Effects of polyol excipient stability during storage and use on the quality of biopharmaceutical formulations / 药物分析学报

Biopharmaceuticals are formulated using a variety of excipients to maintain their storage stability.However,some excipients are prone to degradation during repeated use and/or improper storage,and the impurities generated by their degradation are easily overlooked by end users and are usually not strictly monitored,affecting the stability of biopharmaceuticals.In this study,we evaluated the degra-dation profile of polyol excipient glycerol during repeated use and improper storage and identified an unprecedented cyclic ketal impurity using gas chromatography with mass spectrometry(GC-MS).The other polyol excipient,mannitol,was much more stable than glycerol.The effects of degraded glycerol and mannitol on the stability of the model biopharmaceutical pentapeptide,thymopentin,were also evaluated.The thymopentin content was only 66.4％in the thymopentin formulations with degraded glycerol,compared to 95.8％in other formulations after the stress test.Most glycerol impurities(i.e.,aldehydes and ketones)reacted with thymopentin,affecting the stability of thymopentin formulations.In conclusion,this work suggests that more attention should be paid to the quality changes of excipients during repeated use and storage.Additional testing of excipient stability under real or accelerated conditions by manufacturers would help avoid unexpected and painful results.

Treatment of senile lumbar spinal stenosis by unilateral approach and bilateral decompression with large channel endoscopy / 中国骨伤

OBJECTIVE@#To evaluate clinical effect of unilateral approach and bilateral decompression via large channel endoscopic system for the treatment of lumbar spinal stenosis.@*METHODS@#The clinical data of 32 patients with lumbar spinal tenosis treated by unilateral approach and bilateral decompression via large channel endoscopy from February 2018 to February 2019 were retrospectively analyzed. There were 18 males and 14 females, aged 65 to 84 years old with an average of (70.6± 8.4) years. The course of disease was from 1 to 12 years. All 32 cases were accompanied by numbness or pain in the lower limbs, of which 28 cases were accompanied by intermittent claudication. Narrow segments were L@*RESULTS@#All the patients were followed up for 12-24 (17.68±2.43) months and all operations were successfully completed with the operation time of 70-160(85.64±11.94) min. Spinal dural tear occurred in 1 case during the operation, and sensory disturbance in the other side of lower limb in a short period of time occurred in 2 cases, all improved after corresponding treatment. Postoperative imaging showed that the spinal canal was significantly enlarged and the nerve root was fully released. Before operation and 3 days, 3 months, 1 year after operation, VAS scores of low back pain were 4.62 ±1.41, 2.73 ±1.35, 1.21 ±1.17, 1.11 ±0.34, respectively;VAS scores of leg pain were 6.83 ± 1.71, 3.10±1.50, 1.08±0.19, 0.89±0.24, respectively. VAS scores of low back pain and leg pain each time point after operation were obvious improved (@*CONCLUSION@#It is a safe and effective way to treat lumbar spinal stenosis with unilateral approach and bilateral decompression via large channel endoscopic system. It has the advantages of sufficient decompression, less trauma, fast recovery, high safety and low incidence of postoperative complications. It can minimize the damage to the stable structure of the lumbar spine and is an ideal minimally invasive operation for the treatment of lumbar spinal stenosis.

Analysis of the correlation of PELP1/MNAR expression with expressions of estrogen receptor, human epidermal growth factor receptor 2, Ki-67 and PIK3CA gene mutation in invasive breast cancer / 肿瘤研究与临床

Objective:To investigate the correlation of PELP1/MNAR expression with expressions of estrogen receptor (ER), Ki-67, human epidermal growth factor receptor 2 (HER2) and PIK3CA gene mutation.Methods:A total of 80 paraffin-embedded tissue specimens of primary invasive breast cancer patients in the Fifth People's Hospital of Datong in Shanxi Province from January 2008 to December 2018 were collected. The expression of PELP1/MNAR was examined by immunohistochemistry EliVision tow-step method. The polymerase chain reaction (PCR)-Sanger sequencing method was used to detect the mutation of PIK3CA gene. The expressions of PELP1/MNAR among patients with different expression status of ER, Ki-67, HER2 and with or without PIK3CA gene mutation were compared, and the correlations between each index and the expression of PELP1/MNAR were analyzed.Results:The high expression rates of PELP1/MNAR protein in patients with ER-positive [86.1% (31/36) vs. 59.1% (26/44)], Ki-67 high expression [100.0% (13/13) vs. 65.7% (44/67)], HER2-positive [81.0% (34/42) vs. 60.5% (23/38)] were high, and the differences were statistically significant (all P<0.05). There was no significant difference in the high expression rate of PELP1/MNAR protein between patients with mutant and wild-type PIK3CA [60.0% (12/20) vs. 75.0% (45/60), P = 0.199]. The expression of PELP1/MNAR was negatively correlated with the expression level of ER ( r = -0.195, P < 0.05), positively correlated with the expression level of Ki-67 ( r = 0.198, P < 0.05), positively correlated with the expression level of HER2 ( r = 0.225, P < 0.05), and negatively correlated with lymph node metastasis ( r = -0.269, P < 0.05). Conclusions:The expression of PELP1/MNAR in invasive breast cancer is negatively correlated with the expression level of ER, and positively correlated with the expression level of Ki-67 and HER2. There is no correlation between PELP1/MNAR expression and PIK3CA gene mutation, and the two may play their own role in the PI3K-AKT-mTOR regulatory pathway of breast cancer.

