BACKGROUND:With the development of oral implantology,implant restoration has gradually become the first choice of restoration after missing teeth,and bone augmentation procedures have led to the expansion of implant indications and the improvement of the success rate of implant restoration.However,the long-term stability of bone height,width and volume after bone augmentation surgery has been one of the clinical difficulties for oral implantologists.OBJECTIVE:To measure and analyze the bone width,height,and volume of different sites in the bone augmentation area at different time points using cone-beam CT and an automatic image alignment program.METHODS:Seventeen patients with severe bone defects in the upper anterior region who underwent Onlay bone block grafting in the external oblique region were recruited from the Department of Stomatology,Zhejiang Tongde Hospital.There were 10 males and 7 females,with a mean age of(45.88±12.47)years.The cone-beam CT scans of the patients' Onlay bone grafts were taken at five time points:preoperatively,immediately postoperatively,6 months postoperatively,immediately post implantation,and 6 months post implantation,and then were statistically analyzed for alveolar bone volume,width,and height in the bone augmentation area,as well as for the difference in the alveolar bone volume of the bone incremental area between patients of different sexes and age.RESULTS AND CONCLUSION:(1)The alveolar bone volume in the bone augmentation area was higher immediately and 6 months after bone grafting than before bone grafting(P＜0.05)as well as was higher immediately after bone grafting than 6 months after bone grafting(P＜0.05).The alveolar bone height in the bone augmentation area was higher immediately and 6 months after bone grafting than before bone grafting(P＜0.05).The horizontal width of the alveolar bone at various sites in the bone augmentation area immediately and 6 months after bone grafting was higher than that before bone grafting(P＜0.05).(2)There was no significant difference in the volume of bone graft resorption at various sites in the bone augmentation area between males and females immediately and 6 months after bone grafting(P＞0.05).Pearson correlation analysis showed a positive correlation between age and the change in bone augmentation area volume immediately and 6 months after bone grafting,but the difference was not statistically significant(P＞0.05).(3)Twenty-five dental implants with completed implant restorations functioned normally,and the survival rate of the implants was 100％.To conclude,Onlay bone graft implant restoration in the upper anterior region can significantly improve insufficient bone with favorable outcomes.However,there is some amount of bone resorption in the bone augmentation area at 6 months after Onlay bone grafting and it is necessary to open up the second surgical area.Clinicians should consider different bone augmentation procedures in accordance with the specific circumstances.

BACKGROUND:With the development of oral implantology,implant restoration has gradually become the first choice of restoration after missing teeth,and bone augmentation procedures have led to the expansion of implant indications and the improvement of the success rate of implant restoration.However,the long-term stability of bone height,width and volume after bone augmentation surgery has been one of the clinical difficulties for oral implantologists.OBJECTIVE:To measure and analyze the bone width,height,and volume of different sites in the bone augmentation area at different time points using cone-beam CT and an automatic image alignment program.METHODS:Seventeen patients with severe bone defects in the upper anterior region who underwent Onlay bone block grafting in the external oblique region were recruited from the Department of Stomatology,Zhejiang Tongde Hospital.There were 10 males and 7 females,with a mean age of(45.88±12.47)years.The cone-beam CT scans of the patients' Onlay bone grafts were taken at five time points:preoperatively,immediately postoperatively,6 months postoperatively,immediately post implantation,and 6 months post implantation,and then were statistically analyzed for alveolar bone volume,width,and height in the bone augmentation area,as well as for the difference in the alveolar bone volume of the bone incremental area between patients of different sexes and age.RESULTS AND CONCLUSION:(1)The alveolar bone volume in the bone augmentation area was higher immediately and 6 months after bone grafting than before bone grafting(P＜0.05)as well as was higher immediately after bone grafting than 6 months after bone grafting(P＜0.05).The alveolar bone height in the bone augmentation area was higher immediately and 6 months after bone grafting than before bone grafting(P＜0.05).The horizontal width of the alveolar bone at various sites in the bone augmentation area immediately and 6 months after bone grafting was higher than that before bone grafting(P＜0.05).(2)There was no significant difference in the volume of bone graft resorption at various sites in the bone augmentation area between males and females immediately and 6 months after bone grafting(P＞0.05).Pearson correlation analysis showed a positive correlation between age and the change in bone augmentation area volume immediately and 6 months after bone grafting,but the difference was not statistically significant(P＞0.05).(3)Twenty-five dental implants with completed implant restorations functioned normally,and the survival rate of the implants was 100％.To conclude,Onlay bone graft implant restoration in the upper anterior region can significantly improve insufficient bone with favorable outcomes.However,there is some amount of bone resorption in the bone augmentation area at 6 months after Onlay bone grafting and it is necessary to open up the second surgical area.Clinicians should consider different bone augmentation procedures in accordance with the specific circumstances.

