1.Expert consensus on perioperative rational use and comprehensive clinical evaluation of NSAIDs in Shandong Province
Association CLINICAL ; Association CLINICAL ; Association COMPREHENSIVE ; Association PAIN ; Province WORKING
China Pharmacy 2025;36(4):385-394
OBJECTIVE To provide a basis for the rational use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the perioperative period, and provide practical methods and technical references for the evaluation and selection of NSAIDs in medical institutions. METHODS Initiated by the Affiliated Hospital of Qingdao University, Clinical Pharmacy Professional Committee of the Shandong Pharmacists Association, Clinical Individualised Drug Testing and Guidance Branch of the Shandong Medical Association, Comprehensive Clinical Medication Evaluation Working Committee of the Shandong Pharmacists Association, Pain Branch of the Shandong Medical Association in conjunction with several medical institutions in Shandong Province organized 22 pharmaceutical experts and medical experts from 17 hospitals in Shandong Province to form a consensus on the rational use and comprehensive clinical evaluation of NSAIDs in the perioperative period through the literature research method, expert interview method and questionnaire survey method based on evidence-based medicine. A comprehensive clinical evaluation was also conducted on a total of 13 specifications of 9 commonly used clinical drug varieties in Shandong Province, including celecoxib, etoricoxib, imrecoxib, ibuprofen (containing reference/original drugs and national/Shandong Province’s centralized volume-based procurement varieties). RESULTS & CONCLUSIONS A consensus opinion was formed on preoperative prophylactic use and postoperative use of NSAIDs, as well as contraindications, digestive tract risk, cardiovascular system risk, bleeding risk and kidney injury risk in the perioperative period. The evaluation and selection criteria of perioperative use of NSAIDs were established, involving 6 dimensions of safety, efficacy, economy, innovation, appropriateness, and accessibility. The results of comprehensive clinical evaluation showed that the top 6 drugs (scores over 70) were Celecoxib capsules (Celebrex) and Celecoxib capsules (Naiqi), Diclofenac sodium sustained-release tablets,Etocoxib tablets (Arcoxia) and Etocoxib tablets (Qimingshu), and Parecoxib sodium for injection. With the progress of clinical research, this consensus will be further updated and adjusted, and medical institutions can combine with the practice to develop a comprehensive clinical evaluation system of NSAIDs suitable for their institutions.
2.Exploring the current status of quality management of cold chain medicines in DTP pharmacies and the measures for pre-emptive risk management
Mulan WANG ; Peng LIN ; Siwu TU ; Zhenzhen CHEN ; Hongqiao WANG
China Pharmacy 2025;36(4):395-400
OBJECTIVE To investigate the current status of quality management of cold chain medicines in direct-to-patient (DTP) pharmacies and propose measures for pre-emptive risk management, providing references for the quality risk management of cold chain medicines. METHODS Based on the requirements of national regulations, a survey was conducted on the quality management of cold chain medicines in DTP pharmacies of J Province from November 2023 to February 2024, focusing on the receipt, storage, distribution, and delivery processes, using questionnaires, telephone interviews, and on-site visits. Common quality management issues in the operation of cold chain medicines were identified, and the causes of these issues were analyzed to propose feasible pre-emptive risk management measures. RESULTS & CONCLUSIONS A total of 122 DTP pharmacies participated in the questionnaire survey, and personnel from 30 DTP pharmacies participated in on-site and telephone interviews. Typical problems were identified in some DTP pharmacies, including insufficient personnel allocation or training, incomplete or inadequate implementation of quality system documentation, inadequate provision or management of cold chain facilities and equipment, and non-compliant storage and distribution of cold chain medicines. These issues posed certain risks to the quality management of cold chain medicines. It is recommended that DTP pharmacies strengthen personnel allocation and training, improve quality system documentation, enhance the provision and management of facilities and equipment, standardize storage and transportation operations, and strengthen supervision and assessment as pre-emptive measures. In addition, all sectors of society should also collaborate in governance from the perspective of ensuring the safety of cold chain drug storage and transportation, in order to mitigate the risk of quality and safety issues during the distribution of cold chain drugs and guarantee the safe and effective use of medications for patients.