Effect of combination of acupuncture and psychological intervention on attention, response inhibition and cerebral blood flow in children with attention deficit hyperactivity disorder / 中国针灸

OBJECTIVE@#To observe the clinical curative effect on attention deficit hyperactivity disorder (ADHD) and explore the relevant mechanism of acupuncture in treatment.@*METHODS@#A total of 100 ADHD children were randomized into an observation group (50 cases, 2 cases dropped off) and a control group (50 cases, 1 case dropped off). In the control group, the routine psychological intervention was used. In the observation group, on the base of the treatment as the control group, acupuncture was applied to Taichong (LR 3), Neiguan (PC 6), Shenmen (HT 7), Sanyinjiao (SP 6), Baihui (GV 20), Sishencong (EX-HN 1), etc., once daily, for 3 months. The Cambridge neuropsychological tests automated battery (CANTAB) was adopted to evaluate attention and response inhibition in two groups before and after treatment. Digi-Lite color transcranial Doppler was used to measure cerebral arterial blood velocity. The therapeutic effect was compared between the two groups.@*RESULTS@#Regarding evaluation of attention, the mean delay time in the observation group after treatment was shorter than that before treatment and that in the control group separately (@*CONCLUSION@#Acupuncture combined with psychological intervention may improve attention and response inhibition in ADHD children, which is possibly related to the regulation of cerebral blood flow.

Effect of maternal immune level at different pregnancy stages on cow's milk protein allergy in infants / 中国当代儿科杂志

OBJECTIVE@#To study the association between maternal Th1/Th2 immune level at different pregnancy stages and cow's milk protein allergy (CMPA) in infants.@*METHODS@#The healthy women with a singleton pregnancy, as well as their offspring, who attended Yidu Central Hospital of Weifang and Qingzhou Traditional Chinese Medicine Hospital from July 2016 to December 2018 were enrolled. The maternal levels of interleukin-2 (IL-2), interferon gamma (IFN-γ), interleukin-4 (IL-4), and interleukin-10 (IL-10) at the second and third trimesters of pregnancy were measured. A CMPA questionnaire survey was conducted within one year after birth. Food avoidance and cow's milk oral challenge tests were performed in infants suspected of CMPA. The 48 infants who met the diagnostic criteria for CMPA were included in the observation group, and the remaining 977 normal infants were included in the control group. A univariate analysis was performed on the infants with CMPA. A Poisson regression analysis was used to determine the association between maternal Th1/Th2 immune factors at different pregnancy stages and CMPA.@*RESULTS@#The detection rate of CMPA was 4.68%. The clinical manifestations included the symptoms of the digestive system, skin, and respiratory system and other symptoms. The univariate analysis showed that compared with the control group, the observation group had significantly higher incidence rates of maternal food allergy and maternal history of allergic diseases (P<0.05) and a significantly lower breastfeeding rate (P<0.05). The observation group had significantly lower maternal levels of IL-2 (second and third trimesters) and IFN-γ (third trimester) than the control group (P<0.05). Maternal low IFN-γ at the third trimester and maternal low IL-2 at the second and third trimesters were significantly associated with CMPA in infants (P<0.05). After correction of the factors of breastfeeding, maternal food allergy, and maternal history of allergic diseases, it was found that maternal low IL-2 and IFN-γ at the third trimester were still significantly associated with CMPA in infants (P<0.05).@*CONCLUSIONS@#The maternal decrease in Th1 level at the third trimester of pregnancy may lead to the change in fetal immunity and thus increase the risk of CMPA in offspring.

