Validation of a fast and reliable liquid chromatography tandem mass spectrometry for simultaneous quantitation of Voriconazole, Posaconazole and Linezolid in human serum / 中华检验医学杂志

Objective:To establish a high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of voliconazole (VRC), posaconazole (PCZ), and linazolam (LNZ) in human serum.Methods:This study is a methodological validation by LC-MS/MS. The blood concentration results of VRC, PCZ, and LNZ in our hospital′s anti-infection patients were collected. Voriconazole, Posaconazole, and Linezolid were accurately weighed and prepared. Linezolid-[2H3] was used as the internal standard. After gradient elution on the ACE PFP column, the residuals were analyzed by LC-MS/MS in the positive electrospray ionization mode and multiple reaction monitor (MRM) mode. The method′s linearity, precision, lower limit of detection, and recovery rate were validated according to standard guidelines.Results:The linear correlation coefficient ( r) of the standard curve was above 0.99 ( r>0.99). The linear range of VRC and PCZ were 0.10 mg/L~10.00 mg/L, and the lower limit of detection were 0.01 mg/L. The linear range of LNZ was 0.50 mg/L~50.00 mg/L, and the lower limit of detection was 0.05 mg/L. The recoveries of VRC, PCZ and LNZ were 90.96%-103.18%, 91.84%-99.17%, and 97.04%-100.41%, respectively. Intra-and inter-batch precision (% CV) for VRC were less than 8.30%. Intra-and inter-batch precision (% CV) for PCZ was less than 9.78%. Intra-and inter-batch precision (% CV) for LNZ was less than 7.14%. Drug concentrations in 155 cases of VRC, 44 cases of PCZ, and 59 cases of LNZ were detected. Conclusion:We have established an LC-MS/MS method for the rapid, accurate, highly specific determination of VRC, PCZ, and LNZ concentrations in human serum. This method is suitable for analyzing large clinical sample sets.

Value of urinary C-terminal agrin fragment in monitoring the progression of early kidney injury in type 2 diabetic patients / 中华检验医学杂志

Objective:This study aimed to explore the feasibility and clinical value of monitoring the progression of early kidney injury in type 2 diabetic patients by assessment of the urinary C-terminal agrin fragment (uCAF) with enzymatic chemiluminescence immunoassay.Methods:A total of 251 patients with type 2 diabetes, who attended the Second Affiliated Hospital of Wenzhou Medical University from October 2018 to March 2020, were included in this retrospective analysis. One hundred and fifty-six participants undergoing health check-up at the Second Affiliated Hospital of Zhejiang University School of Medicine in February 2021 served as controls. Basic clinical information, glycosylated hemoglobin type A 1c and serum creatinine values were recorded, and urine specimens were collected for urinary creatinine, urinary α 1 microglobulin(uα 1M), urinary immunoglobulin G (uIgG), urinary albumin, urinary N-Acetyl-B-D-glycosaminidase (uNAG) and uCAF measurements. Based on the estimated glomerular filtration rate (eGFR), 251 patients were classified into G1~G5 stage groups with 116, 22, 28, 55 and 30 patients in each group. One hundred and sixty-six patients with early diabetic kidney disease (stage G1-G3) were divided into subgroups A1 (79), A2 (48) and A3 (39) according to the urinary albumin/creatinine ratio (UACR), the uα1M levels were divided into uα1M subgroup 1 (83 cases), uα1M subgroup 2 (42 cases), and uα1M subgroup 3 (41 cases), and uIgG subgroup 1 (83 cases), uIgG subgroup 2 (42 cases), and uIgG subgroup 3 (41 cases) according to uIgG levels. The Spearman method was used to analyze the correlation between uCAF levels and eGFR, UACR, uα1M and uIgG levels. Results:(1) The linear range of the uCAF detected by enzymatic chemiluminescence immunoassay was 3.97-2 000.00 ng/ml, with a detection limit of 2.28 ng/ml, intra-batch coefficients of variation of 1.15% and 1.57%, inter-batch coefficients of variation of 1.63% and 5.78%, and a biological reference interval of <95.35 μg/g Cr. (2) The uCAF level and positive rate (UACR≥30 mg/g) increased with the decrease of eGFR from G1-G3, uCAF level was negatively correlated with eGFR value ( r=-0.543, P<0.000 1), and the positive rate increased from 24.14% (28/116) to 85.71% (24/28) from G1-G3. The uCAF level and positivity rate decreased with the decrease of eGFR from G4 to G5. uCAF level was positively correlated with eGFR value ( r=0.495, P<0.001), and the positivity rate decreased from 30.91% (17/55) to 23.33% (7/30) from G4 to G5. (3) In patients with early diabetic kidney disease, uCAF levels and positivity rates increased gradually with the increase of UACR. uCAF levels were positively correlated with UACR values ( r=0.602, P<0.001), and the uCAF positivity rate reached 21.52% (17/79) in the A1 subgroup. (4) uCAF level was positively correlated with uα1M and uIgG levels in patients with early diabetic kidney disease ( r=0.757, 0.596, both P<0.001). Conclusion:Analytical performance of enzyme chemiluminescence immunoassay for the detection of CAF is satisfactory and could be used a biomarker for monitoring damage and progression of early diabetic kidney disease in patients with type 2 diabetes.

