OBJECTIVE To introduce the Dutch system of pharmacy academic education， professional practice and continuing education， and provide new ideas for constructing a “demand-driven， industry-education integrated， and sustainably developing” Chinese-style pharmacy education system. METHODS Through literature and public data retrieval， as well as collection of field visit materials， the study systematically combed the stage characteristics， institutional design， and innovative practices of Dutch pharmacy education， extracted its features and advantages， and proposed suggestions for pharmacy education reform in China. RESULTS & CONCLUSIONS The Dutch pharmacy academic education system is characterized by stepped competency-based training， integrating basic theory with early clinical practice at the undergraduate level， emphasizing specialized division of labor and strengthening clinical competence at the master’s level， and promoting industry-university-research collaborative innovation at the doctoral level. The practice qualification certification and continuing education exhibit multi-dimensional synergy. Specifically， the practice qualification certification process adheres to the guiding principle of “evidence-based competency”， implementing an access system centered on competency assessment， which requires passing national examinations and registration. The continuing education for hospital pharmacists is guided by patient safety， while continuing education for community pharmacists and other pharmacists （such as industrial pharmacists， regulatory science pharmacists， etc.） is guided by the frameworks of “digital situational learning” and a “triple tracks encompassing industry， regulation， and emerging fields”， respectively. China may draw on the five-dimensional path of Dutch pharmacy education in “early integration， vertical coherence， unified standards， industry-university-research collaboration， and intelligent empowerment” to reform its pharmacy education in aspects such as curriculum design， credit systems， evaluation criteria， training models， and training methods， aiming to cultivate pharmacy professionals aligned with China’s practical E-mail：cqqianyan@hospital.cqmu.edu.cn requirements.

Although olaparib has demonstrated substantial clinical benefits as maintenance therapy in BRCA mutation-carrying women with newly diagnosed advanced ovarian cancer, its effectiveness in patients without BRCA mutations remains poorly investigated. This study aims to provide the first evidence on the efficacy of mono-olaparib maintenance therapy in such context. Using real-world data from 11 high-volume tertiary care centers in China, a retrospective cohort study was conducted to assess the efficacy and safety of olaparib as first-line maintenance therapy in patients with BRCA wild-type ovarian cancer. The primary objective was 1-year progression-free survival rate. Safety was also evaluated. Fifty patients with a median age of 54 years were included, and all of them tested negative for BRCA mutations but positive for homologous recombination deficiency (HRD). The 1-year PFS rate was 75.2% (95% CI, 63.4 to 89.2), and the median PFS was 21.0 months (95% CI, 13.8 to 28.2). All the patients received olaparib at a starting dose of 300 mg twice daily, and none experienced serious adverse events (AEs). Eight (16%) patients had dose adjustment, but none discontinued olaparib treatment due to AEs. We provide the first evidence that mono-olaparib could be a safe and effective maintenance treatment option for patients newly diagnosed with HRD-positive/BRCA wild-type ovarian cancer.
