Drugging the circadian clock feedback cycle to ameliorate cartilage degeneration.

Dampened peripheral clocks have been linked to osteoarthritis (OA), yet it is unclear whether drugging the clock can ameliorate OA. Given that RORs and REV-ERBs mediate respectively, positive and negative transcriptional feedback of the master clock gene BMAL1, we investigate whether RORs agonist Nobiletin (NOB) and SR1078, and REV-ERBs antagonist SR8278 can enhance BMAL1 expression and attenuate cartilage degeneration. NOB and SR8278 promoted BMAL1 expression and elicited mitigating effects against IL-1ß-induced degeneration of cartilage explants, as evidenced by increased cellular density and collagen synthesis along with alleviated catabolism and collagen denaturation. Despite promoted BMAL1 expression, SR1078 concomitantly suppressed chondrocyte anabolism and catabolism. Consistent with these findings, NOB and SR8278 treatment, but not SR1078, effectively attenuated structural destruction of articular cartilage in surgery-induced OA mouse models. Notably, the beneficial effects of NOB and SR8278 were evidently observed in IL-1ß-induced degeneration of human cartilage explants and immortalized human chondrocytes. Moreover, BMAL1 knockdown assays indicated that NOB and SR8278 enhanced clock function and concordantly rendered protection against altered anabolism and catabolism in a BMAL1-dependent regime. Collectively, our study suggests that targeting RORs and REV-ERBs to promote the dampened peripheral clocks could be a route taken to apply chronotherapy within the context of OA.

Pharmacokinetics of FGF21-164 fusion protein in mice using UHPLC-MS/MS method / 药学学报

FGF21-164 is a fusion protein obtained by structural modification and coupling of endogenous FGF21. It is a candidate drug used in the treatment of glucose and lipid metabolic disorders caused by obesity. In this study, the candidate peptide mass spectrometry information of the protein hydrolyzed by trypsin was predicted by Skyline software and verified by high resolution mass spectrometry. The specific surrogate peptide (YLYTDDAQQTEAHLEIR) with the best mass response was selected after optimizing ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Under ESI positive ion mode, the parent ion m/z 689.3 with 3 charge and the product ion m/z 738.4 with single charge can be monitored. After dilution by PBS, the serum samples were denatured under 60 ℃ and alkylated to reduce the matrix effect, then incubated with trypsin at 37 ℃ for 2 h, to obtain the surrogate peptide. The chromatographic separation was carried out on an EclipsePlus C18 column (2.1 mm×50 mm, 1.8 μm) using aqueous solution containing 0.1% formic acid (phase A) and acetonitrile solution containing 0.1% formic acid (phase B). Finally, the concentration of FGF21-164 fusion protein in mouse serum was quantitatively analyzed by external standard method by monitoring the above ion pairs using triple quadrupole mass spectrometer. This method showed a good linearity in the range of 2.50-500 μg·mL-1 (r = 0.998 8), and was successfully applied to the pharmacokinetic study of FGF21-164 fusion protein in mice. This experiment was approved by the Experimental Animal Ethics Committee of Shanghai Institute of Materia Medica, Chinese Academy of Sciences (batch number: 20180004040450). Compared with the endogenous FGF21, the t1/2 of FGF21-164 fusion protein was prolonged from 0.5 h to 2.6 h, which is expected to prolong the therapeutic efficacy of this protein.