3.Construction and effectiveness evaluation of a closed-loop management system for dispensed oral drugs in the inpatient pharmacy based on SWOT analysis
Jia WANG ; Weihong GE ; Ruijuan XU ; Shanshan QIAN ; Xuemin SONG ; Xiangling SHENG ; Bin WU ; Li LI
China Pharmacy 2025;36(4):401-406
OBJECTIVE To improve the efficiency and quality of dispensed oral drug management in the inpatient pharmacy, and ensure the safety of drug use in patients. METHODS SWOT (strength, weakness, opportunity, threat) analysis method was used to analyze the internal strengths and weaknesses, as well as the external opportunities and threats in the construction of a closed-loop management system for dispensed oral drugs in the inpatient pharmacy of our hospital, and propose improvement strategies. RESULTS & CONCLUSIONS A refined, full-process, closed-loop traceability management system for dispensed oral drugs in the inpatient pharmacies was successfully established, which is traceable in origin, trackable in destination, and accountable in responsibility. After the application of this system, the registration rate of dispensed drug information and the correctness rate of registration content both reached 100%. The proportion of overdue drug varieties in the same period of 2024 decreased by 77.78% compared to March 2020, the inventory volume decreased by 29.50% compared to the first quarter of 2020, the per-bed medication volume decreased by 32.14% compared to the first quarter of 2020; the average workload per post in the same period of 2023 increased by 49.09% compared to 2019, the dispensing accuracy rate reached 100%, and the improvement rate of quality control problem increased by 25.25% compared to 2021. This system effectively improves the safety and accuracy of dispensed oral drug management in the inpatient pharmacy.
4.Ameliorative effects and mechanisms of Miao medicine Euphorbia humifusa on hepatic fibrosis model rats
Weinong WEN ; Zhenxiang AN ; Yuanli HE ; Min WU ; Song HE
China Pharmacy 2025;36(4):407-413
OBJECTIVE To investigate the ameliorative effects and mechanisms of Miao medicine Euphorbia humifusa on hepatic fibrosis (HF) model rats. METHODS Thirty-eight rats were randomly assigned according to a random number table into control group (normal saline, n=7), model group (normal saline, n=7), E. humifusa low-, medium- and high-dose groups (0.675, 1.35, 2.70 g/kg, n=6), and silybin group (positive control, 18.9 mg/kg, n=6). All groups except the control group were subjected to HF induction via intraperitoneal injection of carbon tetrachloride. After modeling, rats were administered their respective drugs/normal saline by gavage, once a day, for 30 days. At the last medication, the liver index was calculated, and serum levels of tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), IL-1β, IL-6, alanine transaminase (ALT), aspartate transaminase (AST), and hydroxyproline (HYP) were measured. Liver morphology and HF changes were observed. Levels of transforming growth factor- β1 (TGF- β1) and α-smooth muscle actin (α-SMA), as well as the expressions of α -SMA, proteins related to TNF- α/NF- κB signaling pathway, mRNA expressions of TNF-α and NF-κB p65 in liver tissue were determined. RESULTS Compared with model group, liver index, serum levels of TNF-α, IL-17, IL-1β, IL-6, ALT, AST and HYP, relative expression of NF-κB p65 mRNA, and the levels of TNF-α and α-SMA proteins and phosphorylated NF-κB p65 in liver tissues of rats from administration groups, the expressions of α-SMA and TGF-β1 in liver tissue of rats from E. humifusa medium-dose and high-dose groups, as well as positive staining percentage and mRNA expression of TNF- α in liver tissue of rats from E. humifusa high-dose group were all decreased significantly (P<0.05 or P<0.01); IκBα protein expression from administration groups was significantly increased (P<0.05 or P<0.01). Pathological changes and the degree of HF in the liver tissues of rats from administration groups were ameliorated to various extents. CONCLUSIONS E. humifusa may alleviate HF in rats by inhibiting the activation of the TNF-α/NF-κB signaling pathway.