Value of the combination of renal resistive index and central venous pressure to predict septic shock induced acute kidney injury / 中华危重病急救医学

Objective:To explore a better indicator that can predict septic shock induced acute kidney injury (AKI) by combining renal resistive index (RRI) and central venous pressure (CVP).Methods:A prospective observational study was conducted. Patients with septic shock admitted to department of critical care medicine of Hebei General Hospital from November 2017 to October 2018 were enrolled. Baseline characteristics such as age, gender, underlying diseases, infection sites, acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) in the first 24-hour, sequential organ failure assessment (SOFA) were recorded; Doppler-based RRI was obtained on the first day when hemodynamics was relatively stable, meanwhile the dose of norepinephrine and hemodynamic parameters were assessed. Urine output per hour, the total duration of mechanical ventilation, the length of intensive care unit (ICU) stay and 28-day mortality were also collected. Observational end point was death at discharge or the 28th day after ICU admission, whenever which came first. The patients were divided into AKI and non-AKI groups according to the 2012 Kidney Disease: Improving Global Organization (KDIGO) clinical practice guideline. The baseline and prognostic indicators, variables potentially associated with AKI were compared between the two groups. The variables independently associated with septic shock induced AKI were identified using multivariable Logistic regression. The predictive value of RRI and RRI combining CVP for AKI were analyzed by the receiver operating characteristic (ROC) curve.Results:A total of 107 patients were enrolled, with 59 patients in AKI group and 48 patients in non-AKI group. There was significant difference in RRI, CVP, percentage of norepinephrine dosage ≥0.5 μg·kg -1·min -1, procalcitonin (PCT), lactate (Lac), and serum creatinine (SCr) between the two groups. Logistic regression analysis showed that high CVP, RRI, Lac and PCT were independent risk factors for septic shock induced AKI [CVP: odds ratio ( OR) = 1.20, 95% confidence interval (95% CI) was 1.03-1.40, P = 0.022; RRI: OR = 3.02, 95% CI was 2.64-3.48, P = 0.006; Lac: OR = 2.43, 95% CI was 1.32-4.50, P = 0.005; PCT: OR = 1.20, 95% CI was 1.05-1.38, P = 0.009]. ROC curve analysis showed that the area under ROC curve (AUC) values of CVP≥9.5 mmHg (1 mmHg = 0.133 kPa) and RRI≥0.695 for predicting septic shock induced AKI were 0.656 and 0.662 respectively. The AUC value of the combination of RRI and CVP was greater compared with either RRI or CVP alone in predicting septic shock induced AKI, which AUC value was 0.712, 95% CI was 0.615-0.809, the sensitivity was 59% and the specificity was 75%. Conclusions:High CVP and RRI were independent risk factors for septic shock induced AKI. The combination of RRI and CVP performs poorly in predicting septic shock induced AKI. Further studies are needed to describe factors influencing Doppler-based assessment of RRI, which may help clinicians to prevent AKI early.

Efficacy of cardiopulmonary ultrasound in guiding volume therapy in patients with sepsis-induced myocardial injury / 中华麻醉学杂志

Objective To evaluate the effect of cardiopulmonary ultrasound in guiding volume ther-apy in the patients with sepsis-induced myocardial injury. Methods Thirty-eight patients of both sexes with septic myocardial injury, aged 28-64 yr, weighing 60-90 kg, received anti-infection, respiratory and circulatory comprehensive treatment. The patients were divided into group Ⅰ ( n=19) and group Ⅱ(n=19) by using a random number table method. Central venous pressure (CVP) was used to guide vol-ume therapy, and fluid replacement was carried out using the CVP 2-5 principle in groupⅠ. Cardiopulmo-nary ultrasound was used to guide volume therapy in group Ⅱ. Blood samples were taken before volume therapy and on 1, 3 and 5 days after volume therapy to determine the concentrations of N-terminal pro-B-type natriuretic peptide, cardiac troponin I and creatine kinase isoenzyme MB in serum. The CVP, positive fluid balance, lactic acid, central venous oxygen saturation and urine volume were recorded at 6, 24, 48 and 72 h after volume therapy. Left ventricular ejection fraction was recorded at 1, 3 and 5 days after vol-ume therapy. The length of intensive care unit stay and 28-day fatality were recorded. Results Compared with groupⅠ, the CVP and fluid positive balance were significantly decreased at each time point after vol-ume therapy, the concentration of serum N-terminal pro-B-type natriuretic peptide was decreased at 5 days after volume therapy ( P<0. 05) , and no significant difference was found in concentrations of cardiac tropo-nin I and creatine kinase isoenzyme MB in serum, lactic acid, central venous oxygen saturation and urine volume, left ventricular ejection fraction, length of intensive care unit stay or 28-day fatality rate at each time point in groupⅡ( P>0. 05) . Conclusion Cardiopulmonary ultrasound can reduce the volume of liq-uid infused, avoid fluid overload and avoid accentuating myocardial injury when used to guide volume thera-py in the patients with sepsis-induced myocardial injury.

