Autoimmune thyroid disease and myasthenia gravis: a study bidirectional Mendelian randomization.

Background: Previous studies have suggested a potential association between AITD and MG, but the evidence is limited and controversial, and the exact causal relationship remains uncertain. Objective: Therefore, we employed a Mendelian randomization (MR) analysis to investigate the causal relationship between AITD and MG. Methods: To explore the interplay between AITD and MG, We conducted MR studies utilizing GWAS-based summary statistics in the European ancestry. Several techniques were used to ensure the stability of the causal effect, such as random-effect inverse variance weighted, weighted median, MR-Egger regression, and MR-PRESSO. Heterogeneity was evaluated by calculating Cochran's Q value. Moreover, the presence of horizontal pleiotropy was investigated through MR-Egger regression and MR-PRESSO. Results: The IVW method indicates a causal relationship between both GD(OR 1.31,95%CI 1.08 to 1.60,P=0.005) and autoimmune hypothyroidism (OR: 1.26, 95% CI: 1.08 to 1.47, P =0.002) with MG. However, there is no association found between FT4(OR 0.88,95%CI 0.65 to 1.18,P=0.406), TPOAb(OR: 1.34, 95% CI: 0.86 to 2.07, P =0.186), TSH(OR: 0.97, 95% CI: 0.77 to 1.23, P =0.846), and MG. The reverse MR analysis reveals a causal relationship between MG and GD(OR: 1.50, 95% CI: 1.14 to 1.98, P =3.57e-3), with stable results. On the other hand, there is a significant association with autoimmune hypothyroidism(OR: 1.29, 95% CI: 1.04 to 1.59, P =0.019), but it is considered unstable due to the influence of horizontal pleiotropy (MR PRESSO Distortion Test P < 0.001). MG has a higher prevalence of TPOAb(OR: 1.84, 95% CI: 1.39 to 2.42, P =1.47e-5) positivity and may be linked to elevated TSH levels(Beta:0.08,95% CI:0.01 to 0.14,P =0.011), while there is no correlation between MG and FT4(Beta:-9.03e-3,95% CI:-0.07 to 0.05,P =0.796). Conclusion: AITD patients are more susceptible to developing MG, and MG patients also have a higher incidence of GD.

[Effect of collagen sponge on the healing process of alveolar fossa after tooth extraction in rats].

PURPOSE: To investigate the effect of collagen sponge on early bone healing process of alveolar fossa after tooth extraction in rats. METHODS: A total of 16 healthy female SD rats were selected. Animal models with tooth extraction were established. The right alveolar fossa inserted with collagen sponge was as the experimental group, and the left alveolar fossa was as the control group with treatment. The rats were sacrificed 1, 2, 4 and 8 weeks after tooth extraction, and the osteogenesis of alveolar fossa was observed. Real-time quantitative PCR (qt-PCR) was used to detect the changes of osteogenesis related gene expression. SPSS 19.0 software package was used for statistical analysis. RESULTS: After surgery, alveolar cavity healing was significantly better in the experimental group than in the control group. Osterix, Runx2 and Vegf genes were expressed in the experimental group and the control group, and the expression levels of related genes in the experimental group were significantly higher than the control group 1, 2, 4 and 8 weeks after surgery(P＜0.05). CONCLUSIONS: Collagen sponge could promote early alveolar bone healing, possibly related to the expression level of osteogenic genes regulated by collagen sponge.

Effect of Puerarin on Osteogenic Differentiation in vitro and on New Bone Formation in vivo.

Purpose: Puerarin (C21H20O10) is a phytoestrogen that possesses various pharmacological effect, and several researches have revealed the relationship between puerarin and bone metabolism. This study was aimed to evaluate the potential influence of puerarin on the proliferation and osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (BMSCs) as well as on new bone formation following rapid maxillary expansion (RME) model in rats. Methods: Rat BMSCs were adopted, and the cell proliferation was detected by cell-counting kit-8 (CCK-8) assay in vitro experiments. Alkaline phosphatase (ALP) activity and alizarin red staining were analyzed quantitatively to show extracellular matrix mineralization. The mRNA and protein expression levels were used to detect osteogenic differentiation of BMSCs. In vivo bone regeneration was analyzed in a rat RME model. Eighteen 6-week-old male Wistar rats were divided into 3 groups: group 1 without any treatment, group 2 received RME and saline solution (15mg/kg), group 3 received RME and puerarin solution (15mg/kg). After 2 weeks, micro-computed tomography (Micro-CT), hematoxylin and eosin (HE) staining, and Masson staining were used to detect the new bone formation and morphological changes. Besides, ALP and bone morphogenetic protein 2 (BMP2) expression levels in mid-palatal suture were evaluated by immunohistochemical staining. Results: The results showed that puerarin upregulates cell proliferation dose-dependently. ALP activity and mineralized matrix generation were clearly enhanced at certain specific concentrations (10-5 and 10-6 mol/L); the expression levels of the osteoblast-related genes and proteins were increased. The measurement of micro-CT imaging revealed that puerarin significantly promoted new bone formation. Concomitantly, the histological examinations showed that puerarin solution enhanced osteogenesis in mid-palatal suture. Conclusion: Those works indicated that puerarin regulates osteogenesis in vitro and exerts a beneficial impact on bone regeneration in vivo, revealing that puerarin treatment may become one of the potential keys for improving the stability and preventing relapse of RME.

