BACKGROUND:The pathogenesis of osteoporosis is complex,and its essence is the weakening of bone formation and the enhancement of bone absorption caused by various reasons,resulting in the imbalance of bone metabolism.In recent years,N6-methyladenosine has been found(N6-methyladenosine,m6A)methylation can prevent and treat osteoporosis by regulating bone metabolism. OBJECTIVE:Taking the regulation of bone metabolism by m6A methylation as an entry point,to systematically sort out and summarize the research progress of m6A methylation in osteoporosis,so as to provide certain theoretical reference bases for the search of new therapeutic targets for osteoporosis. METHODS:CNKI,WanFang,VIP,PubMed,MEDLINE,Nature,and Cochrane databases were retrieved for relevant literature published from database inception to 2023.The keywords were"osteoporosis,m6A methylation,bone metabolism,bone marrow mesenchymal stem cells,osteoblasts,osteoclasts"in Chinese and English.Duplicates and obsolete non-referenced documents were excluded,and a total of 73 standard papers were included for further review. RESULTS AND CONCLUSION:m6A methylation can affect the activity and differentiation of bone marrow mesenchymal stem cells,osteoblasts,and osteoclasts through various pathways to regulate bone metabolism and prevent osteoporosis.The regulatory process of m6A methylation is extremely complex,and its related proteins play different roles in different cells.Even in the same kind of cells,the same type of proteins may have radically different roles,regulating different physiological and pathological processes.

Objective To preliminarily analyze the influencing factors of benign thyroid nodule malignant transformation and provide a basis for early intervention of benign thyroid nodule malignant transformation. Methods Selected 158 patients with benign thyroid nodules who visited our hospital from January 2019 to January 2022 for inclusion in the study, and followed up for 3 year to observe whether the nodules had malignant changes. The age, gender and dietary habits were collected. 3 mL of fasting venous blood of subject were collected , and the level of TT3, TT4, FT3, FT4, TSH, TgAb, CEA, thyroglobulin and calcitonin were collected. Results The results of this study suggest that the plasma levels of serum TgAb, TSH, TT4, TT3, FT3, FT4, CEA, thyroglobulin, and calcitonin of subjects were not statistically significant between sexes. The results of univariate analysis showed that compared with non malignant group, the patients in malignant nodule group were younger, the longest diameter of nodule was smaller, TgAb level was higher, TSH level was higher, FT3 level was lower, the proportion of internal calcification was higher, thyroglobulin level was higher, CEA level was higher, calcitonin level was higher, and the proportion of abnormal lipid metabolism and glucose metabolism was also higher, which was statistically significant (P<0.05). Multivariate logistic regression analysis showed that TgAb positive, internal calcification, increased carcinoembryonic antigen level, dyslipidemia, elevated thyroglobulin level, and abnormal glucose metabolism, elevated calcitonin level were associated with the increased risk of node canceration, and increased total FT3 level was associated with the reduced risk of canceration (P<0.05). Conclusion TgAb positive, internal calcification, increased carcinoembryonic antigen level, small nodule diameter, abnormal blood lipids, elevated thyroglobulin level, low total FT3 level, abnormal glucose metabolism, and elevated calcitonin level are associated with the increased risk of malignant transformation of benign thyroid nodules, which should be paid attention to clinically.

