Objective To investigate the effect of NOD-like receptor family pyrin domain containing 3(NLRP3)knockdown on a mouse model of nonalcoholic steatohepatitis(NASH)induced by high-fat high-carbohydrate(HFHC)diet.Methods A total of 44 mice were randomly divided into normal diet group(CON group)with 20 mice and HFHC group with 24 mice.At the end of week 14 of modeling,4 mice were randomly selected from the HFHC group for the pre-experiment of adeno-associated virus(AAV)by tail vein injection,and NLRP3 knockdown was verified after 4 weeks.After NLRP3 knockdown was verified at the end of week 18,the remaining 40 mice were given a single tail vein injection of AAV,and then they were divided into CON+NLRP3 knockdown negative control group(CON+NLRP3-NC group),CON+NLRP3 knockdown group(CON+NLRP3-KD group),HFHC+NLRP3-NC group,and HFHC+NLRP3-KD group,with 10 mice in each group.At the end of week 24,the activation of NLRP3 inflammasome was observed;related indicators were measured,including body weight,liver weight,liver index,and glucose metabolism(fasting blood glucose,fasting insulin,and Homeostasis Model Assessment of Insulin Resistance[HOMA-IR]index);the indicators of liver lipid content(liver triglyceride[TG]and oil red O staining),liver inflammation(serum alanine aminotransferase[ALT]activity,HE staining,and inflammation-related genes),and liver fibrosis(Sirius Red staining and fibrosis-related genes)were measured.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results Compared with the CON+NLRP3-NC group based on the results of Western Blot,the HFHC+NLRP3-NC group had significant increases in the protein expression levels of NLRP3,pro-Caspase1,Caspase1,ASC,and IL-1β,while the HFHC+NLRP3-KD group had significant reductions in these levels(all P<0.05).The HFHC+NLRP3-NC group showed varying degrees of increase in body weight,liver weight,liver index,and glucose metabolism indicators,while the HFHC+NLRP3-KD group showed significant improvements in these indicators(all P<0.05).As for hepatic fat deposition,compared with the CON+NLRP3-NC group,the HFHC+NLRP3-NC group had a significant increase in liver TG,with a large number of red lipid droplets shown by oil red O staining,and the HFHC+NLRP3-KD group had significant reductions in liver TG and the number of lipid droplets in the liver(all P<0.01).In terms of liver inflammation,compared with the CON+NLRP3-NC group,the HFHC+NLRP3-NC group had significant increases in serum ALT,NAFLD activity score,and inflammation-related genes,while the HFHC+NLRP3-KD group had significant reductions in these indicators(all P<0.01).As for liver fibrosis,compared with the CON+NLRP3-NC group,the HFHC+NLRP3-NC group had significant increases in collagen fiber area and fibrosis-related genes,and the HFHC+NLRP3-KD group had significant reductions in fibrosis-related genes(all P<0.05)and a tendency of reduction in collagen fiber area(P>0.05).Conclusion NLRP3 knockdown can significantly improve hepatic fat deposition and inflammation in a mouse model of HFHC-induced NASH.

Nonalcoholic fatty liver disease(NAFLD)is currently a chronic liver disease with the highest prevalence rate in the world,with complex pathogeneses and limited clinical treatment methods.Over the past 20 years,the discovery of active components for NAFLD treatment from traditional Chinese medicine and compound prescriptions of the components that can exert a multi-target effect has been one of the research hotspots.Based on the chemical components of traditional Chinese medicine,this article elaborates on the active components with a promising future in the treatment of NAFLD,including flavonoids,phenols,terpenoids,alkaloids,and saponins,as well as the compound prescriptions of active components with a synergistic effect,in order to provide new ideas for the strategies of pharmacotherapy for NAFLD.

