MicroRNA-182 inhibits osteogenic differentiation of bone marrow mesenchymal stem cells by targeting Smad1.

The present study aimed to screen abnormally expressed microRNAs (miRs/miRNAs) in patients with postmenopausal osteoporosis (POP) and explore their mechanisms via functional verification. Bone marrow mesenchymal stem cells (BMSCs) were extracted from healthy controls and patients with POP. Differences in osteogenic differentiation and proliferation of human BMSCs were compared between the two groups using Cell Counting Kit-8 (CCK-8) assay and alizarin red staining. A rat model of POP was established. Compared with patients with POP, human BMSCs in healthy controls had significantly enhanced viability at 24, 36, 48 and 72 h. The results of alizarin red staining revealed that the deposition of calcium minerals in human BMSCs were significantly lower in patients with POP. Based on miRNA microarray and reverse transcription-quantitative polymerase chain reaction (PCR) results, the expression levels of miR-7010 and miR-467c decreased, while miR-132 and miR-182 expression increased in the human BMSCs of patients with POP. Alizarin red staining showed that miR-182 markedly suppressed the osteogenic differentiation of primary rat BMSCs in rats. Western blotting and immunofluorescence assay revealed that miR-182 inhibited the expression of osteogenesis markers runt-related transcription factor 2, osterix and actinin-associated LIM protein. The results of the luciferase reporter assay showed that Smad1 is the direct target of miR-182. In rat primary BMSCs, Smad1 overexpression abolished the inhibitory effect of miR-182 on osteogenesis, indicating that miR-182 inhibits osteogenic differentiation of primary rat BMSCs in rats by targeting Smad1. Finally, in vivo experimental results showed that the biomechanical characteristics of bone tissues in POP rats were significantly enhanced by miR-182 inhibition, while they were significantly weakened by miR-182 overexpression. MiR-182 inhibits osteogenic differentiation of rat BMSCs, thus aggravating POP in rats.

The Knife's Edge of Tolerance: Inducing Stable Multilineage Mixed Chimerism but With a Significant Risk of CMV Reactivation and Disease in Rhesus Macaques.

Although stable mixed-hematopoietic chimerism induces robust immune tolerance to solid organ allografts in mice, the translation of this strategy to large animal models and to patients has been challenging. We have previously shown that in MHC-matched nonhuman primates (NHPs), a busulfan plus combined belatacept and anti-CD154-based regimen could induce long-lived myeloid chimerism, but without T cell chimerism. In that setting, donor chimerism was eventually rejected, and tolerance to skin allografts was not achieved. Here, we describe an adaptation of this strategy, with the addition of low-dose total body irradiation to our conditioning regimen. This strategy has successfully induced multilineage hematopoietic chimerism in MHC-matched transplants that was stable for as long as 24 months posttransplant, the entire length of analysis. High-level T cell chimerism was achieved and associated with significant donor-specific prolongation of skin graft acceptance. However, we also observed significant infectious toxicities, prominently including cytomegalovirus (CMV) reactivation and end-organ disease in the setting of functional defects in anti-CMV T cell immunity. These results underscore the significant benefits that multilineage chimerism-induction approaches may represent to transplant patients as well as the inherent risks, and they emphasize the precision with which a clinically successful regimen will need to be formulated and then validated in NHP models.

Follow-up observational study of "bi-ring method" breast surgery for treating hypermastia and mastoptosis.

PURPOSE: This study investigated the efficacy and patient satisfaction of "bi-ring method" breast surgery in 46 patients with hypermastia and/or mastoptosis. MATERIALS AND METHODS: A questionnaire survey, objective data measurements, visual analysis system survey, and various scoring scales were used to qualitatively and quantitatively assess the patients' indicators before and after surgery. RESULTS: Statistical analysis showed the following: symptoms and signs in patients with macromastia improved significantly; all patients' breast shapes improved significantly and became more symmetrical and durable; all patients had minor hidden scars; the nipples and areolas had good feeling postoperatively, and there were relatively few mild complications. CONCLUSIONS: The patients' overall satisfaction was high, indicating that the "bi-ring method" of breast plastic surgery could not only improve the breast shape and boast concealed scars but could significantly improve the patients' signs and symptoms of hypermastia, but the nipples and areolas had good postoperative feeling and there were few complications. Thus, this is a reasonable surgical approach that is worthy of promotion.

