Effect of "Tiaoshen" acupuncture technique on mild depression and its underlying mechanism: A randomized controlled trial study protocol.

Background: Mild depression is not just a mental disease, but also a serious and long-term public health issue. It affects the quality of life of patients and can quickly develop into major depression. There are currently no effective drug treatments with high efficacy and few adverse reactions. Acupuncture may be an alternative treatment option. Preliminary experiments and practices have demonstrated that "Tiaoshen" acupuncture improves symptoms in patients who have depression, however the underlying data and method remain unclear at present. Methods: This is a prospective, single-center, single-blind, randomized controlled trial. We plan to recruit 70 participants and randomly assign them to receive "Tiaoshen" acupuncture or traditional acupuncture at a ratio of 1:1. Then, all the participants will receive the appropriate acupuncture treatment for four weeks. The results of the Hamilton Depression Rating Scale (HDSR-24) will serve as the primary outcome, while the results of the Patient Health Questionnaire-9 (PHQ-9) and the World Health Organization Quality of Life Brief Version (WHOQOL-BREF) will serve as secondary outcomes. Evaluations will be conducted at baseline, 1, 2, and 4 weeks after treatment initiation, and 1 and 3 months after treatment completion. The safety of the intervention will be evaluated every week using the Columbia-Suicide Severity Rating Scale (C-SSRS) and the Treatment Emergent Symptoms Scale (TESS). Serum levels of oxidative stress markers 8-iso-prostaglandin F2α (8-iso-PGF2α), superoxide dismutase (SOD), uric acid (UA), and total bilirubin (TBIL) will be measured at baseline and the end of the treatment. We will conduct a statistical analysis of intention to treat (ITT) and conformance to protocol set (PPS) data. Discussion: This research aims to provide high-quality evidence for the efficacy and safety of "Tiaoshen" acupuncture as a treatment for mild depression. In addition, the mechanism through which acupuncture heals mild depression will be investigated.

Effect of the case-based learning method combined with virtual reality simulation technology on midwifery laboratory courses: A quasi-experimental study.

Objective: This study aimed to evaluate the effect of case-based learning (CBL) method with virtual reality (VR) simulation technology (CBL-VR) on midwifery laboratory courses. Methods: A quasi-experimental design was employed. A total of 135 midwifery students were recruited from Nursing College of Guilin Medical University in China from September 2020 to January 2022. Intervention group recruited students from the Class of 2019 (n = 59) and control group recruited students from the Class of 2018 (n = 76). The intervention group students received the CBL-VR method based on traditional laboratory teaching, the contents of course included four sections: eutocia (6 class hours), dystocia (6 class hours), umbilical cord prolapse (2 class hours), and neonatal asphyxia and resuscitation (4 class hours), 40 min per class hour. The control group students received the traditional laboratory teaching. Students' academic performance, Self-Directed Learning (SDL) Ability Questionnaire, and the education satisfaction questionnaire were used to evaluate the teaching efficacy between two groups. Results: After intervention, the intervention group students achieved higher scores than the control group in individual operation ability (90.88 ± 2.14 vs. 89.24 ± 3.15), team operation ability (90.97 ± 2.33 vs. 81.28 ± 5.45), and midwifery case analysis ability (88.64 ± 3.19 vs. 86.70 ± 2.56) (P ＜0.01). Prior to the implementation of the course, there was no difference in the SDL ability scores between the two groups of students (P ＞ 0.05). However, following the course intervention, the SDL ability scores of the intervention group were higher than those of the control group (94.78 ± 6.59 vs. 88.12 ± 8.36), and the scores in all dimensions of the intervention group were also higher (P < 0.05). Additionally, more than 94% of the students indicated that CBL-VR method developed comprehensive abilities, including independent-study enthusiasm, independent thinking, collaboration, and communication. Conclusion: Using the CBL-VR method in midwifery lab courses improved students' course performance, SDL ability, and comprehensive ability. Students highly recognized the effectiveness of this approach.

"Baihui" (DU20)-penetrating "Qubin" (GB7) acupuncture on blood-brain barrier integrity in rat intracerebral hemorrhage models via the RhoA/ROCK II/MLC 2 signaling pathway.