Change in the expression of the NLRP3 inflammasome signaling pathway in peripheral blood and its significance in children with Mycoplasma pneumoniae pneumonia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the expression of the NLRP3 inflammasome signaling pathway in peripheral blood and its significance in children with Mycoplasma pneumoniae pneumonia (MPP).</p><p><b>METHODS</b>According to the severity, 147 children with MPP were divided into mild group with 83 children and severe group with 64 children. According to the stage of disease, the children were divided into acute group with 77 children and recovery stage with 70 children. A total of 50 healthy children were enrolled as the control group. Quantitative real-time PCR was used to measure the mRNA expression of NLRP3, ASC, and caspase-1. ELISA was used to measure the serum levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18).</p><p><b>RESULTS</b>Compared with the control group, the children with MMP had significantly higher relative mRNA expression levels of NLRP3, ASC, and caspase-1 in peripheral blood and serum levels of IL-1β and IL-18 (P<0.05). Compared with the control group, both mild and severe groups had significantly higher relative mRNA expression levels of NLRP3, ASC, and caspase-1 in peripheral blood and serum levels of IL-1β and IL-18 (P<0.05). The severe group had significantly higher levels of above mentioned parameters than the mild group (P<0.05). Both acute group and recovery group had significantly higher relative mRNA expression levels of NLRP3, ASC, and caspase-1 in peripheral blood and serum levels of IL-1β and IL-18 than the control group (P<0.05). The acute group had significantly higher levels of above mentioned parameters than the recovery group (P<0.05). The relative expression level of NLRP3 was positively correlated with the relative mRNA expression levels of ASC and caspase-1 and the serum levels of IL-1β and IL-18 (r=0.701, 0.717, 0.676, and 0.645 respectively; P<0.05).</p><p><b>CONCLUSIONS</b>The NLRP3 inflammasome signaling pathway might be involved in the pathogenesis of MPP in children and is closely associated with the severity and course of the disease.</p>

Rictor/mTORC2 regulates blood-testis barrier and spermatogenesis in mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the role of Rictor/mTORC2 in the formation of blood testis barrier (BTB), testicular development, and spermatogenesis.</p><p><b>METHODS</b>Amh Cre positive mice homozygous for rictor loxP with Sertoli cell specific deletion of rictor were obtained by cross breeding Amh Cre mice with rictor loxP mice. The histology of the reproductive organs, seminiferous tubules and epididymis of the transgenic mice was observed with HE staining. The cell subgroups of the germ cells in the seminiferous tubule were detected by flow cytometry with propidium iodide labeling. The expression levels of Ki 67 and separase were detected with immunofluorescence assay, and the expression levels of BTB associated proteins were detected with immunofluorescence and Western blotting.</p><p><b>RESULTS</b>Compared with the control (Amh Cre, rictoror rictor) mice, the mice with Sertoli cell specific rictor deletion showed significantly decreased testicular weight and epididymis weight (P<0.05), significantly increased diploid cells (P<0.01), and decreased haploid cells (P<0.01) but comparable tetraploid cells and similar expression levels of Ki 67 and separase. The mice with rictor knockout also showed aberrant localization of BTB associated proteins, which were scattered over the whole seminiferous epithelium, but the expression levels of the protein remained stable.</p><p><b>CONCLUSION</b>Rictor in testicular Sertoli cells is essential for maintaining BTB integrity and function and ensuring normal spermatogenesis in mice.</p>

Differential gene expression profiling for identification of potential pathogenic genes and pathways in carotid unstable plaques / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the molecular mechanism in the formation of unstable plaques.</p><p><b>METHODS</b>The cDNA microarray E-MTAB-2055 was downloaded from ArrayExpress database to screen the differentially expressed genes in 24 ruptured plaques against 24 stable plaques. Functional enrichment analysis was conducted to define the biological processes and pathways involved in disease progression. The protein-protein interaction network was constructed to identify the risk modules with close interactions. Five pairs of carotid specimens were used to validate 3 differentially expressed genes of the risk modules by real-time PCR.</p><p><b>RESULTS</b>A total of 439 genes showed differential expression in our analysis, including 232 up-regulated and 207 down-regulated genes according to the data filter criteria. Immune-related biological processes and pathways were greatly enriched. The protein-protein interaction network and module analysis suggested that TYROBP, VCL and CXCR4 might play critical roles in the development of unstable plaques, and differential expressions of CXCR4 and TYROBP in carotid plaques were confirmed by real-time PCR.</p><p><b>CONCLUSION</b>Our study shows the differential gene expression profile, potential biological processes and signaling pathways involved in the process of plaque rupture. TYROBP may be a new candidate disease gene in the pathogenesis of unstable plaques.</p>

