Objective To discuss the treatment experience of adrenocorticotropic hormone independent macronodular adrenal hyperplasia (AIMAH).Methods The clinical data of 24 cases of AIMAH from August 1972 to December 2016 were retrospectively analyzed.The cases included 10 males and 14 females with a mean age of 43 (range 26 to 59) years.16 patients presented with typical Cushing syndrome (CS) and 8 patients had weight gain, hypertension or diabetes mellitus without any sign of CS.The circadian rhythm of serum cortisol was abnormal.Low and high dose dexamethasone suppression tests failed to suppress cortisol secretion.The preoperative CT scan showed bilateral enlargement of the adrenal glands with multiple macmnodules.14 patients underwent open surgery, including 5 cases of unilateral adrenalectomy, 6 cases of adrenalectomy combined with contralateral subtotal adrenalectomy and 3 cases of bilateral adrenalectomy simuhaneously.6 patients underwent conventional laparoscopic adrenalectomy,including 2 cases of unilateral adrenalectomy, 2 cases of adrenalectomy combined with contralateral subtotal adrenalectomy and 2 cases of bilateral adrenalectomy.4 patients underwent robot-assisted laparoscopic bilateral adrenalectomy.Results The postoperative pathological examination showed that all patients had bilateral adrenal macronodular or adenomatoid hyperplasia.During the mean follow-up of 68 months (range 3 to 192 months), the clinical symptoms of CS disappeared after surgery in all cases.7 patients who received unilateral adrenalectomy had urinary free cortisol and serum cortisol within normal ranges and no further enlargement of the contralateral gland was noticed.Among the 3 patients who received bilateral adrenalectomy simultaneously, 1 case died of adrenal crisis on the seventh day post-operation.The remaining 2 cases presented with adrenal insufficiency but returned to normal after glucocorticoid replacement therapy.Nelson's syndrome was not observed in other patients.Conclusions The use of bilateral adrenalectomy to treat AIMAH may involve risk.Unilateral adrenalectomy is recommended for an alternative treatment for AIMAH.Controlateral adrenalectomy with lifelong corticosteroid replacement or contralateral subtotal adrenalectomy may be performed if the symptoms have not improved or recurred after unilateral adrenalectomy.

This study is to evaluate the therapeutic effect of fibroblast growth factor 21 (FGF21) on NAFLD in MSG-IR mice and to provide mechanism insights into its therapeutic effect. The MSG-IR mice with insulin resistance were treated with high dose (0.1 micromol.kg-1d-1) and low dose (0.025 micromol.kg-1d-1) of FGF21 once a day for 5 weeks. Body weight was measured weekly. At the end of the experiment, serum lipids, insulin and aminotransferases were measured. Hepatic steatosis was observed. The expression of key genes regulating energy metabolism were detected by real-time PCR. The results showed that after 5 weeks treatment, both doses of FGF21 reduced body weight (P<0.01), corrected dyslipidemia (P<0.01), reversed steatosis and restored the liver morphology in the MSG model mice and significantly ameliorated insulin resistance. Additionally, real-time PCR showed that FGF21 significantly reduced transcription levels of fat synthetic genes, decreased fat synthesis and promoted lipolysis and energy metabolism by up-regulating key genes of lipolysis, thereby liver fat accumulation was reduced and liver function was restored to normal levels. In conclusion, FGF21 significantly reduces body weight of the MSG-IR mice, ameliorates insulin resistance, reverses hepatic steatosis. These findings provide a theoretical support for clinical application of FGF21 as a novel therapeutics for treatment of NAFLD.