5.Study on quality evaluation of Mongolian medicine Sanzi powder:fingerprint,chemical pattern recognition and multi-component quantification analysis
Jun LI ; Rongjie LI ; Fengye ZHOU ; Qian ZHANG ; Wei ZHANG ; Bohan ZHANG ; Shu WANG ; Xitong ZHAO ; Jianping CHEN
China Pharmacy 2025;36(4):414-420
OBJECTIVE To establish fingerprint, chemical pattern recognition and multi-component quantification analysis of Sanzi powder, and evaluate its quality. METHODS HPLC method was adopted. The fingerprints of 15 batches of Sanzi powder were established by using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine (2012 edition). Cluster analysis, principal component analysis and orthogonal partial least squares-discriminant analysis were also conducted. The variable importance in projection (VIP) value greater than 1 was used as the index to screen the differential markers, and the contents of the differential markers were determined by the same HPLC method. RESULTS A total of 21 common peaks in the HPLC fingerprints of 15 batches of Sanzi powder were calibrated, and the similarities of them were 0.994- 0.999; 6 common peaks were identified, including gallic acid (peak 3), garminoside (peak 10), corilagin (peak 11), chebulinic acid (peak 16), ellagic acid (peak 18), crocin Ⅰ (peak 19). According to the results of cluster analysis, YKD2024LH005,No.YKD2023LH062) principal component analysis and orthogonal partial least squares-discriminant analysis, 15 batches of samples could be clustered into two categories: S1, S5, S7, S9, S14 were clustered into one category; S2-S4, S6, S8, S10-S13, S15 were clustered into one category. VIP values of 11 differential components such as corilagin, chebulinic acid and ellagic acid were higher than 1. Among 15 batches of samples, the contents of corilagin, chebulinic acid and ellagic acid ranged 2.667-5.152, 9.506- 13.522, 0.891-1.811 mg/g. CONCLUSIONS Established HPLC fingerprint and multi-component quantification analysis of Sanzi powder are rapid and simple, and can be used for quality evaluation of Sanzi powder by combining with chemical pattern recognition. Eleven components such as corilagin, chebulinic acid and ellagic acid are differential markers affecting the quality of Sanzi powder.
6.Effects of jaceosidin on inflammatory injury in osteoarthritis rats by regulating AMPK/NLRP3 signaling pathway
Chao WEI ; Jiang YU ; Guanyun SHENG ; Yi CAI
China Pharmacy 2025;36(4):421-426
OBJECTIVE To investigate the effects of jaceosidin on osteoarthritis (OA) of rats by regulating adenosine monophosphate-activated protein kinase (AMPK)/NOD-like receptor protein 3 (NLRP3) pathway. METHODS Rats were randomly separated into OA group, jaceosidin group (33.33 mg/kg), AMPK inhibitor (Compound C, 20 mg/kg) group, jaceosidin (33.33 mg/kg)+Compound C (20 mg/kg) group, and sham operation group, with 12 rats in each group. Except for the sham operation group, the OA model was induced with modified Hulth method in all other groups. After successful modeling, they were given a relevant dose of jaceosidin or normal saline intragastrically, and Compound C or normal saline intraperitoneally, once a day, for consecutive 8 weeks. Twenty-four h after the last medication, the degree of knee joint swelling in rats from each group was measured. The pathological changes of the articular cartilage tissue in the knee joints, and the Mankin score were assessed. The levels of tumor necrosis factor-α (TNF-α), interleukin-18 (IL-18), and IL-6, as well as the protein expressions of collagen Ⅱ, aggrecan (ACAN), and a disintegrin and metalloproteinase with thrombospondin 5 (ADAMTS5), phosphorylated AMPK (p-AMPK), AMPK, NLRP3, cleaved-caspase-1, and cleaved-IL-1β were detected in the articular cartilage tissue of rats’ knees. RESULTS Compared with OA group, the cartilage tissue defect of jaceosidin group was relieved, the cartilage matrix staining was deepened, and the number of chondrocytes was increased. Knee swelling, Mankin score, the levels of TNF- α, IL-18 and IL-6, and protein expressions of ADAMTS5, NLRP3, cleaved-caspase-1 and cleaved-IL-1β in knee cartilage were significantly decreased or down-regulated. Protein expressions of collagen Ⅱ, ACAN and phosphorylation level of AMPK were significantly increased or up-regulated (P<0.05). Compound C significantly reversed the improvement effects of jaceosidin on the above indexes of OA rats (P<0.05). CONCLUSIONS Jaceosidin may inhibit inflammation and extracellular matrix degradation in OA rats by regulating the AMPK/NLRP3 signaling pathway.