Humans ; Female ; Phthalazines/adverse effects* ; Piperazines/administration & dosage* ; Middle Aged ; Ovarian Neoplasms/genetics* ; Retrospective Studies ; Adult ; Aged ; Poly(ADP-ribose) Polymerase Inhibitors/administration & dosage* ; China ; Maintenance Chemotherapy ; BRCA2 Protein/genetics* ; Antineoplastic Agents/adverse effects* ; Progression-Free Survival ; BRCA1 Protein/genetics*

Objective:To investigate the effect of liraglutide(LRG) on high glucose-induced oxidative stress injury in(H9c2) cardiomyocytes and its underlying mechanisms.Methods:A high glucose treatment was applied to H9c2 cells for 24 hours to establish an in vitro model of myocardial cell injury. Different concentrations of liraglutide(10, 100, 1000 nmol/L) were administered for intervention. Cell viability was evaluated using the CCK-8 assay, and changes in cell morphology were observed under an inverted microscope. After 24 hours of liraglutide(100 nmol/L) intervention following high glucose treatment, the levels of lactate dehydrogenase(LDH), superoxide dismutase(SOD), and malondialdehyde(MDA) in the cell supernatant were measured. RT-PCR and Western blotting were used to detect the mRNA and protein levels of silent information regulator factor 1(SIRT1) and forkhead box protein O1(FOXO1). Western blotting was also used to assess the acetylation level of FOXO1 protein. Small interfering RNA(siRNA) technology was employed to silence SIRT1 in H9c2 cells to confirm its role in the study. Results:Compared to the control group, the high glucose group showed decreased cell viability, cell structure damage, increased levels of LDH and MDA in the cell supernatant, decreased SOD levels, aggravated oxidative stress, decreased SIRT1 expression, and increased acetylation level of FOXO1(all P<0.05). Compared to the high glucose group, liraglutide intervention resulted in increased cell viability, improved cardiac cell morphology, reduced oxidative stress levels, increased SIRT1 expression, and decreased acetylation level of FOXO1(all P<0.05). When SIRT1 was downregulated, the protective effects of liraglutide were weakened(all P<0.05). Conclusions:Liraglutide has a protective effect against high glucose-induced oxidative stress injury in H9c2 cells, which may be associated with the upregulation of SIRT1 expression.

OBJECTIVES: To investigate the level and significance of serum γ-glutamyl transferase-to-platelet ratio (GPR) and monocyte count to high-density lipoprotein ratio (MHR) in patients with essential hypertension (EH) and unstable angina (UA). METHODS: A total of 218 patients with coronary angiography aged ≥60 years, who were admitted to the EH hospital of the Department of Cardiac Medicine, Affiliated Hospital of Chengde Medical College, were selected from September 2018 to September 2019. They were divided into an EH+UA group ( RESULTS: Compared with the control group, patients in the EH+UA group and the EH group had higher body mass index (BMI), tyiglyceride (TG), GPR, and MHR, and lower high-density lipoprotein-cholesterol (HDL-C) (all CONCLUSIONS There is a correlation between GPR, MHR and EH combined with UA pectoris, and the combined detection of the two indicators has adjuvant diagnostic value for elderly EH combined with UA.
Aged ; Angina, Unstable ; Cholesterol, HDL ; Coronary Angiography ; Essential Hypertension ; Humans ; Lipoproteins, HDL ; Monocytes

Objective:To explore the influence of parental compliance on the treatment of hypertrophic scars in burn children.Methods:A retrospective cohort study method was used. From June 2014 to June 2019, 49 children with post-burn hypertrophic scars who met the inclusion criteria and visited the outpatient department of the Department of Burns of the First Affiliated Hospital of Anhui Medical University were included in this study. In the follow-up of 9 months, according to the registration form and the results of the compliance questionnaire for parents, the children were divided into good compliance group (34 cases, 21 males and 13 females, aged 2.0 (2.0, 3.5) years) and poor compliance group (15 cases, 6 males and 9 females, aged 3.0 (2.0, 4.0) years). At the first attendance and in the follow-up of 3, 6, and 9 months, the scar scores of children in good compliance group were evaluated by Vancouver Scar Scale (VSS). At the first attendance and in the follow-up of 9 months, the scar scores of children in poor compliance group were evaluated by VSS. At the first attendance and in the follow-up of 9 months, the scar pruritus scores of children in the 2 groups were evaluated by Verbal Rating Score (VRS). Data was statistically analyzed with chi-square test, Wilcoxon rank sum test, Mann-Whitney U test, independent sample t test, and paired sample t test. Results:At the