The functional role of P2 purinergic receptors in the progression of gastric cancer.

Studies have confirmed that P2 purinergic receptors (P2X receptors and P2Y receptors) expressed in gastric cancer (GC) cells and GC tissues and correlates with their function. Endogenous nucleotides including ATP, ADP, UTP, and UDP, as P2 purinergic receptors activators, participate in P2 purinergic signal transduction pathway. These activated P2 purinergic receptors regulate the progression of GC mainly by mediating ion channels and intracellular signal cascades. It is worth noting that there is a difference in the expression of P2 purinergic receptors in GC, which may play different roles in the progression of GC as a tumor promoting factor or a tumor suppressor factor. Among them, P2 × 7, P2Y2 and P2Y6 receptors have certain clinical significance in patients with GC and may be used as biological molecular markers for the prediction of patients with GC. Therefore, in this paper, we discuss the functional role of nucleotide / P2 purinergic receptors signal axis in regulating the progression of GC and that these P2 purinergic receptors may be used as potential molecular targets for the prevention and treatment of GC.

Mechanisms of inflammation modulation by different immune cells in hypertensive nephropathy.

Hypertensive nephropathy (HTN) is the second leading cause of end-stage renal disease (ESRD) and a chronic inflammatory disease. Persistent hypertension leads to lesions of intrarenal arterioles and arterioles, luminal stenosis, secondary ischemic renal parenchymal damage, and glomerulosclerosis, tubular atrophy, and interstitial fibrosis. Studying the pathogenesis of hypertensive nephropathy is a prerequisite for diagnosis and treatment. The main cause of HTN is poor long-term blood pressure control, but kidney damage is often accompanied by the occurrence of immune inflammation. Some studies have found that the activation of innate immunity, inflammation and acquired immunity is closely related to the pathogenesis of HTN, which can cause damage and dysfunction of target organs. There are more articles on the mechanism of diabetic nephropathy, while there are fewer studies related to immunity in hypertensive nephropathy. This article reviews the mechanisms by which several different immune cells and inflammatory cytokines regulate blood pressure and renal damage in HTN. It mainly focuses on immune cells, cytokines, and chemokines and inhibitors. However, further comprehensive and large-scale studies are needed to determine the role of these markers and provide effective protocols for clinical intervention and treatment.

Surgical approach for complete resection of giant retroperitoneal liposarcoma with diaphragmatic hernia via ninth rib thoracotomy.

Background: Resection of a giant retroperitoneal liposarcoma is difficult and technically demanding, especially for large retroperitoneal tumors accompanied by a diaphragmatic hernia. Technically, the open abdominal approach can be time-consuming and difficult to perform, with possible intraoperative complications and other factors bringing psychological and physical difficulties to the patient. This study reports a safe and feasible approach for the complete resection of a large retroperitoneal tumor complicated by a diaphragmatic hernia. Methods: A 58-year-old male patient with persistent upper abdominal pain and distension was treated at a local hospital on 4 July 2022. Computed tomography showed a mixed-density mass on the right retroperitoneum, and liposarcoma was considered. On 6 July 2022, the patient was transferred to our hospital for further treatment. Computed tomography showed a mass with low-density fatty shadow in the right adrenal region. The boundary with the right adrenal gland was unclear. The mass was 102 mm × 74 mm, and the right lobe of the liver was compressed. Insufficiency of the right middle lobe of the liver was seen due to a right diaphragmatic hernia and left mediastinal deviation. We considered the traditional approach for tumor resection via laparotomy, but we opted to perform a comprehensive evaluation first. The tumor was close to the back of the right kidney and liver, causing the diaphragm to rise because of its proximity to these organs. Exposing the tumor through laparotomy would be difficult, making it challenging to remove. The patient had a diaphragmatic hernia and moderate pulmonary dysfunction; therefore, we decided to enter the abdomen through a thoracotomy of the ninth rib. Results: Using our technique, the tumor was easily visualized and completely removed in approximately 30 min. The intraoperative blood loss was 100 ml, and no postoperative bleeding, pneumothorax, intestinal fistula, infection, or other complications occurred. Conclusion: The transthoracic approach may be a safer and more feasible resection method than the traditional open approach for patients with giant retroperitoneal liposarcoma with a diaphragmatic hernia.

Hydrophobic organic contaminants affiliated with polymer-specific microplastics in urban river tributaries and estuaries.

