Objective To study the role of ubiquitin-conjugating enzyme 9(UBC9)in the pyroptosis of homocysteine-induced macrophages mediated by small ubiquitin-like modifier(SUMO)modification.Methods First,the effects of homocysteine at different concentrations(0 μmol/L,50 μ.mol/L,100 μmol/L,150 μmol/L and 200 μmol/L)on the viability and pyrodeath of mouse macrophages(RAW264.7)were detected by CCK-8 and Western blot.Western blot was used to detect the expression levels of UBC9,SUMO-1,and the inflammatory cytokine IL-1β in different groups of cells.qRT-PCR was used to detect the mRNA expression of UBC9 before and after RNA interference and the expression of UBC9,pyrogen-related protein,and SUMO-1 after RNA interference.Results After stimulation with 100 μmol/L homocysteine,the effect of macrophage activity was minimal,and NLRP3 and Caspase-1 were the proteins with the most obvious increase in expression(P＜0.05).Compared with the Control group,the Hcy group's expression of IL-1β and SUMO-1 was increased(P＜0.01).Compared with the Control group,the Hcy group's UBC9 protein and mRNA levels were increased(P＜0.05).The expression of NLRP3,Caspase-1,IL-1β,UBC9,and SUMO-1 was decreased in the si-UBC9+Hcy group compared with the si-NC+Hcy group(P＜0.01).Conclusions Homocysteine induces pyroptosis in macrophages,and its mechanism of action is related to the up-regulation of UBC9 to induce SUMO modification.

Objective Through factor analysis of the quantified syndrome information of 558 cases of kidney yang deficiency syndrome,the constructing feature of kidney yang deficiency syndrome was revealed,which provides clinical data support for the objectification,standardization and normalization of kidney Yang deficiency syndrome.Methods Firstly,the frequency analysis of symptoms,tongue and pulse signs of 558 patients with kidney Yang deficiency syndrome was carried out,and then the main syndrome information of the patients with kidney Yang deficiency syndrome was quantified.Finally,the common factors and their representative variables of kidney Yang deficiency syndrome were screened out through factor analysis,and the constructing feature of kidney Yang deficiency syndrome was analyzed combined with TCM syndrome knowledge.Results Eight common factors with eigenvalues greater than 1 were extracted by principal component analysis,and the cumulative contribution rate was 60.483%.After the factor rotation,the representative variables with the absolute value of load coefficient greater than 0.45 in each common factor were selected.The representative variables of F1 are afraid of cold and fond of warmth(0.947)and intolerance to cold(0.932).The representative variables of F2 are waist pain(0.754),waist and knee weakness(0.720)and cold in waist and knees(0.466).The representative variables of F3 are depression(0.749),insomnia(0.711)and diarrhoea(0.470).The representative variables of F4 are thin fur(0.819)and white fur(0.768).The representative variable of F5 are tinnitus and deafness(0.687),frequent nocturnal urination(0.591)and decreased libido(0.587).The representative variables of F6 are pulse sinking(0.766)and pulse weakness(0.736).The representative variables of F7 is thready pulse(0.942).The representative variable of F8 is pale tongue(0.961).External syndrome of disease location involved in these common factors are waist,bone,brain,ear,anterior Yin,posterior Yin and reproductive function.The disease nature involved in these common factors is deficiency and cold.Conclusion The basic constituent units of kidney Yang deficiency syndrome include disease location syndrome elements and disease nature syndrome elements.The disease location is kidney,and the abnormal changes of kidney location are mainly external symptoms of waist,bone,brain,ear,anterior Yin,posterior Yin and reproductive function.Its disease nature is deficiency and cold.Yang deficiency leads to external cold.Yang Qi deficiency can not warm the body surface resulting in the appearance of external cold syndrome.

