In this paper， the name， origin， producing area， harvesting， processing and functional indications of Arcae Concha were systematically combed and verified by consulting the ancient and modern literature， in order to provide a basis for the development of famous classical formulas containing Arcae Concha. Arcae Concha was first recorded in the name of Han in Bencao Shiyi， but later， due to the influence of LI Shizhen's error of combining Han item with Kuiha in the Ming dynasty， there were aliases such as Kuilu and Fulao， and Yizong Bidu began to include Walengzi as its correct name and has been used ever since. The textual descriptions and illustrations of the medicinal materials of Arcae Concha contained in the materia medica of the past generations were consistent with the modern Arca inflata， A. subcrenata and A. granosa. In ancient times， there were medicinal records of two parts of shell and meat， but now the shell is used as medicine， and the meat is mostly edible. In ancient times， Zhejiang， Shandong， Guangdong and Guangxi were the main producing areas， and Zhejiang was the best. It is now believed that A. inflata is mostly distributed in the northern part of the Huanghai Sea， A. granosa is mostly distributed in the coastal areas south of Shandong Peninsula in China， and A. subcrenata is widely distributed in the coastal areas of China. Its quality is better in a complete， white， no residual meat and sand. In ancient times， there was no clear harvesting period， and the processing was mainly based on vinegar quenching after calcination or powdering of calcined shell， but now the harvesting period is autumn and winter. After harvesting， it is directly washed and crushed for raw use or processed by calcined method. The records of the medicinal materials in the past dynasties on the properties of Arcae Concha were mainly warm， sweet， salty and mild， and it is now believed that Arcae Concha is salty in taste and mild in nature. In ancient times， it was believed that Arcae Concha were mainly used for coldness in the heart and abdomen， coldness in the waist and spine， benefiting the five internal organs， strengthening the stomach. Nowadays， it is believed that Arcae Concha can eliminate phlegm and remove blood stasis， soften the hardness and dissipate the lumps， produce acid and relieve pain. It can be used in the treatment of stubborn phlegm， gall tumor， scrofula and other symptoms. In conclusion， it is suggested that for the famous classical formulas containing Arcae Concha， the corresponding methods should be selected according to the processing requirements of the drug in the formulas， while those without processing requirements can be determined according to the functional position of the products.

OBJECTIVE To investigate the mechanism of the inhibitory effect of total flavonoids from Taraxacum mongolicum on high-fat diet-induced obesity in mice through modulation of intestinal flora. METHODS Twenty-four C57BL/6J mice were randomly divided into blank group， model group and T. mongolicum total flavonoid group， with 8 mice in each group. Except for the blank group， the other 2 groups were given a high-fat diet， while T. mongolicum total flavonoid group was given T. mongolicum total flavonoid [400 mg/（kg·d）] intragastrically， once a day， for 8 consecutive weeks. During the experiment， the food intake of each group of mice was recorded. After the last medication， the body mass， fat weight， blood lipid level and pathological changes of liver and epididymal fat in mice were evaluated to observe the effect of T. mongolicum total flavonoid on the treatment of obesity in mice. The changes in abundance and structure of intestinal flora in mice were detected by amplicon sequencing； the effects of T. mongolicum total flavonoids on fat metabolism related genes were analyzed by qPCR. RESULTS Compared with model group， the body weight of mice in T. mongolicum total flavonoids group was decreased significantly （P＜0.05）； the levels of total lipid cholesterol， triglycerides， and LDL cholesterol were all decreased significantly （P＜0.01）， and the level of HDL cholesterol was increased significantly （P＜0.01）； the fat indexes of inguinal white adipose tissue and epididymal white wind_lz@hactcm.edu.cn adipose tissue were significantly reduced （P＜0.05）； significant improvement in hepatocellular steatosis and adipose cytopathy were significantly improved； mRNA expressions of COX7A1 and COX8B were significantly upregulated （P＜0.05）. The results of bacterial colony detection showed that compared with the model group， there was a rising trend in the diversity of the bacterial colony in T. mongolicum total flavonoids group， and the Sobs index characterization and β diversity were increased significantly （P＜0.05）. Relative abundances of Blautia， norank_f_Ruminococcaceae， Bilophila， Alistipes， classified_f_Ruminococcaceae， Parabacteroides， norank_f_Desulfovibrionaceae， Anaerotruncus were significantly up-regulated（P＜0.05）， while those of Faecalibaculum， Erysipelatoclostridium， GCA-900066575， Tuzzerella， Lactobacillus， norank_f_norank_o_RF39， achnospiraceae_FCS020_group were significantly down-regulated （P＜0.05）. CONCLUSIONS T. mongolicum total flavonoids can reduce body mass， fat weight and blood lipid levels， and repair the pathological damage to liver and epididymal fat in obese mice， which is related to improving intestinal flora disorders caused by high-fat diet.

