Clinical Observation of Treating Ulcerative Colitis with Acupuncture at Front Mu Points Combined with Oral Mesalazine / 昆明医科大学学报

Objective To observe the clinical efficacy of acupuncture at Front Mu point in the treatment of ulcerative colitis.Methods Sixty patients with ulcerative colitis treated at the Traditional Chinese Medicine Hospital in Kunming from August 2022 to June 2023 were collected.Using a random number table method,30 cases were assigned to each of the control group and the combined group.The treatment method involved administering oral mesalazine to the control group for a continuous period of 8 weeks,while the combined group received both oral mesalazine and acupuncture at front Mu points.The clinical efficacy,colonoscopy results score(Baron score),and colonic mucosal healing score(Geboes)before and after treatment were compared.Follow-up was conducted at 3 months to calculate the recurrence rate in the combination and control groups.Results The total effective rate in the combination group was higher than that in the control group(P<0.05),with rates of 93.33%and 67.67%,respectively.After treatment,the disease activity index,Baron score,and Geboes score decreased compared to before treatment(P<0.05),and the combination group had a lower disease activity index,Baron score,and Geboes score than the control group after treatment(P<0.05).Comparing the recurrence rates at 3 months post-treatment,the combination group was lower than the control group.Conclusion Acupuncture at Front Mu Point can significantly improve the clinical symptoms of ulcerative colitis,reduce the recurrence rate compared to patients in the control group,and is safe and reliable without serious adverse reactions.

Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism: WLB-73502, an analgesic with improved efficacy and safety profile compared to strong opioids

Opioids are the most effective painkillers, but their benefit-risk balance often hinder their therapeutic use. WLB-73502 is a dual, bispecific compound that binds sigma-1 (S1R) and mu-opioid (MOR) receptors. WLB-73502 is an antagonist at the S1R. It behaved as a partial MOR agonist at the G-protein pathway and produced no/unsignificant β-arrestin-2 recruitment, thus demonstrating low intrinsic efficacy on MOR at both signalling pathways. Despite its partial MOR agonism, WLB-73502 exerted full antinociceptive efficacy, with potency superior to morphine and similar to oxycodone against nociceptive, inflammatory and osteoarthritis pain, and superior to both morphine and oxycodone against neuropathic pain. WLB-73502 crosses the blood-brain barrier and binds brain S1R and MOR to an extent consistent with its antinociceptive effect. Contrary to morphine and oxycodone, tolerance to its antinociceptive effect did not develop after repeated 4-week administration. Also, contrary to opioid comparators, WLB-73502 did not inhibit gastrointestinal transit or respiratory function in rats at doses inducing full efficacy, and it was devoid of proemetic effect (retching and vomiting) in ferrets at potentially effective doses. WLB-73502 benefits from its bivalent S1R antagonist and partial MOR agonist nature to provide an improved antinociceptive and safety profile respect to strong opioid therapy.

Monoclonal antibody targeting mu-opioid receptor attenuates morphine tolerance via enhancing morphine-induced receptor endocytosis / 药物分析学报

