Role of HMGB1-TLR4-mediated NF-κB signaling in adenosine pretreatment in protection against cerebral ischemia-reperfusion injury / 中国免疫学杂志

Objective:To investigate the role of HMGB1-TLR4-NF-κB signaling pathway in cerebral ischemia-reperfusion in-jury and the effect of adenosine preconditioning on the signaling pathway.Methods:Total 80 adult male Sprague-Dawley rats weighing 220～270 g were selected from the Animal Center of Xinxiang Medical University.The rats were randomly divided into F group(sham operation group),I/R group(ischemia reperfusion group)and AP group(adenosine preconditioning group).The MCAO model of rats was established by wire embolization.Quantitative analysis of neural function in successfully modeled rats using animal behavior scor-ing method,the morphological changes of brain cells were observed by HE staining,TTC staining was used to observe cerebral infarc-tion and cerebral infarction volume was calculated;Immunohistochemical staining was used to detect HMGB1,TLR4 and NF-κB pro-tein expression levels in brain tissues of each group.The data were statistically analyzed by one-way ANOVA in SPSS26.0 software.Results:After ischemia reperfusion,the neurological function of I/R group and AP group showed different degrees of impairment,and the neurological function scores of the two groups were significantly higher than that of F group,the difference was statistically signifi-cant(P<0.05),and the neurological function of the AP group was significantly less than that of I/R group,the difference was also sta-tistically significant(P<0.05).TTC staining showed that AP group,I/R group rat cerebral infarction volume was significantly more than F group[(93.670±4.509)mm3,(123.670±7.234)mm3 vs(0.000±0.000)mm3],and AP group rats infarction volume was signifi-cantly reduced than that in I/R group,the difference had statistical significance(P<0.05).Immunohistochemistry showed that HMGB1,TLR4,NF-κB protein in F group with a small amount of expressions in rats,while significantly expressed in AP group and I/R group relatively,and the AP group of each subgroup rat HMGB1,TLR4,NF-κB protein expressions significantly lower than the amount of I/R group,the difference had statistical significance(P<0.05).Conclusion:Adenosine preconditioning can reduce the expressions of HMGB1,TLR4 and NF-κB protein,and then protect the rats with cerebral ischemia-reperfusion injury.

On the difficulties and pains in managing peritoneal metastasis from gastrointestinal cancer in China / 中华胃肠外科杂志

Modern clinical oncology has made great achievements over the last century. However, peritoneal metastasis from gastrointestinal cancer, as one of three most common metastasis modalities, was not re-recognized until the end of the last century, and a normative diagnosis and treatment system has been gradually beginning to be formed until today. This comment is to review the development history, reflect on the lessons and experiences in clinical practice, analyze the difficulties on redefinition, deep understanding and clinical management, and pain points on theory construction, technique practice and discipline construction, in the field of gastrointestinal cancer peritoneal metastasis. We suggested a solution to the difficulties and pain points by realizing the fact of burden of peritoneal metastasis, reinforcing technical training, and promoting collaborative researches, aiming to provide reference for the steady development of peritoneal surface oncology.

Construction and evaluation of a nomogram for predicting the prognosis of patients with colorectal cancer with peritoneal carcinomatosis treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy / 中华胃肠外科杂志

