AIM To study the effects of Rehmanniae Radix Preparata (A) and Poria (B) on decoction amounts of loganin,morroniside and 5-hydroxymethylfurfural in Corni Fructus (C).METHODS These three medicinal materials were combined one another and divided into seven groups (A,B,C,A + B,A + C,B + C and A + B + C).Then the contents of three constituents were determined by HPLC.RESULTS Compared with the single decoction of Corni Fructus,the decoction amounts of loganin and 5-hydroxymethylfurfural were decreased,and that of morroniside was increased at the time of mixed decoction of Rehmanniae Radix Preparata and Corni Fructus,or Rehmanniae Radix Preparata,Poria and Corni Fructus.This situation was just the contrary at the time of mixed decoction of Poria and Corni Fructus.CONCLUSION The mixed decoction of Corni Fructus,Rehmanniae Radix Preparata and Poria increases the decoction amount of morroniside,which may make mixed decoction liquid show better efficacy.

OBJECTIVE:To study the effects of combined decoctions of alismatis rhizoma and curcumae radix and rehmanniae radix praeparata on the decoction amount of acteoside in rehmanniae radix praeparata,and provide reference for studying the effec-tive ingredients of three-drug effect. METHODS:Single decoction-1(rehmanniae radix praeparata 20 g),single decoction-2(alis-matis rhizoma 20 g),single decoction-3(curcumae radix 20 g),combined decoction-1(rehmanniae radix praeparata 20 g,alisma-tis rhizoma 20 g),combined decoction-2(rehmanniae radix praeparata 20 g,curcumae radix 20 g),combined decoction-3(alisma-tis rhizoma 20 g,curcumae radix 20 g)and combined decoction-4(rehmanniae radix praeparata 20 g,alismatis rhizoma 20 g,cur-cumae radix 20 g)were respectively taken to prepare dry extracts after extracting by refluxing,HPLC was used to detect the acteo-side content and calculate its decoction amount in sample. RESULTS:The decoction amounts of acteoside in single decoction-1, combined decoction-1,combined decoction-2 and combined decoction-4 dry extracts were 0.0354,0.0223,0.0228,0.0110 mg/g,respectively. Compared with single decoction-1 group,the last 3 groups had statistical significances(P<0.01);combined decoc-tion-4 showed lowest decoction amount in three-drug combined decoction group. Acteoside was not detected in the negative control groups(single decoction-2,single decoction-3 and combined decoction-3). CONCLUSIONS:The decoction amount of acteoside is reduced when alismatis rhizoma,curcumae radix and rehmanniae radix praeparata were decocted together,indicating that it may not be the main ingredient of playing effects in three-drug combined decoction liquid.

A new approach based on online coupled liquid chromatography-gas chromatography-mass spectrometry ( LC-GC / MS ) was developed for the rapid determination of 4-( methylnitrosamino )-1-( 3-pyridyl)-1-butanone (NNK) in mainstream cigarette smoke, in which a switching valve was employed to online switching between two-dimensional chromatography. The online LC-GC / MS system used in this study was built by using online gel permeation chromatography-gas chromatography-mass spectrometry except that the micro gel column was replaced by micro alkaline alumina column which was prepared by ourselves before. The NNK in mainstream cigarette smoke was collected by a Cambridge filter pad, then the pad was extracted with dichloromethane, and the extract was quantitatively analyzed by online LC-GC / MS with D4-NNK as an internal standard. Online LC-GC / MS allowed online pretreatment purification, and the sample was subjected to online LC-GC / MS without any prior purification, which reduced human error in analysis process. The injection volume of the present online LC-GC / MS could reach 40 μL, which was 20 times of that of the conventional GC / MS (2. 0 μL of injection volume), and thus significantly improved the sensitivity. Under the optimum conditions, good linearity ( r = 0. 9998) was obtained over the range of 1. 2 - 120 ng / mL. The recoveries at three spiked levels ranged from 93. 9% to 96. 0% , and the limits of detection for qualitative and quantitative detection were 0. 25 ng / mL and 0. 9 ng / mL, respectively. All the results obtained by the present method are comparable to those of standard method recommend by China National Tobacco Company.

