Background and purpose:Studies have proved that the serine/threonine kinases 31 (STK31) gene plays important roles in human cancers. TheSTK31 gene expression was demonstrated to be regulated by the methylation status of its promoter/exon1 region. Viral infection was revealed to be associated with the hypermethylation of some tumor suppressor genes in some tumor samples. The purposes of this paper were to study the roles ofHPV16E6,E7, orE6/E7 oncogenes in methylation status and expression of theSTK31 gene, and potential effects of DNA methyltransferases (DNMTs) onSTK31 gene methylation status.Methods:Ectopically-expressed HPV16 E6, E7, or E6/E7 cells were estab-lished by transfectingHPV16E6,E7, orE6/E7 oncogenes with lentivirus vectors into HPV-negative cervical cancer cell lines HT-3 and C33A. Bisulfite genomic sequencing PCR (BGS) combined with TA clone and MSP (methylation-specific PCR) were used to analyze methylation status of theSTK31 gene promoter/exon1 region in HPV-positive cervical cancer cell lines (HeLa, SiHa, CaSki), HPV-negative cervical carcinoma cell lines (C33A, HT-3) and the transfected cells. The mRNA and protein expression of STK31, DNMT1, DNMT2, DNMT3a, DNMT3b and DNMT3L were detected by RT-PCR and Western blot.Results:Transfection efficiency was tested by Western blot, which showed that the transfected cells successfully expressed E6, E7, or E6/E7 proteins, respectively. TheSTK31 gene promoter/exon1 was hypomethylated in HPV-positive cell lines HeLa, SiHa and CasKi resulting in detection of mRNA and protein expression.STK31 gene promoter/exon1 showed hypermethylation leading to silenced expression in the two HPV-negative cervical cancer cells HT-3 and C33A. Compared with primary HT-3 and C33A cells, the methylation status ofSTK31 promoter/exon1 was down-regulated that led to expression of STK31 in the ectopically-expressed HPV16 E7 and E6/E7 cells. Expressions of DNMT1,DNMT3a andDNMT3b genes at the level of transcription were higher in C33AE6/E7 and HT-3E6/E7 cells than those in C33A-vector and HT-3 vector cells, respectively (P<0.001). mRNA levels of DNMT1, DNMT3a and DNMT3b were higher in HPV16-positive cervical cancer tissues than those in HPV-negative cervical cancer tissues, respectively (t=5.997,P<0.001;t=6.743,P<0.001;t=7.926,P<0.001). DNMT2 mRNA level was lower in C33AE6/E7 and HT-3E6/E7 cells than those in C33A-vector and HT-3 vector cells, respectively (t=7.451,P<0.001;t=2.451,P<0.05). mRNA level of DNMT2 gene was lower in HPV16-positive cervical cancer tissues than in HPV-negative cervical cancer tissues (t=9.134, P<0.001). There was no statistically significant difference in expression levels of DNMT3L mRNA between cervical cancer cell lines before and after transfection, or HPV16-positive and HPV-negative cervical cancer tissues, respectively (P>0.05, data not shown).Conclusion:HPV infection leads to the down-regulated methylation status ofSTK31 promoter/exon1 that results in the expression of STK31.STK31 gene expression is regulated by methylation status of its promoter/exon1 region. HPV16E7 andE6/E7 oncogenes may influence the methylation status ofSTK31 gene promoter/exon1 region by regulating the expression of DNMT2.

The development of liver inflammatory diseases is associated with autoimmunity and inflammatory response. As a negative feedback regulator of cell signal, suppressor of cytokine signaling 1 (SOCS1) plays a key role in the development and progression of inflammatory diseases. This article mainly introduces the mechanism of action of SOCS1 in autoimmunity and inflammatory response and briefly describes its role in the development and progression of liver inflammatory diseases such as viral hepatitis and nonalcoholic steatohepatitis. The analysis shows that the abnormal expression of SOCS1 in inflammatory response is associated with the regulation of cytokine receptor, Toll-like receptor, and hormone receptor signal, which leads to the development of inflammatory diseases. Therefore, SOCS1 has potential prospects as an auxiliary means for the diagnosis and treatment of liver inflammatory diseases.