Correlation analysis of 3D-FLAIR MRI characteristics of the inner ear and vestibular function in the patients with vestibular neuritis / 中华耳鼻咽喉头颈外科杂志

Objective: The characteristics of 3D-FLAIR MRI images of the inner ear of patients with vestibular neuritis were preliminarily studied to explore the possible pathogenesis of vestibular neuritis, and the correlation analysis was conducted in combination with vestibular function to provide a basis for accurate diagnosis of vestibular neuritis. Methods: A total of 36 patients with vestibular neuritis (VN) from December 2019 to October 2020 were collected from the Vertigo Department of Shandong Provincial ENT Hospital, Cheeloo College of Medicine, Shandong University. There were 36 cases (18 females, 18 males) with unilateral acute vestibular neuritis, 17 cases of left ear and 19 cases of right ear. According to the results of 3D-FLAIR MRI in the inner ears, the patients were divided into the enhanced group and the non-enhanced group (the health side served as the normal control group). The results of vestibular function examination in the two groups were compared. SPSS19.0 software was used for statistical processing to analyze the relationship between the vestibular function and the characteristics of 3D-FLAIR imaging in the inner ears. Results: Abnormal enhancement of 3D-FLAIR was found in 31 cases (86.1%) of the 36 cases, including 14 cases of both vestibular nerve and vestibular terminal organ enhancement, eight cases of superior vestibular nerve enhancement alone, seven cases of vestibular terminal organ enhancement alone, and two cases of cochlear enhancement alone. Observation of abnormal reinforcement of vestibular nerve showed: twenty-one cases of superior vestibular nerve reinforcement, one case of superior and inferior vestibular nerve reinforcement. No abnormalities were found in 3D-FLAIR of inner ear in 5 cases. According to the analysis of vestibular function results, there were 19 cases (52.8%) with total vestibular involvement, sixteen cases (44.4%) with superior vestibular involvement alone, and one case (2.8%) with inferior vestibular involvement alone. Comparison of vestibular function between the five cases (non-enhancement group) and the 31 cases (enhanced group) in the 3D-FLAIR group of the inner ears showed that the CP values of caloric tests in the enhanced group were higher (60.81±3.49 vs 34.12±7.37), with statistically significant difference (t=-2.898, P<0.01). Conclusion: In patients with vestibular neuritis, 3D-FLAIR MRI scan of the inner ear provides visual imaging evidence for clinical practice, considering that the lesion site of vestibular neuritis is not only in the vestibular nerve, but also in the vestibular end organ. Patients with 3D-FLAIR enhanced in the inner ear may have more significant vestibular function damage.

Progress of radiotherapy combined with immunotherapy for head and neck cancer / 肿瘤研究与临床

As immunotherapy has become the latest treatment for recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC), radiotherapy combined with immunotherapy has become the focus of this field. It has been reported that radiotherapy combined with immunotherapy can produce synergistic effect, but the mechanism of synergistic effect has not been determined yet. Basic researches involve immune cells and immunoregulation of microenvironment, and clinical researches include timing of combination therapy, radiotherapy site, treatment mode and dose, and selection of beneficiary population. This paper reviews the progress of combined application of radiotherapy and immunotherapy in the field of basic and clinical treatment of head and neck cancer.