Morphine is a frequently used analgesic that activates the mu-opioid receptor(MOR),which has prominent side effects of tolerance.Although the inefficiency of morphine in inducing the endocytosis of MOR underlies the development of morphine tolerance,currently,there is no effective therapy to treat morphine tolerance.In the current study,we aimed to develop a monoclonal antibody(mAb)precisely targeting MOR and to determine its therapeutic efficacy on morphine tolerance and the underlying molecular mechanisms.We successfully prepared a mAb targeting MOR,named 3A5C7,by hybridoma technique using a strategy of deoxyribonucleic acid immunization combined with cell immunization,and identified it as an immunoglobulin G mAb with high specificity and affinity for MOR and binding ability to antigens with spatial conformation.Treatment of two cell lines,HEK293T and SH-SY5Y,with 3A5C7 enhanced morphine-induced MOR endocytosis via a G protein-coupled receptor kinase 2(GRK2)/β-arrestin2-dependent mechanism,as demonstrated by immunofluorescence staining,flow cytometry,Western blotting,coimmunoprecipitation,and small interfering ribonucleic acid(siRNA)-based knock-down.This mAb also allowed MOR recycling from cytoplasm to plasma membrane and attenuated morphine-induced phosphorylation of MOR.We established an in vitro morphine tolerance model using differentiated SH-SY5Y cells induced by retinoic acid.Western blot,enzyme-linked immunosorbent assays,and siRNA-based knockdown revealed that 3A5C7 mAb diminished hyperactivation of adenylate cyclase,the in vitro biomarker of morphine tolerance,via the GRK2/β-arrestin2 pathway.Furthermore,in vivo hotplate test demonstrated that chronic intrathecal administration of 3A5C7 significantly alle-viated morphine tolerance in mice,and withdrawal jumping test revealed that both chronic and acute 3A5C7 intrathecal administration attenuated morphine dependence.Finally,intrathecal electroporation of silencing short hairpin RNA illustrated that the in vivo anti-tolerance and anti-dependence efficacy of 3A5C7 was mediated by enhanced morphine-induced MOR endocytosis via GRK2/β-arrestin2 pathway.Collectively,our study provided a therapeutic mAb,3A5C7,targeting MOR to treat morphine tolerance,mediated by enhancing morphine-induced MOR endocytosis.The mAb 3A5C7 demonstrates promising translational value to treat clinical morphine tolerance.

Supplementing early pulmonary rehabilitation with acupuncture can better promote recovery from stroke-associated pneumonia / 中华物理医学与康复杂志

Objective:To observe any therapeutic effect of combining early pulmonary rehabilitation training with acupuncture at the back-shu and front-mu acupoints in treating stroke-associated pneumonia (SAP).Methods:Eighty SAP patients were randomly divided into a treatment group and a control group, each of 40. Both groups were given routine symptomatic treatment for pneumonia, nutritional support, lipid-lowering and anti-infection measures, as well as acupuncture at the back-shu and front-mu acupoints. The treatment group additionally received pulmonary rehabilitation training. Before and after 14 days of the treatment, both groups were evaluated in terms of their forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), peak flow rate (PEF), white blood cell count (WBC), C-reactive protein (CRP), and procalcitonin (PCT). Chinese medicine (TCM) scores for expectoration of phlegm, shortness of breath, pulmonary rales, cough, fever and weakness were also assigned. The duration of antibiotic use and intensive care unit (ICU) stay were compared between the two groups.Results:Treatment efficacy was significantly higher in the treatment group (97.5%) than in the control group (85.0%). The treatment group′s average duration of antibiotic use and ICU stay were significantly shorter than in the control group. The treatment improved the average FVC, FEV1, PEF, WBC, CRP and PCT of both groups significantly leaving the average FVC and PEF of the treatment group significantly higher than the control group′s average, but its average WBC, CRP, PCT and the total TCM syndrome score significantly lower.Conclusions:Combining early pulmonary rehabilitation training with acupuncture at the back-shu and front-mu acupoints has a definite therapeutic effect on SAP patients. It can significantly shorten the use of antibiotics and ICU stay, promote the recovery of lung function, reduce inflammation and relieve clinical symptoms.

Effect of endomorphin 2 on expression of μ⁃opioid receptors in the dorsal root ganglion in rats with neuropathic pain / 安徽医科大学学报

Objective @#To explore the expression of the μ⁃opioid receptor ( MOR) and the effects of intracellular vesicle transport on the MOR expression during endomorphin 2 ( EM2) analgesia. @*Methods @# Adult male SD rats were randomly divided into 3 groups : control (naive) group , neuropathic pain group and drug group. Spared nerve injury (SNI) induced neuropathic pain rats were employed as the pain model. The drug group rats were the SNI pain ones intrathecally injected with EM2. The methods of immunofluorescence single staining and Western blot were used to detect the expression of MOR total protein , phosphorylated protein and Rab7 protein. Immunofluorescence double staining was used to detect the expression of MOR/Rab7 and MOR/LAMP1 co⁃labeled immunoreactivity.@*Results @#Compared with the control group , the expression of total MOR protein and phosphorylated protein in the dorsal root ganglion (DRG) of the SNI pain rats decreased (P < 0. 05) , and the expression of Rab7 significantly increased (P < 0. 05) . The expression of MOR/Rab7 co⁃labeled immunoreactivity in Rab7 and MOR immunoreactive ( Ⅳir) products and MOR/LAMP1 co⁃labeled immunoreactivity in MOR and LAMP1 ⁃ir products both increased (P < 0. 05) . Multiple intrathecal injection of EM2 significantly increased paw withdrawal threshold in the SNI neuropathic pain rats (P < 0. 01) , the expression of MOR protein and phosphorylated protein in DRG was increased (P < 0. 05) , while the expression of Rab7 decreased (P < 0. 05) . Compared with the control group , the expression of MOR/Rab7 positive products in Rab7 and MOR positive ones decreased , and the expression of MOR/LAMP1 positive products in LAMP1 and MOR positive markers decreased ( P < 0. 05 ) . @*Conclusion @#In the process of analgesia , EM2 inhibits the expression of Rab7 in the DRG of SNI neuropathic pain rats , reduces the transport of MOR to lysosomes , and promotes the re⁃sensitization of MOR.