Secondary ear reconstruction based on the Nagata method after unsatisfactory microtia surgery outcomes.

BACKGROUND: Follow-up studies on auricular reconstruction procedures have reported postoperative complications; some of which can only be reversed with revision surgery. This study aims to provide a feasible surgical strategy based on the Nagata method for patients requiring secondary revision and verify mid-term aesthetic outcomes. METHODS: Secondary auricular reconstructions based on the Nagata method were performed on seven patients seeking secondary revision between 2017 and 2021. Scores of a five-point Likert scale and artificial intelligence ratings based on convolutional nerve networks were used as outcome measures. RESULTS: Five patients underwent complete two-stage ear reconstruction, and the other two patients underwent the first-stage microtia procedure only. Few complications were observed, except in Case 4; this patient required an additional minor surgery after frame exposure 6 weeks after the first-stage procedure. All revised ears showed clear anatomical structures, and all patients were satisfied with the aesthetic results. Statistical analysis showed a significant increase in postoperative versus preoperative scores by convolutional neural network models (p < 0.05). Cases 5 and 6, which involved projection surgeries only, had decreased artificial intelligence appearance scores postoperatively. CONCLUSION: After adequate preoperative evaluation, secondary auricle reconstruction based on the Nagata method can achieve reliable aesthetic outcomes with few complications. CLINICAL TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov ID: NCT05604456.

Distribution of human leukocyte antigen alleles and haplotypes in Oroqen and Ewenki nationality minority in Inner Mongolia Autonomous Region of China.

The frequencies of the human leukocyte antigen alleles HLA-A,-B, DRB1 and the A-B, A-DRB1, B-DRB1, A-B-DRB1 haplotypes were investigated through means of PCR-based reverse line-strip sequence specific oligonucleotide hybridization on 108 Oroqen and 104 Ewenki nationality unrelated healthy individuals from the Inner Mongolia Autonomous Region of China. A total of thirteen different HLA-A alleles, 21 different HLA-B alleles and 13 different HLA-DRB1 alleles were detected in the Oroqen ethnic group and the most frequent HLA alleles found were A*24(35.65%), B*15(17.92%), and DRB1*09(17.59%), respectively. The common HLA-A-B-DRB1 haplotypes were A*24-B*40-DRB1*09(5.09%), A*24-B*48-DRB1*12(2.78%) and A*24-B*51-DRB1*04(2.78%); and the HLA-A*33-B*58, A*30-B*13, A*01-B*37, A*33-DRB1*03, A*01-DRB1*10, A*30-DRB1*07, B*37-DRB1*10, B*58-DRB1*03, B*38-DRB1*08, B*13-DRB1*07 were significant positive linkage disequilibrium in the Oroqen nationality group. In total, 14 different HLA-A alleles, 27 B alleles and 12 DRB1 alleles were found in Ewenki nationality group, and the most frequent HLA alleles found were A*24(24.49%), B*40(17.35%), and DRB1*04(14.80%), respectively. The common HLA-A-B-DRB1 haplotypes were A*33-B*58-DRB1*03(6.25%), A*01-B*51-DRB1*11(2.88%) and A*24-B*40-DRB1*09(2.88%); the HLA-A*33-B*58, A*29-B*44, A*03-B*52, A*33-DRB1*03, A*29-DRB1*07, A*24-DRB1*09, B*58-DRB1*03, B*08-DRB1*03, B*46-DRB1*09 were significant positive linkage disequilibrium in Ewenki nationality group. The distribution of HLA A,-B, DRB1, alleles haplotypes frequencies and phylogenetic tree indicated that the Oroqen and Ewenki population groups belongs to northern group of China, together as a group cluster.