The relationship between angle of puncture and distribution of bone cement of unilateral percutaneous kyphoplasty for the treatment of thoracolumbar compression fractures / 中国骨伤

<p><b>OBJECTIVE</b>To explore the relationship of bone cement distribution and the puncture angle in the treatment of thoracolumbar compression fractures with unilateral percutaneous kyphoplasty (PKP).</p><p><b>METHODS</b>The clinical data of 37 patients with thoracolumbar osteoporotic compression fractures underwent PKP between January 2013 to March 2014 were retrospectively analyzed, all punctures were performed unilaterally. There were 6 males, aged from 65 to 78 years old with an average of (71.83 ± 6.15) years; and 31 females, aged from 57 to 89 years old with an average of (71.06 ± 7.89) years. Imaging data were analyzed and puncture angle and puncture point were measured before operation. According to the measured data, the puncture were performeds during the operation. Distribution area of bone cement were calculated by X-rays data after operation. The effect of bone cement distribution on suitable puncture angle was analyzed; VAS score was used to evaluate the clinical effects.</p><p><b>RESULTS</b>The puncture angle of thoracic vertebrae in T8-T12 was from 28° to 33° with an average 30.4°; and the puncture angle of lumbar vertebrae in L1-L5 was from 28° to 35° with an average of 31.3°. Postoperative X-rays showed the area ratios of bilateral bone cement was 0.97 ± 0.15. Bilateral diffuse area were basic equal. Postoperative VAS score decreased significantly (1.89 ± 1.29 vs 7.03 ± 1.42).</p><p><b>CONCLUSION</b>Through measure imaging data before operation with PKP,the puncture point and entry point can be confirmed. According the measured data to puncture during operation, unilateral puncture can reach the distribution effect of the bilateral puncture in the treatment of thoracolumbar compression fractures.</p>

Analysis on risk factors of endotracheal cuff under inflation in mechanically ventilated patients / 中华危重病急救医学

Objective To investigate the prevalent condition of endotracheal cuff pressure and risk factors for under inflation. Methods A prospective cohort study was conducted. Patients admitted to the Department of Critical Care Medicine of Fuxing Hospital Affiliated to Capital Medical University,who were intubated with a high-volume low-pressure endotracheal tube,and had undergone mechanical ventilation for at least 48 hours,were enrolled. The endotracheal cuff pressure was determined every 8 hours by a manual manometer connected to the distal edge of the valve cuff at 07:00,15:00,and 23:00. Measurement of the endotracheal cuff pressure was continued until the extubation of endotracheal or tracheostomy tube,or death of the patient. According to the incidence of under inflation of endotracheal cuff,patients were divided into the incidence of under inflation lower than 25%group(lower low cuff pressure group)and higher than 25% group(higher low cuff pressure group). The possible influencing factors were evaluated in the two groups,including body mass index(BMI),size of endotracheal tube,duration of intubation,use of sedative or analgesic,number of leaving from intensive care unit(ICU),the number of turning over the patients, and aspiration of sputum. Logistic regression analysis was used to determine risk factors for under-inflation of the endotracheal cuff. Results During the study period,53 patients were enrolled. There were 812 measurements,and 46.3%of them was abnormal,and 204 times(25.1%)of under inflation of endotracheal cuff were found. There were 24 patients(45.3%)in whom the incidence of under inflation rate was higher than 25%. The average of under inflation was 7(4,10)times. Compared with the group with lower rate of low cuff pressure,a longer time for intubation was found in group with higher rate of low cuff pressure〔hours:162(113,225)vs. 118(97,168),Z=-2.034,P=0.042〕. There were no differences between the two groups in other factors,including size of endotracheal tube,the time from intubation to first measurement of endotracheal cuff pressure,number of leaving from ICU during admission, use of sedative agent or analgesic,and the number of body turning and aspiration(all P>0.05). No risk factor was found resulting from under inflation of the endotracheal cuff by logistic regression analysis. No significant difference was found in the incidence of ventilator associated pneumonia,duration of mechanical ventilation,successful rate of weaning on 28th day,or 28-day mortality after weaning from mechanical ventilation,and ICU mortality between the two groups. However,patients in the group of higher rate of low cuff pressure had a longer ICU stay compared with that in the group of lower rate of low cuff pressure group〔days:13(8,21)vs. 10(6,18),Z=-2.120,P=0.034〕. Conclusions Abnormal endotracheal cuff pressure is common in critically ill patients with intratracheal intubation. Duration of intubation is associated with under inflation of the cuff,and it calls for strengthening monitoring and management.