Single - nucleotide polymorphisms of artemisinin resistance - related Pfubp1 and Pfap2mu genes in Bioko Island, Equatorial Guinea from 2018 to 2020 / 中国血吸虫病防治杂志

Objective To investigate the prevalence of single nucleotide polymorphisms (SNPs) of artemisinin resistance-related Pfubp1 and Pfap2mu genes in Plasmodium falciparum isolates from Bioko Island, Equatorial Guinea, so as to to provide baseline data for the formulation of malaria control strategies in Bioko Island. Methods A total of 184 clinical blood samples were collected from patients with P. falciparum malaria in Bioko Island, Equatorial Guinea from 2018 to 2020, and genomic DNA was extracted. The Pfubp1 and Pfap2mu gene SNPs of P. falciparum were determined using a nested PCR assay and Sanger sequencing, and the gene sequences were aligned. Results There were 159 wild-type P. falciparum isolates (88.83%) from Bioko Island, Equatorial Guinea, and 6 SNPs were identified in 20 Pfubp1-mutant P. falciparum isolates (11.17%), in which 4 non-synonymous mutations were detected, including E1516G, K1520E, D1525E, E1528D. There was only one Pfubp1gene mutation site in 19 Pfubp1-mutant P. falciparum isolates (95.00%), in which non-synonymous mutations accounted for 68.42% (13/19). D1525E and E1528D were identified as major known epidemic mutation sites in the Pfubp1 gene associated with resistance to artemisinin-based combination therapies (ACTs). At amino acid position 1525, there were 178 wild-type P. falciparum isolates (99.44%) and 1 mutant isolate (0.56%), with such a mutation site identified in blood samples in 2018, and at amino acid position 1528, there were 167 wild-type P. falciparum isolates (93.30%) and 12 mutant isolates (6.70%). The proportions of wild-type P. falciparum isolates were 95.72% (134/140), 79.25% (126/159) and 95.83% (161/168) in the target amplification fragments of the three regions in the Pfap2mu gene (Pfap2mu-inner1, Pfap2mu-inner2, Pfap2mu-inner3), respectively. There were 16 different SNPs identified in all successfully sequenced P. falciparum isolates, in which 7 non-synonymous mutations were detected, including S160N, K199T, A475V, S508G, I511M, L595F, and Y603H. There were 7 out of 43 Pfap2mu-mutant P. falciparum isolates (16.28%) that harbored only one gene mutation site, in which non-synonymous mutations accounted for 28.57% (2/7). For the known delayed clearance locus S160N associated with ACTs, there were 143 wild-type (89.94%) and 16 Pfap2mu-mutant P. falciparum isolates (10.06%). Conclusions Both Pfubp1 and Pfap2mu gene mutations were detected in P. falciparum isolates from Bioko Island, Equatorial Guinea from 2018 to 2020, with a low prevalence rate of Pfubp1 gene mutation and a high prevalence rate of Pfap2mu gene mutation. In addition, new mutation sites were identified in the Pfubp1 (E1504E and K1520E) and Pfap2mu genes (A475V and S508G).

