BACKGROUND:Shikonin contributes to the promotion of bone defect repair and the treatment of osteoporosis. OBJECTIVE:To summarize the application potential of shikonin and its derivatives in oral soft and hard tissue regeneration. METHODS:A literature review was conducted in databases such as PubMed,Web of Science,Wanfang,China National Knowledge Infrastructure(CNKI),and VIP,spanning articles from 2002 to 2023.The search terms were"shikonin,oral cavity,periodontitis,antibacterial,bone formation,osteoclast,osteoporosis,toxicology"in Chinese and English. RESULTS AND CONCLUSION:Shikonin and its derivatives possess anti-inflammatory effects,inhibit periodontal pathogens such as Porphyromonas gingivalis,promote periodontal wound healing,and regenerate alveolar bone tissue.Shikonin formulations can be used to treat oral diseases such as aphthous ulcers and oral candidiasis.These findings suggest a promising future for shikonin and its derivatives in treating periodontal diseases,preventing oral ailments,and promoting the regeneration of both soft and hard periodontal tissues.Further research is needed to explore how to combine shikonin with tissue engineering to achieve quicker healing of oral soft and hard tissues.

Objective:To analyze the clinical characteristics of gastrointestinal symptoms and liver function injury in patients with coronavirus disease 2019 (COVID-19).Methods:From January 23, 2020 to February 29, 2020, the medical records of 251 patients with COVID-19 admitted to the West Campus of the Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, were collected. The proportion of the patients with gastrointestinal symptoms including anorexia, nausea and vomiting, diarrhea and abdominal pain were analyzed respectively. The patients were divided into common type (76 cases), severe type (65 cases) and critical type (110 cases). The incidence of liver function injury and the changes of liver function parameters such as total bilirubin (TBil), direct bilirubin (DBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), albumin and globulin of the patients with different clinical types and with or without gastrointestinal symptoms were analyzed. Mann-Whitney U test, Chi square test and Fisher′s exact test were used for statistical analysis. Results:The main gastrointestinal symptoms of patients with COVID-19 were anorexia (33.9%, 85/251), diarrhea (12.0%, 30/251), nausea and vomiting (7.6%, 19/251) and abdominal pain (1.2%, 3/251). 143 patients (57.0%) had liver function injury, the rate of liver function injury in critical type patients was 75.5% (83/110), which was higher than that of common type patients (40.8%, 31/76) and severe type patients (44.6%, 29/65), and the differences were statistically significant ( χ2=22.765 and 16.865, both P<0.01). There was no significant difference in the proportion of patients with liver function injury between common type and severe type patients ( P>0.05). There was no statistically significant difference in the proportion of liver function injury between patients with gastrointestinal symptoms and those without gastrointestinal symptoms (57.8%(67/116) vs. 56.3%(76/135), P>0.05). The median values of TBil, DBil, ALT, AST, ALP, GGT, LDH and globulin level of critical type patients were 13.5 μmol/L, 4.9 μmol/L, 44.5 U/L, 50.0 U/L, 64.0 U/L, 41.0 U/L, 527.0 U/L and 33.6 g/L respectively. The proportions of critical type patients with TBil level >34.2 μmol/L, DBil level>13.6 μmol/L, ALT level>80 U/L and AST level>80 U/L were 7.3% (8/110), 7.3% (8/110), 17.3% (19/110) and 17.3% (19/110), respectively. These results were all higher than those of common type patients (9.5 μmol/L, 2.9 μmol/L, 28.5 U/L, 28.5 U/L, 54.0 U/L, 25.5 U/L, 225.5 U/L, 30.1 g/L, 0, 0, 6.6% (5/76) and 2.6% (2/76) ) and severe type patients (10.4 μmol/L, 3.4 μmol/L, 30.0 U/L, 31.0 U/L, 49.0 U/L, 25.0 U/L, 284.0 U/L, 30.7 g/L, 0, 0, 6.2% (4/65) and 1.5% (1/65)), and the differences were statistically significant ( Z=-4.264, -5.507, -4.000, -6.558, -3.112, -4.333, -4.858, -3.873, Fisher′s exact test, Fisher′s exact test, χ2=4.574, 9.620; Z=-3.060, -3.850, -3.923, -5.005, -9.495, -7.651, -3.853, -2.725, Fisher′s exact test, Fisher′s exact test, χ2=4.425, 10.169; all P<0.01). The median values of pre-albumin level, albumin level and the albumin to globulin ratio of critical type patients were 85.3 g/L, 28.2 g/L and 0.8, which were all lower than those of common type patients (157.3 g/L, 32.3 g/L and 1.1, respectively) and severe type patients (133.6 g/L, 31.6 g/L and 1.1, respectively), and the differences were statistically significant ( Z=-6.631, -3.647, -4.924, -4.503, -5.283 and -3.903, all P<0.01). The median albumin level of patients with diarrhea was lower than that of patients without diarrhea (28.2 g/L vs. 30.5 g/L), the proportion of diarrhea patients whose TBil level >20.0 to 34.2 μmol/L was higher than that of patients without diarrhea (70.0%, 21/30 vs. 10.9%, 24/221), and the differences were statistically significant ( Z=-2.182, χ2 =62.788; both P<0.05). Conclusions:Anorexia is the most common digestive symptom in COVID-19 patients, and the incidences of abdominal pain is low. The incidence of liver function injury of critical type patients is high. There is no significant correlation between gastrointestinal symptoms and liver function injury, and patients with diarrhea have lower albumin levels.