Effect of melatonin on proliferation and apoptosis of fibroblasts in human hypertrophic scar / 中华烧伤杂志

<p><b>OBJECTIVE</b>To study the effect of melatonin on proliferation and apoptosis of fibroblasts in human hypertrophic scar and its mechanism.</p><p><b>METHODS</b>Fibroblasts from human hypertrophic scar were isolated and cultured with DMEM medium containing 10% FBS, and then they were divided into control (C, added with ethanol), low concentration (LC, added with 1 × 10(-5) mmol/L melatonin), middle concentration (MC, added with 1 × 10(-3) mmol/L melatonin), and high concentration (HC, added with 1 mmol/L melatonin) groups according to the random number table. After being cultured for 24 hours, cell morphologic change was observed under microscope; XTT-PMS assay was used to examine cell proliferative activity; cell cycle and apoptosis were assessed with flow cytometry after double staining of FITC and PI, and the levels of cyclin E, p53, and Fas mRNA were determined with fluorescence quantitative RT-PCR. Data were processed with analysis of variance and LSD test.</p><p><b>RESULTS</b>(1) Fibroblasts in C group were spindle-shaped with growth in colonies. Along with the increase in melatonin concentration, fibroblasts in LC, MC, and HC groups gradually dispersed, deformed and atrophied, with shrunk cellular membrane, and decrease in ratio of nucleus and cytoplasm. (2) Proliferative activity of fibroblasts in LC, MC, and HC groups decreased along with an increase in melatonin concentration (1.49 ± 0.15, 1.24 ± 0.20, and 0.92 ± 0.09), which were lower that in C group (1.79 ± 0.10, F = 67.61, P < 0.05). Cell ratios of S and G2/M phases in LC, MC, and HC groups decreased along with an increase in melatonin concentration, which were all lower than those in C group [(10.6 ± 1.1)%, (6.1 ± 1.2)%, (3.2 ± 0.8)% vs.(16.9 ± 1.3)%, F = 286.10, P < 0.05; (13.5 ± 1.1)%, (9.8 ± 1.0)%, (6.0 ± 0.7)% vs. (16.7 ± 1.6)%, F = 162.69, P < 0.05]. Apoptotic rates in early and late stages of LC, MC, and HC groups increased along with an increase in melatonin concentration, all higher than those in C group (with F value respectively 424.05, 236.44, P values all below 0.05). The expressions of cyclin E mRNA in LC, MC, and HC groups decreased along with an increase in melatonin concentration, which were lower than that in C group (1.58 ± 0.21, 0.90 ± 0.20, and 0.24 ± 0.12 vs. 2.90 ± 0.30, F = 266.79, P < 0.05), while the expressions of p53 mRNA and Fas mRNA showed opposite tendency (with F value respectively 10.11, 12.03, P values all below 0.05).</p><p><b>CONCLUSIONS</b>Melatonin can inhibit proliferation and induce apoptosis of fibroblasts in hypertrophic scar through regulating the gene expressions of cyclin E, p53, and Fas.</p>

Expression of secretions of hypothalamus-pituitary-adrenal axis in human hypertrophic scar / 中华烧伤杂志

<p><b>OBJECTIVE</b>To explore the expression and significance of secretions of hypothalamus-pituitary-adrenal (HPA) axis in human hypertrophic scar.</p><p><b>METHODS</b>Hypertrophic scar tissues obtained from 12 patients with deep-partial thickness burn or full-thickness burn and normal skin tissues from the same 7 patients with hypertrophic scar were harvested for determination of gene expression of corticotrophin-releasing hormone (CRH), CRH receptor 1 (CRH-R1), pro-opiomelanocortin (POMC), melanocortin receptor 2 (MC-2R), and glucocorticoid receptor α (GR-α) by real-time fluorescence quantitative PCR. After addition of corresponding antibodies, distribution differences of CRH, CRH-R1, adrenocorticotropic hormone (ATCH), MC-2R, and GR-α were observed with immunohistochemical staining. Data were processed with t test.</p><p><b>RESULTS</b>The mRNA expression of CRH, CRH-R1, POMC, and GR-α in hypertrophic scar was respectively 3.1 ± 0.8, 0.05 ± 0.03, 0.020 ± 0.007, and 0.0030 ± 0.0010, which were significantly lower than those in normal skin (20.6 ± 4.7, 0.30 ± 0.12, 0.060 ± 0.020, and 0.0200 ± 0.0070, with t values from 2.10 to 4.75, P values all below 0.05). There was no statistical difference in MC-2R mRNA expression between hypertrophic scar and normal skin (t = 1.48, P = 0.15). Immunohistochemical observation showed CRH, CRH-R1, ACTH, MC-2R, and GR-α in hypertrophic scar were located in basal layer of epidermis, fibroblast of dermis, and tube wall of sweat gland. Expressions of these indexes could also be observed in sebaceous gland and hair follicle besides above-mentioned structures.</p><p><b>CONCLUSIONS</b>Decreasing expression of active material of HPA axis may be related to formation of hypertrophic scar.</p>

