ObjectiveTo evaluate pharmacological effects of Shengmai injection（SMI）on cerebral ischemia and study its neuroprotective mechanism. MethodsMale specific pathogen-free （SPF） Sprague-Dawley （SD） rats were randomly divided into a sham group， a model group， a low-dose SMI group（3 mL·kg^-1）， a middle-dose SMI group（6 mL·kg^-1）， a high-dose SMI group（12 mL·kg^-1）， and a Ginaton group（4 mL·kg^-1）according to the random number table method， with 12 rats in each group. The rat model of cerebral ischemia-reperfusion（MCAO/R）was prepared via the suture method. The administration groups were intraperitoneally injected with corresponding concentrations of SMI or Ginaton injection after reperfusion， which was conducted for 3 consecutive days. The sham group and model group were administered the equivalent volume of physiological saline. The pharmacological effects of SMI on brain injury in MCAO/R rats were evaluated by neurological function scores， cerebral infarction area， hematoxylin-eosin （HE） staining， Nissl staining， terminal deoxynucleotidyl transferase dUTP nick-end labeling （TUNEL） staining， and Western blot. The dominant link and key protein of SMI treating cerebral injury were explored using proteomic analysis. The related mechanisms of SMI were further validated using enzyme-linked immunosorbent assay （ELISA）， Western blot， and chloride ion fluorescence probe with oxygen-glucose deprivation/reoxygenation（OGD/R）-treated PC12 cells and MCAO/R rats. ResultsCompared with the sham group， the model group showed significantly increased neurological function scores， cerebral infarction area， neuronal apoptosis rate， and expression levels of apoptosis related proteins （P<0.05， P<0.01）and significantly decreased density of Nissl bodies and neurons（P<0.01）. Compared with the model group， the SMI groups exhibited significantly decreased neurological function scores， cerebral infarction area， neuronal apoptosis rate， and expression levels of apoptosis related proteins （P<0.05， P<0.01）and significantly increased density of Nissl bodies and neurons （P<0.05）. The proteomic analysis results showed that oxidative stress and inflammatory response were important processes of SMI intervening in MCAO/R injury， and the chloride intracellular channel protein 1 （CLIC1） was one of key proteins in its action network. The levels of representative indicators of oxidative stress and inflammatory response in the MCAO/R rats of the SMI groups were significantly reduced， compared with those in the model group（P<0.05， P<0.01）， and the expression levels of CLIC1 and downstream NOD-like receptor protein 3 （NLRP3） decreased （P<0.01）. In addition， the experimental results based on the OGD/R PC12 cells showed that SMI significantly increased the cell survival rate（P<0.01） and significantly decreased the intracellular chloride ion concentration（P<0.05）. ConclusionSMI has neuroprotective effects. Oxidative stress and inflammatory response are key processes of SMI intervening in MCAO/R injury. The potential mechanism is closely related to the regulation of CLIC1.

Objective To explore the values of translocator protein (TSPO) and serum cell-free mitochondrial DNA (cf-mtDNA) in predicting the disease condition and prognosis of patients with traumatic shock. Methods Eighty patients (traumatic shock group) with traumatic shock and eighty patients (without traumatic shock group) without traumatic shock were selected. Complete demographic and clinical laboratory data of patients were collected. Blood samples of patients with traumatic shock were collected at the time points of immediately after admission (T₁) and the first day (T₂), the third day (T₃) and seventh day (T₄) after admission, the level of TSPO was measured by enzyme-linked immunosorbent assay (ELISA), and level of cf-mtDNA was measured by quantitative real-time polymerase chain reaction (qPCR). The levels of TSPO and cf-mtDNA were compared between patients with and without traumatic shock; the patients with traumatic shock were divided into the poor prognosis group and good prognosis group according to differed prognostic outcome, and the levels of TSPO and cf-mtDNA were compared between the two groups. The predictive values of TSPO and cf-mtDNA for the prognosis of patients with traumatic shock were analyzed by the receiver operating characteristic (ROC) curve. Results Compared with the no traumatic shock group, the traumatic shock group had higher levels of serum TSPO at T₁ to T₄ and higher levels of cf-mtDNA at T₂ to T₃, and the differences were statistically significant (P < 0.05). Compared with the good prognosis group, the poor prognosis group had higher levels of serum TSPO and cf-mtDNA at T₁ to T₄, and the differences were statistically significant (P < 0.05). Taking the prognosis of traumatic shock patients as the state variable to perform ROC curve analysis, the results showed that the area under the curve (AUC) of TSPO from T₁ to T₄ for predicting prognosis in the poor prognosis group was 0.825, 0.829, 0.695 and 0.869 respectively, while those of cf-mtDNA level from T₁ to T₄ for predicting prognosis in the poor prognosis group was 0.766, 0.766, 0.837 and 0.783 respectively, and the differences were statistically significant (P < 0.001). Conclusion Traumatic shock patients have elevated levels of TSPO and cf-mtDNA, with significantly higher levels observed in those with poor prognosis, and the TSPO level on the seventh day and cf-mtDNA level on the third day have the highest predictive value for prognosis.