Frequency characteristics of horizontal semicircular canals damage and the ultrastructure analysis of crista ampullaris in patients with Meniere's disease / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the frequency characteristics and the pathological characteristics of the horizontal crista ampullaris in patients with Meniere's disease,and to analyse its structural basis. Methods: Between March, 2019 and November, 2019, seventy-two patients diagnosed as Meniere's disease (27 males and 45 females, aged from 13 to 74 years, with a course of disease ranging from 4 months to 32 years)in Shandong Provincial ENT Hospital were included.Caloric test, sinusoidal harmonic acceleration test (SHA), video-head impulse test (v-HIT), Gadolinium-enhanced inner-ear 3D-FLAIR MRI and pure tone audiometry were conducted in the patients. The function of the horizontal semicircular canal in these patients were analysed as well as its relationship with the degree of endolymphatic hydrops,clinical stage and duration. Light microscopy and transmission electron microscopy were used to observe the ultrastructure of horizontal semicircular canal crista ampullaris from six patients with refractory Meniere's disease who underwent labyrinthectomy. The number of type Ⅰ and type Ⅱ vestibular hair cells, the common pathophysiological changes of horizontal semicircular canal crista ampullaris were investigated in these patients. Statistical analysis was performed using SPSS 19.0. Results: With the increase of detection frequency, the abnormal rate decreased gradually. The abnormal rate of caloric test was 69.4% (50/72), SHA 51.4% (37/72), V-HIT 36.1% (26/72), comparation of the positive rate among the three tests showed statistically significant differences(P<0.05).Neither caloric test nor SHA had correlation with the degree of hydrops(P>0.05), but v-HIT(r=0.434,P<0.01).There was correlation with clinical stage to SHA and v-HIT(r=0.338,0.462,P<0.01), except caloric test(P>0.05).No significant relation was found with caloric test, SHA, v-HIT and course of disease(P>0.05).Morphological observation found abnormal monolayer epithelialization of the horizontal semicircular canal crista ampullaris significantly decreased number of type Ⅱ hair cells compared with type Ⅰhair cells. Hair cells showed perinuclear vacuolization, cytoplasmic vacuoles, mitochondrial electron density increasement and loss of stereocilia. Conclusions: The horizontal semicircular canal damage in the patients with Meniere's disease has a frequency-dependent characteristic, mainly occurres in low frequency area. With progress of the disease, the high frequency area of ampulla will be impaired gradually, and it is related to the degree of endolymphatic hydrops and hearing level. Hair cell injury would be observed,the frequency characteristics may be more associated with the disorder of type Ⅱ hair cells.

Treatment strategies of Budd-Chiari syndrome during the epidemic period of 2019 coronavirus disease / 中华外科杂志

Prevention and control about the situation of 2019 coronavirus disease (COVID-19) are grim at present. In addition to supporting the frontline actively, medical workers in general surgery spare no efforts in making good diagnosis and treatment of specialized diseases by optimizing treatment process, providing medical advice online, mastering indications of delayed operation and emergency operation reasonably, etc. Budd-Chiari syndrome is a complex disorder, and severity of the disease varies, serious cases can be life threatening. While fighting the epidemic, medical workers should also ensure the medical needs of patients. However, instead of continuing the traditional treatment, a new management system should be developed. Based on the characteristics of Budd-Chiari syndrome patients in China and our experience, we divide the patients into ordinary and critical cases, and treatment strategies suitable for the epidemic period of COVID-19 are put forward for reference and discussion by physicians.

Effect of virus inactivation on weak positive results of nucleic acid test for 2019 novel coronavirus / 中华检验医学杂志