BACKGROUND: Blocking the RhoA/ROCK II/MLC 2 (Ras homolog gene family member A/Rho kinase II/myosin light chain 2) signaling pathway can initiate neuroprotective mechanisms against neurological diseases such as stroke, cerebral ischemia, and subarachnoid hemorrhage. Nevertheless, it is not clear whether and how disrupting the RhoA/ROCK II/MLC 2 signaling pathway changes the pathogenic processes of the blood-brain barrier (BBB) after intracerebral hemorrhage (ICH). The present investigation included the injection of rat caudal vein blood into the basal ganglia area to replicate the pathophysiological conditions caused by ICH. METHODS: Scalp acupuncture (SA) therapy was performed on rats with ICH at the acupuncture point "Baihui"-penetrating "Qubin," and the ROCK selective inhibitor fasudil was used as a positive control to evaluate the inhibitory effect of acupuncture on the RhoA/ROCK II/MLC 2 signaling pathway. Post-assessments included neurological deficits, brain edema, Evans blue extravasation, Western blot, quantitative polymerase chain reaction, and transmission electron microscope imaging. RESULTS: We found that ROCK II acts as a promoter of the RhoA/ROCK II/MLC 2 signaling pathway, and its expression increased at 6 h after ICH, peaked at 3 days, and then decreased at 7 days after ICH, but was still higher than the pre-intervention level. According to some experimental results, although 3 days is the peak, 7 days is the best time point for acupuncture treatment. Starting from 6 h after ICH, the neurovascular structure and endothelial cell morphology around the hematoma began to change. Based on the changes in the promoter ROCK II, a 7-day time point was selected as the breakthrough point for treating ICH model rats in the main experiment. The results of this experiment showed that both SA at "Baihui"-penetrating "Qubin" and treatment with fasudil could improve the expression of endothelial-related proteins by inhibiting the RhoA/ROCK II/MLC 2 signaling pathway and reduce neurological dysfunction, brain edema, and BBB permeability in rats. CONCLUSION: This study found that these experimental data indicated that SA at "Baihui"-penetrating "Qubin" could preserve BBB integrity and neurological function recovery after ICH by inhibiting RhoA/ROCK II/MLC 2 signaling pathway activation and by regulating endothelial cell-related proteins.

[Modulation of autophagy in the rats with acute intracerebral hemorrhage by acupuncture based on JNK pathway].

OBJECTIVE: To investigate the effects of acupuncture on JNK pathway and autophagy level in rats with intracerebral hemorrhage （ICH） and explore the partial mechanism of acupuncture against ICH. METHODS: SD rats were randomly divided into blank group, model group and acupuncture group. Each group was divided into Day 1, Day 3 and Day 7 subgroups respectively, with 5 rats in each group. The autologous blood injection was adopted to duplicate rat model of ICH. In the acupuncture group, the needle was inserted from "Baihui" （GV20） towards "Qubin" （GB7） on the affected side, stimulating for 30 min each time, once daily； the same acupuncture technique was opera-ted in each subgroup for 1, 3 and 7 days, separately. Using Bederson scale, the neurological deficit was evaluated in each group. Western blot was adopted to detect the protein expression levels of Beclin1, LC3Ⅰ/Ⅱ, phosphorylated c-Jun amino-terminal kinase （p-JNK） and the phosphorylated （p）-c-Jun around hematoma lesion of the brain tissue of rats in each group. RESULTS: After treatment, the neurological deficit score of rats in the model group was higher than that of the blank group at each time point （P<0.05）, and the score of the acupuncture group started declining since the 3rd day of treatment when compared with the model group （P<0.05）. At each time point, compared with the blank group, the protein expression levels of LC3Ⅰ/Ⅱ, Beclin1, p-c-Jun and p-JNK was increased （P<0.01）. Compared with the model group, the protein expression level of LC3Ⅰ/Ⅱ was reduced （P<0.05）； the protein expression levels of Beclin1, p-c-Jun and p-JNK was increased （P<0.05, P<0.01） on day 3 and 7 in the acupuncture group. CONCLUSION: Acupuncture can activate the JNK pathway in the brain tissue of rats with ICH and increase the level of autophagy, thereby improving the neurological function of the rats with ICH.

Genome-Wide Investigation of BAM Gene Family in Annona atemoya: Evolution and Expression Network Profiles during Fruit Ripening.