Therapeutic effects of three topical remedies on periodontitis / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare the therapeutic effects of minocycline, metronidazole and iodine glycerin on periodontitis.</p><p><b>METHODS</b>A total of 123 patients were randomly divided into 3 groups to receive the 3 topical remedies administered into the periodontal pockets. The total response rate of the 3 treatments was calculated, and the changes in GI, PL I, PD and BO P were observed.</p><p><b>RESULTS</b>All the clinical indices of the 3 groups showed obvious improvements after the treatments compared with the baseline levels. The clinical indices of minocycline group and metronidazole group showed significant greater improvements than those of iodine glycerin group. The total response rate in minocycline group and metronidazole group was higher than that of iodine glycerin group.</p><p><b>CONCLUSIONS</b>Minocycline and metronidazole as topical remedies can be effective auxiliary treatments of periodontitis.</p>

Investigation on prevalence and dietary structure of drinking-tea fluorosis in Qinghai province in 2007 / 中国地方病学杂志

Objective To investigate epidemical situation of drinking-tea fluomsis in Qinghai province, in order to understand diet structure to provide the scientific basis for the prevention and control and the scientific research. Methods In 2007, according to "Scheme for Survey on Epidemical Drinking-tea Fluorosis", we carried out an customized investigation in 28 counties, 3 townships sampled in each county, 2 villages in each township, 50 adults and 50 school-age children in each village; at same time, 1 monk temple was sampled in each county, 50 clergy adults and 50 children in each temple. Then we investigated the resident income, the diet structure, the brick tea consumption and so on, and applied Dean method to diagnose dental fluorosis. The patient number estimated based on the survey result. Results ①Yeady per capita income of people was mostly 500 - < 1000yuan, next 1000 - < 3000 yuan; economic income in pasturing area was higher than that of agriculture, half area and half agriculture and half pastoral region and township. ②Staple food was bread flour primarily in the animal husbandry agricultural half pastoral area,next were the roasted barley and the rice;the bread flour was the principle food in the agricultural region and the cities,next were the rice and the roasted barley;among non-staple food,meat came fimt and milk foHowed,egg the last.③The frequently edible vegetables Was potato.cabbage and greenpepper,eaten by a majority of people[62.82%(6497/10 343)];as for fruits,apple,pear and orange was primarily consumed,75.95%(7856/10 343)of people ate less than 10 times every month.④Sixty-one thousand nine hundred and ninety-nine residents were registered,153 335 kg ofbrick tea was consumed in villages and towns,2.47 kg per person;in 1001 monks investigated,4120 kg of brick tea was consumed every year,4.12 kg per person.⑤Detection rate of adult dental fluorosis in the villages and towns was 24.11%(2494/10 343),that of the children was 24.38% (3012/12 355);detection rate of dental fluorosis in monks was 26.13%(203/777),that of the children was 39.73% (89/224).⑥Detection rate of adult skeletal fluorosis in villages and towns was 15.60%(17/109);that of monks was 4.88%(2/41).⑦The 95%confidence limit estimated a total number of dental fluorosis patients were 1 084 306- 1 134 170 persons.the median Was 1 109 238 persons;the 95% confidence limit estimated a total number of skeletal fluorosis patients were 309 177-758 199 persons,the median was 533 688 persons.Conclusions Qinghai province has a great quantity of brick tea consumption,having lots of people with drinking-tea fluorosis which is in severe degree.The resident food structure was monotonous and mostly transpolted from other region.

The expression of melatonin receptor in human hypertrophic scar / 中华整形外科杂志

<p><b>OBJECTIVE</b>To investigate the expression and its significance of melatonin receptor in human hypertrophic scarring.</p><p><b>METHODS</b>The expression of melatonin receptor GPR50 was detected with immunohistochemistry and the melatonin receptors (MT1, MT2) mRNA were assessed with RT-PCR method in 10 cases of human hypertrophic scar and normal skin. The positive production was sequenced with auto sequencing instrument.</p><p><b>RESULTS</b>Positive signals of melatonin receptor could be found in the cell membrane and cytoplasm. The melatonin receptor GPR50 was located in the epithelial basal cells,sweat gland cells and hair follicle in both hypertrophic scar and normal skin. The melatonin receptor GPR50 was extensively expressed in fibroblasts of hypertrophic scar, but not in fibroblasts in normal skin. RT-PCR showed that the expression of melatonin receptor (MT1, MT2) mRNA in hypertrophic scar was significantly higher than that in normal skin (P < 0.05). In normal skin and hypertrophic scar group, the expression of MT1 mRNA was higher than MT2 mRNA (P < 0.05). In normal skin and hypertrophic scar group, the expression of MT1 mRNA was 0.99081 +/- 0.26485 and 1.16584 +/- 0.21829 copy number/microl cDNA, respectively; the expression of MT2 mRNA was 0.77083 +/- 0.15927 and 0.99550 +/- 0.14624 copy number/ microl cDNA, respectively. Sequencing results indicated that the positive product coincided with cDNA of human melatonin receptor in GeneBank.</p><p><b>CONCLUSIONS</b>Positive expression of melatonin receptor can be found in human hypertrophic scar and normal skin, but it is higher in scar. The over expression of melatonin receptor in hypertrophic scar may be related to the development of hypertrophic scar.</p>

