This study aims to investigate the pathogenesis of precancerous lesions of gastric cancer(PLGC) and explore the potential molecular mechanism of Weifuchun Capsules(WFC) in treating PLGC via the nuclear factor-κB(NF-κB)/NOD-like receptor protein 3(NLRP3) inflammasome signaling pathway. Ninety male SPF-grade Wistar rats were randomized into a normal feeding group and a modeling group. The normal feeding group received a regular diet, while the modeling group was subjected to the disease-syndrome combined modeling of PLGC. Specifically, the rats had free access to the water containing 120 μg·mL~(-1) N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) and received a diet containing 0.05% ranitidine in an irregular feeding pattern(alternations between fasting and overfeeding). After 15 weeks, the rats in the normal feeding group were randomized into control, control-NF-κB activator betulinic acid(C-BA), and control-NF-κB inhibitor pyrrolidine dithiocarbamaten(C-PDTC) groups. Meanwhile, the rats in the modeling group continuously underwent the modeling procedure and were randomized into model, WFC, model-NF-κB activator(M-BA), and model-NF-κB inhibitor(M-PDTC) groups. The model group and control group were given aseptic water by intragastric administration, once a day. WFC was given at a dose(432 mg·kg~(-1)) 6 times the equivalent dose for adults(body weight: 60 kg) by gavage, once a day. The rats in the C-BA and M-BA groups were administrated with BA by intraperitoneal injection at a dose of 10 mg·kg~(-1), twice a week. The rats in the C-PDTC and M-PDTC groups were administrated with PDTC by intraperitoneal injection at a dose of 50 mg·kg~(-1), twice a week. The interventions were carried out for 4 weeks. Histopathological changes of the gastric mucosa were observed and scored by hematoxylin-eosin(HE) and alcian blue-periodic acid Sthiff(AB-PAS) staining. The levels of inflammatory cytokines including interleukin(IL)-1β, IL-6, IL-18, tumor necrosis factor-alpha(TNF-α), and IL-10 in the gastric tissue were determined by enzyme-linked immunosorbent assay(ELISA). The expression levels of proteins associated with the NF-κB/NLRP3 inflammasome in the gastric mucosa were determined by Western blot. The positive expression areas of proteins related to NF-κB/NLRP3 inflammasome in the gastric mucosa were measured by immunohistochemistry. The results showed that compared with the control group, the model, C-BA, and M-BA groups showed significantly risen scores of mucosal inflammation, degree of inflammatory activity, gland atrophy, and intestinal metaplasia, and the model and M-BA groups showed significanly risen scores of dysplasia. Compared with the model group, the WFC group demonstrated significantly declined scores of mucosal inflammation and degree of inflammatory activity, as well as declined scores of intestinal metaplasia and dysplasia. Compared with the control group, the model and C-BA groups showed significantly elevated levels of IL-1β, IL-6, IL-18, and TNF-α in the gastric tissue, and the model group showed significantly elevated level of IL-10. In addition, the model and C-BA groups showed significantly up-regulated expression of NF-κB p65, NLRP3, cysteine-aspartic acid protease 1(caspase-1), and apoptosis-associated speck-like protein containing a CARD(ASC) in the gastric mucosa and increased positive expression areas of NF-κB p65, NLRP3, and ASC. Compared with the model group, the WFC group showed significantly decreased levels of IL-1β, IL-6, IL-18, TNF-α, and IL-10 in the gastric tissue, and the M-PDTC group showed significantly lowered levels of IL-1β, IL-18, and TNF-α in the gastric mucosa. Both WFC and M-PDTC groups demonstrated significantly down-regulated expression levels of NF-κB p65, phosphorylated NF-κB p65(p-NF-κB p65), NLRP3, and caspase-1 in the gastric mucosa, along with significant decreases in the positive expression areas of NF-κB p65, NLRP3, and ASC. In conclusion, the pathogenesis of PLGC is closely related to the activation of the NF-κB/NLRP3 inflammasome signaling pathway. WFC can alleviate mucosal inflammation, inhibit glandular atrophy, partially reverse intestinal metaplasia, and reduce dysplasia to delay the process of inflammation-cancer transformation, and meanwhile it can effectively lower the levels of inflammatory cytokines and down-regulate the expression of pathway-related proteins in the stomach. Therefore, WFC may treat PLGC by inhibiting the NF-κB/NLRP3 inflammasome signaling pathway.
Animals ; Male ; NF-kappa B/genetics* ; Rats ; Rats, Wistar ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Stomach Neoplasms/pathology* ; Inflammasomes/genetics* ; Humans ; Precancerous Conditions/metabolism* ; Capsules