OBJECTIVE:To investigate the decoction amount changes of verbascoside,gallic acid in single decoction and com-bined decoction of rehmanniae radix preparata,corni fructus and poria,and provide scientific basis for further study of effective substance basis. METHODS:The single decoction,combined decoction with each 2 medicine and combined decoction with the 3 medicines of rehmanniae radix preparata,corni fructus and poria,were respectively prepared. HPLC was adopted to detect and com-pare the decoction amount of active component verbascoside in rehmanniae radix preparata and active component gallic acid in cor-ni fructus in each group. RESULTS:Compared with single decoction of rehmanniae radix preparata,the decoction amount of ver-bascoside was decreased in combined decoction of poria+rehmanniae radix preparata(P<0.01),decoction amount of verbascoside was increased in combined decoction of corni fructus+rehmanniae radix preparata or combined decoction with the 3 medicines(P<0.01). Compared with single decoction of corni fructus,the decoction amount of gallic acid in each combined decoction was de-creased (P<0.01). CONCLUSIONS:The combined decoction of rehmanniae radix preparata,corni fructus and poria has certain promotion and inhibition effects on the decoction of verbascoside in rehmanniae radix preparata and inhibition effect on the decoc-tion of gallic acid in corni fructus. It is speculated verbascoside may be one of the main components in combined decoction playing the role of effectiveness.

Chinese herbal medicines play a great role in disease prevention and treatment， while some may cause adverse effects on the human body after of long-term application. Liver injury， one of such adverse effects， is an important check item in the development of new Chinese medicines for clinical application and has become a major reason for the withdrawal of many listed drugs from the market. With the rising concern about the safety of Chinese herbal medicines， studies about liver injury caused by herbal medicines are increasing. Most of the studies focus on liver injury caused by Chinese herbal medicines or their ingredients. To improve the safety of Chinese herbal medicines， this paper summarizes the material basis and mechanisms of several Chinese herbal medicines that cause liver injury and the measures to reduce liver injury. These measures include reducing the dose and course of administration， changing the route of administration， and altering the dosage form， compatibility， and processing. In addition， this paper introduces the biological effects and mechanisms of single Chinese herbal medicines， Chinese medicine prescriptions， and active components in the prevention and treatment of liver injury. Furthermore， this paper proposes the safe dose and efficacy-toxicity boundary of Chinese herbal medicines that may cause liver injury by referring to the modern research on toxicity reduction， clarifies the mechanisms of toxicity reduction measures， and determines the material basis of liver injury induced by Chinese herbal medicines， which will ensure the safe application of herbal medicines in clinical practice. Finally， this paper suggests that efforts should be made to strengthen the clinical research on the prevention and treatment of liver injury and elucidate the scientific connotation of the prevention and treatment of liver injury by Chinese herbal medicines by using modern science and technology， aiming to provide a scientific basis for the clinical prevention and treatment of liver injury.

Crohn's disease(CD)is a special intestinal immune disease,and its pathogenesis has been a hotspot and difficult issue in the medical field,which cannot be cured clinically.In this paper,we summarized the characteristics of existing CD animal models and clinical diagnostic criteria of Chinese and Western medicine by compiling domestic and international research literature,and assigned values to the clinical fit of CD animal models.The results showed that there are many methods to replicate CD animal models,among which the pathology-evidence combination animal model is the more ideal choice.Most of the models were dominated by Western medicine pathogenic factors without the intervention of Chinese medicine pathogenic factors.Therefore,we can consider applying the intervention factors of Damp-Heat,Cold-Damp Trapped Spleen,Qi Stagnation and Blood Stasis,Liver Stagnation and Spleen Deficiency,and Spleen and Stomach Deficiency Cold on the basis of Western medicine pathogenic factors and differentiate them to obtain the pathogenic CD models with clinical manifestations of Chinese medicine symptoms.In addition,the success criteria of the model need to be further improved,and it is recommended to increase the quantitative scoring criteria of the animal's diet,mental status,weight,hair and feces and other apparent indicators.Improving the modeling methods and model criteria is the key to establishing an animal model of CD that highly simulates the complex pathological manifestations of clinical CD,and provides a more complete experimental research vehicle for in-depth studies of CD.

