ObjectiveTo explore the main mechanism of self-precipitation formed during the decoction of Sinitang（SNT）， and to provide a research basis for exploring the differences in the toxic and effective components of this compound. MethodsThe average precipitation yields of SNT， Glycyrrhizae Radix et Rhizoma（GRR）-Aconiti Lateralis Radix Praeparata（ALRP） decoction（GF）， ALRP-Zingiberis Rhizoma（ZR） decoction（FJ）， GRR-ZR decoction（GJD）， ALRP decoction（FZ）， ZR decoction（GJ） and GRR decoction（GC） were determined. The four main self-precipitation samples of SNT， GF， FZ and GC were physically characterized by particle size， scanning electron microscopy（SEM）， pH， total dissolved solids（TDS）， conductivity， and Fourier transform infrared spectroscopy（FT-IR） analysis. The chemical compositions of SNT decoction and its different phases was identified by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap-MS） for SNT， SNT self-precipitation and SNT supernatant， and the contents of its main toxic and effective components were determined by high performance liquid chromatography（HPLC）. ResultsPrecipitation yield results of the 7 samples of SNT decoction and single decoction showed that SNT had the highest self-precipitation yield. The formation of SNT self-precipitation was mainly related to the reaction between ALRP and GRR components to form complexes， and FT-IR showed that GRR had the greatest influence on the formation of self-precipitation. A total of 110 components were identified in the SNT decoction， including 100 components in the SNT self-precipitation and 106 components in the SNT supernatant. And quantitative results of the main toxic and effective components revealed that the reaction between ALRP and GRR components formed complexes， resulting in the following content hierarchy for free components：SNT decoctionsupernatantself-precipitation， these components included free liquiritin， benzoylmesaconine， benzoylaconitine， benzoylhypacoitine， liquiritigenin， aconitine， hypoaconitine， isoliquiritigenin and ammonium glycyrrhizinate. ConclusionSNT exhibits spontaneous precipitation during compound decoction， with GRR exerting the greatest influence on its formation. This suggests GRR plays a significant role in the detoxification of SNT. The differences in the self-precipitated toxic-effective components of SNT compound decoction primarily manifest as changes in component content， reflecting the characteristics of SNT "deposition in vitro and sustained release in vivo" and the importance of "administered at draught" in the clinical application of SNT.

Natural compounds demonstrate unique therapeutic advantages for cancer treatment, primarily through direct tumor suppression or interference with the tumor microenvironment (TME). Glycyrrhizic acid (GL), a bioactive ingredient derived from the medicinal herb Glycyrrhiza uralensis Fisch., and its sapogenin glycyrrhetinic acid (GA), have been recognized for their ability to inhibit angiogenesis and remodel the TME. Consequently, the combination of GL with other therapeutic agents offers superior therapeutic benefits. Given GL's amphiphilic structure, self-assembly capability, and liver cancer targeting capacity, various GL-based nanoscale drug delivery systems have been developed. These GL-based nanosystems exhibit angiogenesis suppression and TME regulation properties, synergistically enhancing anti-cancer effects. This review summarizes recent advances in GL-based nanosystems, including polymer-drug micelles, drug-drug assembly nanoparticles (NPs), liposomes, and nanogels, for cancer treatment and tumor postoperative care, providing new insights into the anti-cancer potential of natural compounds. Additionally, the review discusses existing challenges and future perspectives for translating GL-based nanosystems from bench to bedside.
Animals ; Humans ; Antineoplastic Agents/therapeutic use* ; Glycyrrhizic Acid/therapeutic use* ; Liposomes/chemistry* ; Micelles ; Nanoparticles/chemistry* ; Neoplasms/pathology* ; Tumor Microenvironment/drug effects* ; Nanoparticle Drug Delivery System/therapeutic use*

OBJECTIVE To study the effects of yunaconitine on myocardial injury in rats and its mechanism related to mitochondrial apoptosis pathway rats. METHODS Forty SD rats were divided into normal group （normal saline）， yunaconitine high-dose and low-dose groups（0.14， 0.09 mg/kg）and aconitine group （positive control， 0.88 mg/kg） by random number method， with 10 rats in each group. They were given relevant medicine intragastrically， once a day， for consecutive 7 days. The levels of lactate dehydrogenase （LDH）， creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， superoxide dismutase （SOD） and malondialdehyde （MDA） in serum as well as the level of reactive oxygen species （ROS） in myocardial tissue were detected. The pathomorphological changes of myocardium and ultrastructural changes of myocardial mitochondria were all observed. The apoptosis of cardiomyocytes was determined. The protein relative expressions of B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， caspase-9， cleaved-caspase-9， caspase-3 and cleaved-caspase-3 were determined in myocardium of rats. RESULTS Compared with normal group， the serum levels of LDH， CK， CK-MB and MDA， the apoptotic numbers of cardiomyocytes， the level of ROS and protein expression of caspase-3 in myocardium were increased significantly in yunaconitine high-dose and low- dose groups （P＜0.05 or P＜0.01）； serum level of SOD and Bcl-2/Bax ratio in myocardium were all decreased significantly （P＜ 0.01）； the protein relative expressions of caspase-9， cleaved-caspase-9， caspase-3 and cleaved-caspase-3 in myocardium were significantly increased in yunaconitine high-dose group （P＜0.05）； some pathomorphological changes were found in 2 groups， such as myocardial fiber disorder， mitochondrial swelling. CONCLUSIONS Yunacotine could cause myocardial injury in rats. Its mechanism might be related to destroying the integrity of cardiomyocyte membrane， causing oxidative stress of cardiomyocyte， and inducing the apoptosis of myocardial cells through mitochondrial pathway.