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Objective To study the bioequivalence of test and reference olmesartan tablet in Chinese healthy subjects after single dose under fasting and fed conditions.Methods A single-center,random,open,single-dose,two-preparations,double-period,crossover study was adopted.A total of 48 healthy adult male and female subjects(24 cases of fasting test and 24 cases of fed test)were included in the random crossover administration.Single oral dose 20 mg of test and reference were taken under fasting and postprandial conditions,respectively.Plasma concentration of olmesartan in plasma were determined by liquid chromatography tandem mass spectrometry.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.0 software.Results The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the fasting group were as follows:Cmax were(653.06±133.53)and(617.37±151.16)ng·mL-1,AUC0-t were(4 201.18±1 035.21)and(4 087.38±889.99)ng·mL-1·h,AUC0-∞ were(4 254.30±1 058.90)and(4 135.69±905.29)ng·mL-1·h.The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the postprandial group were as follows:Cmax were(574.78±177.05)and(579.98±107.74)ng·mL-1,AUC0-t were(3 288.37±866.06)and(3 181.51±801.06)ng·mL-1·h,AUC0-∞ were(3 326.11±874.26)and(3 242.01±823.09)ng·mL-1·h.Under fasting and postprandial conditions,the 90％confidence intervals of the main pharmacokinetic parameters of the test and reference preparations are both 80.00％-125.00％.Conclusion Under fasting and postprandial conditions,a single oral dose of test and reference preparations olmesartan tablets in Chinese healthy adult volunteers showed bioequivalence.

SARS-CoV-2 Omicron variant (B.1.1.529) was first discovered in South Africa in November 2021 and has since become a mainstream strain worldwide. Omicron variant was defined as the fifth "variant of concern (VOC)" by World Health Organization on November 26, 2021. This paper illustrates the mutation trends of Omicron variants in terms of SARS-CoV-2 genome and protein structure as well as nucleic acid site mutations and amino acid site mutations, describes the features of Omicron mutation sites in terms of lineage comparison among the VOCs and Omicron sublineages, and further highlights the influences of Omicron site mutations from the aspects of immune escape, virulence and transmission ability. Moreover, this paper also reviews the development of direct antiviral agents, antibodies and vaccines, aiming to provide reference for further investigation.

Anti-seizure medications (ASMs) are the main therapy for epilepsy.There are many kinds of ASMs with complex mechanism of action, so it is difficult for pharmacists to examine prescriptions.This paper put forward some suggestions on the indications, dosage forms/routes of administration, appropriateness of usage and dosage, combined medication and drug interaction, long-term prescription review, individual differences in pathophysiology of children, and drug selection when complicated with common epilepsy, for the reference of doctors and pharmacists.

