Chemotherapy is one of the commonly used methods for tumor treatment, but the occurrence of multidrug resistance (MDR) in tumors has added great difficulties for tumor treatment, causing serious harm to patients' physiology and psychology. At present, there is a relative lack of research and treatment on tumor resistance in clinical practice, and finding reversal agents and strategies for tumor resistance is an urgent problem to be solved. This article reviews the mechanism of tumor multidrug resistance and its reversal methods and research status of Chinese medicine as reverse agent, aiming to provide reference for future research.

OBJECTIVE To study the factors affecting the generation of the degradation impurity 2-[(4-acetylphenyl)methyl]cyclopentanone (loxoprofen sodium impurityⅠ) in loxoprofen sodium tablets thus to provide reference for the formulation, preparation process and packaging design of loxoprofen sodium tablets. METHODS Stress testing of loxoprofen sodium and loxoprofen sodium tablets were carried out in conditions of high temperature (60 ℃), high humidity (92.5% RH) and strong light irradiation (4 500 lx). The compatibility test of loxoprofen sodium with excipients, and the content of impurity Ⅰ in bare tablets and different packages of loxoprofen sodium tablets were investigated under accelerated test conditions (50 ℃ and 75% RH). The content of impurity Ⅰ was determined by HPLC. RESULTS Loxoprofen sodium impurity Ⅰ is sensitive to humidity. High water content, moisture attracting and hydrophilic excipients such as calcium hydrogen phosphate, silicon dioxide and sodium starch glycolate might cause a significant increase of impurity Ⅰ. Moreover, there was incompatibility between mannitol and loxoprofen sodium, and the sealing performance of the package of aluminum plastic plate plus aluminum foil bag was better than that of the aluminum plastic plate package alone. CONCLUSION In order to reduce the generation of potentially toxic impurity Ⅰ, the excipients of loxoprofen sodium tablets and the granulation after drying should be controlled for water content. The use of aluminum plastic plate plus aluminum foil bag with better sealing performance can effectively reduce the generation of impurity Ⅰ. In addition, mannitol and loxoprofen sodium have compatibility problems and should be avoided in the prescription.

OBJECTIVE To study the in vivo pharmacodynamics of paclitaxel-loaded TPGS-modified carboxymethyl chitosan-rhein conjugate micelles (PTX/TPGS-CR micelles) in tumor-bearing mice. METHODS The pH and osmotic pressure value of PTX/TPGS-CR micelles were determined. The 4T1 subcutaneous transplanted tumor model was established in Balb/c mice. Taxol^® was used as the positive control, and the tumor growth curve and tumor inhibition rate were used as the main indicators. The safety and efficacy of PTX/TPGS-CR micelles were investigated by observing the changes in body weight, organ index and pathological tissue sections of mice, and measuring the expression of P-gp protein in tumor tissues of each group. RESULTS The pH value was similar to that of 0.9% sodium chloride injection (5.0-7.0), and the osmotic pressure value was 736.6-757.2 kPa. The tumor inhibition rates of Taxol^® and PTX/TPGS-CR micelle in low, medium and high dose groups were 29.91%, 20.87%, 41.06% and 41.84%, respectively. The antitumor effect of PTX/TPGS-CR micelles was better than that of Taxol^® at the same dose (P<0.05), and showed a dose-dependent feature. During the administration period, the body weight and organ of the mice in the PTX/TPGS-CR micelle group at the same dose showed no significantly affected, indicating that PTX/TPGS-CR micelles had better safety. The results of P-gp expression in tumor tissue showed that TPGS-CR micelles could inhibit the expression of P-gp protein. CONCLUSION PTX/TPGS-CR micelle preparation is a nano preparation with high efficiency and low toxicity. It has a good antitumor effect and can reduce the toxicity of PTX. Moreover, it can improve the sensitivity of tumor cells to PTX by inhibiting the expression of P-gp, which is conducive to the treatment of tumors.

OBJECTIVE To discuss the risk management methodology of data integrity implementation in drug quality control laboratories. METHODS The regulations and guidelines for data integrity were interpreted. How to apply quality risk management in data management was discussed, and combining the practical experience of laboratory, how to implement data integrity work in drug quality control laboratories through risk management was proposed. The focus was to systematically identify and map the processes, data flows, and systems of the laboratory based on the data life cycle, and analyze the gap between the current data management status and the regulation requirements. Then, using the risk management tools of ICH Q9, risk evaluation, control, and review need to be conducted to form a closed-loop risk management to control the data integrity risk within an acceptable range. RESULTS AND CONCLUSION Drug quality control laboratories should implement data management based on quality risk management principles. The implementation method proposed in this article can comprehensively evaluate and control the data integrity risks of the laboratory, which has strong practicality and can be used as a reference for other drug quality control laboratories.

