Zuotai is the most representative prepared product in Tibetan medicine,with functions such as treating diseases,detoxification,nourishing health,and enhancing efficacy.Zuotai and its formulations has become the core medicines for detoxification in Tibetan medical practice.Currently,research on Zuotai mainly focuses on the historical inheritance of processing techniques and exploration of safety,with relatively less research and confirmation on its detoxification effects.This study systematically organized the literature basis for the detoxification efficacy of"Zuotai"by collecting and compiling classical works of Tibetan medicine.It examined the detoxification effects of Zuotai based on the Tibetan medical theories of"Three Stomach Fires","Seven Essences and Three Impurities",and"Ro Nus ZhurJes"combined with the principles of toxic effects on the body and detoxification treatment.Using Tibetan medicinal property analysis methods,the study interpretd the"taste,nature,and efficacy"of Zuotai's processing ingredients and explored the Tibetan medical principles behind Zuotai's detoxification.The five sources of Zuotai are primarily"water"and"earth,"with the six tastes dominated by"sweetness,"and the seventeen efficacies mainly characterized by"heavy,blunt,cool,oily,stable,and soft".These properties counteract the"light,sharp,hot,fine,unstable,and rough"characteristics of toxins,thereby treating diseases caused by toxins,such as"Lung"and"Tripa"disorders,and restoring balance to the"Three Stomach Fires","Seven Essences and Three Impurities",and"Three Humors".Additionally,the raw materials of Zuotai possess intrinsic properties of detoxification,wound healing,and treating brain injuries,achieving the purpose of detoxification.This study preliminarily clarified the efficacy principles of Zuotai's detoxification,providing a theoretical reference for further research on its effectiveness,mechanisms,and clinical applications.

Zuotai is the most representative prepared product in Tibetan medicine,with functions such as treating diseases,detoxification,nourishing health,and enhancing efficacy.Zuotai and its formulations has become the core medicines for detoxification in Tibetan medical practice.Currently,research on Zuotai mainly focuses on the historical inheritance of processing techniques and exploration of safety,with relatively less research and confirmation on its detoxification effects.This study systematically organized the literature basis for the detoxification efficacy of"Zuotai"by collecting and compiling classical works of Tibetan medicine.It examined the detoxification effects of Zuotai based on the Tibetan medical theories of"Three Stomach Fires","Seven Essences and Three Impurities",and"Ro Nus ZhurJes"combined with the principles of toxic effects on the body and detoxification treatment.Using Tibetan medicinal property analysis methods,the study interpretd the"taste,nature,and efficacy"of Zuotai's processing ingredients and explored the Tibetan medical principles behind Zuotai's detoxification.The five sources of Zuotai are primarily"water"and"earth,"with the six tastes dominated by"sweetness,"and the seventeen efficacies mainly characterized by"heavy,blunt,cool,oily,stable,and soft".These properties counteract the"light,sharp,hot,fine,unstable,and rough"characteristics of toxins,thereby treating diseases caused by toxins,such as"Lung"and"Tripa"disorders,and restoring balance to the"Three Stomach Fires","Seven Essences and Three Impurities",and"Three Humors".Additionally,the raw materials of Zuotai possess intrinsic properties of detoxification,wound healing,and treating brain injuries,achieving the purpose of detoxification.This study preliminarily clarified the efficacy principles of Zuotai's detoxification,providing a theoretical reference for further research on its effectiveness,mechanisms,and clinical applications.

