Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

Senior care workers specializing in traditional Chinese medicine (TCM) healthcare have become an indispensable force in institutional care, community care, and home care. The first Chinese nursing service team aimed to improve the health of the elderly by providing continuous services for physical and mental well-being, disease prevention, physical amelioration, and overall health enhancement using TCM concepts, methods, and technologies. The primary purpose of formulating this TCM health and elderly care worker service specification was to standardize services within the TCM elderly care industry, ensuring that the elderly receive better health and elderly care services supported by technical expertise. This specification outlined the basic requirements for TCM health and elderly care workers, including standards for service content, service quality control, service evaluation, and improvement. It primarily focused on the content and requirements of TCM health and elderly care services, such as constitution identification, life care, acupoint healthcare, and TCM auxiliary nursing for elderly individuals with chronic diseases. This specification is applicable to TCM health and elderly care personnel at various levels of hospitals and healthcare institutions and is noted for its strong applicability and effectiveness.

Objective: To analyze the urination behavior in spring among college students in Hebei Province. Methods: In March 2017, the subjects were recruited in a college in Baoding, Hebei Province. And 156 students completed the investigation. The urine samples of 24 hour was collected for 3 consecutive days by special device, and the volume, the voids and the time of urine were measured. Results: The average volume of urine per day was 1 279 mL, the average void of urine per day was 6.2, and the average volume of urine per time was 209 mL. The volume of urine and void were mainly at the time of after lunch, the volume, the proportion of the volume and void of urine were 406 mL, 31.0% and 1.7 times respectively. The volumes and the voids of urine were different in different time periods(P<0.05). The volume of urine, the proportion of the volume and the voids of urine were mainly at the time of morning, followed by the afternoon. The average volume of urine per day was 535 mL, the proportion of the volume was 44.1% and the average void of urine was 2.3, in the morning. There were significant differences in the voids of urine, the volumes of urine and the voids of urine in different time periods between boys and girls(χ2=73.71, 47.48, 34.92; 35.17, 21.30, 20.69; 37.02, 25.30, 15.32, P<0.05). The void of urine was negatively correlated with the average volume of urine per time(r=-0.61, P<0.01); the volume of urine was positively correlated with the average volume of urine per time(r=0.79, P<0.01); the void was not correlated with the volume of urine(P<0.05). Conclusion The urination behaviour of college students in Hebei Province was mainly at the time of after lunch, in the morning and in the afternoon. The college students had unhealthy urination behavior, which was in need of related health education.

Exosomes are a type of nanoscale vesicles that are actively secreted by various type of cells, and are considered as a new way of cell communication. The exosomes can shuttle bioactive molecules including proteins, lipids, miRNAs and mRNAs from one cell to another, resulting in the exchange of genetic information between cells and the reprogramming of recipient cells. Many evidences show that tumor cells can secrete a large amount of exosomes and regulate tumor progression,metastasis,immune escape, resistance and many other aspects through a variety of ways. In the tumor microenvironment, exosomes transmit between tumor cells,immune cells,and stromal cells,contributing to the escape from immune surveillance.This review summarizes recent advances in exosomes in tumor immune escape.

