Dorsal root ganglion receptor subtype P2X3R mediates postoperative-hyperalgesic priming in mice / 中国药理学通报

Aim To investigate the differences in the role of different purinergic receptor subtypes at different sites in postoperative-hyperalgesic priming in mice. Methods A postoperative-hyperalgesic priming model was constructed by injecting PGE

Carbazole and tetrahydro-carboline derivatives as dopamine D3 receptor antagonists with the multiple antipsychotic-like properties

Dopamine D3 receptor (D3R) is implicated in multiple psychotic symptoms. Increasing the D3R selectivity over dopamine D2 receptor (D2R) would facilitate the antipsychotic treatments. Herein, novel carbazole and tetrahydro-carboline derivatives were reported as D3R selective ligands. Through a structure-based virtual screen, ZLG-25 (D3R Ki = 685 nmol/L; D2R Ki > 10,000 nmol/L) was identified as a novel D3R selective bitopic ligand with a carbazole scaffold. Scaffolds hopping led to the discovery of novel D3R-selective analogs with tetrahydro-β-carboline or tetrahydro-γ-carboline core. Further functional studies showed that most derivatives acted as hD3R-selective antagonists. Several lead compounds could dose-dependently inhibit the MK-801-induced hyperactivity. Additional investigation revealed that 23j and 36b could decrease the apomorphine-induced climbing without cataleptic reaction. Furthermore, 36b demonstrated unusual antidepressant-like activity in the forced swimming tests and the tail suspension tests, and alleviated the MK-801-induced disruption of novel object recognition in mice. Additionally, preliminary studies confirmed the favorable PK/PD profiles, no weight gain and limited serum prolactin levels in mice. These results revealed that 36b provided potential opportunities to new antipsychotic drugs with the multiple antipsychotic-like properties.

Associations of family functioning with sleep disturbance and depressive symptoms among primary and secondary school students / 中国学校卫生

Objective@#The study aims to explore the associations of family functioning with sleep disturbance and depressive symptoms among primary and secondary school students, to provide scientific reference for preventing depression in primary and middle school students.@*Methods@#A convenience sampling method was used to recruit 124 357 primary and secondary school students in Baoan District, Shenzhen. A self administered general information questionnaire, the Youth Self Rating Insomnia Scale, and the Patient Heath Questionnaire-9 were used to assess the students demographic characteristics, family functioning, sleep disturbance, and depressive symptoms.@*Results@#About 34.6% of students reported moderate family dysfunction, and 8.7% reported severe family dysfunction. The prevalence rates of sleep disturbance and depressive symptoms were 13.0% and 13.1% in elementary and secondary school students, respectively. The prevalence rates of sleep disturbance and depressive symptoms were statistically significantly higher in girls(14.6%, 16.8%) than boys(11.6%, 9.9%) ( χ 2=255.25, 1 269.50, P <0.01). Depressive symptoms were positively correlated with sleep disturbance ( r =0.61) and negatively correlated with family functioning ( r =-0.31)( P <0.01). Family functioning moderated the relationship between sleep disturbance and depressive symptoms, and the positive predictive effect of sleep disturbance on depressive symptoms decreases as the level of family functioning increases.@*Conclusion@#Family functioning buffers the effects of sleep disturbance on depressive symptoms among primary and secondary school students. Attention should be paid to sleep quality among primary and secondary school students, to improve their family functioning, and thus decrease and prevent the occurrence of depression in adolescents.

Application of "blended learning + flipped classroom" in medical public elective courses / 中华医学教育探索杂志

Objective:To explore the application effect of "blended learning + flipped classroom" in public elective courses for medical students, and provide reference for the blended construction of related courses.Methods:Totally 229 medical students were selected as research participants, who were taught by "blended learning + flipped classroom". After the courses, the curriculum evaluation questionnaires and focus group interview were used to collect students' evaluation of this course. SPSS 22.0 statistical software was used to make descriptive statistics on the questionnaire data.Results:Totally 98.5% students preferred "blended learning + flipped classroom" teaching mode, and more than 93% students thought this teaching method could improve their learning interest, empathy, understanding and application of knowledge. The results of the qualitative survey extracted two themes, namely "improving learning autonomy" and "expanding comprehensive quality".Conclusion:Perfecting the "blended learning + flipped classroom" teaching mode of the medical public elective courses plays a positive role in improving the learning autonomy and comprehensive quality of medical students and optimizing the learning effect.