Exposure to microplastics (MPs) and hydrophobic organic contaminants (HOCs) combined at high concentrations may induce adverse effects to aquatic organisms in laboratory-scale studies. To determine environmentally relevant concentrations of HOCs in MPs, it is essential to understand the occurrence of MP-affiliated HOCs in the aquatic environment. Here we report the occurrences of HOCs affiliated with polymer-specific floating MPs from 12 tributaries and three estuaries in the Pearl River Delta, South China. Target HOCs include nine synthetic musks (SMs), 14 ultraviolet adsorbents (UVAs), 15 polycyclic aromatic hydrocarbons (PAHs), eight polybrominated diphenyl ethers (PBDEs), and 14 polychlorinated biphenyls (PCBs). Average concentrations of MP-affiliated ∑9SM, ∑14UVA, ∑15PAH, ∑8PBDE, and ∑14PCB were 1790, 5550, 1090, 412, and 107 ng g-1, respectively. The average concentrations of HOCs affiliated with MPs of different polymer types were 9790, 7220, 72,500, and 55,800 ng g-1 for polyethylene (PE), polypropylene, polystyrene, and other MPs, respectively. As the concentration of PE was the highest among all MPs at the average concentration of 0.77 mg m-3, the monthly outflow of PE-affiliated HOCs accounted for the largest proportion (46 %) in the outflow of MP-affiliated HOCs (2.8 g) to the coastal ocean via three estuaries. These results suggest that HOCs were highly concentrated in MPs and varied among different chemicals and polymer types. Due to the differences of polymer characteristics and half-life of affiliated chemicals, future toxicology studies concerning exposure to these combined pollutants may need to specify polymer types and their affiliated chemicals.

Fire acupuncture for anti-LGI1 antibody autoimmune encephalitis: a case report.

Autoimmune encephalitis, a class of encephalitis, is clinically characterized by multifocal or diffuse brain injury, including aberrant mental behavior, convulsions, and near-event memory impairment. In this article, we describe a female patient with autoimmune encephalitis who tested positive for leucine-rich glioma inactivated 1 (LGI1) antibodies and had hippocampal inflammatory edema in the lesion area. During the first 3 months of her illness, the patient primarily experienced memory loss, the onset of rigid twitching in her extremities that lasted for 1 min while in remission, and incontinence. After gamma globulin administration, methylprednisolone shock, and other symptomatic therapies during hospitalization, the patient's psychiatric symptoms and seizures improved considerably; however, she did not fully recover her memory. After receiving fire acupuncture for 6 months, the patient's understanding, orientation, and calculation skills improved considerably. Her memory and mental state were also improved at the follow-up visit. In this case, the use of fire acupuncture for the treatment of autoimmune encephalitis resulted in favorable outcomes with important benefits for conditions affecting the central nervous system; however, more convincing data are required to support the effectiveness of this treatment method.

Chitosan biomaterial enhances the effect of OECs on the inhibition of sciatic nerve injury-induced neuropathic pain.

Neuropathic pain is a common symptom experienced by most clinical diseases at different levels, and its treatment has always been a clinical difficulty. Therefore, it is particularly important to explore new and effective treatment methods. The role of olfactory ensheathing cells (OECs) in nerve injury and pain is recognized by different studies. Our previous study found that transplantation of OECs alleviated hyperalgesia in rats. However, single-cell transplantation lacks medium adhesion and support, and exerts limited analgesic effect. Therefore, on the basis of the previous study, this study investigated the effect of pain relief by co-transplanting OECs with chitosan (CS) (a biological tissue engineering material, as OECs were transplanted into the host medium) to the injured sciatic nerve. The results showed that the pain threshold of sciatic nerve injury of rats was significantly reduced, and the expression level of P2×4 receptor in the spinal cord was significantly increased. While olfactory ensheathing cells combined with chitosan (OECs+CS) transplantation could significantly relieve pain, and the analgesic effect was stronger than that of OECs transplantation alone. OECs+CS transplantation promoted the formation of sciatic nerve remyelination, improved the changes of demyelination, and promoted the repair of sciatic nerve injury more significantly. In addition, the effect of OECs+CS to down-regulate the expression of P2×4 receptor was significantly stronger than that of OECs transplantation, and exerted a better analgesic effect. These data reveal that OECs+CS have a better analgesic effect in relieving neuropathic pain induced by sciatic nerve injury, and provide a new therapeutic strategy for pain treatment.

Acupuncture with twirling reinforcing and reducing manipulation shows a control of hypertension and regulation of blood pressure-related target brain regions in spontaneously hypertensive rat: a preliminary resting-state functional MRI study.