Objective To discuss the diagnosis effect and clinical significance of thrombelastography in chronic kidney disease. Methods From June 2016 to February 2017, two hundred and seventy non-dialysis patients with chronic kidney disease ( CKD) treated in the Fourth Hospital of Hebei Medical University were divided into non-hypercoagulable group and hypercoagulable group according to TEG comprehensive coagulation index. The changes of related clinical indexes between the two groups were analyzed and the related factors affecting the differences between the two groups were studied. Results The correlation between the two groups showed that the coagulation reaction time ( R ) , coagulation formation time ( K ) and albumin in the hypercoagulable group were significantly lower than those in the non-hypercoagulable group ((4. 69±0. 94) min vs. (6. 29±1. 63) min,(0. 93±0. 13) min vs. (1. 51±0. 58) min,(27. 54±7. 81) g/L vs. (34. 26±8. 39) g/L, P= 0. 000 ) Angle angle, maximum thrombus strength ( MA ) , fibrinogen, D-dimer, platelet count, protein/creatinine and protein content in hypercoagulable group were significantly higher than those in non-hypercoagulable group((76. 76±2. 23)°vs. (68. 19±7. 65)°;(75. 13±3. 81)mm vs. (66. 35±7. 81)mm;(4. 28 ±0. 93) g/L vs. (3. 56±1. 10) g/L ;0. 4(0. 15,0. 91) mg/L vs. 0. 22(0. 12,0. 52) mg/L;(276. 03±127. 15) ×109/L vs. (198. 18±78. 46)×109/L;5430(2579,9634) mg vs. 2620(692,5286) mg;4864(2341,7712) mg/g vs. 2557(840,5805) mg/g,P<0. 05). The differences were statistically significant. There was no significant difference in prothrombin, thromboplastin time, thrombin time, total cholesterol, triglyceride, low density lipoprotein,high density lipoprotein,creatinine between the two groups ( P>0. 05) . Correlation analysis of common clinical indicators showed that the comprehensive coagulation index ( CI) was positively correlated with Angle angle,maximum thrombus strength,fibrinogen,platelet count,protein/creatinine and protein quantification (r=0. 532,0. 522,0. 307,0. 354,0. 293,0. 216,P<0. 05),was negatively correlated with coagulation reaction time,coagulation formation time and albumin (r=- 0. 462,- 0. 496,- 0. 360,P<0. 05). Logistic regression analysis showed that platelet count, albumin and fibrinogen were the influencing factors for the grouping of comprehensive coagulation index ( OR ( 95％CI ) :1. 007 ( 1. 002-1. 013 ) , 0. 868 ( 0. 827-0. 912 ) , 1. 510 (1. 042-2. 187),P<0. 05). Conclusion TEG is a more sensitive indicator to reflect the coagulation status of patients with CKD, and has a certain guiding significance for anticoagulation treatment of patients with CKD;platelet count,albumin,fibrinogen are the factors affecting coagulation function of patients.

Clinical data of 113 patients with non-alcoholic fat liver disease (NAFLD) diagnosed by liver biopsy from January 2015 to January 2017 in Taizhou People's Hospital were retrospectively reviewed . Patients all underwent transient elastographic ( TE) examination and the values of fat attenuation index (FAI) were obtained.The hepatocyt fatty changes in pathological examination were scored as 0 (＜5%, n＝40), 1 (5%-33%,n ＝27), 2 (34% -66%,n ＝28) and 3 (＞66%, n ＝18).There were significant differences in AST , Glu, TC and FAI among patients with hepatocyte fatty change scores 0, 1, 2 and 3, and the FAI was significantly correlated with the degree of fatty liver disease .The areas under the ROC curve (AUCs) of FAI in patients with hepatocyte fatty change scores 1, 2 and 3 were 0.78, 0.90 and 0.96, respectively.Logistic regression analysis showed that FAI was correlated with TG , TC and BMI.The results suggest that FAI in TE can be a non-invasive, rapid and objective evaluation method for patients with NAFLD.

Glioma is a serious health threat for humans,so we urgently need to develop a more accurate,efficient and durable method to fight it.Immunotherapy is a fashionable treatment,which can stimulate the body's own immune system stimulation.And finding a reliable therapeutic target becomes the essential for glioma immunotherapy.The toll-like receptor 2 is form Ⅰ transmembrane receptor,which can be highly expressed in a variety of tumors and is closely linked to the aggressiveness and prognosis of the tumors.This article aims to explore the TLR2 expression and its association with tumors to provide new therapeutic targets for glioma immunotherapy.