ß-amylase proteins (BAM) are important to many aspects of physiological process such as starch degradation. However, little information was available about the BAM genes in Annona atemoya, an important tropical fruit. Seven BAM genes containing the conservative domain of glycoside hydrolase family 14 (PF01373) were identified with Annona atemoya genome, and these BAM genes can be divided into four groups. Subcellular localization analysis revealed that AaBAM3 and AaBAM9 were located in the chloroplast, and AaBAM1.2 was located in the cell membrane and the chloroplast. The AaBAMs belonging to Subfamily I contribute to starch degradation have the higher expression than those belonging to Subfamily II. The analysis of the expression showed that AaBAM3 may function in the whole fruit ripening process, and AaBAM1.2 may be important to starch degradation in other organs. Temperature and ethylene affect the expression of major AaBAM genes in Subfamily I during fruit ripening. These expressions and subcellular localization results indicating ß-amylase play an important role in starch degradation.

Association between p73 RS2273953 to RS1801173 polymorphism and risk of lung cancer: a meta-analysis of 2,897 cases and 3,317 controls.

BACKGROUND: Lung cancer is one of the most common and deadly cancers in humans. P73, a member of the p53 family, is a vital gene for the carcinogenesis of lung cancer. Single nucleotide polymorphism (SNP) of P73 gene may affect the risk of lung cancer. Therefore, we performed a meta-analysis of p73 SNP and lung cancer risk using the most recent data. METHODS: A total of 1407 articles from EMBASE, Web of science, PubMed and Chinese National Knowledge Infrastructure (CNKI) databases were identified initially from the search. A meta-analysis of the association between P73 polymorphism and lung cancer risk was performed based on various genetic models and by type of lung cancer and race. RESULTS: Seven articles published in either English or Chinese with English abstract were eventually selected for final analysis. The total pooled population included 6214 subjects (2,897 cases and 3,317 controls). The results showed that p73 RS2273953 to RS1801173 polymorphism was associated with increased risk of lung cancer in Caucasians but not in Asians. Within Asians, those with p73 GC/GC may have an increased risk for squamous carcinoma compared to those with GC/AT+AT/AT polymorphism. CONCLUSIONS: Our analysis suggested a lack of association between p73 RS2273953 to RS1801173 polymorphism and risk of lung cancer overall. However, patients with GC/GC polymorphism showed an increased risk for squamous carcinoma in the lung compared to those with GC/AT+AT/AT in Asians.

Efficacy and Clinical Value of Negative-Pressure Wound Therapy with Instillation (NPWTi) of Compound Phellodendron Liquid in the Treatment of Diabetic Foot Ulcer: A Prospective Cohort Study.

Objective: To evaluate the efficacy and application value of compound Phellodendron liquid (CPL) for negative-pressure wound therapy with instillation (NPWTi) in the treatment of diabetic foot ulcers by observing the improvement of diabetic foot ulcers. Methods: Sixty patients with diabetic foot ulcers who met the inclusion criteria were admitted to the Department of Peripheral Blood Vessels (Wound Repair) of Chongqing Hospital of Traditional Chinese Medicine from August 2020 to August 2021. The random number table method divided it into the CPL NPWTi group and normal saline NPWTi group, with 30 cases in each group. The experimental group adopted FufangHuangbaiye for NPWTi, and the control group used normal saline for NPWTi. The treatment effect was evaluated by baseline index, wound healing observation index, inflammatory factor index, pain scores during dressing change, and the number of days in hospital. Results: After 10 days of treatment, the symptom integration, procalcitonin (PCT), and C reactive protein (CRP) of the CPL NPWTi group were significantly reduced compared with the normal saline NPWTi group, while there was no obvious difference between wound area and erythrocyte sedimentation rate (ESR). The wound area, symptom integral, PCT, ESR, and CRP of the CPL NPWTi group were significantly reduced compared with the normal saline NPWTi group after treatment for 20 days and 30 days. The positive proportion of bacterial culture in the CPL NPWTi group was significantly reduced compared with the normal saline NPWTi group after treatment for 10 days, 20 days, and 30 days. After treatment, the pain scores during dressing change and the number of days in hospital in normal saline NPWTi group were significantly lower than those in the CPL NPWTi group. Conclusion: Compound Phellodendron liquid NPWTi therapy can improve diabetic foot ulcers, providing a safe and effective method for treating diabetic foot ulcers.

Scalp Acupuncture Protects Against Neuronal Ferroptosis by Activating The p62-Keap1-Nrf2 Pathway in Rat Models of Intracranial Haemorrhage.