Objective To explore the mechanism of total saponin from Panax japonicus(TSPJ)in alleviating neuroinflammation in experimental autoimmune encephalomyelitis(EAE)based on the activation of microglia mediated by MAPK signaling pathway.Methods In vivo experiments,mice were divided into normal group,model group and TSPJ low-and high-dosage groups.EAE mouse model was induced by myelin oligodendrocyte glycoprotein polypeptide.Each medication group was gavaged with corresponding drug solution once a day for 28 days.The number of Iba-1-positive cells was assessed using immunofluorescence,the protein expressions of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-1β and MAPK signaling pathway related factors were detected by Western blot.In vitro experiments,murine microglia BV2 were divided into normal group,model group and TSPJ low-and high-dosage groups.LPS+IFN-γ was used to induce M1 polarization of BV2 cells,medication groups were given TSPJ intervention,the content of nitric oxide(NO)in cell supernatant,the expression of M1 microglia markers and MAPK signaling pathway related factors were detected,and ERK and JNK signaling pathway inhibitors were further used to clarify the molecular mechanism of TSPJ antagonizing neuroinflammation.Results The results of in vivo experiments showed that compared with the normal group,the cell body and number of microglia in cerebral cortex of the model group mice increased significantly(P<0.01),and the protein expressions of TNF-α,IL-6,IL-1β,p-p38/p38,p-JNK/JNK,p-ERK1/2/ERK1/2 significantly increased(P<0.05,P<0.01);compared with the model group,the number of microglia in cerebral cortex of TSPJ low-and high-dosage groups significantly decreased(P<0.01),the expressions of TNF-α,IL-6,p-p38/p38,p-JNK/JNK,p-ERK1/2/ERK1/2 protein significantly decreased(P<0.05,P<0.01),and the expression of IL-1β protein in TSPJ high-dosage group significantly decreased(P<0.05).The results of in vitro experiments showed that compared with the normal group,the content of NO in cell supernatant of the model group significantly increased(P<0.01),the protein expressions of CD16,CD86,p-p38/p38,p-JNK/JNK,p-ERK1/2/ERK1/2 significantly increased(P<0.01);compared with the model group,the content of NO in cell supernatant of TSPJ low-and high-dosage groups significantly decreased(P<0.01),and the protein expressions of CD16,CD86,p-p38/p38,p-JNK/JNK,p-ERK1/2/ERK1/2 significantly decreased(P<0.05,P<0.01).TSPJ combined with ERK and JNK pathway inhibitors could further inhibit the expressions of TNF-α and IL-6,but there was no significant difference compared with inhibitors alone.Conclusion TSPJ can inhibit the activation of microglia by regulating MAPK signaling pathway,thereby reducing EAE induced central nervous inflammation.

Esophageal cancer is one of the leading causes of death from cancer worldwide. Radiotherapy plays an important role in the treatment of esophageal cancer. Compared with photon radiotherapy, proton radiotherapy significantly reduces normal organ dose due to its unique biophysical properties, which makes this modality potential ideal for esophageal cancer treatment. Proton radiotherapy plays an important role in radical radiotherapy, neoadjuvant radiotherapy and re-radiotherapy for esophageal cancer. The efficacy is equivalent to or better than that of photon radiotherapy, and proton radiotherapy is superior than photon radiotherapy in security. The combination of proton radiotherapy and immunotherapy, the increase of radiotherapy dose, and large-scale randomized controlled studies based on intensity-modulated proton radiotherapy technology will be hot topics for further research.

