With the development of implant technology and materials, the aesthetic of implant prosthesis has been paid more and more attention. Implant prosthesis should be coordinated with patients’ characteristics, the existing aesthetic indices have no unified standard. Based on current research and clinical experiences, this review narrated the esthetic indices of implant crowns and peri-implant soft tissue and influencing factors of dental implant in the aesthetic area.

Objective To investigate the curative effect of benidipine hydrochloride on patients with coronary slow flow angina pectoris(CSFA).Methods Sixty cases patients with CSFA were randomly divided into two groups of 30 patients each.In the control group patients were received aspirin(100 mg,1 times/d) and atorvastatin(20 mg,1 times/d) as basic treatment;in the treatment group patients were received basic treatment plus benidipine hydrochloride(4 mg,1 times/d).Follow up for 6 mouths,the effectiveness rate of treatment(relief of angina and electrocardiogram of myocardial ischemia),the correction of thrombolysis in myocardial infarction(TIMI) frame count(CTFC) before and after the different intervention,and the incidence of adverse cardiovascular events were compared between the treatment group and the control group.Results The effectiveness rate of treatment in the treatment group(86.7%,26/30) was significantly higher than that in the control group(63.3%(19/30);χ2=4.356,P=0.037).There were significant reductions of CTFC in both groups after the different intervention(treatment group:(28.43±3.95) frames vs.(18.40±3.73) frames,t=10.254,P=0.000;control group:(27.87±4.14) frames vs.(21.87±4.17) frames,t=5.580,P=0.000).There was more significant reductions of CTFC in the treatment group as compared to the control group(t=2.138,P=0.037).The incidence of adverse cardiovascular events in the treatment group(10.0%(3/30)) was significantly lower than that in the control group(33.3%(10/30),P=0.028).Conclusion Benidipine hydrochloride is effective in the treatment of CSFA.

Objective: To investigate the correlation between the level of P34H expression and the activity of hyaluronidase in human spermatozoa. Methods: Eighty eight semen samples were collected, 68 cases were in the infertile group, and 20 in the normal control group. Semen routine analysis was referred to the WHO standard method. According to the difference of semen parameters, 68 cases of infertile males were divided into the infertile group with normal semen parameters and the abnormal semen parameters. Western blotting was used to detect the level of P34H expression on spermatozoa. The P34H-positive rate on human spermatozoa was determined by indirect immunofluorescent staining using anti-P34H antibody. The HYD-positive rate and HYD-activity intensity in all samples were examined by improved fixedsubstrate film method. Results: The level of P34H protein expression and the percentage of the P34H-positive rate in infertile groups with normal semen parameters and abnormal semen parameters were significantly lower than that in the control group (P<0.05). The activity of HYD (HYD-positive rate, HYD-activity intensity) in the infertile groups with normal semen parameters and abnormal semen parameters were also significantly lower than that in control group (P < 0.05). The relation between the P34H protein expression and HYD-positive rate, HYD-activity intensity had a significant positive correlation (r = 0. 449, 0. 431; P < 0.01); the relation between the the percentage of P34H-positive rate and HYD-positive rate, HYD-activity intensity had a significant positive correlation (r=0.727, 0.691;P <0.01). Conclusion: The level of P34H protein expression and the percentage of the P34H-positive rate are decreased, while the activity of HYD (HYD-positive rate, HYD-activity intensity) is reduced in male infertility.

OBJECTIVE: To investigate the effect of melatonin (MLT) on the proliferation and apoptosis of human multiple myeloma cell line RPMI 8226 and its possible mechanism. METHODS: RPMI 8226 cells were cultured in vitro, and different concentrations of MLT were treated on RPMI 8226 cells. The effects of MLT on RPMI 8226 cell proliferation were detected by CCK-8 assay and methylcellulose cloning assay, and the effects of MLT on cell apoptosis were detected by AnnexinV-FITC /PI, flow cytometry. Western blot was used to determine the expression of apoptosis and endoplasmic reticulum stress-related proteins in each group, and CCK-8 assay was used to determine the effect of MLT combined with bortezemib on the viability of RPMI 8226 cells. RESULTS: MLT inhibited the proliferation of RPMI 8226 cells in a dose- and time-dependent manner (r=-0.9777，r=-0.9951). With the increase of MLT concentration, the number of clones decreased, the apoptosis of RPMI 8226 cells increased (P<0.05), the expression of anti-apoptotic protein XIAP decreased, the expression of apoptotic proteins Bax and Caspase3 increased, and the expression of endoplasmic reticulum stress-related proteins increased. Compared with the control group, the survival of RPMI 8226 cells in the MLT and BTZ combined group significantly decreased (P<0.01). CONCLUSION MLT can inhibit the proliferation of RPMI 8226 cells, promote the apoptosis of RPMI 8226 cells, and enhance the anti-tumor effect of BTZ on RPMI 8226 cells. The mechanism may be related to endoplasmic reticulum stress.
Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Endoplasmic Reticulum Stress ; Humans ; Melatonin/pharmacology* ; Multiple Myeloma/pathology* ; Sincalide/pharmacology*

