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.

Aneurysmal Subarachnoid Hemorrhage and Sex Differences: Analysis of Epidemiology, Outcomes, and Risk Factors.

BACKGROUND: The differences in outcomes after aneurysmal subarachnoid hemorrhage (aSAH) between the sexes have not been concretely determined. This study aimed to evaluate the differences in epidemiology, outcomes, and risk factors between male and female patients with aSAH. METHODS: We performed a multicenter, retrospective study of patients with aSAH from 2017 to 2020. We investigated the epidemiological differences between the two sexes. Propensity score matching (PSM) was used to compare short-term outcomes between the sexes. Binary logarithmic regression was performed to investigate the odds ratio (OR) for dependent survival in patients of different sexes. RESULTS: A total of 5,407 consecutive patients with aSAH were included in this study, and the female-to-male ratio was 1.8:1. The peak incidence of aSAH occurred in the 6th and 7th decades in males and females, respectively. There were more female patients with internal carotid artery or posterior communicating artery aneurysms (53.2%), and there were more male patients with anterior cerebral artery or anterior communicating artery aneurysms (43.2%). The incidence of multiple aneurysms was greater in female patients (21.5% vs. 14.2%, P < 0.001). There was no significant difference in outcomes before and after PSM at discharge. The dependent survival risk was related only to the clinical condition on admission in women. In addition, age > 50 years (OR 1.88, 95% confidence interval 1.17-3.02; P = 0.01) and hypertension (OR 1.81, 95% confidence interval 1.25-2.61; P = 0.002) were also risk factors for male patients. CONCLUSIONS: There were more female patients with aneurysms than male patients in this study. Most aneurysm locations were different between the two groups. There was no significant difference in discharge outcomes before and after PSM. The risk factors for dependent survival were different between female and male patients.

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.

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.

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.

[Investigation and analysis on the current situation of clinical practice guidelines for acupuncture and moxibustion at home and abroad].

To provide directional suggestions for the establishment of international clinical practice guidelines for acupuncture and moxibustion by investigating the current situation of clinical practice guidelines for acupuncture and moxibustion at home and abroad. The clinical practice guidelines were obtained by questionnaire survey, database retrieval and experts consulting. The guidelines were read carefully, and the content was analyzed. A total of 27 acupuncture-moxibustion clinical practice guidelines were retrieved, of which most of the guidelines came from China. The definition and scope of "acupuncture and moxibustion "vary according to different guidelines; and the focus of the content and the method of establishing the guidelines are quite different, so it is very necessary to unify the formulation methods of acupuncture-moxibustion clinical practice guidelines. Chinese clinical practice guidelines for acupuncture and moxibustion were characterized by taking the ancient literature as the evidence. Excavating the value of ancient literature and clinical experience of acupuncture-moxibustion experts are the key points and difficulties in the developing of clinical practice guidelines of acupuncture and moxibustion in the future.

A protocol for systematic review and meta-analysis of the effect of acupoint therapy for essential hypertension.

BACKGROUND: Essential hypertension remains an enormous public health concern, imposing a major burden of morbidity and mortality worldwide. Relevant studies showed that acupuncture therapy might be effective in treating essential hypertension. However, there is no consistent conclusion so far. The aim of this study was to assess the efficacy and safety of acupuncture therapy for patients with essential hypertension. METHODS: We searched the PubMed, Embase, the Cochrane Library, Web of Science, the Chinese National Knowledge Infrastructure (CNKI), and the Wan-fang databases from inception through November 29, 2019. Randomized controlled trials investigating acupuncture therapy for hypertension were included. We will use Endnote software X8 for studies selection, Review Manager software 5.3 for the data analysis. RESULTS: We will synthesize current studies to evaluate the safeties and effectiveness of acupuncture for essential hypertension. CONCLUSIONS: Our study will provide the evidence of acupuncture therapy for essential hypertension.

[Origin and relationship of jing-well points and Shixuan (EX-UE 11)].

