Criminological Characteristics and Criminal Responsibility Capacity of Offenders with Alcoholism / 中山大学学报(医学科学版)

ObjectiveTo analyze the criminal behavior characteristics of alcohol-related crime offenders and explore the relationship between criminal behavior characteristics and criminal responsibility capacity. MethodsBasic information， alcohol use information， psychiatric symptoms before and after the crime， criminological behavioral characteristics and conclusion of judicial evaluation were collected. ResultsThe drinking history of the chronic alcoholism group 25.0 （13.3~30.0） years was significantly longer than that of the acute alcoholism group 1.2 （0~14.3） years. In the chronic alcoholism group， 85.0% drank alcohol at least once a day， 52.5% had morning or bedtime drinking habits， and 92.5% drank mainly alone. Violent crimes accounted for 57.6%. Delirium existed in 52.5% of the chronic alcoholics' mental state at the time of the crime， and 84.6% of the acute alcoholics' mental state was hazy. In the chronic alcoholism group， 42.5% committed the crime with pathological motive， and in the acute alcoholism group， 69.2% committed the crime with realistic motive. Acute alcoholism group 96.2% were assessed as complete criminal responsibility capacity， and chronic alcoholism group 50.0% were assessed as complete criminal responsibility capacity. ConclusionCompared with acute alcoholism offenders， chronic alcoholics had a longer drinking duration， more frequency drinking， and obvious morning drinking or bedtime drinking habits. The nature of alcoholism crime cases was mostly violent. Compared with the chronic alcoholism group， the acute alcoholism group had highly selective motives for committing crimes and were mostly rated as complete criminally responsibility.

Protective Effect of Flos Puerariae，Hoveniae Semen， and Their Compatibility on Acute Alcoholic Gastric Mucosal Injury in Mice and Mechanism / 中国实验方剂学杂志