Early intervention of bone-nearby acupuncture combined with electroacupuncture on morphine tolerance in bone cancer pain rats and its effect on the expression of HDAC and MOR in dorsal root ganglia / 中国针灸

OBJECTIVE@#To observe the effect of early intervention of bone-nearby acupuncture (BNA) combined with electroacupuncture (EA) on the expression of histone deacetylase1(HDAC1), histone deacetylase 2 (HDAC2) andμ-opioid recepter (MOR) in dorsal root ganglia (DRG) of bone cancer pain-morphine tolerance (BCP-MT) rats, and to explore its possible mechanism.@*METHODS@#A total of 35 SD rats were randomized into a sham BCP group (=6), a BCP group (=7), a MT group (=7), a BNA+EA group (=8) and a shame BNA group (=7). Except of the sham BCP group, cancer cell inoculation operation at left tibia was given in the other 4 groups to establish the bone cancer pain model. In the MT group, the BNA+EA group and the shame BNA group, intraperitoneal injection of morphine hydrochloride was given to establish the morphine tolerance model. After the operation, bone-nearby acupuncture combined with electroacupuncture was applied at "Zusanli" (ST 36) and "Kunlun" (BL 60) in the BNA+EA group, with dilatational wave, 2 Hz/100 Hz in frequency, 0.5 to 1.5 mA in intensity. Intervention in the shame BNA group was applied at the same time and acupoints as those in the BNA+EA group, the needles were pierced the skin without any electrical stimulation. The needles were retained for 30 min, once a day for continuous 7 days in both BNA+EA and shame BNA groups. Before and 10, 11, 15, 22 days after the operation, the left paw withdrawal threshold (PWT) was measured in the 5 groups. The levels of HDAC1, HDAC2 and MOR in DRG were detected by Western blot.@*RESULTS@#Ten days after the cancer cell inoculation operation, the PWT of the BCP, MT, BNA+EA and sham BNA groups was decreased compared with the sham BCP group (0.05); the PWT of the BNA+EA group was increased compared with the MT and sham BNA group (<0.01). In the BCP group, the DRG levels of HDAC1 and HDCA2 were increased, while the level of MOR was decreased compared with the sham BCP group (<0.05, <0.01). In the MT group, the DRG level of HDAC1 was increased compared with the BCP group (<0.05). In the BNA+EA group, the DRG level of HDAC1 was decreased compared with the MT group and the sham BNA group (<0.01, <0.05), while the level of MOR was increased (<0.01).@*CONCLUSION@#Early intervention of bone-nearby acupuncture combined with electroacupuncture can relieve the morphine tolerance in bone cancer pain rats, it may relate to down-regulating the expression of HDAC1 and up-regulating the expression of MOR in the dorsal root ganglia.

Effect of electroacupuncture on expression of GABA receptor mRNA in different brain regions in rats with chronic inflammatory pain / 中国针灸