first attendance, the color, vascular distribution, softness, and thickness scores, and total score in VSS scoring of scars of children in the two groups were similar ( Z=0.834, 0.026, 0.837, 0.076, 1.074, P>0.05). In the follow-up of 9 months, the softness and thickness scores, and total score in VSS scoring of scars of children in good compliance group were significantly lower than those in poor compliance group ( Z=5.518, 4.732, 5.042, P<0.01). Compared with those in the first attendance, the color, vascular distribution, softness, and thickness scores, and total score in VSS scoring of scars of children in good compliance group were significantly decreased in the follow-up of 9 months ( Z=5.241, 5.273, 5.214, 5.245, 3.451, P<0.01); the color and vascular distribution scores, and total score in VSS scoring of scars of children in poor compliance group were significantly decreased in the follow-up of 9 months ( Z=3.606, 3.542, 3.448, P<0.01). At the first attendance, the VRS score of scar pruritus of children in good compliance group was 6.00 (5.00, 6.25) points, which was similar to (5.47±1.69) points in poor compliance group ( Z=0.607, P>0.05). In the follow-up of 9 months, the VRS score of scar pruritus of children in good compliance group was 1.00 (1.00, 1.25) points, which was significantly lower than (3.27±1.71) points in poor compliance group ( Z=2.606, P<0.01). Compared with those in the first attendance, the VRS score of scar pruritus of children in good compliance group was significantly decreased in the follow-up of 9 months ( Z=4.002, P<0.01), while there was no obvious change in poor compliance group in the follow-up of 9 months ( t=3.550, P>0.05). Conclusions:Under the same treatment plan, good parental compliance has a positive effect on the treatment of hypertrophic scars in burn children decreasing the degree of scar hyperplasia and pruritus.

Objective:To investigate the correlation of the gamma-glutamyl transpeptidase to platelet ratio(GPR)and monocyte count to high-density lipoprotein cholesterol(HDL-C)ratio(MHR)with the severity of coronary artery disease in elderly patients with essential hypertension(EH)combined with unstable angina pectoris(UA).Methods:A total of 218 EH patients aged 60 years and over undergoing coronary arteriography admitted to cardiology department of our hospital were enrolled from September 2018 to September 2019.They were divided into the EH plus UA group(n=113)and the simple EH group(n=105)according to whether UA was combined.In addition, 106 patients with normal coronary angiography who were suspected with coronary heart disease were selected as the healthy group.General data of patients between three groups were compared.Severity of coronary artery disease was evaluated using a Gensini score.The correlation of GPR and MHR with coronary Gensini scores was analyzed in the EH plus UA group.Patients in the EH plus UA group were sub-grouped into the single-, double- and triple-vessel disease groups according to the number of disease branches.Differences in coronary Gensini scores, GPR and MHR were compared among subgroups.A receiver operating characteristic(ROC)curve was used to evaluate the auxiliary diagnostic efficacy of GPR, MHR and the combined GPR and MHR in the EH plus UA group.Results:Compared with the healthy group, both EH plus UA group and EH group showed that the BMI(25.8±3.4 kg/m 2, 25.4±3.6 kg/m 2vs.24.2±2.3 kg/m 2), triglyceride(1.9±1.2, 2.0±1.2 vs.1.5±1.1 mmol/L), and MHR(6.6±1.4, 5.8±1.7 vs.4.9±1.7)were increased, and the HDL-C(1.1±0.2 mmol/L, 1.1±0.3 mmol/L vs.1.3±0.3 mmol/L)were reduced( P<0.05), and only EH plus UA group showed that white blood cells(6.7±1.5×10 9/L vs.6.1±1.8×10 9/L), LDL-C(2.3±0.6 mmol/L vs.2.1±0.6 mmol/L)and GPR(0.3±0.1 vs.0.2±0.1)were higher than in the healthy group( P<0.05). Compared with the EH group, the EH plus UA group showed that the GPR(0.3±0.1 vs.0.2±0.1), and MHR(6.6±1.4 vs.5.8±1.7)were increased( P<0.05). The correlation analysis showed that the levels of GPR and MHR were positively correlated with Gensini scores in the EH plus UA group( r=0.537, 0.333, P<0.05), and the correlation was better along with the increased number of diseased branches( P<0.05). The ROC curve analysis showed that GPR had a high specificity and positive predictive value with the specificity of 68.9% and the area under the ROC curve( AUC)of 0.842, while MHR had a high sensitivity with the sensitivity of 92.9%.The combined detection of GPR and MHR had a higher specificity and positive predictive value with a specificity of 84.0% and the AUC of 0.871. Conclusions:The increase of GPR and MHR can be used as a marker to assist the diagnosis of EH combined with UA, and to assess the severity of coronary artery disease in the elderly.