Objective:To explore the efficacy of bibliotherapy to improve stigma and social function for patients with schizophrenia in rehabilitation.Methods:From June, 2018 to June, 2020 at Shandong Mental Health Center, a total of 115 patients with schizophrenia in rehabilitation were randomly divided into study group (58 cases) and control group (57 cases). The study group received bibliotherapy and the control group received general rehabilitation nursing based on original antipsychotic treatment and routine nursing. They were assessed with Link Disgrace Scale (LDS) and Inpatient Psychiatric Rehabilitation Outcome Scale (IPROS) before and after intervention.Results:There was no significant difference in the scores of all factors and total scores of LDs and IPROS before intervention between the two groups ( P>0.05). After intervention, the scores of all factors and total scores of LDS in the study group were 29.08±3.25, 63.69 ± 4.09, 12.54 ± 2.15, 105.31 ± 5.22 respectively, which were lower than those in the control group 37.17 ± 3.41, 74.00 ± 4.63,20.17 ± 2.89, 131.33 ± 8.51, there were significant differences between the two groups ( t values were 5.91-9.30, all P<0.05). After intervention, the scores of all factors and total scores of IPROS in the study group were 3.92 ± 1.32, 5.38 ± 1.56, 5.15 ± 1.63, 4.69 ± 1.44, 4.46 ± 1.66, 23.62 ± 3.31 respectively, which were lower than those in the control group 5.58 ± 2.11, 7.33 ± 2.67, 6.83 ± 1.12, 6.75 ± 2.73, 6.42 ± 2.31, 32.92 ± 5.07, there were significant differences between the two groups ( t values were 2.25-5.48, all P<0.05). Conclusions:Bibliotherapy can effectively improve the stigma and social function of patients with schizophrenia in rehabilitation.

The pathophysiology of visceral pain in patients with irritable bowel syndrome remains largely unknown. Our previous study showed that neonatal maternal deprivation (NMD) does not induce visceral hypersensitivity at the age of 6 weeks in rats. The aim of this study was to determine whether NMD followed by adult stress at the age of 6 weeks induces visceral pain in rats and to investigate the roles of adrenergic signaling in visceral pain. Here we showed that NMD rats exhibited visceral hypersensitivity 6 h and 24 h after the termination of adult multiple stressors (AMSs). The plasma level of norepinephrine was significantly increased in NMD rats after AMSs. Whole-cell patch-clamp recording showed that the excitability of dorsal root ganglion (DRG) neurons from NMD rats with AMSs was remarkably increased. The expression of β adrenergic receptors at the protein and mRNA levels was markedly higher in NMD rats with AMSs than in rats with NMD alone. Inhibition of β adrenergic receptors with propranolol or butoxamine enhanced the colorectal distention threshold and application of butoxamine also reversed the enhanced hypersensitivity of DRG neurons. Overall, our data demonstrate that AMS induces visceral hypersensitivity in NMD rats, in part due to enhanced NE-β adrenergic signaling in DRGs.
Adrenergic Agents ; pharmacology ; Animals ; Ganglia, Spinal ; drug effects ; Hyperalgesia ; drug therapy ; physiopathology ; Hypersensitivity ; drug therapy ; Male ; Maternal Deprivation ; Neurons ; drug effects ; Patch-Clamp Techniques ; methods ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Stress, Physiological ; physiology ; Visceral Pain ; chemically induced ; metabolism

