Objective:To explore the mechanism of zoledronic acid (ZOL) affects osteogenic differentiation and bone formation through the regulation of sirtuin 3 (SIRT3) / P53 expression.Methods:Bone marrow mesenchymal stem cells (BMSCs) were induced to differentiate into osteogenic cells, the expression of SIRT3 in the cells was detected, and the targeting regulation relationship between SIRT3 and P53 was analyzed. The intracellular expressions of SIRT3 and P53 were intervened and ZOL was used to treat the cells. MTT method, Western blot method and kit were used to detect cell viability, osteogenesis-related genes Osteoprotegerin (OPG), runt-related transcription factor 2 (Runx2) expression, alkaline phosphatase (ALP) activity and alizarin red S (ARS) staining, respectively. Ovariectomy (OVX) was used to construct a rat model and explore the effect of ZOL on the progression of osteoporosis (OP) in vivo.Results:ZOL promoted osteogenic differentiation of BMSCs. The expression of SIRT3 was down-regulated in the serum of OP patients (0.78±0.23) compared with that of healthy subjects (1.00±0.26 vs. 0.78±0.23. t=3.85, P<0.001). During the osteogenic differentiation of BMSCs, the expression level of SIRT3 gradually increased with the prolonged induction of osteogenesis. Compared with the p53 protein expression and BMSCs activity in the control group, SIRT3 knockout could increase the expression level of p53 protein (0.59±0.05 vs. 1.01±0.11. t=6.02, P=0.004) but inhibited the activity of BMSCs (100.00±8.41 vs. 51.26±5.59. t=8.36, P=0.001). After ZOL treatment, the inhibitory effect of SIRT3 on cell viability (49.61±5.11 vs. 87.61±7.31. t=7.38, P=0.002) and osteogenesis was relieved, and the level of P53 was inhibited (1.10±0.10 vs. 0.69±0.04. t=6.59, P=0.003). P53 overexpression partially offseted the effects of ZOL on cell viability (84.61±6.52 vs. 66.54±5.47. t=3.68, P=0.021) and osteogenesis. Compared with the sham surgery group, the OVX group showed inhibition of osteogenesis in rats, and ZOL treatment significantly improved osteogenic inhibition. ZOL treatment increased the expression level of SIRT3 protein in bone tissue of OVX rats, but inhibited the expression level of P53. Conclusion:ZOL promoted osteogenic differentiation and bone formation of BMSCs by promoting the ubiquitination and degradation of P53 by SIRT3.

Objective To summarize the postoperative complications of reconstruction of mandible defect with titanium reconstruction plate.Methods A total of 111 cases of the mandibular defect caused by various reasons and repaired by titanium reconstruction plate in the Department Oral and Maxillofacial Surgery of the affiliated Hospital of Qingdao University from 2003 to 2012 were collected and followed up.The complications were analyzed.Results Thirty-seven percent of 111 cases showed long term complications.The titanium fracture was the main complication(16％[18/111]),followed by stress-shielding (9％[10/111]),infection(8％[9/111]),and titanium plate exposure(4％[4/111]).Titanium plate fracture occurred within 8 months and 3 years after surgery.The simple titanium plate reconstruction had the highest rate of plate fracture(30％[15/50]).Stress-shielding in non-vascularized bone graft was more significant than that in vascularized bone graft(P＜0.05).When replaced by mini-titanium plate,the stress-shielding effect disappeared gradually.When the retention of mandibular margin height was less than 1 cm with the use of reconstruction plate,the postoperative complications were prone to occur.Conclusions Bone graft is the best way to reconstruct mandibular defect,and simple reconstruction plate repair is applied only as a transitional means for high degree of malignancy,obvious recurrence tendency tumor or special reasons such as age etc,which are not suitable for bone graft.The reconstruction plate fixation is not recommended for bone graft,especially non-vascularized bone graft.The retention of mandibular margin with reconstruction plate fixation is open to discussion.

Objective To determine the spectrum of mutations responsible for Phenylalanine hydroxylase (PAH) deficiency on phenylketonuria (PKU) patients of Han Chinese people in the Huaihai region of central China.Methods One hundred and one patients diagnosed with PKU were referred to Xuzhou Maternity and Child Health Care Hospital for genetic counseling/analysis from January 2003 to December 2013.Thirteen exons of PAH gene mutations,as well as their flanking introns,were identified in 202 of chromosomes using polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP) and sequencing.Results (1) The spectrum was composed of 24 different mutation types,which had been submitted to the National Center for Biotechnology Information(NCBI) dbSNP databases under accession number SS#2137543837_SS#C2137543860.(2)The most commonly affected region was exon 7 and its flanking introns.The most prevalent mutations were c.728G ＞ A (p.R243Q),followed by c.721C ＞ T (p.R241C),c.1155G ＞ C(p.L385L),c.1068C ＞ A(p.Y356X),c.-71A ＞ C(-71A ＞ C) and c.60 + 62C ＞ T (IVS1 +62C ＞T),accounting for 18.317％,8.416％,4.950％,3.960％,3.465％ and 2.970％ of the mutant chromosomes,respectively.(3)Two novel mutations were identified in PAH gene in PKU patients of Han Chinese people:c.60+62C＞T(IVS1 +62C ＞T) and c.782G ＞T(p.R261L).Conclusions The vast majority of PAH mutations identified corresponded to those observed for the PKU populations in the other regions in China,whereas a few are considerably different from others.The mutational spectrum of PAH gene found in patients with PKU in the Huaihai region exhibit regional association.

