ObjectiveTo explore the possible mechanism of Pingwei Capsules （平胃胶囊） for chronic atrophic gastritis from rapidly accelerated fibrosarcoma / mitogen-activated protein kinase /extracellular-signal-regulated kinase （Raf/MEK/ERK） pathway that influences the activation of fibrosarcoma protein/mitogen. MethodsFifteen SD rats were randomly divided into 5 rats in the blank group and 10 rats in Pingwei Capsules group. The rats in the blank group were given 1 ml/100 g of saline by gavage， and the rats in Pingwei Capsules group were given 0.63 g/（kg·d） of Pingwei Capsule suspension by gavage， and serum was collected for 3 consecutive days. N-methyl-N'-nitro-N-nitrosoguanidine （MNNG） was used to induce human gastric mucosal epithelial cells GES-1 to establish a precancerous lesion cell model. The successful cells were divided into control group （10% fetal bovine serum）， blank serum group （10% fetal bovine serum plus 10% blank serum）， and medication-containing serum group （serum with medication of Pingwei Capsule）， and the volume fraction and time of intervention of Pingwei Capsule-containing serum were screened by CCK-8 assay. Human gastric mucosal epithelial cells GES-1 were divided into normal group， model group， blank serum group， medication-containing serum group， U0126 group， and combined group， with 6 replicate wells in each group. After successful modelling of the cells in all groups except the blank group， an equal volume of fetal bovine serum was added to the normal and model groups， an equal volume of blank serum was added to the blank serum group， a screening volume fraction of Pingwei Capsule-containing serum was added to Pingwei Capsule group， a 10 μmol/L mitogen-activated extracellular signal regulated kinase 1 （MEK1） inhibitor U0126 was administered in the U0126 group， an equal dose of Pingwei Capsule-containing serum plus 10 μmol/L of U0126 was administered to the combined group. After the selected incubation time， the level of interleukin 6 （IL-6） was detected in the cells by ELISA， the expression of IL-6 and MEK1 was detected by immunofluorescence， and the expression of IL-6， Raf， MEK1， and ERK mRNA was detected by RT-qPCR， and the expression of IL-6， Raf， MEK1， and ERK mRNA in the cells was detected by Western blot. ResultsThe 5.35% volume fraction， 48 h intervention of Pingwei Capsule-containing serum was selected for subsequent experiments. Compared with the normal group， the IL-6 content in cell supernatants and the expression of IL-6， Raf， MEK1， ERK mRNA and ERK1/2 proteins in cells increased in the model group and blank serum group （P＜0.01）. Compared with the model group， all of the above indexes were improved in medication-containing serum group， U0126 group， and combined group （P＜0.05 or P＜0.01）. Compared with medication-containing serum group， the expression of IL-6， MEK1 expression， the expression of IL-6， Raf， MEK1 and ERK mRNA， and the expression of IL-6， Raf， MEK1 and ERK1/2 proteins reduced in the cells of combined group （P＜0.05 or P＜0.01）. Compared with the U0126 group， IL-6 expression reduced and IL-6， MEK1 and ERK1/2 protein expression reduced in cells of combined group （P＜0.05 or P＜0.01）. ConclusionThe Pingwei Capsule-containing serum may play a role in the treatment of chronic atrophic gastritis by improving the inflammation-cancer transformation of GES-1 cells through inhibiting the Raf/MEK/ERK pathway.