In recent years, the number of advanced non-small cell lung cancer (NSCLC) patients has gradually increased, and the treatment methods have also been significantly increased. However, there are no standard treatment plans at home and abroad for third-line and above patients who are refractory to targeted therapy epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) or chemotherapy. The clinical treatment effect is also not satisfactory. Anlotinib is a novel TKI targeting the vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and c-Kit. ALTER0303 trail, phase III study has demonstrated that Anlotinib significantly prolonged overall survival (OS) and progression-free survival (PFS) in advanced NSCLC patients as 3rd line treatment.Here we report a case of advanced lung adenocarcinoma harboring KRAS mutation treated with Anlotinib.
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Adenocarcinoma ; drug therapy ; enzymology ; genetics ; pathology ; Adenocarcinoma of Lung ; Aged ; Antineoplastic Agents ; therapeutic use ; Humans ; Indoles ; therapeutic use ; Lung Neoplasms ; drug therapy ; enzymology ; genetics ; pathology ; Male ; Mutation ; Proto-Oncogene Proteins p21(ras) ; genetics ; metabolism ; Quinolines ; therapeutic use

OBJECTIVE:To compare the clinical efficacy of erlotinib between late non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) exon 19 mutation and those with exon 21 mutation.METHODS:Late NSCLC patients with EGFR mutation positive enrolled in our hospital during Oct.2013-Nov.2014 were selected.Patients with EGFR exon 19 Del mutant were regarded as group A,and patients with exon 21 L858R mutant were regarded as group B,45 cases in each group.All patients were orally administered with Edotinib hydrochloride tablets till progression.The disease control rate (DCR),median survival time (MST),median time to progress (mTTP),one-year survival rate and incidence of adverse reactions in 2 groups were compared.RESULTS:The DCR (93.02％) and one-year survival rate (81.40％) in group A were obviously higher than that of group B (72.09％,60.47％) (P＜0.05),MST [(15.47 ± 2.87) month] and mTTP [(182.00 ± 8.24) d] were obviously longer than that of group B [(12.55 ± 2.92) month,(162.00 ± 7.22) d] (P＜0.01).There was no statistical significance in the incidence of adverse reactions in 2 groups (P＞0.05),and there were no severe adverse reactions.CONCLUSIONS:For patients with late NSCLC,erlotinib shows superior efficacy in patients with EGFR exon 19 mutation to patients with EGFR exon 21 mutation.

Objective: To study the effects of UV treatment of different zirconia surfaces on the function of MC3T3-E1 osteoblasts. Methods: Disks of zirconia-based materials with smooth(S) and rough(R) surfaces were treated and with and without UV light(15 W) for 48 h,respectively. MC3T3-E1 cells were cultured on zirconia disks and divided into 4 groups: smooth group(S),UV treated smooth group(S-UV),rough group(R) and UV treated rough group(R-UV). Cell proliferation was assessed by MTT 3 and 5 days after culture. Alkaline phosphatase(ALP) activity was determined 3 and 7 days after culture. Cell mineralization was observed by Alizarin red dye staining 21 days after culture. The mRNA expression of OCN and OPG were examined by RT-PCR 7 and 14 days after culture. Results: Proliferation and mineralization of MC3T3-E1 cells in R-UV group were more than in other groups(P ＜ 0. 05). R groups showed higher ALP activity than S groups at day 7. R-UV treatment increased the mRNA expressions of OPG and OCN in a time-dependent manner(P ＜ 0. 05). Conclusion: Ultraviolet light-treated zirconia surface may promote the proliferation,mineralization and the expression of OCN and OPG of MC3T3-E1 cells.