Exploration of the diagnosis and treatment for benign prostatic hyperplasia with acupuncture based on jingjin theory / 中国针灸

Benign prostatic hyperplasia is caused by kidney deficiency and impaired qi transformation of the urinary bladder and is manifested by the stagnation of essence chamber. Based on jingjin (muscle region of meridian, sinew/fascia) theory and taking the visceral membrane as the principal, acupuncture is delivered at sinew/fascia to promote qi circulation, resolve stasis and open the orifice. Guided by CT, the needle is inserted at Zhongji (CV 3), the front-mu point of the urinary bladder, and then goes to the prostatic capsule, meaning "the disease of zang organ is treated by needling the front-mu point". In treatment of benign prostatic hyperplasia, this acupuncture therapy stimulates the different layers of fascia, by which, the defensive qi on the exterior is regulated and "essence orifice" in the interior is adjusted so that the urination can be promoted.

Effect of electroacupuncture on enteric neuronal autophagy in functional constipation mice / 中国针灸

OBJECTIVES@#To explore the effect mechanism of electroacupuncture (EA) on functional constipation (FC) at the combined lower he-sea and front-mu points of large intestine based on enteric neuronal autophagy.@*METHODS@#A total of 40 SPF Kunming mice were randomly divided into 5 groups (n = 8), i.e. a control group, a model group, an acupuncture group, a 3-methyl adenine (3-MA) group, and a 3-MA + acupuncture group. Except the control group, the FC model was established by gavage with compound diphenoxylate suspension for 14 days in the other 4 groups. After successful modeling, the mice of the acupuncture group and the 3-MA + acupuncture group received EA at bilateral "Tianshu" (ST 25) and "Shangjuxu" (ST 37), stimulated for 30 min with disperse-dense wave, 2 Hz/15 Hz of frequency, 1 mA of intensity. EA was delivered once daily. One course of treatment was composed of 5 days and 2 courses were needed, with an interval of 2 days. An intraperitoneal injection of 3-MA (15 mg/kg) was administered 30 min before EA in the mice of the 3-MA group and the 3-MA + acupuncture group, once daily. Before and after intervention, the time of the first black stool defecation and defecation behaviors in 6 h were observed in each group. After intervention, in every group, the small intestine propulsion rate was calculated, the colon tissue morphology was observed using HE staining, the ultrastructure of enteric neuronal autophagy was observed under transmission electron microscope, and the expressions of microtubule-associated protein 1 light chain 3 (LC3), Beclin-1 and neuronal nuclear antigen protein (NeuN) in neurons of colonic muscularis were determined by immunohistochemistry.@*RESULTS@#Before intervention, when compared with those in the control group, the time of the first black stool defecation was prolonged (P<0.01, P<0.05), and numbers (P<0.01), wet weight (P<0.01, P<0.05) and water content (P<0.05, P<0.01) of stool in 6 h were reduced in the model, acupuncture, 3-MA and 3-MA + acupuncture groups. After intervention, compared with those in the control group, the time of the first black stool defecation was longer (P<0.05), and numbers (P<0.01), wet weight (P<0.01) and water content (P<0.01) of stool in 6 h were decreased in the model group. The time of the first black stool defecation was shortened (P<0.01), and numbers (P<0.01), wet weight (P<0.01) and water content (P<0.01) of stool in 6 h were increased in the acupuncture group when compared with those in the model group. The time of the first black stool defecation was extended (P<0.01), and numbers (P<0.01), wet weight (P<0.01) and water content (P<0.01) of stool in 6 h were declined in the 3-MA + acupuncture group in comparison with those in the acupuncture group. All layers of colon tissue were normal and intact in each group. When compared with the control group, the small intestine propulsion rate and the average optical density (OD) values of LC3, Beclin-1 and NeuN in neurons of colonic muscularis were decreased (P<0.01), and autophagosomes were dropped in the model group. In the acupuncture group, the small intestine propulsion rate and the average OD values of NeuN, LC3 and Beclin-1 in neurons of colonic muscularis increased (P<0.01,P<0.05), and autophagosomes were elevated when compared with those in the model group. The small intestine propulsion rate and the average OD values of NeuN, LC3 and Beclin-1 in neurons of colonic muscularis were dropped (P<0.05,P<0.01) in the 3-MA + acupuncture group in comparison with those in the acupuncture group.@*CONCLUSIONS@#Electroacupuncture may promote enteric neuronal autophagy and increase the number of neurons so that the intestinal motility can be improved and constipation symptoms can be relieved in FC mice.