Objective This study aimed to explore the prescription regularity of Mercury(Zuotai)detoxification formula in Tibetan classic medical literatures based on data mining.Methods Mercury(Zuotai)detoxification formula of were collected from 22 ancient Tibetan medical literatures including the Four Medical Tantras,Medicine of Moon King,One Hundred Thousand Fists and Eight Essential Collections of Medicine,et al.The database of drugs,medicinal properties,five-source,six-flavor,and three-chemical flavor was established.R 4.2.2,IBM SPSS Modeler 18.0,Origion 2024 and other software were used to conduct frequency statistical analysis,Apriori association rule analysis and cluster analysis of the category,property and flavor,and five-source of Mercury(Zuotai)detoxification compound drugs,and interpret the statistical results in combination with the theory of Tibetan medicine.Results A total of 52 formulas were collected,containing 213 Tibetan medicines,with a cumulative frequency of 1066 times.The medicines involved in the prescription are mainly plant-based,and most of them are"cold"drugs;the medicinal flavor of drugs is mainly bitter,sweet,and pungent,with the five sources of emptiness,wind and water predominating;the most frequently occurring medicine was Mercury(Zuotai),followed by Terminalia Chebula,Musk,Geranium,Saffron,and Nutmeg.High-frequency medicines such as Mercury(Zuotai),Musk,Strychni Semen,Aconitum Tanguticum,Pedicularis Trichoglossa,Swertia Verticillifolia,and Sinapis Alba have detoxification effects.Musk also has the effect of aromatherapy,Terminalia Chebula can reconcile the nature of the medicine and the three causes of the disease effectively.The"six good medicines",including Geranium,Saffron,Nutmeg,White cardamom,Cloves,and Tsaoko Amomum Fruit,can harmonize qi and blood,and treat diseases of internal organs of the body.The analysis of association rules showed 24 pairs of medicines combinations with a support degree exceeding 59.62,and 9 groups of three-drug combinations,predominantly involving Mercury(Zuotai),Terminalia Chebula,Musk,and"six good medicines".The cluster analysis of medicines with a frequency of>10 produced 7 clustered formulas,primarily characterized by their efficacy in clearing away heat and toxins,as well as regulating the five internal organs and six viscera.Conclusion Most medicines in the Mercury(Zuotai)detoxification formula are primarily composed of botanicals,cold and bitter drugs,which is consistent with the heat-clearing and detoxifying therapy in Tibetan medicine.The medication pattern of the Mercury(Zuotai)detoxification formula is characterized by the use of Terminalia Chebula to reconcile the medicinal properties,detoxifying medicines to detoxify,aromatic drugs to rapidly eliminate or expel toxins,and six good medicines to protect the viscera.The combined use of these medicines plays a role in clearing away heat and toxins,opening up the orifices and collaterals,and harmonizing the functions of the viscera.The study provides data to support the medication rules of the Tibetan medicine Mercury(Zuotai)detoxification prescription.

Zuotai(mercury preparation)is considered the treasure of Tibetan medicine and is commonly referred to as the"King of Medicines".It is widely utilized in clinical practice as a core ingredient in the precious Tibetan medicine compounds,which possesses multiple therapeutic properties such as disease treatment,detoxification,health maintenance,and tonic effect.This paper conducted a comprehensive review of the classical Tibetan medical literature and recent research literature to elucidate the historical development and modern applications of the"Zuotai"concoction method.There are three main representative approaches of Zuotai concoction,including the mercury concoction method in the"Four Medical Tantras"by Udo-Yundan Pao(708-833),the concoction method in the"Mercury Concoction Classics"by Dongshun Nu Gyatso(13th century),and the mercury concoction method by Master Tsuru Tsering(1926-2004),who has imparted the Zuotai concoction process since the establishment of New China.In addition,Zuotai has been extensively studied by researchers in the fields of modern pharmacochemistry,pharmacokinetics,and toxicology.Overall,this paper provides a comprehensive review of the concoction methods of"Zuotai"in the classical Tibetan medical literature and modern pharmacological and toxicological research,so as to provide important reference value for in-depth understanding of the origin and history of"Zuotai".

Colorectal cancer (CRC), a malignant tumor worldwide consists of microsatellite instability (MSI) and stable (MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing was performed to explore the role of SHP2 in all cell types of tumor microenvironment (TME) from murine MC38 xenografts. Intratumoral cells were found to be functionally heterogeneous and responded significantly to SHP099, a SHP2 allosteric inhibitor. The malignant evolution of tumor cells was remarkably arrested by SHP099. Mechanistically, STING-TBK1-IRF3-mediated type I interferon signaling was highly activated by SHP099 in infiltrated myeloid cells. Notably, CRC patients with MSS phenotype exhibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68⁺ macrophages than MSI-high phenotypes, suggesting the potential role of macrophagic SHP2 in TME. Collectively, our data reveals a mechanism of innate immunosuppression mediated by SHP2, suggesting that SHP2 is a promising target for colon cancer immunotherapy.

