Osteonecrosis of the mandible is also called avascular necrosis of the jaw, and it is a rare complication of bisphosphonates. It is characterized with pain, swelling, exposure of bone, local infection and pathologic fractures of the jaw. With the widespread usage of bisphosphonates in bone metastasis of malignant tumors and osteoporosis, this rare complication has received more attention in recent years. Here, we reported a case of bisphosphonates-related osteonecrosis of the jaw (BRONJ) caused by intravenous zoledronic acid for osteoporosis. A 62-year-old female patient with 7-year history of Sjögren's syndrome and 3-year history of osteoporosis developed BRONJ after 3-year treatment of zoledronic acid. Two months before she went to the Peking University International Hospital, she visited the dentist for periodontal purulent secretion and extracted one tooth from the right mandible. However, the condition was not improved and she felt persistent pain and swelling in the right mandible. Hence, she received repeated root curettage, but there was no improvement. Finally, she was diagnosed with osteonecrosis of the mandible based on the digital volume tomography scan, which showed right mandibular osteonecrosis bone destruction. She underwent surgical debridement of the necrotic bone and administered intravenous antibio-tics at the Peking University International Hospital. Histopathological analysis of the bone biopsy further confirmed the diagnosis of BRONJ. Her condition was improved successfully during a 3-year follow-up. Osteonecrosis of the mandible become more common with the increased use of bisphosphonates. Recent study has reported that osteonecrosis of the mandible is more likely to occur in patients with Sjögren's syndrome. In addition, age, long-term and irregular administration of glucocorticoids, irregular oral examination and treatment also might be the risk factors in the pathogenesis of osteonecrosis of the mandible. For the elder osteoporosis patients who would receive or had received bisphosphonate-related drugs, oral health status and the disease states associated with necrosis of the mandible such as Sjögren's syndrome should be comprehensively measured and fully evaluated during the whole process. Furthermore, to better understand and prevent or reduce the occurrence of this complication, we reviewed the patho-genesis, diagnosis, treatment, and prevention of BRONJ.
Humans ; Female ; Middle Aged ; Bisphosphonate-Associated Osteonecrosis of the Jaw/etiology* ; Diphosphonates/administration & dosage* ; Zoledronic Acid ; Imidazoles/administration & dosage* ; Bone Density Conservation Agents/adverse effects* ; Osteoporosis/drug therapy*

OBJECTIVE: To investigate the serum level of lumican (LUM) and its clinical correlation with disease and immune activities in patients with rheumatoid arthritis (RA). METHODS: The serum LUM levels in both RA patients and health controls (HCs) were detected by enzyme-linked immunosorbent assay (ELISA). The clinical and laboratory data of the patients were collected. The LUM levels in the patients with different clinical features were analyzed. The correlation between the clinical data, laboratory parameters, and serum LUM levels were also analyzed. Independent samples t test, Spearman correlation were used for statistical analysis. Analysis of variance and Kruskal-Wallis test, the least significant difference (LSD)-t test and Bonferroni correction were used for statistical analysis. The Pearson Chi-square test was used for comparison of the rates between the groups. Statistical significance was set at P < 0.05. RESULTS: The levels of LUM were elevated in the RA patients than in the HCs (P < 0.000 1). Serum LUM levels were correlated with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), immunoglobulin A (IgA), titers of platelet (PLT) and 28-joint disease activity score (DAS28, all P < 0.05). Next, we compared the serum LUM levels in the RA patients with different characteristics, and no difference was found in serum LUM levels between early-RA and RA, the same to RA with different gender (P>0.05). The levels of serum LUM were elevated in the RF positive patients (P < 0.000 1), and in the RF and anti-CCP positive patients (P < 0.05) than in the RA patients with negative RF whether the anti-CCP was positive. In addition, no differences were found between the RA patients with negative RF whether the anti-CCP was positive (P>0.05). All the levels of serum LUM were elevated in the RA patients with different CRP or ESR than in the HCs (P < 0.05), and the serum LUM levels in the RA patients with elevated ESR and CRP were significantly elevated in those with normal ESR and CRP (P < 0.05). Additionally, the results demonstrated that serum LUM levels were positively associated with RA disease activity, and they were declined in RA sustained remission than those in middle or high disease activity (P < 0.05). Furthermore, no difference was found between the RA patients in remission and HCs (P>0.05). No differences were found in the RA patients with and without complications including interstitial pneumonia disease, Sjögren's syndrome, thyroid gland diseases and osteoporosis (P>0.05). The LUM positivity rates were significantly elevated in the RF positive patients than the RF negative patients in RA (P < 0.05). CONCLUSION LUM, a cyclocitrullinated protein, might be a promising biomarker which could reflect both disease activity and immune activity in RA.
Humans ; Arthritis, Rheumatoid/immunology* ; Lumican/blood* ; C-Reactive Protein/metabolism* ; Female ; Male ; Rheumatoid Factor/blood* ; Middle Aged ; Adult ; Chondroitin Sulfate Proteoglycans/blood* ; Blood Sedimentation ; Keratan Sulfate/blood* ; Enzyme-Linked Immunosorbent Assay ; Aged