Objective:To identify the risk factors of heart failure in elderly patients with hip fracture by Meta-analysis.Methods:The clinical studies on perioperative heart failure in elderly patients with hip fracture were searched by computer in Pubmed, EMbase, Cochrane Library, Medline, Web of Science, CNKI, CBM, Wanfang and VIP database. The retrieval period was from the establishment of the databases to October 2021. The literature screening, data extraction and quality evaluation were completed by two researchers, and the selected literature were statistically analyzed by RevMan5.3 software.Results:A total of 17 articles were included in this study, involving 1 76 611 patients and 24 related risk factors. Cardiac history ( OR= 4.47, 95% CI 3.56-5.62), positive balance of perioperative inflow and outflow ( OR=5.99, 95% CI 3.30-10.87), anemia ( OR= 3.78, 95% CI 2.50-5.69), and the number of complications >4 ( OR=6.21, 95% CI 3.71-10.38), electrolyte disorder ( OR=7.40, 95% CI 3.77-14.54), preoperative cognitive impairment ( OR=3.60, 95% CI 1.39-9.31) and American Society of Anesthesiologists (ASA) grade ≥ 3 ( OR= 4.73, 95% CI 2.73-8.12) were statistically significant risk factors ( P<0.05). Conclusions:Cardiac history, positive balance of perioperative inflow and outflow, anemia, number of complications >4, electrolyte disorder, preoperative cognitive impairment and ASA grade ≥3 were the risk factors of perioperative heart failure in elderly patients with hip fracture.

Objective To explore the clinical manifestations, imaging and pathology features, treatment, and prognosis of endocrine glands involved patients with IgG4-related disease ( IgG4-RD) . Methods Ten patients admitted in Peking Union Medical College Hospital from 1 January 2014 to 30 June 2018 diagnosed as IgG4-RD with endocrine glands involved were enrolled in this study. All the clinical data were collected and analyzed. Results Ten patients, 4 males and 6 females, median 55 years old at the onset were enrolled, five patients with single organ involvement ( 1 case involved in pituitary, and 4 cases involved in thyroid) , while another 5 patients with 2 and more organs involved. C-reactive protein or erythrocyte sedimentation rate was elevated in 8 patients, antinuclear antibodies were positive in 7, and serum total IgE was elevated in 6 patients. Nine patients were treated with oral glucocorticoids, among whom 3 patients were treated in combination with immunosuppressive agents or rituximab. After treatment, the clinical symptoms were alleviated and imaging was improved in all patients. Serum IgG levels were significantly decreased in all patients and normalized in 5 patients. Conclusion For the patients with multiple endocrine gland diseases and elevated IgG4 level, the possibility of IgG4-RD should be carefully considered and should be confirmed by tissue biopsy and histopathology.