Clinical application and research progress of angle Kappa in ophthalmic surgery / 国际眼科杂志(Guoji Yanke Zazhi)

The human eye has various axes and angles, of which the angle Kappa is an important indicator of the centrality of the human eye and is widely used in ophthalmic surgery. Proper preoperative evaluation and application of the angle Kappa facilitated the achievement of optimal postoperative visual quality. Chord mu is a new term that has emerged recently to better express the angle Kappa. The two concepts are not well understood clinically, limiting their usefulness. Therefore, to better understand the angle Kappa and chord mu, the definitions and connections between them are presented separately in this paper. Meanwhile, the application of angle Kappa in strabismus surgery was summarized, the method for compensating large angle Kappa in corneal refractive surgery and the clinical significance of angle Kappa in predicting postoperative centrality of multifocal intraocular lens(MIOL)in phacoemulsification combined with MIOL implantation were discussed, with a view to providing references for clinical work.

Determining the protective effects of Ma-Mu-Ran Antidiarrheal Capsules against acute DSS-induced enteritis using 16S rRNA gene sequencing and fecal metabolomics / 中国天然药物

Ma-Mu-Ran Antidiarrheal Capsules (MMRAC) is traditional Chinese medicine that has been used to treat diarrhea caused by acute enteritis (AE) and bacillary dysentery in Xinjiang (China) for many years. However, the potential therapeutic mechanism of MMRAC for AE and its regulatory mechanism on host metabolism is unclear. This study used fecal metabolomics profiling with GC/MS and 16S rRNA gene sequencing analysis to explore the potential regulatory mechanisms of MMRAC on a dextran sulfate sodium salt (DSS)-induced mouse model of AE. Fecal metabolomics-based analyses were performed to detect the differentially expressed metabolites and metabolic pathways. The 16S rRNA gene sequencing analysis was used to assess the altered gut microbes at the genus level and for functional prediction. Moreover, Pearson correlation analysis was used to integrate differentially expressed metabolites and altered bacterial genera. The results revealed that six intestinal bacteria and seven metabolites mediated metabolic disorders (i.e., metabolism of amino acid, carbohydrate, cofactors and vitamins, and lipid) in AE mice. Besides, ten altered microbes mediated the differential expression of eight metabolites and regulated these metabolisms after MMRAC administration. Overall, these findings demonstrate that AE is associated with metabolic disorders and microbial dysbiosis. Further, we present that MMRAC exerts protective effects against AE by improving host metabolism through the intestinal flora.

Research progress of Guizhi Shaoyao Zhimu Decoction in the treatment of rheumatoid arthritis / 国际中医中药杂志

Guizhi Shaoyao Zhimu Decoction combined with drugs taken internally or external therapy show the benefits for rheumatoid arthritis patients. It can control the clinical symptoms such as swelling and pain of the joints, reduce inflammatory indicators, and has less adverse reactions. Modern pharmacological researches show that it can regulate a variety of inflammatory signaling pathways to achieve anti-inflammatory and analgesic effects, induce apoptosis of synovial cells, resist bone damage, and regulate immunity with multiple treatment targets to rheumatoid arthritis.

Multisystem inflammatory syndrome in children

@#Multisystem inflammatory syndrome in children (MIS-C) is a condition which is associated with Coronavirus that mimics Kawasaki Disease (KD) where organ dysfunction is evident which includes the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal organs. This report describes the first case of Multisystem Inflammatory Syndrome in children in Region 1. Our patient is a 3 year old female who presented with sudden onset of high grade fever, abdominal pain and diarrhea, a month after recovering from COVID-19 infection. On admission, the patient was irritable, febrile with conjunctiva! erythema, reddish dry lips, slightly distended and non-tender abdomen, erythematous rash over umbilicus, feet and hands, minimal edema of hands and feet. Laboratories requested showed elevated inflammatory markers, elevated BNP, Troponin I, elevated D-dimer, fibrinogen and prolonged activated partial thromboplastin time (APTT) and prothrombin time (PT) (Appendix A,B,C,H). 2Dechocardiography showed left ventricular dysfunction, moderate mitral regurgitation, minimal pericardia! effusion and right coronary artery ectasia (Appendix F). On second hospital day, she had hypotension hence was transferred to Intensive Care Unit which required initiation of inotropes and close care monitoring. Intravenous lmmunoglobulin (IVlg) and corticosteroids were also started. She was discharged stable and improved on seventh hospital day with a repeat 2D-echocardiogram showing improved left ventricular function and decrease in right coronary artery dilation. Prompt recognition of this syndrome allows clinicians to acquire appropriate laboratory testing, initiate treatment and provide families with accurate prognostic information.