Oral erythema is a rare and potentially malignant disease of oral mucosa with a high tendency to cancer.Traditional surgery is difficult to remove the lesion while preserving the beauty and function of the affected area.Erbium laser is widely used in the treatment of oral diseases and has certain advantages in the treatment of oral erythema.This paper reports a case of excision of large area of oral erythema with erbium laser fractional treatment.

The development, progression, and curative efficacy of head and neck squamous cell carcinoma (HNSCC) are influenced by complex interactions between epithelial and immune cells. Nevertheless, the specific changes in the nature of these interactions and their underlying molecular mechanisms in HNSCC are not yet fully understood. Cuproptosis, a form of programmed cell death that is dependent on copper, has been implicated in cancer pathogenesis. However, the understanding of cuproptosis in the context of HNSCC remains limited. In this study, we have discovered that cuproptosis-related long non-coding RNAs (CRLs) known as JPX play a role in promoting the expression of the oncogene urokinase-type plasminogen activator (PLAU) by competitively binding to miR-193b-3p in HNSCC. The increased activity of the JPX/miR-193b-3p/PLAU axis in malignant epithelial cells leads to enhanced cell proliferation, migration, and invasion in HNSCC. Moreover, the overexpression of PLAU in tumor epithelial cells facilitates its interaction with the receptor PLAUR, predominantly expressed on macrophages, thereby influencing the abnormal epithelial-immune interactome in HNSCC. Notably, the JPX inhibitor Axitinib and the PLAU inhibitor Palbociclib may not only exert their effects on the JPX/miR-193b-3p/PLAU axis that impacts the malignant tumor behaviors and the epithelial-immune cell interactions but also exhibit synergistic effects in terms of suppressing tumor cell growth and arresting cell cycle by targeting epidermal growth factor receptor (EGFR) and cyclin-dependent kinase (CDK4/6) for the treatment of HNSCC.
Humans ; MicroRNAs/metabolism* ; RNA, Long Noncoding/metabolism* ; Head and Neck Neoplasms/metabolism* ; Cell Proliferation ; Squamous Cell Carcinoma of Head and Neck/genetics* ; Urokinase-Type Plasminogen Activator/genetics* ; Cell Movement ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Carcinoma, Squamous Cell/genetics* ; Neoplasm Invasiveness

Shunt-dependent hydrocephalus (SDHC) is a common and serious complication of aneurismal subarachnoid hemorrhage (aSAH). The incidence of SDHC after aSAH was 9%-36%, and it is associated with the poor outcome of patients. This article reviews the predictors and prediction scores of SDHC after aSAH.