Electrospun nanofibers containing chitosan-stabilized bovine serum albumin nanoparticles for bone regeneration.

Bone tissue engineering is becoming a key approach in bone repair and regeneration. In the present study, we fabricated a nanofiber scaffold containing chitosan-stabilized bovine serum albumin (BSA) nanoparticles for the delivery of abaloparatide and aspirin (ASA). The chitosan-stabilized BSA nanoparticles acted as a release barrier for the encapsulated abaloparatide. Polymeric nanofibers were produced by electrospinning from a mixture of abaloparatide-loaded nanoparticles, ASA, poly(ε-caprolactone) (PCL), and nanohydroxyapatite (n-HA). The nanoparticle and nanofiber scaffolds were characterized in terms of their morphology, construction, surface hydrophilicity, degradation, and drug release efficiency. In vitro osteogenesis as well as in vitro cell adhesion, viability, and proliferation were determined to assess their osteoinductive activity. The results showed that the drugs were successfully encapsulated in the scaffolds. Most of the ASA was released within seven days, whereas abaloparatide was released for more than 30 days. The dual-drug-loaded nanofiber scaffolds enhanced the proliferation and osteogenic differentiation of osteoblasts. These findings indicate that electrospun nanofibers containing chitosan-stabilized BSA nanoparticles may be useful in bone tissue engineering.

Analysis of Cosmetic Effect of Nanocomposite Resin on Anterior Teeth.

The problems of anterior teeth include dental plaque, dental caries, and fracture, which are usually treated with common composite resin clinically. Although good repair effect can be achieved, patients are prone to anterior tooth sensitivity after surgery. Therefore, the purpose of this study is to analyze the cosmetic effect of nanocomposite resin on anterior teeth. Up to 176 patients (176 teeth) undergoing anterior dental cosmetic restoration in our hospital were selected and assigned to the LR group (n = 88) and the NR group (n = 88) according to patients' voluntary choice of prosthetic materials. The LR group was cured with light-cured composite resin, while the NR group was cured with nanocomposite resin. By comparing the related indexes of patients in the two groups, it was discovered that in the NR group, the excellent and good rate and patients' evaluation of the repair effect were higher, while the periodontal attachment, gingival index, dental plaque index, VAS score, and the incidence of tooth sensitivity were lower, all P < 0.05. The results indicated that the nanocomposite resin had significant cosmetic effect on anterior teeth and had application value.

Correlation between PTEN gene polymorphism and oral squamous cell carcinoma.

Correlation between phosphatase and tensin homolog deleted on chromosome ten (PTEN) gene polymorphism and oral squamous cell carcinoma (OSCC) was investigated. A total of 33 OSCC patients were studied and 33 healthy individuals were included as the control group. Correlation between PTEN gene and OSCC was explored via quantitative polymerase chain reaction (qPCR), immunohistochemistry and western blot analysis. The PTEN gene polymorphism was detected via PCR-restriction fragment length polymorphism (PCR-RFLP), and its correlation with OSCC was explored. The immunohistochemical assay showed that the PTEN protein expression level significantly declined in OSCC patients (2.37±1.01 µg/l) compared with that in healthy subjects (3.09±0.95 µg/l). There was no significant difference in the rs2943773 genotype between control and experimental group (χ2=0.863, P=0.712), but there was a significant difference in the rs9651495 genotype between the two groups (P<0.05). The C/C genotype frequency of rs9651495 in OSCC patients (50.15%) was significantly higher than that in healthy subjects (23.71%) (P<0.05). The C/T genotype frequency of rs9651495 had no significant difference between the two groups (18.52 vs. 19.01%) (P>0.05). The T/T genotype frequency of rs9651495 in OSCC patients (31.33%) was obviously lower than that in healthy subjects (57.19%) (P<0.05). According to statistics, the PTEN protein expression level in patients with C/C genotype was remarkably lower than that in patients with other genotypes. There is a correlation between PTEN gene polymorphism and OSCC. Thereby, the higher C/C genotype frequency corresponds to the lower PTEN protein expression level, thus inducing OSCC.