Masterpiece of reconstruction of theoretical system of traditional Chinese medicine-revelation of / 中国针灸

For the first time, at the early Ming Dynasty, the theoretical system of traditional Chinese medicine (TCM) are integrated with clinical diagnosis and treatment system in

Application and clinical significance of TCGA molecular classification in endometrial cancer / 中华妇产科杂志

Objective:To explore the application and clinical significance of the cancer genome atlas (TCGA) molecular classification in endometrial cancer (EC).Methods:Sixty-six EC patients collected from December 2018 to March 2021 from Peking University People′s Hospital were categorized into four subgroups based on TCGA molecular classification tested by next generation sequencing. The correlation among four molecular subgroups and the clinical-pathological features including prognosis were analyzed.Results:(1) Clinical and pathological features: median age at diagnosis was 56 years (range: 24-78 years). The cases were distributed as follows: 3 (5%) cases DNA polymerase epsilon (POLE) ultra-mutated, 11 (17%) cases high microsatellite instability (MSI-H) including 2 Lynch syndrome, 42 (64%) cases low copy-number (CN-L) and 10 (15%) cases high copy-number (CN-H). There were significant differences among four subtypes in the combination of other tumors, tumor family history, surgical method, International Federation of Gynecology and Obstetrics (FIGO, 2009) stage, depth of muscle invasion and lymph vascular space invasion (all P<0.05). The proportions of patients in CN-H subgroup with advanced FIGO stage (stage Ⅲ-Ⅳ), deep muscle invasion and positive lymph-vascular space invasion were significantly increased. There were no significant differences in age, menopausal status, body mass index, metabolic syndrome-related complications, preoperative serum CA 125 and human epididymis protein 4 levels, tumor size, pathological grade (only endometrioid cancer), and lymph node metastasis among the 4 TCGA molecular types (all P>0.05). (2) Immuno-related molecular analysis: among 66 EC patients, 27 patients underwent immunohistochemical analysis of programmed cell death 1 ligand 1 (PD-L1) protein, and 28 patients underwent tumor mutation burden (TMB) detection. POLE and MSI-H subgroups contained TMB than those in CN-L and CN-H ( P<0.05).(3) Prognosis: the median follow-up time was 10 months (range: 0-28 months). The progression-free survival rate of TCGA molecular types were 100% (POLE ultra-mutated), 100% (MSI-H), 98% (CN-L), and 80% (CN-H) respectively and had significant differences ( P=0.034). The overall survival were 100% (POLE ultra-mutated), 100% (MSI-H), 98% (CN-L), and 90% (CN-H) respectively, but there were not statistically significant difference ( P=0.361). POLE ultra-mutated and MSI-H subgroups had the best survival, while CN-H had the worst. Conclusion:TCGA molecular classification has feasibility and clinical value in clinical application of EC, which is helpful to identify the prognosis of patients.

Study on Electromagnetic Interference Risk of Active Implantable Medical Devices in Multiple Unit Environment / 中国医疗器械杂志

Concerning on the safety risks caused by electromagnetic interference of patients implanted with high-risk active implantable medical devices in the environment of domestic MUs, this study evaluates and focuses on the requirements of electromagnetic compatibility in domestic and international standards for rail transit vehicles, the main mechanism of risks caused by EMI, the actual measurement of environmental data in MUs and the working performance of various active implantables in the compartment. The test results shows that all kinds of active implantable medical device samples works normally in the CRH2A EMU in China, and there is still a large margin between the measured radiation emission in MU and the limit required by the standards.