Objective To explore the feasibility and clinical effect of laparoscopic radical cystectomy with intracorporeal Xing's orthotopic neobladder.Methods Forty-one patients who underwent laparoscopic radical cystectomy with intracorporeal Xing's orthotopic neobladder from July 2013 to August 2019.There were 31 cases performed in Beijing Chaoyang hospital and 10 cases in National Cancer Center.Mean age was 59 (range 44-78) years,mean BMI was 25.3 (range 20.1-34.7) kg/m2,and mean CCI was 3 (range 2-6).No urethral stricture or urinary incontinence was found by preoperative examination.No distant metastasis was identified by bone scans,chest X-ray and sonography.Cystoscopy or TURBT was performed on all patients and biopsy was taken to confirm the diagnosis.Preoperative pathology showed 30 cases (73.2％) of MIBC,9 cases of NMIBC (22.0％) and 2 cases (4.9％) of in-situ cancer.Laparoscopic radical cystectomy and lymphadenectomy were performed under general anesthesia.Urinary diversion was completed in the peritoneal cavity,by intercepting the terminal ileum about 60 cm,and taking the proximal ileum 10 cm as input loop on the right side with proximal to distal way,and the middle 40 cm ileum was detubated.After u-shaped suture,the ileum was folded back and stitched into a sphere building a novd orthotopic neobladder with bilateral isoperistaltic afferent limbs.The prognosis of perioperative data and postoperative satisfaction regarding continence were analyzed,continence was defined as 0-1 pad/day.The 41 patients were divided into two groups to compare the difference in term of operation time and blood loss between the first 21 patients and the last 20 patients.Results Mean total operative time was 324.9 mins (range 210-480) mins,and mean estimated blood loss was 177.6(range 50-700) ml.There were significant statistical differences in term of total operation time,construction time and blood loss between the first 21 patients and the next 20 patients (P ＜ 0.05).Postoperative pathological results were urothelial carcinoma in 40 cases (2 in situ carcinoma) and small cell carcinoma in 1 case.Mean number of dissected lymph nodes was 19 (range 11-58),with 7 cases(17.1％)of positive lymph nodes,and 3 cases(7.3％) had positive surgical margin.At a mean follow up of 17.6 (range 2-64) months,36 patients (87.8％) survived,including 2 patients (4.9％) with metastasis and 1 patient (2.4％) with recurrence,and 5 cases (12.2％)died.All patients were able to urinate without catheterization.Thirty-seven patients (90.2％) were satisfied with voiding control during the daytime (0-1 urinal pad),and 29 patients (70.7％) were satisfied with voiding control at nighttime (0-1 urinal pad) by the follow-up 12 months after the operation.Conclusions Total laparoscopic radical cystectomy combined with Xing's orthotopic ileum neobladder is a simple method with fewer postoperative complications and a satisfactory continence rate.

Objective To investigate the expression of Smad4 in gastric carcinoma and its relationship with clinicopathological characteristics. Methods Immunohistochemistry method was used to detect the expression of Smad4 in 85 gastric carcinoma tissue and 36 normal gastric mucosa from January 2014 to December 2016. Results (1)The positive expression rate of Smad4 in gastric carcinoma tissues was 35. 29% (30/ 85), which was significantly lower than that in normal gastric mucosa (91. 67% (33/ 36)),and the difference was statistically significant (χ2=32. 201,P<0. 001). (2) The expression of Smad4 was correlated with the depth ofinvasion(χ2=13. 626,P<0. 001),lymph nodes metastasis(χ2=7. 267,P=0. 007),TNM staging(χ2=18. 226,P<0. 001) and tumor differentiation level (χ2 = 9. 134, P= 0. 010) . ( 3) Multivariate unconditional logistic regression analysis showed that depth of invasion(OR=7. 892,95CI 1. 649-37. 790,P=0. 010),TNM staging ( OR=15. 042, 95CI 0. 026-0. 977, P=0. 005 ) and tumor differentiation level ( OR=15. 042, 95CI2. 292-98. 751, P = 0. 005 ) may be independent influencing factors for Smad4 expression in gastric carcinoma. Conclusion Smad4 may performed an important role during the progression of gastric carcinoma and may be a new biological marker of gastric carcinoma.

BACKGROUND:Hemiarthroplasty is a proven method for reconstruction of the hip joint function, especialy for the elderly patients who cannot tolerate the total hip arthroplasty. However, for the patients with osteoporosis, there are stil more controversial in clinical practice about using cemented or cementless femoral prosthesis for hemiarthroplasty. OBJECTIVE: To observe the repair effect of cemented or cementless femoral prosthesis when were used for hemiarthroplasty in patients with osteoporosis. METHODS:The clinical data from 105 patients treated with hemiarthroplasty were retrospectively analyzed. Osteoporosis was diagnosed in these patients using the dual energy X-ray absorptiometry before surgery.Patients were divided into bone cement group (n=56) and cementless group (n=49) depending on different types of femoral stem prosthesis. The difference of efficacy between cemented or cementless femoral prosthesis when were used for hemiarthroplasty in patients with osteoporosis was analyzed by comparing the operative time, volume of drainage, post-operative Harris scores of hip joint function and radiographic assessment (prosthesis subsidence, osteolysis, severe stress shielding, heterotopic ossification) during the folow-up after the replacement. RESULTS AND CONCLUSION:In the process of hemiarthroplasty in patients with osteoporosis, the operative time in the cement group was significantly longer than that in the cementless group (P < 0.05). However, there was no significant difference in the postoperative volume of drainage between these two groups (P > 0.05). At the 1, 3, 6 and 12 of folow-up after replacement, there were no significant differences in the Harris score of hip joint function, total effective rate and radiographic assessment between these two groups (P> 0.05). These results suggest that in the process of hemiarthroplasty in patients with osteoporosis, the clinical efficacy of cementless femoral prosthesis is similar to the cement femoral prosthesis, therefore two prostheses can al be selected; however, the operative time of the cement femoral prosthesis is longer than the cementless femoral prosthesis, so we can give priority to the cementless femoral prosthesis for patients with osteoporosis who can’t tolerate a long operative time because of the poor basic condition.

