Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17's inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na⁺/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.

Objective: To investigate the role of body fat ratio in the evaluation of obstructive sleep apnea(OSA). Methods: A retrospective analysis was made on 174 cases (between November, 2017 and April, 2018 showed that) of sleep monitoring in the Department of Otorhinolaryngology in Peking University Third Hospital. The data included the gender, age, body fat rate, body mass index (BMI), neck circumference, and apnea-hypopnea index (AHI). The above data were analyzed by non parametric correlation analysis, receiver operating characterristic (ROC) curve analysis and multiple factor Logistic regression analysis to study the relationship between the gender,age,body fat rate,BMI,neck circumference and other indexes of the patients with AHI. Results: Nonparametric correlation analysis showed that the correlation from strong to weak to AHI among women was BMI (r=0.621, P<0.001),body fat rate (r=0.602, P<0.001), age (r=0.570, P<0.001), neck circumference (r=0.402, P=0.014), respectively. BMI (r=0.599, P<0.001), neck circumference (r=0.493, P<0.001), body fat rate (r=0.318, P<0.001), and age (r=0.256, P=0.003) among men. ROC curve analysis showed that the strong to weak index (area under curve,AUC) of the AHI>15/h among women was the body fat rate (AUC=0.884, P=0.001), BMI(AUC=0.810, P=0.008), neck circumference (AUC=0.759, P=0.027), age (AUC=0.750, P=0.033), and the male was BMI (AUC=0.765,P<0.001), neck circumference (AUC=0.720, P<0.001), age (AUC=0.634, P=0.008), and body fat rate (AUC=0.632, P=0.010), respectively. Multifactor Logistic regression analysis showed that the body fat rate (OR=1.704,95%CI=1.012-2.870) in women was an independent risk factor for AHI greater than 15/h; the age of male (OR=1. 044, 95%CI=1.005-1.085) and BMI (OR=1.285, 95%CI=1.056-1.562) were independent risk factors for AHI greater than 15/h. Conclusion Body fat rate can be used as a new indicator for predicting the severity of OSA,especially in adult female population. In adult female moderate to severe OSA patients (AHI>15/h), compared with BMI,neck circumference and age,the body fat rate has the greatest correlation with AHI. Compared with BMI,neck circumference and age,the body fat rate has a decisive role in predicting moderate to severe OSA (AHI>15/h).

Objective: To explore the effect of salinomycin on the metastasis and invasion of bladder cancer cell line T24 by regulating the related protein expression in the process of epithelial-mesenchymal transition (EMT), and to provide experimental basis for the treatment of urological tumors. Methods: The bladder cancer cell line T24 was cultured in vitro. The rat bladder tumor model was established in vivo. The rats were randomized into two groups, among which the rats in the experiment group were given intraperitoneal injection of salinomycin, while the rats in the control group were given intraperitoneal injection of normal saline. The change of tumor cells in the two groups was observed. Transwell was used to detect the cell migration and invasion abilities, Real-time PCR was used to detect the expression of mRNA, while Western-blot was utilized for the determination of the expressions of E-cadherin and vimentin proteins. Results: The metastasis and invasion abilities of serum bladder cancer cell line T24 after salinomycin treatment in the experiment group were significantly reduced when compared with those in the control group, and the tumor metastasis lesions were decreased from an average of 1.59 to 0.6 (P < 0.05). T24 cell proliferation in the experiment group was gradually decreasing. T24 cell proliferation at 48 h was significantly lower than that at 12 h and 24 h (P < 0.05). T24 cell proliferation at 24 h was significantly lower than that at 12 h (P < 0.05). T24 cell proliferation at each timing point in the experiment group was significantly lower than that in the control group (P < 0.05). The serum mRNA level and E-cadherin expression in the tumor tissues in the experiment group were significantly higher than those in the control group, while vimentin expression level was significantly lower than that in the control group (P < 0.05). Conclusions: Salinomycin can suppress the metastasis and invasion of bladder cancer cells, of which the mechanism is probably associated with the inhibition of EMT of tumor cells.