Both the twelve jing-well points and Shixuan (EX-UE 11) are the commonly used first-aid points. These two kinds of acupoints are located closely and similar in function, hence, they are often confused in application. In order to explore the origin of their location and theory as well as their relationship, the relevant data were retrieved. It has been found that the relationship between jing-well points and Shixuan (EX-UE 11) is traced at the earliest time to Huangdi Neijing (Yellow Emperor's Internal Classics). It is believed that the jing-well points refer to the starting points or the ending points of the twelve regular meridians and Shixuan (EX-UE 11) are located at the crossing sites of yin-yang related meridians of the regular meridians. These two kinds of acupoints are interconnected, share the same source and are also different from each other. Qiduan (EX-LE 12) is also named as foot-Shixuan. Shixuan (EX-UE 11) and Qiduan (EX-LE 12) can be regarded as the same category, just like jing-well points. In clinical practice, the jing-well points are generally selected in treatment of internal diseases, local diseases and those on the running course of meridians. They can be used separately in treatment. Shixuan (EX-UE 11) is the first option, or combined with Qiduan (EX-LE 12) in the emergent treatment of tense syndrome and syncope. The jing-well points and Shixuan (EX-UE 11) are different even though sharing the same origin. They are mutually benefited and supplemented with each other in clinical practice.

[Acupuncture strategy for Bu-yi in Inner Canon of Yellow Emperor].

This article focuses on the Bu-yi (the disease has not been cured after treatment) recorded in the Inner Canon of Yellow Emperor and discusses four aspects, including acupuncture feasibility, acupuncture treatment transformation, acupuncture point selection and acupuncture treatment principles. We hope to explain the virtual acupuncture in the Inner Canon of Yellow Emperor from a deeper level and provide new ideas for clinical acupuncture treatment.

[Exploration into the simplex reinforcing-reducing manipulation of acupuncture].

Four controversial types of simplex reinforcing-reducing manipulation of acupuncture and their possible meanings were summarized to explore several key elements of reinforcing-reducing manipulation of acupuncture, in addition, the simplex reinforcing-reducing manipulation of acupuncture was classified by single factor. It is concluded that the definition of simplex reinforcing-reducing manipulation of acupuncture should try not to include other non-manipulative elements. According to single factor, it can be divided into: needle-oriented reinforcing-reducing manipulation, twisting reinforcing-reducing manipulation, lifting and interpolating reinforcing-reducing manipulation, fast and slow reinforcing-reducing manipulation, breathing reinforcing-reducing manipulation, opening and closing reinforcing-reducing manipulation. In addition, after considering the effect and principle of number reinforcing-reducing manipulation, it can be considered.

[Regulating effect of electroacupuncture on left ventricular function and autophagy-specific proteins in spontaneously hypertension rats].

OBJECTIVE: To investigate the effect of electroacupuncture (EA) on cardiac hypertrophy and expression of myocardial autophagy-specific proteins in spontaneously hypertensive rats (SHRs). METHODS: Twelve male Wistar Kyoto (WKY) rats were selected as the normal control group, and 24 male SHRs were randomized into model and EA groups (n＝12 in each). EA (2 Hz /15 Hz, 1 mA) was applied to "Taichong" (LR3) and "Baihui" (GV20) for 20 min, once a day for successive 30 days. The other two groups only received the same grasping and fixation procedures. The systolic blood pressure (SBP) was measured using a non-invasive blood detector, and the left ventricular function including the left ventricular anterior wall diameter (LVAWd), left ventricular posterior wall diameter (LVPWd) and left ventricular internal diameter at end-diastolic dimension (LVIDd) was detected using a real-time echocardiography imaging system, and the left ventricular mass index (left ventricle weight / body weight, LVMI) was calculated. The expression of Beclin-1 and LC3 proteins in the left ventricle tissue was detected by Western blot. Pathological changes of the myocardial tissue were observed by Masson staining and transmission electron microscope (TEM). RESULTS: After the intervention, the elevated SBP was significantly lowered in the EA group relevant to the model group (P<0.01) and the increased LVAWd, LVPWd and LVMI were markedly decreased in the EA group (P<0.01, P<0.05), while the reduced LVIDd was significantly ameliorated in the EA group (P<0.01). Masson staining showed that in SHRs, disorder of arrangement of cardiac myofibers, swelling of cardiomyocytes, widened space among myocardial cells with a large number of collagenous fibers were observed, and under TEM, aggregation and unequal size of myocardial mitochondria with vacuolation and rupture, autophagosomes and autophagic lysosomes were seen. These changes were relatively milder in the EA group. Western blot showed that hypertension induced up-regulation of Beclin-1 and LC3-II and ratio of LC3-II/LC3-I, and down-regulation of LC3-I were significantly suppressed in the EA group (P<0.01, P<0.05). CONCLUSION: EA at LR3 and GV20 may improve the left cardiac function, myocardial morphological changes and the degree of autophagy in SHRs, which is related to its effects in down-regulating the expression of myocardial Beclin-1 and LC3-II and in up-regulating expression of LC3-I.