OBJECTIVE@#To observe the expression of GABA receptor mRNA in different brain regions of the central nervous system in chronic inflammatory pain rats and the intervention effect of electroacupuncture (EA).@*METHODS@#A total of 48 SPF male SD rats were randomly divided into a blank control group, a model control group, an EA group and a sham EA group, 12 rats in each group. The model of chronic inflammatory pain was established by injecting Freund's complete adjuvant into the foot. The EA group was treated with EA 28 days after the model establishment. The "Housanli" (ST 36) and "Kunlun" (BL 60) were selected and treated with dilatational wave, 2 Hz/100 Hz in frequency, 0.5-1.5 mA for 30 min; EA was given only once. In the sham EA group, the same acupoints were selected but the needles were only inserted into subcutaneous area; EA was connected for 30 min without electrical stimulation. The behavior changes of mechanical pain threshold and thermal pain threshold before model establishment, 1 day, 3 days, 7 days, 14 days, 21 days and 28 days after the model establishment as well as emotional behavior 29 days after the model establishment were observed; the relative expressions of GABA receptor mRNA in anterior cingulate cortex, amygdala and hypothalamus were observed.@*RESULTS@#Compared with the blank control group, the change rates of mechanical pain threshold and thermal pain threshold in the model control group were decreased significantly 1 day, 3 days, 7 days, 14 days, 21 days, 28 days after model establishment (0.05). Compared with the blank control group, the expression of GABA receptor mRNA in the amygdala was decreased significantly in the model control group (<0.01); compared with the model control group and the sham EA group, the expression of GABA receptor mRNA in amygdala was increased after intervention in the EA group (<0.01).@*CONCLUSION@#Single treatment of EA could significantly increase the mechanical pain threshold and thermal pain threshold, improve abnormal emotional behavior in rats with chronic inflammatory pain, which may be related to the increasing of expression of GABA receptor mRNA in the amygdala.

Effect of levosimendan combined with freeze-dried recombinant human brain natriuretic peptide on cardiac function and hemodynamics in elderly patients with heart failure / 实用医学杂志

Objective To investigate the clinical effects of levosimmentan combined with freeze-dried recombinant human brain natriuretic peptide in elderly patients with heart failure. Methods Eighty patients with heart failure diagnosed in our hospital from January 2015 to January 2018 were selected as subjects. According to the random number table prepared in Excel 2007,40 patients in the experimental group and the control group were given. For basic treatments such as diuresis,the experimental group was treated with levosimtan combined with lyophilized recombinant human brain natriuretic peptide,and the control group was treated with levosimtan and dobutamine. The left ventricle of the two groups before and after treatment was compared. End-diastolic period (LVEDD),left ventricular ejection fraction(LVEF),cardiac index(CI),stroke volume(SV),serum cystatin C (Cys-C),amino terminal brain natriuretic peptide precursor(NT-proBNP),mean arterial pressure(MAP), pulmonary capillary pressure(PCWP). Results Before treatment,the differences of LVEDD,LVEF,CI and SV levels between the experimental group and the control group were not statistically significant(P > 0.05). After treatment,the LVEDD of the experimental group was significantly lower than that of the control group(P < 0.05).The LVEF,CI and SV values in the experimental group were significantly higher than those in the control group (P < 0.05). There was no significant difference in serum Cys-C and NT-proBNP levels between the experimental group and the control group before treatment(P > 0.05). After treatment,the serum levels of Cys-C and NT-proB-NP in the experimental group were significantly lower than those in the control group(P < 0.05). Before treatment,the difference of MAP and PCWP levels between the experimental group and the control group was not statistically significant(P > 0.05). After treatment,the MAP and PCWP levels in the experimental group were significantly lower than those in the control group(P < 0.05). The incidence of adverse reactions in the experimental group was 10.00％ and the difference between the control group and the control group was not statistically significant(P > 0.05). Conclusions Levosimmentan combined with freeze-dried recombinant human brain natriuretic peptide in patients with senile heart failure can significantly improve cardiac function,reduce Cys-C,NT-proBNP levels,and improve hemodynamic parameters.

