BACKGROUND: Craniomaxillofacial tissue defects are clinical defects involving craniomaxillofacial and oral soft and hard tissues.They are characterized by defect-shaped irregularities, bacterial and inflammatory environments, and the need for functional recovery.Conventional clinical treatments are currently unable to achieve regeneration of high-quality oral craniomaxillofacial tissue. As a natural biomaterial, silk fibroin (SF) has been widely studied in biomedicine and has broad prospects for use in tissue regeneration.Hydrogels made of SF showed excellent water retention, biocompatibility, safety and the ability to combine with other materials. METHODS: To gain an in-depth understanding of the current development of SF, this article reviews the structure, preparation and application prospects in oral and craniomaxillofacial tissue regenerative medicine. It first briefly introduces the structure of SF and then summarizes the principles, advantages and disadvantages of the different cross-linking methods (physical cross-linking, chemical cross-linking and double network structure) of SF. Finally, the existing research on the use of SF in tissue engineering and the prospects of using SF with different cross-linking methods in oral and craniomaxillofacial tissue regeneration are also discussed. CONCLUSIONS This review is intended to show the advantages of SF hydrogels in tissue engineering and provides theoretical support for establishing novel and viable silk protein hydrogels for regeneration.

Objective To compare clinical and pathological features between autoimmune hepatitis (AIH) patients with positive and negative autoantibodies, and to summarize the experience in diagnosis. Methods A retrospective analysis was performed for the patients who attended Beijing Ditan Hospital from January 2010 to August 2021 and were diagnosed with AIH by liver histopathology, and according to the presence or absence of autoantibodies, they were divided into positive autoantibody group and negative autoantibody group. The two groups were compared in terms of biochemical parameters, immunological features, histopathological features, disease stage, and clinical symptoms and signs. The t -test or the Mann-Whitney U test was used for comparison of continuous data between groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data. Results A total of 110 patients were enrolled, among whom 78 (71%) had positive autoantibodies and 32 (29%) had negative autoantibodies. Anti-nuclear antibody (ANA), anti-mitochondrial antibody (AMA), and anti-smooth muscle antibody (ASMA) were the main autoantibodies detected, and of all 110 patients, 74 (67.27%) had positive ANA, 1 (0.91%) had positive AMA, 5 (4.55%) had positive ASMA, and 14 (12.73%) had positive anti-Ro-52 antibody. As for clinical and immunological features, compared with the positive autoantibody group, the negative autoantibody group had significantly lower incidence rates of jaundice of the skin and sclera (21.90% vs 50.00%, χ 2 =7.377, P =0.007) and poor appetite (18.80% vs 41.00%, χ 2 =4.979, P =0.026) and significantly lower median levels of direct bilirubin [7.30(4.05~12.10) μmol/L vs 16.80(6.48~69.75) μmol/L, Z =-2.304, P =0.021], IgG [16.40(13.15~18.05) g/L vs 20.30(16.00~27.15) g/L, Z =-2.715, P =0.007], and GLo [30.60(26.00~34.90) g/L vs 37.30(30.50~42.50) g/L, Z =-3.356, P =0.001]. In terms of liver histopathology, compared with the negative autoantibody group, the positive autoantibody group had a significantly higher proportion of patients with lymphocyte infiltration (91.03% vs 68.75%, χ 2 =6.997, P =0.008) and plasma cell infiltration (82.05% vs 50.00%, χ 2 =11.572, P =0.001); compared with the ANA-negative patients, the ANA-positive patients had significantly higher inflammation grade (G1-G4) (9.46%/16.22%/44.59%/29.73% vs 5.56%/27.78%/63.89%/2.78%, Z =-2.179, P =0.029) and fibrosis degree (S1-S4) (37.84%/25.68%/32.43%/4.05% vs 13.89%/41.67%/30.56%/13.89%, Z =-0.082, P =0.037). Conclusion Compared with AIH patients with positive autoantibodies, AIH patients with negative autoantibodies are mostly in the early stage of the disease and tend to have a low level of IgG, with a relatively high rate of missed diagnosis in clinical practice. Early and active liver biopsy is of particular importance.