Objectives: To construct a nomogram incorporating important prognostic factors for predicting the overall survival of patients with colorectal cancer with peritoneal metastases treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), the aim being to accurately predict such patients' survival rates. Methods: This was a retrospective observational study. Relevant clinical and follow-up data of patients with colorectal cancer with peritoneal metastases treated by CRS + HIPEC in the Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University from 2007 January to 2020 December were collected and subjected to Cox proportional regression analysis. All included patients had been diagnosed with peritoneal metastases from colorectal cancer and had no detectable distant metastases to other sites. Patients who had undergone emergency surgery because of obstruction or bleeding, or had other malignant diseases, or could not tolerate treatment because of severe comorbidities of the heart, lungs, liver or kidneys, or had been lost to follow-up, were excluded. Factors studied included: (1) basic clinicopathological characteristics; (2) details of CRS+HIPEC procedures; (3) overall survival rates; and (4) independent factors that influenced overall survival; the aim being to identify independent prognostic factors and use them to construct and validate a nomogram. The evaluation criteria used in this study were as follows. (1) Karnofsky Performance Scale (KPS) scores were used to quantitatively assess the quality of life of the study patients. The lower the score, the worse the patient's condition. (2) A peritoneal cancer index (PCI) was calculated by dividing the abdominal cavity into 13 regions, the highest score for each region being three points. The lower the score, the greater is the value of treatment. (3) Completeness of cytoreduction score (CC), where CC-0 and CC-1 denote complete eradication of tumor cells and CC-2 and CC-3 incomplete reduction of tumor cells. (4) To validate and evaluate the nomogram model, the internal validation cohort was bootstrapped 1000 times from the original data. The accuracy of prediction of the nomogram was evaluated with the consistency coefficient (C-index), and a C-index of 0.70-0.90 suggest that prediction by the model was accurate. Calibration curves were constructed to assess the conformity of predictions: the closer the predicted risk to the standard curve, the better the conformity. Results: The study cohort comprised 240 patients with peritoneal metastases from colorectal cancer who had undergone CRS+HIPEC. There were 104 women and 136 men of median age 52 years (10-79 years) and with a median preoperative KPS score of 90 points. There were 116 patients (48.3%) with PCI≤20 and 124 (51.7%) with PCI>20. Preoperative tumor markers were abnormal in 175 patients (72.9%) and normal in 38 (15.8%). HIPEC lasted 30 minutes in seven patients (2.9%), 60 minutes in 190 (79.2%), 90 minutes in 37 (15.4%), and 120 minutes in six (2.5%). There were 142 patients (59.2%) with CC scores 0-1 and 98 (40.8%) with CC scores 2-3. The incidence of Grade III to V adverse events was 21.7% (52/240). The median follow-up time is 15.3 (0.4-128.7) months. The median overall survival was 18.7 months, and the 1-, 3- and 5-year overall survival rates were 65.8%, 37.2% and 25.7%, respectively. Multivariate analysis showed that KPS score, preoperative tumor markers, CC score, and duration of HIPEC were independent prognostic factors. In the nomogram constructed with the above four variables, the predicted and actual values in the calibration curves for 1, 2 and 3-year survival rates were in good agreement, the C-index being 0.70 (95% CI: 0.65-0.75). Conclusions: Our nomogram, which was constructed with KPS score, preoperative tumor markers, CC score, and duration of HIPEC, accurately predicts the survival probability of patients with peritoneal metastases from colorectal cancer treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy.

Blood flow restriction therapy applied to sports training / Terapia de restrição do fluxo sanguíneo aplicada ao treinamento esportivo / Terapia de restricción del flujo sanguíneo aplicada al entrenamiento deportivo

ABSTRACT Introduction: Blood flow restriction therapy, also known as KAATSU pressurization training or ischemic exercise training is a controlled method of vascular occlusion combined with resistance training, with the great growth of its research in recent years. Regular strength training, prevention of lean mass loss, and post-operative rehabilitation are some areas in which the therapy has been prominent. It is believed that it can also be beneficial in sports performance. Objective: Study the effects of an intervention with blood flow restriction therapy on athletes during training. Methods: 32 college athletes with more than two years of experience in sports training, free of injuries, and 20±3 years old were volunteers. They were randomly divided into groups A (no pressure), B (training pressure), C (intermittent pressure), D (full compression). Results: The athletes in the no pressurization group, intermittent pressurization group, training pressurization group, and full-time pressurization group showed significant differences (P<0.05). It can be considered that there is a significant difference in the muscular endurance indexes of the athletes in the non-compression group before and after training, while the athletes in the non-compression group achieved a significant increase in muscular endurance after 6 weeks of training Conclusion: Blood flow restriction therapy can effectively enhance the training effect with various strength qualities, and play a role as a promoter of hypertrophy and vascularization. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A terapia de restrição do fluxo sanguíneo, também conhecida como treinamento de pressurização da KAATSU ou treinamento de exercício isquêmico é um método controlado de oclusão vascular combinado ao treino de resistência, com grande crescimento de suas pesquisas nos últimos anos. Treinos regulares de força, prevenção de perda de massa magra e reabilitação pós-operatória são algumas áreas em que a terapia tem se destacado. Acredita-se que possa ser benéfica também no desempenho esportivo. Objetivo: Estudar os efeitos de uma intervenção com terapia de restrição do fluxo sanguíneo nos atletas durante o treinamento. Métodos: Foram voluntários 32 atletas universitários com mais de dois anos de experiência em treinamento esportivo, livres de lesões e com 20±3 anos de idade. Foram divididos aleatoriamente em grupos A (sem pressão), B (pressão de treinamento), C (pressão intermitente), D (compressão integral). Resultados: Os atletas do grupo sem pressurização, do grupo de pressurização intermitente, do grupo de pressurização de treinamento e do grupo de pressurização em tempo integral, mostraram diferenças significativas (P<0,05). Pode-se considerar que existe uma diferença significativa nos índices de resistência muscular dos atletas do grupo sem compressão antes e depois do treinamento, enquanto os atletas do grupo sem compressão conseguiram um aumento significativo na resistência muscular após 6 semanas de treinamento Conclusão: A terapia de restrição do fluxo sanguíneo pode efetivamente melhorar o efeito de treinamento com várias qualidades de força, além de desempenhar um papel como promotor de hipertrofia e vascularização. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: La terapia de restricción del flujo sanguíneo, también conocida como entrenamiento de presurización KAATSU o entrenamiento de ejercicio isquémico es un método controlado de oclusión vascular combinado con entrenamiento de resistencia, con gran crecimiento de su investigación en los últimos años. El entrenamiento regular de la fuerza, la prevención de la pérdida de masa magra y la rehabilitación postoperatoria son algunas de las áreas en las que la terapia se ha destacado. Se cree que también puede ser beneficioso para el rendimiento deportivo. Objetivo: Estudiar los efectos de una intervención con terapia de restricción del flujo sanguíneo en atletas durante el entrenamiento. Métodos: 32 atletas universitarios con más de dos años de experiencia en el entrenamiento deportivo, libres de lesiones y con 20±3 años de edad fueron voluntarios. Se dividieron aleatoriamente en los grupos A (sin presión), B (presión de entrenamiento), C (presión intermitente), D (compresión total). Resultados: Los atletas del grupo sin presurización, del grupo con presurización intermitente, del grupo con presurización de entrenamiento y del grupo con presurización a tiempo completo mostraron diferencias significativas (P<0,05). Se puede considerar que existe una diferencia significativa en los índices de resistencia muscular de los atletas del grupo sin compresión antes y después del entrenamiento, mientras que los atletas del grupo sin compresión lograron un aumento significativo de la resistencia muscular después de 6 semanas de entrenamiento Conclusión: La terapia de restricción del flujo sanguíneo puede mejorar eficazmente el efecto del entrenamiento con diversas cualidades de fuerza, y desempeñar un papel como promotor de la hipertrofia y la vascularización. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Fundamental pathological mechanisms underlying gastro-intestinal cancer peritoneal metastasis / 中华胃肠外科杂志