Objective To investigate the levels of plasma bile acids(BA)in patients with primary liver cancer(PLC)or metastatic liver cancer(MLC)and their correlation with clinical indicators,as well as the value of plasma BAs combined with alpha-fetoprotein(AFP)in the diagnosis of PLC.Methods This study was conducted among 75 patients with PLC and 79 patients with MLC who attended Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from August 2020 to September 2021 and had a confirmed diagnosis based on histopathological and imaging findings.Peripheral blood samples were collected from all patients,and serum and plasma were separated.Colorimetry and chromatography were used to measure biochemical parameters;electrochemiluminescence immunoassay was used to measure the levels of tumor markers;liquid chromatography-tandem mass spectrometry was used to measure the content of BA.The t-test was used for comparison of normally distributed continuous data,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data;the Spearman's coefficient was used for correlation analysis;the receiver operating characteristic(ROC)curve was used to evaluate clinical diagnostic efficacy.Results The PLC group had significantly lower levels of total cholesterol,triglyceride,low-density lipoprotein cholesterol,and apolipoprotein B than the MLC group(U=1 598,1 255,909,and 889,all P＜0.05).Compared with the MLC group,the PLC group had a significantly higher level of AFP and a significantly lower level of carcinoembryonic antigen(U=1 873 and 926,both P＜0.05).Compared with the MLC group,the PLC group had significantly higher levels of TBA,CA,CDCA,UDCA,TCA,TCDCA,GCA,GCDCA,TUDCA,and GUDCA and a significantly lower level of DCA(all P＜0.05).In the total population,the levels of TBA,CDCA,GCA,GCDCA,GUDCA,TCA,TCDCA,and TUDCA were significantly positively correlated with the level of AFP(all P＜0.05).In the patients with PLC,the levels of GCA,TCA,TCDCA,and TUDCA were significantly positively correlated with the level of AFP(all P＜0.05).Combined measurement of AFP+TCA+GCA+TCDCA had an area under the ROC curve of 0.822(95%confidence interval:0.746-0.898,P＜0.000 1),suggesting that it had the highest diagnostic efficacy.Conclusion There are significant differences in the levels of plasma BA between the patients with PLC and those with MLC,and the differentially expressed BAs are closely associated with liver function impairment and the increase in AFP.BAs combined with AFP has a better clinical value in the diagnosis of PLC.

Objective To establish the rapid identification method of Hedysari Radix wild and cultivated products by integrating the identification characteristics of TCM traits obtained by intelligent senses such as electronic nose and colorimeter based on the multivariate statistical analysis method;To provide new ideas and methods for the formulation of commodity specification standards and the application research of market quality control for Hedysari Radix.Methods Totally 29 batches of samples of Hedysari Radix were detected based on colorimeter and electronic nose technology to obtain their sensory information,and the effective components of Hedysari Radix were determined by high performance liquid chromatography(HPLC)and other methods for joint analysis.After establishing the optimal experimental conditions of Hedysari Radix electronic nose,multivariate statistical analysis methods,such as principal component analysis(PCA),orthogonal partial least squares-discriminant analysis(OPLS-DA)and clustering analysis,were used to establish the identification model of Hedysari Radix wild and cultivated commodities.Results The optimum test conditions of Hedysari Radix electronic nose(particle size of 65 mesh):the sample weight was 2.0 g,the optimum temperature of the sample was 50℃,and the time was 25 min.A single intelligent sensory result could not quickly and accurately identify the two,but the fusion information could quickly identify the wild and cultivated commodities of Hedysari Radix,and the chemical composition had a certain correlation with the color and taste.Conclusion Electronic nose and colorimeter can quickly and accurately distinguish wild and cultivated Hedysari Radix after multivariate statistical analysis,which is simple and feasible.The combined analysis of its related properties and active components can be used for the quality evaluation of Hedysari Radix.

