Digital guided therapy (DGT) has been advocated as a contemporary computer-aided technique for treating endodontic diseases in recent decades. The concept of DGT for endodontic diseases is categorized into static guided endodontics (SGE), necessitating a meticulously designed template, and dynamic guided endodontics (DGE), which utilizes an optical triangulation tracking system. Based on cone-beam computed tomography (CBCT) images superimposed with or without oral scan (OS) data, a virtual template is crafted through software and subsequently translated into a 3-dimensional (3D) printing for SGE, while the system guides the drilling path with a real-time navigation in DGE. DGT was reported to resolve a series of challenging endodontic cases, including teeth with pulp obliteration, teeth with anatomical abnormalities, teeth requiring retreatment, posterior teeth needing endodontic microsurgery, and tooth autotransplantation. Case reports and basic researches all demonstrate that DGT stand as a precise, time-saving, and minimally invasive approach in contrast to conventional freehand method. This expert consensus mainly introduces the case selection, general workflow, evaluation, and impact factor of DGT, which could provide an alternative working strategy in endodontic treatment.
Humans ; Consensus ; Endodontics/methods* ; Tooth ; Printing, Three-Dimensional ; Dental Care ; Cone-Beam Computed Tomography ; Root Canal Therapy

Currently the main treatment of acute myeloid leukemia (AML) is chemotherapy combining hematopoietic stem cell transplantation. However, the unbearable side effect of chemotherapy and the high risk of life-threatening infections and disease relapse following hematopoietic stem cell transplantation restrict its application in clinical practice. Thus, there is an urgent need to develop alternative therapeutic tactics with significant efficacy and attenuated adverse effects. Here, we revealed that umbilical cord-derived mesenchymal stem cells (UC-MSC) efficiently induced AML cell differentiation by shuttling the neutrophil elastase (NE)-packaged extracellular vesicles (EVs) into AML cells. Interestingly, the generation and release of NE-packaged EVs could be dramatically increased by vitamin D receptor (VDR) activation in UC-MSC. Chemical activation of VDR by using its agonist 1α,25-dihydroxyvitamin D3 efficiently enhanced the pro-differentiation capacity of UC-MSC and then alleviated malignant burden in AML mouse model. Based on these discoveries, to evade the risk of hypercalcemia, we synthetized and identified sw-22, a novel non-steroidal VDR agonist, which exerted a synergistic pro-differentiation function with UC-MSC on mitigating the progress of AML. Collectively, our findings provided a non-gene editing MSC-based therapeutic regimen to overcome the differentiation blockade in AML.

Humans ; Neoplasms, Second Primary/epidemiology* ; Neoplasms/epidemiology* ; Risk Factors ; Prognosis

A fundamental challenge that arises in biomedicine is the need to characterize compounds in a relevant cellular context in order to reveal potential on-target or off-target effects. Recently, the fast accumulation of gene transcriptional profiling data provides us an unprecedented opportunity to explore the protein targets of chemical compounds from the perspective of cell transcriptomics and RNA biology. Here, we propose a novel Siamese spectral-based graph convolutional network (SSGCN) model for inferring the protein targets of chemical compounds from gene transcriptional profiles. Although the gene signature of a compound perturbation only provides indirect clues of the interacting targets, and the biological networks under different experiment conditions further complicate the situation, the SSGCN model was successfully trained to learn from known compound-target pairs by uncovering the hidden correlations between compound perturbation profiles and gene knockdown profiles. On a benchmark set and a large time-split validation dataset, the model achieved higher target inference accuracy as compared to previous methods such as Connectivity Map. Further experimental validations of prediction results highlight the practical usefulness of SSGCN in either inferring the interacting targets of compound, or reversely, in finding novel inhibitors of a given target of interest.
Drug Delivery Systems ; Proteins ; Transcriptome