Textual Research of Origin and Clinical Application of Banxia Baizhu Tianma Tang / 中国实验方剂学杂志

After a comprehensive analysis and research of ancient books and literatures， we discovered that six Banxia Baizhu Tianma Tang prescriptions have the same name. It was originally created by LI Gao. The idea of composition has a certain inheritance relationship with ZHANG Yuan-su′s Tianma Banxia Tang and Huatan Yuhu Wan， which are recorded in Prescription of Peaceful Benevolent Dispensary. In later generations， four doctors developed five prescriptions of the same name. CHENG Guo-peng of the Qing dynasty reformed the prescription based on the theory of phlegm and dampness. He reduced tonic components based on LI's ideas to strengthen the expectorant function， and then transformed the prescription into two of the same name， one for headache and the other for vertigo. The latter was recorded in the textbook of Chinese Herbal Medicine and The Catalogue of Classic Prescriptions （batch 1）， which has the greatest impact on the contemporary prescriptions. Its composition is Pinelliae Rhizoma Praeparatum Cum Zingbere et Alumine （5.595 g）， Atractylodis Macrocephalae Rhizoma （11.19 g）， Gastrodiae Rhizoma， Poria， Citri Exocarpium Rubrum （each 3.73 g）， Glycyrrhizae Radix et Rhizoma （2 g）， 2 pieces of fresh Zingberis Rhizoma Recens （about 2 g） and 2 Jujubae Fructus. The botanical origin of these herbs is clear， and the dosage of herbs is safe in accordance with the Pharmacopoeia of the People's Republic of China.P. The total amount of each dose is about 37.975 g， while the daily dosage is not far different from that of invention. Since its invention， it has been mainly used in the treatment of phlegm headache and vertigo caused by wind phlegm disturbance. In modern clinical practice， it is widely used in treating various diseases with vertigo and headache as the main symptoms， mainly including hypertension， acute ischemic stroke， vertebrobasilar insufficiency， cervical spondylosis， primary headache， Meniere's disease and benign paroxysmal positional vertigo. When the syndrome differentiation is consistent with relevant syndrome type with phlegm as the main pathological factor in traditional Chinese medicine， we can modify the prescription as appropriate.

Analysis of Banxia Houpo Tang Based on Ancient Literatures / 中国实验方剂学杂志

Banxia Houpo Tang is widely used in modern clinics with definite curative effect. It is one of the classic famous prescriptions in the Catalogue of Ancient Classic Famous Recipes（First Batch） published by the State Administration of Traditional Chinese Medicine（TCM） in 2018. Using bibliometrics methods，collect relevant literatures of Banxia Houpo Tang in ancient medical books，analyze and verify the origin，historical evolution，composition，prescription，function，dosage，artillery，preparation method and decoction method of prescription. A total of 259 related ancient literature data were obtained，involving 107 TCM books. The inductive analysis found that Banxia Houpo Tang originated from ZHANG Zhong-jing's Synopsis of the Golden Chamberin the Han dynasty and consisted of the five flavors of Pinelliae Rhizoma，Magnoliae Officinalis Cortex，Poria，Perillae Folium and Zingiberis Rhizoma Recens. Houpo Tang，Qiqi Tang，Siqi Tang，Daqiqi Tang and other synonyms have appeared in the records of medical records of all dynasties. The prescription composition，preparation method and decoction method are used by later generations of medical practitioners. The analysis of related prescriptions is also rarely disputed. The dosage of drugs used in Banxia Houpo Tang can be calculated as 1g or 3 g. The drug processing method is different from the original one. Pinelliae Rhizoma should choose Pinelliae Rhizoma Praeparatum Cum Zingibere et Alumine and Magnoliae Officinalis Cortex as "Jianghoupu". The rest of the drug processing methods respect the 2015 edition of Chinese Pharmacopoeia. The cardiology of its treatment has also been extended and expanded. In addition to the symptoms of "burning in the pharynx" recorded by the original party，this side can also be used for heart diseases such as heartache，chest tightness，sorrow，vomiting，choking noisy and other spleen and stomach disease syndrome and spermatorrhea，turbidity，scorching and other lower coke disease syndrome.

