Wi-Fi access in the homes of older adults in a western area of China. A convenience sample of 225 older adults with chronic diseases in two tertiary hospitals was interviewed regarding smartphone ownership, WeChat use, and access to Wi-Fi at home. Participant ability in performing the activities of daily living was also assessed. Logistic regressions were used to analyze the independently associated factors of smartphone ownership, WeChat use, and Wi-Fi access at home. The results show that the prevalence of smartphone use was 19.6%, only 8.9% of those surveyed used WeChat, but 39.6% had access to Wi-Fi at home. Education level was the only factor significantly associated with the three dependent variables. Ability in performing activities of daily living was positively correlated with access to Wi-Fi at home (odds ratio, 2.549; P = .011). It will be difficult to implement telemedicine through smartphones in such relatively poor areas of China. Better-educated older adults who are less dependent in performing activities of daily living are potential users of telemedicine.
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http://dx.doi.org/10.1097/CIN.0000000000000638DOI Listing
July 2020

The neuro-immune microenvironment of acupoints-initiation of acupuncture effectiveness.

J Leukoc Biol 2020 07;108(1):189-198

Acu-moxibustion and Tuina Department, Tianjin University of Traditional Chinese Medicine, Tuanbo, Jinghai, Tianjin, China.

Acupuncture is a centuried and unfading treatment of traditional Chinese medicine, which has been proved to exert curative effects on various disorders. Numerous works have been put in to uncover the effective mechanisms of acupuncture. And the interdependent interaction between acupuncture and acupoint microenvironment is a crucial topic. As a benign minimally invasive stimulation, the insertion and manipulation of needle at acupoint could cause deformation of local connective tissue and secretion of various molecules, such as high mobility group box 1 and ATP. The molecules are secreted into extracellular space and bind to the corresponding receptors thus active NF-κB, MAPK, ERK pathways on mast cells, fibroblasts, keratinocytes, and monocytes/macrophages, among others. This is supposed to trigger following transcription and translation of immune factors and neural active substance, as well as promote the free ion movement (such as Ca influx) and the expansion of blood vessels to recruit more immune cells to acupoint. Finally, acupuncture could enhance network connectivity of local microenvironment at acupoints. The earlier mentioned substances further act on a variety of receptors in local nerve endings, transmitting electrical and biochemical signals to the CNS, and giving full play to the acupuncture action. In conclusion, we portrayed a neuro-immune microenvironment network of acupoints that medicates the acupuncture action, and would lay a foundation for the systematic study of the complex network relationship of acupoints in the future.
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http://dx.doi.org/10.1002/JLB.3AB0420-361RRDOI Listing
July 2020

Spatiotemporal variations of nitrate sources and dynamics in a typical agricultural riverine system under monsoon climate.

J Environ Sci (China) 2020 Jul 9;93:98-108. Epub 2020 Apr 9.

Key Laboratory of Cenozoic Geology and Environment, Institute of Geology and Geophysics, Chinese Academy of Sciences, Beijing 100029, China; CAS Center for Excellence in Life and Paleoenvironment, Beijing 100044, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Nitrogen pollution is a serious environmental issue in the Danjiangkou Reservoir region (DRR), the water source of the South-to-North Water Diversion Project of China. In this research, seasonal surveys and a bi-weekly time series survey were conducted in the Qihe River Basin, one of the most densely populated agricultural basins in the DRR. Hydrochemical compositions (NO and Cl), dual isotopes (δD-HO, δO-HO, δN-NO, and δO-NO), and a Markov Chain Monte Carlo isotope mixing model were jointly applied to unravel the sources, migrations, and transformations of the nitrate (NO) in the basin. It was revealed that the mixing between different sources was the main process controlling the isotopic compositions of the riverine NO in the upper-middle reaches. In contrast, denitrification occurred in the lower reaches. For the first time, the sources of NO were quantified at a basin scale in the DRR. Overall, the river transported 484.2 tons/year of NO-N to the reservoir, of which 32.6%, 36.4%, 28.0%, and 3.0% was from soil organic nitrogen, chemical fertilizer, residential sewage and atmospheric precipitation, respectively. The NO-N fluxes of the different sources were regulated by the monsoon climate and anthropogenic activities. For example, high precipitation and intense fertilization resulted in severe nonpoint source pollution. Denitrification thrived in soils and reservoirs in wet seasons. Temperature could regulate the migration, nitrification and denitrification processes. Based on the results, we suggest that the management strategies dealing with nitrogen pollution issue in the DRR should follow the specific spatiotemporal characteristics of NO sources, migration and transformation mechanisms.
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http://dx.doi.org/10.1016/j.jes.2020.03.007DOI Listing
July 2020

AMPK and its Activator Berberine in the Treatment of Neurodegenerative Diseases.

Curr Pharm Des 2020 ;26(39):5054-5066

Acupuncture Research Center, Tianjin University of Traditional Chinese Medicine, Tianjin, China

Neurodegenerative disorders are heterogeneous diseases associated with either acute or progressive neurodegeneration, causing the loss of neurons and axons in the central nervous system (CNS), showing high morbidity and mortality, and there are only a few effective therapies. Here, we summarized that the energy sensor adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), and its agonist berberine can combat the common underlying pathological events of neurodegeneration, including oxidative stress, neuroinflammation, mitochondrial disorder, glutamate excitotoxicity, apoptosis, autophagy disorder, and disruption of neurovascular units. The abovementioned effects of berberine may primarily depend on activating AMPK and its downstream targets, such as the mammalian target of rapamycin (mTOR), sirtuin1 (SIRT1), nuclear factor erythroid-2 related factor-2 (Nrf2), nuclear factor-κB (NF-κB), phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), nicotinamide adenine dinucleotide (NAD+), and p38 mitogen-activated protein kinase (p38 MAPK). It is hoped that this review will provide a strong basis for further scientific exploration and development of berberine's therapeutic potential against neurodegeneration.
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http://dx.doi.org/10.2174/1381612826666200523172334DOI Listing
April 2021
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