BACKGROUND/OBJECTIVES: Previous research has shown maternal betaine supplementation alleviates fetal-derived hepatic steatosis. Therefore, this study examined the anti-inflammatory effect of maternal betaine intake in offspring mice and its mechanism.MATERIALS/METHODS: Female C57BL/6J mice and their offspring were randomly divided into 3 groups according to the treatment received during gestation and lactation: control diet (CD), fatty liver disease (FLD), and fatty liver disease + 1% betaine (FLD-BET). The FLD group was given a high-fat diet and streptozotocin (HFD + STZ), and the FLD-BET group was treated with HFD + STZ + 1% betaine. After weaning, the offspring mice were given a normal diet for 5 weeks and then dissected to measure the relevant indexes. RESULTS: Compared to the CD group, the offspring mice in the FLD group revealed obvious hepatic steatosis and increased serum levels of alanine aminotransferase, interleukin (IL)-6, and tumor necrosis factor (TNF)-α; maternal betaine supplementation reversed these changes. The hepatic mRNA expression levels of IL-6, IL-18, and Caspase-1 were significantly higher in the FLD group than in the CD group. Maternal betaine supplementation reduced the expression of IL-1β, IL-6, IL-18, and apoptosis-associated speck-like protein containing C-terminal caspase recruitment domain (ASC). Maternal betaine supplementation also reversed the increasing protein expressions of nitric oxide dioxygenase-like receptor family pyrin domain containing 3 (NLRP3), ASC, Caspase-1, IL-1β, and IL-18 in offspring mice exposed to HFD + STZ. Maternal betaine supplementation decreased the homocysteine (Hcy) and s-adenosine homocysteine (SAH) levels significantly in the livers. Furthermore, the hepatic Hcy concentrations showed significant inverse relationships with the mRNA expression of TNF-α, NLRP3, ASC, and IL-18. The hepatic SAH concentration was inversely associated with the IL-1β mRNA expression. CONCLUSIONS The lipotropic and anti-inflammatory effect of maternal betaine supplementation may be associated with the inhibition of NLRP3 inflammasome in the livers of the offspring mice.

Objective:To evaluate the efficay of different doses of remimazolam for anesthesia induction during reoperation in asthenic patients with tracheotomy.Methods:One hundred and twenty patients of both sexes, aged 19-64 yr, with a modified frailty index score ≥3, of American Society of Anesthesiologists physical status Ⅳ, scheduled for reoperation after tracheotomy, were divided into 4 groups ( n=30 each)using a random number table method: propofol group (group C) and different doses of remimazolam groups (R 1, R 2 and R 3 groups). Anesthesia was induced with intravenous sufentanil 5 μg, propofol 1.5 mg/kg in group C and with remimazolam 0.1, 0.2 and 0.3 mg/kg in R 1, R 2 and R 3 groups, respectively.The tracheotomy cannula was replaced with a reinforced endotracheal intubation (ID=6.0 mm) when bispectral index value ≤ 65.Mean arterial pressure and heart rate were recorded before induction (T 0), immediately before replacement of the tube (T 1) and immediately after replacement of the tube (T 2). The onset time of anesthesia and adverse reactions such as hypotension, bradycardia and bucking during replacement of the tube, and requirement for rescue sedation were recorded. Results:Compared with group C, mean arterial pressure was significantly increased at T 1, 2 in group R 1 and group R 2, the onset time of anesthesia was significantly prolonged, the incidence of hypotension and bradycardia was decreased in R 1, R 2 and R 3 groups, and the requirement for rescue sedation in group R 1 and incidence of bucking in group R 1 and group R 2 were increased ( P<0.05 or 0.01). Compared with group R 1, heart rate at T 2 was significantly decreased, the onset time of anesthesia was shortened, and the requirement for rescue sedation and incidence of bucking were decreased in C, R 2 and R 3 groups, and the incidence of hypotension was significantly increased in group R 3 ( P<0.05 or 0.01). Compared with group R 2, the onset time of anesthesia was significantly shortened in group R 3 ( P<0.05). Conclusions:Remimazolam 0.2 mg/kg provides good efficacy when used for anesthesia induction with fewer side effects during reoperation in asthenic patients with tracheotomy.