Through consulting the ancient herbal books and modern literature， this paper has carried out the textual research on the name， origin， place of origin， harvesting and processing， and other contents of Bruceae Fructus， combed its ancient and modern medicinal history， so as to provide reference for the development of famous classical formulas containing Bruceae Fructus. Through the herbal textual research， It can be verified that， since the Qing dynasty， Bruceae Fructus has been recorded in the materia medica， most of the materia medica in previous dynasties took Bruceae Fructus as its proper name， and Laoyadan， Kushenzi and Yadanzi as the aliases. The main origin of Bruceae Fructus is Brucea javanica， its medicinal part is the fruit， which is harvested from August to October every year， the fruit can be harvested when it is ripe. Bruceae Fructus was first distributed in Fujian， Guangdong and Guangxi， and gradually expanded to the south of China with the change of time. The traditional processing method of Bruceae Fructus is mainly to remove the shell and kernel， and remove the oil by frosting. The 2020 edition of Chinese Pharmacopoeia stipulates that its processing method is to remove the shell and impurities. Based on the research results， it is suggested that the dried mature fruit of B. javanica should be selected for the development of famous classical formulas containing this herb， and the raw products can be used if the original formula does not specify the processing requirements.

OBJECTIVE To determine the contents of N-nitroso impurities in raw materials/formulations of propranolol， metoprolol， atenolol， esmolol and bisoprolol， and clarify the attention threshold. METHODS Ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q/Orbitrap HRMS）was adopted. An ACE Excel 3 C18-AR column was used for the separation and a mixture of 0.2% formic acid solution with 0.01 mol/L ammonium acetate and methanol was employed as the mobile phase by gradient elution， at a flow rate of 0.60 mL/min. The column temperature was set at 40 ℃ ， and the sample size was 5 μL. The heated electrospray ionization source was employed in the positive full mass spectra-selected ion monitoring mode. The contents of N-nitroso impurities in raw materials/formulations of 15 batches of β-blockers from 10 manufacturers were determined by this method. Discovery Studio software was applied to predict the toxicity of the impurities and estimate the attention threshold. RESULTS Among 5 kinds of β-blockers， the linear ranges of N-nitroso propranolol， N-nitroso metoprolol， N-nitroso atenolol， N-nitroso esmolol and N-nitroso bisoprolol were 1.01-503.38， 1.02-508.38， 0.97-483.63， 1.11-554.27 and 1.05-523.92 ng/mL， respectively （r＞0.999）. The limits of quantitation were 1.04， 0.25， 0.05， 0.55 and 1.05 ng/mL， and the limits of detection were 0.52， 0.08， 0.02， 0.17 and 0.52 ng/mL， respectively. RSDs of precision， reproducibility， recovery， stability and durability tests were all lower than 7.5% （n＝6 or n＝5）. Among the 15 batches of samples， except for 1 batch， N-nitroso propranolol （1.07-8.91 ng/mg）， N-nitroso metoprolol （1.43-3.37 ng/mg）， N-nitroso atenolol （1.33 ng/mg）， N-nitroso esmolol （0.19 ng/mg） and N-nitroso bisoprolol （1.27 ng/mg） were detected in all other batches. According to predictions， the above 5 impurities had varying degrees of reproductive toxicity， mutagenicity and carcinogenicity， with attention thresholds of 1.0， 0.4， 4.3， 0.2 and 46.7 ng/mg， respectively. CONCLUSIONS The established method is simple， rapid， sensitive and specific， the estimated attention thresholds are clear， which can be used for the control of N-nitroso impurities in various β-blockers.