Purpose To investigate the clinicopathological characteristics,diagnosis,and differential diagnosis of invasive mucinous adenocarcinoma(IMA)and mixed invasive mucinous and non-mucinous adenocarcinoma(mIMA).Methods The clinical data were collected in 36 patients with primary IMA and 17 patients with mIMA,and the expression of TTF-1,CK7,CK20,SATB2,CDX2,EGFR,HNF4a,etc.was detected by immunohistochemical EnVision two-step method.The Sanger se-quencing and the FISH were used for KRAS mutation and NRG1 gene rearrangement detection.The clinicopathological character-istics were analyzed with review of relevant literature.Results There were 9 cases(25.0％)and 3(8.3％)cases of papillary and micropapillary structures in IMA,while 13 cases(76.5％)(P＜0.001)and 9 cases(52.9％)(P=0.001)were present in mIMA.There were 5 cases(13.9％)of high nuclear grade of IMA and 10 cases(58.8％)of high nuclear grade of mIMA(P=0.002).TTF-1 had a positive rate of 37.5％in IMA,but 60.0％and 80.0％in the mucinous adenocarcinoma and non-mucinous adenocarcinoma components of mIMA(P=0.021),respectively.The positive rates of CK7,CK20,and CDX2 in IMA were 90.6％,21.9％,and 9.4％,and the positive rates in mucinous adenocarcinoma and non-mucinous adenocarcinoma components of mIMA were 100％,20％,20％and 100％,6.7％,6.7％,respectively and no SATB2 expression was found in all cases.There was no significant difference in the expres-sion of total EGFR and two EGFR mutation-specific antibodies(L858R,DEL19)between IMA and mIMA.There were 3 cases of mucinous adenocarcinoma with L858R positive in mIMA,and 2 of them were negative for non-mueinous adenocarcinoma.In another case,the non-mueinous adenocarcinoma component of mIMA expressed DEL19,but the mucinous adenocarcinoma component was not expressed.The positive rate of HNF4a in IMA was 72.0％(18/25),and those of HNF4a in mucinous adenocarcinoma and non-mucinous adenocarcinoma in mIMA were 41.7％(5/12)and 33.3％(4/12),respectively(P=0.048).KRAS gene sequencing was carried out in 19 cases of IMA,among which 9 cases(47.4％)had mutations,G12D and G12V were most commonly detected,and 4 cases of mIMA were sequenced,but none of them showed KRAS mutations.FISH detection showed that 2 cases(7.1％)IMAs had NRG1 translocation rearrangement.Conclusion Pulmonary mIMA is more aggressive than IMA.For example,mIMA has significantly more papillary structure,micropapillary structure,and high nu-clear grade cases than IMA.The differences in immunohisto-chemical expression and KRAS mutation between the two are sta-tistically significant.

Humans ; Pyoderma Gangrenosum ; Myeloproliferative Disorders ; Neoplasms

Objective:To investigate the clinical significance of vertebral body partition in the unipedicular percutaneous vertebroplasty (PVP) for osteoporotic vertebral fractures.Methods:From July 2019 to October 2021, 89 patients with osteoporotic vertebral fracture were treated by unipedicular PVP at Department of Spinal Surgery, Zhengzhou Orthopaedic Hospital. They were 37 males and 52 females, with a mean age of (70.5±4.8) years (from 60 to 80 years). According to the vertebral body partition, the patients were divided into group a (32 cases), group b (20 cases), group c (21 cases), group d (11 cases), group e (0 case) and group f (5 cases). The therapeutic effects were evaluated by comparing the improvement rates of visual analogue scale (VAS) and Oswestry disability index (ODI) between preoperation and postoperative 1-day among all partition groups. The imaging efficacy was evaluated by comparing the proportions of bone cement diffusion area in the posteroanterior and lateral DR films and the leakage of bone cement among all partition groups.Results:The improvement rates of VAS score between preoperation and postoperation: group a [77.8 (75.0, 82.5) %] > group b [71.4 (71.4, 71.4) %] > group c [66.7 (66.7, 66.7) %] > group d [60.0 (60.0, 62.5) %] > group f [57.1 (50.0, 57.1)%], showing a statistically significant difference between any 2 groups ( P<0.001). The improvement rates of ODI score: group a (58.0%±4.2%) > group b (47.5%±2.5%) > group c (42.9%±2.9%) > group d (39.6%±3.2%) > group f (34.2%±8.4%), showing a statistically significant difference between any 2 groups ( P<0.001). The proportions of bone cement diffusion area: group a (76.9%±3.5%) > group b (71.3%±3.1%) > group c (66.1%±3.6%) > group d (60.2%±2.6%) > group f (54.0%±4.2%), showing a statistically significant difference between any 2 groups ( P<0.001). Bone cement leakage occurred in 7 cases, including 3 ones of anterior vertebral leakage (1 case in group a and 2 cases in group b), and 4 ones of leakage into the paravertebral venous plexus (2 cases in group c and 2 cases in group d). There was no intraspinal leakage, or symptoms of nerve compression or lesion. Conclusion:In the unipedicular PVP for osteoporotic vertebral fractures, our vertebral body partition can guide puncturing for bone cement injection because it indicates the optimal and the risky partitions.

