Objective To investigate the relationship between hepatitis B virus (HBV) basic core promoter(BCP)/precore(PreC) mutations and severity of liver dis ease. Methods In 113 patients chronically infected with HBV, do uble mutations in BCP(T1762/A1764) and PreC mutation(A1896) were determined by INNO-LiPA and HB V genotype was determined by S gene sequencing. Results Whether in all patients or in patients infected by single genotype C, compared with AsC, the prevalence of double mutations in BCP(T1762/A1764) was higher in patients with CHB, LC and HCC[(24.1% vs 2.8%,? 2=5.93, P0.05). Conclusions The doubl e mutations in BCP(T1762/A1764 ) may be related to progressive liver disease in patients with chronic HBV infec tion.

Background and purpose: The position of thymidine kinase 1 (TK1) expression during cell division is in the cytoplasm. It is a catalytic enzyme to convert deoxythymidine into thymidylate. It is the key enzyme of pyrimidine salvage pathway. The aim of this study was to analyze the serum expression level of TK1 in patients with breast cancer, and explore the application of serum TK1 test in clinical assessments of diagnosis, treatment and prognosis for breast cancer. Methods: Patient data were collected from the patients admitted in Comprehensive Breast Health Center at Rui Jin Hospital. Chemiluminesence dot blot assay was used to detect serum TK1 levels in 145 breast cancer patients and 55 patients with breast ifbroadenoma. The correlations of serum TK1 levels with breast tumor biological behavior was further studied. Results:Serum TK1 expression levels was signiifcantly increased in breast cancer patients [(2.749±0.122)pmol/L] when compared to breast fibroadenoma patients[(1.319±0.126)pmol/L, P<0.000 1]. Serum TK1 levels were statistically increased in patients with lymph node metastasis (P=0.049), distal metastasis (P=0.003 1), and late TNM stages (P=0.01). No serum TK1 level differences were found in patients with different ages (P>0.05), different tumor grades (P=0.453) and different tumor size (P=0.908). Preoperative imaging results including breast ultrasound, breast mammography and breast magnetic resonance were analyzed by assessments of BI-RADS category, and serum TK1 levels in patients with different BI-RADS categories were studied. Serum TK1 levels in patients with breast ultrasound BI-RADS categories 4C-6 were signiifcantly higher than those with category 0-4B (P<0.001). Consistently, the serum TK1 levels in patients with MR BI-RADS categories 4C-6 were higher than categories 0-4B (P=0.005). The serum TK1 levels in patients with mammography BI-RADS categories 4C-6 were higher than categories 0-4B (P=0.032). The serum TK1 levels were signiifcantly increased in patients with ER high expression in breast tumor tissues than those with low expression (P=0.034). Serum TK1 levels had no differences in patients with different expression levels of PR, HER-2 and MIB-1 (P>0.05). Most patients were followed up in our outpatient department for about 2 years. No progression-free survival differences were found in 2years. Conclusion:Serum TK1 test might be a potential tool for screening, prognosis determination and effect evaluations of targeted therapy in breast carcinoma.

AIM: To study effects of urokinase-type plasminogen activator (uPA) signal transduction on expression of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-3 (TIMP-3) in giant cell tumor of bone (GCT). METHODS: Expression of uPAR, MMP-2 and TIMP-3 in GCT tissue was detected by immunohistochemistry. Phosphorylation level of mitogen-activated protein kinase (p44) in uPA/uPAR signal pathway in cultured GCT cells was detected by immunoprecipitation. The expression of MMP-2 and TIMP-3 in cultured cells after treatment with uPA-ATF or anti-uPAR antibody was also detected by Western blotting. RESULTS: 1) Urokinase-type plasminogen activator receptor (uPAR) was positive on the cell membrane and in cytoplasm of some mononuclear stromal cells (MSCs) and multinucleated giant cells (MGCs); 2) MMP-2 was positive in the cytoplasm and on the cell membrane of almost all of MSCs and some of MGCs. The polar distribution of MMP-2 in the cytoplasm of MGCs was especially obvious; 3) The expression of TIMP-3 of some MSCs and MGCs in GCT was much lower than MMP-2. The positive signal also showed a prominent polarity; 4) After treatment with uPA-ATF, the phosphorylation level of p44 in GCT cultured cells was much higher than the control. Addition of anti-uPAR antibody in the cells remarkably down-regulated the phosphorylation level of p44 as compared with the control group, suggesting that uPA-ATF participates cell signal transduction and this reaction can be inhibited by anti-uPAR antibody; 5) uPA-ATF cell signal pathway up-regulated expression of MMP-2 and TIMP-3, while anti-uPAR antibody down-regulated the expression of MMP-2 and TIMP-3. CONCLUSION: These results demonstrate for the first time that uPA-ATF directly regulates the expression of MMP-2 and TIMP-3 by signal transduction pathway, and the over-expression of MMP-2 and TIMP-3 may play an important role in local osteolysis of GCT. [