7.Effects and mechanism of paeoniflorin on oxidative stress of ulcerative colitis mice
Xin DAI ; Ying WANG ; Xinyue REN ; Dingxing FAN ; Xianzhe LI ; Jiaxuan FENG ; Shilei LOU ; Hui YAN ; Cong SUN
China Pharmacy 2025;36(4):427-433
OBJECTIVE To investigate the effects and potential mechanism of paeoniflorin on oxidative stress of ulcerative colitis (UC) mice based on adenosine monophosphate-activated protein kinase (AMPK)/nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway. METHODS Male BALB/c mice were randomly divided into control group, model group, inhibitor group (AMPK inhibitor Compound C 20 mg/kg), paeoniflorin low-, medium- and high-dose groups (paeoniflorin 12.5, 25, 50 mg/kg), high- dose of paeoniflorin+inhibitor group (paeoniflorin 50 mg/kg+Compound C 20 mg/kg), with 8 mice in each group. Except for the control group, mice in all other groups were given 4% dextran sulfate sodium solution for 5 days to establish the UC model. Subsequently, mice in each drug group were given the corresponding drug solution intragastrically or intraperitoneally, once a day, for 7 consecutive days. The changes in body weight of mice were recorded during the experiment. Twenty-four hours after the last administration, colon length, malondialdehyde (MDA) content, and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in colon tissues were measured; histopathological morphology of colon tissues, tight junctions between intestinal epithelial cells, and histopathological scoring were all observed and evaluated; the mRNA expressions of AMPK and Nrf2, as well as the protein expressions of heme oxygenase-1(HO-1), occludin and claudin-1, were all determined in colon tissue. RESULTS Compared with model group, paeoniflorin groups exhibited recovery from pathological changes such as inflammatory cell infiltration and crypt damage in the colon tissue, as well as improved tight junction damage between intestinal epithelial cells. Additionally, significant increases or upregulations were observed in body weight, colon length, activities of SOD and GSH-Px, phosphorylation level of AMPK, and protein expression of Nrf2, HO-1, occludin, claudin-1, and mRNA expressions of AMPK and Nrf2; concurrently, MDA content and histopathological scores were significantly reduced (P< 0.05 or P<0.01). In contrast, the inhibitor group showed comparable (P>0.05) or worse (P<0.05 or P<0.01) indicators compared to the model group. Conversely, the addition of AMPK inhibitor could significantly reverse the improvement of high- dose paconiflorin (P<0.01). CONCLUSIONS Paeoniflorin can repair intestinal epithelial cell damage in mice, improve tight junctions between epithelial cells, upregulate the expression of related proteins, and promote the expression and secretion of antioxidant-promoting molecules, thereby ameliorating UC; its mechanism may be associated with activating AMPK/Nrf2 antioxidant pathway.