The curative effect observation of different frequency of TEAS combined with wristband pressing on Neiguan (PC 6) for nausea and vomiting after laparoscopic cholecystectomy / 中国针灸

OBJECTIVE@#To compare the effects of different frequency of transcutaneous electrical acupoint stimulation (TEAS) combined with wristband pressing on Neiguan (PC 6) for nausea and vomiting (PONV) after laparoscopic cholecystectomy, and optimize the TEAS frequency selection for treatment of PONV.@*METHODS@#Eighty patients undergoing laparoscopic cholecystectomy were randomly divided into a postoperative routine care group, a 2 Hz TEAS combined with wristband pressing group (2 Hz TEAS group), a 100 Hz TEAS combined with combined with wristband pressing group (100 Hz TEAS group) and a 2 Hz/100 Hz TEAS wristband pressing group (2 Hz/100 Hz TEAS group), 20 cases in each group (1 patient dropped off in the postoperative routine care group). All the four groups underwent laparoscopic cholecystectomy, and routine nursing was given after the operation. In the postoperative routine nursing group，only routine nursing was received. In the other three groups, 2 Hz TEAS combined with wristband pressing, 100 Hz TEAS combined with wristband pressing, 2 Hz/100 Hz TEAS combined with wristband pressing to simulate Neiguan (PC 6) were treated on the basis of postoperative routine care after surgery. The treatment was given for 30 min each time for a total of 4 treatments. The incidence of PONV in each group was observed at 0-2 h, 2-8 h, 8-24 h and 24-48 h after operation, and the severity of PONV and postoperative pain were evaluated.@*RESULTS@#Compared with the postoperative routine care group, the incidence and severity of PONV in the four time periods after surgery were significantly reduced in the 2 Hz/100 Hz TEAS group (all <0.05), the incidence and severity of PONV in patients at 2 h and 2-8 h after surgery were significantly reduced in the 2Hz TEAS group and the 100 Hz TEAS group (all <0.05), the postoperative pain at 8 h and 24 h after surgery was alleviated in the 100 Hz TEAS group and the 2 Hz/100 Hz TEAS group (all <0.05).@*CONCLUSION@#Different frequency of TEAS combined with wristband pressing to stimulating Neiguan (PC 6) have certain therapeutic effects on PONV in patients undergoing laparoscopic cholecystectomy. 2 Hz/100 Hz TEAS combined with wristband pressing at Neiguan (PC 6) is more effective in PONV. 2 Hz/100 Hz TEAS and 100 Hz TEAS combined with wristband pressing at Neiguan (PC 6) have postoperative analgesic effect, and 2 Hz/100 Hz TEAS has the better analgesic effect.

Clinical effects of needle free (INJEX30) versus traditional injection of botulinum toxin A for bromhidrosis / 中华医学美学美容杂志

Objective To investigate the clinical efficacy of bromhidrosis with botulinum toxin A by needle free injection.Methods A total of 40 patients with bromhidrosis were collected and divided into needle free group and needle group.A comparative study was carried out in those subjects.Patients in needle free group received needle free injection of botulinum toxin A by INJEX30;Needle group received traditional injection by 26 G needles.Results In needle free group,16 cases were cured,3 cases were effective,1 case was ineffective,no significant pain,hematomas or necrosis were found.In needle group,15 cases were cured,4 cases were effective,and 1 case was ineffective;localized hematoma occurred in 2 cases.And cases in group needle experienced pain more intensely than cases in needle free group.Conclusions The INJEX30 improves the security,comfort and therapy compliance of botulinum toxin A injection in the bromhidrosis patients,with similar efficacy with traditional injection.