Objective To investigate the onset of liver inflammation and related predictive factors in patients with HBeAg-positive chronic hepatitis B virus (HBV) infection who have normal alanine aminotransferase (ALT) and a high viral load. Methods A retrospective analysis was performed for the clinical data of 183 patients with HBeAg-positive chronic HBV infection who had normal ALT and a high viral load and were treated from October 2008 to May 2015, and according to the results of liver biopsy, they were divided into hepatitis group and non- hepatitis group. The t -test or Mann-Whitney U testwas used for comparison of normally distributed continuous data between groups, the chi-square test was used for comparison of categorical data. The predictive factors were analyzed by univariate binary logistic regression, the multivariate binary logistic regression was carried out by stepback method, and the cut-off values were analyzed by receiver operating characteristic curve (ROC) and Jordan index. Results There were 37 patients (20.2%) in the hepatitis group and 146 patients (79.8%) in the non-hepatitis group. Compared with the non-hepatitis group, the hepatitis group had a significantly lower proportion of male patients (45.9% vs 68.5%, χ 2 =6.508, P =0.011), a significantly higher level of aspartate aminotransferase [24 (21.25~35.55) U/L vs 21.2 (18.08~ 24.65) U/L, Z =-3.344, P =0.001], and a significantly lower log(HBsAg) value [4.4(4.28~4.49) vs 4.46(4.4~4.74), Z =-2.184, P =0.029]. Log(HBsAg) value was a predictive factor for hepatitis (odds ratio=0.077, P =0.017), and the cutoff value of HBsAg was 33884.4I U/mL. Conclusion Among the patients with HBeAg-positive chronic HBV infection who have normal ALT and a high viral load, 20.2% have liver inflammation, and HBsAg may be a predictive factor for liver inflammation.

Objective:To summarize the clinical features and prognosis of acute kidney injury in patients with HBV related acute on chronic liver failure (ACLF).Methods:A total of 150 patients who developed acute kidney injury (AKI) in patients with HBV related ACLF from Sep. 2010 to Sep. 2019 were reviewed retrospectively, and the gender, age, laboratory examination, Child-pugh scores, and model for end-stage liver disease (MELD) were collected and the survival of the patients were followed up to analyze the prognosis.Results:Ninety-three percent of the patients were complicated with ascites, 81% with spontaneous peritonitis, 65% with hepatic encephalopathy and 58.7% with pulmonary infection; 60 patients (60.0%) were AKI stage 1, 44 patients (29.3%) were AKI stage 2, 16 patients (10.7%) were AKI stage 3. The patients with hyponatremia had lower albumin ( t=2.571, P=0.011), higher blood urea nitrogen, serum potassium and white blood cell levels than those without hyponatremia ( t=3.184, P=0.002; t=2.069, P=0.040; t=2.251, P=0.026); 74.7% of the patients died within 30 days, and the 90 days survival rate was 16.7%. The 30 days and 90 days mortality of patients with hyponatremia was higher than that of patients without hyponatremia ( χ2=4.11, P=0.044; χ2=3.901, P=0.049 7). Kaplan-Meier analysis revealed that the patients who had abnormal uric acid pre-diagnosis of AKI, hyponatremia when diagnosis of AKI, organ damage other than liver and kidney, metabolic acidosis, upper gastrointestinal tract bleeding, hepatic encephalopathy had a poor survival. Cox regression analysis showed that other organ function damage other than liver and kidney, metabolic acidosis, and the old age, were independent risk factors of death. Conclusions:Most of the AKI patients with HBV related ACLF had ascites and spontaneous bacterial peritonitis when AKI occurred, and AKI stage 1 was common. The mortality of patients with hyponatremia was high, and the risk of death was high in patients with severe organ damage other than liver and kidney, metabolic acidosis and the old age.

After hepatitis B virus (HBV) infects the body, HBV clearance and liver damage mediated by host immune response play a key role in clinical outcome. In chronic hepatitis B, the inflammatory response is a characteristic manifestation of the host immune response. The long-term inflammation promotes the development of liver fibrosis and cirrhosis. Innate immunity is the host’s first line of defense against hepatitis B virus infection, and plasmacytoid dendritic cells (pDCs) are a vital part of innate immunity and play a key role in chronic HBV infection, hepatitis occurrence, HBV clearance and recovery of infection. Exploring the function of plasmacytoid dendritic cells in chronic hepatitis B virus infection may provide a theoretical basis for clinical practice. In this article the research progress of the role of pDCs in the pathogenesis of chronic hepatitis B is reviewed.