ObjectiveTo explore the improvement effect of Flos Puerariae， Hoveniae Semen， and their compatibility on acute alcoholic gastric mucosal injury， and lay a foundation for further development of Flos Puerariae， Hoveniae Semen， and their compatibility in the prevention and treatment of alcohol-induced multiple organ injury. MethodThe acute alcohol-induced gastric mucosal injury model of mice was established by multiple intragastric administration of 56% Hongxing Erguotou liquor （15 mL·kg-1）. A total of 120 male ICR mice were randomly divided into 8 groups， namely， the blank group， model group， omeprazole group （0.026 g·kg-1）， Flos Puerariae-Hoveniae Semen （compatibility） high， medium， and low-dose groups （29.2，14.6， 7.3 g·kg-1）， Flos Puerariae group （19.5 g·kg-1）， and Hoveniae Semen group （19.5 g·kg-1）， with 15 mice in each group. After one week of adaptive feeding， the animals were pre-administrated with the corresponding drug at the rate of 10 mL·kg-1 for 3 d. From the 4th day， after 1 h of administration， Erguotou liquid was administrated at the rate of 15 mL·kg-1 and the blank group was administrated with the same volume of deionized water to record the drunkenness and sober up time. The administration was lasted for 3 d. One hour after the last administration， the eyeballs were removed and the mice were sacrificed. The concentration of ethanol in serum was determined by gas chromatograph， and the activity of ethanol dehydrogenase （ADH） in gastric mucosa was determined by ultraviolet-vis spectrophotometer. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in gastric mucosa. Serum inflammatory factors were determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression of nuclear transcription factor-κB （NF-κB） p65 and NF-κB inhibitory protein α （IκBα） were detected by real-time polymerase chain reaction （Real-time PCR）. ResultAs compared with the normal group， the content of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in serum of mice in the model group was increased （P<0.05）， the mRNA expression of NF-κB p65 in gastric mucosa tissues was increased （P<0.01）， and the mRNA expression of IκBα was decreased （P<0.01）. As compared with the model group， the drunkenness time of the omeprazole group， high and medium-dose compatibility groups， and Flos Puerariae group was prolonged （P<0.05）， the sober up time of the high and medium-dose compatibility groups was shortened （P<0.05）， the ethanol concentration in the serum of the high-dose compatibility group was decreased （P<0.05）， the ADH activity in the gastric mucosa of the omeprazole group and high and medium-dose compatibility groups was increased （P<0.05）， the macroscopic injury score of the high， medium， and low-dose compatibility groups and Flos Puerariae group was decreased （P<0.05）， the score of pathological injury in the omeprazole group， high， medium， and low-dose compatibility groups， and Flos Puerariae group was decreased （P<0.01）， the expression of IL-6 in serum of all drug groups was decreased （P<0.05）， the expression of IL-1β in serum of the omeprazole group， high， medium， and low-dose Flos Puerariae groups， and Hoveniae Semen group was decreased （P<0.05）， the expression of TNF-α in serum of high and medium-dose groups was decreased （P<0.05）， the mRNA expression of NF-κB p65 in gastric mucosa tissues of all drug groups was decreased （P<0.05）， and the mRNA expression of IκBα in gastric mucosa tissues of the omeprazole group and high， medium， and low-dose compatibility groups was increased （P<0.05）. As compared with the high-dose compatibility group， the drunkenness time in the low-dose compatibility group and Hoveniae Semen group was shortened （P<0.01）， the sober up time in the Flos Puerariae and Hoveniae Semen groups was prolonged （P<0.01）， the concentration of ethanol in the serum of the medium and low-dose compatibility groups， Flos Puerariae group， and Hoveniae Semen group increased （P<0.05）， the macroscopic injury score of the medium and low-dose compatibility groups and Hoveniae Semen group was increased （P<0.05）， the pathological injury score of the medium and low-dose compatibility groups， Flos Puerariae group， and Hoveniae Semen group was increased （P<0.01）， the content of IL-1β in serum of low-dose compatibility group， Flos Puerariae group， and Hoveniae Semen group was increased （P<0.01）， and the mRNA expression of IκBα in gastric mucosa of the Flos Puerariae group and Hoveniae Semen group was decreased （P<0.05）. As compared with the medium-dose compatibility group， the drunkenness time in the Hoveniae Semen group was shortened （P<0.05）， the sober up time in the Flos Puerariae group was prolonged （P<0.05）， the pathological injury score in the Flos Puerariae group and Hoveniae Semen group was increased （P<0.01）， and the content of IL-1β in serum of the low-dose compatibility group， the Flos Puerariae group， and Hoveniae Semen group was increased （P<0.05）. As compared with the low-dose compatibility group， the pathological injury score of the Hoveniae Semen group was increased （P<0.05）. ConclusionFlos Puerariae， Hoveniae Semen， and their compatibility play a role in preventing and treating acute alcoholic gastric mucosal injury in mice， which may be related to the inhibition of the expression of NF-κB signal pathway in gastric mucosa， and the high-dose compatibility group has the optimal effect.

Tetrahedral DNA nanostructures synergize with MnO2 to enhance antitumor immunity via promoting STING activation and M1 polarization

Stimulator of interferon genes (STING) is a cytosolic DNA sensor which is regarded as a potential target for antitumor immunotherapy. However, clinical trials of STING agonists display limited anti-tumor effects and dose-dependent side-effects like inflammatory damage and cell toxicity. Here, we showed that tetrahedral DNA nanostructures (TDNs) actively enter macrophages to promote STING activation and M1 polarization in a size-dependent manner, and synergized with Mn2+ to enhance the expressions of IFN-β and iNOS, as well as the co-stimulatory molecules for antigen presentation. Moreover, to reduce the cytotoxicity of Mn2+, we constructed a TDN-MnO2 complex and found that it displayed a much higher efficacy than TDN plus Mn2+ to initiate macrophage activation and anti-tumor response both in vitro and in vivo. Together, our studies explored a novel immune activation effect of TDN in cancer therapy and its synergistic therapeutic outcomes with MnO2. These findings provide new therapeutic opportunities for cancer therapy.