AIM:To observe the effect of Pingwei capsule on the precancerous lesions of gastric cancer(PLGC)cell model induced by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG),and to preliminarily explore its mecha-nism.METHODS:Blank serum and Pingwei capsule-containing serum were prepared for later use.A PLGC cell model was established by MNNG-induced human gastric mucosal epithelial cell line GES-1.To evaluate the model,cell morpho-logical changes were observed under inverted microscope,and the expression of proliferating cell-related antigen Ki67 was detected by immunofluorescence staining.CCK-8 assay was used to screen the optimal intervention concentration and time of serum containing drugs.Reactive oxygen species(ROS)content in cells was detected using a fluorescent probe DCFH-DA.Malondialdehyde(MDA)content was detected by ELISA,and the activity of superoxide dismutase(SOD)and gluta-thione peroxidase(GSH-Px)was detected using biochemical reagents.A novel fluorescent probe JC-10 was used to detect mitochondrial membrane potential.The mRNA expression levels of Ki67 and melanoma differentiation-associated gene-7(MDA-7)were detected by real-time fluorescence quantitative PCR.The protein expression levels of Ki67,interleukin-6(IL-6)and MDA-7 were detected by Western blot.RESULTS:Compared with normal group,the ROS and MDA levels in model group and blank serum group were significantly increased(P<0.01),while the activity of SOD and GSH-Px was significantly decreased(P<0.01).The mitochondrial membrane potential was significantly decreased(P<0.01).The protein expression levels of Ki67 and IL-6 were significantly increased(P<0.01),while the protein expression level of MDA-7 was significantly decreased(P<0.01).There were no significant differences of the above indicators between model group and blank serum group(P>0.05).Compared with blank serum group,the Pingwei capsule-containing serum group showed significantly decreased ROS and MDA levels(P<0.01),significantly increased activity of SOD and GSH-Px(P<0.05),significantly increased mitochondrial membrane potential(P<0.01),significantly decreased protein expres-sion levels of Ki67 and IL-6(P<0.01),and significantly increased protein and mRNA expression levels of MDA-7(P<0.01).CONCLUSION:Pingwei capsule can significantly alleviate MNNG-induced oxidative damage and inflammatory response,and regulate the expression of oncogenes and tumor suppressor genes,thereby playing a role in prevention and treatment of PLGC.

Objective:To explore the application value and operation skills of ultrasound-guided percutaneous thermal ablation assisted by artificial ascites or/and soft tissue edema in the treatment of special hepatic tumors located nearby the diaphragm, heart, stomach, gastrointestinal tract, gall bladder, kidney, and other organs.Methods:The clinical data of 132 patients with special-region hepatic tumors treated with ultrasound-guided percutaneous thermal ablation aided by artificial ascites and/or artificial soft tissue edema were retrospectively analyzed. Intraoperative contrast-enhanced ultrasound was used to guide ablation when necessary. During the operation, the ablation needle was lifted or pressed down, or the direction of the needle handle was changed to protect vital organs. The technical success rate of artificial ascites and/or soft tissue edema formation, the complete in activation rate of the tumor, and the complications were observed.Results:There were 74 patients (108 lesions) treated with radiofrequency ablation and 58 patients (82 lesions) treated with microwave ablation. Among them, 81 cases was successfully injected artificial abdominal ascites, with a water volume of (1 301±685) ml; artificial soft tissue edema was successfully formed for 19 patients, with a water volume of (534±258) ml. Both artificial ascites and artificial soft tissue edema were built for 30 patients. The success rate of this hydro-isolation technique was 98.5% (130/132). 129 patients successfully completed the treatment, and the complete inactivation rate of the tumor was 92.5% (172/186). The average postoperative hospital stay was three days. No patient had serious complications, such as surface tumor rupture, gastrointestinal injury, or diaphragm perforation.Conclusions:For hepatic tumors located adjacent to other organs such as the diaphragm, heart, gastrointestinal tract, gallbladder, and kidney, the application of artificial ascites and/or artificial soft tissue edema can reduce the damage to these organs, as well as reduce the possibility of tumor rupture and diaphragm perforation. These methods are safe and effective in ultrasound-guided percutaneous thermal ablation.

Objective:To explore the application value and operation skills of ultrasound-guided percutaneous thermal ablation assisted by artificial ascites or/and soft tissue edema in the treatment of special hepatic tumors located nearby the diaphragm, heart, stomach, gastrointestinal tract, gall bladder, kidney, and other organs.Methods:The clinical data of 132 patients with special-region hepatic tumors treated with ultrasound-guided percutaneous thermal ablation aided by artificial ascites and/or artificial soft tissue edema were retrospectively analyzed. Intraoperative contrast-enhanced ultrasound was used to guide ablation when necessary. During the operation, the ablation needle was lifted or pressed down, or the direction of the needle handle was changed to protect vital organs. The technical success rate of artificial ascites and/or soft tissue edema formation, the complete in activation rate of the tumor, and the complications were observed.Results:There were 74 patients (108 lesions) treated with radiofrequency ablation and 58 patients (82 lesions) treated with microwave ablation. Among them, 81 cases was successfully injected artificial abdominal ascites, with a water volume of (1 301±685) ml; artificial soft tissue edema was successfully formed for 19 patients, with a water volume of (534±258) ml. Both artificial ascites and artificial soft tissue edema were built for 30 patients. The success rate of this hydro-isolation technique was 98.5% (130/132). 129 patients successfully completed the treatment, and the complete inactivation rate of the tumor was 92.5% (172/186). The average postoperative hospital stay was three days. No patient had serious complications, such as surface tumor rupture, gastrointestinal injury, or diaphragm perforation.Conclusions:For hepatic tumors located adjacent to other organs such as the diaphragm, heart, gastrointestinal tract, gallbladder, and kidney, the application of artificial ascites and/or artificial soft tissue edema can reduce the damage to these organs, as well as reduce the possibility of tumor rupture and diaphragm perforation. These methods are safe and effective in ultrasound-guided percutaneous thermal ablation.

Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia and dyslipidemia. Carvacrol (CAR) has demonstrated the potential to mitigate dyslipidemia. This study aims to investigate whether CAR can modulate blood glucose and lipid levels in a T2DM rat model by regulating short-chain fatty acids (SCFAs) and the GPR41/43 pathway. The T2DM rat model was induced by a high-fat diet combined with low-dose streptozocin injection and treated with oral CAR and/or mixed antibiotics. Fasting blood glucose, oral glucose tolerance, and insulin tolerance tests were assessed. Serum lipid parameters, hepatic and renal function indicators, tissue morphology, and SCFAs were measured. In vitro, high glucose (HG)-induced IEC-6 cells were treated with CAR, and optimal CAR concentration was determined. HG-induced IEC-6 cells were treated with SCFAs or/and GPR41/43 agonists. CAR significantly reduced blood lipid and glucose levels, improved tissue damage, and increased SCFA levels in feces and GPR41/43 expression in colonic tissues of T2DM rats. CAR also attenuated HG-induced apoptosis of IEC-6 cells and enhanced GPR41/43 expression.Overall, these findings suggest that CAR alleviates blood lipid and glucose abnormalities in T2DM rats by modulating SCFAs and the GPR41/43 pathway.

OBJECTIVES: The mechanism for traditional Chinese medicine in treating of recurrent spontaneous abortion is not clear. This study aims to explore the mechanism of baotaiyin in the treatment of recurrent abortion by regulating the immune inflammatory axis of interleukin (IL)-23/helper T cell (Th)17. METHODS: Spontaneous abortion model mice were randomly divided into a model group, 3 dose (low, medium, and high) groups of baotaiyin, with 10 mice in each group. After 14 days of medication, the levels of IL-17, IL-23, IL-10, and TGF-β in serum were detected with enzyme-linked immunosorbent assay. The proportion of Th17 and regulatory T cells (Treg) cells in spleen lymphocytes was tested with flow cytometry. The expressions of (retinoid-related orphan receptor γt, ROR-γt) and forkhead box P3 (FOXP3) mRNA in decidua tissues was detected with RT-PCR. Embryo absorption rate was counted. RESULTS: Compared with the model group, the absorption rate of embryo and Th17/Treg cell ratio in baotaiyin medium- and high-dose groups were decreased significantly (all P<0.05); the levels of IL-17 and IL-23 in serum were decreased (both P<0.05), while the levels of TGF-β and IL-10 in baotaiyin medium- and high-dose groups were increased (P<0.05, P<0.01, respectively); the expression of ROR-γt mRNA was decreased and the expression of FOXP3 mRNA was increased (all P<0.01) in decidua tissues of baotaiyin medium- and high-dose groups. CONCLUSIONS Baotaiyin inhibits the positive feedback cycle of IL-23/Th17 immune inflammatory axis, which regulates Th17/Treg cell balance, mediates the maternal and fetal immune tolerance, and prevents the recurrent abortion.
Mice ; Animals ; Female ; Humans ; Pregnancy ; Interleukin-23 ; Interleukin-17/genetics* ; Interleukin-10 ; Abortion, Habitual ; Transforming Growth Factor beta/genetics*