BACKGROUND:Chinese herb, bushen yizhi formula protects at certain extent learning and memory in rat model of Alzheimer disease. The drug serum in this formula can alleviate neurotoxic reaction of nerve tumor cell NG 108-15 to beta-amyloid protein. In order to understand further the mechanism and compatibility of the formula, it is necessary to carry on the study on the broken formulas.OBJECTIVE:To study the effect of drug serum in subgroups of broken bushen yizhi formulas on growth and differentiation of cell model of Alzheimer disease and probe into the compatibility rule of bushen yizhi formula in view of serum pharmacology.DESIGN: Randomized controlled experiment.SETTING: DME Center of Clinical Pharmacological Institute Affiliated to Guangzhou University of Traditional Chinese Medicine.PARTICIPANTS:The experiment was performed in DME Center of Clinical Pharmacological Institute Affiliated to Guangzhou University of Traditional Chinese Medicine from January to August 2003, in which, 40 healthy male SD rats of 3 months old were employed and NG108-15 cell line was frozen-preserved.into the control, original formula group (No. 1 group) [shechuanzi (Cnidium monnieri (L.) Cuss), gouqizi (Lycium barbarum L.), renshen (Panax ginseng C.A.Mey.), heshouwu (Polygonum multiflorum Thunb.), danpi (Paeonia Suffruticisa Andr.) and bingpian (Borneolum)], kidney replenishment group (No.2 group) [shechuanzi (Cnidium monnieri (L.) Cuss), gouqizi (Lycium barbarum L.), etc.], group for benefiting qi and nourishing blood (No.3 group)[renshen (Panaz ginseng C.A.Mey), zhishouwu (Polygonum multiflorum Thunb.), etc.] and group with bingpian (Borneolum) removed (No.4 group)[Panax ginseng C.A.Mey.], heshouwu (Polygonum multiflorum Thunb.) and danpi (Paeonia Suffruticisa Andr.)], 8 rats in each group. The concentrated Chinese herbal solutions of every group were applied at 10 μL/g (equal to 6 g/kg of raw herbs) for gastric infusion successively,continuously for 1 month. In the control, the physical saline solution of equal dosage was used for infusion. Two hours after the last gastric infusion in rats of each group,the blood was collected from heart after anesthesia and the serum was sepaNG108-15 cell cultured in vitro was divided into 6 groups. In the control and model group, normal rat serum was contained in proliferated culture solution. In the rest 4 groups, the drug serum of No. 1 group and 3 sub-groups was contained.Simultaneously, beta-amyloid protein 25-35 in each hole was prepared to the terminal concentration 5 μmol/L (except in the control) and the culture went on for 48 hours.MAIN OUTCOME MEASURES:MTT method was used to determine proliferated number and survival rate of cells. Simultaneously, the ratio of neurite cells to total cell count and average length of neurit were determined.icantly than the control (0.520±0.022, 0.665±0.037, P ＜ 0.01), and that in every drug serum group was higher than model group, of which, the result vival rate of differentiated cells: That in model group was lower significantly than the control (58.4%, 100%) and that in every drug serum group was higher than model group, of which, the result in No.4 group was the most tal cell count: That in model group was lower significantly than the control [(42.95±11.42)%, (58.75±12.84)%, P ＜ 0.01] and that in every drug serum group was higher than model group, of which, the result in No.4 group was rite: That in model group was shorter significantly than the control [(356.0 ±109.0), (493.8±133.0) μm, P ＜ 0.01] and that in every drug serum group was longer than model group, of which, the result in No.4 group was the most significant [(486.8±79.2) μm, P ＜ 0.01].CONCLUSION: The drug serum in all of bushen yizhi formula and every subgroup inhibits at certain extent the injury of beta-amyloid protein 25-35 to NG108-15 cell, but the results of each group are various. The protection of drug serum to the cell in every group is in the sequence from strong to weak as group with bingpian removed ＞ original formula group ＞ kidney replenishment group ＞ group for benefiting qi and nourishing blood. It is to expect a further study on the efficacy of group with bingpian removed.