Intracerebral haemorrhage (ICH) can be a catastrophic event; even if the initial stages of the pathology were well-managed, a number of patients experience varied residual neurological deficits following the insult. Ferroptosis is a recently identified type of cell demise which is tightly linked to the neurological impairment associated with ICH. In the current work, the prophylactic impact of scalp acupuncture (SA) therapy on autologous blood injection murine models of ICH was investigated in order to establish whether SA could mitigate the secondary damage arising following ICH by moderating ferroptosis. The pathophysiological mechanisms associated with this process were also explored. Ludmila Belayev tests were utilised for the characterisation of neurological damage. Haematoxylin-eosin staining was employed in order to determine the cerebral impact of the induced ICH. Malondialdehyde (MDA) and iron titres in peri-haemorrhagic cerebral tissues were appraised using purchased assay kits. Transmission electron microscopy delineated mitochondrial appearances within nerve cell bodies from the area of haemorrhage. Western blotting techniques were utilised to assay the degree of protein expression of NeuN, sequestosome 1 (p62), nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1). The frequencies of Nrf2, GPX4 and FTH1 positive cells, respectively, were documented with immunohistochemical staining. The results demonstrated that therapy with SA after ICH mitigated MDA and iron sequestration, diminished the appearance of contracted mitochondria with increased outer mitochondrial membrane diameter within the nerve cell bodies, and suppressed neuronal ferroptosis. The pathways responsible for these effects may encompass amplified p62, Nrf2, GPX4 and FTH1 expression, together with decreased Keap1 expression. Application of SA reduced identified neurobehavioural abnormalities after ICH; no disparities were observed between the consequences of SA therapy and deferoxamine delivery. It can be surmised that intervention with SA enhanced recovery after ICH by triggering the antioxidant pathway, p62/Keap1/Nrf2, and causing FTH1 and GPX4 upregulation, factors that participate in diminishing excess iron and thus in mitigating lipid peroxidation insults arising from ferroptosis following ICH.

Electroacupuncture at GV20­GB7 regulates mitophagy to protect against neurological deficits following intracerebral hemorrhage via inhibition of apoptosis.

The acupuncture penetrating line of Baihui (GV20) to Qubin (GB7) spans the parietal, frontal and temporal lobes. The present study aimed to elucidate the mechanism by which electroacupuncture (EA) at GV20­GB7 regulates mitophagy in intracerebral hemorrhage (ICH) and whether it serves a neuroprotective role. A whole blood­induced ICH model was used. Mitophagy­regulating proteins, including BCL/adenovirus E1B 19 kDa­interacting protein 3 (BNIP3), PTEN­induced putative kinase 1 (PINK1), Parkin and apoptosis­associated proteins were detected by western blotting; autophagy following ICH was evaluated by immunofluorescent techniques; morphological characteristics of mitophagy were observed using transmission electron microscopy; and TUNEL assay was performed to determine the number of apoptotic cells. Immunohistochemistry was used to detect p53 expression. The protective role of EA (GV20­GB7) via enhanced mitophagy and suppressed apoptosis in ICH was further confirmed by decreased modified neurological severity score. The results showed that EA (GV20­GB7) treatment upregulated mitochondrial autophagy following ICH and inhibited apoptotic cell death. The mechanism underlying EA (GV20­GB7) treatment may involve inhibition of p53, an overlapping protein of autophagy and apoptosis. EA (GV20­GB7) treatment decreased neurobehavioral deficits following ICH but pretreatment with 3­methyladenine counteracted the beneficial effects of EA (GV20­GB7) treatment. In conclusion, EA (GV20­GB7) improved recovery from ICH by regulating the balance between mitophagy and apoptosis.

Scalp Acupuncture Attenuates Brain Damage After Intracerebral Hemorrhage Through Enhanced Mitophagy and Reduced Apoptosis in Rats.