BACKGROUND/AIMS: Currently, there exists no biomarker for visceral hypersensitivity in irritable bowel syndrome (IBS). Piezo proteins have been proven to play an important role in the mechanical stimulation to induce visceral pain in other tissues and may also be a biomarker candidate. The aim of this study was to test the expressions of Piezo1 and Piezo2 proteins in the intestinal epithelial cells from different intestinal segments and to explore the correlation between Piezo proteins expression and visceral pain threshold. METHODS: Post-infectious IBS was induced in mice via a Trichinella spiralis infection. Visceral sensitivity was measured with abdominal withdrawal reflex to colorectal distention. Inflammation in the small intestine and colon was scored with H&E staining. Expression location of Piezo proteins was confirmed by immunohistochemistry. Abundance of Piezo proteins were measured with real-time reverse transcriptase polymerase chain reaction. RESULTS: Piezo1 and Piezo2 proteins were expressed in the intestinal epithelial cells. The expression levels of Piezo1 and Piezo2 were abundant in the colon than the small intestine (P < 0.001 for Piezo1, P = 0.003 for Piezo2). Expression of Piezo2 in the colon significantly correlated to the visceral sensitivity (r = −0.718, P = 0.001) rather than the mucosal inflammation. CONCLUSION: Piezo2 is a candidate biomarker for visceral hypersensitivity in IBS.
Animals ; Colon ; Epithelial Cells ; Humans ; Hyperalgesia ; Hypersensitivity* ; Immunohistochemistry ; Inflammation ; Intestine, Small ; Ion Channels ; Irritable Bowel Syndrome* ; Mice ; Reflex ; Reverse Transcriptase Polymerase Chain Reaction ; Trichinella spiralis ; Visceral Pain

Objective:To investigate the effects of bone morphogenetic protein 7 (BMP-7) on the biological properties of osteoblasts exposed to high glucose.Methods:MC3T3 cells were cultured in the high glucose condition and were divided into 4 groups according to BMP-7 concentration (ng/ml):0 (control group),50,100 and 200 ng/mL BMP-7 (test groups).The cell proliferation and ALP activity were examind 1,3,5 and 7 d after exposure.The number of intracellular calcium nodules were observed with Alizarin red staining after osteogenesis induction for 21 days.The F-actin cytoskeleton of MC3T3 was stained with Rhodamine and examined 24 h after culture.The mRNA expression of OCN and Runx2 were quantified by RT-qPCR 48h after exposure to BMP-7.Results:BMP-7 significantly promoted proliferation of MC3T3 cells and enhanced ALP activity(P ＜ 0.05),increased the number and volume of intracellular calcium nodules.In the cells exposed to BMP-7,the osteoblast form was improved and F-actin cytoskeleton started to change with network structure.Compared with control group,the mRNA levels of OCN and Runx2 were up-regulated in BMP-7 groups (P ＜ 0.05).The mRNA levels of OCN and Runx2 were the highest in 200 ng/ml BMP-7 group(P ＜ 0.05).Conclusion:BMP 7 may inhibit the action of the high concentration of glucose on MC3T3 cells.BMP-7 may be benificial to osseointegration of dental implant in patietents with diabetics.