OBJECTIVE To analyze the characteristics of methylphenidate (MPH) related treatment emergent adverse events (TEAE) in children, so as to provide recommendations for prevention of MPH safety events. METHODS Case reports of MPH-induced TEAE in children were retrieved from CNKI, VIP, Wan Fang, PubMed, Web of Science, EMbase and other databases, and the gender, age, dosage, drug combination, time of adverse reactions and clinical manifestations of the patients were statistically analyzed. RESULTS A total of 39 case reports were collected, involving 50 cases, including 47 cases in the treatment group and 3 cases in the non-treatment group. In the treatment group, the ratio of male to female was 3.7∶1, with 40 cases (80%) in patients aged 6-15 years. Most TEAEs occurred within 1-30 d after drug administration (32 cases, 64%), and the TEAEs mainly involved mental system (12 cases, 21.43%) and nervous system (11 cases, 19.64%). In the non-treatment group, 2 patients were overdosed, and adverse reactions occurred within 1 h, mainly involving mental system and nervous system. Among the 50 cases, 49 cases were improved after drug withdrawal and/or symptomatic treatment, and 1 case had unknown prognosis. CONCLUSION It is necessary to prevent the possible safety problems in the use of MPH, so as to improve the level of rational drug use.

OBJECTIVE To evaluate the microbial contamination levels of 14 kinds of mold-prone TCM decoction pieces and the diversity of fungi on the surface. METHODS The total aerobic microbial count (TAMC), total yeasts and molds count (TYMC), heat-resistant microbial count (HRMC), and three types of control bacteria of mold-prone TCM decoction pieces were analyzed by referring the Chinese Pharmacopoeia 2020 Edition Volume Ⅳ 1108 microbiological limit test method. Furthermore, the fungi on the surface were cultivated using the plate method, and the single strain was isolated by the top purification method, which was further identified by colony morphology and molecular identification. RESULTS The results showed that TAMC of sample ranged 250-2.45×10⁶ cfu·g^-1, TYMC ranged 5-6.6×10⁵ cfu·g^-1, and HRMC ranged 0-30 cfu·g^-1. The remaining samples of cholesterol-resistant progestin-negative bacteria did not reach 1×10⁴ cfu·g^-1, with the exception of one batch of Polygalae Radix and one batch of Glycyrrhizae Radix et Rhizoma. Although only one batch of Citri Reticulatae Pericarpium tested Escherichia coli and no Salmonella was detected in all samples, significant conditional pathogenic bacteria such as Enterobacter cloacae, Klebsiella pneumoniae, and Cronobacter sakazakii were found in the control bacterial examination items. ITS sequence sequencing comparison identified 106 strains in total, grouped into 16 genera, with Aspergillus, Penicillium, and Cladosporium accounting for 31%, 18%, and 17%, respectively, of the major bacteria. Among the genus Aspergillus, 11 strains of A. niger, 7 strains of A. flavus, 2 strains of A. fumigatus, and 1 strain of A. miscellaneous were isolated as pathogenic fungi. CONCLUSION It can provide early risk warning for its potential fungi toxins contamination through research on microbial pollution and surface fungi diversity.

OBJECTIVE To investigate the effects of carbohydrate components of fungus S7 (Tulasnella sp.) on seed germination of Dendrobium officinale. METHODS The polysaccharides of S7 mycelia (MP) and of S7 fermentation broth (FP) were prepared by water extraction and alcohol precipitation. MP and FP were hydrolyzed by trifluoroacetic acid to obtain hydrolysates, MPH and FPH. The monosaccharide composition of MP and FP were determined by PMP-HPLC. MP, FP, MPH, FPH, and the unique and mixed monosaccharide of MP were added to water agar (WA) and 1/2 MS media respectively to study the effects of carbohydrate on the seed germination of Dendrobium officinale. RESULTS The germination rate of WA medium group (WACK1) was (88.65±4.71)%, and seeds germinated to stage 3 (protocorm). Compared with WACK1, adding MP and MPH had no significant effect on germination rate (P>0.05), and seeds could germinate to stage 4 (having one leaf), while adding FPH could significantly reduce germination rate (P<0.05). MP was composed of glucose, galactose, glucuronic acid, xylose, mannose, fucose, ribose and arabinose in a molar ratio of 15.05∶1.00∶0.70∶0.35∶0.30∶0.29∶0.13∶0.13. FP was composed of arabinose, galactose, xylose and glucuronic acid in a molar ration of 1.22∶1.00∶0.71∶0.47. Fucose was the unique monosaccharide component of MP. The germination rate and stage 5 (having two leaves) germination rate of 1/2 MS medium group(MSCK) was (98.10±0.46)% and (50.97±4.33)%, respectively. Compared with MSCK, adding 0.20-20 mg·L^-1 fucose had no significant effect on germination rate (P>0.05), while significantly increased stage 5 germination rate (P<0.05), which was 1.36-1.47 times that of MSCK. CONCLUSION MP and MPH promote the development of protocorm of D.officinale. Fucose is an active component in MPH that could promote the further differentiation and development of seeds after germination.