Effect of Tiaoshen Qianyang acupuncture on blood pressure and sleep quality in patients with stroke-related sleep disorders complicated with hypertension / 中国针灸

OBJECTIVE@#To observe the effect of Tiaoshen Qianyang acupuncture on morning blood pressure, sleep quality and post-stroke nerve function recovery in patients with stroke-related sleep disorders (SSD) complicated with hypertension.@*METHODS@#A total of 120 patients were randomized into an observation group (60 cases) and a control group (60 cases, 1 case dropped off). Both groups were treated with Xingnao Kaiqiao acupuncture (Neiguan [PC 6], Shuigou [GV 26], Sanyinjiao [SP 6], Jiquan [HT 1], Chize [LU 5] and Weizhong [BL 40]). In addition, Tiaoshen Qianyang acupuncture was applied in the observation group, deep needling at Baihui (GV 20) and Sishencong (EX-HN 1) for 5 h. Once a day, 5 times a week, 30 times in total. The morning blood pressure was measured during treatment in the two groups, the Pittsburgh sleep quality index (PSQI) and National Institute of Health stroke scale (NIHSS) scores before and after treatment were observed in the two groups.@*RESULTS@#Compared before treatment, the morning systolic blood pressure (SBP) after treatment were decreased in the two groups (P<0.05), and the morning diastolic blood pressure (DBP) after treatment was decreased in the observation group (P<0.05). The levels of SBP and DBP after treatment in the observation group were lower than the control group (P<0.05). Compared before treatment, the total score of PSQI and NIHSS score after treatment in the observation group were decreased (P<0.01, P<0.05), which were lower than the control group (P<0.01, P<0.05), the decreasing rate of NIHSS score in the observation group was higher than the control group (P<0.05).@*CONCLUSION@#On the basis of Xingnao Kaiqiao acupuncture, Tiaoshen Qianyang acupuncture could improve morning blood pressure and sleep quality for patients with SSD complicated with hypertension, promote the recovery of nerve function.

Impact of statistical uncertainty on esophagus cancer plan for dose to water and dose to medium / 中国辐射卫生

Objective To study the dosimetry effect of Dw and Dm middle and lower esophageal cancer in Monaco treatment planning system (TPS). Methods 30 patients with T3N0M0StageⅡa middle and lower esophageal cancer were selected for experiment. For each patient, optimize the plan using dose to water (Dw) and dose to medium (Dm) dose calculation mode, then rescale prescription dose to 95% volume of PTV. Compare the difference in the two mode, conformity index (CI), Homogeneity index (HI), Mean dose (Dmean), Minimum dose (Dmin), Maximum dose (D2), Dose to Organ at risk (OAR), MU, Optimization time, photon usage, and QA results of MatriXX and Arc Check. Use SPSS for multivariate analysis. Results In the dose evaluation of the middle and lower esophageal cancer cases under different dose calculation methods, the spinal cord, trachea, V20 of the whole lung, and D2 of the liver have significant dosimetric differences, the dose value, the sequential dose results were compared as (37.92 ± 1.11)/(35.85 ± 1.08), (59.91 ± 1.43)/(60.25 ± 0.98), (22.52 ± 1.75)/(21.38 ± 2.01), (42.89 ± 0.52)/(41.73 ± 0.58). In the comparison of dose cloud distribution, the difference is mainly located in the cavity and the inner wall of the lung in the target area, the dose in the target cavity in the Dw group is higher than that in the Dm group. The dose in the inner and outer walls of the lung cavity in the Dw group are slightly adducted than that in the Dm group, especially in the central area.Dose QA of MartiXX (3%-3 mm) and Arc Check (2%-2 mm) with different dose calculation methods of 60 plans of 30 cases have all passed clinical requirements. Dm Group is better than Dw group. Conclusion It is recommended to use Dm dose calculation method for Monaco 5.11 TPS in the condition of treatment planning for middle and lower esophageal cancer.