OBJECTIVE：To study the toxicity mechanism of yunacotine-induced arrhythmia in rats. METHODS ：Totally 32 rats were randomly divided by random number table method into normal control group ，yunacotine low-dose and high-dose groups （0.09，0.14 mg/kg），aconitine group （positive control ，0.88 mg/kg），with 8 rats in each group. Administration groups were given the corresponding drugs once a day ，and normal control group was given the constant volume of normal saline ，for consecutive 7 d. After last intragastric administration ，the changes of electrocardiogram （ECG） were observed. The contents of adenosine triphosphate（ATP）in myocardial tissue and Ca 2+ in myocardial cells ，the activities of Na +-K+-ATPase and Ca 2+-Mg2+-ATPase as well as the protein expression of ranolidine receptor 2（RyR2）and Ca 2+-ATPase（SERCA2）in myocardial tissue were determined. RESULTS：Compared with normal control group ，time limit of QRS wave and QTc intervals of rats were prolonged significantly in yunaconitine low-dose group （P＜0.01）. The content of Ca 2 + in myocardial cells ， the ATP contents ， the activities of Ca2+-Mg2+-ATPase and Na +-K+-ATPase as well as the protein expression of SERCA 2 in myocardial tissue were reduced significantly （P＜0.05 or P＜0.01）. The heart rate of rats in yunaconitine high-dose group and aconitine group were increased significantly （P＜ 0.05 or P＜0.01），and time limit of QRS wave and QTc intervals were significantly prolonged （P＜0.01）；the content of Ca 2+ in myocardial cells was increased significantly （P＜0.01）；ATP content ，the activities of Ca 2+-Mg2+-ATPase and Na +-K+-ATPase，and protein expression of RyR 2 and SERCA 2 in myocardial tissue were decreased significantly （P＜0.01）. CONCLUSIONS ： Yunaconitine can induce arrhythmia in rats ，the mechanism of which may be associated with Ca 2+ overload that resulted from reducing the activities of Na +-K+-ATPase and Ca 2+-Mg2+-ATPase and down-regulating the expression of related calcium transporter RyR2 and SERCA 2.

Corona virus disease 2019 (COVID-19) patients with trauma are at high risk of venous thromboembolism (VTE), which must be taken seriously in the therapeutic processes. Hypercoagulable state is induced by 2019 novel coronavirus (2019-nCoV) in many ways, such as increasing the level of inflammatory factors and fibrinogen, and inducing endothelial cell injury. The venous wall injuries from trauma and operation directly or indirectly trigger off the exogenous coagulation pathway and the microcirculation can be damaged at the same time, which may initiate the exogenous pathway of VTE. Immobilization of limbs and forced bed rest during the treatment of traumatic patients will slow venous blood flow. Chronic non-communicable diseases such as diabetes in the elderly were independent risk factors for VTE. Furthermore, the persistent fever, severe lung disease, respiratory failure, sepsis and invasive technology application add the risk of VTE and the difficulty of treatment. In order to help effective prevention VTE of for COVID-19 patients with trauma, the authors put forward relevant technical suggestions for prevention and nursing of VTE to provide basis for nursing work during pandemic of COVID-19.

Objective To analyze the effects of Hual qi huang granules on children with mycoplasma pneumoniae pneumonia.Methods A randomized,multicenter parallel controlled clinical trial was carried out.A total of 3 000 cases of hospitalized children with mycoplasma pneumoniae pneumonia were selected.All of them were given treatment for mycoplasma pneumoniae pneumonia with macrolide antibiotics and symptomatic treatment.They were randomly divided into 2 groups:research group and control group.The children of research group were give oral Huai qi huang granules for three months.According to the classification of pneumonia,these two groups were divided into:lobar pneumonia research group,lobar pneumonia control group,lobular pneumonia research group,lobular pneumonia control group.The hospitalization duration of fever,length of hospital stay,the absorption area of lung inflammation and pneumonia severity sores were observed.The frequency of upper respiratory infections,bronchitis,pneumonia were observed in 3 months after discharge.Results 2 378 cases were investigated.The hospitalization duration of fever,length of hospital stay of research group were significantly shorter than that of in control group (P ＜ 0.001).The children with lobar pneumonia,2 weeks after treatment,the absorption of consolidation of the lobar pneumonia research group is significantly better than lobar pneumonia control group (P ＜0.001).After two weeks treatment,the pneumonia scores of lobar pneumonia research group is lower than lobar pneumonia control group (P ＜ 0.05).Followup of 3 months after hospital discharge,frequency of upper respiratory infection and bronchitis of research group,were significantly lower than that of control.In addition,appetite increased significantly in research group than control (P ＜ 0.001).There are 21 cases with drug associated adverse reactions (mild diarrhea),including 12 cases of research group,9 cases of control group,and there was no statistical significance (P ＞0.05).Conclusion Standard treatment combined with oral Huai qi huang granules in the treatment of mycoplasma pneumoniae pneumonia,can significantly shorten hospitalization duration of fever,length of hospital stay and reduce the severity score of pneumonia.Three months oral Huai qi huang granules can significant reduce the frequency of respiratory infections and bronchitis,also can increase patients appetite,and be safe.