Objective To investigate the changes of serum soluble factor-related apoptosis (sFas) and soluble Fas ligand (sFasL) and their relations with cognition disorders in the patients with vascular dementia (VaD). Methods Serum concentrations of sFas and sFasl were detected by enzyme-linked immunosorbent assay (ELISA) and compared between 70 patients with VaD aged (72.5± 7.5)years and 50 healthy elderly people aged(72.5 ± 7.5)years.The VaD patient's cognitive functions were evaluated by activity of daily living scale (ADL),mini mental state examination (MMSE) and hachinski ischemia score (Hachinski). Results The serum levels of sFas and sFasL in VaD patients were (228.0±60.7)μg/L and (146.8±30.1)μg/L,and in the healthy elderly were (62.4±22.6)μg/L and (82.3 ± 18.7)μg/L,respectively.The serum levels of apoptosis factors in VaD patients were significantly higher than in the healthy controls (t=20.883,14.453,P＜0.01).sFas level was negatively correlated with age,the scores of ADL and Hachiuski while positively with the scores of MMSE (r=-0.956,-0.943,-0.950 and 0.904,all P＜0.01). sFasL level was negatively correlated with the scores of MMSE while positively with age,the scores of ADL and Hachinski (r=-0.899,0.963,0.948 and 0.939,a11 P＜0.01). Conclusions Apoptosis may be involved in the pathological change during VaD and the serum levels of sFas and sFasL might be related with cognition disorders.

AIM:To explore the effects of atorvastatin (Atorv) on atherosclerosis in streptozotocin (STZ)-in-duced diabetic apolipoprotein E knockout ( ApoE-/-) mice with fat-rich diet and the possible mechanism .METHODS:C57 mice served as control.ApoE-/-mice (n=34) fed with high-fat diet were randomly divided into ApoE-/-group, STZ-ApoE-/-group and STZ-ApoE-/-+Atorv group.Intraperitoneal injection of streptozotocin was performed to create di-abetic animal model .Blood glucose was determined by glucose oxidase method .Blood lipid levels were detected by enzymic method or selective homogeneous method .The plaque area in the thoracic aorta was measured by HE staining .The protein level of nicotinamide-adenine dinucleotide phosphate ( NADPH) oxidase subunit gp91phox in the thoracic aorta was deter-mined by Western blotting .The levels of reactive oxygen species ( ROS) in blood and thoracic aorta homogenates were de-tected by Fenton reaction and Griess reagent .Human umbilical vein endothelial cells ( HUVECs ) were isolated from healthy umbilical cords by collagenase I and cultured .ROS production was detected by flow cytometry .NADPH oxidase ac-tivity was measured using lucigenin assay .Effects of retinoid X receptor α( RXRα) on inhibition of oxidative stress by ator-vastatin were evaluated by RNA interference and plasmid transfection .RESULTS: (1) Compared with C57 group, the plaque areas of the thoracic aorta in ApoE-/-group were increased .No difference of the fasting glucose between the 2 groups was observed.The levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), thoracic aorta gp91phox protein and ROS in blood and thoracic aorta homogenates were higher in ApoE-/-group than those in C57 group.(2) Compared with ApoE-/-group, the plaque areas of the thoracic aorta in STZ-ApoE-/-group were further enlarged [(314.13 ±35.72) μm2 vs (215.88 ±34.19) μm2, P<0.05].The levels of blood glucose, TG, TC and LDL-C, thoracic aorta gp91phox protein and ROS in blood and thoracic aorta homogenates were higher in STZ-ApoE-/-group than those in ApoE-/-group (P<0.05).(3) Compared with STZ-ApoE-/-group, the plaque areas of the thoracic aorta in STZ-ApoE-/-+Atorv group were reduced [(217.47 ±24.56) μm2 vs (314.13 ±35.72) μm2, P<0.05].The levels of blood glucose , LDL-C, TC, HDL-C and TG showed no significant difference between the 2 groups.Thoracic aorta gp91phox protein level and ROS production in blood and thoracic aorta homogenates were lower in STZ -ApoE-/-+Atorv group than those in STZ-ApoE-/-group (P<0.05).(4) High glucose-induced increases in NADPH oxidase activity and gp91phox expression were significantly inhibited by atorvastatin (10-6 mol/L) in HUVECs.The inhibitory effects of atorvasta-tin on high glucose-induced ROS production and NADPH oxidase activation were largely impaired when the cells were trans -fected with RXRαsiRNA.However , the effect of atorvastatin was significantly strengthened when RXRαwas over-expressed in the HUVECs transfected with RXRαplasmid.CONCLUSION: Atorvastatin inhibits atherogenesis by depressing high glucose-induced oxidative stress in diabetic ApoE-/-mice with fat-rich diet.The anti-oxidative stress effect of atorvastatin is mediated by RXRα.