Aim: To observe the effects of acupuncture manipulations on blood pressure and brain function in spontaneously hypertensive rats and elucidate the anti-hypertensive effect of the manipulations' central mechanism. Methods: This study used acupuncture twirling reinforcing, acupuncture twirling reducing, and acupuncture twirling uniform reinforcing-reducing manipulations to act on the bilateral TaiChong point of rats. The depth of acupuncture was 1.5-2 mm, and twisting was performed at a frequency of 60 times/min within ±360° for 3 min, followed by the needle being retained for 17 min. Functional magnetic resonance imaging was performed at the end of the intervention. Regional homogeneity and amplitude of low-frequency fluctuations were used to assess the differences in brain regions in each group of rats, and the core brain region (left hypothalamus) among the differential brain regions was selected as the seed for functional connectivity analysis. Results: (1) The anti-hypertensive effect was achieved by acupuncture manipulations, and the anti-hypertensive effect of twirling reducing manipulation on spontaneously hypertensive rats was better than that of twirling uniform reinforcing-reducing and twirling reinforcing manipulations. (2) After regional homogeneity and amplitude of low-frequency fluctuations analyses, the hypothalamus, the brain region related to blood pressure, was activated in the twirling uniform reinforcing-reducing manipulation group; the corpus callosum and cerebellum were activated in the twirling reinforcing manipulation group; and the hypothalamus, olfactory bulb, corpus callosum, brainstem, globus pallidum, and striatum were activated in the twirling reducing manipulation group. (3) According to the functional connectivity analysis, different acupuncture manipulations increased the functional connections between seed points and the brainstem, olfactory bulb, and cerebellum, etc. Conclusion: These results suggest that acupuncture manipulations achieved the hypotensive effect and the twirling reducing manipulation had a better hypotensive effect on spontaneously hypertensive rats than twirling uniform reinforcing-reducing and twirling reinforcing manipulations; the central mechanism of the anti-hypertensive effect of twirling reinforcing and reducing manipulation may be related to the activation of brain regions associated with blood pressure regulation and the functional connections between them. Furthermore, brain regions involved in motor control, cognition, and hearing were also activated. We hypothesize that activation of these brain regions may help prevent or mitigate the onset and progression of hypertensive brain damage.

Olfactory ensheathing cells and neuropathic pain.

Damage to the nervous system can lead to functional impairment, including sensory and motor functions. Importantly, neuropathic pain (NPP) can be induced after nerve injury, which seriously affects the quality of life of patients. Therefore, the repair of nerve damage and the treatment of pain are particularly important. However, the current treatment of NPP is very weak, which promotes researchers to find new methods and directions for treatment. Recently, cell transplantation technology has received great attention and has become a hot spot for the treatment of nerve injury and pain. Olfactory ensheathing cells (OECs) are a kind of glial cells with the characteristics of lifelong survival in the nervous system and continuous division and renewal. They also secrete a variety of neurotrophic factors, bridge the fibers at both ends of the injured nerve, change the local injury microenvironment, and promote axon regeneration and other biological functions. Different studies have revealed that the transplantation of OECs can repair damaged nerves and exert analgesic effect. Some progress has been made in the effect of OECs transplantation in inhibiting NPP. Therefore, in this paper, we provided a comprehensive overview of the biology of OECs, described the possible pathogenesis of NPP. Moreover, we discussed on the therapeutic effect of OECs transplantation on central nervous system injury and NPP, and prospected some possible problems of OECs transplantation as pain treatment. To provide some valuable information for the treatment of pain by OECs transplantation in the future.

Schwann cells as a target cell for the treatment of cancer pain.

Tumor erosion and metastasis can invade surrounding tissues, damage nerves, and sensitize the peripheral primary receptors, inducing pain, which can potentially worsen the suffering of patients with cancer. Reception and transmission of sensory signal receptors, abnormal activation of primary sensory neurons, and activation of glial cells are involved in cancer pain. Therefore, exploring promising therapeutic methods to suppress cancer pain is of great significance. Various studies have found that the use of functionally active cells is a potentially effective way to relieve pain. Schwann cells (SCs) act as small, biologically active pumps that secrete pain-relieving neuroactive substances. Moreover, SCs can regulate the progression of tumor cells, including proliferation and metastasis, through neuro-tumor crosstalk, which emphasizes the critical role of SCs in cancer and cancer pain. The mechanisms by which SCs repair injured nerves and exert analgesia include neuroprotection, neurotrophy, nerve regeneration, neuromodulation, immunomodulation, and enhancement of the nerve-injury microenvironment. These factors may ultimately restore the damaged or stimulated nerves and contribute to pain relief. Strategies for pain treatment using cell transplantation mainly focus on analgesia and nerve repair. Although these cells are in the initial stages of nerve repair and pain, they open new avenues for the treatment of cancer pain. Therefore, this paper discusses, for the first time, the possible mechanism of SCs and cancer pain, and new strategies and potential problems in cancer pain treatment.