Impact of fluence smoothing on the dosimetry of cervical cancer radiotherapy / 中国辐射卫生

Objective To explore the dosimetric differences of radiotherapy plan for cervical cancer with 4 different fluence smoothing (FS) parameters using Monaco treatment planning system (Monaco TPS). Methods Fifteen patients with ⅠB2 stage cervical cancer in our hospital were enrolled in this study. And a 2 Volumetric Modulated Arc Therapy (VMAT) plan for each patient were completed by Monaco 5.11 TPS according to the X-Ray Voxel Monte Carlo (XVMC) method. For each plan was optimized by FS function, with the level of Off, Low, Medium and High. To compare the difference of plan optimization time, conformity index (CI), Homogeneity index (HI), Dmean, Dmin, D2% of PTV，dose to the organ at risk (OAR)，the number of Segments# and MU#，estimated total delivery time (ETDT), quantum Efficiency (QE) of the plans, the formation of Segments# with the same angle and verification of inserting 729 two-dimensional matrix into PTW octavius 4D module of different FS function levels, with the precondition of the Prescription isodose curve covering 95% of the target area. The data was analysed by multivariate factor analysis with the application of SPSS, and P < 0.05 was considered as statistically significant. And the Planned revenue score of different FS levels was also calculated. Results Except for the Dmin of PTV (the lowest value is (32.09 ± 0.26) Gy for the Off group, and the highest value is (35.98 ± 0.42) Gy for the High group), V40 of the rectum (the lowest value in the Medium group is 55.88% ± 2.02%, and the highest value in the High group was 61.90% ± 2.98%) and bladder (the lowest value was 45.01% ± 2.08% in the Medium group, and the highest value is 50.45% ± 1.98% in the High group), the V20 (the lowest value High group was 49.05% ± 1.98%, the highest value Off group was 56.52% ± 1.75%) of femoral head (P < 0.05), there was no significant difference of the dose assessment results for PTV and OARs in 4 different FS function levels. In the High level, the ETDT, QE and MU# were showed better than other groups evidently, however, the number of Segments# showed no significant difference. The plan validation results was increased with the improvement of FS function level, and the level of High was considered to be the optimal. To compare the score of overall benefits of the plan, the level of Medium (−17.18 ± 0.05) got the highest score, and the Low group (−17.58 ± 0.05) and the High group (−17.42 ± 0.06) have similar scores, and Off group (−18.81 ± 0.08) has the lowest score. Conclusion Different FS levels of the Monaco 5.11 TPS can optimize the radiotherapy plan for cervical cancer, but the level of Medium is considered to be the most applicable.

Investigation on mechanism and active components of Shufeng Jiedu Capsule in treatment of COVID-19 based on network pharmacology and molecular docking / 中草药

Objective: To explore the novel coronavirus disease 2019 (COVID-19) treatment mechanism and active ingredients of Shufeng Jiedu Capsule by network pharmacology and molecular docking. Methods: TCMSP databases were used to search the chemical composition and target of Shufeng Jiedu Capsule, which was composed of Isatidis Radix, Polygonum cuspidatum, Forsythia suspensa, Phragmitis Rhizoma, Patrinia, Verbena officinalis, Bupleurum chinense, and Glycyrrhiza uralensis. The Swiss target prediction database was used to remove the target with possibility of 0. The corresponding targets of the disease were searched in the GeneCards and OMIM databases with the key words of "coronavirus", "pneumonia", "cough", and "fever". Through the UniProt databases to correct the name of the target point, take the intersection of Shufeng Jiedu Capsule and the disease target point, then use the software of Cytoscape 3.7.2 to build the network of traditional Chinese medicine-compound-target for visualization, through DAVID databases to carry out the GO function enrichment analysis and KEGG pathway enrichment analysis, predict the interaction mechanism of the target, and draw the column and bubble chart for visualization. The novel coronavirus (SARS-CoV-2) 3CL hydrolase was then docking with all compounds and the first five compounds with the least binding energy were selected for docking with angiotensin-converting enzyme II (ACE2). Results: The traditional Chinese medicine-compound-target compound target network contains eight kinds of traditional Chinese medicine-compound-target, 157 compounds and 260 corresponding targets. The key targets were PTGS2, ESR1, AR, etc. There were 393 items in GO functional enrichment analysis (P < 0.05), and 139 signaling pathways in KEGG pathway enrichment analysis. Molecular docking results showed that SARS-CoV-2 3CL hydrolase and ACE2 binding energy of the five core compounds, including 6-(3-oxoindolin-2-ylidene) indolo [2,1-b] quinazolin-12-one, bicuculline, physciondiglucoside, dihydroverticillatine, and licoisoflavanone, was smaller than that of recommended chemical drugs, and the binding energy to ACE2 was similar to that of the recommended chemical drug. Conclusion: The compounds in Shufeng Jiedu Capsule can regulate the signaling pathway of human cytomegalovirus infection, Kaposi's sarcoma associated herpesvirus infection, IL-17 signaling pathway, small cell lung cancer, etc. to treat COVID-19 by binding with SARS-CoV-2 3CL hydrolase and ACE2.