Objective To explore the mechanism of total saponin from Panax japonicus(TSPJ)in alleviating neuroinflammation in experimental autoimmune encephalomyelitis(EAE)based on the activation of microglia mediated by MAPK signaling pathway.Methods In vivo experiments,mice were divided into normal group,model group and TSPJ low-and high-dosage groups.EAE mouse model was induced by myelin oligodendrocyte glycoprotein polypeptide.Each medication group was gavaged with corresponding drug solution once a day for 28 days.The number of Iba-1-positive cells was assessed using immunofluorescence,the protein expressions of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-1β and MAPK signaling pathway related factors were detected by Western blot.In vitro experiments,murine microglia BV2 were divided into normal group,model group and TSPJ low-and high-dosage groups.LPS+IFN-γ was used to induce M1 polarization of BV2 cells,medication groups were given TSPJ intervention,the content of nitric oxide(NO)in cell supernatant,the expression of M1 microglia markers and MAPK signaling pathway related factors were detected,and ERK and JNK signaling pathway inhibitors were further used to clarify the molecular mechanism of TSPJ antagonizing neuroinflammation.Results The results of in vivo experiments showed that compared with the normal group,the cell body and number of microglia in cerebral cortex of the model group mice increased significantly(P<0.01),and the protein expressions of TNF-α,IL-6,IL-1β,p-p38/p38,p-JNK/JNK,p-ERK1/2/ERK1/2 significantly increased(P<0.05,P<0.01);compared with the model group,the number of microglia in cerebral cortex of TSPJ low-and high-dosage groups significantly decreased(P<0.01),the expressions of TNF-α,IL-6,p-p38/p38,p-JNK/JNK,p-ERK1/2/ERK1/2 protein significantly decreased(P<0.05,P<0.01),and the expression of IL-1β protein in TSPJ high-dosage group significantly decreased(P<0.05).The results of in vitro experiments showed that compared with the normal group,the content of NO in cell supernatant of the model group significantly increased(P<0.01),the protein expressions of CD16,CD86,p-p38/p38,p-JNK/JNK,p-ERK1/2/ERK1/2 significantly increased(P<0.01);compared with the model group,the content of NO in cell supernatant of TSPJ low-and high-dosage groups significantly decreased(P<0.01),and the protein expressions of CD16,CD86,p-p38/p38,p-JNK/JNK,p-ERK1/2/ERK1/2 significantly decreased(P<0.05,P<0.01).TSPJ combined with ERK and JNK pathway inhibitors could further inhibit the expressions of TNF-α and IL-6,but there was no significant difference compared with inhibitors alone.Conclusion TSPJ can inhibit the activation of microglia by regulating MAPK signaling pathway,thereby reducing EAE induced central nervous inflammation.

Purpose To investigate the effect of MYD88 gene overexpression on the proliferation and apoptosis of human diffuse large B cell lymphoma(DLBCL)cells,and to prelimi-narily explore the mechanism of MYD88 gene action.Methods PEGFP-C2-MYD88 overexpressing MYD88 L265P gene was transfected into DLBCL cells by plasmid transfection.The exper-iment was divided into blank control group,negative control group and MYD88 L265P overexpression group.The fluores-cence expression of MYD88 L265P after overexpression was ob-served under inverted fluorescence microscope.RT-PCR and Western blot were used to detect the mRNA and protein expres-sion of MYD88 L265P,IRAK4,NF-κB and BCL2 in DLBCL cells before and after overexpression of MYD88 L265.CCK8 method was used to detect DLBCL cells proliferation and Ho-echst staining was used to detect DLBCL cells apoptosis.Re-sults After overexpression of MYD88 L265P,compared with the blank control group(0.670 4±0.017 5)and the negative control group(0.715 3±0.019 6),the MYD88L265P overex-pression group(1.157 2±0.010 2)increased significantly,with statistical significance(all P＜0.05).After overexpression of MYD88 L265P,compared with the blank control group(0.69 ±0.04)and the negative control group(0.81±0.07),the MYD88L265P overexpression group(0.48±0.05)was signifi-cantly decreased,with statistical significance(all P＜0.05).After overexpression of MYD88 L265P,compared with the blank control group(mRNA:1.0158±0.0115,0.987 3±0.010 2,1.007 6±0.015 3,protein:0.183 4±0.058 9,0.096 8± 0.015 7,0.147 5±0.0418)and negative control group(mR-NA:0.9132±0.0098,1.0032±0.0156,0.9327± 0.011 2,protein:0.187 9±0.042 3,0.088 9±0.0513,0.134 8±0.050 1),the mRNA(3.243 2±0.013 6,2.976 6 ±0.0213,1.585 9±0.019 8)and protein expressions(0.452 7±0.052 4,0.218 9±0.047 5,0.301 4±0.059 8)of IRAK4,NF-κB and anti-apoptosis protein BCL2 in MYD88L265P overexpression group were significantly increased,which was statistically significant(all P＜0.05).Conclusion After overexpression of MYD88 L265P,the apoptosis rate of DLBCL cells decreased and the cell proliferation rate increased.The mechanism may be related to the mutation of MYD88 L265P gene,activation and amplification of NF-κB pathway,and pro-motion of the overexpression of antiapoptotic protein BCL2.