Mu-Opioid Receptors Expressed in Glutamatergic Neurons are Essential for Morphine Withdrawal / 神经科学通报·英文版

Although opioids still remain the most powerful pain-killers, the chronic use of opioid analgesics is largely limited by their numerous side-effects, including opioid dependence. However, the mechanism underlying this dependence is largely unknown. In this study, we used the withdrawal symptoms precipitated by naloxone to characterize opioid dependence in mice. We determined the functional role of mu-opioid receptors (MORs) expressed in different subpopulations of neurons in the development of morphine withdrawal. We found that conditional deletion of MORs from glutamatergic neurons expressing vesicular glutamate transporter 2 (Vglut2) largely eliminated the naloxone-precipitated withdrawal symptoms. In contrast, conditional deletion of MORs expressed in GABAergic neurons had a limited effect on morphine withdrawal. Consistently, mice with MORs deleted from Vglut2 glutamatergic neurons also showed no morphine-induced locomotor hyperactivity. Furthermore, morphine withdrawal and morphine-induced hyperactivity were not significantly affected by conditional knockout of MORs from dorsal spinal neurons. Taken together, our data indicate that the development of morphine withdrawal is largely mediated by MORs expressed in Vglut2 glutamatergic neurons.

Comparative study on effect of electroacupuncture at lower -sea point of stomach and -sea matching front- points for gastroparesis / 中国针灸

OBJECTIVE@#To explore the efficacy difference of electroacupuncture at lower -sea point and -sea matching front- points for the treatment of gastroparesis.@*METHODS@#A total of 63 patients with gastroparesis were randomly divided into a lower point group (group A, 32 cases, 2 cases dropped off) and a matching points group (group B, 31 cases, 1 case dropped off). The group A was treated with electroacupuncture at Zusanli (ST 36), and the group B was treated with electroacupuncture at Zusanli (ST 36) and Zhongwan (CV 12). Both groups were treated with continuous wave (2 Hz in frequency) for 30 min, once a day, 5 times a week for 3 weeks. The gastroparesis cardinal symptom index (GCSI) score, gastric half-emptying time (T) and the 180 min gastric residual rate of the two groups before and after treatment were observed, and the clinical effective rate was compared.@*RESULTS@#After treatment, the total GCSI scores, T and the 180 min gastric residual rates in both groups were lower than those before treatment (<0.01), and the 180 min gastric residual rate and T in the group A were lower than those in the group B (<0.05). The total effective rate was 93.3% (28/30) in the group A, which was superior to 70.0% (21/30) in the group B (<0.05).@*CONCLUSION@#Electroacupuncture at lower -sea point and -sea matching front- points can both be used to treat gastroparesis, but electroacupuncture at Zusanli (ST 36) has a better effect. The acupoints of Zusanli (ST 36) and Zhongwan (CV 12) may have antagonistic effects.

Efficacy and mechanism of acupuncture combined with for diarrhea-type irritable bowel syndrome of liver depression and spleen deficiency / 中国针灸

OBJECTIVE@#To observe the clinical effect of acupuncture at lower- acupoints and front- acupoints combined with (TXYF) for diarrhea-type irritable bowel syndrome (IBS-D) of liver depression and spleen deficiency, and to explore its possible mechanism.@*METHODS@#A total of 123 IBS-D patients with syndrome of liver depression and spleen deficiency were randomly divided into an acupuncture+TXYF group, a TXYF group and a medication group, 41 cases in each group. The patients in TXYF group were treated with oral administration of TXYF, three times a day. The patients in acupuncture+TXYF group were treated with oral administration of TXYF and routine acupuncture at Shangjuxu (ST 37), Tianshu (ST 25), Taichong (LR 3), Sanyinjiao (SP 6) and Zusanli (ST 36), once a day. The patients in medication group were treated with oral administration of pinaverium bromide, 50 mg, three times a day. All the treatment was given for four weeks. The total score of TCM syndrome scale, self-rating anxiety scale (SAS), self-rating depression scale (SDS) scores as well as the expression of calcitonin gene-related peptide (CGRP), vasoactive peptide (VIP) and MAPK signal pathway indicators of ERK1 mRNA and ERK2 mRNA were compared before and after treatment; the clinical effect was also compared.@*RESULTS@#After treatment, the total score of TCM syndrome scale and SAS and SDS scores in each group were significantly reduced (<0.05), and the scores in the acupuncture+TXYF group were lower than those in TXYF group and medication group (<0.05). The total effective rate was 87.8% (36/41) in the acupuncture+TXYF group, which was higher than 78.0% (32/41) in the TXYF group and 68.3% (28/41) in the medication group (<0.05). After treatment, the levels of CGRP and VIP in each group were decreased (<0.05), and the levels in the acupuncture+TXYF group were lower than those in the TXYF group and the medication group (<0.05). After treatment, the levels of ERK1 mRNA and ERK2 mRNA in each group were decreased (<0.05), and the levels in acupuncture+TXYF group were lower than those in medication group (<0.05).@*CONCLUSION@#The acupuncture at lower- acupoints and front- acupoints combined with TXYF could effectively alleviate the clinical symptoms, improve anxiety and depression in IBS-D patients with syndrome of liver depression and spleen deficiency, and its mechanism may be related to regulating the expression of ERK1 mRNA and ERK2 mRNA in MAPK signaling pathway, and reducing the serum levels of CGRP and VIP.