[Progress of the application of PET technology in acupuncture research].

To further investigate the application of positron emission tomography (PET) technology in acupuncture research field, with "PET" and "acupuncture" as keywords, the related literature published from 1997 to 2018 was searched in PubMed, CNKI and WANFANG database; then the literature was classified and analyzed. The results showed that in clinical and experimental studies, whether in physiological or pathological conditions, PET technology has verified the specificity of acupoints, bidirectional regulation of acupoints, and the clinical effect of qi-arrival from the level of brain functional activity. It has deeply revealed the central mechanism underlying that acupuncture has multi-target, multi-channel and multi-level overall effects. The purpose of this study is to provide objective scientific basis for acupuncture research, and then potentially guide the clinical practice.

Knockdown of AGR2 induces cell apoptosis and reduces chemotherapy resistance of pancreatic cancer cells with the involvement of ERK/AKT axis.

BACKGROUND: Pancreatic cancer (PC), an aggressive human malignancy, presents with a striking resistance to chemotherapy. Interesting, AGR2 has been found to be upregulated in various cancers and has been found to promote the dissemination of PC cells. Thereby, a series of in-vitro experiments were performed to investigate the relationship between AGR2 and the ERK/AKT axis, and to explore whether it affects PC cells. METHODS: Positive expression of AGR2 protein in the PC and paracancerous tissues collected from 138 patients with PC was detected using immunohistochemistry. After treatment with FGF2 (an ERK/AKT axis agonist), siRNA against AGR2 or their combination respectively, cell viability, chemotherapy resistance, radiotherapy resistance, migration, invasion and apoptosis in PC cells were detected using CCK8 assay, MTT assay, clone formation assay, wound healing assay, Transwell assay and flow cytometry, respectively. The expressions of AGR2 and ERK/AKT axis-related genes and proteins in tissues and cells were detected using reverse transcription quantitative polymerase chain reaction and Western blot assay. RESULTS: PC tissues exhibited highly-expressed AGR2 and abnormally activated ERK/AKT axis. FGF2 promoted the expression of AGR2, ERK/AKT axis activation, cell viability, chemotherapy resistance, migration and invasion, but decreased cell apoptosis in PC cells. However, knockdown of AGR2 resulted in inhibition of the ERK/AKT axis, reduced PC cell viability, chemotherapy resistance, migration and invasion but increased cell apoptosis in PC cells. CONCLUSION: The findings reveal that AGR2 silencing could promote cell apoptosis and inhibit cell migration, invasion and chemotherapy resistance of PC cell with the involvement of the ERK/AKT axis.

[Hypothalamic Transcription Profiles Associated with Twirling-reducing Needling in Rats with Stress-induced Prehypertension].

OBJECTIVE: To observe the effect of twirling-reducing needling on changes of profile of differentially-expressed genes in the hypothalamus in rats with stress-induced prehypertension (SI-PHT), so as to explore its mechanism under-lying improvement of prehypertension. METHODS: Wistar male rats were randomly divided into blank control group (n=12), model group (n=12) and acupuncture group (n=10). The SI-PHT model was established by planta-electric-shock stimulation (30 V, 5 s) plus noise stimulation (80-100 db, 50 ms), twice daily, continuously for 11 days. Manual acupuncture stimulation (twirling-reducing needling) was applied to bilateral "Taichong" (LR 3) and "Quchi" (LI 11) for about 1 min (60 cycles/min), followed by retaining the needles for 20 min during modeling preparation, once daily for 11 days. The systolic blood pressure (SBP) and behavior changes were recorded before intervention and on the 3rd, 5th, 7th, 9th and 11th day during modeling. The expression (Fold change,|FC| ≥ 1.5) profile of genes in the hypothalamus was analyzed using Affymetrix GeneChip Rat Gene 2.0 ST Array, followed by analyzing the differentially-expressed genes involving the related biological process,molecular function, and signaling pathways by using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), separately. RESULTS: After modeling, the systolic pressure levels were remarkably increased from the 3rd day to the 11th day in both model and acupuncture groups relatively to their respective baseline levels (P<0.01), and were significantly lower in the acupuncture group than in the model group (P<0.01) from the 5th day to the 11th day. Meanwhile, 93 genes were up-regulated and 153 down-regulated in the model group relative to the control group (P<0.05,|FC| ≥ 1.5), while in comparison with the model group, 59 genes were up-regulated and 86 down-regulated in the acupuncture group (P<0.05,|FC| ≥ 1.5). The expression levels of the 40 differen-tially-expressed genes (24 up-regulated and 16 down-regulated) in the model group were evidently reversed after acupuncture stimulation (P<0.05,|FC| ≥ 1.5). After acupuncture stimulation, the expression of acyl-CoA synthetase medium-chain family member 3 (Acsm 3) gene was down-regulated, and chorionic gonadotropin-alpha (Cgα), crystal (Cry) αB and thyroid stimulating hormone beta (Tshß) genes and the autoimmune thyroid disease (AITD) pathway were up-regulated (P<0.05,|FC| ≥ 1.5), suggesting an involvement of fatty acid biosynthetic processing, G-protein coupled receptor protein signaling, and hormone activity, etc. in acupuncture-induced blood-pressure lowering. CONCLUSIONS: Twirling-reducing needling of acupuncture can lower blood pressure in prehypertension rats, which may be related to its effects in regulating expression of Acsm 3, Cgα, CryαB, Tshß genes and in activating AITD pathway.