8.Effects and mechanism of astilbin on renal injury in chronic renal failure rats
Xiaowei GAO ; Yingying LIU ; Cong HAN ; Shifei HAO
China Pharmacy 2025;36(4):434-439
OBJECTIVE To investigate the effect and potential mechanism of astilbin (AST) on renal injury in chronic renal failure (CRF) rats based on the Jagged-1/Notch-1 signaling pathway. METHODS CRF model was constructed by 5/6 nephrotomy. The successfully modeled rats were randomly separated into Model group, AST low-dose group (AST-L group), AST high-dose group (AST-H group), high-dose of AST+Notch pathway activator (Jagged-1/FC chimerin, referred to as “JFC”) group (AST-H+ JFC group), and control group (CK group) for open surgery without resection was set up, with 10 rats in each group. The rats in the AST-L group and AST-H group were given 40 and 80 mg/kg AST, respectively; the rats in the AST-H+JFC group were simultaneously given 80 mg/kg AST and 0.5 mg/kg JFC, and the rats in the CK group and Model group were given an equal volume of normal saline, once a day, for 4 weeks. After the last administration, the serum levels of blood urea nitrogen (BUN), serum creatinine (SCr), and the level of 24 h urinary protein (UP) in urine, as well as the serum levels of lactate dehydrogenase (LDH), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-10 in each group were detected. The morphology and fibrosis of renal tissue were observed. The content of adenosine triphosphate (ATP) and the activities of sodium-potassium ATPase and calcium-magnesium ATPase in mitochondria of renal tissue were detected. The protein expressions of transforming growth factor- β (TGF- β), hypoxia-inducible factor-1α (HIF-1α), α-smooth muscle actin (α-SMA), cleaved-caspase-3, Jagged-1 and Notch-1 in renal tissue were also observed. RESULTS Compared with CK group, the renal tissue of rats in the Model group was obviously damaged, renal tissue fibrosis was severe; the serum BUN and SCr levels, urine UP level, serum 4 LDH, TNF-α and IL-6 levels, as well as the protein expressions of TGF-β, HIF-1α, α-SMA, cleaved-caspase-3, Jagged-1 and Notch-1 in renal tissue were significantly increased, while the serum IL-10 level, ATP content and activities of sodium-potassium ATPase and calcium-magnesium ATPase in mitochondria of renal tissue were significantly decreased (P<0.05). Compared with Model group, the renal tissue damage and fibrosis in the AST groups were reduced, the serum BUN and SCr levels, urine UP level, serum LDH, TNF-α and IL-6 levels, and the protein expressions of TGF-β, HIF-1α, α-SMA, cleaved-caspase-3, Jagged-1 and Notch-1 were significantly decreased, while the serum IL-10 level, ATP content and the activities of sodium-potassium ATPase and calcium-magnesium ATPase in mitochondria were significantly increased; the changes in the aforementioned indicators in AST- H group were more significant than those in the AST-L group(P<0.05). JFC could significantly reverse the improvement effect of high dose of AST on renal injury in CRF rats (P<0.05). CONCLUSIONS AST can reduce inflammation in CRF rats, alleviate renal tissue damage and fibrosis, and improve renal mitochondrial capacity metabolism, possibly by inhibiting the Jagged-1/Notch-1 signaling pathway.