ObjectiveTo study the correlations of the characteristics of kidney Yang deficiency syndrome in patients with chronic kidney disease （CKD） with clinical indicators and to explore the risk factors of kidney Yang deficiency in CKD. MethodThe differentiation of traditional Chinese medicine （TCM） syndrome classified the 225 CKD patients who met the inclusion criteria into two groups： one group of kidney Yang deficiency syndrome （99 patients） and one group of non-kidney Yang deficiency syndrome （126 patients）. The symptoms， tongue manifestation， pulse manifestation， and accompanied symptoms of the kidney Yang deficiency syndrome group were recorded. The syndrome characteristics were summarized by factor analysis and clustering analysis. The levels of hemoglobin, red blood cell count, urinary protein, urinary glucose, creatinine, urea nitrogen and glomerular filtration rate were compared between the kidney Yang deficiency syndrome group, the non-kidney Yang deficiency syndrome group and the normal control group by ANOVA and non-parametric test. The binary logistic regression model was employed to analyze the correlations of lifestyle， body mass index （BMI） with syndrome. ResultThe high-frequency symptoms of CKD patients with kidney Yang deficiency syndrome were waist pain， fear of cold， favor of warm， lethargy， fear of cold at waist and knees， etc. The patients mainly presented deep pulse， thready pulse， or weak pulse， and the tongue with white coating， greasy coating， or thin coating. A total of 13 common factors were obtained， which can be classified into 5 categories. The patients with kidney Yang deficiency syndrome mainly had symptoms in limbs （especially lower limbs）， chest， bladder， fleshy exterior， and stomach， with the main manifestations of deficiency-cold， Qi deficiency， fluid retention， and blood stasis. The clustering analysis classified the patients into 11 categories， which reflected that kidney Yang deficiency syndrome mainly presented the symptoms of Qi deficiency， blood stasis， and fluid retention， with fleshy exterior， limbs， spleen， stomach， ears， mind， and bladder involved. The results of clustering analysis and factor analysis were consistent， both of which indicated that the patients were weak with deficiency-cold， accompanied by fluid retention and blood stasis. Frequency analysis also showed that common symptoms mainly included Qi deficiency， fluid retention， cold-dampness， and blood stasis. Compared with the non-kidney Yang deficiency group， the kidney Yang deficiency group showed a large proportion of patients in stage 3-5 CKD， elevated urea nitrogen （P<0.05）， decreased glomerular filtration rate， hemoglobin， and red blood cell count （P<0.05）， and increased qualitative grade of urine protein. In addition， the results of regression analysis showed that female， little or no exercise， and diet preference were the risk factors for kidney Yang deficiency syndrome in CKD （P<0.05）. ConclusionThe disease location and manifestations have correspondence in the CKD patients with kidney Yang deficiency syndrome. The TCM symptoms are correlated with clinical indicators. Hemoglobin， red blood cell count， glomerular filtration rate， urea nitrogen， and urine protein can reflect the connotation of kidney Yang deficiency syndrome in CKD to a certain extent. Additionally， related risk factors in life can affect the occurrence of kidney Yang deficiency syndrome in CKD.

Objective To compare the efficacy of different doses of dexmedetomidine for sedation in patients with Parkinson's disease (PD) undergoing deep brain stimulation (DBS) surgery.Methods Seventy-five patients of both sexes with PD,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,aged 48-72 yr,with body mass index of 18-24 kg/m2,undergoing elective DBS surgery,were divided into 3 groups (n =25 each) using a random number table method:different doses of dexmedetomidine groups (D1-3 groups).Dexmedetomidine was intravenously infused in a loading dose of 0.5 μg/kg at 10 min before local infiltration anesthesia with 0.25 ％ ropivacaine 10-20 ml,followed by an infusion of 0.3,0.5 and 0.8 μg · kg-1 · h-1 in D1-3 groups,respectively.The infusion of dexmedetomidine was suspended during neurological test,the patients were awakened,and dexmedetomidine was infused at 0.3,0.5 and 0.8 μg · kg-1 · h-1 until the end of the surgery after the test.Bispectral index (BIS) value was recorded immediately before anesthesia (T0),immediately after administration prior to wake-up (T1) and during neurological test (T2).The wake-up time and adverse reactions such as requirement for rescue analgesics,pulse oxygen saturation (SpO2) ＜ 90％ and snoring were recorded.Results Compared with group D1,the requirement for rescue analgesics and BIS value at T1,2 were significantly decreased in D2 and D3 groups,and the wake-up time was significantly prolonged,and the incidence of SpO2 ＜ 90％ and snoring was increased in group D3 (P＜0.05 or 0.01).Compared with group D2,the requirement for rescue analgesics and BIS value at T1 were significantly decreased,the wake-up time was prolonged,and the incidence of SpO2 ＜90％ and snoring was increased in group D3 (P＜0.05 or 0.01).Conclusion Dexmedetomidine 0.5 μg · kg-1 · h-1 can produce good sedative efficacy and safety for DBS surgery in patients with PD.

Diabetic kidney disease (DKD) is a serious long-term complication and major death cause of patients who have suffered from diabetes mellitus (DM),which is a serious threat to the health of human being.Professor Zhao Zongjiang first came up with the of DKD "consumptive kidney disease" scientific theory,and led the scientific research team for DKD research.Our team had achieved some results,which were mainly focused on the animal experiments and cell culture experiment.And the research fields covered pharmacodynamics,oxidative stress levels and signal transduction pathways.Focusing on the reduction of extracellular matrix in the glomerular mesangial area and tubulointerstitial deposition,inhibition of podocyte injury,inhibition of podocyte apoptosis,inhibition and reversal of podocyte transdifferentiation,inhibition of renal tubular epithelial cell transdifferentiation and other scientific issues,this paper systematically explored the biological mechanism of DKD "consumptive kidney disease" scientific theory.This paper explained how "consumptive kidney disease" scientific theory was proposed and summarized related research results of our research team and developed traditional Chinese medicine (TCM) theory by supplying the TCM "consumptive organ disease" theory.