Diagnosis of liver pathologies based on apparent diffusion coefficient of magnetic resonance diffusion-weighted imaging in a rabbit model of liver fibrosis / 南方医科大学学报

<p><b>OBJECTIVE</b>To assess the value of apparent diffusion coefficient (ADC) of magnetic resonance diffusion-weighted imaging (MR-DWI) for diagnosis of the liver pathologies in rabbit model of liver fibrosis.</p><p><b>METHOD</b>MR-DWI with four different b values (200, 500, 300 and 600 s/mm(2)) was performed in 4 normal New Zealand white rabbits and 13 rabbits with experimental liver fibrosis. For each rabbit, 4 ADC values were obtained in the left and right lobes of the liver. According to the ISHAK criteria of liver histopathological scoring and fibrosis staging system, all the liver specimens were histopathologically graded (scores 1-6 for grade I, 7-12 for grade II, and 13-18 for grade III) and assessed for fibrosis staging (stages I to VI). The variation of ADC values were analyzed based on the results of histopathological grading and fibrosis staging.</p><p><b>RESULTS</b>The 4 ADC values were obviously lower in rabbits with liver fibrosis than in the normal control rabbits. Statistical analysis showed significant differences in the ADC values between the normal control and liver fibrosis groups, and between the rabbits with different histopathological grades and fibrosis stages (P=0.000).</p><p><b>CONCLUSIONS</b>Liver fibrosis results in significantly lowered ADC values of the liver depending on the histopathological grades and fibrosis stages. The pathological basis for these changes lies in reduced water content and restricted Brownian motion of water in the liver due to hepatocyte degeneration and swelling, inflammatory cell infiltration, and collagen fiber deposition in the interstitial space.</p>

Hepatitis B virus P22(e) inhibit hepatocyte apoptosis via nuclear factor kappa B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To test whether nuclear factor kappa B plays an important role in the apoptosis-inhibitory effect of hepatitis B virus (HBV) P22(e) protein.</p><p><b>METHODS</b>HepG2 cells were transfected with recombination plasmid pEGFP-HBVP22(e). The Act-D and TNF alpha were used to induce apoptosis. NF-kappa B inhibitor ALLN were used to inhibit the signaling pathway. The activation of NF-kappa B was EMSA, and the nulear translocation of NF-kappa B was determined by immuno-staining.</p><p><b>RESULTS</b>Laser scanning confocal microscopy and EMSA indicated that HBV P22(e) protein enhanced the nuclear translocation of NF-kappa B after apoptosis induction. ALLN treatment inhibited the nuclear translocation of NF-kappa B, and blocked the apoptosis-inhibiting effect of HBV P22(e) protein.</p><p><b>CONCLUSION</b>This study indicates that HBV P22(e) protein inhibits apoptosis of hepatocyte via the NF-kappa B signaling pathway.</p>

Effect of liquorice decoction on rat intestinal P-glycoprotein / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of liquorice in functional modulation of intestinal P-glycoprotein (P-gp) in rats.</p><p><b>METHODS</b>An in vitro diffusion chamber system (Ussing chamber) was used to examine the direct effect of liquorice decoction on rhodamine 123 (a subtrate of P-gp) transport and evaluate the permeability of rhodamine 123 or fluorescein sodium through rat jejunum membranes after oral administration of liquorice decoction.</p><p><b>RESULTS</b>Direct application of liquorice decoction did not obviously affect rhodamine 123 transport across the intestinal mucosa. Oral administration of liquorice decoction (10 g/kg, twice daily for a week) significantly increased the absorption of rhodamine 123 and also enhanced rhodamine 123 secretion across the jejunum mucosa. Liquorice had no obvious effect on the transport of CF across the jejunum mucosa.</p><p><b>CONCLUSION</b>Liquorice may slightly inhibit P-gp function in the intestinal mucosa to increase the intestinal absorption of rhodamine 123.</p>