Mu-Opioid Receptors Expressed in Glutamatergic Neurons are Essential for Morphine Withdrawal / 神经科学通报·英文版

Although opioids still remain the most powerful pain-killers, the chronic use of opioid analgesics is largely limited by their numerous side-effects, including opioid dependence. However, the mechanism underlying this dependence is largely unknown. In this study, we used the withdrawal symptoms precipitated by naloxone to characterize opioid dependence in mice. We determined the functional role of mu-opioid receptors (MORs) expressed in different subpopulations of neurons in the development of morphine withdrawal. We found that conditional deletion of MORs from glutamatergic neurons expressing vesicular glutamate transporter 2 (Vglut2) largely eliminated the naloxone-precipitated withdrawal symptoms. In contrast, conditional deletion of MORs expressed in GABAergic neurons had a limited effect on morphine withdrawal. Consistently, mice with MORs deleted from Vglut2 glutamatergic neurons also showed no morphine-induced locomotor hyperactivity. Furthermore, morphine withdrawal and morphine-induced hyperactivity were not significantly affected by conditional knockout of MORs from dorsal spinal neurons. Taken together, our data indicate that the development of morphine withdrawal is largely mediated by MORs expressed in Vglut2 glutamatergic neurons.

Mu-opioid receptors in the paraventricular nucleus regulate ejaculatory behaviors via the sympathetic nerve system in male rats / 中华男科学杂志

Objective@#To explore the effects of the mu-opioid receptor (MOR) in the paraventricular nucleus (PVN) on the ejaculatory behaviors of male rats and its potential mechanisms.@*METHODS@#Male SD rats with normal ejaculation ability were mated with female ones in hormone-induced estrus. After bilateral PVN microinjection of D-Ala-2-Me-Phe-4-Gly-ol enkephalin (DAGO) or D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) with an inserted catheter, the male animals were observed for mount latency (ML), mount frequency (MF), intromission latency (IL), intromission frequency (IF), ejaculation latency (EL), ejaculation frequency (EF), post-ejaculation interval (PEI), and intromission ratio (IR). The lumbar sympathetic nerve activity (LSNA) of the rats was recorded using the PowerLab data acquisition hardware device, and the levels of norepinephrine (NE) in the peripheral plasma were measured by ELISA following microinjection of saline or different doses of DAGO or CTAP.@*RESULTS@#Neither CTAP nor DGAO significantly affected the ML of the male rats (P > 0.05). DGAO remarkably increased IF (P < 0.01) and MF (P < 0.01), prolonged IL (P < 0.01), EL (P < 0.01) and PEI (P < 0.01), and reduced EF (P <0.01) and IR (P < 0.05). On the contrary, CTAP markedly decreased IF (P < 0.01) and MF (P < 0.01), shortened IL (P < 0.01), EL (P < 0.01) and PFI (P < 0.01), and elevated EF (P < 0.01) and IR (P < 0.01). Additionally, DAGO decreased LSNA in a dose-dependent manner and reduced the NE level in the peripheral plasma. CTAP, however, not only offset the effects of DAGO on LSNA, but also significantly increased LSNA.@*CONCLUSIONS@#MOR in PVN inhibits ejaculatory behaviors in male rats by weakening LSNA, which has provided some theoretical evidence for the use of highly selective opioids in the treatment of premature ejaculation.