Objective To explore the effect of retinoid X receptor (RXR) agonist bexarotene on atherosclerosis and the potential mechanism in streptozotocin (STZ) induced diabetic apolipoprotein E knockout (apoE-/-) mice.Methods Eight C57BL/6 mice served as control,46 apoE-/-mice were randomized into 4 groups:apoE-/-group (n =10),STZ + apoE-/-group (n =12),STZ + apoE-/-+ Bex 10 (10 mg · kg-1 · d-1)group (n=12),STZ+ apoE-/-+Bex 30 (30 mg · kg-1 · d-1)group (n=12).Diabetic apoE-/-animal model was established by intraperitoneal injection of STZ.Blood glucose was determined by glucose oxidase method.Patch area in thoracic aorta was measured by HE staining.Western blotting was used to determine the RXR and gp91 phox protein level in thoracic aorta.Reactive oxygen species (ROS) level in blood and thoracic aorta homogenates was detected by Fenton and Griess method.Results (1) Patch areas of thoracic aorta were larger in apoE-/-group than in C57BL/6 group[(38.40 ± 8.95) μm2 vs.(0.10 ±0.01) μm2,P ＜0.01],further increased in STZ + apoE-/-group [(94.06 ± 8.04) μm2,P ＜0.05 vs.apoE-/-group] and significantly reduced in STZ + apoE-/-+ Bex 10 group [(78.72 ± 4.62)μm2,P ＜0.05 vs.STZ + apoE-/-group] and further educed in STZ + apoE-/-+ Bex 30 group[(46.13 ±7.56) μm2,P ＜ 0.05 vs.STZ + apoE-/-+ Bex 10 group].(2) Blood glucose level,TG,TC,LDL-C,thoracic aorta gp91 phox protein level and ROS level in blood and thoracic aorta homogenates were significantly higher in STZ + apoE-/-group than in apoE-/-group (all P ＜ 0.05).Blood glucose level and TG,TC,LDL-C levels were similar between STZ + apoE-/-+ Bex10 and STZ + apoE-/-group.Thoracic aorta gp91 phox protein level and ROS level in blood and thoracic aorta homogenates were lower in STZ + apoE-/-+ Bex 10 group than in STZ + apoE-/-group (P ＜ 0.05).Blood glucose level,TG,TC,LDL-C levels,gp91 phox expression in thoracic aorta,ROS level in blood and thoracic in STZ + apoE-/-+ Bex 30 group were lower than in STZ + apoE-/-group (all P ＜ 0.05).Conclusion Bexarotene treatment could attenuate arteriosclerosis progression in STZ induced diabetic apoE-/-mice,the underlying mechanism might be related to suppressing oxidative stress and decreasing blood glucose level and improving lipids metabolism.

[Objective] To evaluate the clinical efficacy and safety of different chemotherapeutic regimens combined with sintilimab as first-line treatment for Her-2 negative advanced gastric cancer. [Methods] We retrospectively collected the clinical data of patients with Her-2 negative advanced gastric cancer treated with albumin-bound paclitaxel plus S-1 combined with sintilimab (n=40) and oxaliplatin plus S-1 combined with sintilimab (n=36) at The Affiliated Hospital of Xuzhou Medical University from September 1, 2021 to July 1, 2023. The clinical efficacy and adverse reactions were evaluated separately in patients treated with albumin-bound paclitaxel plus S-1 combined with sintilimab and in those treated with oxaliplatin plus S-1 combined with sintilimab. Factor analysis was made on two sets of clinical data separately. [Results] The objective response rate (ORR) of albumin-bound paclitaxel group and oxaliplatin group was 57.5% and 52.8%, respectively. The disease control rate (DCR) of albumin-bound paclitaxel group and oxaliplatin group was 85.0% and 80.6%, respectively. The median progression-free survival (PFS) of patients in albumin-bound paclitaxel group and oxaliplatin group was 8.3 months and 9.0 months. The incidence of adverse reactions in albumin-bound paclitaxe group was 87.5% (35/40), and that in the oxaliplatin group was 91.7% (33/36). Factor analysis of the clinical data of albumin-bound paclitaxel group and oxaliplatin group revealed that liver metastasis was an independent risk factor for PFS. [Conclusion] Both albumin-bound paclitaxel combined with S-1 and sintilimab, and oxaliplatin combined with S-1 and sintilimab show promising efficacy and manageable side effects when used as first-line treatment for Her-2 negative advanced gastric cancer.