Objective: To design the proficiency testing (PT) project (No. NIFDC-PT-183) for assays of bismuth potassium citrate capsules and organize to assess the proficiency of complexometric titration in laboratories, and provide some technical analyses and advices.
Methods: Two groups of samples with different concentration were prepared. The uniformity was evaluated with one-way analysis of variance and the stability was confirmed with t-test, whose results all conformed the requirements. The samples with three combinations were randomly distributed to 279 laboratories. The determination was performed according to the assays of bismuth potassium citrate capsules in Volume Ⅱ of the Chinese Pharmacopoeia 2015. The median value and normalized interquartile range (NIQR) of robust statistical analysis was adopted and Z-scores were used to evaluate the results from each of laboratories.
Results: Among 279 laboratories, 240 laboratories results were satisfactory, 23 were questionable, and the other 16 were unsatisfied. The satisfaction rate was 86.0%.
Conclusion: The overall capacity of national laboratories for assays of bismuth potassium citrate capsules is good while a portion of participants require further improvement.

Objective To explore the corneal wound healing mechanism after 3.74 μm infrared laser irradiation.Methods Twenty-seven C57BL/6J mice(six to eight weeks old)were randomly divided into a normal group(3 mice)and an experimental group(24 mice).Mice in the normal group were not subjected to any treatment.The corneas of mice in the experimental group were damaged by infrared laser at a wavelength of 3.74 μm.The spot diameter was 2 mm,the exposure duration 0.8 s,and the radiant exposure 23.2 J·cm-2.Pathological sectioning of corneas was performed at 3 h,6 h,12 h,1 d,3 d,7 d,14 d,and 21 d after laser irradiation in the experimental group,with 3 mice at each time point.It was the same for mice in the normal group.Immunohistochemical staining was conducted to examine neutrophil elastase,CD68,CD163 and thrombomodulin-positive cells and identify neovascularization.Results Neutrophil elastase,CD68,CD163,and thrombomodulin-positive cells were not detected in the corneal stroma of mice in the normal group.Neutrophil elastase-positive cells were detected in the damaged corneal periphery of mice in the experimental group at 3 h,migrated to the damaged area at 12 h,peaked at 1 d,and then decreased gradually with time,but still existed slightly at 21 d after laser irradiation.CD68-positive cells were detected in the damaged corneal periphery of mice in the experimental group at 12 h and in the damaged area at 1 d through 21 d after laser irradiation.CD163-positive cells were found in the damaged corneal periphery of mice in the experimental group at 7 d and in the damaged area at 14 d and 21 d after laser irradiation.Throm-bomodulin-positive cells were found in the damaged area of the corneal stroma at 14 d and 21 d after laser irradiation.Con-clusion During the wound healing process after 3.74 μm infrared laser-induced full-thickness corneal injury in mice,a large number of inflammatory cells migrate from the damaged corneal periphery or limbus to the damaged area.Neutrophils and M1 macrophages infiltrate in the early stage,while M2 macrophages are involved in the later stage,accompanied by neovascularization.

Objective To construct a carbon dioxide(CO2)laser-induced corneal injury model in mice and observe the process of corneal wound healing.Methods Twenty eyes of ten C57BL/6J mice were divided into 4 groups.The cen-tral corneas in each group were irradiated by CO2 laser with a wavelength of 10.6 μm,spot diameter of 2 mm and power of 0.94 W.The exposure doses were 3.0 J·cm-2,4.5 J·cm-2,7.5 J·cm-2 and 10.5 J·cm-2,with corresponding expo-sure durations of 0.10 s,0.15 s,0.25 s and 0.35 s.Corneal injury severity was assessed using a slit lamp microscope,opti-cal coherence tomography and histopathological evaluation at 1 day after the exposure to determine the proper exposure dose for constructing a corneal injury model.Subsequently,the corneal injury model was constructed and the same meth-ods were used to monitor wound healing before,and 0 hours to 6 months after the exposure.Results No obvious corne-al injury was observed at an exposure dose of 3.0 J·cm-2.At an exposure dose of 4.5 J·cm-2,an off-white injury area appeared on the central cornea with loss of epithelium and endothelium.At an exposure dose of 7.5 J·cm-2 or 10.5 J·cm-2,the injury area became porcelain white,the cornea was thickened,and the iris was seen adhering to the margin of the cornea.Therefore,4.5 J·cm-2 CO2 laser was selected to construct a corneal injury model.At this exposure dose,the cornea swelled and thickened rapidly after injury,reached the maximum thickness 1 day after the exposure,and then grad-ually recovered,returning to normal by 14 days after the exposure.In the early stage(0 hours to 3 days after the expo-sure),the cornea showed shedding of injured epithelium and endothelium,migration of new epithelium and endothelium,and infiltration and regression of inflammatory cells.At the late stage(7 days to 6 months after the exposure),the cornea gradually returned to a normal physiological state,but some of the injured cornea exhibited stromal hyperplasia.Conclu-sion A CO2 laser with an exposure dose of 4.5 J·cm-2 can be used to construct a corneal injury model in mice.The a-cute phase of corneal injury primarily occurs within 3 days after the exposure.The cornea tends to restore its original physi-ological structure,but the corneal transparency cannot return to a normal state.