9.Effects of serum containing Sanchong tongluo sanjie formula on the proliferation and apoptosis of Lewis lung cancer cells and its mechanism
Yang LI ; Lei CHEN ; Qiachun ZHANG ; Jing ZHANG ; Jingyu FENG ; Qi LIANG
China Pharmacy 2025;36(4):440-446
OBJECTIVE To study the effects of Sanchong tongluo sanjie formula on the proliferation and apoptosis of Lewis lung cancer cells. METHODS The rats were given Sanchong tongluo sanjie formula powder [0.946 g/(kg·d)], Sanchong tongluo sanjie formula decoction [2.730 g/(kg·d)], and normal saline intragastrically, and injected with Cisplatin injection (4.2 mg/kg) intra-peritoneally to prepare powder-containing serum, decoction-containing serum, positive control serum and negative control serum. Lewis lung cancer cells were divided into negative control serum group, positive control serum group, and 5%, 10%, 20% drug-containing serum groups. The cell proliferation inhibition rates at 24, 48, and 72 hours post- intervention were measured to screen the optimal intervention concentrations of powder-containing serum and decoction-containing serum. The cell invasion ability, metastasis ability and apoptotic rate were detected in the negative control serum group, positive control serum group, 20% powder-containing serum group, and 20% decoction-containing serum group. Protein expressions of vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1α (HIF-1α), prolyl hydroxylase-2 (PHD2), matrix metalloproteinase-2 (MMP-2), extracellular regulated protein kinases (ERK),c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) were detected. RESULTS The cell proliferation inhibition rates for both the 20% powder-containing serum group and the 20% decoction-containing serum group, when intervened for 48 hours, were not less than 50%. Compared with negative control serum group, the number of invasive Lewis lung cancer cells and migration distance were decreased significantly, while the apoptotic rate was increased significantly (P<0.05); the apoptotic rate in the 20% powder- containing serum group was significantly higher than 20% decoction-containing serum group (P<0.05). The protein expressions of PHD2 and p38 MAPK were increased significantly in the 20% powder-containing serum group (P<0.05), while the protein expression of HIF-1α was decreased significantly in the 20% decoction-containing serum group (P<0.05). CONCLUSIONS Sanchong tongluo sanjie formula can inhibit the proliferation, invasion and metastasis of Lewis lung cancer cells while promoting their apoptosis. The mechanism of action may be related to regulating the PHD2/HIF-1α signaling pathway. Furthermore, the powder demonstrates superior efficacy compared to the decoction, suggesting that they may possess different mechanisms of action.
10.Study on preparation technology and quality standard of Jineijin danggui ruchuang ointment
Xiaojun PANG ; Yan XIE ; Xing CHEN
China Pharmacy 2025;36(4):447-453
OBJECTIVE To optimize the preparation technology of Jineijin danggui ruchuang ointment and to establish its quality standard. METHODS Using oil phase dosage, emulsifier dosage and emulsification temperature as the indicators, the preparation technology of Jineijin danggui ruchuang ointment was optimized by response surface method. Gallus gallus domesticus and Angelica sinensis in the ointment were identified by TLC. The property of the ointment was observed, and its particle size and deliverable volume were inspected according to Chinese Pharmacopoeia. The contents of uridine, ferulic acid and ligustilide in the ointment were determined by high-performance liquid chromatography. RESULTS The optimal preparation technology of Jineijin danggui ruchuang ointment was as follows: 4.0 g of white vaseline, 7.0 g of liquid paraffin, 5.0 g of lanolin (oil phase), 0.44 g of triethanolamine as the emulsifier, and emulsification temperature of 78 ℃ . Jineijin danggui ruchuang ointment prepared according to the optimal preparation method was a beige paste, and its particle size and deliverable volume inspection all met the requirements of the Chinese Pharmacopoeia. The identification of TLC for G. gallus domesticus and A. sinensis obtained satisfactory results. The linear ranges of uridine, ferulic acid and ligustilide were 1.6-25.6 μg/mL, 0.003 15-0.100 8 mg/mL, 0.006- 0.192 mg/mL (all r>0.999). RSD for the inspection, stability, reproducibility and recovery tests were all less than 2%( n=6). The average contents of uridine, ferulic acid and ligustilide were 0.081 2, 0.100 0 and 0.396 9 mg/g, respectively. CONCLUSIONS The optimal preparation technology can be used for the production of the in-hospital preparation of Jineijin danggui ruchuang ointment; the content determination method can be used for the quality control of the ointment.
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