[Efficacy Comparison of Different Salvage Treatment Regimens for Patients with Refractory/Relapsed Acute Myeloid Leukemia].

OBJECTIVE: To compare the efficacy and safety of 3 different regimens, namely MAC, FLAG and CAG, as the re-induction chemotherapy for acute myeloid leukemia(AML) patients with primary induction failure and relapse. METHODS: The clinical data of 156 AML patients with primary induction failure and relapse, except patients with acute promyelocytic leukemia(APL), treated with any of the above 3 regimens in our center from January 2008 to April 2016 were analyzed retrospectively. According to the treatment regimens, 156 patients were divided into MAC group (n=60), FLAG group (n=45) and CAG group (n=51). The complete remission(CR), partial remissison(PR), overall survival(OS), disease-free survival(DFS) and adverse events during the treatment were analyzed, so as to compare and evaluate the efficacy and safety of the 3 different regimens. RESULTS: After 1 course of re-induction chemotherapy, CR in MAC group was significantly higher than that in FLAG and CAG group (55.4% vs 34.1% vs 34.0%)(P<0.05). The OS was not statistically significantly different among 3 groups (P>0.05) with a median OS of 11 months, 5.46 months and 10.2 months, respectively. The myelosuppression was the main adverse event with no significant difference among the groups(P>0.05). More patients treated with MAC regimen underwent febrile neutropenia (93.3% vs 86.7% vs 64.7%)(P<0.001). However, the incidence of fatal infections was not signicantly different among 3 groups(5% vs 8.9% vs 5.9%)(P>0.05). CONCLUSION: Compared with FLAG and CAG regimen, the MAC regimen can enable more AML patients with primary induction failure and refractory to achieve CR without increasing severe adverse events,therefore,this regimen may provide a opportunity for patients to recieve hematopoietic stem cell transplantation.

[Preliminary Clinical Efficiency of Autologous Peripheral Blood Mononuclear Cells for Treating Critical Limb Ischemia of Thromboangiitis Obliterans].

OBJECTIVE: To evaluate the long-term clinical effect of autologous peripheral blood mononuclear cells (PB-MNC) on critical limb ischemia (CLI) in patients with thromboangiitis obliterans (TAO) patients. METHODS: The clinical data of 22 patients with CLI caused by TAO from July 2004 to May 2013 were analyzed retrospectively, 22 patients were divided into 2 groups; out of them 12 cases in one group were treated with granulocyte colony-stimulating factor (G-CSF)-mobilized autologous peripheral blood mononuclear cells (auto-PBMNC group), 10 cases in another group received conservative treatment (CT group). The log-rank test was used to compare the long-term outcomes in auto-PBMNC group and CT group. RESULTS: The wound healing rate (P=0.016) and CLI-free rate (P=0.013) were significantly higher in PB-MNC group compared with that in CT group. No difference was found in amputation rates between the 2 groups (major amputation: P=0.361, minor and major amputation: P=0.867). No patients died or no serious adverse events occurred during the follow-up period. CONCLUSION: The auto-PBMNC therapy can significantly promote the wound healing, and protect against CLI in TAO patients, but the risk of amputation is not low in comparison with conservative treatment.

[Effects of acupotomy intervention on regional pathological changes and expression of carti- lage-mechanics related proteins in rabbits with knee osteoarthritis].