Chronic visceral hypersensitivity is an important type of chronic pain with unknown etiology and pathophysiology. Recent studies have shown that epigenetic regulation plays an important role in the development of chronic pain conditions. However, the role of miRNA-325-5p in chronic visceral pain remains unknown. The present study was designed to determine the roles and mechanism of miRNA-325-5p in a rat model of chronic visceral pain. This model was induced by neonatal colonic inflammation (NCI). In adulthood, NCI led to a significant reduction in the expression of miRNA-325-5p in colon-related dorsal root ganglia (DRGs), starting to decrease at the age of 4 weeks and being maintained to 8 weeks. Intrathecal administration of miRNA-325-5p agomir significantly enhanced the colorectal distention (CRD) threshold in a time-dependent manner. NCI also markedly increased the expression of CCL2 (C-C motif chemokine ligand 2) in colon-related DRGs at the mRNA and protein levels relative to age-matched control rats. The expression of CXCL12, IL33, SFRS7, and LGI1 was not significantly altered in NCI rats. CCL2 was co-expressed in NeuN-positive DRG neurons but not in glutamine synthetase-positive glial cells. Furthermore, CCL2 was mainly expressed in isolectin B4-binding- and calcitonin gene-related peptide-positive DRG neurons but in few NF-200-positive cells. More importantly, CCL2 was expressed in miR-325-5p-positive DRG neurons. Intrathecal injection of miRNA-325-5p agomir remarkably reduced the upregulation of CCL2 in NCI rats. Administration of Bindarit, an inhibitor of CCL2, markedly raised the CRD threshold in NCI rats in a dose- and time-dependent manner. These data suggest that NCI suppresses miRNA-325-5p expression and enhances CCL2 expression, thus contributing to visceral hypersensitivity in adult rats.

BACKGROUND/AIMS: This study was to investigate whether transforming growth factor-β1 (TGF-β1) plays a role in hyperalgesia in chronic pancreatitis (CP) and the underlying mechanisms. METHODS: CP was induced in male adult rats by intraductal injection of trinitrobenzene sulfonic acid (TNBS). Abdominal hyperalgesia was assessed by referred somatic behaviors to mechanical stimulation of rat abdomen. Dil dye injected into the pancreas was used to label pancreas-specific dorsal root ganglion (DRG) neurons. Whole cell patch clamp recordings and calcium imaging were performed to examine the effect of TGF-β1 on acutely isolated pancreas-specific DRG neurons. Western blot analysis was carried out to measure the expression of TGF-β1 and its receptors. RESULTS: TNBS injection significantly upregulated expression of TGF-β1 in the pancreas and DRGs, and TGF-β1 receptors in DRGs (T9-T13) in CP rats. Intrathecal injection of TGF-β receptor I antagonist SB431542 attenuated abdominal hyperalgesia in CP rats. TGF-β1 application depolarized the membrane potential and caused firing activity of DRG neurons. TGF-β1 application also reduced rheobase, hyperpolarized action potential threshold, and increased numbers of action potentials evoked by current injection of pancreas-specific DRG neurons. TGF-β1 application also increased the concentration of intracellular calcium of DRG neurons, which was inhibited by SB431542. Furthermore, intrathecal injection of TGF-β1 produced abdominal hyperalgesia in healthy rats. CONCLUSIONS: These results suggest that TGF-β1 enhances neuronal excitability and increases the concentration of intracellular calcium. TGF-β1 and its receptors are involved in abdominal hyperalgesia in CP. This and future study might identify a potentially novel target for the treatment of abdominal pain in CP.
Abdomen ; Abdominal Pain ; Action Potentials ; Adult ; Animals ; Blotting, Western ; Calcium ; Diagnosis-Related Groups ; Fires ; Ganglia, Spinal ; Humans ; Hyperalgesia ; Injections, Spinal ; Male ; Membrane Potentials ; Neurons* ; Pancreas ; Pancreatitis, Chronic* ; Rats*