Objective To investigate the effects of GO-CoA-Tat,an inhibitor of ghrelin O-acyltransferase(GOAT),on lipid metabolism and oxidative stress in mice with non-alcoholic fatty liver disease(NAFLD)induced by high-fat diet(HFD).Methods Twenty-four C57BL/6 male mice were selected and divided into control group,HFD group and GO-CoA-Tat group,with 8 mice in each group.The mice in control group was given standard diet,the mice in HFD group and GO-CoA-Tat group were given HFD,and the mice in GO-CoA-Tat group was given daily intraperitoneal injection of GO-CoA-Tat from 3rd week of feeding.Food intake and body mass of mice were measured weekly.After 8 weeks,serum and liver samples were collected,liver weight was measured,and fat droplets were detected by hepatocyte oil red O staining;biochemical indexes such as serum triglyceride(TG),total cholesterol(TC),alanine aminotransferase(ALT),aspartate aminotransferase(AST)and oxidative stress indexes of liver such as glutathione(GSH),superoxide dismutase(SOD)and malondialdehyde(MDA)were measured.Results Hepatic steatosis was observed after feeding with HFD for 8 weeks,which was significantly relieved in GO-CoA-Tat group compared with HFD group.Compared with HFD group,the food intake,body weight and liver weight of mice in GO-CoA-Tat group decreased(P＜0.05).Compared with HFD group,the content of TG in liver of mice in GO-CoA-Tat group decreased,the concentrations of serum TG and TC decreased(P＜0.05),and the concentrations of liver GSH and SOD increased(P＜0.01),liver MDA decreased(P=0.005),and the serum ALT and AST decreased(P＜0.05).Conclusion GO-CoA-Tat can improve lipid metabolism and oxidative stress in the liver of NAFLD mice,thus play a protective role in the liver.

ObjectiveTo explore the regulatory effect of Quyu Huatan Tongmai prescription on intestinal mircoflora of hyperlipidemia golden hamster and scientific evidence for the compatibility. MethodSyrian golden hamsters were randomized into normal， model， prescription， stasis-dispelling （Quyu）， phlegm-dissolving （Huatan）， and detoxification （Jiedu） groups， with 8 in each group. Hyperlipidemia in golden hamsters was induced by high-fat diet （4 weeks）. Then hamsters in the Quyu group （1.11 g·kg^-1）， Huatan group （0.39 g·kg^-1）， Jiedu group （0.07 g·kg^-1）， and prescription group （1.42 g·kg^-1） were given （ig） corresponding drugs and those in the normal group and the model group received （ig） distilled water of equivalent volume， once a day for 6 weeks. Serum lipids were determined， and hematoxylin-eosin （HE） staining was used to observe the pathological morphology of the liver. Feces were collected for 16S rRNA gene high-throughput sequencing of intestinal flora. ResultCompared with normal group， the model group demonstrated increase in body weight （P<0.05， P<0.01） and blood lipids （P<0.01）， decrease in intestinal flora diversity （P<0.05， P<0.01）， and variation of the relative abundance of intestinal flora at phylum， family， and genus levels （P<0.05， P<0.01）. Compared with the model group， Quyu Huatan Tongmai prescription controlled the body weight change， reduced the serum triglyceride （TG）， total cholesterol （TC）， and low density lipoprotein cholesterol/high density lipoprotein cholesterol ratio （LDL-C/HDL-C） （P<0.05， P<0.01）， improved the structure of intestinal flora， decreased the ratio of Firmicutes to Bacteroides （P<0.01）， raised the abundance of Bacteroidaceae， Porphyromonadaceae， Rikenellaceae， and Pasteurella （P<0.05， P<0.01）， and lowered the relative abundance of Coriobacterium （P<0.05） in hyperlipidemia golden hamsters. All the split prescriptions improved blood lipids and intestinal flora of the hamsters and particularly， the lipids-lowering effect of the Jiedu group and the regulation of flora in the Huatan group were closer to those of the prescription group. ConclusionQuyu Huatan Tongmai prescription and the split prescriptions all alleviated the hyperlipidemia of golden hamsters to different degrees possibly by regulating intestinal flora structure and improving intestinal microecology. The effect of the prescription group was most significant， and coming in second was the Huatan group. This study also provides scientific evidence for the effect of Quyu Huatan Tongmai prescription.