The annual incidence of neurodegenerative disease has been increasing with the aging of the global population,seriously affecting the quality of life of elderly patients and imposing a heavy burden on society.Glycyrrhetinic acid,which inhibits neuroinflammation and protects neurons,is one of the main active ingredients of the traditional Chinese medicine Glycyrrhiza glabra.Increasing numbers of studies are focusing on the mechanism of action of glycyrrhetinic acid and its derivatives in neurodegenerative disease.This review summarizes studies on the effects and mechanisms of action of glycyrrhetinic acid and its derivatives in Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,multiple sclerosis,and cerebellar atrophy.Additionally,the future applications of glycyrrhetinic acid and its derivatives in neurodegenerative disorders are discussed.

Objective To explore the clinical efficacy and safety of off-clamping in robotic-assisted partial nephrectomy (RAPN) for the treatment of renal tumors.Methods From January 2015 to March 2017,the data of 48 patients who underwent off-clamping RAPN were reviewed retrospectively.There were 31 males and 17 females,and the mean age was 57 years (range:23-84 years).The mean tumor size was 3.1 cm (range:1.2-6.4 cm),with the upper,middle,and lower polar tumors account for 35.4％,27.1％,and 37.5％,respectively.The clinical tumor stage was T1N0M0 in all 48 cases,according to the AJCC tumor staging system for renal cancer.Results RAPNs were performed successfully in all 48 cases,without conversion to open surgery.In those patients,the application of off-clamping in robotic-assisted partial nephrectomy was performed in 44 cases.The renal artery and vein was exposed,dissected,isolated and then clamped in 4 cases due to bleeding.The mean surgical time was 85 min (range:75-185 min).The mean estimated blood loss was 134 ml (range:60-270 ml),and no blood transfusion was needed.The wound surface was closed using interrupted suture with Hem-o-lok clips securing each needle point.The mean time for renorrhaphy was 22 min (rang:11-31 min).No intraoperative severe complications such as vascular injury,trauma of abdominal organ occurred.There were 5 complications,including 2 cases of hematuria,2 cases of delayed healing of incision,and 1 case of pneumohypoderma.The pathological diagnosis included 40 cases of renal clear cell carcinoma,3 cases of papillary renal cell carcinoma,and 5 cases of angiomyolipomas.No tumor recurrence or distant metastasis was observed during the average follow-up of 17 months (range 3-27 months).Conclusions Off-clamping RAPN is safe and feasible approach to excise certain kidney tumors.It carries the benefits of less complication,quick recovery,and less ischemia reperfusion renal injury.Off-clamping RAPN would be suitable for those patients with solitary kidneys,renal insufficiency,and bilateral tumors.

The claustrum located between the striatum and cortex is composed of glutamate neurons and gamma-aminobutyric neurons. There are extensive and mutually projected nerve fiber connections between cerebral cortex and parietal nucleus. The claustrum integrates sensory information and regulates the formation of consciousness through various ways, playing an important role in sensory processing and cognitive functions. In this paper, the neuronal characteristics, fiber projection, physiological characteristics and consciousness integration function of the claustrum are reviewed to provide references for further understanding physiological and pathophysiological effects of the pterygoid nucleus.