Objective:To investigate the effect of virus inactivation on weak positive result of 2019 novel coronavirus(2019-nCoV) nucleic acid test.Methods:A retrospective study was conducted on the nasopharyngeal swabs of three patients with positive PCR nucleic acid test for 2019-nCoV at different concentrations in the Second affiliated Hospital of Zhejiang University Medical College from January to February 2020.The virus in nasopharyngeal swab specimens were inactivated by water bath at 56 ℃ for 30 min, dry bath at 56 ℃ for 60 min and dry bath at 60 ℃ for 30 min respectively. After treatment, these samples RNA were extracted and then detected by three new commercial quantitative real-time polymerase chain reaction reagent kits for 2019-nCoV.Cycle threshold (Ct) value was used to evaluate the effect of virus inactivation on nucleic acid detection of 2019-nCoV.Results:There was no significant difference between the groups before and after inactivation. Ct values of ORF1ab gene before inactivation were 23.28±0.28, 25.25±0.25, 28.93±0.44, 32.06±0.47, 35.20±0.38, 32.89±0.38, 36.24±0.23, 33.30±0.46, and those after inactivation were, group 1:23.60±0.20, 27.29±0.30, 31.83±0.51, 37.41±0.46, group 2: 24.25±0.34, 27.18±0.42, 31.84±0.61, 34.99±1.01, 34.89±0.45,group 3: 23.37±0.17, 26.89±0.52, 32.05±0.50.Ct value of N gene before inactivation were 24.38±0.09, 26.64±0.11, 30.35±0.12, 33.29±0.33, 36.93±0.11, 34.50±0.12, 35.63±0.12, those after inactivation were, group 1: 24.66±0.11, 28.52±0.14, 32.71±0.14, 37.00±0.13;group 2: 25.41±0.10, 28.79±0.15, 33.29±0.28; group 3: 23.37±0.11, 28.68±0.11, 33.54±0.13, 37.18±0.23(ORF1ab gene: t=-1.416; N gene: t=-1.379, P>0.05). There was no significant difference among the three inactivation groups, the specific Ct values are shown above(ORF1ab gene: t=-0.460; N gene: t=-0.132, P>0.05). However, the Ct values of the inactivated groups (1,2,3) and the non-inactivated group at different dilution times were different (10 ×:Ct value of ORF1ab was 25.25±0.25 in the non-inactivated group, and 27.29±0.30, 27.18±0.42 and 26.89±0.52 in the inactivated group1,2 and 3, t(ORF1ab)=-7.327, P<0.01.Ct value of N gene in the non-inactivated group was26.64±0.11, those in inactivated group 1, 2 and 3 were 28.52±0.14, 28.79±0.15 and 28.68±0.11, respectively, t (N)=-19.340, P<0.01. 100 ×:Ct value of ORF1ab was 28.93±0.44 in the non-inactivated group, and 31.83±0.51,31.84±0.61 and 32.05±0.50 in the inactivated group1,2 and 3, t (ORF1ab)=-9.462, P<0.01. Ct value of N gene in the non-inactivated group was 30.35±0.12, those in the inactivated group 1, 2 and 3 were 32.71±0.14, 33.29±0.28 and 33.54±0.13, respectively, t (N)=-18.583, P<0.01. The positive detection rate of the non-inactivated group (7/11, 8/11, 5/11) was significantly different from that of the inactivated group (inactivated group 1:4/11, 4/11, 3/11, inactivated group 2:3/11, 3/11, 3/11, and inactivated group 3:3/11, 3/11, 2/11) ( Z=-2.670, P<0.01). There were no significant difference among the inactivated groups(inactivated group 1:4/11, 4/11, 3/11, inactivated group 2:3/11, 3/11, 3/11, inactivated group 3:3/11, 3/11, 2/11) ( Z=4.413, P>0.05) and among the three reagents(reagent 1:7/11, 4/11, 3/11, 3/11, reagent 2:8/11, 4/11, 3/11, 3/11, reagent 3:5/11, 3/11, 3/11, 2/11)(χ 2=1.199, P>0.05). Conclusion:The virus inactivation can degrade the nucleic acid of the 2019-nCoV, resulting in the decrease of the Ct value and the false negative results of the low-concentration specimens.

Comparative study of different operative approachs for the treatment of upper thyroid gland / 中国实用外科杂志

OBJECTIVE: To explore the feasibility of different operative approaches for the treatment of upper thyroid gland. METHODS: The clinical data of 87 patients underwent lobectomy in Department of Oncological Surgery, the First Affiliated Hospital of Bengbu Medical College from January 2016 to December 2018 were analyzed retrospectively.Preoperative ultrasound was used to evaluate the location of the tumor in the upper thyroid gland or thyroid gland hypertrophy.According to the operative approach,87 cases were divided into two groups including 42 cases of the cricothyroid approach and 45 cases of viacervical strap muscles approach. The intraoperative exposure of superior laryngeal nerve and postoperative complications of superior laryngeal nerve function and parathyroid gland were compared. RESULTS: Compared with the superior laryngeal nerve finding rate(83.3%)in the cricothyroid approach,the superior laryngeal nerve finding rate was higher(95.6%)(P0.05). CONCLUSION: The viacervical strap muscles approach compares the cricothyroid approach to the laryngeal nerve with a high rate of finding and a short searching time. Applying viacervical strap muscles approach in the case of an upper thyroid tumor and glandular hypertrophy helps to expose the upper pole and protect the external nerve branch of the larynx.

Mechanism of Sishenwan in Treatment of Ulcerative Colitis Based on Network Pharmacology and Bioinformatics / 中国实验方剂学杂志

Objective:To investigate the mechanism of Sishenwan in the treatment of Ulcerative Colitis and to explore the key targets and signal pathway on the treatment of Ulcerative Coltis based on network pharmacology and bioinformatics. Method:To obtain the active ingredients and predicted target genes of Sishenwan by searching the Encyclopedia of Traditional Chinese Medicine(ETCM) database, from the Gene Expression Omnibus (GEO) database and Database of Gene-disease Associations (DisGeNET), Online Mendelian Inheritance in Man (OMIM), Drug-targetDatabase (DrugBank), The Comparative Toxicogenomics Database (CTD) and Pharmacogenetics and Pharmacogenomics Knowledge Base (PharmGKB) disease database collection of Ulcerative Colitis target genes, the drug-disease protein target gene was obtained by intersecting the two and to display the results by Cytoscape software, through the algorithm of network topology to screen out the key target genes, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out on key target genes using Gene Ontology Enrichment Analysis Softword Toolkit (GOEAST) and The Database for Annotation, Visualization and Integrated Discovery (DAVID) online tools, analyze the mechanism of Sishenwan in preventing and treating Ulcerative Colitis combined with relevant literature. Result:There are 182 active ingredients and 611 predicted targets in Sishen Wans, 914 known disease targets related to the occurrence and development of Ulcerative Colitis were retrieved through the disease database, it was concluded that the effect of Sishenwan on Ulcerative Colitis mainly involves steroid hormone-mediated signal pathway, exogenous metabolic process, positive regulation of transcription of RNA polymerase II promoter, lipid metabolic process, detoxification of cell oxidant, signal transduction and other biological functions, and participates in arachidonic acid, drug metabolism-cytochrome P450, cytochrome P450 for xenobiotics, chemical carcinogenesis and other key signal pathways. Conclusion:Sishenwan has the characteristics of multi-target, multi-channel and multi-level in the treatment of Ulcerative Colitis. Its multiple signal pathways are directly or indirectly related, participating in lipid protein metabolism, drug metabolism and anti-cancer mechanism, etc. It exerts its efficacy through comprehensive intervention on the digestive system, circulatory system, immune system and other multiple systems of the body, thus being consistent with the comprehensive effect mechanism of Ulcerative Colitis induced by multiple factors.