ObjectiveTo study the effect of Bushen Huoxuetang on the apoptosis and the expression of B-cell lymphoma （Bcl-2）-associated X protein （Bax）/ Bcl-2 and cleaved cysteine-containing aspartate proteolytic enzyme-3 （cleaved Caspase-3） in the nude mouse model of bone metastasis of breast cancer， and explore the mechanism of Bushen Huoxuetang in inhibiting bone destruction. MethodThirty BALB/c female nude mice were randomly assigned into blank group （n=6） and model group （n=24）. The suspension of 4T1 breast cancer cells was injected into the tibia of mouse right lower limb to establish model of bone metastasis of breast cancer. The successfully modeled nude mice were randomly assigned into model group， Bushen Huoxuetang group， zoledronic acid group， and combined drug group， with 6 mice in each group. Bushen Huoxuetang was administrated at a dose of 36.67 g·kg^-1， once a day， and zoledronic acid was administrated by subcutaneous injection at a dose of 100 μg·kg^-1， twice a week. The combined drug group was administrated with the same doses of Bushen Huoxuetang group by gavage and zoledronic acid by subcutaneous injection. The mice in the blank group and the model group were administrated with the same volume of distilled water by gavage for 14 days. On the next day at the end of drug administration， the mice were sacrificed by cervical dislocation. The general situation and weight changes of the mice were examined. The right lower limb was collected， and X-ray scanning and hematoxylin-eosin （HE） staining methods were used for observation of pathological changes in the bone. The terminal deoxynucleotidyl transferase dUTP nick-end labeling （TUNEL） was employed to detect the apoptosis of bone tissue in nude mice， and Western blot to determine the expression of Bax/Bcl-2 and cleaved Caspase-3 in the bone tissue. ResultCompared with the blank group， the modeling reduced the body weight （P<0.01） and increased the right lower limb weight of the nude mice （P<0.01）. Compared with the model group， Bushen Huoxuetang， zoledronic acid， and their combination increased the body weight （P<0.01） and decreased the right lower limb weight （P<0.01）. Compared with the blank group， the other groups showed obvious tumor cell atypia， deep nuclear staining， and clear bone metastasis， and the model group showed obvious osteolytic damage in right lower limb and loss of proximal tibia and knee joint. Compared with the model group， Bushen Huoxuetang， zoledronic acid， and their combination reduced the osteolytic lesions in the right lower limb and recovered part of the bone structure， demonstrating an inhibitory effect on bone destruction. The TUNEL assay showed that the model group had lower apoptosis rate of bone metastatic tumor cells than the blank group， Bushen Huoxuetang group， zoledronic acid group， and combined drug group （P<0.01）. Compared with the blank group， the modeling down-regulated the expression of Bax and cleaved Caspase-3 （P<0.01） and up-regulated the expression of Bcl-2 （P<0.01）. Compared with the model group， Bushen Huoxuetang， zoledronic acid， and their combination up-regulated the expression of Bax （P<0.01） and cleaved Caspase-3 （P<0.05， P<0.01） and down-regulated the expression of Bcl-2 （P<0.05， P<0.01）. ConclusionBushen Huoxuetang may inhibit bone destruction in the nude mouse model of bone metastasis of breast cancer by up-regulating the expression of Bax， down-regulating the expression of Bcl-2， activating cleaved Caspase-3， and further inducing apoptosis.

Without artificial airway though oral, nasal or airway incision, the bi-level positive airway pressure (Bi-PAP) has been widely employed for respiratory patients. In an effort to investigate the therapeutic effects and measures for the respiratory patients under the noninvasive Bi-PAP ventilation, a therapy system model was designed for virtual ventilation experiments. In this system model, it includes a sub-model of noninvasive Bi-PAP respirator, a sub-model of respiratory patient, and a sub-model of the breath circuit and mask. And based on the Matlab Simulink, a simulation platform for the noninvasive Bi-PAP therapy system was developed to conduct the virtual experiments in simulated respiratory patient with no spontaneous breathing (NSB), chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS). The simulated outputs such as the respiratory flows, pressures, volumes, etc, were collected and compared to the outputs which were obtained in the physical experiments with the active servo lung. By statistically analyzed with SPSS, the results demonstrated that there was no significant difference ( P > 0.1) and was in high similarity ( R > 0.7) between the data collected in simulations and physical experiments. The therapy system model of noninvasive Bi-PAP is probably applied for simulating the practical clinical experiment, and maybe conveniently applied to study the technology of noninvasive Bi-PAP for clinicians.
Humans ; Respiration, Artificial/methods* ; Positive-Pressure Respiration/methods* ; Respiration ; Ventilators, Mechanical ; Lung