Objective To explore the analgesic initiation mechanism of"three-manipulations and three-acupoints"of tuina on minor chronic constriction injury(minor CCI)model rats.Methods According to the random number table method,35 SD rats were randomly divided into five groups:normal group,sham group,model group,tuina group,and tuina+MK-801 group.The model group,tuina group,and tuina+MK-801 group were subjected to ligation of the right sciatic nerve trunk to establish a minor CCI rat model.The sham group was only exposed to the right sciatic nerve without ligation,and the normal group was not subjected to any operation.The normal group was not subjected to any intervention measures.On the seventh day after modeling,the model group and the sham group underwent 9 minutes of grasping restraint,while the tuina group underwent one intervention of three-manipulations(point method,dialing method,and kneading method)and three-acupoints(right"Yinmen"(BL37),"Chengshan"(BL57),and"Yanglingquan"(GB34)acupoints)with each manipulation and acupoint intervention for 1 minute for a total of 9 minutes.The tuina+MK-801 group received intrathecal injection of MK-801 from the fifth to seventh days after modeling,with a dose of 6 μg(10 μL)per day,tuina intervention was performed 30 minutes after the last intrathecal injection,and the specific operation of tuina was the same as that of the tuina group.Before modeling,after modeling,and after intervention,each group of rats was subjected to cold sensitivity threshold(CST)and mechanical withdrawal threshold(MWT)testing.After intervention,immunohistochemistry was used to detect the positive expression of cyclic guanosine monophosphate(cGMP)in the spinal dorsal horn(SDH)at L4-6 segments;protein expressions of N-methyl-D-aspartate receptor 1(NMDAR1),neurogenic nitric oxide synthase(nNOS),soluble guanylyl cyclase β(sGCβ),and protein kinase G1(PKG1)in SDH at L4-6 segments were detected by Western blotting;mRNA expressions of NMDAR1,nNOS,sGCβ,cGMP,and PKG1 in SDH at L4-6 segments were detected by real-time PCR.Results Compared with the normal and sham groups,after modeling,CST increased and MWT decreased in the model group,tuina group and tuina+MK-801 group(P＜0.05);after intervention,the positive protein expression of cGMP was increased,the protein expressions of NMDAR1,nNOS,sGCβ,and PKG1 were increased,and mRNA expressions of NMDAR1,nNOS,sGCβ,cGMP,and PKG1 were increased in SDH at L4-6 segments in the model group(P＜0.05).Compared with the model group,after intervention,CST decreased and MWT increased in the tuina group and tuina+MK-801 group(P＜0.05);the positive protein expression of cGMP was decreased,the protein expressions of NMDAR1,nNOS,sGCβ,and PKG1 were decreased,and mRNA expressions of NMDAR1,nNOS,sGCβ,cGMP,and PKG1 were decreased in SDH at L4-6 segments in the tuina group and tuina+MK-801 group(P＜0.05).Conclusion One-time tuina intervention can effectively improve the symptoms of thermal and mechanical hyperalgesia induced by peripheral nerve injury,which may initiate analgesia through the NMDAR1/cGMP/protein kinase G signaling pathway,thereby exerting immediate analgesic effect.

Objective:To investigate the changes in the hypothalamic metabolites of lipopolysaccharide(LPS)febrile young rabbits after the treatment with pediatric tuina.Methods:A total of 30 young rabbits were randomly assigned into three groups:the normal group,the model group,and the tuina group.Both the model group and the tuina group were injected intrave-nously with LPS."Six antipyretic manipulations"(pushing Tianmen,pushing Kangong,kneading Taiyang,kneading Erhougaogu,clearing Tianheshui,and pushing Jizhu)were administered 1 h after the LPS in-jection in the tuina group.The rectal temperatures of the young rabbits were monitored during the experiment to explore the antipyretic effect.Three hours after the injection,the content of interleukin-1 β(IL-1β),tumor necrosis factor(TNF)-α,and prostaglandin E2(PGE2)in the serum was detected.In addition,liquid chromatography-mass spectrometry(LC-MS)was used for the hypothalamus metabolomics.Results:Compared with the model group,the rectal temperature of the tuina group was decreased at 2 h and 3 h after the LPS injection(P=.04,P=.03,respectively),and the content of IL-1β,TNF-α,and PGE2 was decreased(P=.03,P=.003,and P=.008,respectively).The metabolomics results showed that there were 23 potential biomarkers after the tuina intervention,enriching 27 pathways.Lipid metabolites,especially glycerophospholipids,were a majority of the altered metabolites.The primary metabolic pathways affected by tuina included the arachidonic acid metabolism,the GABAergic synapse,D-gluta-mine and D-glutamate metabolism,and the glutamatergic synapse.Conclusion:Pediatric tuina reduced the temperature of the febrile rabbits and downregulated the expression of IL-1β,TNF-α,and PGE2,and the antipyretic mechanism may be related to changes in metabolites and metabolic pathways in the hypothalamus.