Effects of inhibitory concentration minocycline on the proliferation, differentiation, and mineralization of osteoblasts / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To study the effect of the inhibitory concentration minocycline on the proliferation, differentiation, and expression of Runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and osteopontin (OPN) mRNA of osteoblasts.</p><p><b>METHODS</b>Primary osteoblasts were cultured in osteogenic induction medium containing 0, 0.1, 0.5, 1, 10 μg·mL⁻¹ minocycline. Cell counting kit-8 was used to observe cell proliferation. ALP activity assay, alizarin red S staining, and real-time quantitative polymerase chain reaction (PCR) were used to determine cell differentiation and mineralization.</p><p><b>RESULTS</b>The groups with 0.1, 0.5, 1 μg·mL⁻¹ minocycline promoted cell proliferation. The mRNA expression levels of ALP and Runx2 were up-regulated. Osteoblast-mediated mineralization was increased. The group with 1 μg·mL⁻¹ showed maximal promotion effect (P<0.05). When the concentration increased to 10 μg·mL⁻¹, the promoting effect began to decline, and the ALP activity and OPN expression were significantly inhibited (P<0.01).</p><p><b>CONCLUSIONS</b>Appropriate concentration of minocycline can promote osteoblasts proliferation, up-regulate the expression levels of Runx2, ALP and OPN, and increase the differentiation and mineralization of osteoblasts.</p>

Effect of interpersonal and social rhythm therapy combined drugs on sleep quality and quality of life in patients with insomnia / 中华行为医学与脑科学杂志

Objective To explore the effect of interpersonal and social rhythm therapy combined drugs on sleep quality and quality of life in patients with insomnia.Methods A total of 100 patients with insomnia treated in hospital from January 2016 to October 2017 were selected as subjects.The patients were divided into experimental group (n=50) and control group (n=50) according to the random number table.The control group was given conventional drug only,and the experimental group was combined with interpersonal and social rhythm therapy on the basis of the drugs treatment.The clinical efficacy was compared between the two groups.Pittsburgh Sleep Quality Index (PSQI) and Sleeping Personal Beliefs and Attitudes (DBAS) were used to assess the recent sleep quality of the two groups.The WHO Quality of Life Measurement Profile (WHOQOL-BREF) was used to compare of the quality of life between two groups.Results The clinical effective rate was 94.0％ in the experimental group and 80.0％ in the control group.There was significant difference between the two groups (x2=4.332,P＜0.05).Before treatment,there was no significant difference in PSQI ((13.61±2.09) vs (13.60±2.08),t=0.03,P＞0.05) and DBAS((80.96±10.11) vs (80.87±11.03),t =0.02,P＞ 0.05) scores between experimental group and control group.After treatment,D BAS score ((125.74 ±21.53) vs (104.22±20.97),t=4.93,P＜0.05) of both groups increased significantly,and PSQI score decreased significantly((7.51±2.35) vs (10.02±2.40),t=16.73,P＜0.05).The PSQI score in experimental group was significantly lower than that of the control group(t=7.97,P＜0.05),and the DBAS score was significantly higher than that of the control group (t =13.72,P＜0.05).Before treatment,scores in the psychological,physiological,environmental and social relations fields of the two groups were not statistically different (P ＞0.05).After the treatment,all the scores in the four fields of the two groups were significantly increased (P ＜0.05),and the scores in the experimental group were significantly higher than those in the control group (P ＜0.05).Conclusion Interpersonal and social rhythm therapy combined with drugs can effectively improve sleep quality and the quality of life.