Electroacupuncture attenuates spinal nerve ligation-induced microglial activation mediated by p38 mitogen-activated protein kinase / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate whether analgesic effect of electroacupuncture (EA) is affected by p38 mitogen-activated protein kinase (p38 MAPK) on microglia.</p><p><b>METHODS</b>There were two experiments. The experiment 1: 40 male Sprague-Dawley (SD) rats were randomly divided into the normal, surgery, EA and sham EA groups, and the L5 spinal nerve ligation (SNL) on the right side was used to establish neuropathic pain model. EA was applied to bilateral Zusanli (ST36) and Kunlun (BL60) at 24, 48 and 72 h after SNL for 30 min, once per day. The paw withdrawal thresholds (PWTs) were measured before surgery (as base) and at 24, 25, 49 and 73 h after surgery. Phospho-p38 MAPK (p-p38 MAPK), oxycocin-42 (OX-42, marker of microglia), and glial fibrillary acidic protein (GFAP, marker of astrocyte) in bilateral spinal cord dorsal horn (SCDH) were detected by immunofluorescence, respectively. The experiment 2: 40 male SD rats were cannulated for SNL-induced neuropathic pain, and then were randomly divided into the dimethyl sulfoxide (DMSO), EA plus DMSO, 4-(4-fluorophenyl)-2-(4-methylsulfonylpheny)-5-(4-pyridyl)-1H-imidazole (SB203580) and EA plus SB203580 groups. SB203580 (30 nmol/L) was administered 5 min prior to EA treatment. The PWTs and OX-42 in bilateral SCDH were measured as mentioned above.</p><p><b>RESULTS</b>SNL-induced neuropathic pain reduced PWTs and increased the expression of p-p38 MAPK and OX-42 in bilateral lumbar SCDH of rats (P<0.01). Spinal p-p38 MAPK was only co-localized with OX-42 in our study. EA treatment significantly alleviated SNL-mediated mechanical hyperalgesia, and suppressed the expression of p-p38 MAPK and OX-42 in lumbar SCDH (P<0.05 or P<0.01). Intrathecal injection of low dose SB203580 had no influence on PWTs (P>0.05), but significantly inhibited the expression of OX-42 positive cells in bilateral SCDH (P<0.01 or P<0.05). EA plus SB203580 synergistically increased PWTs, and reduced the expression of bilateral spinal OX-42 (P<0.01 or P<0.05).</p><p><b>CONCLUSIONS</b>The central mechanism of EA-induced anti-hyperalgesia may be partially associated with the reduced expression of p-p38 MAPK, and subsequently reducing the activation of OX-42 in neuropathic pain. Therefore, EA may be a new complementary and alternative therapy for neuropathic pain.</p>

Trilobed flaps for reconstructio n of nasal tip defects / 中华皮肤科杂志

Objective To evaluate the performance of trilobed flaps for reconstruction of nasal tip defects. Methods Totally, 23 patients with nasal tip defects after tumor resection were enrolled into this study. Skin defects varied from 1.5 cm × 1.5 cm to 2.5 cm × 2.5 cm in size. According to the location and size of skin defects, trilobed flaps were designed, and the angle between two lobes ranged from 45° to 50°. The size of the first lobe was approximately equal to that of the skin defect, while the size of the second and third lobes decreased successively. During flap design, the integrity of nasal subunits was sufficiently considered, and the incision lines were placed along the boundary lines of the nasal subunit as far as possible, so as to conceal the incision scar with natural skin folds. Results After the operation, skin flaps survived with primary healing of incisions in all the patients. After 6 - 24 months of follow up, the color, texture and thickness of flaps were similar to those of their surrounding skin, and incision scars were inconspicuous. No malformation occurred in the nasal ala, nostril, nasal columella or surrounding organs, and satisfactory nasal appearance and function were achieved. Conclusion Trilobed flaps can be used to effectively repair relatively large skin defects of the nasal tip with satisfactory nasal appearance and function.

Effect of electroacupuncture on phosphorylation of NR2B at Tyr 1742 site in the spinal dorsal horn of CFA rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of electroacupuncture (EA) on phosphorylation of spinal NR2B at Tyr 1742 site in complete Freund's adjuvant (CFA) induced inflammatory pain rats. METHods Forty male Sprague Dawley rats were randomly divided into normal group (N group, n = 10), the model group (CFA group, n = 15), and the EA group (n = 15). The inflammatory pain model was established by subcutaneous injecting CFA (0.1 mL per rat) into the right hind paw. Paw withdrawal thresholds (PWTs) were measured before CFA injection (as the base), as well as at 24 h, 25 h, 3rd day, and 7th day after CFA injection. Phosphorylation of NR2B at Tyr 1742 site in the ispilateral spinal dorsal horn at the 3rd day post-injection were detected using immunohistochemical assay.</p><p><b>RESULTS</b>PWTs in the CFA group were significantly lower than those of the N group at every detective time point post-injection (P < 0.01). PWTs were obviously lower in the EA group than in the N group at 24 h post-injection (P < 0.01). It showed increasing tendency, markedly higher than those of the CFA group at 25 h and 3rd day post-injection (P < 0.01). Compared with the N group, the ratio of p-NR2B positive cells in the ispilateral spinal dorsal horn of rats in the CFA group was up-regulated. Compared with the CFA group, the ratio of p-NR2B positive cells in the ispilateral spinal dorsal horn of rats showed a decreasing tendency in the EA group.</p><p><b>CONCLUSION</b>EA might effectively inhibit CFA-induced inflammatory pain possibly associated with down-regulating phosphorylation of NR2B at Tyr 1742 site in the ispilateral spinal dorsal horn.</p>