Objective Dexmedetomidine is known to have a neuroprotective effect.The aim of this study was to investigate the effects of dexmedetomidine on ketamine-induced apoptosis of primarily cultured cortical neurons and its action mechanisms. Methods Rat cortical neurons were primarily cultured for 7 days and treated with ketamine (100μmol/L) and different concentrations of dexmedetomi-dine (0.001, 0.01, 0.1, and 1 μmol/L) for 24 hours, followed by measurement of the viability of the neurons by MTT assay.The neurons were divided into four groups:vehicle control, ketamine ( trea-ted with 100 μmol/L ketamine), dexmedetomidine+ketamine (DD+K, treated with 0.1 μmol/L DD and 100 μmol/L ketamine), and LY294002 ( treated with 0.1 μmol/L DD, 100 μmol/L ketamine, and 10 μmol/L LY294002) .After 24 hours of treatment, the apoptosis rate of the neurons was determined by Hoechst33258 staining, and the expressions of pAkt and cleaved-caspase-3 in the neu-rons detected by Western blot. Results The apoptosis rate of neurons was dramatically increased in the LY294002 and ketamine groups in comparison with the vehicle control and DD+K groups ([36.8 ±4.4] and [43.4 ±4.5]%vs [7.5 ±1.1] and [16.4 ± 3.6]%, P<0.01), the pAkt level remarkably decreased (0.26 ±0.02 and 0.15 ±0.01 vs 0.61 ±0.05 and 0.50 ±0.04, P<0.01), and the expression of cleaved caspase-3 significantly upregulated in the former two as compared with the latter two groups (0.40 ±0.02 and 0.65 ±0.03 vs 0.10 ±0.02 and 0.12 ±0.01, P<0.01). Conclusion Dexmedetomidine exerts a neuroprotec-tive effect against ketamine-induced apoptosis of neurons by activating the PI3K-Akt signaling pathway.

Objective:To investigate the effects of titanium spcimens with different surface character on the proliferation and mRNA expression of IL-6 and Cbfα1 in osteoblasts.Methods:Titanium surface was treated by smooth pretreatment(PT),sandblast and acid etch(SLA)and anodic oxidation(AD)respectively.The morphology and the elements analysis of the spcimens were inspected and detected by SEMand EDS.The surface contact angle was measured by contact angle meter.MC3T3-E1 cells were cultured on the titanium surface and cells cultured on tissue culture plate were served as the control group.The proliferation was measured by MTT assay.The mRNA expression of IL-6 and Cbfα1 was quantified by RT-qPCR.Results:The sample surface in PT group showed scrat-ches,in SLA group showed multiple three dimensional structure,in AD group exhibited porous structure.The elements of the sample surface of group PT,SLA and AD were Ti,Ti/Al and Ti/O respectively;the contact angles were 54.47°±3.33°,75.42°±8.32° and 38.91 °±4.00°respectively(P<0.05).The cells in AD group showed higher proliferation than those in PT and SLA groups(P<0.05).In AD group IL-6 mRNA expression decreased and Cbfα1 mRNA increased more than in PT and SLA groups(P<0.05). Conclusion:Titanium spcimens treated with AD may promote cell proliferation,decrease IL-6 mRNA expression and increase Cbfα1 mRNA expression in MC3T3 cells.Implats treated with AD might have some advantages in early osseointegration.

BACKGROUND:Studies have confirmed that nicotine affects the activity of osteoblasts, osteoclasts, fibroblasts and erythrocytes.
OBJECTIVE:To study the nicotine effects on osseointegration and the expression of osteoprotegerin and bone morphogenetic protein 2 after implantation of dental implants with surface treatment by sandblasting or acid etching.
METHODS:Twenty-four Sprague-Dawley rats were randomly assigned to two groups and received daily injections for 2 weeks as folows: Nicotine 2 mg/kg twice for experimental group, saline solution for control group. Then the titanium implants with surface sandblasting or acid etching were implanted into the tibiae folowed by continuous nicotine or normal saline injection. At weeks 2 and 4 after implantation, the implants and surrounding bone tissue were prepared for CT, X-ray and hematoxylin-eosin staining examinations to evaluate bone healing and expression levels of bone-related genes were measured by quantitative RT-PCR.
RESULTS AND CONCLUSION: Compared with the control groups, the degree of osseointegration and the expression of osteoprotegerin and bone morphogenetic protein 2 in the experimental groups were decreased significantly (P < 0.05), except that the expression of bone morphogenetic protein 2 in the experimental group with acid etching was not significantly reduced. In addition, the expression of bone morphogenetic protein 2 in the experimental group with acid etching was higher than that in the experimental group with sandblasting at 2 weeks after implantation (P < 0.05). The X-ray and CT show that the quantities of new generation bone and the degree of bone mineralization of the sandblasting group were significant lower than those of the acid etching group under the intervention of nicotine. Hematoxylin-eosin staining showed that the activity and quantity of osteoblasts around the implants down-regulated significantly, but acid etching-treated implants showed better outcomes than sandblasting-treated implants.