Electroacupuncture and manual acupuncture at LR3 and ST36 have attenuating effects on hypertension and subsequent cognitive dysfunction in spontaneously hypertensive rats: A preliminary resting-state functional magnetic resonance imaging study.

Introduction: Chronic hypertension may have a contributory role toward cognitive impairment. Acupuncture exerts protective effects on cognitive functions while controlling the blood pressure. However, the neural mechanism underlying the dual attenuating effect of acupuncture remains unclear. In this study, we investigated the effects of electroacupuncture (EA) and manual acupuncture (MA) on the functional activity of the brain regions of spontaneously hypertensive rats (SHRs) by through resting-state functional magnetic resonance imaging (rs-fMRI). We also evaluated the differences in these functional activities between the EA and MA groups. Methods: We randomly assigned 30 SHRs into the EA, MA, and model (SHR) groups. Wistar Kyoto rats (n = 10) were used as normal control (WKY). The interventions were administered once every alternate day for 12 weeks. The systolic blood pressure of all rats was recorded every 2 weeks until the end of the intervention. After the intervention, rs-fMRI scanning was performed to access the whole brain data of rats randomly selected from each group evenly. The amplitude of low frequency fluctuation (ALFF) analysis, regional homogeneity (ReHo) analysis, and functional connectivity (FC) analysis were also conducted. The Morris water maze (MWM) test was conducted to evaluate the learning and memory of the rats. Hematoxylin-eosin staining and Nissl staining were performed to observe histopathological changes in the key brain regions. Results: We demonstrated that, when compared with the SHR group, the EA and MA groups had significantly lower blood pressure and better performance for behavioral test indices, and that the effect of EA was better than that of MA. ALFF and ReHo analyses revealed enhancement of the neuronal activity of some functionally impaired brain areas in the EA and MA groups. The main callback brain regions included the hypothalamus, entorhinal cortex, brain stem, prelimbic cortex, cingulate cortex, corpus callosum, and cerebellum. The FC analysis demonstrated that EA and MA enhanced the functional connectivity between the seeds and brain regions such as the brain stem, entorhinal cortex, hippocampus, prelimbic cortex, and cerebellum. The pathological test of the entorhinal cortex also verified the protective effect of acupuncture on the neuronal functional activity. Discussion: Our findings suggested that EA and MA exhibited attenuating effects on hypertension and cognitive dysfunction by enhancing the functional activities in the corresponding brain regions. Moreover, EA activated more callback brain regions and functional connectivity than MA, which may explain why the effect of EA was better than that of MA.

ATP ion channel P2X purinergic receptors in inflammation response.

Different studies have confirmed that P2X purinergic receptors play a key role in inflammation. Activation of P2X purinergic receptors can release inflammatory cytokines and participate in the progression of inflammatory diseases. In an inflammatory microenvironment, cells can release a large amount of ATP to activate P2X receptors, open non-selective cation channels, activate multiple intracellular signaling, release multiple inflammatory cytokines, amplify inflammatory response. While P2X4 and P2X7 receptors play an important role in the process of inflammation. P2X4 receptor can mediate the activation of microglia involved in neuroinflammation, and P2X7 receptor can mediate different inflammatory cells to mediate the progression of tissue-wide inflammation. At present, the role of P2X receptors in inflammatory response has been widely recognized and affirmed. Therefore, in this paper, we discussed the role of P2X receptors-mediated inflammation. Moreover, we also described the effects of some antagonists (such as A-438079, 5-BDBD, A-804598, A-839977, and A-740003) on inflammation relief by antagonizing the activities of P2X receptors.

P2X7 receptor in inflammation and pain.