Objective:To explore the clinical characteristics of liver function of patients with autoimmune liver disease (AILD) complicated with gallbladder stone (GS), so as to guide clinical practice.Methods:From November 2009 to October 2018, at General Hospital of Tianjin Medical University, the clinical data of 386 patients with AILD were retrospectively analyzed. According to the relevant diagnostic criteria, 208 cases of autoimmune hepatitis (AIH), 129 cases of primary biliary cholangitis (PBC) and 49 cases of PBC-AIH overlap syndrome were screened out. The incidence, clinical characteristics and the changes of laboratory indicators including albumin, alkaline phosphatase (ALP) and γ-glutamyl transferase (GGT) of AILD patients complicated with GS were analyzed. Chi-square test, t test and rank sum test were performed for statistical analysis. Results:There was no significant difference in the incidence between AILD, AIH, PBC and PBC-AIH overlap syndrome patients complicated with GS (32.9%, 127/386; 28.8%, 60/208; 36.4%, 47/129 and 40.8%, 20/49; respectively; P>0.05). Gallstones of AILD patients complicated with GS mostly were multiple and small stones with maximum diameter <1 cm (45.7%, 58/127 and 57.7%, 60/104, respectively). The age of initial diagnosis, the proportion of liver cirrhosis at inital diagnosis and the levels of ALP and GGT were higher in AILD patients complicated with GS than those of AILD patients without GS ((60.5±11.5) years vs. (57.6±11.5) years; 53.5%, 68/127 vs. 42.1%, 109/259; 154.00 U/L (89.00 U/L, 257.00 U/L) vs. 125.00 U/L (86.00 U/L, 212.00 U/L); 169.00 U/L (79.00 U/L, 343.00 U/L) vs. 128.60 U/L (48.00 U/L, 284.00 U/L); respectively); however the albumin level was lower than that of AILD patients without GS ((36.46±7.30) g/L vs. (38.34±7.58) g/L), and the differences were statistically significant ( t=-2.361, χ2=4.506, Z=-2.192, -2.443, t=2.322; all P<0.05). The incidence of GS in AILD patients≥60 years old was higher than that AILD patients<60 years old (37.6%, 73/194 vs. 28.1%, 54/192), and the difference was statistically significant ( χ2=3.948, P=0.047). The incidence of GS in AILD patients and AIH patients complicated with liver cirrhosis was higher than that in patients without liver cirrhosis (38.4%, 68/177 vs. 28.2%, 59/209; 35.7%, 35/98 vs. 22.7%, 25/110; respectively), and the differences were statistically significant ( χ2=4.506 and 4.259, P=0.034 and 0.039). Conclusions:AILD patients complicated with GS are common, most are multiple and small stones. When complicated with GS, the initial diagnosis may be delayed and the rate of liver cirrhosis at initial diagnosis may increase. The incidence of GS is high in AILD patients with older age and liver cirrhosis.

Objective To construct a non-drug intervention program for acute chemotherapy-related nausea and vomiting in children with cancer and to evaluate its efficacy.Methods Through literature review and Delphi expert correspondence,a non-drug intervention program for acute chemotherapy-related nausea and vomiting in children with cancer was constructed.By the convenience sampling method,200 consecutive children who received chemotherapy in the neurosurgery department of a tertiary children's hospital in Zhejiang province from February 1 to October 31,2023 were included as the application subjects,with 100 cases in an experimental group and 100 cases in a control group.The experimental group applied the non-drug intervention program of acute chemotherapy-related nausea and vomiting in children with cancer,and the routine measures were applied in the control group.The incidence of nausea and vomiting,severity of vomiting,compliance rate of normal sleep duration and incidence of negative emotions were compared between the 2 groups.Results The recovery rate of the valid questionnaire in 2 rounds of expert letter inquiry was 100％,and the expert authority coefficient was 0.836.The Kendall harmony coefficients were 0.471 and 0.820(P＜0.001),and the final non-drug intervention program for pediatric acute chemotherapy-related nausea and vomiting included 5 primary,14 secondary and 18 tertiary items.The results showed that the incidence of nausea,vomiting and negative emotions in the experimental group were lower than that in the control group,with statistically significant differences(P＜0.05).The severity of vomiting was less than it in the control group,with statistically significant difference(P＜0.05).The standard rate of normal sleep time was higher than that of the control group,and the difference was statistically significant(all P＜0.05).Conclusion The non-drug intervention program of chemotherapy-related nausea and vomiting in children is scientific and feasible,and the implementation of the program can reduce the incidence of nausea,vomiting and negative emotions,reduce the severity of vomiting,and improve the standard rate of normal bedtime in children.