To study the effect of scalp acupuncture (SA) on the mitophagy signaling pathway in the caudate nucleus of Sprague-Dawley rats following intracerebral hemorrhage (ICH). An ICH model was established by injecting autologous arterial blood into the caudate nucleus in 200 male Sprague-Dawley rats, which were divided into five groups: sham, ICH, 3-methyladenine group (3-MA, 30 mg/kg), SA, and SA+3-MA. Animals were analyzed at 6 and 24 h as well as at 3 and 7 days. Composite neurological scale score was significantly higher in the SA group than in the ICH group. Transmission electron microscopy showed less structural damage and more autophagic vacuoles within brain in the SA group than in the ICH group. SA group showed higher levels of Beclin1, Parkin, PINK1, NIX protein, and a lower level of Caspase-9 in brain tissue. These animals consequently showed less neural cell apoptosis. Compared with the SA group, however, the neural function score and levels of mitophagy protein in the SA+3-MA group were decreased, neural cell apoptosis was increased with more severe structural damage, which suggested that 3-MA may antagonize the protective effect of SA on brain in rats with ICH. SA may mitigate the neurologic impairment after ICH by enhancing mitophagy and reducing apoptosis.

Acupuncture promotes functional recovery after cerebral hemorrhage by upregulating neurotrophic factor expression.

Acupuncture is widely used in the treatment of cerebral hemorrhage, and it improves outcomes in experimental animal models and patients. However, the mechanisms underlying the effectiveness of acupuncture treatment for cerebral hemorrhage are still unclear. In this study, a model of intracerebral hemorrhage was produced by injecting 50 µL autologous blood into the caudate nucleus in Wistar rats. Acupuncture at Baihui (DU20) and Qubin (GB7) acupoints was performed at a depth of 1.0 inch, 12 hours after blood injection, once every 24 hours. The needle was rotated at 200 r/min for 5 minutes, For each 30-minute session, needling at 200 r/min was performed for three sessions, each lasting 5 minutes. For the positive control group, at 6 hours, and 1, 2, 3 and 7 days after induction of hemorrhage, the rats were intraperitoneally injected with 1 mL aniracetam (0.75 mg/mL), three times a day. The Bederson behavioral test was used to assess palsy in the contralateral limbs. Western blot assay was used to examine the expression levels of Nestin and basic fibroblast growth factor in the basal ganglia. Immunohistochemistry was performed to count the number of Nestin- and glial cell line-derived neurotrophic factor-positive cells in the basal ganglia. Acupuncture effectively reduced hemorrhage and brain edema, elevated the expression levels of Nestin and basic fibroblast growth factor in the basal ganglia, and increased the number of Nestin- and glial cell line-derived neurotrophic factor-positive cells in the basal ganglia. Together, these findings suggest that acupuncture promotes functional recovery after cerebral hemorrhage by increasing the expression of neurotrophic factors. The study was approved by the Committee for Experimental Animals of Heilongjiang Medical Laboratory Animal Center (approval No. 2017061001) on June 10, 2017.

Activation of Brainstem Neurons During Mesencephalic Locomotor Region-Evoked Locomotion in the Cat.

The distribution of locomotor-activated neurons in the brainstem of the cat was studied by c-Fos immunohistochemistry in combination with antibody-based cellular phenotyping following electrical stimulation of the mesencephalic locomotor region (MLR) - the anatomical constituents of which remain debated today, primarily between the cuneiform (CnF) and the pedunculopontine tegmental nuclei (PPT). Effective MLR sites were co-extensive with the CnF nucleus. Animals subject to the locomotor task showed abundant Fos labeling in the CnF, parabrachial nuclei of the subcuneiform region, periaqueductal gray, locus ceruleus (LC)/subceruleus (SubC), Kölliker-Fuse, magnocellular and lateral tegmental fields, raphe, and the parapyramidal region. Labeled neurons were more abundant on the side of stimulation. In some animals, Fos-labeled cells were also observed in the ventral tegmental area, medial and intermediate vestibular nuclei, dorsal motor nucleus of the vagus, n. tractus solitarii, and retrofacial nucleus in the ventrolateral medulla. Many neurons in the reticular formation were innervated by serotonergic fibers. Numerous locomotor-activated neurons in the parabrachial nuclei and LC/SubC/Kölliker-Fuse were noradrenergic. Few cholinergic neurons within the PPT stained for Fos. In the medulla, serotonergic neurons within the parapyramidal region and the nucleus raphe magnus were positive for Fos. Control animals, not subject to locomotion, showed few Fos-labeled neurons in these areas. The current study provides positive evidence for a role for the CnF in the initiation of locomotion while providing little evidence for the participation of the PPT. The results also show that MLR-evoked locomotion involves the parallel activation of reticular and monoaminergic neurons in the pons/medulla, and provides the anatomical and functional basis for spinal monoamine release during evoked locomotion. Lastly, the results indicate that vestibular, cardiovascular, and respiratory centers are centrally activated during MLR-evoked locomotion. Altogether, the results show a complex pattern of neuromodulatory influences of brainstem neurons by electrical activation of the MLR.