MicroRNA-1266 suppresses papillary thyroid carcinoma cell metastasis and growth via targeting FGFR2.

OBJECTIVE: To explore the effects of microRNA-1266 (miR-1266) on metastasis and growth in papillary thyroid carcinoma cells and to provide therapeutic targets for papillary thyroid carcinoma. PATIENTS AND METHODS: By quantitative Real-time polymerase chain reaction (PCR), miR-1266 expression level in 38 pairs of papillary thyroid carcinoma tissues and three breast cancer-derived cell lines was examined. After transfection with miR-1266 mimics, the effects of miR-1266 over-expression on cell proliferation, invasion and migration were analyzed. Further, we employed several databases for the target gene prediction. Dual-luciferase activity assay was performed to verify whether FGFR2 was the direct target gene of miR-1266. Western blotting was conducted to detect protein levels. RESULTS: MiR-1266 was significantly downregulated in papillary thyroid carcinoma tissue samples and cell lines. Over-expression of miR-1266 in papillary thyroid carcinoma cells significantly attenuated the cell proliferation, invasion, and migration. Dual-luciferase report assay and Western blotting confirmed that FGFR2 was a target gene of miR-1266. Furthermore, up-regulation of FGFR2 partially reversed the suppressive effects of miR-1266 over-expression on cell growth and progression. CONCLUSIONS: miR-1266 could inhibit cell proliferation and progression of papillary thyroid carcinoma via targeting FGFR2. Our findings might provide a new target for the diagnosis and treatment of papillary thyroid carcinoma.

Hyperphosphorylation of protein Tau in hippocampus may cause cognitive dysfunction of propofol-anesthetized rats.

OBJECTIVE: We aimed to explore the effect of hyperphosphorylation of Tau on cognitive function of propofol-anesthetized rats. MATERIALS AND METHODS: Thirty 2-month-old male Wistar rats weighing 180-220 g were randomly divided into 3 groups (n=10): group of treating with saline (C group), group of treating with propofol for 1 hour (P1) and 24 h (P24 group). The cognitive function of rats was tested by Morris water maze before and 1 h or 24 h after drug administration. The rats were then sacrificed. The protein and mRNA expression levels of GSK-3ß, total and phosphorylated Tau, cyclin D1, p27kip1 and c-caspase 3 in hippocampus were determined by Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. RESULTS: Compared with group C, the incubation period of P1 group and P24 group was prolonged, and the target quadrant retention time was shortened (p<0.05). There was no statistical difference between P1 and P24 group (p>0.05). Immunohistochemistry showed that compared with group C, p-Tau in hippocampus of P1 group and P24 group was highly expressed, with statistical difference (p<0.05). Western blot and RT-PCR showed that protein and mRNA expressions of GSK-3ß, phosphorylated Tau, cyclin D1 and c-caspase 3 in hippocampus of P1 and P24 groups were up-regulated (p<0.05). CONCLUSIONS: Propofol-induced cognitive dysfunction in rats may be related to the hyperphosphorylation of Tau that causes neuronal cells to re-enter the cell cycle, thus leading to apoptosis.

Has-MiR-196a-2 is up-regulated and acts as an independent unfavorable prognostic factor in thyroid carcinoma.

OBJECTIVE: To identify the role of hsa-miR-196a-2 in thyroid cancer by bioinformatics analysis. MATERIALS AND METHODS: The expression profiles of thyroid cancer was download from TCGA. The dysregulated microRNAs were obtained by edger R package. Then, the prognostic data were analyzed by K-M plot. The difference between different groups was analyzed by the t-test. At last, the biological processes of has-miR-196a-2 were obtained with GSEA. RESULTS: In this study, we found that has-miR-196a-2 was upregulated in thyroid carcinoma by analyzing the TCGA database, which was inversely proportional to the prognosis of patients with thyroid carcinoma. Univariate and multivariate COX analysis showed that has-miR-196a-2 was an independent prognostic risk factor for thyroid carcinoma. Higher expressions of has-miR-196a-2 were found in patients with older age, advanced tumor stage, lymph node metastasis, and local infiltration through the t-test. We found that has-miR-196a-2 was enriched in adherent junction, focal adhesion, and actin cytoskeleton, which are closely related to the invasion and migration of the function pathway. Moreover, it is mainly enriched in tumor progression pathways, such as the PPAR pathway and WNT pathway. CONCLUSIONS: Hsa-miR-196a-2 is overexpressed in thyroid tumors and is an independent prognostic risk factor for thyroid carcinoma.