Identification of CDK6 and RHOU in Serum Exosome as Biomarkers for the Invasiveness of Non-functioning Pituitary Adenoma / 中国医学科学杂志(英文版)

Objective To explore circulating biomarkers for screening the invasiveness of non-functioning pituitary adenomas (NF-PAs). Methods The exosomal RNAs were extracted from serum of patients with invasive NF-PA (INF-PA) or noninvasive NF-PA (NNF-PA). Droplet digital PCR was adapted to detect the mRNA expression of candidate genes related to tumor progression or invasion, such as cyclin dependent kinase 6 (CDK6), ras homolog family member U (RHOU), and spire type actin nucleation factor 2 (SPIRE2). Student's -test was used to analyze the statistical difference in the mRNA expression of candidate genes between the two groups. Receiver operating characteristic (ROC) curve was used to establish a model for predicting the invasiveness of NF-PAs. The accuracy, sensitivity, specificity and precision of the model were then obtained to evaluate the diagnostic performance. Results CDK6 (0.2600±0.0912 . 0.1789±0.0628, =3.431, =0.0013) and RHOU mRNA expressions (0.2696±0.1118 . 0.1788±0.0857, =2.946, =0.0052) were upregulated in INF-PAs patients' serum exosomes as compared to NNF-PAs. For CDK6, the area under the ROC curve (AUC) was 0.772 (95% : 0.600-0.943, =0.005), the accuracy, sensitivity, specificity and precision were 77.27%, 83.33%, 75.00% and 55.56% to predict the invasiveness of NF-PAs. For RHOU, the AUC was 0.757 (95% : 0.599-0.915, =0.007), the accuracy, sensitivity, specificity and precision were 72.73%, 83.33%, 68.75% and 50.00%. In addition, the mRNA levels of CDK6 and RHOU in serum exosomes were significantly positively correlated (=0.935, <0.001). After combination of the cut-off scores of the two genes, the accuracy, sensitivity, specificity and precision were 81.82%, 83.33%, 81.25% and 62.50%. Conclusions CDK6 and RHOU mRNA in serum exosomes can be used as markers for predicting invasiveness of NF-PAs. Combination of the two genes performs better in distinguishing INF-PAs from NNF-PAs. These results indicate CDK6 and RHOU play important roles in the invasiveness of NF-PAs, and the established diagnostic method is valuable for directing the clinical screening and postoperative treatment.

Effect of Traditional Chinese Medicine and Western Medicine Therapy on Gestational Diabetes Mellitus / 中国实验方剂学杂志

In recent years, as the level of economic life has improved, the incidence of gestational diabetes mellitus has increased year by year. Gestational diabetes mellitus (GDM) has been a serious threat to maternal and newborn health. The pathogenesis of gestational diabetes is not very clear, and may be closely associated with insulin resistance, genetic susceptibility, inflammatory response, metabolic disorders. According to the gestational diabetes diagnostic standard,24-28 weeks pregnant women keep an empty stomach over 8 h, taken 75 g oral glucose directly, and then receive the oral glucose tolerance test. GDM is diagnosed as fasting blood-glucose> 5.1 mmol · L-1,1-hour postprandial blood glucose>10.0 mmol · L-1,and 2-hour postprandial blood glucose>8.5 mmol · L-1. Western medicine treatment is mainly based on diet, exercise, drugs, education, monitoring and insulin therapy according to blood glucose. Meanwhile, GDM is a type of diabetes in traditional Chinese medicine. GDM is prevented and treated with diets and traditional method sports and Chinese herbs. Therefore, integrated Chinese and western medicine therapy can maximize the curative effect, reduce the incidence of gestational diabetes mellitus, and effectively improve the adverse outcome and prognosis of patients with gestational diabetes mellitus from mother to child.