Background/Aims: Epstein-Barr virus-associated gastric cancers (EBVaGCs) have unique molecular and clinicopathological characteristics. The cyclic GMP-AMP synthase-stimulator of interferon genes (STING) pathway is recently recognized as the critical innate immunity against pathogens and tumors. STING is also a master regulator in the cancer-immunity cycle and targeting STING could synergize with existing immune-checkpoint therapies. However, the role of STING in GC, especially in EBVaGC, and its correlation with programmed death-ligand 1 (PD-L1) remain largely unclear. Methods: We collected 78 cases of EBVaGCs and 210 cases of EBV-negative GC (EBVnGC) from a total of 1,443 cases of GC analyzed by EBV-encoded small RNA in situ hybridization. We investigated STING and PD-L1 expression and their concomitant prognostic value in EBVaGCs and EBVnGCs using tissue microarray and immunohistochemistry. The effects of STING and PD-L1 expression on the overall survival of patients with EBVaGC or EBVnGC were assessed by univariate and multivariate analysis. Results: We found that both STING and PD-L1 exhibited significantly higher expression in the EBVaGCs than that in the EBVnGCs. The expression of STING was positively correlated with that of PD-L1 in EBVaGCs. Simultaneous negative expression of STING and PD-L1, and positive expression of STING were independent prognostic risk factors for EBVaGC and EBVnGC, respectively. Conclusions This is the first prognostic retrospective study of STING and PD-L1 expression and the prognosis among EBVaGC and EBVnGC. The expression and prognostic value of STING and PD-L1 are different in the two types of GCs. STING and PD-L1 are promising prognostic biomarkers and therapeutic targets for EBVaGC and EBVnGC.

Objective:To study the variation in activity in patient′s body with differentiated thyroid cancer (DTC) treated with 131I and external dose level, analyze the relationship between the both, and estimate the correction factor for the dose equivalent rate for the patients with residual activity of 400 MBq. Methods:A total of 43 DTC patients who received 131I therapy for the first time after total thyroidectomy were studied. The dose was 1 850-3 700 MBq and average dose was (2 405±777) MBq. The measurements of residual activity in patient′s body and of dose equivalent rate at 0.3, 1 and 3 m in front of the patients were performed at 2, 6, 20, 22, 24, 27, 30, 44, 46, 48, 54, 68 and 72 h after administration of 131I. Results:The residual activity in patient′s body after 131I therapy varied with time as a function of A= A0 (1.033 16e -0.062 4t+ 0.017 17). It can be estimated that the effective half-life of DTC patients treated with thyroid remnant 131I ablation therapy is 12.19 h. It needs only 26.4-38.9 h to reduce the internal activity to the 400 MBq. The functions of variation with time of normalized dose equivalent rate at 0.3, 1, and 3 m away from patients were: H· 0.3=127.220 7e -0.054 8t+ 3.765 71; H· 1=30.225 8e -0.064 4t+ 0.824 67; and H· 3=4.161 9e -0.061 5t+ 0.167 97, respectively. There was a positive correlation between residual activity and dose equivalent rate at 1 m ( r=0.982, P<0.05), and the function is H· 1=0.025 A+ 1.245. When residual activities in DTC patient′s body were 1 000, 700 and 400 MBq, the corresponding dose equivalent rates at 1 m from patients were 26.2, 18.7 and 11.2 μSv/h, respectively. The correction factors for dose equivalent rate at 0.3, 1 and 3 m from patients with 400 MBq were 0.25, 0.49 and 0.70, respectively. Conclusions:DTC patients with administration of 131I activity below 3 700 MBq need only to be hospitalized for two days to reach the discharge standards. When the residual activity in DTC patient′s body drops to 400 MBq, the dose equivalent rate at 1 m is far less than 25 μSv/h. Simply using the point source formula to estimate the dose equivalent rate around the patient will result in overestimation. Therefore, the correction factor used in the estimation of radiation doses to patients by using the formula needs to be further studied so as to make the model-based estimated result more consistent with the actual situation.

PURPOSE: This study was aimed to investigate the role of poly(A)-binding protein-interacting protein 1 (Paip1) in cervical carcinogenesis. MATERIALS AND METHODS: The expression of Paip1 in normal cervical epithelial tissues and cervical cancer (CC) tissues were detected by immunohistochemistry. In vivo and in vitro assays were performed to validate effect of Paip1 on CC progression. RESULTS: Paip1 was found to be up-regulated in CC, which was linked with shorter survival. Knockdown of Paip1 inhibited cell growth, induced apoptosis and cell cycle arrest in CC cells, whereas its overexpression reversed these effects. The in vivo tumor model confirmed the pro-tumor role of Paip1 in CC growth. CONCLUSION: Altogether, the investigation demonstrated the clinical significance of Paip1 expression, which prompted that the up-regulated of Paip1 can presumably be a potential prognostic and progression marker for CC.
Apoptosis ; Carcinogenesis ; Cell Cycle ; Cell Cycle Checkpoints ; Immunohistochemistry ; In Vitro Techniques ; Prognosis ; Uterine Cervical Neoplasms