Immediate analgesic effect of electroacupuncture and its regulation mechanism via spinal p-ERK1/2 / 中国针灸

<p><b>OBJECTIVE</b>To observe influence of electroacupuncture (EA) on phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) in spinal cord dorsal horn (SCDH) in rats with acute inflammatory pain induced by complete Freund's adjuvant (CFA), further elucidate the immediate analgesic mechanism of EA via cellular signal transduction.</p><p><b>METHODS</b>Fifty-three healthy male SD rats were divided into two batches. The inflammatory pain models of the first batch of 23 rats were established by using CFA. The changes of the paw withdrawal thresholds (PWTs) of rats were observed and positive cells of p-ERK1/2 in affected SCDH were detected by using immunohistochemistry method. The second batch of 30 rats were randomly divided into a blank control group (N group), CFA group and EA group, 10 rats in each group. The rats of CFA group and EA group were induced inflammatory pain by using CFA, and the EA group was treated with EA at 5.5 h after the model establishment. The changes of PWTs and the positive cells of p-ERK1/2 in SCDH were observed.</p><p><b>RESULTS</b>The PWTs of the first batch of rats obviously decreased at 5 h, 3 d, 7 d and 14 d after CFA administration (all P< 0.01). However, the p-ERK1/2 positive cells in affected SCDH only increased at 5 h after CFA-injection and returned to normality at 3 d after the model establishment. In the second batch, compared with that of N group at the same time point, PWTs of rats in both CFA and EA group obviously decreased after the model establishment (both P<0.01). PWTs of rats in EA group which accepted EA treatment once were longer than those before EA treatment and corresponding PWTs in CFA group at the same time point (both P<0.01). Moreover, the numbers of p-ERK1/2 positive cells of affected SCDH increased significantly in CFA group at 6 h after the model establishment (P<0.01), however, which were decreased significantly in EA group (P<0.01).</p><p><b>CONCLUSION</b>Inhibiting ERK1/2 activation of SCDH may be one of the pivotal mechanism of cellular signal transduction of the immediate analgesic effect educed by EA.</p>

The reconstruction of erectile function with rabbit segmental gracilis musculocutaneous flap / 中华整形外科杂志

<p><b>OBJECTIVE</b>To design an animal model for the reconstruction of penile erectile function with segmental gracilis musculocutaneous flap.</p><p><b>METHODS</b>The rabbit gracilis muscle was split longitudinally into two approximately equal halves completely according to the principles of muscle compartmentalization. An animal model was designed for the reconstruction of erectile function with segmental musculocutaneous flap based on the anterior gracilis muscle bundle, with a silicone stick implanted as a supporter. A multi-channel physiological signal acquisition and processing system were used to stimulate the reconstructed penis and its CMAP was measured synchronously.</p><p><b>RESULTS</b>When its nerve was electric stimulated, the muscle bundle contracted, which made the reconstructed penis moving accordingly. It satisfactorily simulated the way of a normal penis's erection.</p><p><b>CONCLUSIONS</b>The reconstructed penis with rabbit segmental gracilis musculocutaneous flap according to the principles of muscle compartmentalization has achieved the erectile function satisfactorily. It has met the requirements of both improving reconstructive penis's appearance and retaining muscle' s contractive function.</p>