OBJECTIVE: To observe the effect of acupotomy (needle-knife) therapy on local pathological changes and cartilage-mechanics related protein expression in rabbits with knee osteoarthritis (KOA) so as to study its mechanisms underlying improving KOA. METHODS: Forty New Zealand rabbits were randomly divided into normal control group, model group, acupotomy group, and electroacupuncture (EA) group (n = 10 in each group). The KOA model was established by immobilization of the left knee-joint (modified Videman method) for 6 weeks. After modeling, acupotomy relaxing was applied to the lateral collateral ligament and patellar ligament of the left knee-joint, once a week for 3 times, and EA (2 Hz/100 Hz, 3 mA) was applied to the left "Yanglingquan" (GB 34), "Yinlingquan" (SP 9), "Neixiyan" (EX-LE 4) and "Waixiyan" (ST 35) for 20 min, 3 times a week for three weeks. The expression levels of Integrin ß1, type II collagen (Col-II), matrix metalloproteinase (MMP)-3 and Aggrecan proteins of the cartilage tissue of the left femoral medial and external condyles were observed by Western blot. Pathological changes of the knee-joint by X-ray scanning and those of the femoral condyle tissue were evaluated by Mankin's scores under light microscope after H. E. staining. RESULTS: X-ray showed successful modeling, and pathological changes of the articular cartilage belonged to the early and moderate lesion of knee osteoarthritis. The Mankin's score was significantly higher in the model group than in the control group (P < 0.01) , and after the treatment, the Mankin's scores were significantly decreased in the acupotomy. group (P < 0.01), rather than in the EA group (P > 0.05). The results of Western blot showed that after modeling, the expression levels of Integrin ß 1, Col-II and Aggrecan proteins of the femoral articular cartilage were considerably decreased (P < 0.01), while that of MMP-3 protein was significantly increased (P < 0.01). Compared with the model group, the decreased expression levels of Integrin ß 1, Col-II and Aggrecan proteins in the acupotomy group and Integrin ß 1 protein in the EA group were notably up-regulated (P < 0.01 , P < 0.05), and MMP-3 expression in the acupotomy group was significantly down-regulated (P < 0.01). No significant changes were found in the EA group in the expression levels of Col-II , Aggrecan and MMP-3 proteins compared with the model group (P > 0.05). CONCLUSION: Acupotomy intervention can relieve KOA-induced injury of the knee-joint in KOA rats, which is associated with its actions in raising expression levels of Integrin ß 1, Col-II and Aggrecan proteins and in lowering the expression of MMP-3 proteins in the articular cartilage, probably by adjusting the mechanics-related signal pathway of the articular chondrocytes.

[Effect of twirling-reinforcing-reducing needling manipulations on contents of serum acetylcholine and arterial NOS and cGMP in stress-induced hypertension rats].

OBJECTIVE: To observe the effect of twirling-reinforcing or reducing needling manipulations on plasma acetylcholine (Ach) content and expression of nitric oxide synthetase (NOS) and cyclic guanosine monophosphate (cGMP) in thoracic artery tissue in stress-induced hypertension rats. METHODS: A total of 60 male rats were randomly divided into blank control, model, acupuncture (no-needle-manipulation) , twirling-reinforcing needling and twirling-reducing needling groups (n = 12 in each group). The stress hypertension model was established by giving the animals with noise and electric shock stimulation (paw), twice a day for 15 days. Acupuncture stimulation was applied to bilateral "Taichong" (LR 3) for 1 min, followed by retaining the needles for 20 min. The treatment was conducted once daily for 7 days. Systolic blood pressure of the rat's tail was detected with non-invasive method and plasma Ach, and NOS and cGMP contents in the thoracic artery tissue were measured using ELISA method. RESULTS: Compared with the control group, the systolic blood pressure was significantly higher in the model group after 15 days' stress stimulation (P < 0.01), while the contents of plasma Ach, arterial NOS and cGMP were markedly down-regulated (P < 0.01). Following 7 days' acupuncture interventions, the increased blood pressure was down-regulated in the no-needle-manipulation, twirling-reinforcing needling and twirling-reducing needling groups (P < 0.05, P < 0.01); and the decreased Ach and NOS in the 3 treatment groups, and cGMP levels in the twirling-reinforcing and twirling-reducing needling groups were remarkably up-regulated (P < 0.01, P < 0.05). No significant change of arterial cGMP content was found in the no-needle-manipulation group (P > 0.05). The effect of the twirling-reducing needling was superior to that of no-needle-manipulation and twirling-reinforcing needling in lowering blood pressure and raising plasma Ach content (P < 0.05, P < 0.01). CONCLUSION: The twirling-reducing needling of acupuncture has a significant anti-hypertensive effect in stress hypertension rats, which may be associated with its effects in raising blood Ach, and arterial NOS and cGMP levels.