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Metastasis is crucial for the mortality of non-small cell lung carcinoma (NSCLC) patients. The epithelial-mesenchymal transition (EMT) plays a critical role in regulating tumor metastasis. Glioma-associated oncogene 1 (Gli1) is aberrantly active in a series of tumor tissues. However, the molecular regulatory relationships between Gli1 and NSCLC metastasis have not yet been identified. Herein, we reported Gli1 promoted NSCLC metastasis. High Gli1 expression was associated with poor survival of NSCLC patients. Ectopic expression of Gli1 in low metastatic A549 and NCI-H460 cells enhanced their migration, invasion abilities and facilitated EMT process, whereas knock-down of Gli1 in high metastatic NCI-H1299 and NCI-H1703 cells showed an opposite effect. Notably, Gli1 overexpression accelerated the lung and liver metastasis of NSCLC in the intravenously injected metastasis model. Further research showed that Gli1 positively regulated Snail expression by binding to its promoter and enhancing its protein stability, thereby facilitating the migration, invasion and EMT of NSCLC. In addition, administration of GANT-61, a Gli1 inhibitor, obviously suppressed the metastasis of NSCLC. Collectively, our study reveals that Gli1 is a critical regulator for NSCLC metastasis and suggests that targeting Gli1 is a prospective therapy strategy for metastatic NSCLC.

Objective To evaluate the effect of transversus abdominis plane (TAP) block on postoperative cognitive function in elderly patients undergoing laparoscopic surgery under general anesthesia.Methods Forty-eight male patients undergoing laparoscopic tension-free repair of inguinal hernia under general anesthesia,aged 65-75 yr,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,with body mass index of 20-28 kg/m2,were divided into 2 groups (n =24 each) using a random number table method:TAP block combined with general anesthesia group (group TG) and general anesthesia group (group G).Anesthesia was induced with midazolam,cisatracurium besylate,sufentanil and etomidate,and the patients were mechanically ventilated after laryngeal mask airway insertion.TAP block was performed through the anterior superior iliac spine approach,and 0.25％ ropivacaine 30 ml was injected in group TG.Anesthesia was maintained by target-controlled infusion of propofol and remifentanil and muscle relaxation by intravenously injecting cisatracurium.The occurrence of cerebral regional oxygen saturation (rSO2) and low rSO2 events (rSO2 ＜60％) was recorded at 1 min before anesthesia induction (T0),5 min after inserting the laryngeal mask airway (T1),at skin incision (T2),30 min after skin incision (T3),and at the end of surgery (T4).The consumption of propofol and remifentanil was recorded during surgery.Montreal Cognitive Assessment (MoCA) was used to evaluate the cognitive function of patients at 1 day before surgery and 7 days after surgery,and the development of postoperative cognitive dysfunction (POCD,MoCA scores＜ 26) was recorded.Results Compared with group G,the intraoperative consumption of propofol and remifentanil was significantly reduced,rSO2 was increased at T2~,and the incidence of low rSO2 events was decreased,MoCA scores were increased at 7 days after surgery,and the incidence of POCD was decreased in group TG (P＜0.05).Conclusion TAP block can reduce the incidence of POCD in elderly patients undergoing laparoscopic surgery under general anesthesia.

Objective To explore the mechanism of thymoquinone (TQ) on NSCLC cytotoxicity.Methods SK-MES-1 was inoculated into 96-well plates and cultured at 20,40,60,80 and 100 μmol/L TQ for 24 h,and the IC50 of TQ was calculated.SK-MES-1 was cultured in close proximity to IC50 concentration TQ,and time-dependent was observed.The ERK inhibitor U0126 and the p38 inhibitor SB203580 were applied to SK-MES-1 and 95-D,respectively,then TQ-activated MAPK-mediated cytotoxicity were observed.The SK-MES-1 expression of p-p38,p38,p-ERK1/2,ERK1/2,pJNK and JNK protein were detected by U0126 pretreatment for 1 h and TQ-cultured for 30 min.Results ① TQ was used to mediate NSCLC cells in a concentration and time-dependent manner,and the viability of NSCLC cells was decreased.② The cell viability of 30 μmol/L TQ and 10 μmol/L U0126 +30 μmol/L TQ showed significant differences (P =0.000),but no significant difference was found when compared with 10 μmol/L SB203580 + 30 μmol/L TQ (P =1.00).10 μmol/L SB203580 + 30 μmol/L TQ was significantly different from 10 μmol/L U0126 + 30 μmol/L TQ (P =0.000).60μmol/LTQ,10μmol/LU0126 + 60μmol/LTQ,10μmol/LSB203580 + 60 μmol/L TQ showed no significant differences between every two groups (P ＞ 0.0 5).With the increase of TQ concentration,the protective effect of SB203580 on 95-D cells gradually decreased,and 10 μmol/L SB203580 +40 μmol/L TQ group was significantly different from 40 μmol/L TQ group (P =0.033).③ Western blot analysis showed that U0126 could significantly inhibit the phosphorylation of ERK1/2,phosphorylated p38 increased with the increasing of TQ concentration.However,ERK1/2 phosphorylation decreased,and JNK phosphorylation did not change significantly.Conclusion TQ can mediate NSCLC cytotoxicity through phosphorylation of p38 pathway,but not ERK1/2 pathway.