Long-term primary culture of mammalian cells has been always difficult due to unavoidable senescence. Conventional methods for generating immortalized cell lines usually require manipulation of genome which leads to change of important biological and genetic characteristics. Recently, conditional reprogramming (CR) emerges as a novel next generation tool for long-term culture of primary epithelium cells derived from almost all origins without alteration of genetic background of primary cells. CR co-cultures primary cells with inactivated mouse 3T3-J2 fibroblasts in the presence of RHO-related protein kinase (ROCK) inhibitor Y-27632, enabling primary cells to acquire stem-like characteristics while retain their ability to fully differentiate. With only a few years' development, CR shows broad prospects in applications in varied areas including disease modeling, regenerative medicine, drug evaluation, drug discovery as well as precision medicine. This review is thus to comprehensively summarize and assess current progress in understanding mechanism of CR and its wide applications, highlighting the value of CR in both basic and translational researches and discussing the challenges faced with CR.

Objective:The matria-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF MS) and sequencing methods were performed to assess the methodology (biochemistry methods) for identifying the Pandoraea sputorum and provide the more preferred approach to identify Pandoraea species. Methods:This paper is a study on performance evaluation of identification method. Ten lines of Pandoraea sputorum were isolated from blood cultures of inpatients were collected at Zhongnan Hospital of Wuhan University from July to October 2018 and were confirmed by the cultural characteristics, colonial morphology and Gram′s stain. Further identification was carried out by using the manual biochemical method (API 20NE), automatic biochemistry systems(BioMerieuxVITEK 2 Compact, BD Phoenix-100andThemo ARIS 2X), MALDI-TOF MS (BioMerieuxVITEK MS and Bruker MALDI Biotyper) and the sequencing methods of the 16S rRNA to identify the Pandoraea sputorum. Results:Pandoraea sputorum was non-fermented gram-negative bacteria that are non-motile, oxidase positive, and catalase positive. Ten lines of Pandoraea sputorum were identified as Achromobacter denitrificans, Alcaligenes faecalis or Cupriavidus pauculus and the accuracy rate of genus and species identification was 0 by API 20NE. Among all the samples, six lines were identified as the Pandoraea spp. with the accuracy rate of genus identification was 6/10 by VITEK 2 Compact; whereas the other four lines were identified as the Burkholderia cepacia, Sphingomonas paucimobilis, Ralstonia pickettii, or "Low Discrim" . All of these were identified as "No Identification" by Phoenix-100, which the accuracy rate of genus and species identification was 0. Seven isolates were identified by ARIS 2X as Stenotrophomonas maltophilia, Acinetobacter lwoffii, Sphingomonas paucimobilis, Pseudomonas luteola, Acinetobacter baumannii/Acinetobacter haemolyticus; whereas the other three lines were identified as rare species, thus, the accuracy rate of genus and species identification was 0. Both VITEK MS and MALDI Biotyper indicated all the isolates were Pandoraea sputorum with the accuracy rate of genus and species identification was 10/10. 16S rRNA sequencing for the 10 isolates showed they have 100% of similarity to Pandoraea sputorum by blasting with Genebank. Conclusions:Methods based on biochemical reactions often failed to accurately identify the Pandoraea sputorum to species level. MALDL-TOF MS and 16S rRNA sequencing technology identify Pandoraea sputorum efficiently and precisely enough.