Different studies have confirmed P2X7 receptor-mediated inflammatory mediators play a key role in the development of pain. P2X7 receptor activation can induce the development of pain by mediating the release of inflammatory mediators. In view of the fact that P2X7 receptor is expressed in the nervous system and immune system, it is closely related to the stability and maintenance of the nervous system function. ATP activates P2X7 receptor, opens non-selective cation channels, activates multiple intracellular signaling, releases multiple inflammatory cytokines, and induces pain. At present, the role of P2X7 receptor in inflammatory response and pain has been widely recognized and affirmed. Therefore, in this paper, we discussed the pathological mechanism of P2X7 receptor-mediated inflammation and pain, focused on the internal relationship between P2X7 receptor and pain. Moreover, we also described the effects of some antagonists on pain relief by inhibiting the activities of P2X7 receptor. Thus, targeting to inhibit activation of P2X7 receptor is expected to become another potential target for the relief of pain.

Avicularin reversed multidrug-resistance in human gastric cancer through enhancing Bax and BOK expressions.

5-Fluorouracil (5-Fu) and cisplatin (DDP) as important therapies in treatment of human gastric cancer have been widely determined. However, the therapeutic effects are usually hampered due to drug resistance or toxicity at high concentrations for application. Avicularin (AL, quercetin-3-α-l-arabinofuranoside), a bio-active flavonol isolated from a number of plants, has been reported to display diverse pharmacological properties. In this study, we explored the hypothesis by which AL reversed 5-Fu or DDP resistance in gastric cancer and the underlying molecular mechanism. Here, in vitro, the drug-resistant cancer cells were incubated to AL or DDP alone or the combination of AL and DDP. Then, MTT, colony formation, Hoechst 33258, flow cytometry and western blot analysis were used to investigate the effects of AL in the regulation of drug-resistance gastric cancer cells. The results indicated that AL treatment markedly re-sensitizes the drug resistant cells (SGC-7901/5-Fu and SGC-7901/DDP) to cytotoxicity of 5-Fu or DDP. Molecular mechanism analysis indicated that AL and DDP combination treatment enhanced apoptosis in SGC-7901/DDP cells, accompanied with the up-regulation of cleaved Caspase-3 and PARP, as well as the activation of pro-apoptotic signals, including Bax and BOK. Significantly, down regulation of Bax or BOK expressions using Bax siRNA or BOK siRNA decreased the inhibitory role of DDP in apoptosis of SGC-7901/DDP cells pretreated with AL, demonstrating that AL-reversed DDP resistance was associated with Bax and BOK expression. In vivo, AL and DDP combination significantly reduced gastric tumor growth. Immunohistochemical analysis indicated that co-treatment of AL and DDP significantly induced apoptosis, and reduced tumor cell proliferation in tumor tissue samples. Furthermore, we also found that the Bax, BOK, cleaved Caspase-3 and PARP expression in tumor tissues were highly induced by AL and DDP co-treatment. Together, our findings may provide a novel combination therapeutic strategy in treatment of human gastric cancer.

[Radiographic imaging feature and differential diagnosis of early femoral head necrosis].

OBJECTIVE: To study early femoral head necrosis radiographic imaging features to provide objective basis for the clinical differential diagnosis and therapeutic schedule's choice. METHODS: Ninty-one patients with femur head necrosis of ARCO stage I and II whom were diagnosed by clinic and MRI and treated from March 2007 to June 2008 were analyzed retrospectively. There were 32 males and 59 females with an average age of (34.83 +/- 9.57) years ranging from 21 to 60 years. The course of disease were from 2 to 12 months. There were 17 cases of unilateral and 74 of bilateral; 48 cases caused by steroid, 35 cases by alcohol and 8 cases for unknown reasons. The images of X-ray, CT and MRI of femoral head were analyzed to summarize the characteristic and to distinguish with the imaging of similar osteonecrosis. RESULTS: Ninety-one cases had linear low signal on T1WI in weight-bearing area of femoral head and high signal of the "dual taxation" on T2WI. But the shapes had different characteristics. There were 36 cases (39.56%) of line type shapes, 28 cases (30.77%) of oval shapes, 14 cases (15.38%) of map-like shapes, 13 cases (14.29%) of wedge shapes. The X-rays of the disease similar to bone necrosis including primary hip osteoarthritis, developmental dysplasia of hip arthritis, femoral head epiphysitis (coxa plana), rheumatoid hip arthritis, hip arthritis of ankylosing spondylitis, transitional synovitis of hip joint, femoral head bone marrow edema etc, had the similar performance to femur head necrosis like cystic changes, joint space narrowing, femoral head deformation. MRI performance had their own characteristics. CONCLUSION: Mastering the image features of the early femoral head necrosis will help the early diagnosis and treatment of hip joint necrosis disease.