OBJECTIVE To analyze the impurity profile of irbesartan and its preparations by LC-MS/MS. METHODS ZORBAX SB-C₁₈ column (4.6 mm×150 mm, 3.5 μm) was used for the separation of the related substances with a mixture of 0.1% formic acid solution (adjusted to pH 3.5 with ammonia) and acetonitrile (62∶38) as the mobile phase by isocratic elution. The structures of the related substances were speculated by ESI-TOF-MS/MS and verified further by reference substances. RESULTS Irbesartan and its related substances were separated under the established chromatographic condition, and a total of 16 related substances were detected. The structures of 10 related substances were verified by reference substances. CONCLUSION The established LC-MS/MS method is effective for separation and identification of the related substances of irbesartan and its preparations, and the results obtained are valuable for its quality control and manufacturing process.

OBJECTIVE To investigate the effect of tangeretin (TAN) on neuronal pyroptosis in rats with cerebral ischemia/reperfusion injury (CIRI) and its mechanism. METHODS The CIRI model of rats was established by reperfusion after occlusion of the middle cerebral artery for 2 h using thread occlusion method. Experiment 1: SD rats were randomly divided into sham group, CIRI group, TAN-5 mg·kg^-1, TAN-10 mg·kg^-1, TAN-20 mg·kg^-1, and positive control edaravone group (EDA-10 mg·kg^-1), with 10 rats in each group. The rats in each group were subjected to index detection and pathological sampling 24 hours after reperfusion. Zea Longa method was used to score neurological deficits; the rate of cerebral infarction was detected using the 2,3,5-triphenyl tetrazolium chloride (TTC) method; hematoxylin eosin (HE) staining was used to observe the morphology and structure of brain tissue, and the optimal dosage of TAN was selected; propidium iodide staining (PI) was used to detect the ratio of neuronal focal death; immunofluorescence double staining was used to detect the positive expression rate of LC3-Ⅱ in neurons; Western blot was performed for detection of the expressions of pyroptosis-related proteins, PI3K/Akt pathway-related proteins, and autophagy-related proteins (LC3-Ⅱ/LC3-Ⅰ, p62) in brain tissue. Experiment 2: SD rats were randomly divided into sham group, CIRI group, TAN group, and TAN+PI3K inhibitor group (LY294002), with 10 rats in each group. After 24 hours of reperfusion, indicators were tested and pathological samples were taken from each group of rats. Zea Longa method was used to score neurological deficits; TTC staining was used to detect the rate of cerebral infarction; Western blot was used to detect the expressions of pyroptosis-related proteins and autophagy-related proteins in brain tissue. RESULTS Compared with the CIRI group, the neurological deficit score, cerebral infarction volume ratio, and pathological damage to brain tissue of rats in each dose group were reduced. The TAN-20 mg·kg^-1 was selected as the optimal dose group. Compared with the CIRI group, the rate of pyroptosis of neurons was reduced, and the expressions of pyroptosis-related proteins were downregulated, and the positive cell rate of neuron LC3-Ⅱ and the expression of LC3-Ⅱ/LC3-Ⅰ were reduced, the expressions of p-PI3K/PI3K, p-Akt/Akt, and p62 were increased in TAN-20 mg·kg^-1 group. Compared with the TAN-20 mg·kg^-1 group, the PI3K inhibitor LY294002 inhibited the changes in the above indicators and reverse the neuroprotective effect of TAN on CIRI rats. CONCLUSION TAN can inhibit neuronal pyroptosis via regulating PI3K/Akt-mediated autophagy induced by cerebral ischemia-reperfusion.

OBJECTIVE To observe the inhibitory effect of cordycepin on platelet aggregation and activation induced by different shear rates. METHODS Polydimethylsiloxane (PDMS)-glass microchannel chips were fabricated by soft lithography. The whole blood of normal people anticoagulated with sodium citrate was collected and incubated with different concentrations of cordycepin in vitro, the blood flowed through the straight microchannel or channel with 80% narrow for 150 seconds at the speed of 14.7 μL·min^-1 and 50 μL·min^-1 respectively. The adhesion and aggregation images of fluorescent labeled platelets on glass surface were photographed with the microscope, and the fluorescent images were analyzed with Image J. The platelet surface coverage percent was used as a quantitative index of platelet aggregation behavior. The effect of cordycepin on platelet calcium mobilization and monocyte-platelet aggregate(MPA) was analyzed by flow cytometry. The risk of cordycepin was assessed through test of blood coagulation. RESULTS Cordycepin inhibits platelet aggregation and the inhibition effect is related to the shear rates. At 14.7 and 50 μL·min^-1, platelet aggregation can be inhibited by cordycepin. Cordycepin inhibits platelet calcium mobilization and MPA effectively. It has no effect on exogenous and endogenous coagulation pathways. CONCLUSION Cordycepin can effectively inhibit shear-induced platelet aggregation and is a potential antiplatelet drug.