Objective:To explore the effects of early exogenous L-carnitine supplementation on renal function in severely scalded rats.Methods:According to the random number table, sixty-six adult female Sprague-Dawly rats were divided into healthy control group ( n=6), scald alone group ( n=30), and scald+ carnitine group ( n=30). In the latter two groups, the rats were inflicted with full-thickness scald of 30% total body surface area on the back, and the lactated Ringer′s solution was injected through the tail vein for resuscitation immediately after scald. At post injury hour (PIH) 1, rats in scald+ carnitine group were intraperitoneally injected with 100 mg/mL L-carnitine solution 400 mg/kg, while rats in scald alone group were intraperitoneally injected with the same volume of normal saline. Rats in these two groups were injected once every 24 hours thereafter. Six rats were taken from each of scald alone group and scald+ carnitine group to collect the renal tissue and abdominal aorta blood at PIH 6, 12, 24, 48, and 72, respectively. The serum content of total protein, albumin, urea nitrogen, creatinine, and cystatin C were determined by the automatic biochemical analyzer. Renal tissue was stained with hematoxylin-eosin to observe histopathological changes. Rats in healthy control group did not undergo any treatment, and their renal tissue and blood sample were extracted and analyzed in the same way as those of severely scalded rats. Data were statistically analyzed with one-way analysis of variance and Bonferroni method. Results:(1) The serum content of total protein and albumin of rats in scald alone group at each time point after injury was significantly lower than that in healthy control group ( P<0.05). The serum content of total protein of rats in scald+ carnitine group was significantly higher than that in scald alone group at PIH 12 and 24 ( P<0.05), and the serum content of albumin of rats in scald+ carnitine group was significantly higher than that in scald alone group at PIH 12 ( P<0.05). The serum content of total protein and albumin of rats in scald alone group and scald+ carnitine group showed a trend of decrease followed by an increase, with the lowest value at PIH 24. (2) The serum content of urea nitrogen and creatinine of rats in scald alone group at each time point after injury was significantly higher than that of healthy control group ( P<0.05). The serum content of urea nitrogen of rats in scald+ carnitine group was significantly lower than that in scald alone group at PIH 6, 48, and 72 ( P<0.05). The serum content of creatinine of rats in scald+ carnitine group was significantly lower than that in scald alone group at PIH 12, 24, 48, and 72 ( P<0.05). The serum content of urea nitrogen and creatinine of rats in scald alone group and scald+ carnitine group showed a trend of increase followed by a decrease, with the peak value at PIH 12. (3) The serum content of cystatin C of rats in scald alone group at PIH 6, 12, 24, 48, and 72 was (0.250±0.030), (0.330±0.070), (0.300±0.060), (0.240±0.060), and (0.190±0.030) mg/L, and the content at the first 4 time points were significantly higher than (0.170±0.020) mg/L of healthy control group ( P<0.05). At PIH 24, the serum content of cystatin C of rats in scald+ carnitine group was (0.210±0.040) mg/L, which was significantly lower than that of scald alone group ( P<0.05). The serum content of cystatin C of rats in scald alone group and scald+ carnitine group showed a trend of increase followed by a decrease, with the peak value at PIH 12. (4) The renal tissue of rats in healthy control group was almost normal, and the degree of renal tissue injury of rats in scald+ carnitine group was lighter than that in scald alone group at each time point after injury. At PIH 24, the renal tissue of rats in scald alone group showed extensive swelling of the renal tubular epithelial cells, vacuolar degeneration and necrosis, loss of brush borders, and nuclear shrinkage; more than 2/3 of the renal tubular cell nuclei disappeared, the tubular lumen was narrowed, necrotic exfoliated cells could be seen in the lumen, and edema and inflammatory cell infiltration could be seen in the renal interstitial. Compared with those of scald alone group, significantly reduced severity of edema and necrosis of renal tubular epithelial cells, as well as less inflammatory cell infiltration were observed in the renal tissue of rats in scald+ carnitine group. Conclusions:Early supplement of L-carnitine in severely scalded rats can reduce the damage of renal cells, accelerate the restoration of the content of total protein, albumin, urea nitrogen, creatinine, and cystatin C, thereby maintaining the stability of renal function metabolism level.

