Family with sequence similarity 3 (FAM3) gene family is closely related to human tumors, and plays an important role in glucose and lipid metabolism and angiogenesis, and it is related to the occurrence and development of esophageal squamous cell carcinoma, gastric cancer, colon cancer, pancreatic cancer, oral squamous cell carcinoma and breast cancer. Analysis of the role of the FAM3 gene family in glycolipid metabolism and tumors may be of great significance for understanding the occurrence and development of human tumors.

The aim of this study was to elucidate the mechanism of nuciferine on alleviating obesity based on modulating gut microbiota, ameliorating chronic inflammation, and improving gut permeability. In this study, the obese model mice were induced by high-fat diet and then randomly divided into model group, and nuciferine group; some other mice of the same week age were fed with normal diet as normal group. In the modeling process, the mice were administered intragastrically(ig) for 12 weeks. In the course of both modeling and treatment, the body weight and food intake of mice in each group were measured weekly. After modeling and treatment, the Lee's index, weight percentage of inguinal subcutaneous fat, and the level of blood lipid in each group were measured. The pathological changes of adipocytes were observed by HE staining to evaluate the efficacy of nuciferine treatment in obese model mice. 16 S rRNA sequencing analysis was conducted to study the changes in diversity and abundance of gut microbiota after nuciferine treatment. Enzyme-linked immunosorbent assay(ELISA) and quantitative Real-time polymerase chain reaction(qPCR) were used to detect the levels of inflammatory factors interleukin-6(IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α) and the expression of related genes in adipose tissue of mice in each group, so as to evaluate the effect of nuciferine on chronic inflammation of mice in obese model group. qPCR was used to detect the expression of occludin and tight junction protein 1(ZO-1)gene in colon tissure, so as to evaluate the effect of nuciferine on intestinal permeability of mice in obese group. Nuciferine decreased the body weight of obese mice, Lee's index, weight percentage of inguinal subcutaneous fat(P<0.05), and reduced the volume of adipocytes, decreased the level of total cholesterol(TC), triglyceride(TG), and low density lipoprotein cholesterol(LDL-C)(P<0.05) in serum, improved dysbacteriosis, increased the relative abundance of Alloprevotella, Turicibacter, and Lactobacillus, lowered the relative abundance of Helicobac-ter, decreased the expression of inflammatory cytokines IL-6, IL-1β, and TNF-α genes in adipose tissue(P<0.01), decreased the levels of inflammatory cytokines IL-6, IL-1β, and TNF-α in serum(P<0.05), and increased the expression of occludin and ZO-1 genes related to tight junction in colon tissue(P<0.01). Nuciferine could treat obesity through modulating gut microbiota, decreasing gut permeability and ameliorating inflammation.
Animals ; Aporphines ; Diet, High-Fat/adverse effects* ; Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Obesity/genetics*

Fel Ursi is a dried product obtained from the gallbladder of Ursidae animals, such as Selenarctos thibetanus or Ursus arctos, through gallbladder surgery for bile drainage. It is one of the rare animal medicinal materials in China and is known for its therapeutic effects, including clearing heat, removing toxins, extinguishing wind, relieving spasms, clearing the liver, and improving vision. Research has also found that Fel Ursi has pharmacological effects against cardiovascular and cerebrovascular diseases, such as anti-inflammatory, anti-apoptotic, and antioxidant stress properties. Recently, numerous studies have confirmed the close relationship between cardiovascular and cerebrovascular diseases and the gut microbiota as well as gut metabolites. Fel Ursi contains bile acid components that may have bidirectional regulatory effects on the gut microbiota and gut metabolites. This aspect could represent a potential therapeutic pathway for Fel Ursi in the treatment of cardiovascular and cerebrovascular diseases. This article comprehensively summarized relevant literature in China and abroad, reviewed the research progress on the pharmacological effects of Fel Ursi against cardiovascular and cerebrovascular diseases, and explored the impact of Fel Ursi on gut microbiota and gut metabolites, thereby aiming to provide references for further in-depth research and clinical application of Fel Ursi.
Animals ; Cerebrovascular Disorders/drug therapy* ; Bile Acids and Salts ; Lung ; Liver ; Ursidae ; Cardiovascular Diseases/drug therapy*