Although methyltransferase has been recognized as a major element that governs the epigenetic regulation of the genome during temozolomide (TMZ) chemotherapy in glioblastoma multiforme (GBM) patients, its regulatory effect on glioblastoma chemoresistance has not been well defined. This study investigated whether DNA methyltransferase (DNMT) expression was associated with TMZ sensitivity in glioma cells and elucidated the underlying mechanism. DNMT expression was analyzed by western blotting. miR-20a promoter methylation was evaluated by methylation-specific PCR. Cell viability and apoptosis were assessed using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and TdT-mediated dUTP-biotin nick end labeling assays, respectively. The results showed that compared with parental U251 cells, DNMT1 expression was downregulated, miR-20a promoter methylation was attenuated and miR-20a levels were elevated in TMZ-resistant U251 cells. Methyltransferase inhibition by 5-aza-2\'-deoxycytidine treatment reduced TMZ sensitivity in U251 cells. In U251/TM cells, DNMT1 expression was negatively correlated with miR-20a expression and positively correlated with TMZ sensitivity and leucine-rich repeats and immunoglobulin-like domains 1 expression; these effects were reversed by changes in miR-20a expression. DNMT1 overexpression induced an increase in U251/TM cell apoptosis that was inhibited by the miR-20a mimic, whereas DNMT1 silencing attenuated U251/TM cell apoptosis in a manner that was abrogated by miR-20a inhibitor treatment. Tumor growth of the U251/TM xenograft was inhibited by pcDNA-DNMT1 pretreatment and boosted by DNMT1-small hairpin RNA pretreatment. In summary, DNMT1 mediated chemosensitivity by reducing methylation of the microRNA-20a promoter in glioma cells.
Animals ; Antineoplastic Agents, Alkylating/*pharmacology/therapeutic use ; Apoptosis/drug effects ; Brain/drug effects/metabolism/pathology ; Brain Neoplasms/drug therapy/*genetics/pathology ; DNA (Cytosine-5-)-Methyltransferase/antagonists & inhibitors/*genetics/metabolism ; DNA Methylation ; Dacarbazine/*analogs & derivatives/pharmacology/therapeutic use ; Drug Resistance, Neoplasm ; Female ; Gene Expression Regulation, Neoplastic ; Glioma/drug therapy/*genetics/pathology ; Humans ; Mice, Inbred C57BL ; MicroRNAs/*genetics ; Promoter Regions, Genetic

Objective To compare the effects of different doses of FTY720 on inhibiting expression of Caspase-3 and neural apoptosisin rats with acute spinal cord injury (SCI), and find out the suitable dose. Methods 200 female SD rats were randomly divided into 5 groupswith 40 in each group. Group A (laminectomy but not contusion) were administered 0.3 ml normal saline by gavage. SCI model was establishedby Allen's WD method at the T9 level of spinal cord in other groups. Group B were administered 0.3 ml normal saline after modeling.Groups C, D and E were administered 0.3 ml FTY720- saline solution of 1, 3 and 5 mg/kg respectively. All the groups were sacrificed at 6 h,12 h, 24 h, 48 h, 72 h (n=8, per each time-point). Caspase-3 expression was detected with streptavidin-peroxidase immunohistochemistry,and neural apoptosis was detected with the TUNEL method. Results Positive Caspase-3 expression and neural apoptosis were not observedin Group A at 6 h. In Groups B、C、D and E, the number of apoptotic cells increased with increased time of acute SCI, peaked at 24 h afterinjury, and then gradually reduced. Caspase-3 expression was at equal pace with neural apoptosis. The difference of the number of apoptoticand Caspase-3 expression cells among all groups were significant, with the order Group B>Group C>Group D>Group A (P<0.05). However,there was no significant difference between Group D and Group E (P>0.05). The number of apoptotic and Caspase-3 expression cells negativelycorrelated with the dose of FTY720 when the dose was less than 3 mg/kg (P<0.05), and there was no relationship when the dose wasmore than 3 mg/kg (P>0.05). Conclusion FTY720 significantly reduces Caspase-3 expression and neural apoptosis in rats with acute SCI.There is a dose-effect relationship between the dose of FTY720 and the Caspase-3 expression and neural apoptosis. It's indicated that 3 mg/kg is the most appropriate dosage.