The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs (lncRNAs). However, the dynamics of lncRNA expression during human tooth development remain poorly understood. In this research, we examined the lncRNAs present in the dental epithelium (DE) and dental mesenchyme (DM) at the late bud, cap, and early bell stages of human fetal tooth development through bulk RNA sequencing. Developmental regulators co-expressed with neighboring lncRNAs were significantly enriched in odontogenesis. Specific lncRNAs expressed in the DE and DM, such as PANCR, MIR205HG, DLX6-AS1, and DNM3OS, were identified through a combination of bulk RNA sequencing and single-cell analysis. Further subcluster analysis revealed lncRNAs specifically expressed in important regions of the tooth germ, such as the inner enamel epithelium and coronal dental papilla (CDP). Functionally, we demonstrated that CDP-specific DLX6-AS1 enhanced odontoblastic differentiation in human tooth germ mesenchymal cells and dental pulp stem cells. These findings suggest that lncRNAs could serve as valuable cell markers for tooth development and potential therapeutic targets for tooth regeneration.
Humans ; RNA, Long Noncoding/metabolism* ; Odontogenesis/genetics* ; Tooth Germ/embryology* ; Cell Differentiation ; Gene Expression Regulation, Developmental ; Mesoderm/metabolism* ; Tooth/embryology* ; Gene Expression Profiling ; Sequence Analysis, RNA ; Dental Pulp/cytology*

Inducing the degradation of KRAS represents a novel strategy to combat cancers with KRAS mutation. In this study, we identify ubiquitin-specific protease 2 (USP2) as a novel deubiquitinating enzyme of KRAS in multiple myeloma (MM). Specifically, we demonstrate that gambogic acid (GA) forms a covalent bond with the cysteine 284 residue of USP2 through an allosteric pocket, inhibiting its deubiquitinating activity. Inactivation or knockdown of USP2 leads to the degradation of KRAS, resulting in the suppression of MM cell proliferation in vitro and in vivo. Conversely, overexpressing USP2 stabilizes KRAS and partially abrogates GA-induced apoptosis in MM cells. Furthermore, elevated USP2 levels may be associated with poorer prognoses in MM patients. These findings highlight the potential of the USP2/KRAS axis as a therapeutic target in MM, suggesting that strategically inducing KRAS degradation via USP2 inhibition could be a promising approach for treating cancers with KRAS mutations.

Objective:To evaluate the value of combined measurement of urinary insulin-like growth factor-binding protein 7 (IGFBP7) and urinary metalloproteinase inhibitor-2 (TIMP-2) in the early diagnosis and prognosis of cardiac surgery-associated acute kidney injury (CSA-AKI).Methods:From March 2018 to June 2018, cardiac surgery patients admitted to the cardiac macrovascular surgery department of the First Affiliated Hospital of Nanjing Medical University were prospectively included, and the blood creatinine was monitored to observe the presence of acute kidney injury (AKI). The prognostic information of the patients was collected, including in-hospital dialysis, in-hospital death, complete recovery of kidney function at discharge, death in one year after surgery, and progression to chronic kidney disease. The levels of urine IGFBP7 and TIMP-2 at 6 h, 24 h and 48 h after cardiac surgery were detected by enzyme linked immunosorbent assay (ELISA), and the urine creatinine (Cr) was also measured. Moreover, receiver operating characteristic curves (ROC) were plotted and the areas under the curves ( AUC) were calculated to evaluate the predictive value and prognostic value of urinary [TIMP-2]·[IGFBP7] (T*I for short) and urine T*I/urine Cr 2 in CSA-AKI. Results:A total of 74 patients with age of (58.43±10.91) years old and 47 males, were enrolled in this study, of which 24 cases (32.4%) had AKI and 10 cases (13.5%) had stage 2-3 AKI. Compared with the non-AKI group, the AKI group had significantly higher levels of urine T*I levels at 6 h and 24 h (both P<0.05). The AUC of T*I at 24 h predicting for AKI was 0.71(95% CI 0.59-0.81, P=0.001, cutoff value 0.020, sensitivity 79.2%, specificity 56.0%), while the AUC for stage 2-3 AKI was 0.85 (95% CI 0.75-0.92, P<0.001, cutoff value 0.083, sensitivity 70.0%, specificity 90.6%). Urinary T*I normalized for urinary creatinine excretion did not show better predictive value. In addition, of T*I at 24 h predicting for poor hospitalization outcome, renal recovery, and one year postoperative death, the AUC was 0.82(95% CI 0.71-0.90, P=0.001), 0.80(95% CI 0.66-0.86, P<0.001), and 0.81(95% CI 0.70-0.89, P=0.047), respectively. Conclusion:The combined detection of TIMP-2 and IGFBP7 in urine is expected to be a biomarker for early diagnosis of CSA-AKI and has certain clinical value in predicting the prognosis of CSA-AKI.

Objective To examine whether the marginal division of the striatum(MrD)is involved in the associative learning and memory function of human brain with the help of functional magnetic resonance imaging(fMRI)technique.Methods Sixteen right-handed normal volunteers participated in a test of paired-word associative learning and memory,while the fMRI data were recorded.Control tasks were performed for the block-design.Statistcs parameter mapping 99 was used to analyze the data and to obtain the activated brain regions.Results When the threshold was set as P＜0.005.using a one-sample T-test,the left occipital lobe and the superior and middle gyrus of the left frontal lobe were activated remarkably during the encoding process of the paired-word associative learning and memory task,with the maximum intensity T value being 13.87 and 9.36.respectively.The left MrD was also obviously activated during this stage(T value was 5.46).But during the retrieval process,the left parietal lobe was prominently activated(T value was 8.73).Conclusion The resuhs of this study reveal that the subcortical structures such as MrD as well as the cerebral cortex are involved in the associative learning and memory of paired-word in human brain.

BACKGROUNDThe mini-invasive surgery is now performed widely and these operations have been used in complete resection of lung cancer. The aim of this study is to summarize the results and to explore practicability of bronchial sleeve resection and reconstruction of pulmonary artery by video-assisted thoracic small incision surgery for lung neoplasms.

METHODSA total of 109 patients were retrospectively reviewed, who underwent sleeve lobectomy and bronchoplasty by video-assisted thoracic small incision surgery for lung neoplasms from January 1995 to December 2005.

RESULTSOperations were performed successfully for all the patients. The small incisions' length ranged from 3 to 15 cm and the mean length was 10 cm. The surgical time was 125-180 min and the mean was 150 min; blood loss was 210-450 mL and the mean was 320 mL. There was no operative mortality, occurrence of anastomosis stenosis and fistula. Follow-up results showed that there was no sign of re-perfusion hurt and no edema in remaining lobes. There was no blood transfusion in 80.7% of cases (88/109), no shoulder hurt in 94.5% of cases (103/109). The stay in hospital was 7-15 days, and the average was 9 days.

CONCLUSIONSThe bronchial sleeve resection and reconstruction of pulmonary artery by video-assisted thoracic small incision surgery for lung cancer could finish the same work as traditional thoracic lateral incision, with less trauma, less bleeding and blood transfusion, less time in opening and closing thorax.

The paper sums up the experience of Tianjin in conducting mass QC group activities for the past 12 years. The major steps taken include:(1)enhancing the awareness of the importance of and willingness to conduct QC group activities; (2)stepping up personnel training, improving their general quality and giving them correct guidance; (3)taking pains to organize and manage QC group activities; and (4)working hard to assess and release the results of QC groups. Persistent conduction of mass QC group activities has led to a higher QC level of the hospital and better delivered services to patients.