Objective To explore the pharmacokinetic changes of single dose of fentanyl in rats in a simulated high-altitude and contributing factors.Methods Thirty-six healthy female SD rats(6～8 weeks old,250±20 g)were randomly divided into high-altitude-acute-exposure group(group A),high-altitude-chronic-exposure group(group S)and control group(group C)through random number table,with 12 rats in each group.The group A and S were housed in a low-pressure chamber simulating the high altitude of 5000 m above sea level for 3 and 30 d respectively,and the group C was housed out of the chamber(at an altitude of 300 m).A single dose of fentanyl was administered through the femoral vein to 6 rats randomly selected from each group.Liquid chromatography tandem mass spectrometry(LC-MS/MS)was used to detect blood concentrations of fentanyl and WinNonlin 8.2 software was used to calculate the pharmacokinetic parameters,while blood samples were taken through the femoral artery before and in 1,2,4,8,15,30,60,120 and 180 min after administration.The remaining 6 rats were ultrasonographically assessed for portal vein internal diameter(PVD),peak flow velocity(PVV)and blood flow(PVF),and liver tissues were collected for CYP3A1 protein content assay.Results The blood drug concentrations of fentanyl in the group A and group S were significantly lower than those in the group C at 60,120,and 180 min(P=0.002,P＜0.001,P= 0.001).Compared with the group C,the clearance rate(CL)of the group A was increased by 54.06%(P=0.021),and the mean residence time(MRTlast)was shortened by 24.21%(P=0.033);CL of the group S was increased by 50.10%(P=0.041),the area under the concentration-time curve(AUC0-t,AUC0-∞)and MRTlast were reduced by 18.92%(P=0.039),27.54%(P=0.018)and 33.61%(P= 0.004),respectively.PVD and PVF in the group S increased by 10.87%(P=0.006)and 42.50%(P= 0.006)when compared with the group C.The CYP3A1 protein content in the group A was 28.74%,which was higher than that in the group C(P=0.048).Conclusion Fentanyl is cleared significantly faster after a single dose in rats in simulated high-altitude,which may be related to the increased liver blood flow and increased CYP3A1 protein expression in liver.

Pharmacodynamics material basis and effective mechanisms are the two main issues to decipher the mechnisms of action of Traditional Chinese medicines (TCMs) for the treatment of diseases. TCMs, in "multi-component, multi-target, multi-pathway" paradigm, show satisfactory clinical results in complex diseases. New ideas and methods are urgently needed to explain the complex interactions between TCMs and diseases. Network pharmacology (NP) provides a novel paradigm to uncover and visualize the underlying interaction networks of TCMs against multifactorial diseases. The development and application of NP has promoted the safety, efficacy, and mechanism investigations of TCMs, which then reinforces the credibility and popularity of TCMs. The current organ-centricity of medicine and the "one disease-one target-one drug" dogma obstruct the understanding of complex diseases and the development of effective drugs. Therefore, more attentions should be paid to shift from "phenotype and symptom" to "endotype and cause" in understanding and redefining current diseases. In the past two decades, with the advent of advanced and intelligent technologies (such as metabolomics, proteomics, transcriptomics, single-cell omics, and artificial intelligence), NP has been improved and deeply implemented, and presented its great value and potential as the next drug-discovery paradigm. NP is developed to cure causal mechanisms instead of treating symptoms. This review briefly summarizes the recent research progress on NP application in TCMs for efficacy research, mechanism elucidation, target prediction, safety evaluation, drug repurposing, and drug design.
Drugs, Chinese Herbal/pharmacology* ; Network Pharmacology ; Artificial Intelligence ; Medicine, Chinese Traditional ; Metabolomics