Mitophagy, a potential therapeutic target for stroke.

Mitochondria autophagy, termed as mitophagy, is a mechanism of specific autophagic elimination of mitochondria. Mitophagy controls the quality and the number of mitochondria, eliminating dysfunctional or excessive mitochondria that can generate reactive oxygen species (ROS) and cause cell death. Mitochondria are centrally implicated in neuron and tissue injury after stroke, due to the function of supplying adenosine triphosphate (ATP) to the tissue, regulating oxidative metabolism during the pathologic process, and contribution to apoptotic cell death after stroke. As a catabolic mechanism, mitophagy links numbers of a complex network of mitochondria, and affects mitochondrial dynamic process, fusion and fission, reducing mitochondrial production of ROS, mediated by the mitochondrial permeability transition pore (MPTP). The precise nature of mitophagy's involvement in stroke, and its underlying molecular mechanisms, have yet to be fully clarified. This review aims to provide a comprehensive overview of the integration of mitochondria with mitophagy, also to introduce and discuss recent advances in the understanding of the potential role, and possible signaling pathway, of mitophagy in the pathological processes of both hemorrhagic and ischemic stroke. The author also provides evidence to explain the dual role of mitophagy in stroke.

Baihui (DU20)-penetrating-Qubin (GB7) acupuncture inhibits apoptosis in the perihemorrhagic penumbra.

Baihui (DU20)-penetrating-Qubin (GB7) acupuncture can inhibit inflammatory reactions and activate signaling pathways related to proliferation after intracerebral hemorrhage. However, there is no research showing the relationship between this treatment and cell apoptosis. Rat models of intracerebral hemorrhage were established by injecting 60 µL of autologous blood into the right side of the caudate-putamen. Six hours later, the needle traveled subcutaneously from the Baihui acupoint to Qubin acupoint. The needle was alternately rotated (180 ± 10 turns/min) manually along clockwise and counter-clockwise directions. Stimulation lasted for 7 days, and was performed three times each for 6 minutes with 6-minute intervals between stimulations. Rats intraperitoneally receiving Sonic hedgehog pathway activator, purmorphamine (1 mg/kg per day), served as positive controls. Motor and sensory function were assessed using the Ludmila Belayev test. Extent of pathological changes were measured in the perihemorrhagic penumbra using hematoxylin-eosin staining. Apoptosis was examined by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling assay. Expression of smoothened (Smo) and glioma-associated homolog 1 (Gli1) was determined by western blot assay. Our results showed that Baihui-penetrating-Qubin acupuncture promoted recovery of motor and sensory function, reduced the apoptotic cell percentage in the perihemorrhagic penumbra, and up-regulated Smo and Gli1 expression. We conclude that Baihui-penetrating-Qubin acupuncture can mitigate hemorrhage and promote functional recovery of the brain in a rat model of intracerebral hemorrhage, possibly by activating the Sonic hedgehog pathway.

Acupuncture through Baihui (DU20) to Qubin (GB7) mitigates neurological impairment after intracerebral hemorrhage.

Inflammation plays an important role in nerve defects caused by intracerebral hemorrhage. Repairing brain damage by inhibiting the macrophage-inducible C-type lectin/spleen tyrosine kinase (Mincle/Syk) signaling pathway is a potential new target for treating cerebral hemorrhage. In this study, we aimed to determine whether acupuncture through Baihui (DU20) to Qubin (GB7) is an effective treatment for intracerebral hemorrhage through the Mincle/Syk signaling pathway. An intracerebral hemorrhage rat model was established by autologous blood infusion into the caudate nucleus. Acupuncture through Baihui to Qubin was performed for 30 minutes, once every 12 hours, for a total of three times. Piceatannol (34.62 mg/kg), a Syk inhibitor, was intraperitoneally injected as a control. Modified neurological severity score was used to assess neurological function. Brain water content was measured. Immunohistochemistry and western blot assay were used to detect immunoreactivity and protein expression levels of Mincle, Syk, and CARD9. Real-time polymerase chain reaction was used to determine interleukin-1ß mRNA levels. Hematoxylin-eosin staining was performed to observe histopathological changes. Our results showed that acupuncture through Baihui to Qubin remarkably improved neurological function and brain water content, and inhibited immunoreactivity and expression of Mincle, Syk, CARD9, and interkeukin-1ß. Moreover, this effect was similar to piceatannol. These findings suggest that acupuncture through Baihui to Qubin can improve neurological impairment after cerebral hemorrhage by inhibiting the Mincle/Syk signaling pathway.