[Genetic polymorphisms of 9 STR loci in Achang ethnic group in Yunnan Province].

Blood samples were collected from the unreleatled individuals in the Achang ethnic group in Yunnan Province. Genetic distribution for nine STR loci and amelogenin locus were determined in Achang ethnic group based on GeneScan. 96 samples were denatured of gel electrophoresis. The databanks in Achang ethnic group were generated by using GeneScan, genotyper, and genetic distribution analysis. 69 alleses and 166 genotypers were observed, with the corresponding frequency being 0.0050-0.6100 and 0.0100-0.3900. The average H is 0.7381. The comulated DP is 0.9999999. The comulated EPP is 0.9999989. The allele distribution of the loci was in good agreement with the Handy-Weibeng equilibrium. It is useful to establishing DNA databanks for studying gene natural resources, very valuable in the study of forensic science, anthropology and ethnic.

[STR polymorphisms in five Chinese ethnic groups(2)].

Population genetic studies were performed in Chinese Han, Hui, Mongolian, Tibetan and Uygur. Allele frequency distributions were analyzed for ten loci, i.e., D3S1358, VWA, CSF1PO, FGA, THO1, TPOX, D5S818, D13S317 and D7S820 by GeneScan. The results showed that there were 60 STR alleles and 149 genotypes in Han; 63 STR alleles and 144 genotypes in Hui; 69 STR alleles and 173 genotypes in Mongolian; 77 STR alleles and 168 genotypes in Tibetan; 70 STR alleles and 148 genotypes in Uygur. Significant differences were identified among ethnic groups (African-American, US-Caucasian and Chinese-Oriental), but similarity was found among the five Chinese populations, and immunogenomics and pharmacogenomics studied in this report. These findings indicated that the nine STR loci and amelogenin locus were very useful for individual identification in forensic science.

[An epidemiological survey of goiter caused by excessive iodine in potable water in Cangzhou region].

This article describes a relationship between iodine and function and shape of thyroid gland. There was positive correlation between the prevalence rate of goiter and iodine content in drinking water [ln (10x)] and urine [ln (5x)]. Their curve fitting regression equations were y = 36.36 - 10.94 x + 0.83x2 and y = 22.39 - 6.36 x + 0.48x2 respectively. Use 3 per cent as criterion of disease area, threshold upper limit value of water and urinary iodine content should be 400 micrograms/L and 890 micrograms/gCr respectively.

Koro epidemics in Guangdong, China. A questionnaire survey.

Koro epidemics, characterized by panic due to fear of genital retraction, involving more than 2000 victims, mainly young men, occurred in Hainan Island and Leizhou Peninsula of Guangdong Province, China, in 1984-85 and 1987. A questionnaire survey of 214 victims of these epidemics was conducted in 1988. The survey focused on symptom manifestation, personality profile, life problems, and folk belief. The results of the "koro" group were compared with those of a "clinic" group with minor psychiatric disorder and a "control" group from the non-clinical, non-koro episode population in the epidemic area. The results revealed that the victims of the koro epidemics were characterized by low intellectual endowment and strong acceptance of koro-related folk beliefs. The results support the hypotheses that: a) a koro attack is a psychologically induced anxiety-panic condition; b) the presence of an intensive belief in the culturally related concept of koro makes the subject vulnerable to the attack; and c) social crisis or tension serves as a trigger for the occurrence of the epidemic.