JAK2/STAT3 is associated with the inflammatory process in periapical granuloma.

OBJECTIVE: It has been shown that JAK2/STAT3 is involved in the occurrence of various inflammatory diseases. The purpose of this study was to associate the expression of Janus kinase 2 (JAK2) and its receptor signal transducer and activator of transcription 3 (STAT3) and suppressors of cytokine signaling 3 (SOCS3), to periapical granuloma. METHODS: Samples were collected from 40 patients who were divided into two groups, namely, healthy control (N=20) and periapical granuloma (N=20) groups in accordance with classified standards. The samples were prepared for histological analysis, immunohistochemistry, and double immunofluorescence staining. RESULTS: Only slight inflammatory cell infiltration was observed in the tissues from the healthy control group. Extensive infiltration of inflammatory cells was observed in patients with chronic periapical disease. The periapical granuloma group had higher levels of JAK2, STAT3, p-JAK2, p-STAT3 and SOCS3 (all P<0.05) than the control group. Double immunofluorescence staining results showed the presence of JAK2-positive and STAT3-positive cells in the periapical lesion areas. CONCLUSIONS: This study demonstrated that JAK2, STAT3, and SOCS3 can be observed and may be associated with the inflammatory process in periapical lesions. The results of this study will provide new insights into the pathological mechanisms of human periapical granuloma.

miR-184 promotes cell proliferation in tongue squamous cell carcinoma by targeting SOX7.

The aim of this study was to investigate whether the miR-184 could regulate the proliferation of the tongue squamous cell carcinoma (TSCC) through sex-determining region Y-box 7 (SOX7) gene. miR-184 expression was upregulated in TSCC cell lines and tissues. MTT assay revealed that overexpression of miR-184 significantly promoted the proliferation of the TSCC cells in vitro. SOX7 was the direct target of miR-184 and luciferase reporter assay confirmed that miR-184 downregulated the expression of SOX7. MTT assay verified that knockdown of SOX7 remarkably promoted the proliferation of TSCC cells in vitro. miR-184 promoted the proliferation of TSCC by targeting SOX7. Taken together, our results provided a new potential therapeutic target for TSCC treatment.

[Expression and clinical significance of PUMA gene in salivary adenoid cystic carcinoma].

PURPOSE: To explore the expression of p53 up-regulated modulator of apoptosis (PUMA) gene in salivary adenoid cystic carcinoma (SACC) and its clinical significance. METHODS: The expressions of PUMA gene and protein were detected in 27 SACC tumor-adjacent tissues (group A) and 27 SACC tumor tissues (group B) with real-time quantitative PCR and Western blot. Statistical analysis was performed using SPSS 19.0 software package. RESULTS: The expression of PUMA gene in groups A as calibrator was 1，and expression of PUMA gene in group B was 0.57±0.17. The expression of PUMA protein in groups A and B were 0.94±0.12 and 0.36±0.12，respectively. The expressions of PUMA gene and protein were significantly lower in group B than in group A (P<0.05). CONCLUSIONS: The expression of puma gene in SACC tissues is down-regulated, which is negatively correlated with the development of SACC.

[The clinical value of combining multiple features of CT in discriminating between benign and malignant lung lesions].

OBJECTIVE: To develop a set of combined criteria of multiple features of chest CT for discriminating between benign and malignant lung lesions. METHODS: Patients whose chest CT showed abnormalities were recruited from the West China Hospital in March and April 2010. The patients were examined with bronchoscopy and the results of CT and pathology were compared. RESULTS: A total of 105 patients participated in this study and 85 had confirmed pathological results. The CT identified 27 cases of malignant lesions, 22 of which were confirmed by the pathology. The CT identified 58 cases of benign lesions, 55 of which were confirmed by the pathology. The set of combined criteria of multiple features of chest CT had an accuracy of 90.59%, a sensitivity of 88.00%, and a specificity of 91.67% in diagnosing benign and malignant lung lesions. CONCLUSION: The combined criteria of multiple imaging signs of CT have good clinical values for diagnosing malignant lung lesions.

Adrenal and extra-adrenal nonfunctioning composite pheochromocytoma/paraganglioma with immunohistochemical ectopic hormone expression: comparison of two cases.