This study was aimed to explore the renoprotective effects of Tang-Shen-Ping (TSP) on RhoA/ROCK signaling pathway in KKAy mice with diabetic kidney disease (DKD).A total of 60 female 10-week SPF degree KKAy mice,which were fed with KK special food for 10 weeks,were made into DKD model.Mice were randomly divided in the model group,irbesartan group,low-,medium-and high-dose TSP group (0.525 g· kg-1,1.05 g· kg-1,and 2.1 g· kg-1).Ten female C57BL/6J mice were used as the normal control group.Mice of each group were intragastrically administered with corresponding medicine,respectively,while mice of the control group and the model group were given deionized water of the equal volume.The body weight was measured and the 24-hour urine protein quantification was detected every 4 weeks.At the end of the 26th week,all mice were sacrificed and the biochemical indicators,such as fasting blood glucose (FBG),serum blood urea nitrogen (BUN),serum creatinine (Scr),and triglyceride (TG) were measured.HE staining,Mallory staining and PAS staining were used to observe the pathological morphology of kidney tissues.Immunohistochemistry (IHC) and in situ hybridization (ISH) were used in the detection of transforming growth factor-β1 (TGF-β1),Ras homolog gene family member A (RhoA),Rho-associated coiled-coil-containing protein kinase 1 (ROCK1),α-smooth muscle actin (α-SMA),E-Cadherin (E-Cad) mRNA and protein expression.The results showed that compared with the model group,there were significant differences on body weight,the ratio of kidney weight to body weight,and urinary protein in the middle-and high-dose TSP group (P ＜ 0.01);the renal pathological damage was obviously decreased;contents of FBG,BUN,Scr and TG decreased (P ＜ 0.01);mRNA and protein expression of E-Cadherin increased;mRNA and protein expression of TGF-β1,RhoA,ROCK1 and α-SMA decreased with significant difference in the middle-and high-dosc TSP group (P ＜ 0.01).It was concluded that the renoprotective effects and epithelial-mesenchymal transdifferentiation (EMT) of renal tubular epithelial cells of TSP on DKD KKAy mice may be related to the regulation of RhoA/ROCK signaling pathway.

BACKGROUND:Studies have shown that pulsed electromagnetism has a good effect in promoting peripheral nerve regeneration after cerebral infarction and spinal cord injury, and improving memory function in patients with neurological disorders. OBJECTIVE: To investigate the impact of pulsed magnetic field on brain function and endogenous neural stem cell factor in the brain tissue of rats with brain injury. METHODS: Totally 320 adult male Sprague-Dawley rats were randomly divided into model group, pulsed magnetic field 0.1 mT group, pulsed magnetic field 0.3 mT group and pulsed magnetic field 0.5 mT group (n=80 per group). After brain injury models were established using lateral hydraulic strike method, rats in the latter three groups were exposed to pulsed magnetic fields 0.1, 0.3, 0.5 mT, respectively. After electromagnetic radiation 1, 3, 7, 14 days, the motor function of rats was evaluated by beam-walking test and water maze test. Rats were intraperitoneally injected 5-deoxy-uridine (BrdU) at 1 day prior to different radiation time points, and BrdU and nestin expressions in the cerebral cortex were measured by immunohistochemical method. RESULTS AND CONCLUSION: (1) The time of water maze test and the beam-walking test at 1, 3 and 7 days after irradiation was ranked as follows: pulse magnetic field 0.5 mT < pulse magnetic field 0.3 mT < pulse magnetic field 0.1 mT < model group, and there were significant differences between groups (P < 0.05). (2) The expressions of BrdU and nestin at 1, 3 and 7 days after irradiation were highest in the pulse magnetic field 0.5 mT group, successively followed by pulse magnetic field 0.3 mT group, pulse magnetic field 0.1 mT group and model group (P < 0.05). In summary, the pulse magnetic field exhibits remarkable protective effects on the brain function of rats with craniocerebral injury in an intensity-dependent manner. The possible mechanism is related to the activation of neural stem cells and the proliferation of neural stem cells in the brain tissue of rats with craniocerebral injury.

Anhedonia is the loss of pleasure or lack of reaction to pleasurable stimuli, which is a promising phenotype of depression. In order to explore the potential biological mechanism, the recent ad?vances were summarized from researches focused on depression with anhedonia from neuroanatomy,inflamma?tion and immunology,and molecular genetics. The structural and functional brain imaging showed that the ac?tivity in reward?related brain regions of the depressive disorder with an anhedonia was changed during re?ward?related tasks.In addition,some other genetic studies based on the related neurotransmitter,such as do?pamine, together with the findings from the researches on immunological inflammation, may shed light on finding the potential targets for novel antidepressants,besides the 5?HT.