Effect of ropivacaine on painless delivery and its effect on mother and infant / 中国基层医药

Objective To investigate the effect of ropivacaine on painless delivery and its effect on mother and infant.Methods From March 2016 to May 2017,64 cases of maternal painless labor demand in the Eighth People's Hospital of Taiyuan were chosen as the observation group ,42 cases of natural childbirth pregnant women in the Eighth People's Hospital of Taiyuan were selected as control group .The degree of labor pain,pregnancy outcome and the effect on mother and infant were compared .Results The excellent rate of normal delivery ,oxytocin usage rate in the observation group were 50%,7.81%,respectively,which were better than those in the control group ( all P＜0.05).The Apgar scores of newborns at 1 min 5 min after birth in the observation group were (8.92 ±1.20)points, (9.43 ±0.56)points,respectively,which were higher than those in the control group (t ＝5.362,4.036,all P＜0.05).The postpartum lactation of the observation group was 54.69%,and had no statistically significant difference compared with the control group .After delivery,the level of NO in the observation group was higher than that in the control group [(94.2 ±9.6) μmol/L vs.(82.6 ±5.6) μmol/L],and the cortisol level was lower than that in the control group [(726.3 ±68.1)ng/mL vs.(892.7 ±136.4)ng/mL],the differences were statistically significant (all P＜0.05).Conclusion Ropivacaine combined with spinal and epidural anesthesia is an ideal way for painless delivery, with good analgesic effect ,which can improve the natural delivery rate and has little effect on mother and child .

Paeoniflorin improves regional cerebral blood flow and suppresses inflammatory factors in the hippocampus of rats with vascular dementia / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore the delayed neuroprotection induced by paeoniflorin (PF), the principal component of Paeoniae radix prescribed in Chinese medicine, and its underlying mechanisms in rats subjected to vascular dementia (VD).</p><p><b>METHODS</b>A rat model of VD was induced by bilateral common carotid arteries occlusion (BCCAO). Low-dose or high-dose PF (20 or 40 mg/kg once per day) was administrated for 28 days after VD. The behavioral analysis of rat was measured by water morris. Regional cerebral blood volume (rCBV), regional cerebral blood flflow (rCBF) and mean transit time (MTT) were measured in the bilateral hippocampus by perfusion-weighted imaging (PWI). The levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) were measured by commercially available enzyme-linked immunosorbent assay kits. Protein levels were evaluated by western blot analysis. mRNA levels were evaluated by real time-polymerase chain reaction. Western blotting was used to estimate p65 translocation.</p><p><b>RESULTS</b>The behavioral analysis showed that PF could decrease the escape latency time (P<0.05), and increase the residence time of the original platform quadrant and the across platform frequency in water maze in VD rats (P<0.05). Likewise, PF remarkably promoted the rCBV (P<0.05), rCBF and decreased per minute MTT (P<0.05) in hippocampus of VD rats. Furthermore, PF decreased the release of IL-1β, IL-6 and TNF-α as well as inhibited the mRNA expression of IL-1β, IL-6 and TNF-α in the hippocampus of VD rats (P<0.05 or P<0.01). PF also could decrease the protein expressions of inducible nitric oxide synthase and cyclooxygenase-2 in the hippocampus of VD rats (P<0.05 or P<0.01). In addition, PF signifificantly inhibited the nuclear factor κB (NF-κB) pathway in the hippocampus of VD rats.</p><p><b>CONCLUSIONS</b>PF signifificantly attenuates cognitive impairment, improves hippocampus perfusion and inhibits inflflammatory response in VD rats. In addition, the anti-inflflammatory effects of PF might be due to inhibiting the NF-κB pathway. PF may be a potential clinical application in improving VD.</p>

Progress on rheumatoid arthritis in elderly / 中国骨伤

During choosing non-steroidal anti-inflammatory drugs(NSAIDs), risk factors should be evaluated in elder patients with rheumatoid arthritis. The present study focused on biological therapies, and elderly patients should be more concerned about the risk of infection when used it. Traditional Chinese medicine has advantages of obvious curative effect, especially for tripterygium wilfordii, large clinical trial on western and Chinese medical accurate drug strategies for old patients with rheumatoid arthritis. Old patients are easier to suffer from cardiac diseases and interstitial lung disease, rheumatoid arthritis could be controlled along with the treatment for coexistent disease. The incidence of rheumatoid arthritis in old patients is the same with other RA, and need to treat to target based on the aim of relieve pain and reduce activity of diseases, while the clinical charteristic and treatment target in elder patients with rheumatoid arthritis were not similar with other aged patient, so treatment standard target would vary with aging. Resent clinical studies excluded old patients, lead to lack of evidence-based medicine data. Clinical study for elder patients with rheumatoid arthritis are energetically carrying out, and could provide base and guide for clinical treatment.