Objective To establish a method to qualitatively identify and quantitatively determine a new impurity from beclomethasone propionate inhalation aerasol.Methods Ultra-performance liquid chromatography-Q-exactive orbitrap-mass spectrometry(UPLC-QE-MS)technology and Discovery Studio software were used to identify and predict the toxicity of a new impurity in beclomethasone propionate inhalation aerasol,and the content of this new impurity was determined by UPLC.Results The new impurity in beclomethasone propionate inhalation aerasol was polybutylene terephthalate(PBT)cyclic dimer.Discovery Studio software predicted that PBT dimer had potential developmental toxicity,with no mutagenicity,no ocular and skin irritancy and no rodent carcinogenicity.The content range of PBT dimer in 9 batches of beclomethasone propionate inhalation aerasol was 20.5-116.6 pg per bottle.Conclusion This study can realize the rapid identification and toxicity prediction of the new impurity in the preparation,and provide a theoretical basis for the quality control of the preparation by determining their content.

Inflammation, abnormal cholesterol metabolism, and macrophage infiltration are involved in the destruction of the extracellular matrix of the nucleus pulposus (NP), culminating in intervertebral disc degeneration (IDD). Whether nimbolide (Nim), a natural extract, can alleviate IDD is unclear. In this study, we demonstrated that Nim promotes cholesterol efflux and inhibits the activation of the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways by activating sirtuin 1 (SIRT1) in nucleus pulposus cells (NPCs) during inflammation. Thus, Nim balanced matrix anabolism and catabolism of NPCs. However, the inhibition of SIRT1 significantly attenuated the effects of Nim. We also found that Nim promoted the expression of SIRT1 in RAW 264.7, which enhanced the proportion of M2 macrophages by facilitating cholesterol homeostasis reprogramming and impeded M1-like macrophages polarization by blocking the activation of inflammatory signaling. Based on these results, Nim can improve the microenvironment and facilitate matrix metabolism equilibrium in NPCs. Furthermore, in vivo treatment with Nim delayed IDD progression by boosting SIRT1 expression, modulating macrophage polarization and preserving the extracellular matrix. In conclusion, Nim may represent a novel therapeutic strategy for treating IDD.

By reviewing the ancient materia medica， medical books and modern literature， this paper made a systematic textual research on Haliotidis Concha in famous classical formulas， including the name， origin， producing area， quality evaluation， harvesting and processing， in order to provide a basis for the development of famous classical formulas containing Haliotidis Concha. The textual research showed that Shijueming was the official name of Haliotidis Concha in past dynasties， and there were also aliases such as Qianliguang， Jiukongluo and Zhenzhumu named after its efficacy， properties and near-phonetic characters. Before the Tang dynasty， the original description of Haliotidis Concha was too concise， which could only be identified as the animal of genus Haliotis， family Haliotidae. During the Song， Yuan， Ming and Qing dynasties， the main varieties were H. diversicolor and H. discus hannai. At the beginning of the Republic of China， a variety of animals from genus Haliotis were used as Haliotidis Concha， and varieties were numerous and continued to this day. In ancient and modern times， the main producing areas in China are Hainan， Guangdong and Shandong， while the foreign producing areas are mainly Japan and Vietnam. The quality evaluation of Haliotidis Concha in ancient books was roughly determined by the number of openings of the expiratory orifice， and seven-hole and nine-hole abalone shells were preferred. In modern times， characters as big， neat， unbroken， clean inside and outside， lustrous， thick shells are preferred. Based on the textual research results and combined with the record years of the Shijueming San， it is suggested that the shells of H. diversicolor or H. discus hannai should be used in the development of this formula， and the raw products should be used as medicine.