Objective:To analyze the association between thrombocytopenia and clinical manifestations in patients with antiphospholipid syndrome (APS), and the significance of adding thrombocytopenia to the classification criteria of APS.Methods:One hundred and sixty one APS patients admitted to Peking University People's Hospital from January 2003 to August 2017 were retrospectively analyzed. Clinical and laboratory data were compared between patients with and without thrombocytopenia. Chi-square test, Fisher's exact test and t test were used for statistical analysis. Results:Among 161 APS patients, 48 patients (29.8%) were primary APS and 113 patients (70.2%) were secondary APS. Ninety-one patients (56.5%) experienced thrombocytopenia, while 62 patients (38.5%) had thrombocytopenia as the initial symptom. Among primary APS patients, compared with patients without thrombocytopenia, the prevalence of thrombosis was significantly lower in patients with thrombocytopenia (40.0% vs 69.6%, χ2=4.218, P=0.040), especially venous thrombosis (20.0% vs 47.8%, χ2=4.174, P=0.041). Among secondary APS patients, compared with patients without thrombocyt-openia, the prevalence of thrombosis, arterial thrombosis (21.2% vs 42.6%, χ2=5.944, P=0.015) and venous thrombosis (22.7% vs 51.1%, χ2=9.753, P=0.002) was significantly lower in patients with thrombocytopenia (43.9% vs 80.9%, χ2=15.496, P<0.01). As for laboratory findings, primary APS patients with thrombocytopenia showed a higher proportion of positive aCL findings (80.0% vs 52.2%, χ2=4.174, P=0.041), while secondary APS patients with thrombocytopenia experienced more leukopenia (25.8% vs 10.6%, χ2=4.002, P=0.045), lower complement C3 levels (78.7% vs 44.4%, χ2=13.205, P<0.01) and complement C4 levels (74.6% vs 46.7%, χ2=8.485, P=0.004). The proportion of patients fulfilling 1988, 1989, 1999 and 2006 APS classification criteria in our cohort was 88.2%, 87.0%, 64.0% and 70.8%, respectively. Inclusion of thrombocytopenia into 2006 criteria improved the proportion to 96.3%. Conclusion:The prevalence of thrombosis in APS patients with thrombocytopenia is significantly low. Thrombocytopenia is an important clinical manifestation of APS which can improve the diagnostic accuracy of APS.

Identification of genetic variants via high-throughput sequencing (HTS) technologies has been essential for both fundamental and clinical studies. However, to what extent the genome sequence composition affects variant calling remains unclear. In this study, we identified 63,897 multi-copy sequences (MCSs) with a minimum length of 300 bp, each of which occurs at least twice in the human genome. The 151,749 genomic loci (multi-copy regions, or MCRs) harboring these MCSs account for 1.98％of the genome and are distributed unevenly across chromosomes. MCRs containing the same MCS tend to be located on the same chromosome. Gene Ontology (GO) anal-yses revealed that 3800 genes whose UTRs or exons overlap with MCRs are enriched for Golgi-related cellular component terms and various enzymatic activities in the GO biological function cat-egory. MCRs are also enriched for loci that are sensitive to neocarzinostatin-induced double-strand breaks. Moreover, genetic variants discovered by genome-wide association studies and recorded indbSNP are significantly underrepresented in MCRs. Using simulated HTS datasets, we show that false variant discovery rates are significantly higher in MCRs than in other genomic regions. These results suggest that extra caution must be taken when identifying genetic variants in the MCRs via HTS technologies.

Objective To evaluate the effect of intrathecal oxytocin on neuropathic pain in rats.Methods Thirty-six SPF male Sprague-Dawley rats,aged 4-6 weeks,weighing 100-150 g,were divided into 4 groups (n =9 each) using a random number table:control group (group C),neuropathic pain group (group NP),neuropathic pain plus normal saline group (group NPN) and neuropathic pain plus oxytocin group (group NPO).The neuropathic pain model was made by partial sciatic nerve injury in NP,NPN and NPO groups.In group NPO,oxytocin l0 μl (0.1 μg) was intrathecally injected on the day of establishing the model and 1 and 2 days after establishing the model,and then normal saline 10 μl was given for tube sealing at 9 a.m.and 4 p.m.every day.In group NPN,normal saline 20 μl was given for tube sealing at the corresponding time points.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before establishing the model and 1,2,3,4,5,6 and 7 days after establishing the model.The expression of the astrocyte marker glial fibrillary acidic protein (GFAP) and a specific marker of microglia ionized calcium-binding adaptor molecule 1 (IBa-1) was detected by Western blot at 1 day before establishing the model and 3 and 7 days after establishing the model.Results Compared with group C,the MWT was significantly decreased,TWL was shortened and the expression of GFAP and IBa-1 was up-regulated at each time point in NP and NPN groups (P＜0.05).There was no significant difference in MWT,TWL GFAP and IBa-1 at each time point between group NPN and group NP (P＞0.05).Compared with NP group,MWT was significantly increased at 2-4 days after establishing the model,TWL was prolonged at 1-4 days after establishing the model,the expression of IBa-1 was down-regulated on 3 days after establishing the model,and the expression of GFAP was downregulated on 3 and 7 days after establishing the model in group NPO (P＜0.05).Conclusion Oxytocin can reduce neuropathic pain,and the mechanism may be related to inhibiting activation of glial cells in the spinal cord of rats.