Gastrointestinal cancer peritoneal metastasis(GICPM) is one of the biggest challenges of clinical treatment. The ultimate solution to the problem requires the clinicians to accurately understand cytologic and molecular pathological mechanisms behind GICPM, and apply such knowledge in the clinical decision-making process for diagnosis and treatment of individual patient, so as to realize "prevention" and "treatment" proactively. The core cytopathological mechanisms behind GICPM, which are closely related to clinical treatment decisions, are as follows: (1) free cancer cells or clusters in peritoneal cavity colonize the peritoneum, resulting in irreversible pathological damage to peritoneal mesothelial cells; (2) the colonized cancer cells further invade the specific structure of the peritoneal milky spots and initiate an accelerated invasive growth process; (3) the process of peritoneal interstitial fibrosis aggravates the structural destruction of the peritoneum; (4) the interaction between cancer cells and immune cells in the milk spots forms a permissive immune microenvironment that promotes the growth of peritoneal metastatic cancer. These four core cytopathological mechanisms are mutually causal and promote each other, forming a vicious circle of GICPM development. As long as clinicians accurately understand these four points, it is possible to grasp the opportunity of clinical diagnosis and treatment, change reactive and passive treatment into preventive and proactive treatment, and improve the clinical diagnosis and treatment landscape of GICPM.

Efficacy of 1 384 cases of peritoneal carcinomatosis underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy / 中华胃肠外科杂志