Autophagy, Endoplasmic Reticulum Stress and the Unfolded Protein Response in Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is a subtype of stroke that is followed by primary and secondary brain injury. As a result of the injury, cell metabolism is disrupted and a series of stress responses are activated, such as endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), leading to the re-establishment of cell homeostasis or cell death. As an important mechanism of cell homeostasis, autophagy has been widely studied, and the associations between autophagy, ER stress, and the UPR have also been demonstrated. Whether these mechanisms are beneficial or detrimental remains a matter of controversy, but there is no doubt as to their vital functions. An understanding of the mechanisms of injury and recovery after ICH is crucial to develop therapeutic strategies. In this review, we summarize the related studies and highlight the roles of autophagy, ER stress, and the UPR in disease, especially in ICH. We also provide an overview of therapeutic approaches that target autophagy, and we discuss the prospects for modulating autophagy, ER stress, and UPR mechanisms in ICH therapy.

[Traditional Chinese medicine fumigation combined with Levofloxacin for type â ¢A prostatitis with the symptoms of damp heat and blood stasis].

OBJECTIVE: To investigate the clinical effects of traditional Chinese medicine (TCM) fumigation on type ⅢA prostatitis with the symptoms of damp heat and blood stasis. METHODS: We randomly divided 72 cases of type ⅢA prostatitis with the symptoms of damp heat and blood stasis into an experimental and a control group of equal number, the former treated with TCM fumigation plus oral Levofloxacin while the latter with oral Levofloxacin only. After 4 weeks of treatment, we compared the National Institute of Health Chronic Prostatitis Symptom Index (NIHCPSI) score, TCM symptoms score, maxinum flow rate (Qmax), and average urinary flow rate (Qave) between the two groups of patients. RESULTS: The total effectiveness rate was significantly higher in the experimental than in the control group (91.7% vs 61.1%, P< 0.01), while the NIHCPSI score in the experimental group was markedly decreased after treatment as compared with the baseline (14.5 ± 8.2 vs 26.5 ± 9.3, P< 0.05) and significantly lower than that in the control (14.5 ± 8.2 vs 20.6 ± 7.9, P< 0.05). Qmax was remarkably increased in the experimental group after treatment in comparison with the baseline (ï¼»21.2 ± 4.3ï¼½ vs ï¼»15.8 ± 3.6ï¼½ ml/s, P< 0.05) and the control group, and so was Qave as compared with pretreatment (ï¼»16.3 ± 3.5ï¼½ vs ï¼»10.5 ± 2.8ï¼½ ml/s, P< 0.05) and the control. However, the patients of the control group showed no statistically significant differences before and after treatment either in Qmax (ï¼»15.4 ± 3.4ï¼½ vs ï¼»16.1 ± 2.9ï¼½ ml/s, P>0.05) or in Qave (ï¼»10.9 ± 2.4ï¼½ vs ï¼»11.1 ± 2.9ï¼½ ml/s, P>0.05). CONCLUSIONS: TCM fumigation combined with Levofloxacin is an effective therapy for type ⅢA prostatitis with the symptoms of damp heat and blood stasis, which can significantly improve the symptoms, reduce the NIHCPSI score, and increase the Qmax and Qave of the patient.

[Penetrative Needling from "Baihui" (GV 20) to "Qubin" (GB 7) Antagonizes Inflammatory Injury in Rats with Cerebral Hemorrhage].