At present, the passive simulated lung including the splint lung is an important device for hospitals and manufacturers in testing the functions of a respirator. However, the human respiration simulated by this passive simulated lung is quite different from the actual respiration. And it is not able to simulate the spontaneous breathing. Therefore, including" the device simulating respiratory muscle work "," the simulated thorax" and" the simulated airway", an active mechanical lung to simulate human pulmonary ventilation was designed:3D printed human respiratory tract was developed and connected the left and right air bags at the end of the respiratory tract to simulate the left and right lungs of the human body. By controlling a motor running to drive the crank and rod to move a piston back and forth, and to deliver an alternating pressure in the simulated pleural, and so as to generate an active respiratory airflow in airway. The experimental respiratory airflow and pressure from the active mechanical lung developed in this study are consistent with the target airflow and pressure which collected from the normal adult. The developed active mechanical lung function will be conducive to improve the quality of the respirator.
Adult ; Humans ; Lung/physiology* ; Respiration ; Pulmonary Ventilation ; Respiration, Artificial ; Ventilators, Mechanical

OBJECTIVES: With the increasing detection rate of lung nodules, the qualitative problem of lung nodules has become one of the key clinical issues. This study aims to evaluate the value of combining dynamic contrast-enhanced (DCE) MRI based on time-resolved imaging with interleaved stochastic trajectories-volume interpolated breath hold examination (TWIST-VIBE) with T₁ weighted free-breathing star-volumetric interpolated breath hold examination (T₁WI star-VIBE) in identifying benign and malignant lung nodules. METHODS: We retrospectively analyzed 79 adults with undetermined lung nodules before the operation. All nodules of patients included were classified into malignant nodules (n=58) and benign nodules (n=26) based on final diagnosis. The unenhanced T₁WI-VIBE, the contrast-enhanced T₁WI star-VIBE, and the DCE curve based on TWIST-VIBE were performed. The corresponding qualitative [wash-in time, wash-out time, time to peak (TTP), arrival time (AT), positive enhancement integral (PEI)] and quantitative parameters [volume transfer constant (Ktrans), interstitium-to-plasma rate constant (Kep), and fractional extracellular space volume (Ve)] were evaluated. Besides, the diagnostic efficacy (sensitivity and specificity) of enhanced CT and MRI were compared. RESULTS: There were significant differences in unenhanced T₁WI-VIBE hypo-intensity, and type of A, B, C DCE curve type between benign and malignant lung nodules (all P<0.001). Pulmonary malignant nodules had a shorter wash-out time than benign nodules (P=0.001), and the differences of the remaining parameters were not statistically significant (all P>0.05). After T₁WI star-VIBE contrast-enhanced MRI, the image quality was further improved. Compared with enhanced CT scan, the sensitivity (82.76% vs 80.50%) and the specificity (69.23% vs 57.10%) based on MRI were higher than that of CT (both P<0.001). CONCLUSIONS T₁WI star-VIBE and dynamic contrast-enhanced MRI based on TWIST-VIBE were helpful to improve the image resolution and provide more information for clinical differentiation between benign and malignant lung nodules.
Adult ; Humans ; Retrospective Studies ; Magnetic Resonance Imaging ; Plasma ; Tomography, X-Ray Computed ; Lung