Objective: To investigation HER2 status in gastric adenocarcinoma of Chinese and contributing factors to the HER2 expression. Methods: HER2 status of 40 842 gastric adenocarcinomas and clinical data were retrospectively collected from 23 hospitals dated from 2013 to 2016. The association between HER2 positivity and clinicopathologic features was analyzed. Results: Of the 40 842 patients the median age was 62 years, the male female ratio was 2.6∶1.0. The rate of HER2 positivity was 8.8% (3 577/40 842). HER2 expression was related to the tissue type, tumor location, Lauren classification and tumor differentiation (P values: 0.009, 0.001, <0.01 and <0.01, respectively). Different HER2 expression status was observed between primary and recurrent tumors in 7.6% (48/635) cases. The rates of HER2 positivity ranged from 2% to 10% among different institutions. The rates of HER2 FISH amplification were dramatically different among the 23 hospitals (0-100%) with an average rate of 10% (810/8 156) in patients with HER2 IHC 2+ . Conclusions HER2 expression is associated with clinicopathologic characteristics. HER2 re-assessment of tumor tissue and use of in situ hybridization techniques increase HER2 positivity. The current retrospective study should reflect the HER2 status in gastric adenocarcinoma of Chinese patients.

Objective To analyze the features of diagnosis, treatment and prognosis of primary renal neuroendocrine tumors, and to improve the understanding of primary renal neuroendocrine tumors. Methods From January 2008 to June 2015, 5 cases of primary renal neuroendocrine tumors were hospitalized and their data was analyzed retrospectively, with 1 male 4 females, aged 40-73 years with the middle age of 48 years.Tumors were all located in the left kidney, whose diameters arranged from 4 to 9 cm, with an average of 6.5cm.One case presented with hematuria, one case was identified because of abdominal pain, and the other three cases were identified via physical examination.Four cases underwent a renal contrast-enhanced ultrasound, which indicated a medium-hypoechoic mass in three cases and a hyperechoic mass in one case.All five cases underwent CT scan, presenting irregularly shape and density. Calcification was found in three cases on plain scanning.Significantly heterogeneous enhancement was found in three cases and moderate heterogeneous enhancement was found in one case on enhanced scanning. Results All five cases underwent operations, with two cases undergoing radical nephrectomy and three cases undergoing partial nephrectomy.Pathological examination showed three cases of tumor cells arranged in a nest slug or ribbon-like infiltrative growth, with no or rare mitosis and no necrosis, which is consistent with renal carcinoids.Three out of 4 renal hilar lymph nodes containing tumor cells were identified in one case. The tumor cells in another case exhibited a ribbon-like arrangement, with some round nuclei, no significant atypia, and rare mitosis, which is consistent with renal atypical carcinoid.Two out of two renal hilar lymph nodes containing tumor cells were identified in this case. The tumor tissue of one case showed morphologically uniform, medium-sized cells arranged in nest slug form with necrosis, a high nuclear cytoplasm ratio, an obvious allotype and frequent mitosis, which is consistent with renal small cell carcinoma.The immunohistochemistry of the five cases indicated synaptophysin( Syn) and chromogranin A ( CgA) positive in varying degree.One case of renal carcinoid relapsed approximately 78 months after partial nephrectomy, following with radical surgery.The other two cases were followed up for 8 or 27 months and no recurrence or metastasis was detected.One case of renal atypical carcinoid was followed up for 4 months after radical nephrectomy and no recurrence or metastasis was detected.One case of renal small cell carcinoma died of multiple organ failure 11 months after radical nephrectomy plus hepatic metastatic carcinoma radio-frequency ablation approximately.Conclusions Primary renal neuroendocrine tumors are rare clinically. Renal neuroendocrine tumors may be expressed as carcinoid, atypical carcinoid or small cell carcinoma, and the clinical manifestations, pathological characteristics and prognosis varied.Primary renal carcinoids may be treated by surgery with a nice prognosis.Patients with primary renal small cell carcinoma require comprehensive treatment, and their prognosis is poor.