Adrenal composite pheochromocytoma is rare, most of which is functional, and extra-adrenal composite paraganglioma is extremely rare. We describe and compare the clinicopathological and immunohistochemical features of a retroperitoneal extra-adrenal composite paraganglioma and an adrenal composite pheochromocytoma. Both tumors were nonfunctioning and laboratory tests revealed no biochemical abnormalities. Both tumors were composed of typical paraganglioma/pheochromocytoma closely admixed with ganglioneuroma component. In addition to typical immunohistochemical phenotypes characteristic of each component, both tumors showed focal staining of somatostatin, and the adrenal tumor was also regionally positive for insulin and prolactin. Despite this aberrant immunohistochemical expression, relevant clinical symptoms or laboratory abnormalities were absent. These tumors serve to exemplify the extremely rare occurrences of clinically silent, nonfunctioning composite pheochromocytoma or paraganglioma with aberrant expression of hormones.

Distribution and patterns of lymph nodes metastases and micrometastases in the mesorectum of rectal cancer.

BACKGROUND AND OBJECTIVES: Facts buried in the mesorectum remain to be unveiled. This study investigated the number, size, and detailed distribution of lymph nodes metastases and micrometastases within the mesorectum of rectal cancer. METHODS: Thirty-one patients who underwent total mesorectal excision (TME) were treated with lymph node revealing solution to retrieve lymph nodes, which were submitted to hematoxylin and eosin (HE) examination and immunohistochemical (IHC) staining. RESULTS: The mean number of mesorectal nodes per case was 17.7. The mean size of metastatic, micrometastatic, and isolated tumor cells (ITC) harbored nodes was 5.2 mm, 4.5 mm, and 3.3 mm, respectively. Most of the metastatic (92.1%), micrometastatic and ITC-involved nodes (69.2%) were located along the superior rectal artery (SRA). Posterior-wall located tumor might spread along both sides of the mesorectum simultaneously (P = 0.34), while lateral-wall located tumor spread preferably to ipsolateral side versus contralateral side (P = 0.012). CONCLUSION: Most of the metastases and micrometastases positive lymph nodes were smaller than 5 mm and distributed along the SRA. The patterns of lymph nodes spread were related to the circumferential situation of tumor in the rectal wall. Surgical excision of the rectal cancer should completely remove the whole mesorectum, especially to avoid any damage of the mesorectum on tumor side.

The microvascular thrombi of colonic tissue in ulcerative colitis.

Mucosal microvascular thrombi in rectal biopsies were observed in some ulcerative colitis (UC). Heparin may be effective in steroid resistant UC in some studies, however, the new results of meta-analysis demonstrated a non-significant effect of heparin in controlled clinical trials, differing markedly from observational studies. The objective of this study was to identify colonic microvascular thrombi in larger cases with UC, and analyse its possible risk factors: age, gender, histologic score, extent of lesions and operation or biopsy specimens, and assess the significance of microvascular thrombosis in patients with UC. The microvascular thrombi were identified by immunohistochemical staining with anti-CD61 monoclonal antibody and Martius scarlet blue (MSB) staining in 40 colonic tissue samples of UC (31 biopsy specimens and nine operated cases) and 12 cases of normal colon tissue from operated colonic carcinoma. Logistic regression analysis was used to assess the relationship of age, gender, degree of histology, origin of the specimens, extent of lesions and microvascular thrombi examined. Microvascular thrombi were positive in 14 of 40 UC cases, and none in the controls. The presence of microvascular thrombi was related to operation specimens with odds ratio 11.667, P=0.0179, it might be also related to histologic score (OR=1.350) and extent of lesions (OR=1.619). These results suggest that microvascular thrombosis may be one of the important pathogenesis in some UC, and that the effect of anticoagulant treatment still needs to be assessed.

[Establishment of an experimental animal model with alveolar bone defect by surgery in rats].

PURPOSE: To establish an animal model for experimental study of orthodontic treatment of alveolar bone defect and other relative research. METHODS: The experiment was carried out on forty SPF female Wistar rats,which were 6 weeks old. With the rats anaesthetized, one side of the alveolar bone in the maxillary first molar of the rats was removed partly. The defects were filled with Bio-glass. The tissue slices from the defects were observed under light microscope 2 weeks after surgery. RESULTS: Only one of the forty rats was infected after operation, and the survival rate was 97.5%. The wounds of the survived rats healed well, and new bone was found around the Bio-glass 2 weeks after operation. CONCLUSION: Animal model of alveolar bone defect established by surgery is simple and reliable, which can be used for further studies. Supported by National Natural Science Foundation of Shandong Province (Grant No.Y2004C13) and Medical Science and Technology Enhancement Award Project of Shangdong Province (Grant No.2005H2038).