Objective: Peritoneal carcinomatosis refers to a group of heterogeneous (primary or secondary) malignancies in the surface of the peritoneum. Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is a comprehensive treatment strategy aiming at peritoneal carcinomatosis. This study analyzed the efficacy and safety of CRS+HIPEC in patients with peritoneal carcinomatosis, and explored prognostic factors. Methods: In this descriptive case-series study, the clinicopathological data of 1384 consecutive patients with peritoneal carcinomatosis treated in Zhongnan Hospital of Wuhan University (330 patients) and Shijitan Hospital of Capital Medical University (1054 patients) from January 2004 to January 2020 were collected retrospectively. Treatment patterns of CRS+HIPEC characteristics (operative time, number of resected organs, number of stripped peritoneum, number of anastomosis, and HIPEC regimens), safety [blood loss volume, postoperative severe adverse event (SAE) and treatment outcome], survival time and prognostic factors influencing survival were analyzed. The SAE was defined as grade III-IV adverse event according to the Peritoneal Surface Oncology Group International Textbook. Perioperative period was defined from the day of CRS+HIPEC to postoperative 30th day. OS was calculated from the day of CRS+HIPEC to the date of death or the last follow-up. Kaplan-Meier method was used for survival analysis, and log-rank test was used for comparison between groups. Cox regression model was used to identify the prognostic factors. Results: Among 1384 peritoneal carcinomatosis patients, 529 (38.2%) were male; median age was 55 (10-87) years old; median body mass index (BMI) was 22.6 kg/m(2); peritoneal carcinomatosis of 164 (11.8%) patients were from gastric cancer, 287 (20.7%) from colorectal cancer, 356 (25.7%) from pseudomyxoma peritonei, 90 (6.5%) from malignant peritoneal mesothelioma, 300 (21.7%) from gynecological cancer or primary peritoneal carcinoma, and 187 (13.5%) from retroperitoneal sarcoma, lung cancer, breast cancer, and other rare tumors. The median duration of CRS+HIPEC was 595 (90-1170) minutes, median number of resected organs was 2 (0-10), median number of resected peritoneal area were 4 (0-9), median peritoneal cancer index (PCI) was 21(1-39). Completeness of cytoreduction (CC) score of 0-1 was observed in 857 cases (61.9%). Regarding HIPEC regimens, there were 917 cases (66.3%) with cisplatin plus docetaxel, 183 cases (13.2%) with cisplatin plus mitomycin, 43 cases (3.1%) with adriamycin plus ifosfamide, and the other 240 cases (17.3%) with modified regimens. Perioperative SAE developed in 331 peritoneal carcinomatosis patients (23.9%) with 500 cases, of whom 21 patients (1.5%) died during the perioperative period due to ineffective treatment, while the others recovered after active treatment. During median follow-up time of 8.6 (0.3-82.7) months, there were 414 deaths (29.9%). The median OS was 38.2 months (95% CI: 30.6-45.8), and the 1-, 3-, 5-year survival rate was 73.5%, 50.4% and 39.3%, respectively. The median OS of peritoneal carcinomatosis patients from gastric cancer, colorectal cancer, pseudomyxoma peritonei, malignant peritoneal mesothelioma and female genital cancer or primary peritoneal carcinomatosis was 11.3 months (95% CI: 8.9-13.8), 18.1 months (95% CI: 13.5-22.6), 59.7 months (95% CI: 48.0-71.4), 19.5 months (95% CI: 6.0-33.0) and 51.7 months (95% CI: 14.6-88.8), respectively, and the difference among groups was statistically significant (P<0.001). Univariate and multivariate analyses revealed that the primary gastric cancer (HR=4.639, 95% CI: 1.692-12.724), primary colorectal cancer (HR=4.292, 95% CI: 1.957-9.420), primary malignant peritoneal mesothelioma (HR=2.741, 95% CI: 1.162-6.466), Karnofsky performance status (KPS) score of 60 (HR=4.606, 95% CI: 2.144-9.895), KPS score of 70 (HR=3.434, 95% CI: 1.977-5.965), CC score of 1 (HR=2.683, 95% CI: 1.440~4.999), CC score of 2-3 (HR=3.661,95% CI: 1.956-6.852) and perioperative SAE (HR=2.588, 95% CI: 1.846-3.629) were independent prognostic factors influencing survival with statistically significant differences (all P<0.05). Conclusions: CRS+HIPEC is an effective integrated treatment strategy for patients with peritoneal carcinomatosis, which can prolong survival with acceptable safety. Preoperative evaluation of patients' general condition is necessary and CRS+HIPEC should be carefully considered to perform for patients with preoperative KPS score <80. During the operation, the optimal CRS should be achieved on condition that safety is granted. In addition, it is necessary to prevent perioperative SAE to reduce the risk of death in peritoneal carcinomatosis patients.

Resveratrol inhibits progression of IgA nephropathy in rats by inhibiting proliferation of mesangial cells and down regulating expression of PDGF-B and TGF-β1 / 中国药理学通报

Aim To investigate the therapeutic effect of SirTl agonist resveratrol on IgA nephropathy rats and its mechanisms. Methods An IgA nephropathy rat model was established. The rats were divided into four groups randomly: control group, IgA nephropathy group, control treated with Res group and IgA nephropathy treated with Res group. The urine protein was detected by Ponceau S; the biochemical indexes were detected by automatic biochemical analyzer; the pathological changes of kidney were observed by PAS and Masson staining; IgA deposition was observed by immunofluorescence; the expressions of PDGF-B and TGF-fil were detected by immunohistochemistry. Results Compared with IgA nephropathy group, the volume of 24-hour urinary protein and the expression of BUN and Scr in Res group decreased significantly, and the fluorescence of IgA in glomerulus was less in resveratrol group; mesangial cells and matrix proliferated and glomerular volume increased in IgA nephropathy group at the later stage, and both of them were significantly inhibited. Resveratrol could significantly reduce the high expression of PDGF-B and TGF-β1 in IgA nephropathy group. Conclusions Res can inhibit the deposition of IgA immune complex in mesangial region of IgA nephropathy rats and reduce glomerulosclerosis by down-regulating the expression of PDGF-B and TGF-β1, in turn it suppresses cell proliferation in mesangial region. It suggests that resveratrol plays an important role in slowing down the progression of IgA nephropathy.