Objective To investigate the effect of Xuefu Zhuyu decoction on nonalcoholic fatty liver disease (NAFLD) and its material basis. Methods In experiment 1 for exploring the effect of Xuefu Zhuyu decoction on mice with NAFLD induced by high-fat diet, 50 healthy male C57BL/6J mice were randomly divided into normal group, model group, high- and low-dose Xuefu Zhuyu decoction groups, and obeticholic acid control group, with 10 mice in each group. The mice in the normal group were given control diet, and those in the other groups were given high-fat diet. Gastric administration was started at week 13, and related samples were collected at the end of week 16. Food intake and body weight were recorded, enzyme-linked immunosorbent assay was used to measure the serum level of fasting insulin, fasting blood glucose was measured, and insulin resistance index was calculated. HE staining and NAFLD activity score (NAS) were used to observe liver histopathology in mice, oil red O staining was used to observe lipid deposition, and triglyceride (TG) level in liver tissue and serum alanine aminotransferase (ALT) level were measured. In experiment 2 for exploring the effect of different extracts of Xuefu Zhuyu decoction on mice with NAFLD induced by high-fat diet, the methods of water decocting, water extraction and alcohol precipitation, and petroleum ether extraction were used to obtain the extracts 1, 2, and 3 of Xuefu Zhuyu decoction, and 54 healthy male C57BL/6J mice were randomly divided into normal group, model group, Xuefu Zhuyu decoction extract 1, 2, and 3 groups, and Xuefu Zhuyu decoction control group, with 9 mice in each group. The mice in the normal group were given control diet, and those in the other groups were given high-fat diet. Gastric administration was started at week 13, and related samples were collected at the end of week 16. Food intake and body weight were recorded, and enzyme-linked immunosorbent assay was used to measure the serum level of fasting insulin, fasting blood glucose was measured, and insulin resistance index was calculated. HE and NAS were used to observe liver histopathology in mice, oil red O staining was used to observe lipid deposition, and the levels of TG and gamma-glutamyl transpeptidase (GGT) in liver tissue and the serum level of ALT were measured. The t -test was used for comparison of normally distributed continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t -test was used for further comparison between two groups. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups and further comparison between two groups. Results In experiment 1, compared with the model group, the high- and low-dose Xuefu Zhuyu decoction groups and the obeticholic acid control group had significant reductions in body weight, insulin resistance index, the distribution of vacuolar lipid droplets in liver tissue, intralobular inflammation, the ballooning degeneration of hepatocytes, NAS score, the level of TG in liver tissue, and the serum level of ALT (all P < 0.05). Compared with obeticholic acid, high- and low-dose Xuefu Zhuyu decoction had a significantly better effect in reducing body weight, insulin resistance index, and total NAS score (all P < 0.05), and low-dose Xuefu Zhuyu decoction had a significantly better effect in improving serum ALT ( P < 0.05). In experiment 2, compared with the model group, the Xuefu Zhuyu decoction extract 1, 2, and 3 groups had significant reductions in fasting blood glucose, insulin resistance index, the distribution of lipid droplets in liver tissue, intralobular inflammation lesions, the ballooning degeneration of hepatocytes, total NAS score, and the level of TG in the liver (all P < 0.05). Compared with the model group, the extract 1 group had a significant reduction in body weight ( P < 0.05); the extract 2 and 3 groups had a significant reduction in the serum level of ALT ( P < 0.05); the extract 2 group had a significant reduction in the level of GGT in liver tissue ( P < 0.05). The extract 2 of Xuefu Zhuyu decoction had the closest effect to compound Xuefu Zhuyu decoction. Conclusion Xuefu Zhuyu decoction and its extracts can help to achieve varying degrees of improvement in NAFLD induced by high-fat diet in mice, and the extract 2 of Xuefu Zhuyu decoction might be the main material basis for Xuefu Zhuyu decoction.

Objective:To evaluate the use of serosa muscular layers circumferential incision combined with mucosal layer cutting and closure by laparoscopic or robotic surgery for gastrointestinal mesenchymal tumors at difficult sites of the stomach.Methods:From Jul 2019 to Apr 2021, 18 gastric mesenchymal tumor patients undergoing serosa muscular layers circumferential incision combined with mucosal layer cutting and closure by laparoscopic or robotic surgery at the Department of Surgery, the Fourth Hospital of Hebei Medical University were retrospectively analyzed.Results:All 18 patients had successful surgery, including 7 cases of robotic surgery, 11 cases of laparoscopic surgery, and there was no conversion to open surgery. Tumors were at the gastric in cardia, 8 cases at the gastric body and lesser curvature in 4 cases, and at the gastric antrum in 6 cases, respectively. Eleven cases were of endogenous and 7 cases were of dumbbell type. The average operation time was (99±29) min, the intraoperative blood loss was (10±5) ml, the first time taking food per mouth was (2.0±1.0) d, and the postoperative hospital stay was (4.9 ± 1.2) d. Pathology showed gastrointestinal stromal tumor in 11 cases, leiomyoma in 5 cases and schwannoma in 2 cases. All were with negative margins. The average tumor diameter was (4.7±1.4) cm. The median follow-up time was 16.5 months, and there was no sign of tumor recurrence or metastasis.Conclusion:The serosa muscular layers circumferential incision combined with mucosal layer cutting and closure technique in laparoscopic or robotic surgery is a safe and feasible procedure for treating gastrointestinal mesenchymal tumor at difficult sites of the stomach.