OBJECTIVE：To e stablish the method for simultaneous determination of 10 kinds of active components in Tibetan medicine Siwei jianghuang prescription ，and to optimize its decoction technology. METHODS ：HPLC method was adopted. Using soaking time ，the amount of added water ，decoction time and decoction times as factors ，comprehensive score of the contents of 10 kinds of components and solid extracts rate as response values ，one the basis of single factor test ，Box-Behnken response surface method was used to optimize its decoction technology. RESULTS ：The linear range of gallic acid ，corilagin，magnoflorine， ellagic acid ， hydrochloric jatrorrhizine ， hydrochloride palmatine ， hydrochloride berberine ， bisdemethoxycurcumin， demethoxycurcumin and curcumin were 0.280 6-1.683 6，0.289 6-1.737 6，0.320 8-1.924 8，0.116 0-0.696 0，0.018 9-0.113 5， 0.013 3-0.079 9，0.092 3-0.553 8，0.025 5-0.153 0，0.036 1-0.216 3，0.041 0-0.245 7 µg（all r were 0.999 9），respectively. The limits of quantitation were 0.28，14.48，3.21，11.60，1.89，4.44，0.46，0.26，0.36，0.41 ng，respectively. The limits of detection were 0.11，4.14，1.24，3.32，0.58，1.33，0.13，0.09，0.14，0.12 ng，respectively. RSDs of precision ，stability and reproducibility tests were all lower than 3％. The recoveries were 92.56％-103.69％（RSDs were 0.90％-3.81％，n＝6）. The optimal decoction technology included soaking 60 min，adding 8-fold（mL/g）water，decoction for twice ，lasting for 65 min each time. In 6 validation tests ，comprehensive scores were 3.323 2-3.422 4，and the absolute value of the relative error with the predicted value （3.437 4）was less than 2％.CONCLUSIONS：Established method is simple and repeatable ，and can be used for simultaneous determination of 10 kinds of active components in Siwei jianghuang prescription. Optimized decoction technology is stable and feasible.

OBJECTIVE： To make a textual research on the normal name， synonym and Chinese translation name aiming at the phenomenon of more than one name of Tibetan medicine “Riguan”， and to determine the standard name suitable for standardization and popularization. METHODS： The representative classical Tibetan medicine books from the 7th to the 21st century were studied. The names of “Riguan” in various books and their occurrence frequency， naming basis and succession were sorted out， and the standard names of “Riguan” in Tibetan and Chinese were screened for easy understanding and popularization. RESULTS： According to the 17 representative Tibetan medicine classics books and 6 Chinese version Tibetan medicine books， “Riguan” had 19 Tibetan names. Among them， the most frequently recorded name was “Zimagangjiu”， which had been recorded in 11 books. Secondly， “Riguan” and “Puronggang” were recorded in 8 books respectively， and “Riguanzima” was recorded in 7 books. Naming basis could be summarized into four categories， i.e. simple naming （such as “Riguan”）， emphasizing morphological characteristics （such as “Zimagangjiu”）， emphasizing medicinal properties （such as “Daweitou”）， simple naming+emphasizing morphological characteristics （such as “Riguanzima”）. “Zimagangjiu” “Riguan” and “Riguanzima” were used as normal names in the 7th to 8th century， 8th to 19th century and 19th to 21st century respectively. Among them， “Riguanzima” was first recorded in the official book Tibetan Medicine Subvolume of Chinese Medical Encyclopedia as a formal name， which symbolized the milestone of the development of Tibetan medicine in the new era of our country. CONCLUSIONS： According to the naming basis and current application situation， it is suggested that “Riguanzima” can be used as the Tibetan and Chinese standard name of Tibetan medicine “Riguan” to promote and standardize its application.