OBJECTIVE：To optimi ze the optimal composition proportion of 4 ingredients （Panax ginseng ，Astragalus membranaceus，Polygonatum sibiricum ，Lycium chinensis ）in Compound ginseng immune-enhancing formula （CGIF），and to study immune activity and acute toxicity of the extracts with the optimal ratio. METHODS ：The cell activity test was used to screen the crude drug concentration range of 4 ingredients. After treated with different crude drug concentrations of each medicinal material，using the contents of NO ，IL-6 and TNF-α as indexes，uniform design was used to determine the optimal ratio of each ingredient in CGIF. Totally 240 mice were taken and randomly divided into 4 batches，with 60 mice in each batch. Each batch of mice was randomly divided into blank group （normal saline ），model group （normal saline ），positive drug group [levamisole ，4 mg/（kg·d）]，and optimal proportion extract of CGIF low-dose ，medium-dose and high-dose groups [ 0.952 8，1.905 6，3.811 2 g/（kg·d）]，with 10 mice in each group ；they were given medicine intragastrically ，qd，for consecutive 30 d. Except for blank group，mice in the other groups were intraperitoneally injected with cyclophosphamide [ 40 mg/（kg·d）] on the 24th day after first administration，qd，for consecutive 3 d to induce immunocompromised model. The immune activity of the optimal proportion extract was evaluated by determining visceral coefficients ，spleen lymphocyte transformation capacity ，serum contents of hemolysin，IL-2，IgM，IgG and IgA ，phagocytosis function of peritoneal macrophages. Another 20 mice were collected and given the optimal proportion extract 20 mL/kg intragastrically ，twice；acute toxicity of the formula was investigated with oral maximum tolerated dose （MTD）. RESULTS ：The optimal ratio of CGIF was that crude drug mass ratio of P. ginseng ， membranaceus，P. sibiricum ，L. chinensis was 1 ∶ 2 ∶ 2 ∶ 4. The immunological activity experiment showed that theoptimal proportion extract can significantly improve visceral indexes of mice ， spleen lymphocyte proliferation ability serum contents of hemolysin ，IL-2，IgM，IgG and IgA as well as macrophage phagocy tosis ability （P＜0.05 or P＜ 0.01）. The acute toxicity test indicated that oral MTD was over 15 g/kg，which was non-toxic. CONCLUSIONS ：The optimal proportion extract of CGIF can significantly enhance the immune function of mice and are non-toxic.

OBJECTIVE：To optimi ze the ratio of four comp onents of Compound renshen jianti formulation （Panax ginseng ， Dioscorea oppositifolia ，Lycium barbarum fruit，Alpinia oxyphylla ），and to investigate its anti-fatigue activity and acute toxicity. METHODS：The water extract of Compound renshen jianti formulation was prepared by water extraction ，concentration and decompression drying. By single factor tests ，using weight-bearing swimming time as index ，the effects of four factors were investigated，such as the amount of P. ginseng ，D. oppositifolia ，L. barbarum fruit，A. oxyphylla . On the basis of single factor tests，using comprehensive score of weight-bearing swimming time ，serum urea nitrogen content ，liver glycogen content and AUC of blood lactate after exercise as index ，the formulation was optimized by Box-Behnken response surface method. The mice was divided into blank control group （water），positive control group （Renshen hongjingtian capsules ，0.135 g/kg）and compound low-dose，medium-dose and high-dose groups [the optimal ratio of Compound renshen jianti formulation extract （called“optimal compound formulation ”for short ）4.08，8.16，12.24 g/kg，by crude drug] ，intragastric administration of drug or distilled water 20 mL/kg，once a day ，for consecutive 30 d. The weight-bearing swimming time ，the contents of serum urea nitrogen ，liver glycogen and blood lactate AUC after exercise were used to optimize its anti-fatigue activity of optimal compound formulation. The comprehensive score was calculated based on the measured data of mice in the compound formulation middle-dose group ， and the difference between it and the theoretical prediction value was compared. The mice were given optimal compound formulation intragastrically （total dose 16.00 g/kg， by extract）. The general state ， body mass change ， toxic characteristics and death of mice were observed and recorded for 14 days. Median lethal dose （LD50）and maximum tolerated dose （MTD）were measured. RESULTS ：The optimal formulation ratio of Compound renshen jianti formulation included that P. ginseng 1.5 g，D. oppositifolia 10 g，L. barbarum fruit 10 g，A. oxyphylla 3 g. Results of anti-fatigue activity validation test showed that the optimal compound formulation could significantly prolonged weight-bearing swimming time ，reduced serum content of urea nitrogen ，blood lactate content and its AUC （except for low-dose group ），while significantly increased the content of liver glycogen （P＜0.05 or P＜0.01）. Average comprehensive score of medium-dose group was 96.95，which was only 0.06％ different from the theoretical prediction value of 97.01. The results of acute toxicity test showed that there was no death in mice. The oral MTD of the optimal compound formulation was more than 15 g/kg，which was non-toxic. CONCLUSIONS ：The optimal Compound renshen jianti formulation has effective anti-fatigue activity of mice ，and has no significant toxic effect.