Keratitis, ichthyosis, and deafness syndrome: a case report / 中华皮肤科杂志

A 10 year-old female child developed erythema on the scalp,perioral area,neck,trunk,buttocks,palms and soles within 1 month after birth.Her skin was dry and rough,and the hairs were fine,soft,sparse and easily broken.As age advanced,typical hyperkeratosis and thickening of the skin occurred on an erythematous base.At the age of 5 years,the child developed photophobia and vision impairment.When the child was 8 years old,progressive hearing loss was observed.Physical examination revealed that the height and weight were 109 centimeters and 19 kilograms respectively.Skin examination showed fine,soft,sparse and easily-broken hair,large areas of brown plaques with crusts on the scalp,perioral area,neck,trunk and buttocks,and fissured,purulent and foul-smelling verrucous hyperplasia over these plaques.Brown to black hyperkeratotic plaques were scattered over the extremities,and diffuse hyperkeratosis occurred on the palms and soles.Both fingernails and toenails became thickened,cloudy and white with distal separation and deformation of the nail plate.As ophthalmic examination showed,the patient had photophobia,bilateral bulbar conjunctival hyperemia,corneal opacity and corneal vascular proliferation,and the visual acuity was 0.5 in the left eye and 0.2 in the right eye.Otolaryngological examination revealed moderate binaural sensorineural deafness.Stomatological examination showed enamel hypoplasia and diastema widening.Genetic testing showed a heterozygous mutation (c.C50T) in exon 2 of the gap junction protein beta 2 (GJB2) gene.Based on these clinical manifestations and examinations,the patient was diagnosed with keratitis,ichthyosis,and deafness (KID) syndrome.Skin lesions of the patient were significantly improved after the treatment with oral acitretin.

Expression of BATF, a member of the activator protein-1 family, in renal tissues of MRL/lpr mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expression of BATF, a member of the activator protein-1 family, in the renal tissues of mice with lupus nephritis.</p><p><b>METHODS</b>The renal tissues from 24-week-old female MRL/lpr mice and age- and sex-matched C57BL/6 mice were examined for BATF protein expressions using Western blotting and for expressions of BATF, RORγt and IL-17A mRNA using quantitative real-time PCR. The results of laboratory examinations were analyzed in relation with the histopathology of the mice.</p><p><b>RESULTS</b>The urinary protein and ds-DNA levels were significantly higher in MRL/lpr mice than in the control mice (P<0.05). Compared to normal control mice, MRL/lpr mice showed obvious glomerular fibrosis and inflammatory cell infiltrating with significantly increased BATF protein and mRNA expressions (P<0.05) and RORγt and IL-17 mRNA expressions in the renal tissues (P<0.05). In MRL/lpr mice, the expression of BATF mRNA was positively correlated with the RORγt and IL-17A mRNA expressions in the renal tissues.</p><p><b>CONCLUSION</b>The renal expressions of BATF protein and mRNA is increased in MRL/lpr mice. BATF may participate in the immunopathogenesis of lupus nephritis by enhancing Thl7 cell response.</p>

Proton transfer-mediated GPCR activation

G-protein coupled receptors (GPCRs) play essential roles in signal transduction from the environment into the cell. While many structural features have been elucidated in great detail, a common functional mechanism on how the ligand-binding signal is converted into a conformational change on the cytoplasmic face resulting in subsequent activation of downstream effectors remain to be established. Based on available structural and functional data of the activation process in class-A GPCRs, we propose here that a change in protonation status, together with proton transfer via conserved structural elements located in the transmembrane region, are the key elements essential for signal transduction across the membrane.