BACKGROUND/AIMS: Patients with long-standing diabetes often demonstrate intestinal dysfunction and abdominal pain. However, the pathophysiology of abdominal pain in diabetic patients remains elusive. The purpose of study was to determine roles of voltage-gated sodium channels in dorsal root ganglion (DRG) in colonic hypersensitivity of rats with diabetes. METHODS: Diabetic models were induced by a single intraperitoneal injection of streptozotocin (STZ; 65 mg/kg) in adult female rats, while the control rats received citrate buffer only. Behavioral responses to colorectal distention were used to determine colonic sensitivity in rats. Colon projection DRG neurons labeled with DiI were acutely dissociated for measuring excitability and sodium channel currents by whole-cell patch clamp recordings. Western blot analysis was employed to measure the expression of NaV1.7 and NaV1.8 of colon DRGs. RESULTS: STZ injection produced a significantly lower distention threshold than control rats in responding to colorectal distention. STZ injection also depolarized the resting membrane potentials, hyperpolarized action potential threshold, decreased rheobase and increased frequency of action potentials evoked by 2 and 3 times rheobase and ramp current stimulation. Furthermore, STZ injection enhanced neuronal sodium current densities of DRG neurons innervating the colon. STZ injection also led to a significant upregulation of NaV1.7 and NaV1.8 expression in colon DRGs compared with age and sex-matched control rats. CONCLUSIONS: Our results suggest that enhanced neuronal excitability following STZ injection, which may be mediated by upregulation of NaV1.7 and NaV1.8 expression in DRGs, may play an important role in colonic hypersensitivity in rats with diabetes.
Abdominal Pain ; Action Potentials ; Adult ; Animals ; Architectural Accessibility ; Blotting, Western ; Citric Acid ; Colon* ; Diagnosis-Related Groups ; Female ; Ganglia, Spinal ; Humans ; Hypersensitivity* ; Injections, Intraperitoneal ; Membrane Potentials ; Neurons ; Rats* ; Sensory Receptor Cells* ; Sodium ; Sodium Channels ; Streptozocin ; Up-Regulation ; Voltage-Gated Sodium Channels*

Objective:In oder to investigate the effect of Chuanmingshen violaceum polysaccharides ( CVP) and Solfated Chua-nmingshen violaceum polysaccharides ( SCVP) on immunosuppression induced by cyclophosphamide ( CY) in mice.Methods: CY were used to induce immunosuppression in mice;Spleen and thymus indexes were used to evaluate the immune organs indexes;the [3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltet-razolium bromide,MTT] method was used to detect the proliferation of spleen lymphocytes of each group;the concentrations of IFN-γand IL-2 were assayed by ELISA kit.Results: SCVP and CVP could resist immunosuppression by promoting lymphocyte proliferation, increasing the contents of IFN-γ and IL-2, promoting immune organs development in immunosuppressive mice induced by CY.Conclusion:SCVP and CVP exhibited the potential to used as immunopotentiator.

Objective To explore the influencing factors of ALT abnormality among workers from food industry and related people from public places in Shenzhen and influencing factors.Methods 2,411 workers from food industry and people from public places who had physical examinations in our department from May to October in 2013 were involved in the investigation.ALT abnormality rate and the influencing factors were analyzed.Results The incidence of ALT abnormalities among workers from food industry and related people from public places in Shenzhen was 9.37%.The ALT abnormalities were correlated with censue register,gender,age,marital status,work duration in Shenzhen,education level and monthly income respectively(all P<0.05). Conclusion The ALT abnormality has a higher rate among people from cities,of male gender and old age,with longer work duration in Shenzhen and relatively high level of education and higher monthly income.Therefore,for the population,the health education should be strengthened and the healthy lifestyles should be advocated to effectively reduce the ALT abnormality rate.

Objective To know the attitude about palliative care and its influence factors in nurses.Methods Interviewed 8 nurses deeply by qualitative research to know their attitude about pallia-tive care.Results 4 theme,including 9 subtheme were found: nurses' negative emotion caused by job; imperfect of special organization and criterion; characteristics of nursing work.Conclusions Hospital managers should enhance training of nurses' coping capacity with bad feelings, death education and culti-vation of empathy; improve medicare system;develop palliative care routine ; establish palliative care orga-nizations, and relieve nurses' job burden and increase wages.