Objective To observe the effects of Bushen Yizhi Decociton (BYD) on somatostatin-like (SS-like)neurons in hippocampal gyrus of rat models with Alzheimer's disease(AD). Methods Fifteen-month_old AD rat models were established by intraperitoneral injection of D-galactose for 4 weeks combined with ibotenic acid injection into bilateral nucleus basalis of Meynert. AD model rats were randomly allocated to AD model group(Group C), Hup-A treatment group(Group D) and BYD treatment groups (Group E and Group F,treated with high dosage and low dosage respectively), and 10 normal aged rats (Group B)and 10 normal youth rats (Group A)served as the normal control groups. The methods of immunohistochemistry and dig_labeling c-DNA probe in situ hibridization were used to detect the number of SS-like immunoreactive positive and SS mRNA expressed positive neurons in hippocampal CA1 and CA3 fields and the dentate gyrus. Results The number and optic density of SS-like immunoreactive positive and SS mRNA expressed positive neurons were higher in BYD treatment groups than those in Group C (P

Objective　To develop a new method to induce the gene transfection in high efficiency for eukaryotic cells in vitro. Methods　 Four kinds of p14ARF gene primarily deleted human carcinoma cell line including H460,A549,U251,and PC-3 were transfected with the human p14ARF expression vector (pCI-neo-p14ARF) by using the new nonliposomal transfection reagent Fugene 6. The efficiency of gene transfer was determined by screening the cells in G418. Results　 After 21 days' selection, G418-resistant clones were shown in all the transfected plate. PCR product of p14ARF gene was positive in all the G418-resistant clones. Cytotoxicity of Fugene 6 was detected. The cell proliferation activity was not affected when it was cultured in a high dose of Fugene 6. Conclusion　 These results demonstrate that Fugene 6 is a rapid, feasible, reproducible, and noncytotoxic gene transfection approach for eukaryotic expression vector in vitro.

Objective　To examine whether wild-type p14ARF gene is a candidate suppressor gene for lung cancer. Methods　Human lung cancer cell lines having various endogenous backgrounds in INK4a, p53 and Rb genes were used as the recipients of the wild-type p14ARF gene. The expression of p14ARF mRNA and protein was detected with RT-PCR, immunohistochemistry and Western blot after G418 selection. Clones which expressed both p14ARF mRNA and protein were identified and selected for further experiements. By comparing with the parental and negative control cells treated with empty vectors, the effects of exogenously transfected p14ARF on cell division rate, cell cycle distribution and morphologic alteration were analyzed. In vivo evaluation of the growth rate was also made with the experiment of nude mice tumor formation. Results　Upon transfection with p14ARF gene, cells were arrested at G1 or G1／G2 phase of cell cycle in three wtp53 lung cancer cell lines and their proliferation rates were also inhibited. Conclusion　Human wild-type p14ARF gene has suppressive effect on abnormal proliferation of lung cancer cells, especially in some wtp53 lung cancer cells, and it might be an ideal candidate for gene therapy of human lung cancer.

Objective To observe the effect of Bushen Yizhi Prescription(BYP) on long-term potentiation (LTP) in hippocampus of ovariectomized (OVX) rats. Methods Three-month-old female SD rats were randomized into mimic operation group, model group, low dosage BYP group, high dosage BYP group and estrogen control group. Ovariectomy was operated in the three latter groups. After operation, BYP group was treated with gastric infusion of BYP and estrogen group with subcutaneous injection of estrogen. The changes of LTP of dentate gyms in hippocampus of OVX rats were observed by electrophysiological method and the effect of BYP on LTP was also evaluated. Result & Conclusion The increased amplitude of population spike of LTP was significantly low and maintained a short time in model group as compared with that in mimic operation group. There were insignificant difference between the high-dosage BYP group and estrogen control group. It is indicated that synaptic transmission in hippocampus can be protected and sustained by BYP and the estrogen replacement.