Mechanisms of rapamycin on regulating rat mesangial cell proliferation and cell cycle through mTORC1/p70S6K pathways / 药学学报

To explore the affect and mechanisms of rapamycin on mesangial cell proliferation and cell cycle, rat mesangial cells (HBZY-1) were cultured and divided into the six groups: normal; normal with platelet derived growth factor (PDGF) 20 ng·mL-1; PDGF + rapamycin 1, 10, 100, 1 000 nmol·L-1. The cell proliferation was measured by MTT in 24 and 48 h; flow cytometry was used to detect the cell cycle phase. Western blot was performed to determine cyclin D1,cyclin E, cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 4 (CDK4), p27, p70S6K/p-p70S6K protein expression. The p27 mRNA was detect by Real-time PCR. The results showed that rapamycin significantly suppressed PDGF induced glomerular mesangial cells (MCs) proliferation in a dose and time-dependent manner, but with the dose increased (1 to 1 000 nmol·L-1), the time dependence gradually weakened. Rapamycin inhibited mesangial cell proliferation and arrested the cell cycle in the G0/G1 phase. PDGF at 20 ng·mL-1 significantly increased the expression of cyclin D1, cyclin E and CDK2, CDK4 (P < 0.05), but rapamycin did not affect the expression of cyclin D1, cyclin E and CDK2, CDK4. Rapamycin can significantly inhibited p70S6K phosphorylation, up-regulated the expression of p27 protein and mRNA. Collectively, rapamycin has the effect of inhibiting the glomerular mesangial cells proliferation of mesangial cells by regulating the transcription of p27 mRNA, increasing its protein expression through the mTORC1/p70S6K pathway, resulting in decreased activity of cyclin-CDK, and blocking cell cycle in G0/G1 phase.

Risperidone Monotherapy in Children and Adolescents with Autism Spectrum Disorders: A Naturalistic Study

OBJECTIVES: We retrospectively investigated the efficacy and tolerability of risperidone monotherapy in subjects with autism spectrum disorder (ASD). In addition, we did mixed effect model analysis of the effects of risperidone in patients with ASDs naturalistically treated in a routine clinical setting to determine whether the clinical effects were maintained and the side effects were tolerable. METHODS: This retrospective study assessed children and adolescents with ASD, who were on risperidone monotherapy from July 2010 to July 2011 at the Child and Adolescent ASD Clinic at Seoul National Hospital. Outcome measures included the Clinical Global Impression-Severity of Illness (CGI-S) and the CGI-Improvement (CGI-I) scales along with other clinical indices: dosage, target symptoms, and side effects. RESULTS: The mean dose of risperidone in 47 children and adolescents with ASD (40 males, 7 females; age range 5-19 years) who were on risperidone monotherapy was 1.6+/-0.8 mg/day, and the mean duration of the treatment period was 20.2+/-17.3 months. Aggressive behavior, stereotypic behavior, irritability, and self-injurious behavior were the most frequent target symptoms of risperidone. The most common side effects were weight gain followed by somnolence and extrapyramidal symptoms. In a mixed effects model analysis of CGI-I scores, the mean CGI-I score at the 1 month follow-up was significantly different from the mean CGI-I score of the 3-month follow-up (p=.046), and the CGI-I scores were equally maintained over 3 to 48 months [F(6, 28.9)=4.393, p=.003]. Of the 47 patients, 33 patients (70.2%) were identified as the response group, showing an end point CGI-I rating of 3 or under and having continued risperidone treatment for at least 6 months. The baseline CGI-S score showed significant association with clinical response to risperidone (p=.005), the mean baseline CGI-S was higher in the response group compared to the non-response group. CONCLUSION: In this study, clinical improvement of risperidone stabilized around 3 months and was equally maintained up to 48 months with tolerable side effects, supporting maintenance of risperidone treatment in children and adolescents with ASDs.

Effectiveness of different waist circumference cut-off values in predicting metabolic syndrome prevalence and risk factors in adults in China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To study the effectiveness of waist circumference cut-off values in predicting the prevalence of metabolic syndrome (MetS) and risk factors in adults in China.</p><p><b>METHODS</b>A cross-sectional survey was condcuted in 14 provinces (autonomous region, municipality) in China. A total of 47,325 adults aged⋝20 years were selected by multistage stratified sampling, and questionnaire survey and physical and clinical examination were conducted among them. MetS was defined according to the International Diabetes Federation (IDF) criteria and modified IDF criteria.</p><p><b>RESULTS</b>The age-standardized prevalence of MetS was 24.2% (22.1% in men and 25.8% in women) and 19.5% (22.1% in men and 18.0% in women) according to the IDF criteria and modified IDF criteria respectively. The age-standardized prevalence of pre-MetS was 8.1% (8.6% in men and 7.8% in women) according to the modified IDF criteria. The prevalence of MetS was higher in urban residents than rural residents and in northern China residents than in southern China residents. The prevalence of central obesity was about 30% in both men and women according to the ethnicity-specific cut-off values of waist circumference for central obesity (90 cm for men and 85 cm for women). Multivariate regression analysis revealed no significant difference in risk factors between the two MetS definitions.</p><p><b>CONCLUSION</b>Using both the modified IDF criteria and ethnicity-specific cut-off values of waist circumference can provide more useful information about the prevalence of MetS in China. Conclusion Using both the modified IDF criteria and ethnicity-specific cut-off values of waist circumference can provide more useful information about the prevalence of MetS in China.</p>