When antiphospholipid syndrome(APS)and neuropsychiatric systemic lupus erythematosus(NPSLE)involve the central nervous system,the two diseases tend to have similar clinical symptoms and auxiliary examination re-sults and different diagnosis and treatment strategies,which may lead to potential misdiagnosis and mistreatment.This ar-ticle analyzes the causes of misdiagnosis and performs a literature review.A retrospective analysis was performed for one patient with thrombocytopenia and stroke as initial symptoms.The patient was initially diagnosed with NPSLE and was treated with hydroxychloroquine,glucocorticoids,mycophenolate mofetil to induce remission,and aspirin was given to prevent platelet aggregation.Subsequently,the patient developed a positive spectrum of antiphospholipid antibodies and venous thrombosis;therefore,the patient was diagnosed with APS and was given maintenance treatment with hydroxychlo-roquine and low-dose glucocorticoids and sequential therapy with low-molecular-weight heparin as an anticoagulant and in-dobufen for antiplatelet aggregation therapy.The patient had stable conditions without recurrence during follow-up for 5 months.Recognizing the initial symptoms and thrombotic events is crucial for the early diagnosis of APS and NPSLE.Fur-ther studies are needed to explore the long-term efficacy of indobufen as an alternative to aspirin in APS.

Objective To explore the analgesic initiation mechanism of three-manipulation and three-acupoint tuina in model rats with minor chronic constriction injury(CCI).Methods Fifty-six SD rats were divided randomly into eight groups:normal group,sham group,model 1 group,model 2 group,tuina 1 group,tuina 2 group,tuina 1+transient receptor potential vanilloid-1(TRPV1)antagonist group,and tuina 2+transient receptor potential ankyrin 1(TRPA1)antagonist group.The model,tuina,and tuina+antagonist groups were established with minor CCI models.The tuina and tuina+antagonist groups received the three-method three-point intervention(point method,dial method,kneading method,Yinmen point,Chengshan point,Yanglingquan point)7 days after modeling.The model and sham groups were subjected to grasping restraint,and the normal group received no intervention.After the respective interventions,each group was tested for changes in mechanical withdrawal threshold(MWT)and thermal withdrawal latency(TWL)to detect different types of pain.The nitric oxide(NO)content of the dorsal root ganglion(DRG)was determined by the nitrate reductase method,and changes in protein and gene expression levels of components of the TRPV1/TRPA1-NO-cGMP-protein kinase G(PKG)signaling pathway in the DRG of each group were determined by enzyme-linked immunosorbent assay,Western blot,and qPCR.Results Compared with the model group,MWT and TWL were prolonged in the tuina 1 and tuina 2 groups.Expression levels of TRPV1,TRPA1,NO,soluble guanylate cyclase-β,cGMP,and PKG1 in the DRG were significantly decreased in the tuina 1,tuina 2,tuina 1+TRPV1 antagonist,and tuina 2+TRPA1 antagonist groups.Conclusions Tuina can effectively improve the symptoms of thermal and mechanical hyperalgesia caused by peripheral nerve injury after one-time intervention.Tuina can exert immediate and continuous analgesic effects via the TRPV1/TRPA1-NO-cGMP-PKG signaling pathway.

The medial prefrontal cortex engages in various higher brain functions,including attention,transition of consciousness,and information integration,and is the central structure for the action of general anesthetics.In addition,it is considered both the end point for the bottom-up model of the layer-by-layer transmission of information and the starting point for the top-down modulation and integration of information.Classically,the medial prefrontal cortex can be divided into six layers of different functions in the vertical direction,and there are rich neural connections among the layers.In this review,we describe the laminar flow structures found in the medial prefrontal cortex,then discuss how general anesthetics change consciousness via the cortical laminar flow structures.To this aim,the article reviews the available evidence from current studies using rodents,primates,and human subjects that highlight the role of the medial prefrontal cortex in anesthesia.