Association of MTHFR C677T polymorphism with weight gain induced by risperidone in schizophrenia / 中华行为医学与脑科学杂志

Objective To explore the association of methylenetetrahydrofolate reductase (MTHFR)gene C677T polymorphism with weight gain induced by risperidone.Methods 356 patients with schizophrenia according to the DSM-IV criteria in this study.The height and body weight of the patients were measured before starting risperidone treatment and 8-week later.The MTHFRC677T polymorphism was genotyped using direct DNA sequencing method.Results A significant association was found between MTHFR gene C677T and body weight mass index (BMI) change after 8-week risperidone treatment.CC-carriers experienced higher BMI gain than CT/TT-carriers (CC (4.47 ± 1.09),CT (4.54 ± 1.27),TT (2.31 ± 0.75),F =5.634,P＜0.01).The frequency of allele C in bodyweight gain (＞7％) was higher than that in non-bodyweight gain groups (48.4％ vs 32.4％,x2=11.342,P＜0.01).Conclusion MTHFRC677T polymorphism is associated with risperidone induced weight gain in Chinese Han population.

Association of MTHFR C677T polymorphism with weight gain induced by risperidone in schizophrenia / 中华行为医学与脑科学杂志

Objective To explore the association of methylenetetrahydrofolate reductase (MTHFR)gene C677T polymorphism with weight gain induced by risperidone.Methods 356 patients with schizophrenia according to the DSM-IV criteria in this study.The height and body weight of the patients were measured before starting risperidone treatment and 8-week later.The MTHFRC677T polymorphism was genotyped using direct DNA sequencing method.Results A significant association was found between MTHFR gene C677T and body weight mass index (BMI) change after 8-week risperidone treatment.CC-carriers experienced higher BMI gain than CT/TT-carriers (CC (4.47 ± 1.09),CT (4.54 ± 1.27),TT (2.31 ± 0.75),F =5.634,P＜0.01).The frequency of allele C in bodyweight gain (＞7％) was higher than that in non-bodyweight gain groups (48.4％ vs 32.4％,x2=11.342,P＜0.01).Conclusion MTHFRC677T polymorphism is associated with risperidone induced weight gain in Chinese Han population.

Allicin attenuates macrophage-derived foam cell apoptosis by inhibiting caspase-12 / 中国病理生理杂志

AIM:To investigate the inhibitory effect of allicin on apoptosis and caspase-12 activation of macro-phage-derived foam cells,and to elucidate the underlying molecular mechanisms. METHODS:RAW264.7 macrophages were pretreated with allicin (12.5,25 and 50 mg/L) or 4-phenylbutyric acid(PBA,4 mmol/L) for 1 h and then treated with oxidized low-density lipoprotein(ox-LDL,100 mg/L) or tunicamycin(TM,4 mg/L) for 24 h. The cell viability and apoptosis were examined by MTT assay and flow cytometry with Annexin V-FITC/PI staining,respectively. The activities of caspase-3 in the cells and lactic dehydrogenase (LDH) in the medium were measured. The protein levels of caspase-12 were determined by Western blot. The intracellular lipid accumulation was measured with oil red O staining and the content of intracellular total cholesterol was determined by enzymatic colorimetry. RESULTS:Similar to the endoplasmic reticulum stress (ERS) inhibitor PBA, allicin inhibited ox-LDL-induced injury of RAW264.7 macrophages in a concentration-de-pendent manner,as determined by the increased cell viability and the decreased LDH leakage,apoptosis and caspase-3 ac-tivity. The decrease in cell viability and increases in LDH leakage and apoptosis induced by TM (an ERS inducer) were also suppressed by allicin. Moreover, similar to PBA, allicin remarkably inhibited ox-LDL- or TM-induced activation of caspase-12. Furthermore, allicin remarkably attenuated ox-LDL-induced lipid accumulation in the RAW264.7 cells and foam cells formation in a concentration-dependent manner. CONCLUSION:Allicin may inhibit macrophage-derived foam cell apoptosis induced by ox-LDL,and the mechanism is partially related to suppressing the activation of caspase-12.