OBJECTIVE: To observe the effect of penetrative needling of "Baihui" (GV 20) to "Qubin" (GB 7) on neurologic functions and expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and toll-like receptor 4 (TLR-4, involving in inflammatory reactions) in the tissue around the local cerebral hematoma in rats with intracerebral hemorrhage (ICH), so as to provide evidence for clinical treatment of ICH. METHODS: Fifty-four male Wistar rats were randomly divided into sham control, mo-del and acupuncture groups, and then further divided into three time-point subgroups(1,3,7 days after modeling, n=6/subgroup). The ICH model was established by injection of the rat's autoblood (50 µL) into the putaman region (P:0.2 mm, R:3.5 mm) in a stereotaxic apparatus and confirmed by Berderson's neurologic examination grading system (0-3 points). The neurologic function was assessed by using Longa's scoring (5-points) and footfault asymmetry testing[footfault index=(contra faults-ipsi faults)/total steps in 2 min]. For penetrative needling, an acupuncture needle was inserted into GV 20 and controlled to advance to GB 7 on the affected side and retained for 30 min, once daily. The expression of TNF-α, IL-6 and TLR-4 in the cerebral tissue around the putaman was detected by immunohistochemistry. RESULTS: After penetrative needling stimulation, the increased Longa's score and footfault asymmetry score in ICH rats were significantly decreased on day 1, 3 and 7 after modeling (P<0.01), suggesting an improvement of neurologic function after the treatment. Immunohistochemical staining outcomes of the cerebral tissue surrounding the autoblood injection site showed that the expression levels of TNF-α, IL-6 and TLR-4 proteins on day 1, 3 and 7 were considerably higher in the model group than in the control group (P<0.01), and markedly lower in the acupuncture group than in the model group (P<0.01), suggesting a suppression of the proinflammatory factors and TLR-4 levels around the locus of the brain after needling intervention. A positive correlation existed between the expression levels of TLR-4 and IL-6/TNF-α. CONCLUSIONS: Penetrative needling stimulation of GV 20 to GB 7 can reduce the levels of proinflammatory factors TNF-α and IL-6, and TLR-4 in the ICH tissues in rats with cerebral hemorrhage, which may contribute to its effect in improving neurological function.

Acupuncture inhibits Notch1 and Hes1 protein expression in the basal ganglia of rats with cerebral hemorrhage.

Notch pathway activation maintains neural stem cells in a proliferating state and increases nerve repair capacity. To date, studies have rarely focused on changes or damage to signal transduction pathways during cerebral hemorrhage. Here, we examined the effect of acupuncture in a rat model of cerebral hemorrhage. We examined four groups: in the control group, rats received no treatment. In the model group, cerebral hemorrhage models were established by infusing non-heparinized blood into the brain. In the acupuncture group, modeled rats had Baihui (DU20) and Qubin (GB7) acupoints treated once a day for 30 minutes. In the DAPT group, modeled rats had 0.15 µg/mL DAPT solution (10 mL) infused into the brain. Immunohistochemistry and western blot results showed that acupuncture effectively inhibits Notch1 and Hes1 protein expression in rat basal ganglia. These inhibitory effects were identical to DAPT, a Notch signaling pathway inhibitor. Our results suggest that acupuncture has a neuroprotective effect on cerebral hemorrhage by inhibiting Notch-Hes signaling pathway transduction in rat basal ganglia after cerebral hemorrhage.

Reversal of diabetes-induced rat graft transplant coronary artery disease by metformin.

BACKGROUND: Induction of diabetes in rat heterotopic heart transplantation models leads to an accelerated form of severe transplant coronary artery disease (TxCAD). We undertook this study to determine whether treatment of diabetes with metformin would favorably affect TxCAD. METHODS: Heterotopic abdominal heart transplantation was performed in rat isograft and allograft models. After transplantation, diabetes was induced with streptozotocin. Fifty percent of the animals received metformin at 500 mg/kg twice daily. We quantitatively assessed TxCAD using histologic sections of harvested hearts at 30 and 60 days with computer-assisted morphometry. We compared vessels in the first tertile of the area distribution with vessels in the last tertile. RESULTS: Fasting glucose levels in metformin-treated animals were 161 +/- 45 mg/dl compared with 400 +/- 120 mg/dl (p < 0.05) in untreated rats. Treatment with metformin led to decreased diabetes-induced TxCAD in the larger vessels. This effect was sustained during the study course in the isografts but not in the allografts. Treatment with metformin did not prevent progression of TxCAD in the smaller vessels at 60 days. CONCLUSIONS: Metformin reduced luminal occlusion and severe TxCAD in the larger vessels but did not alter the course of TxCAD in the smaller vessels. These results may have therapeutic implications for patients.