Background Fluorine accumulates in the brain tissue after long-term excessive intake and subsequently cause nerve damage and decline of learning and memory ability. Receptor of advanced glycation end-products (RAGE)/p38 mitogen-activated protein kinase (p38MAPK)/nuclear factor kappa-B (NF-κB) signaling pathway is considered to be involved in the associated mechanism. Objective To study the changes of RAGE/ p38MAPK/ NF-κB signaling pathway in rats with subchronic fluorosis, and to explore the protective effects of extract of Ginkgo biloba 761 (EGb761) and RAGE antagonist (FPS-ZM1) on neuromemory ability. Methods Ninety male clean SD rats were divided into 9 groups with 10 rats in each group. The modeling period was 6 months. Control group (C group): free drinking tap water (fluoride content <0.5 mg·L⁻¹), low- and high-dose fluoride groups (LF group, HF group): free drinking tap water with 10 or 50 mg·L⁻¹ fluoride; intervention group of Ginkgo biloba extract (CE, LFE, and HFE groups): on the basis of the C group, LF group, and HF group, 100 mg·kg⁻¹·d⁻¹ EGb761 was given daily via intragastric administration; FPS-ZM1 intervention groups (CF, LFF, and HFF groups): 7 d before the end of modeling, 1 mg·kg⁻¹·d⁻¹ FPS-ZM1 was injected intraperitoneally daily on the basis of the C group, LF group, and HF group. The contents of fluoride in brain and blood of each group were detected. The learning and memory ability was tested by water maze experiment. The histopathologic changes of the hippocampus were detected by Nissl staining. The protein expression levels of RAGE and its ligand high mobility group protein B1 (HMGB1), NF-κB, p38MAPK, phospho-p38MAPK (p-p38MAPK), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α) in brain tissue were detected by Western blotting. The mRNA expression levels of RAGE, HMGB1, and p38MAPK were detected by quantitative real-time PCR. Results Compared with the C group, the contents of blood fluoride and brain fluoride in the LF and the HF groups were increased (P<0.05). The results of the water maze experiment showed that, compared with the C group, the escape latency time of the LF group and the HF group was longer and the crossing times were reduced; compared with the HF group, the escape latency time of the HFE group and the HFF group was shortened, and the crossing times were increased (P<0.05). The Nissl staining results showed that the number of Nissl body in the HF group decreased compared with the C group; compared with the HF group, the number of Nissl body in the HFE group and the HFF group increased. The Western blotting results showed that compared with the relative protein expression levels of RAGE, HMGB1, NF-κB, p38MAPK, p-p38MAPK, IL-6, and TNF-α in the C group , the levels of above indicators in the HF group and the levels of RAGE, HMGB1, NF-κB, p-p38MAPK, and IL-6 in the LF group were up-regulated (P<0.05); compared with the HF group, the levels of above indicators in the HFE group and the HFF group were all down-regulated (P<0.05); compared with the relative protein expression levels of RAGE and HMGB1 in the LF group, the levels in the LFE group and the LFF group were all down-regulated (P<0.05). The quantitative real-time PCR results showed that compared with the C group, the mRNA expression levels of RAGE and HMGB1 in the LF group and the HF group were up-regulated; compared with the LF group, the mRNA expression levels of RAGE in the LFE group and the LFF group were down-regulated ; compared with the HF group, the mRNA expression levels of RAGE and HMGB1 in the HFE group and the HFF group were down-regulated (P<0.05). Conclusion The central nervous system injury caused by subchronic fluorosis may be related to the activation of RAGE/p38-MAPK/NF-κB signaling pathway, which can impair the learning and memory ability of rats, while EGb761 and FPS-ZM1 may have certain protective effects on the nerve injury.