OBJECTIVE To investigate the potential mechanism of procyanidin on rats with gingivitis by regulating phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt）/vascular endothelial growth factor （VEGF） signaling pathway. METHODS The rat model of gingivitis was constructed by sewing the neck of the first maxillary molar with silk thread+applying maltose on the gum+feeding with 20% sucrose solution and soft food. Forth-eight model rats were randomly divided into model group， procyanidin group （160 mg/kg）， 740Y-P group （PI3K/Akt signaling pathway activator， 0.02 mg/kg）， and procyanidin+ 740Y-P group （procyanidin 160 mg/kg+740Y-P 0.02 mg/kg）， with 12 rats in each group； another 12 rats were selected as control group； each medication group was treated with corresponding drugs intragastrically or/and intraperitoneally， once a day， for 7 consecutive days. Twenty-four hours after the last administration， the gingival index of rats was measured； the levels of interleukin- 18 （IL-18）， inducible nitric oxide synthase （iNOS） and alkaline phosphatase （ALP） in gingival crevicular fluid， as well as the levels of superoxide dismutase （SOD）， catalase （CAT） and reactive oxygen species （ROS） in gingival tissues of rats were detected； the pathological changes in gingival tissues were observed； the expression levels of PI3K/Akt/VEGF signaling pathway- related proteins in gingival tissues of rats were detected. RESULTS Compared with control group， the gingival tissues of rats in the model group had severe pathological damage，which was manifested as local tissue expansion and congestion， new capillaries， degeneration and loss of collagen fibers and disorder of arrangement， and a large number of inflammatory cell infiltration in the gingival sulcus wall. The gingival index， the levels of IL-18， iNOS， ALP in gingival crevicular fluid， the level of ROS in gingival tissues， the phosphorylations of PI3K and Akt， as well as the protein expression of VEGF in gingival tissues were significantly increased； the levels of SOD and CAT in gingival tissues of rats in model group were significantly decreased （P＜0.05）. Compared with model group， the pathological damage to the gingival tissues of rats in procyanidin group was reduced， and all quantitative indicators were significantly improved （P＜0.05）； 740Y-P could reverse the improvement effect of procyanidin on various indicators （P＜0.05）. CONCLUSIONS Procyanidin may alleviate gingival tissue damage， and improve gingival inflammation and oxidative stress in rats with gingivitis by inhibiting PI3K/Akt/VEGF signaling pathway.

Reflux esophagitis is an inflammatory disease of esophageal mucosa damage caused by the reflux of gastric contents into the esophagus. Its incidence is on the rise， and it has become an important precancerous disease of esophageal cancer. Studies have shown that the continuous inflammatory response stimulates the esophageal mucosa， causing abnormal proliferation of esophageal epithelial cells and damage to esophageal mucosal tissue， which eventually leads to the occurrence of heterogeneous hyperplasia and even carcinogenesis. The nuclear transcription factor-kappa B （NF-κB） signaling pathway is one of the most classical inflammatory and cancer signaling pathways. It has been found that abnormal activation of the NF-κB signaling pathway is crucial to the development and prognosis of reflux esophagitis and esophageal cancer. It is widely involved in the proliferation， autophagy， apoptosis， and inflammatory response of esophageal epithelial cells and tumor cells， accelerating the transformation of reflux esophagitis to esophageal cancer and making it a potential target for the treatment of reflux esophagitis and esophageal cancer. Currently， there is no specific treatment for reflux esophagitis and esophageal cancer， and large side effects often appear. Therefore， finding a promising and safe drug remains a top priority. In recent years， traditional Chinese medicine scholars have conducted a lot of research on NF-κB signaling pathway， and the results indicate that NF-κB signaling pathway is an important potential target for traditional Chinese medicine to prevent and treat reflux esophagitis and esophageal cancer， but there is a lack of comprehensive and systematic elaboration. Therefore， this paper summarized the relevant studies in recent years， analyzed the relationship among NF-κB signaling pathway， reflux esophagitis， esophageal cancer， and transformation from inflammation to cancer， and reviewed the research literature on the regulation of the NF-κB signaling pathway in traditional Chinese medicine to prevent and treat reflux esophagitis and esophageal cancer， so as to provide new ideas for the prevention and treatment of reflux esophagitis and esophageal cancer.

Colorectal cancer （CRC） is one of the leading causes of cancer-related deaths worldwide， with increasing incidence and mortality rates. The disease often develops covertly and lacks specific symptoms in its early stages， leading to late-stage diagnoses in most patients. It has become a prominent research topic in the field of digestive system tumors. The exact mechanisms underlying CRC are not yet clear and involve factors such as genetics， gene mutations， inflammatory responses， and aberrant activation of tumor-related signaling pathways. Nuclear factor-kappa B （NF-κB） is a crucial transcription factor that participates in various biological processes， including inflammatory responses， immune responses， cell proliferation， and apoptosis. Research suggests that NF-κB， serving as a molecular link between inflammation and cancer， is highly expressed in CRC. It promotes the occurrence and development of CRC by regulating the activity of target genes such as cell pro-inflammatory factors， chemokines， angiogenic factors， metastasis factors， and anti-apoptotic proteins. Currently， common treatments for CRC include surgery， radiation therapy， and chemotherapy drugs like 5-fluorouracil. However， these treatments have limitations such as significant adverse reactions， high metastasis rates， and the development of drug resistance. Therefore， the search for effective， low-adverse-reaction drugs to replace or supplement current treatments is essential. In recent years， traditional Chinese medicine （TCM） has shown some effectiveness in preventing and treating CRC. TCM has been found to inhibit the growth of CRC cells by modulating the NF-κB signaling pathway， playing a positive role in the occurrence and progression of CRC. Based on the asthenia in origin and sthenia in superficiality and deficiency-excess in complexity in CRC， this article summarized and analyzed the mechanisms and effects of TCM interventions targeting the NF-κB signaling pathway in CRC， and reviewed advances of 10 Chinese medicinal compound formulas and 37 Chinese medicinal monomer components of different types， including flavonoids， phenols， alkaloids， glycosides， and terpenoids with the effects of dispelling pathogenic factors， reinforcing healthy qi， and removing toxins in the prevention and treatment of CRC by targeting the NF-κB pathway. It is found that Chinese medicine can inhibit CRC cell proliferation， invasion， metastasis， angiogenesis， and inflammation by modulating the NF-κB signaling pathway， induce cell apoptosis， restore drug and radiation sensitivity， and counteract CRC. This article is expected to provide insights and references for the in-depth exploration and treatment of CRC mechanisms.