Ethylene treatment improves diosgenin accumulation in in vitro cultures of Dioscorea zingiberensis via up-regulation of CAS and HMGR gene expression

Background: The perennial medicinal herb Dioscorea zingiberensis is a very important plant used for steroid drug manufacturing for its high level of diosgenin in rhizome. Although the stimulation of diosgenin accumulation by ethylene has been reported in a few of plant species, its regulation is not yet characterized at the molecular level, the underlying molecular mechanism remains elusive. Results: In this study, the effects of ethylene on diosgenin biosynthesis in in vitro cultures of D. zingiberensis were described. The results showed that, in samples treated with ethylene at concentration E3 (10(4) dilution of 40% ethephon), the diosgenin biosynthesis was significantly promoted in comparison with the control samples. Treatment with high concentrations of ethylene had inhibitory effect, whereas with low concentration of the gas elicitor brought about no detectable deleterious effect on the growth rate and diosgenin content of the cultures. The considerable increase of diosgenin level in in vitro cultured Dioscorea zingiberensis by ethylene application is accompanied by the concomitant increase of soluble proteins and chlorophyll content. The gene expressions of cycloartenol synthase and 3-hydroxy-3-methylglutaryl-CoA reductase but not of squalene synthase or farnesyl pyrophosphate synthase were up-regulated by applied ethylene. Conclusions: Our results suggest that ethylene treatment enhanced diosgenin accumulation via up-regulation of the gene expressions of cycloartenol synthase and 3-hydroxy-3-methylglutaryl-CoA reductase.

Comparison of parathyroid hormone (1-34) and elcatonin in postmenopausal women with osteoporosis: an 18-month randomized, multicenter controlled trial in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recombinant human parathyroid hormone (1-34) (rhPTH (1-34)) is the first agent in a unique class of anabolic therapies acting on the skeleton. The efficacy and safety of long-term administration of rhPTH (1-34) in Chinese postmenopausal women had not been evaluated. This study compared the clinical efficacy and safety of rhPTH (1-34) with elcatonin for treating postmenopausal women with osteoporosis in 11 urban areas of China.</p><p><b>METHODS</b>A total of 453 postmenopausal women with osteoporosis were enrolled in an 18-month, multi-center, randomized, controlled study. They were randomized to receive either rhPTH (1-34) 20 µg (200 U) daily for 18 months, or elcatonin 20 U weekly for 12 months. Lumbar spine (L1-4) and femoral neck bone mineral density (BMD), fracture rate, back pain as well as biochemical markers of bone turnover were measured. Adverse events were recorded.</p><p><b>RESULTS</b>rhPTH (1-34) increased lumbar BMD significantly more than did elcatonin after 6, 12, and 18 months of treatment (4.3% vs. 1.9%, 6.8% vs. 2.7%, 9.5% vs. 2.9%, P < 0.01). There was only a small but significant increase of femoral neck BMD after 18 months (2.6%, P < 0.01) in rhPTH groups. There were larger increases in bone turnover markers in the rhPTH (1-34) group than those in the elcatonin group after 6, 12, and 18 months (serum bone-specific alkaline phosphatase (BSAP) 93.7% vs. -3.6%; 117.8% vs. -4.1%; 49.2% vs. -5.8%, P < 0.01; urinary C-telopeptide/creatinine (CTX/Cr) 250.0% vs. -29.5%; 330.0% vs. -41.4%, 273.0% vs. -10.6%, P < 0.01). rhPTH (1-34) showed similar effect of pain relief as elcatonin. The incidence of clinical fractures was 5.36% (6/112) in elcatonin group and 3.2% (11/341) in rhPTH (1-34) group (P = 0.303). Both treatments were well tolerated. Hypercaluria (9.4%) and hypercalcemia (7.0%) in rhPTH (1-34) group were transient and caused no clinical symptoms. Pruritus (8.2% vs. 2.7%, P = 0.044) and redness of injection site (4.4% vs. 0, P = 0.024) were more frequent in rhPTH (1-34). Nausea/vomiting (16.1% vs. 6.2%, P = 0.001) and hot flushes (7.1% vs. 0.6%, P < 0.001) were more common in elcatonin group.</p><p><b>CONCLUSIONS</b>rhPTH (1-34) was associated with greater increases in lumbar spine BMD and bone formation markers. It could increase femoral BMD after 18 months of treatment. rhPTH could improve back pain effectively. The results of the present study indicate that rhPTH (1-34) is an effective, safe agent in treating Chinese postmenopausal women with osteoporosis.</p>