Objective: To analyze the reasons for failure of Meek micro-skin grafting in children with severe burns and to observe the clinical effects of the treatment measures. Methods: Thirty children with severe burns hospitalized in the First Affiliated Hospital of Anhui Medical University (hereinafter referred to as the author′s affiliation) from January 2012 to January 2018, conforming to the inclusion criteria were included to failed skin graft group. Children in failed skin graft group were performed with Meek micro-skin grafting operation and the operation failed, including 17 males and 13 females aged 1 to 12 year(s). Thirty children with severe burns hospitalized in the author′s affiliation during the same period of time, conforming to the inclusion criteria, were included to successful skin graft group. Children in successful skin graft group were performed with Meek micro-skin grafting operation and the operation succeeded, including 16 males and 14 females aged 1 to 12 year(s). Main treatment measures and effects before operation, area and survival rate of Meek micro-skin graft, infected pathogens status, selection status of sensitive antibiotics, preoperative nutrition status, and wound infection status in plum rain season of children in the two groups, and nutritional status before and after strengthening nutritional support of postoperative surviving children in failed skin graft group were analyzed retrospectively. Data were processed with chi-square test and t test. Results: (1) The numbers of children in the two groups performed with main treatment measures of dilatation and anti-shock, tracheotomy intubation, ventilator-assisted respiration, and limb incision decompression after admission were close (χ²=0, 0.016, 0.025, 0.009, P>0.05). After taking the above-mentioned main treatment measures, effects of correcting shock, preventing asphyxia, correcting breathing difficulty, and improving peripheral circulation of limb were achieved. (2) The area of Meek micro-skin grafting of children in successful skin graft group was (20.6±2.5)% total body surface area (TBSA), close to (21.2±2.2)% TBSA in failed skin graft group (t=0.534, P>0.05). The survival rate of Meek micro-skin graft of children in successful skin graft group was (79±5)%, significantly higher than (26±3)% in failed skin graft group (t=2.956, P<0.01). (3) The microbial culture of wound secretion of 5 (16.67%) children in 30 patients in successful skin graft group was positive, with Pseudomonas aeruginosa of 2 children, and Escherichia coli, Staphylococcus aureus, and Aspergillus of one patient respectively. As children in successful skin graft group were with no symptom of systemic infection, no blood microbial culture was done. The microbial culture of wound secretion of 30 (100.00%) children in 30 patients in failed skin graft group was positive, and blood microbial culture of 8 (26.67%) children was positive. The main pathogen was Pseudomonas aeruginosa of 11 (36.67%) children in 8 pathogens caused infection with gram-negative bacteria of 22 (73.33%), gram-positive bacteria of 11 (36.67%) children, and fungi of 6 (20.00%) children. (4) Ten kinds of sensitive antibiotics such as cephalosporins, glycopeptides, carbapenems, and tetracyclines antibiotics were used in children in failed skin graft group, of which the use rate of imipenem of 9 (30.00%) was the highest. Only 4 kinds of sensitive antibiotics such as ceftazidime were used in 30 children in successful skin graft group. (5) The preoperative levels of albumin and prealbumin of children in successful skin graft group were (32±4) g/L and (133±41) mg/L respectively, significantly higher than (27±4) g/L and (93±35) mg/L in failed skin graft group (t=5.090, 4.064, P<0.01). The albumin and prealbumin levels of postoperative surviving children in failed skin graft group after nutritional support treatment were (35±4) g/L and (168±49) mg/L, significantly higher than (27±4) g/L and (94±38) mg/L before nutritional support treatment (t=6.911, 6.315, P<0.01). (6) Wound infection of 9 children in 30 children with wound infection in failed skin graft group happened in the plum rain season, and fungi infection of 3 children in 6 children with fungi infection happened in the plum rain season. Wound infection of 2 children in 5 children with wound infection in successful skin graft group happened in the plum rain season, and the only one children with fungi infection happened in the plum rain season. Conclusions The main reasons for the failure of Meek micro-skin grafting in children with severe burns include infection, nutrition, and season factors, etc. Measures of strengthening wound dressing change, reasonable use of sensitive antibiotics to control infection, internal and external intestinal nutritional support, and reducing disturbance of the plum rain season by enhancing ventilation are effective and worthy of clinical promotion.