Objective To explore the expression levels of chemokine (C-C motif) ligand 18 (CCL18) in human glioma tissues and its effects on the invasion,migration and proliferation ofglioma cells.Methods (1) Sixty samples were harvested from the glioma which was excised surgically and confirmed pathologically from the patients at the Department of Neurosurgery,Affiliated Hospital to Binzhou Medical College from January 2012 to December 2017.Of the samples,by the WHO grading,26 belonged to grade Ⅱ,18 to grade Ⅲ and 16 to grade Ⅳ.Ten samples of normal brain tissue were harvested as controls from the contemporary patients who underwent intracranial decompression and excision due to brain injury.CCL18 mRNA expression was determined by real-time RT-PCR and CCL18 protein expression in tumor cells by immunochemically histological staining.(2) U251 glioma cells cultured in vitro were incubated with CCL18 serum-free culture media (0 ng/mL,5 ng/mL and 10 ng/mL) for 24 h before they were subjected to Transwell,scarification and CCK-8 assays to measure cellular invasion,migration and proliferation.Results (1) The expression of CCL18 mRNA was significantly increased in the order from normal brain,glioma of grade Ⅱ,glioma of grade Ⅲ to glioma of grade Ⅳ (P＜0.05);the expression of CCL18 protein was significantly increased in the order from glioma of grade Ⅱ,glioma of grade Ⅲ to glioma of grade Ⅳ (P＜0.05).(2) The 24 h Transwell assay for invasion showed that the number of transmembrane cells was significantly increased in the order from 0 ng/mL group to 5 ng/mL group to 10 ng/mL group (43.5±8.3,202.0±18.5 and 279.7±18.6 cells) (P＜0.05).The widths of scratch (pixels) in the scarification assay for migration were 498.4±75.3,381.3±21.4 and 347.7±14.2 at 12 h,and 299.5±15.3,284.6±7.8 and 237.3±20.6 at 24 h,respectively,showing significant differences between the groups of 0 ng/mL,5 ng/mL and 10 ng/mL recombinant CCL18 (P＜0.05).The cell growth in CCK-8 assay for proliferation was 1.000±0.019,1.260±0.094 and 2.070±0.138 fold at 24 h,respectively,also showing significant differences between the groups of 0 ng/mL,5 ng/mL and 10 ng/mL recombinant CCL18 (P＜0.05).Conclusions Expression of CCL18 in glioma is associated with the malignancy of the tumor.As CCL 18 promotes invasion,migration and proliferation of glioma cells,it may be a potential biomarker for detecting and grading human glioma.

Objective To study the mechanism of bromocriptine (BRC) inducing autophagy-dependent cell death in pituitary adenomas and to explore its significance.Methods Thirty pituitary adenomas excised in our hospital from June 2013 to December 2015 were collected;the expressions of LC3 and Bcl-2 in these pituitary adenomas and normal brain tissues were examined by immunohistochemical staining.The rat hypophysoma MMQ cells were conventionally cultured in vitro;after 24 h of treatment with 60 μmol/L BRC,cytometry was performed to detect the variation of these cell cycle;the protein expressions of microtubule-associated protein light chain 3-Ⅰ (LC3-Ⅰ) and light chain 3-1Ⅱ (LC3-1Ⅱ) and the ratio of Bcl-2/Bax were measured by Western blotting after 24 h of treatment with various concentrations BRC (0,30 and 60 μ moi/L) for the MMQ cells.Results The LC3 protein expression rate in the pituitary adenomas was 80％ (24/30) and that in the normal brain tissues was 0％ (0/30);Bcl-2 protein expression rate in the pituitary adenomas was 83.33％ (25/30) and that in the normal brain tissues was 0％ (0/30).The high expression rates of LC3 and Bcl-2 in pituitary adenomas were significantly higher than those of the normal brain tissues (P＜0.05).Patients with increased prolactin after BRC treatment had significantly higher expression rates of LC3 and Bcl-2 than those with decreased prolactin after BRC treatment (P＜0.05).After treatment with 60 μmol/L BRC for 24 h,the number of MMQ cells in G0-G1 phase was significantly larger than controls (P＜0.05).After 24 h of induction with various concentrations BRC,Western blotting showed that the conversion ratio of LC3-Ⅰ to LC3-Ⅱ in MMQ cells was significantly increased following the increase of BRC concentration (P＜0.05);the ratio of Bcl-2 and Bax showed no significant difference among the 0,30 and 60 μ mol/L BRC treatment groups (P＞0.05).Conclusion The death manner of BRC-treated pituitary adenoma cells is mainly autophagic cell death rather than apoptosis.