Objective:To investigate the in vitro inhibitory activity of a novel class Ⅰ and Ⅱb selective histone deacetylase (HDAC) inhibitor, purinostat mesylate (PM) , in diffuse large B-cell lymphoma and its mechanism.Methods:The 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyl tetrazolium bromide method was used to detect the effect of PM on cell proliferation. The effects of PM on cell cycle and apoptosis were detected by flow cytometry. The acetylation levels of HDAC substrate, cell cycle protein, apoptosis-related protein, and oncogene protein expression were detected by Western blot.Results:PM significantly inhibited the proliferation of lymphoma SUDHL-4 and SUDHL-6 cells and increased the acetylation levels of HDAC substrates H3, H4, and α-tubulin. In cell cycle experiments, PM induced G 0/G 1 phase arrest in SUDHL-4 and SUDHL-6 cells. Western blot experiment showed that PM could significantly downregulate the expression of cyclin-dependent kinases Cdk2, Cdk4, Cdk6, cyclin D1, and cyclin E and upregulate the expression of CDK inhibitor protein p21. In the apoptosis experiment, PM could induce the apoptosis of SUDHL-4 and SUDHL-6 cells. Western blot experiment demonstrated that PM promoted endogenous apoptosis by activating caspase-3 kinase and affecting antiapoptotic protein Bcl-2. In addition, PM could downregulate the expression of oncogene marker proteins MYC, IKZF1, and IKZF3. Conclusion:PM has an efficient biological activity in vitro for diffuse large B-cell lymphoma, including double-hit lymphoma, and provides valuable experimental evidence for PM in clinical treatment.

COVID-19/virology* ; China/epidemiology* ; Disease Outbreaks ; Genetic Linkage ; Humans ; Phylogeny ; Polymorphism, Single Nucleotide ; SARS-CoV-2/isolation & purification*

Objective:To explore the effective mode of ultrasound-guided radiofrequency ablation for the treatment of hepatocellular carcinoma (HCC).Methods:The morphological changes of human liver cancer cells HepG2 and human permanent liver cells LO2 after high temperature treatment were observed. The cell counting kit 8 (CCK-8) array was used to detect cell proliferation ability. The HepG2 cells (ΔHepG2 cells) and LO2 cells (ΔLO2 cells) those were still alive after treatment with 47℃ were collected and subjected to secondary high temperature treatment, and their proliferation ability was tested by the CCK-8 array. The ablation was performed at different locations of the ex-vivo porcine liver. The consistency of the vaporization area of the ultrasound image with that of the actual ablation was compared, the temperature of each area in the ultrasonic image was observed.Results:After incubated water was heated to 50℃, with the extension of the culture time, the number of adherent cells of HepG2 and LO2 cells became less and less, and gradually lost their normal cell morphology. After 50℃ and above, all of the proliferation rates of HepG2 cells, LO2 cells, ΔHepG2 cells and ΔLO2 cells were decreased. Compared with the 37℃ group, the differences were statistically significant ( P<0.05), and the cells were irreversible damaged. There was no significant difference between the transverse diameters of the sonographic vaporization zones and the actual ablation zones ( P>0.05). Nine minutes was considered to be an effective ablation time point since the temperatures in the hyperechoic areas were all above 53℃. Conclusion:The HCC cells within the vaporization zone observed by ultrasound can be damaged irreversibly when they were effectively ablated for over 9 minutes at 105℃ and 200 W.

Objective:To explore the applied value of super-selective cervical lymph node dissection in papillary thyroid carcinoma (PTC) patients with clinically suspicious lateral lymph node metastasis (LNM).Methods:We retrospectively analyzed the clinical data of 232 cN1b PTC patients who underwent surgery from September 2013 to May 2018 in the Department of Head and Neck Surgical Oncology, National Cancer Center. Among them, 90 cases received super-selective neck dissection (level Ⅲ and IV) and 142 cases underwent selective neck dissection (level Ⅱ-Ⅳ). The LNM of two groups were analyzed.Results:Postoperative pathological results showed that 173 cases had LNM in the central compartment. The LNM cases of level Ⅱ-Ⅳ were 47, 147 and 130, respectively. Eight patients of super-selective neck dissection and 6 of selective neck dissection had postoperative lymphatic fistulas ( P=0.146). No patients in super-selective neck dissection group while 9 patients in the selective lymph node dissection group had postoperatively permanent impairment of shoulder mobility, the difference was statistically significant ( P=0.015). In the super-selective neck dissection group, 2 patients had long-term postoperative incision discomfort, and 5 cases had obvious cicatrix after surgery. In the patients with selective neck dissection, 27 cases experienced long-term incision discomfort after surgery, and 26 patients had apparent scar tissue, the differences were statistically significant ( P<0.005). There was no recurrence during the follow-up. Conclusions:Super-selective neck dissection is a feasible, safe and effective treatment for cN1b PTC patients. It can improve the quality of postoperative life and avoid the over treatment for patients.