Major challenges for cancer treatment are how to effectively eliminate primary tumor and sufficiently induce immunogenic cell death (ICD) to provoke a robust immune response for metastasis control. Here, a self-assembled cascade bioreactor was developed to improve cancer treatment with enhanced tumor penetration and synergistic therapy of starvation, chemodynamic (CDT) and photothermal therapy. Ultrasmall FeS-GOx nanodots were synthesized with glucose oxidase (GOx) as template and induced by paclitaxel (PTX) to form self-assembling FeS-GOx@PTX (FGP)

This study aims to investigate the effect of Huaier aqueous extract on the growth and metastasis of human non-small cell lung cancer NCI-H1299 cells and its underlying mechanisms. MTT assay was used to detect the effect of Huaier aqueous extract on the proliferation of NCI-H1299 cells. Flow cytometry was used to examine the effect of Huaier aqueous extract on the apoptosis, cell cycle, and ROS level of NCI-H1299 cells. Wound healing assay was used to evaluate the effect of Huaier aqueous extract on the migration ability of NCI-H1299 cells. Western blot was used to detect the levels of proteins involving apoptosis, epithelial-mesenchymal transition(EMT), and MAPK signaling pathway in NCI-H1299 cells exposed to Huaier aqueous extract. The results showed that Huaier aqueous extract inhibited the proliferation of NCI-H1299 cells, and induced cell-cycle arrest at the phase S. Huaier aqueous extract promoted the apoptosis of NCI-H1299 cells by down-regulating the expression of anti-apoptotic protein Bcl-2. Moreover, Huaier aqueous extract increased ROS level and induced ferroptosis in NCI-H1299 cells. EMT played a critical role in cancer metastasis. Huaier aqueous extract reduced the migration ability of NCI-H1299 cells by inhibiting EMT of NCI-H1299 cells. In addition, this study revealed that Huaier aqueous extract inhibited MAPK signaling pathway in human non-small cell lung cancer NCI-H1299 cells, which may be one of Huaier's mechanisms in inhibiting growth and metastasis of NCI-H1299 cells. This study provides a new theoretical basis for the clinical treatment of lung cancer with Huaier, and important reference significance for further studies on the anti-tumor mechanisms of Huaier.
Apoptosis ; Carcinoma, Non-Small-Cell Lung ; Cell Line, Tumor ; Cell Proliferation ; Complex Mixtures ; Humans ; Lung Neoplasms ; Trametes

OBJECTIVE: To study the effect of periodontal non-surgical treatment on serum interleukin-6 (IL-6) expression and carotid vascular wall in a rat model of chronic periodontitis (CP) with type 2 diabetes mellitus (T2DM). METHODS: Twenty-eight 6-week-old SD rats were randomly divided into group A (control group, 7 rats) and group B (T2DM+CP group, 21 rats). According to different intervention measures, group B was randomly subdivided into B1 (natural process), B2 (periodontal mechanical treatment), and B3 (periodontal mechanical treatment + 2% minocycline hydrochloride + systemic metronidazole plus amoxicillin). Serum IL-6 was measured by enzyme-linked immunosorbent assay, and carotid tissue was observed under light microscopy after hematoxylin-eosin (HE) staining. RESULTS: The carotid artery wall of group A was normal. In group B1, the endothelial cells disappeared, the elastic fibers of the middle membrane were disordered, the local necrosis of smooth muscle tissue was amorphous particles, a small amount of calcium salt was deposited, and the wall thickening was obvious. The endothelial cells in groups B2 and B3 disappeared, and the smooth muscle cells in the middle membrane underwent denaturation. No significant thickening of the vessel wall was noted. The serum IL-6 level in group B1 continually increased with time, and it was higher than that in group A (P<0.001). The IL-6 levels of groups B2 and B3 peaked a week after the first intervention. Subsequently, IL-6 levels gradually decreased. At the last point (five weeks after the second intervention ), the IL-6 levels of groups B2 and B3 were significantly lower than that of group B1 (P<0.001). CONCLUSIONS For rats with periodontitis and diabetes, periodontal mechanical treatment may elevate serum IL-6 levels in the short term but might reduce the whole inflammatory state in the long term. Thus, this treatment might be valuable to the improvement of vascular disease. The adjunctive benefits of systemic metronidazole and amoxicillin in non-surgical periodontal therapy are decreased serum IL-6 expression and normal carotid artery.
Animals ; Carotid Arteries ; Chronic Periodontitis ; Diabetes Mellitus, Type 2 ; Endothelial Cells ; Interleukin-6 ; Rats ; Rats, Sprague-Dawley