Objective: The purpose is to investigate the validity of a surgical technique that utilizes autologous costal cartilage grafts in primary rhinoplasty for female patients. Methods: From July 2015 to July 2017, 137 cases received primary rhinoplasty with various types of grafts originated from autologous costal cartilage to correct the unpleasant nasal appearances including low dorsum, poorly defined nasal tip and wide alar base. Results: With 6 to 36 months follow-up, six patients(4.3%) exhibited noticeable changes in nasal contour due to graft warping. Revision surgeries were commenced to correct those minor deformities, resulting in satisfactory outcome.All other cases presented significant improvements of the nasal appearance. Conclusions Autologous costal cartilage is a good source for primary rhinoplasty cases.

Objective:To investigate the validity of a simple technique of drilling nasal spine in costal cartilage based rhinoplasty.Methods:From August 2018 to October 2020, the clinical data of patients whom received costal cartilage rhinoplasty in Plastic Surgery Hospital of Chinese Academy of Medical Sciences were retrospectively analyzed. During the operation, the towel clamp was slid into the space of the nasal spine, with minor adjustments of its position, slowly and steadily, the towel clamps were tightened until the bilateral tips were met, and the perforation procedure was successful. Then, based on this aperture, the columellar strut was firmly fixed to the nasal spine, and the cartilage framework was established. Postoperative follow-up was conducted to investigate the satisfaction of the patients, as well as a third-party plastic surgeon was introduced to evaluate the pre-and post-operative photos of the patients by the observer’s overall cosmetic improvement score (IGAIS).Results:A total of 35 female patients with the age of (27.7±2.3) years (22-37 years old) were included. All patients presented low tip and dorsum, with flat, flaring alae. There were no significant short-term complications such as infection, mucosal perforation and graft exposure. The patients were followed up for 6 to 24 months. Two cases presented cartilage warping, and was corrected after revision surgery. The appearance of the nose was significantly improved, and the subjective satisfaction was 97.1% (34/35). The third-party physician evaluation results were: in 35 cases, 33 cases achieved significant improvement, 2 cases achieved moderate improvement, 100% (35/35) of the patients reached the improvement, and the improvement score was 1.08±0.28.Conclusions:The drilling technique of utilizing a towel forcep is simple and practical which facilitates stable fixation of nasal columellar support graft, and renders a good outcome in the clinical application of autologous costal cartilage rhinoplasty.

Objective:To introduce a new method of lateral nasal osteotomy. The key of this method is to fully dissect the tissue around the piriform foramen to achieve nasal osteotomy under direct vision. The osteotomy line in the whole process can be seen, which provides a more reliable control for the degree of osteotomy during the operation, and also makes the postoperative outcome more predictable.Methods:Patients whom were treated with open external osteotomy combined with autologous costal cartilage implantation for augmentation rhinoplasty (with 24 cases of hump nose correction) from October 2018 to October 2020. During the surgery, the whole nasal dorsum was exposed, the superior lateral cartilage was separated from the nasal septum, and the whole process was carried out through the mucosa from the intranasal approach under direct view. The osteotomy line was evaluated at the same time.Results:A total of 33 female patients were retrospectively analyzed. All the operations were successful, and the local swelling occurred after operation. The follow-up time was 3-18 months. After 3 months, the nasal contour and dorsal curves were smooth. Severe infections, major injuries like nasolacrimal duct, lacrimal sac, medial canthus ligament, nerve branches were not noticed in all patients. During the long-term follow-up, two patients exhibited slightly widened nasal bone, but did not require surgical intervention. The shape of nose was greatly improved. Patients were satisfied with the result . The subjective evaluation had "very satisfactory" in 24 cases (72.7%) and "satisfactory" in 9 cases (27.3%). The IGAIS evaluation were also positive: the average score of 33 patients was 1.26±0.34, including 30 cases (90.9%) scoring 1 point and 3 cases (9.1%) scoring 2 points.Conclusions:The open osteotomy technique has better control than that of conventional blind operation. It is more reliable, safer for the surgeons who are new to rhinoplasty and the experienced ones.