Association of urinary albumin excretion rate and hyperuricemia with macrovascular atherosclerosis in type 2 diabetic patients / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the association of urinary albumin excretion rate (UAER) and hyperuricemia with macrovascular atherosclerosis in type 2 diabetic patients.</p><p><b>METHODS</b>Ninety-seven type 2 diabetic patients were divided into two groups according to the UAER, namely group A with UAER between 20 and 200 microg/min (n=63) and group B with UAER > or = 200 microg/min (n=34); the patients were also classified into hyperuricemia group (group C, n=59) and normal blood uric acid (BUA) group (group D, n=38). The disease course, BUA, fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoproteins (HDL), UAER and arteria carotis intima-media thickness (IMT) were determined in these patients. The relationship of UAER and hyperuricemia with carotid arterial IMT was analyzed statistically.</p><p><b>RESULTS</b>The levels of TG, TC, LDL and HDL showed no significant differences between the 4 groups (P>0.05). The disease course, BUA, UAER, and FBG levels and IMT in groups A and C were significantly higher than those in groups C and D (P<0.05), but no such differences were found between groups A and C or between groups B and D (P>0.05). Arotid arterial IMT was independently correlated to the disease course, BUA and UAER (r=0.201, 0.1999, 0.211, respectively, P<0.05), and a significant positive correlation was noted between BUA and UAER (r=0.221, P<0.05).</p><p><b>CONCLUSION</b>Macrovascular atherosclerosis in type 2 diabetic patients is significantly correlated to the disease course, BUA and UAER levels, which can be used to evaluate and predict macrovascular atherosclerosis in type 2 diabetic patients.</p>

A randomized, multicenter controlled trial to compare the efficacy of recombinant human parathyroid hormone (1-34) with elcatonin in postmenopausal women with osteoporosis in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recombinant human parathyroid hormone (1-34) (rhPTH (1-34)) given by injection is a new seventh class drug of biological products, which is prepared by adopting gene recombination technique. rhPTH (1-34) is mainly used to treat osteoporosis, especially for postmenopausal women. This study compared the clinical efficacy and safety of rhPTH (1-34) with elcatonin for treating postmenopausal women with osteoporosis in 11 urban areas of China.</p><p><b>METHODS</b>Two hundred and five women with osteoporosis were enrolled in a 6-month, multicenter, randomized, controlled study. They were randomized to receive either rhPTH (1-34) 20 microg (200 U) daily or elcatonin 20 U weekly. Lumbar spine (L1-4) and femoral neck bone mineral density (BMD), as well as biochemical markers of bone turnover were measured. Adverse events were recorded.</p><p><b>RESULTS</b>rhPTH (1-34) increased lumbar BMD significantly more than did elcatonin at 3 months and 6 months (2.38% vs 0.59%, P < 0.05; 5.51% vs 1.55%, P < 0.01), but there were no significant increases of BMD in these two groups at femoral neck. There were larger mean increases in bone markers in the rhPTH (1-34) group than in the elcatonin group at 3 months and 6 months (serum bone-specific alkaline phosphatase (BSAP) 36.79% vs 0.31%; 92.42% vs -0.17%; urinary N-telopeptide/creatinine (NTX/Cr) 48.91% vs -5.32%; 68.82% vs -10.86%). Both treatments were well tolerated and there were no significant differences detected between the two groups in the proportion of any adverse events and any serious adverse events (67.0% vs 59.0%; 0 vs 0).</p><p><b>CONCLUSIONS</b>rhPTH (1-34) has more positive effects on bone formation, as shown by the larger increments of lumbar BMD and bone formation markers, than elcatonin, with only mild adverse events and no significant change in the liver, kidney or hematological indices.</p>

Clinical evaluation of efficacy and safety of nateglinide in the treatment of type 2 diabetes / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of nateglinide, a new antidiabetic agent, in the treatment of type 2 diabetes.</p><p><b>METHODS</b>A total of 219 treatment-naïve patients with type 2 diabetes from 6 centers were enrolled in this study and blindly divided into nateglinide group (n = 105) and repaglinide group (n = 114). In all patients, the disease was confirmed for at least three months. The whole observation lasted for 12 weeks. The efficacy indicators measured include glycohemoglobin A1c (HbA1c), fasting blood glucose, and 2 hours postprandial blood glucose, and the safety parameters measured included renal and hepatic function, serum lipids, and blood and urea profiles.</p><p><b>RESULTS</b>Similar decreases in fasting blood glucose, 2 hours postprandial blood glucose, and HbA1 c were found in both nateglinide group and repaglinide group without significant differences. No severe adverse events were noted. The hypoglycemia event reports were not significantly different between these two groups.</p><p><b>CONCLUSION</b>Nateglinide is an effective and safe drug in treating type 2 diabetes.</p>

Simultaneous determination of six main constituents in Swertia of Qinghai Province and Sichuan Province by HPLC / 中国中药杂志