Preparation and cytotoxicity evaluation of cobalt doped nanotubular implant coating / 实用口腔医学杂志

Objective:To prepare a kind of titanium implant doped with cobalt and to study its cytotoxicity.Methods:The surface of the titanium was anodized to form TiO2 nanotube arrays.Different amount of cobalt was doped by hydrothermal treatment,which was controlled by tuning the hydrothermal treatment duration.The cytotoxicity of the cobalt doped nanotubular implant coating on bone marrow stromal cells (BMSCs)was measured by CCK-8.Results:The nanotubular implant coating with different amount of cobalt was fabricated.The proliferation of BMSCs was inhibited by the nanotubular morphology and cobalt doping.Samples formed by hydro-thermal treatment in 0.1 M cobalt acetate showed significantly cytotoxicity.Conclusion:Hydrothermal treatment of anodized titanium is an effective way for developing novel cobalt doped nanotubular implant coating.The proper dose of cobalt doping needs to be further investigated.

Therapeutic effect of Astragalus and Angelica mixture on the renal function and TCM syndrome factors in treating stage 3 and 4 chronic kidney disease patients / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To compare the therapeutic effect of Astragalus and Angelica Mixture (AAM) on treating CKD patients according to different CKD primary diseases, staging and TCM syndromes.</p><p><b>METHODS</b>A multicentre, open-label, and self control clinical design was used, and thirty-two patients in line with inclusive criteria were recruited. Based on maintaining their previous basic CKD treatment, patients additionally took AAM (Astragalus and Angelica each 30 g), once a day, three months consisted of one therapeutic course. Serum creatinine (SCr), estimated glomerular filtration rate (eG- FR), 24 h urinary total protein (UTP), plasma albumin (ALB), hemoglobin (Hb), and changes of TCM syndrome factor integrals were compared before treatment, at the end of month 1, 2, and 3. The differences in the aforesaid indices were compared between CKD patients with different CKD primary diseases (chronic glomerulonephritis, chronic renal tubulointerstitial disease, hypertensive renal damage), different CKD stages (CKD 3 and CKD 4), and patients of qi-blood deficiency syndrome (QBDS) and non-QBDS.</p><p><b>RESULTS</b>AAM could improve 78.12% (25/32) patients' renal function. Compared with before treatment, SCr decreased (12.08% +/- 10.11%), eGFR increased (21.14% +/- 18.55%), and ALB increased (2.76% +/- 1.97%) at the end of 3-month treatment (all P < 0.05). As for TCM syndrome factor integrals, compared with before treatment, the integrals for qi deficiency syndrome, blood deficiency syndrome, and yin deficiency syndrome decreased, while the integrals for dampness heat syndrome and turbid-toxin syndrome increased (all P < 0.05). There was no obvious difference in all indices except the integral for hypertensive renal damage patients of yin deficiency syndrome (P > 0.05). The SCr decreasing percent was 19.82% +/- 8.30% for patients of non-QBDS and 5.24% +/- 10.75% for patients of QBDS. The latter was higher with statistical difference (P < 0.05). As for TCM syndrome factor integrals, the integral differences of qi deficiency and blood deficiency were obviously higher in patients of QBDS, when compared with patients of non-QBDS (P < 0.05).</p><p><b>CONCLUSION</b>AAM could improve the renal function of CKD patients, elevate their ALB levels, and ameliorate associated qi deficiency syndrome, blood deficiency syndrome, and yin deficiency syndrome, especially for CKD patients of QBDS.</p>

GPCR activation: protonation and membrane potential

GPCR proteins represent the largest family of signaling membrane proteins in eukaryotic cells. Their importance to basic cell biology, human diseases, and pharmaceutical interventions is well established. Many crystal structures of GPCR proteins have been reported in both active and inactive conformations. These data indicate that agonist binding alone is not sufficient to trigger the conformational change of GPCRs necessary for binding of downstream G-proteins, yet other essential factors remain elusive. Based on analysis of available GPCR crystal structures, we identified a potential conformational switch around the conserved Asp2.50, which consistently shows distinct conformations between inactive and active states. Combining the structural information with the current literature, we propose an energy-coupling mechanism, in which the interaction between a charge change of the GPCR protein and the membrane potential of the living cell plays a key role for GPCR activation.