Objective To investigate the effect of supine regulating on maternal fetal occiput posterior position during the delivery after epidural analgesia. Methods Totally600 cases of parturient with intravaginal posterior occipital position with 3cm voluntary labor analgesia were selected,who were born in Dalian maternity hospital from October 2015 to October 2016.The(Visual Analogue Scale/Score) VAS pain score at 15min after epidural labor analgesia was as effective as less than 3 points.They were randomly divided into the control group and the observation group by random number table method,with 300 cases in each group.The control group monitored parturient respiration, pulse, blood pressure, heart rate and fetal heart rate according to routine treatment.The control group monitored parturient respiration, pulse, blood pressure, heart rate and fetal heart rate according to routine treatment.In the observation group,except for routine treatment according to the labor process,after the opening of 5cm,the pregnant women were instructed to take the lateral prone position,so that the maternal side and the fetal side of the spinal column should be the same side. To observe the difference between the two groups in the rate of spontaneous vaginal delivery, delivery rate, cesarean section rate, fetal cardioversion rate, time of birth process and neonatal Apgar score. Results Totally 283 cases delivery through vagina and 17 cases of cesarean section in observation group,while 257 cases of vaginal delivery and 43 cases of cesarean section in the control group.The successful rate of fetal position transfer in the observation group was 74.6%(211/283) which was significantly higher than 45.9% (118/257) of the control group (Χ2=62.782, P<0.01), natural labor rate was also 87.3% (262/300) which increased significantly according to 64.7% (194/300) (Χ2=42.251, P<0.01),the rate of midwifery (7.0%, 21/300) and cesarean section (5.7%, 17/300) were significantly lower than 21.0% (63/300)and 14.3% (43/300) of the control group (Χ2=24.419, 12.519,P<0.01),the second stage of labor was(1.60±0.56)h which was significantly shortened than(2.19±0.53)h also(t=-12.589,P<0.01).In the observation group, the ratio of the posterior occipital position to the occipital transverse position after the opening of 8-10 cm and the complete dilation of the cervical were 7.4%(21/283)and 13.1%(37/283),which were also significantly increased than 3.4%(9/264),6.8%(18/264) of the control group (Χ2=4.240, 5.911, P<0.05). Conclusions Supine adjustment after the cervix dilatation larger than 5cm is more conducive to fetal rotation and to avoid the adverse complications, reduce the rate of vaginal delivery and cesarean section rate,improve the rate of natural childbirth,shorten delivery time,improve the quality of delivery.

Aim To explore whether total flavonoids of Verbena officinalis L(TFV)can induce apoptosis of HepG-2 cells through targeting topoisomerase Ⅱ.Methods HepG-2 cells were cultured with TFV at 200,100,50 mg·L-1.Cell apoptosis was evaluated by TUNEL-DAPI double staining.TopⅡ activity was detected by supercoiled pBR322 DNA relaxation assay.The levels of the mRNA of TOP Ⅱα,TOP Ⅱβ were analyzed by real time PCR.Expression of Bcl-2,Bax,TOP Ⅱα,TOP Ⅱβ and caspase-3 was analyzed by Western blot.

Objective To explore the correlations of vascular endothelial growth factor (VEGF) and paraoxonase 1 (PON1) gene polymorphism with diabetic retinopathy. Methods A total of 168 patients with diabetes mellitus(DM) in the Second People's Hospital of Xining City were selected from January 2013 to December 2015, and were divided into the DM group (48 cases), proliferative diabetic retinopathy (PDR) group (66 cases) and non-proliferative diabetic retinopathy (NPDR) group (54 cases). A total of 104 healthy subjects were selected as the control group (NC group). The VEGF and PON1 gene polymorphisms were detected by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and levels of superoxide dismutase (SOD) and malondialdehyde (MDA) of all subjects were detected by using UV spectrophotometer. Results Compared with the NC group, the systolic blood pressures and glycated hemoglobin levels in the DM group, NPDR group and PDR group were significantly increased,there were statistically significant differences (P<0.05). No statistically significant difference was found in diastolic blood pressure and levels of cholesterol,triglyceride, high density lipoprotein among these groups (P>0.05). There was statistically significant difference in systolic blood pressure between PDR group and NPDR group (P< 0. 05), while no statistically significant difference was found in diastolic blood pressure and levels of cholesterol, triglyceride,high density lipoprotein and glycated hemoglobin between the two groups (P>0.05). The incidence rate of DR in the patients with CC,CT and TT genotype was 71.05%, 56.27 % and 38.64 %, respectively. The incidence rate of DR in the patients with CCgenotype was significantly higher than that in the patients with CT or TT genotype (P< 0.05). No statistically significant difference was found in SOD and MDA levels of healthy subjects with different PON1 192 genotypes (P>0.05). The SOD level of DR patients with QQ genotype was lower than that of patients with QR or RR genotype,and the MDA level of DR patients with QQ genotype was higher than that of patients with QR or RR genotype,the difference was statistically significant (P<0.05). Conclusion The expression of VEGF and PON1 genes could affect the development and progression of DR. PON1 gene might control the progression of DR by affecting the expression of oxidative kinase in DR patients.