Correlation of DNase I in serum and synovial fluid with inflammatory activity in patients with rheumatoid arthritis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the potential role of deoxyribonuclease I (DNase I) in the pathogenesis of rheumatoid arthritis (RA).</p><p><b>METHODS</b>DNase I activity was measured by radial enzyme-diffusion method in serum samples from 83 RA patients and 60 healthy volunteers and in the synovial fluid (SF) from 27 RA patients and 38 patients with other inflammatory arthritis. SF cfDNA level was measured with Pico Green Kit, and the correlation among DNase I activity, cfDNA level and clinical parameters of RA patients was analyzed.</p><p><b>RESULTS</b>Serum DNase I activity was significantly lower in RA patients than in the healthy control subjects (0.3065∓0.1436 vs 0.4289∓0.1976 U/mL, P<0.001), and was negatively correlated with ESR (r=-0.2862, P=0.0122), CRP (r=-0.2790, P=0.0184) and neutrophil cell counts (r=-0.287, P=0.011). SF DNase I activity was almost negative in patients with RA, ankylosing spondylitis (AS) and gouty arthritis (GA). SF cfDNA level in RA patients was significantly higher than that in patients with osteoarthritis (100.81∓142.98 vs 18.98∓31.40 µg/mL, P=0.002), but similar to that in patients with AS (45.85∓47.67 µg/mL, P=0.428) and GA (162.95∓97.49 µg/mL, P=0.132). In patients with inflammatory arthritis, SF cfDNA level was positively correlated with ESR (r=0.4106, P=0.0116) and CRP (r=0.5747, P=0.0002).</p><p><b>CONCLUSION</b>Impairment of DNase I activity may be responsible for the enhanced NETs generation and plays a role in the pathogenesis of RA.</p>

Decreased Prognostic Value of International Prognostic Score in Chinese Advanced Hodgkin Lymphoma Patients Treated in the Contemporary Era / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The International Prognostic Score (IPS) was developed based on the data of Western advanced Hodgkin lymphoma (HL) patients treated before 1992. Only a few studies ever evaluated the application value of IPS in Chinese population or in patients treated in the contemporary era whose outcomes has improved significantly than before.</p><p><b>METHODS</b>We conducted a retrospective study involving 208 previously untreated Chinese advanced HL patients, who were admitted to Cancer Hospital Chinese Academy of Medical Sciences from January 1, 1999 to April 30, 2015 and received uniform first-line treatment. The prognostic value of both IPS and the seven IPS factors for freedom-from progression (FFP) and overall survival (OS) was assessed in this population. The statistical methods included Kaplan-Meier methodology, log-rank testing, and Cox proportional hazard regression analysis.</p><p><b>RESULTS</b>With a median follow-up time of 79 months (range, 15-210 months), the 5-year FFP and OS were 78.8% and 86.0% respectively, which improved obviously compared with the original IPS study. The IPS remained prognostic for both FFP (P = 0.041) and OS (P = 0.013), but the range narrowed obviously, with 5-year FFP ranging from 87.2% to 61.5%, 5-year OS ranging from 94.1% to 69.2%, and the separation of survival curves was not as good as before. Only two of the seven IPS factors showed a significant independent prognostic value in the multivariate analysis: Stage IV (for FFP, hazard ratio [HR] = 2.219, 95% confidence interval [CI]: 1.148-3.948, P = 0.016; for OS, HR = 2.491, 95% CI: 1.159-5.355, P = 0.019) and hemoglobin <105 g/L (for FFP, HR = 2.136, 95% CI: 1.123-4.060, P = 0.021; for OS, HR = 2.345, 95% CI: 1.099-5.042, P = 0.028). A simple prognostic score calculated by adding one point each for any of the two factors was prognostic both for FFP (P < 0.001) and OS (P < 0.001) with the survival curves separating very well, but the range still narrowed.</p><p><b>CONCLUSIONS</b>The IPS has decreased the prognostic value in Chinese advanced HL patients treated in the contemporary era. More prognostic factors are needed to supplement this original scoring system so as to identify different risk populations more accurately.</p>

The Effects of Genders,Language Material and Region on the Mandarin Long-term Average Speech Spectrum / 听力学及言语疾病杂志

Objective To study the Mandarin long-term average speech spectrum (LTASS),the effects of gender,language and region material on LTASS were explored.This research would provide reference for clinical and academic use of Mandarin LTASS.Methods One hundred and sixty subjects from eight major dialectic regions of China,aging 16~30 (average 22.3±3.3),were asked to read two materials (storybook,newspaper)in Manda-rin at a steady speed and conversational level inside a standard soundproof booth.Ten males and ten females were in each dialectic region.A microphone (B&K 4192)was used to monitor each subject's speech which was analyzed with a real-time spectrum analyzer to obtain the long-term spectrum (B&K PULSE 3560C).Results Different Man-darin LTASS spectra were obtained based on gender,material and regions.The spectra were tested with profile a-nalysis.Language material had no significant effects on the Mandarin LTASS (F =2.52,P =0.11 ).There was, however,significant gender difference (F =116.39,P =0.00).Males had spoken with intensity levels higher than females at 100 Hz to 200 Hz.There was also a dialectic difference in the Mandarin LTASS (F =1.29,P =0.02). Speakers from Guangdong had the lowest intensity levels compared to those from other regions.Conclusion Genders and regions are factors that need to be considered when LTASS is used for clinical purpose and academic study.