Objective To explore the correlation between the posterior vertebral muscle group aging degeneration and body mass index (BMI) in normal middle-aged and elderly women.Methods One hundred and fifteen women(48-75 years old) were divided into the middle-aged group (＜60 years old) and elderly group (≥60 years old).The muscle area of posterior vertebral muscle group and fat area at lumbar levels L3 were measured by quantitative computed tomography (QCT).The muscle fat infiltration (MFI),e.g.fat area/(muscle area + fat area),was calculated.The differences between the two groups were compared by using independent-samples t test.The correlation and linear regression analysis were used for analyzing the correlations between the muscle area,fat area and MFI with age and BMI.Results The BMI had no statistical difference between the two groups (P＞0.05),while the muscle area of posterior vertebral muscle group,fat area and MFI had statistical difference (t=2.182,-1.997,-2.604,P=0.031,0.048,0.010);the correlation and linear regression analysis showed that controlling the body height,body mass factor and age were positively correlated with the fat area of posterior vertebral muscle group and MFI(r=0.275,0.320,t=2.915,3.445,P=0.004,0.001),while had no obvious correlation with the muscle area(r=-1.109,P =0.270);controlling age factor and BMI were positively correlated with the fat area of posterior vertebral muscle group and MFI(r=0.361,0.307,t=3.945,3.277,P≤0.001),while had no obvious correlation with the muscle area(t=1.653,P=0.101).Conclusion In middle-aged and elderly women,the fat content of posterior vertebral muscle group is increased with the age increase.In evaluating the degeneration,especially greater body mass,the fat content of muscles and their proportion have more significance than the muscle area.

Aim To investigate the effect of SM-1 on seven main cytochrome P450(CYP450)in human liver microsomes.Methods Substrate or SM-1 was incubated with human liver microsomes for 30 min in vitro,and divided into control group and experimental group.The effects of SM-1 on the main phase I metabolic enzymes in human liver microsomes was detected by HPLC.Phenacetin,bupropion,paclitaxel,tolbutamide,omeprazole,dextromethorphan,testosterone were investigated as probe drugs.Results Inhibition rate of SM-1 on the classical substrate of human liver microsomal CYP was 0.05％,3.37％,0.08％,2.07％,4.20％,-0.15％and 10.84％,respectively.Conclusions SM-1 may have inhibitory effect on CYP3A4.Attention should be paid to the interaction of clinical drug induced by CYP enzyme inhibition.

Objective To know the blood lead level of children in Handan city and the influence factors. Methods In Oct. 2004,211 children aged 2-6 years,living in Handan city for more than one year and without eliminating lead medicine treatment in recent three months,were chosen from a kindergarten. The blood lead was determined by WFC atomic absorption spectrometer. The influence factors were investigated by questionnaire.Results The blood lead level was(89.2?13.6) ?g/L,the prevalence of lead poisoning was 11.85%,no significant difference was seen between boys and girls. As for the blood lead level,the children living in the industrial areas or near traffic road was higher,the children living in the newly decorated house was higher,the children often eat preserved eggs was higher,the children whose parents engaged in the work of lead exposure was higher,the children whose parents smoke heavily at home everyday was higher,the children whose parents had lower education was higher. Conclusion More attention should be paid to prevent and control child lead poisoning in Handan city.

Objective: To develop a therapeutic adjuvantfree protein vaccine against HPV16 which is closely related to cervical cancer of China. Method: First the E6/E7 gene by PCR technology from HPV16z virus strain was isolated in the highrisk cervical cancer area of Shanxi province of China in1990s, and again got the gene segment of Hsp65 from BCG by the same method, mutated the transforming codes in sequences of HPV 16 E6/E7 genes and thus constructed the expression vector pET28aHsp65E6/E7, expressed the Hsp65E6/E7 fusion protein in E.coli BL21(DE3) strain and researched optimal protein purification procedures. Results: The expression vector pET28aHsp65E6/E7 was constructed successfully and E6/E7 gene was mutated correctly. Hsp65E6/E7 fusion protein was renatured and purified on the affinity chromatography column simultaneously. The protein purity achieved 95% after the anionic exchange chromatograph purification. conclusions: This research laid a foundation for further functional study of the therapeutic adjuvantfree protein vaccine——Hsp65E6/E7.