Objective:To investigate the distribution characteristics and related factors of HBsAb in infants born to women with chronic hepatitis B virus (HBV) infection.Methods:A total of 605 infants born to women with chronic HBV infection who met the requirements for inclusion were selected as the subjects. Information about the mother′s previous HBV infection, biochemical indicators during pregnancy, pregnancy complications, information about delivery, and hepatitis B test result after birth were collected. HBsAg and HBsAb at the age of 1 year were determined, and HBsAg and HBsAb at the age of 7 months were retrospectively collected. The factors influencing HBsAb in infants were analyzed by ordered logistic regression.Results:In 605 infants, the infection rate was about 1%. Among them, 6 infants were positive for HBsAg and HBV DNA at 7 months and 1 year of age. Uninfected infants were divided into groups according to HBsAb titers. The result showed that there were significant differences in prothrombin activity (PTA) ( χ2=11.17, P=0.01), positive rate of HBeAg ( χ2=7.87, P=0.049) and HBsAg positive rate at birth ( χ2=10.52, P=0.02) among different groups. Multivariate ordered Logistic regression analysis showed that HBsAg negative at birth was an independent protective factor for HBsAb at 7 months of age ( OR=1.564, 95% CI 1.092-2.239, P=0.015). Logistic regression analysis of HBsAb at 1 year of age showed maternal gestational diabetes mellitus ( OR=1.578, 95% CI 1.126-2.210, P=0.008), infant enhanced immunization ( OR=81.207, 95% CI 31.202-211.352, P < 0.001) and antibody level at 7 months of age ( OR=42.123, 95% CI 22.824-77.739, P < 0.001) were independently associated with HBsAb at 1 year of age. Conclusions:HBsAg negative in venous blood at birth was an independent protective factor for HBsAb at 7 months of age, and enhanced immunization was an independent protective factor for HBsAb at 1 year of age.

Objective:To observe the effects of applying ultrasound-guided balloon dilatation in the treatment of post-stroke cyclopthyroid achalasia.Methods:Thirty-eight stroke survivors with cyclopneaful achalasia were divided into a control group ( n=19) and an experimental group ( n=19). All had been diagnosed with cycloparyngeal achalasia using videofluoroscopic swallowing study (VFSS). The controls were treated with conventional oral balloon dilatation, while the experimental group underwent ultrasound-guided oral balloon dilatation. The treatment was performed once every 2 days. During the treatment period, the durations and the number of expansions were recorded, and the patient′s comfort and throat pain were evaluated. The Kubota drinking water test (KDWT), standardized swallowing assessment (SSA) scoring and VFSS scoring were compared before and after the 2 weeks of treatment. Results:The average daily duration of expansions in the experimental group was significantly less than in the control group and their number was significantly greater. Comfort and larynx pain were also significantly better in the experimental group. The effective rate in the KDWT was 78.95% in the treatment group, significantly higher than the control group′s 31.58%. Significant differences were also found in the average SSA scores, VFSS pharyngeal phase scores and in the incidence of achalasia between the experimental and control groups.Conclusions:Using ultrasound to guide balloon dilatation can shorten the operation, reduce the throat pain involved and allow for more expansions, greater comfort and thus more effective treatment.