Pancreatic cancer is one of the most destructive malignant tumors； the pathogenesis of this disease is complex and is closely related to genetic susceptibility， chronic pancreatitis， and gene mutations in signaling pathways. The phosphoinositide 3- kinase （PI3K）/protein kinase B （Akt） signaling pathway is a classical cancer signaling pathway that is aberrantly activated in pancreatic cancer cells. In recent years， it has been found that traditional Chinese medicine （TCM） monomers show special activity in the treatment of pancreatic cancer and can be potential drug for the treatment of pancreatic cancer. Based on PI3K/Akt signaling pathway， this paper summarizes the mechanism of TCM monomer intervening in pancreatic cancer and finds that TCM monomer of alkaloids （sinomenine， dictamnine， dauricine， etc.）， terpenoids （saikosaponin A， linderalactone， isoalantolactone， etc.）， phenols （6-gingerol， curcumin， pterostilbene， etc.）， flavonoids （fisetin， kaempferol， quercetin， etc.） and quinones （β-hydroxyisovaleryl shikonin， rhein， lucidone， etc.） can inhibit the proliferation， invasion and migration of pancreatic cancer cells， regulate autophagy and apoptosis， and then inhibit the pathological process of pancreatic cancer by inhibiting PI3K/Akt signaling pathway.

Esophageal cancer （EC） is a common malignant tumor of the digestive system with an extremely poor prognosis. MicroRNA （miRNA） is an important regulator in tumor occurrence and development， and can participate in malignant biological behaviors such as tumor cell proliferation， invasion， metastasis and apoptosis. Traditional Chinese medicine has the characteristics of accurate curative effects， wide range of effects， and few side effects. The review uses miRNA as the entry point to systematically elaborate on the mechanism of traditional Chinese medicine-mediated miRNA intervening in EC. The results showed that active ingredients of traditional Chinese medicine （including curcumin， Tussilago farfara polysaccharides， Atractylodes macrocephala polysaccharides and ophiopogonin B） and Dougen guanshitong oral liquid could up-regulate the expressions of miRNAs such as miRNA-532-3p （miR-532-3p）， miR-551b-3p， miR-99a， miR-34a， miR-199a-3p and miR-377； and the active ingredients/parts of traditional Chinese medicine （including chrysin and Actinidia arguta extract）， and Chinese herbal formulas （including Chaihu shugan san combined with Xuanfu daizhe decoction and Modified jupi zhuru decoction） could down-regulate the expressions of miRNAs such as miR-199a-3p， miR-451 and miR-21， which could regulate the expressions of signaling pathways （phosphoinositide 3-kinase/protein kinase B， etc.） or their downstream protein（zinc-finger and homeobox protein 1， etc.） or enzymes（thymidine kinase-1， etc.）， inhibit the proliferation， invasion and metastasis of EC cells and induce apoptosis， thereby ultimately achieving the purpose of preventing the disease from aggravating.

Silicon carbide (SiC) film and silicon dioxide (SiO ) film were deposited on the surface of carbon/carbon composite (C/C) by low pressure chemical vapor deposition (LPCVD). The biocompatibility of the three carbon-based composites, e. g. C/C, C/C-SiC, C/C-SiO were investigated by cytotoxicity test, cell direct contact and cell adhesion experiments. Cytotoxicity, cell direct contact and cell adhesion showed that the three materials had no toxic effect on mouse fibroblasts (L929 cells). However, the particles dropped off from the three materials had a great impact on evaluation accuracy of the thiazolyl blue (MTT) test. More the particles were lost, more growth inhibition to L929 cells. The evaluation accuracy of MTT method can be kept with the filtered extract of materials. Furthermore, the results of surface particles shedding experiment showed that the amount of surface particles shed from C/C-SiO was the most, followed by C/C and C/C-SiC in 72 hours. Particles shedding curves showed there was a peak reached at eighth hour and then declined to the thirty-sixth hour. The filtrate analysis showed that there was no ion exchange between the three materials and simulated body fluid (SBF) solution. The results of this study on biocompatibility of carbon-based composites have certain guiding significance for their future application in clinical filed.