Origin and evolution of the thunder-fire moxibustion therapy / 中国针灸

Through analyzing the origin and evolution of the thunder-fire moxibustion therapy, the mysteries and misunderstandings of it were revealed. As a result, a more objective and comprehensive recognition of this ancient therapy was displayed to the people nowadays. The thunder-fire moxibustion therapy maybe originate from the Taoism magic arts before the Dynasty and became matured in the middle of the Dynasty. Two categories were divided during the long-term evolution in the history. In one category, the peach twig was taken as the moxa material rather than moxa stick and the incantation of Taoism remained. Regarding the other category, the herbal medicine was mixed in the moxa stick and the herbal composition was relatively specified. The incantation was removed. The moxibustion in the first category vanished at the end of the Dynasty. The latter one kept on development from the middle of the Dynasty through the modern times. Additionally, the herbal composition of moxa material has been modified; the indication enlarged and the operation improved. This therapy is still developed and applied by many doctors at the present times.

From to ：the formation of early acupuncture safety regulation / 中国针灸

Acupuncture safety is an unavoidable problem in acupuncture clinical. is the earliest ancient literature on acupuncture taboo, which has a far-reaching influence on the clinical acupuncture safety regulation. of - absorbs the essence of , retaining most of the contents of the theory and rearranging it. This paper tries to explore the discussions about , compared with , from the point of "anatomy" and "spirit", to describe the early understanding of acupuncture taboo, to emphasize the importance of acupuncture safety from three aspects, as human anatomy, needle and operation, and mental and functional status. It is suggested that a relatively preliminary acupuncture safety regulation was being formed at the time, in order to bring inspiration to the contemporary acupuncture clinical .

Experimental Study of the Heat Transfer Characteristics of Thunder-fire Wonder Moxibustion / 上海针灸杂志

Thunder-fire wonder moxibustion is one of pressing moxibustion therapies and has a very good therapeutic effect on limb pains, furuncle-carbuncle and cold syndrome. To reveal the mechanism of clinical action of ancestors’ thunder-fire wonder moxibustion and seek the physical basis of its therapeutic advantage, this study, by a series of experiments, compared heat transfer regularities of thunder-fire wonder moxibustion versus pure moxa stick in simulated biological tissues under different conditions, preliminarily revealed heat radiation and heat transfer regularities of thunder-fire wonder moxibustion, tried to find pressing strength suitable for clinical operation of pressing moxibustion and had thoughts about changes in the clinical operation of past dynasties.

[Comprehensive characterization of main components and microstructures in five different species of Salvia miltiorrhiza bge].

Studied with X-ray fluorescence spectrum analytic (XRF), powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FTIR) for five different species of Salvia miltiorrhiza bge grew in Anguo, the intrinsic components and microstructures were determined and comprehensive characterization was carried out. The figure of comprehensive characterization can describe characteristics of intrinsic components from elements, crystal and amorphous active component, it can give an intuitive description for the same components and subtle differences in the intrinsic components of Salvia miltiorrhiza bge, which are different idioplasmatic and same species. It is the ideal method because of the simple preparation of sample, rapid and fine accurate measurement with reproducibility and objectivity, so that it can be used for breeding of fine varieties of Chinese medicinal materials, Chinese medicinal materials GAP guidance of growing conditions, medicinal origin characteristics, the intrinsic composition and microstructure characterization, quality control and authenticity of the identification.

Blockade of paeoniflorin on sodium current in mouse hippocampal CA1 neurons.

AIM: To study the blockade of paeoniflorin (Pae) on I(Na) in the acutely isolated hippocampus neurons of mice. METHODS: The whole-cell patch clamp technique was used. RESULTS: Pae inhibited I(Na) in frequency-dependent and concentration-dependent manners, with an IC50 of 271 micromol/L. Pae 0.3 mmol/L shifted the activation potential of the maximal I(Na) from -40 mV to -30 mV, shifted the steady-state activation and inactivation curves toward more positive and negative potentials by 10.8 mV, and 18.2 mV, respectively, and postponed the recovery of I(Na) inactivation state from (4.2+/-0.7) ms to (9.8+/-1.2) ms. CONCLUSION: Pae inhibited I(Na) in mouse hippocampus neurons.