ObjectiveTo investigate the risk factors of patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) complicated with Yangming Fushi syndrome.Methods A prospective study was conducted. From August 2009 to July 2013, 206 patients with Yangming Fushi syndrome combined with ALI/ARDS were enrolled in the intensive care units ( ICUs ) of the following five hospitals: Tianjin Nankai Hospital, Dongzhimen Hospital Affiliated to Beijing Traditional Chinese Medicine University, General Hospital of Tianjin Medical University, the First Affiliated Hospital of Dalian Medical University, and Wuxi Third People's Hospital in Jiangsu Province. According to the mortality occurring in ICU, the patients were divided into death group and survival group. The gender, age, acute physiology and chronic health evaluation Ⅱ ( APACHE Ⅱ ) score within the first 24 hours after admission, the length of invasive mechanical ventilation, usage of vasoactive agents, ratio of operative intervention, the length of stay in ICU, application of continuous renal replacement therapy ( CRRT ), amount of blood transfusion, the level of C-reactive protein ( CRP ), lactulose/mannitol ( L/M ) ratio, the number of organs with dysfunction, oxygenation index ( PaO2/FiO2 ), levels of lactate and serum creatinine ( SCr ) of both groups were recorded. Logistic regression analysis was used to look for the independent risk factors of death of patients. Results There were 124 cases with severe acute pancreatitis ( SAP ), which was the most common disease with manifestation of Yangming Fushi syndrome combined with ALI/ARDS, accounting for 60.19% of all the patients. During the period of hospitalization in ICU, 171 patients survived and 35 died, and the mortality rate was 16.99%. The risk factors of the two groups were analyzed by variable analysis, and it was shown that compared with those in survival group, the age ( years: 57.26±16.23 vs. 48.07±13.48, t = 3.544, P = 0.000 ), APACHE Ⅱ score ( 20.83±9.73 vs. 12.61±6.63, t = 4.777, P = 0.000 ), the length of invasive mechanical ventilation ( days: 10.97±7.71 vs. 6.91±2.48, t = 2.555, P = 0.015 ) and the number of dysfunction organs ( 3.11±1.21 vs. 1.60±1.34, t = 6.222, P = 0.000 ) in death group were significantly higher. The level of PaO2/FiO2 [ mmHg ( 1 mmHg = 0.133 kPa ): 218.56±64.90 vs. 244.58±85.10, t = -2.024, P = 0.044 ] in the death group was significantly lower than that of the survival group, while the length of ICU stay ( days: 14.33±10.81 vs. 9.11±7.37, t = 2.600, P = 0.010 ), the usage rates of CRRT [ 28.57% ( 10/35 ) vs. 15.20% ( 26/171 ), χ2 = 3.968, P = 0.046 ], vasoactive agents [ 28.57% ( 10/35 ) vs. 12.28% ( 21/171 ), χ2 = 6.511, P = 0.011 ], and blood transfusion ratio [ 42.86% ( 15/35 ) vs. 23.39% ( 40/171 ), χ2 = 7.042, P = 0.008 ] were all obviously higher in the death group than those in the survival group. There were no statistically significant differences in gender, number of operation, the levels of CRP, L/M ratio, lactate and SCr between the two groups ( all P > 0.05 ). Multivariate logistic regression analysis showed that age [ odds ratio ( OR ) = 0.938, 95% confidence interval ( 95%CI ) = 0.898-0.980, P = 0.004 ], APACHE Ⅱ score ( OR = 0.914, 95%CI = 0.839-0.996, P = 0.041 ), the number of dysfunction organs ≥ 3 ( OR = 0.223, 95%CI = 0.066-0.754, P = 0.016 ), and the level of PaO2/FiO2 ( OR = 0.990, 95%CI = 0.982-0.998, P = 0.015 ) were independent risk factors for mortality. Conclusions The age, APACHE Ⅱ score, number of dysfunction organs ≥ 3 and the level of PaO2/FiO2 are of significance in predicting the prognosis of patients with Yangming Fushi syndrome combined with ALI/ARDS. Patients with risk factors of high mortality should be more carefully monitored and treated aggressively.