ObjectiveTo investigate the clinical efficacy and safety of iguratimod combined with the Chinese medicine Runzaoling in the treatment of primary Sjögren's syndrome （pSS）. MethodSeventy-two patients treated in the Department of Rheumatology and Immunology of the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine（TCM） from January 2021 to June 2022 who met the Western medical diagnosis of pSS and had the TCM syndrome of Yin deficiency and heat toxin syndrome were randomly assigned into an observation group and a control group， with 36 patients in each group. The observation group was treated with iguratimod combined with Runzaoling， and the control group was treated with iguratimod. The treatment in both groups lasted for 12 weeks. The clinical symptoms， EULAR Sjogren's syndrome patient reported index （ESSPRI）， EULAR Sjögren's syndrome disease activity index （ESSDAI）， erythrocyte sedimentation Rate （ESR）， C-reactive protein （CRP）， immunoglobulin （IgG）， Schirmer score， and saliva flow of the two groups were determined before and after treatment. Furthermore， the incidence of adverse reactions was compared between the two groups. ResultThe total response rate in the observation group was 75.0% （27 patients with response and 9 patients with no response）， which was higher than that （61.11%， 22 patients with response and 14 patients without response） in the control group （P<0.05）. After treatment， the ESSPRI， ESSDAI， and TCM syndrome scores in both groups decreased and the decreases were more obvious in the observation group than in the control group （P<0.05）. The treatment in both groups recovered the ESR， CRP， IgG， Schirmer score， and saliva flow （P<0.05）. Moreover， the observation outperformed the control group in terms of the ESR， CRP， IgG， and saliva flow （P<0.05） and had no significant difference in the Schirmer score compared with the control group. During the treatment period， 2 patients in the observation group had nausea， and 1 patient had an abnormal liver function， which were relieved after symptomatic treatment and did not affect the treatment. In the control group， 1 patient withdrew from the study due to rashes and showed no special discomfort in the follow-up 4 weeks， and 1 patient had nausea， which was relieved after symptomatic treatment. ConclusionIguratimod combined with Runzaoling has good clinical efficacy and safety in the treatment of pSS.

BACKGROUND: Autoimmune diseases are a class of diseases that cause a strong immune response to the continuous lack of self-tissue-specific antigens in the thymus. Hypothyroidism and unstable expression of tissue-specific antigens in the thymus can limit the therapeutic effect. The thymus is mainly composed of thymic epithelial cells, but the limited number of mature thymic epithelial cells and thymic epithelial progenitor cells in the thymus has greatly limited related research. OBJECTIVE: To detect the expression of autoimmune regulator (AIRE) when mouse embryonic stem cells were transformed into thymic epithelial progenitor cells. METHODS: A two-step differentiation method was used to induce the differentiation of mouse embryonic stem cells into endoderm and then into thymic epithelial progenitor cells. The cells were collected at 0, 3, and 13 days of induced differentiation. Immunofluorescence, flow cytometry, western blot and real-time PCR were used to detect the expression of cell-associated genes and proteins. RESULTS AND CONCLUSION: Positive expression of OCT4 and SSEA1 was detected by immunofluorescence at 0 day of induction. The double positive expression of SOX17 and FoxA2 was measured by immunofluorescence at 3 days of induction. The positive expression of EpCAM, K5 and K8 were analyzed by flow cytometry at 13 days of induction. During the directional differentiation of mouse embryonic stem cells, real-time PCR indicated that the expression of PAX1, PAX9, FOXN1 and PLET1 showed an increasing trend. The expression of AIRE gene increased significantly at 0, 3, and 13 days of induction. At the same time, the expression of INS2 gene and GAD67 gene also increased. Western blot assay showed that the expression of AIRE protein gradually decreased at 0, 3, and 13 days of induction; however, insulin protein and GAD67 protein were not detected. Overall findings indicate that mouse embryonic stem cells can successfully differentiate into thymic epithelial progenitor cells with highly expressed AIRE gene, which promotes the expression of INS2 and GAD67 genes, and provides an evaluation basis for cell transplantation in the treatment of autoimmune diseases.