<p><b>OBJECTIVE</b>To establish a quantitative method of simultaneously determination of swertiamarin, gentiopicroside, mangiferin, swertianolin, isoorientin, 1,8-drihydroxy-3-methoxy-xthanone in Swertia from Qinghai province and Sichuan province by HPLC.</p><p><b>METHOD</b>The samples were separated on the column of Kromasil C18 (4. 6 mm x 250 mm, 5 microm) which eluted with methanol and water (content 0.02% phosphoric acid). The ratio of methanol increased from 20% to 80% during 20-50 min, and from 80% to 100% during 50-60 min, with detected wavelength 254 nm, flow rate at 1 mL x min(-1), column temperature 35 degrees C.</p><p><b>RESULT</b>Six compounds were base-isolated, the linear ranges of swertiamarin, gentiopicroside, mangiferin, 4-swertianolin, 5-isoorientin, 1,8-drihydroxy-3-methoxy-xthanone were excellent.</p><p><b>CONCLUSION</b>The method was rapid and precise, and can be use for controlling medicinal materials quality.</p>

Study on HPLC fingerprint of Swertia mussotii var. mussotii from north-west area of Sichuan Province I / 中国中药杂志

<p><b>OBJECTIVE</b>To constitute HPLC fingerprint of the methanol extract from Swertia mussotii grown in Sichuan Province.</p><p><b>METHOD</b>RP-HPLC, methanol and water including 0.02% acid as mobile phase, gradient elution, flow rate 1.0 mL x min(-1), the detection wavelength was 260 nm, temperature was 30 degrees C.</p><p><b>RESULT</b>The RSD values of peak area and retention time of common peaks in precision, repeatability and stability were lower than 5.0%, respectively, similarity was over 0.805 in S. mussotii collected from 10 different habitats.</p><p><b>CONCLUSION</b>All results above exhibit that this method is simple, practicable, and reliable as a standard method in controlling the quality of S. mussotii.</p>

Differential protein analysis in rat renal proximal tubule epithelial cells in response to acetazolamide and its relation with the inhibition of AQP1 / 药学学报

<p><b>AIM</b>To study the endogenous mechanism for the inhibition of aquaporin-1 expression in rat renal proximal tubule epithelial cells in response to acetazolamide.</p><p><b>METHODS</b>Primary cultured rat renal proximal tubule epithelia cells were divided into two groups: one was subjected to 1 x 10(-5) mol.L-1 acetazolamide, the other served as normal control. When grown to sub-confluency, the cells were disintegrated to perform isoelectrofocusing electrophoresis in order to find the differential proteins induced by the acetazolamide treatment. The differential proteins were defined by peptide mass fingerprinting technology.</p><p><b>RESULTS</b>Two differential proteins were found in the cell disintegrant. The pI 3.8 protein was reduced after treatment, which showed 21.4% similarity with the brush border membrane myosin from rat brain and testis, and 27% with glycogen phosphorylase; The pI 5.5 protein was increased on the contrary, with 20% similarity to phosphatidylinositol transfer protein alpha isoform.</p><p><b>CONCLUSION</b>Acetazolamide inhibited AQP1 expression probably by affecting the expression of pI 3.8 and pI 5.5 proteins.</p>

Protective effects of doxepin on focal cerebral ischemia-reperfusion injured rats / 中国药理学通报

AIM To observe protective effects of doxepin on focal cerebral ischemia-reperfusion(I-R)injured rats. METHODS 120 rats were randomly divided into ischemia-reperfusion group,doxepin, nimodipine group and sham-operated group respectively, ischemia-reperfusion model was made by using the suture emboli method, the content of NO and MDA, activities of NOS and SOD in the cerebral tissues and the intracellular [Ca 2+ ] i in the cerebral cortex were determined respectively. RESULTS The content of NO, MDA and [Ca 2+ ] i and the activities of NOS decreased and the activities of SOD increased significantly in the doxepin and nimodipine group compared with ischemia-reperfusion group respectively(P

Iodine excess induces TRAIL expression of thyrocytes in rats / 中华内分泌代谢杂志

Experimental autoimmune thyroiditis (EAT) animal model was established in female SD rats fed with high iodine diet.The concentrations of FT_3 and FT_4 were increasing in order of normal control group, iodine excess control group,EAT control group and EAT iodine excess group (Pl＜0.05 or P＜0.01).Semi- quantitative RT-PCR and Western-blotting results showed that the expression of TNF-related apoptosis-inducing ligand (TRAIL) existed in thyrocytes of each group,while the expression was increasing in order of normal control group,iodine excess control group,EAT control group and EAT iodine excess group (P＜0.01).The results suggested that high iodine diet might induce thyrocytes' apoptosis by increasing the expression of TRAIL and hence influencing functional and pathologic changes of thyroid grand.