TWIST-1 promotes cell growth, drug resistance and progenitor clonogenic capacities in myeloid leukemia and is a novel poor prognostic factor in acute myeloid leukemia.

Alterations of TWIST-1 expression are often seen in solid tumors and contribute to tumorigenesis and cancer progression. However, studies concerning its pathogenic role in leukemia are scarce. Our study shows that TWIST-1 is overexpressed in bone marrow mononuclear cells of patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). Gain-of-function and loss-of-function analyses demonstrate that TWIST-1 promotes cell growth, colony formation and drug resistance of AML and CML cell lines. Furthermore, TWIST-1 is aberrantly highly expressed in CD34+CD38- leukemia stem cell candidates and its expression declines with differentiation. Down-modulation of TWIST-1 in myeloid leukemia CD34+ cells impairs their colony-forming capacity. Mechanistically, c-MPL, which is highly expressed in myeloid leukemia cells and associated with poor prognosis, is identified as a TWIST-1 coexpressed gene in myeloid leukemia patients and partially contributes to TWIST-1-mediated leukemogenic effects. Moreover, patients with higher TWIST-1 expression have shorter overall and event-free survival (OS and EFS) in AML. Multivariate analysis further demonstrates that TWIST-1 overexpression is a novel independent unfavourable predictor for both OS and EFS in AML. These data highlight TWIST-1 as a new candidate gene contributing to leukemogenesis of myeloid leukemia, and propose possible new avenues for improving risk and treatment stratification in AML.

[Effects of twirling-rotating reinforcing and reducing technique for left ventricular morphology, concentration of ET-1 and expression of type I, III collagen mRNA in spontaneous hypertensive rats].

OBJECTIVE: To explore the effect differences between twirling-rotating reinforcing and reducing technique of acupuncture on cardiac damage in spontaneous hypertensive rats (SHR). METHODS: Sixty male 11-week-old SHR were randomly divided into four groups: a model control group (group A), a twirling-rotating reinforcing technique group (group B), a twirling-rotating reducing technique group (group C) and a needle retaining group (group D), 15 rats in each one. In addition, twelve male 11-week-old Wistar rats were used as a blank control group (group E). Acupuncture was not used in group A and group E, only with grasp, capture and binding stimulation that was also adapted in the rest groups. Rats in the group B were treated with acupuncture at "Taichong" (LR 3) by twirling-rotating reinforcing technique for 1 min and then the needles were retained for 9 min; rats in the group C were treated with acupuncture at "Taichong" (LR 3) by twirling-rotating reducing technique for 1 min and then the needles were retained for 9 min; rats in the group D were treated with acupuncture at "Taichong" (LR 3) but without any technique and then needles were retained for 10 min. Before and after acupuncture, blood pressure monitor was used to measure the rats' systolic pressure and diastolic pressure every 6 days. Twenty-eight days after the treatment, HE and Masson staining were adopted to observe the status of left ventricular hypertrophy and myocardial fibrosis. ELISA method was applied to test the content of endothelin-1 (ET-1). PCR semiquantitative method was used to analyze Type I and III collagen mRNA in the left ventricular. RESULTS: (1) Blood pressure: after the treatment, the systolic pressure and diastolic pressure were both increased in the group A and the group B (P < 0.05); while the two pressures were both lowered in the group C and the group D (P < 0.05), which was more obvious in the group C (P < 0.05). (2) According to HE and Masson staining, except for the group E, the myocardial hypertrophy and fibrosis could be found in the rest groups, in which the group C was the modest, followed by the group D, while the group A and the group B were more severe. (3) Concentration of ET-1: there were differences of concentration of ET-1 among 5 groups (P < 0.05), and the concentration value from high to low was the group A, B, C, D and E. (4) Type I collagen mRNA: the difference of level of Type I collagen mRNA between group C and D was not statistically significant (P > 0.05); compared with the group A and B, the level was lower in the group C; the level was the lowest in the group E. Type III collagen mRNA: the difference between the group A and B was not statistically significant (P > 0.05); compared with the group A, B and D, the level was lower in the group C. CONCLUSION: The twirling-rotating reducing could reduce the systolic pressure and diastolic pressure in SHR, effectively prohibit the production of ET-1 and expression of Type I and III collagen mRNA, and it has more obvious inhibiting effect on Type III collagen mRNA. There is biological effect difference between twirling-rotating reinforcing and reducing technique.