Objective: To evaluate the efficacy and safety of different positions external physical vibration lithecbole (EPVL) therapy for ureteral calculi related renal colic. Methods: This study was a prospective multicenter randomized controlled trial. The inclusion criteria was that patients volunteered to participate in the trial and signed informed consent, patients’age ranged from 18-65 years old, ureteral calculi related with renal colic, stone diameter was less than 7 mm, patients were not treated with analgesia, antispasmodic drugs. The exclusion criteria was that combination of severe urinary tract infection, severe hydronephrosis, urinary malformation, severe hypertension, history of cerebrovascular disease, vital organ dysfunction, obesity (BMI>35 kg/m²), history of ureteral calculi exceeded 2 months, abnormal blood coagulation. Patients were randomized into observation group and control group using random number table method. The observation group and the control group were placed on the physical vibration stone arranging machine with head low foot high position and head high foot low position respectively. The inclination angle was 24°. The secondary vibrator vibrated for 6 minutes, then the patient took the prone position and opened the main, the secondary vibrator. The treatment is completed after 6 minutes of vibration. The analgesic effect, stone removal, follow-up effects and adverse reactions in the two groups was compared. We defined the pain relief rate as(VAS score before treatment-VAS score after treatment)/VAS score before treatment×100%. Results: A total of 100 patients were included in the study, 50 in the observation group and 50 in the control group. There were no statistical difference in the age of the two groups [(41.8±11.7)years and (46.6±13.9 years)], gender distribution [37(male)/13(female) and 42(male)/ 8(female)], location of stones (in the observation group, 19 cases in upper ureter, 7 cases in the middle ureter and 24 cases in the lower ureter; in the control group, 12 cases in the upper ureter, 3 cases in the middle ureter, and 35 in the lower ureter), left and right distribution of stones [21(right)/ 29 (left) and 22 (right)/ 28(left)], long diameter of stones [(5.2±0.9)mm and(5.1±1.1)mm], VAS scores before treatment (7.5±1.4 and 7.6±1.5), and readmission rate [22%(11/50)With 18%(9/50)], 1 week stone removal rate [70%(35/50) and 64%(32/50)]. The incidence of adverse reactions was 8%(4/50) in the observation group including 3 cases of nausea, 1 case of vomiting. The incidence of adverse reactions was 4% in the control group (2/50), which 2 cases showed nausea. The number of patients who chose EPVL, ESWL or surgery for the subsequent treatment in observation group was 35 cases, 9 cases, and 6 cases respectively. The number of patients who chose EPVL, ESWL or surgery for the subsequent treatment in the control group was 35 cases, 10 cases and 5 cases respectively. There was no significant difference between the two groups (P>0.05). The VAS score after treatment of the observation group was lower than that of the control group (2.4±1.3 and 3.7±1.5, P<0.01). The total effective rate of the observation group was higher than that of the control group [94%(47/50) and 76%(38/50), P<0.01]. 46 patients underwent urinary ultrasonography to check the degree of hydronephrosis. The reduction rate of hydronephrosis was higher in the observation group than in the control group [54.5%(18/33) and 30.8%(4/13)], but there was no significant difference between the two groups (P=0.146). In the upper ureteral calculi, the VAS score of the observation group was lower than that of the control group (2.4±0.3 and 3.9±0.4, P<0.01). There was no significant difference in the total effective rate between the two groups. In the lower ureteral calculi, the observation group had low VAS score after treatment. In the control group (2.4±0.2 and 3.5±0.2, P<0.01), there was no significant difference in the total effective rate between the two groups; the middle segment stones were less included (10 in total) and were not discussed. Conclusions The external physical vibration lithecbole adopts " head high and low position" has better effect than "head low foot high position" in treatment of ureteral calculi with renal colic, and security is acceptable.