Objective: to explore the effect of non nutritive sucking combined with maternal voice stimulation on feeding process in premature infants. Methods: A total of 129 premature infants admitted to the neonatal department of a tertiary hospital from July 2016 to July 2017 were randomly selected. According to the random number table method, there were 3 groups: NNS group, control group (routine nursing group), and NNS+MSS group, each with 43 cases. Non-nutritive sucking was given in the NNS group, general routine treatment and nursing in the control group, and non-nutritive sucking combined with mother's voice stimulation in the NNS+MSS group. The duration of feeding, initial feeding and hospitalization were observed in 3 groups. Results: NNS + MSS group feeding transition time, the first feeding duration, hospitalization days three points respectively (8.60 ± 1.24)d, (8.16±1.74)min, (13.26 ± 1.84)d, and NNS group respectively (12.09 ± 2.10) d, (4.72±1.45) min, (14.70±1.79) d, the control group, respectively (17.70±2.30) d (2.28 ± 1.39) min (19.81± 4.17) d. The differences between the three groups were statistically significant (F=242.085, 159.313, 63.856, all P<0.05). Conclusions Non nutritive sucking combined with mother sound stimulation can promote early feeding from nasal feeding to complete transoral feeding as soon as possible, reduce intermediate conversion time, accelerate feeding process and shorten hospitalization time.

Hot spring is a kind of precious natural water resource formed under specific geological conditions and obtained by natural gushing or artificial drilling, and is rich in minerals and trace elements peculiar to deep strata. Hot spring bathing is a physical therapy with a long history. An increasing number of studies have shown the positive effects of hot spring bathing in maintaining health and the auxiliary treatment and rehabilitation of chronic diseases. This paper reviews the distribution, classification and application history of hot springs, and further explores the research on the effect of hot springs on the improvement of sub-health status and the adjuvant treatment of chronic diseases such as skin diseases, cardiovascular diseases and joint diseases, so as to provide reference for further understanding of the physiotherapy value of hot spring bathing and boost its role in the development of big health industries.

ObjectiveTo study the effect of isoflavones from Sojae Semen Praeparatum （ISSP） on lipid metabolism in atherosclerotic mice， and decipher the underlying mechanism via the peroxisome proliferator-activated receptor gamma/liver X receptor alpha/ATP-binding cassette transporter A1 （PPARγ/LXRα/ABCA1） signaling pathway. MethodFifty ApoE^-/- mice were randomly assigned into the model group， western medicine （atorvastatin calcium， 3.03 mg·kg^-1） group， and low-， medium-， and high-dose ISSP （2.5， 5， 10 mg·kg^-1， respectively） groups， with 10 rats in each group. Atherosclerosis model mice were established by bilateral ovariectomy and feeding high-fat diet. Another 10 ApoE^-/- mice receiving ovariectomy and high-fat diet were taken as the sham group. Some mice died of postoperative infection， and finally 6 mice were included in each group. One week after operation， each group was administrated with corresponding drugs or equivalent amount of normal saline. After 12 weeks， the levels of triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， and non-esterified fatty acids （NEFAs） in serum and liver tissue were measured. The levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining and oil red O staining were used for observation of aortic plaque formation and liver lipid deposition. The mRNA and protein levels of PPARγ， LXRα， ABCA1， and ATP-binding cassette transporter G1 （ABCG1） in liver were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultCompared with the sham group， the modeling of atherosclerosis increased the aortic plaque area （P<0.01）， elevated the serum TC， TG， LDL-C， TNF-α， and IL-6 levels （P<0.01）， decreased the level of HDL-C （P<0.01）， increased the liver index （P<0.05） and the levels of TC， TG， and NEFAs in liver （P<0.01）， and caused obvious hepatic fat vacuoles and lipid deposition. In addition， the modeling down-regulated the mRNA levels of PPARγ， LXRα， ABCA1 in liver （P<0.05， P<0.01），and regulated the mRNA and protein levels of ABCG1（P<0.05， P<0.01）. Compared with the model group， atorvastatin calcium and middle-， high-dose ISSP reduced the serum TC， TG， LDL-C， TNF-α， and IL-6 levels （P<0.01）， decreased the liver index （P<0.01）， alleviated the liver fat vacuoles and lipid deposition， and increased the levels of TC， TG， and NEFAs in the liver （P<0.05， P<0.01）. Furthermore， they up-regulated the mRNA and protein levels of PPARγ， LXRα， ABCA1， and ABCG1 in the liver （P<0.05， P<0.01）. ConclusionISSP may regulate lipid metabolism through PPARγ/LXRα/ABCA1 signaling pathway to down-regulate the expression of inflammatory cytokines in serum and alleviate liver lipid deposition， thereby suppressing the formation of atherosclerotic plaque.