[Correlation study between sex and age of patients and root resorption after orthodontic treatment].

PURPOSE: To investigate the relationship between root resorption related to fixed appliance and the variables including sex, age. METHODS: 44 patients were divided into four groups according to sex and age: juvenile males, juvenile females, adult males, adult females. The length of incisors was calculated according to orthopantomograph and study models of pre- and post-treatment, and the relationship between patients' sex and age and root absorption pre- and post-treatment was analyzed by paired t test. RESULTS: Root absorption occurred in every patient. There was no significant difference between the same-age groups of males and females (P<0.05); However, there was significant difference between adult groups (both males and females) and juvenile groups (P<0.01). CONCLUSION: Root absorption occurs in every fixed-appliance case. Fixed-appliance-caused root absorption has no significant correlation with sex;however, absorption of adult groups is of higher level than that of juvenile groups.

[Study with large slice technique and tissue microarray on lymph node involvement and micro-metastasis of rectal cancer].

OBJECTIVE: To study lymph node involvement and micro-metastasis of rectal cancer with large slice technique and tissue microarray. METHODS: Large slice technique, combined with tissue microarray,was used in pathologic study of 31 patients after total mesorectal excision (TME) for rectal cancer. RESULTS: Nine hundred and ninety- two lymph nodes were harvested and 148 were positive. More than 40% of positive lymph nodes were located in the outer layer of the mesorectum and in the same side of the mesorectum as the primary tumor was. Circumferential margin involvement was observed in 12 cases and correlated with the numbers of metastatic lymph nodes (Beta =1.166, P=0.041). Micrometastasis was found in 9 cases with negative pathological lymph nodes, but not correlated with tumor differentiation and stage (P> 0.05). CONCLUSION: Large slice technique combined with tissue microarray facilitates the detection of lymph node involvement and micrometastasis. There is a predominance of lymph node metastasis in the outer layer and the same side of the mesorectum. Micrometastasis can be discovered in different stages of rectal cancer.

[Hemangioma and vascular malformation of small intestine: a clinicopathologic analysis of fifty-one cases].

OBJECTIVE: To investigate the clinicopathologic features of small intestinal hemangioma and vascular malformation. METHODS: A retrospective analysis was performed on 51 cases of hemangioma and vascular malformation involving the duodenum, jejunum and ileum in the past 30 years. RESULTS: The patient's age ranged from 1.4 to 75.0 years, with an average/median age of 40 years for the 51 cases. The ratio of male and female was almost equal. In most cases, the lesions were located in the ileum (18 cases) and jejunum (16 cases) accounting for 66.7%. The predominant symptoms and signs were either intestinal hemorrhage or obstruction. Grossly, the lesions appeared as polyp-like, ulcerative, varices, solitary mass, diffuse infiltration or in an occult status. Histologically, arteriovenous hemangioma also called arteriovenous malformation was more common seen accounting for 86.3%. Other less common vascular lesions included cavernous hemangioma, capillary hemangioma, Rendu-Osler-Weber syndrome and Dieulafoy disease. CONCLUSIONS: Histologic classification and denomination for hemangioma and vascular malformation of small intestine are still controversial. It is very important to correlate clinical manifestations with arteriography findings in histologic diagnosis of hemanigoma and vascular malformation of the small intestine.

Mesorectal spread and micrometastasis of rectal cancer studied with large slice technique and tissue microarray.

BACKGROUND AND OBJECTIVES: Mesorectal tissue seems to be an ideal substrate for the spreading of tumors. The aim was to study the distribution of mesorectal neoplastic foci, examine occurrence of circumferential margin involvement and investigate micrometastasis of the lymph nodes. METHODS: A large slice technique, combined with tissue microarray, was used in the pathologic study of 31 specimens operated on following the principles of total mesorectal excision (TME). RESULTS: Three hundred and forty-nine mesorectal neoplastic foci were examined from 18 specimens. Almost one third of them were in the outer layer of mesorectum. Concerning position of primary tumor, ipsolateral neoplastic foci were significantly more than contralateral neoplstic foci. Twelve specimens were diagnosed to have circumferential margin involved. Nine hundred and ninety-two lymph nodes were harvested with 148 involved by tumor. No significant difference in occurrence of micrometastasis was observed among tumors of different stage. CONCLUSION: Combination of large slice and tissue microarray provided a more detailed method in studying the spread of rectal cancer. Complete excision of the mesorectum with fascia propria circumferentially intact is essential since there is an outer scattering and lateral discrepancy for neoplastic foci distribution. Circumferential margin involvement and micrometastasis observed suggested adoption of preoperative and/or postoperative radiochemotherapy.