Objective Antiviral therapy should be adopted for chronic hepatitis B (CHB) patients with significant liver fibrosis to decrease the risk of liver related complications.Fibrosis assessment during antiviral treatment is a key step in antiviral therapy evaluation.Liver biopsy is the gold standard for assessing the degree of liver fibrosis.However,liver biopsy is difficult to perform more than one time after a long-term effective treatment because of the cost and risk of life-threatening complications.In this study we aimed to evaluate changes of liver fibrosis during 4 years of entecavir(ETV) treatment by non-invasive fibrosis markers in CHB patients who need antiviral therapy.Methods Totally 268 HBeAg negative treatment-naive CHB patients were enrolled and liver biopsy were performed before starting antiviral therapy in this study.Totally173 patients who needed antiviral therapy (liver fibrosis stages≥ F2,Metavir scoring system) were treated with ETV for at least 4 year.A clinical and virological evaluation was performed at baseline and again at 12,24,36 and 48 months during ETV treatment.Fibrosis-4 (FIB-4) index was used to assess dynamic changes of liver fibrosis in HBeAg negative CHB patients after 1,2,3 and 4 years of ETV treatment.Results Liver biopsy was performed for all enrolled patients at baseline.According to Metavir fibrosis stages,numbers of patients with FI,F2,F3 and F4 were 95,108,50 and 15,respectively.The FIB-4 index enabled the effective identification of patients with severe fibrosis (Metavir F3-F4) with an area under the ROC curve of 0.775 (95％CI 0.716-0.834).The FIB-4 values significantly decreased in F2 and F3 patients after 1 and 2 years ETV therapy (P＜0.01),respectively.But for F4 patients,FIB-4 values decreased significantly at year 4 (P＜0.05).Conclusions FIB-4 values decreased significantly during 4-year ETV treatment in HBeAg-negative CHB patients indicating that these noninvasive fibrosis tests might be useful for monitoring improvement of liver fibrosis and assessing treatment efficacy during long-term ETV treatment.

Objective:To investigate the association between the pathogenesis of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B and the frequency and function of plasmacytoid dendritic cell (pDC) in patients HBeAg-positive chronic hepatitis B virus infection.Methods:A total of 49 HBeAg (+ ) patients with chronic hepatitis B virus infection in immune tolerance phase (IT) and 100 patients in immune clearance phase (IC) were enrolled. The viral serological indicators and liver function were detected. Peripheral venous blood samples were collected. The peripheral blood pDC frequency and the quantitative expression of co-stimulatory molecule CD86 were detected by flow cytometry, and the correlation between the onset of chronic hepatitis B and the frequency and function of pDC was analyzed.Results:In IC group, hepatitis B surface antigen (HBsAg) levels, HBeAg levels and hepatitis B virus (HBV) DNA loads were significantly lower than those in IT group, and alanine aminotransferase (ALT) levels in IC group were significantly higher than that in IT group; pDC% in IC group was significantly lower than that in IT group; CD86 + pDC% and CD86 mean fluorescentintensity (MFI) showed no significant difference between the two groups. In the IC group, the baseline pDC% was negatively correlated with ALT levels, while CD86 + pDC%, CD86MFI, and CD86 antibody binding capacity (ABC) had no remarkable correlation with ALT levels. Conclusions:The frequency of pDC was correlated with the pathogenesis of CHB. The lower the frequency of pDC in patients with CHB, the more prone to hepatitis. Therefore, increasing the frequency of pDC may inhibit the occurrence of hepatitis.

Objective: We aimed to evaluate changes towards liver fibrosis during entecavir(ETV)treatment by non-invasive fibrosis markers in chronic hepatitis B (CHB) patients who need antiviral therapy. Methods: Totally 303 HBeAg negative treatment-naive CHB patients were enrolled and liver biopsy was performed before starting antiviral therapy in this study. Totally 196 patients who need antiviral therapy were treated with ETV for at least 3 years. A clinical and virological evaluation was performed at baseline and again after 1, 2 and 3 years during ETV treatment. AST-to-platelet ratio index (APRI) was used to assess dynamic changes of liver fibrosis in HBeAg negative CHB patients after 1, 2, 3 years of ETV treatment. Results: All enrolled patients experienced liver biopsy at baseline. According to Metavir fibrosis stages, F1, F2, F3 and F4 patients were 107, 125, 54 and 17, respectively. The APRI score enabled the correct identification of patients with severe fibrosis (METAVIR F3-F4). The APRI values significantly decreased in F2 and F3 patients after 1 year ETV therapy (P<0.01). But for F4 patients, APRI values decreased significantly at year 3 (P<0.05). Conclusions APRI values decreased significantly during ETV treatment in HBeAg-negative CHB patients indicating that these noninvasive fibrosis tests might be useful for monitoring improvement of liver fibrosis and assessing treatment efficacy during long-term ETV treatment.