Objective To explore the mechanism of thymoquinone (TQ) on NSCLC cytotoxicity.Methods SK-MES-1 was inoculated into 96-well plates and cultured at 20,40,60,80 and 100 μmol/L TQ for 24 h,and the IC50 of TQ was calculated.SK-MES-1 was cultured in close proximity to IC50 concentration TQ,and time-dependent was observed.The ERK inhibitor U0126 and the p38 inhibitor SB203580 were applied to SK-MES-1 and 95-D,respectively,then TQ-activated MAPK-mediated cytotoxicity were observed.The SK-MES-1 expression of p-p38,p38,p-ERK1/2,ERK1/2,pJNK and JNK protein were detected by U0126 pretreatment for 1 h and TQ-cultured for 30 min.Results ① TQ was used to mediate NSCLC cells in a concentration and time-dependent manner,and the viability of NSCLC cells was decreased.② The cell viability of 30 μmol/L TQ and 10 μmol/L U0126 +30 μmol/L TQ showed significant differences (P =0.000),but no significant difference was found when compared with 10 μmol/L SB203580 + 30 μmol/L TQ (P =1.00).10 μmol/L SB203580 + 30 μmol/L TQ was significantly different from 10 μmol/L U0126 + 30 μmol/L TQ (P =0.000).60μmol/LTQ,10μmol/LU0126 + 60μmol/LTQ,10μmol/LSB203580 + 60 μmol/L TQ showed no significant differences between every two groups (P ＞ 0.0 5).With the increase of TQ concentration,the protective effect of SB203580 on 95-D cells gradually decreased,and 10 μmol/L SB203580 +40 μmol/L TQ group was significantly different from 40 μmol/L TQ group (P =0.033).③ Western blot analysis showed that U0126 could significantly inhibit the phosphorylation of ERK1/2,phosphorylated p38 increased with the increasing of TQ concentration.However,ERK1/2 phosphorylation decreased,and JNK phosphorylation did not change significantly.Conclusion TQ can mediate NSCLC cytotoxicity through phosphorylation of p38 pathway,but not ERK1/2 pathway.

Objective To observe the complications and mortality of hyponatremia in patients with acute exacerbation of chronic obstructive pulmonary disease.Methods The patients with acute exacerbation of chronic obstructive pulmonary disease were selected and divided into non -hyponatremia group(252 cases)and hyponatremia group(65 cases).The differences in the general status,serum ions,blood gas,APACHE Ⅱ score,complications dur-ing the hospitalization,using of ventilator and mortality between the two groups were compared,and drew the receiver operating characteristic(ROC)curve,to acquire higher serum sodium cut -off values.Results In the hyponatremia group,the body weight was (68.3 ±14.4)kg,BMI was (25.5 ±4.9)kg/m2 ,those in the non -hyponatremia group were (74.9 ±15.9)kg and (28.2 ±5.3)kg/m2 respectively,there were statistically significant differences(t =2.009,8.494,all P <0.05).The incidence rate of pneumonia in the hyponatremia group was 23.1%,which was higher than 13.1% in the non -hyponatremia group(χ2 =4.007,P =0.045).The hospital days of the hyponatremia group was (13.1 ±8.9)d,which was longer than (7.8 ±4.9)d of the non -hyponatremia group(t =15.638,P =0.000).The invasive ventilation days of the hyponatremia group was (1.1 ±0.4)d,which was longer than (0.9 ± 0.1)d of the non -hyponatremia group(t =2.885,P =0.004).The non invasive ventilation days of the hyponatremia group was (3.1 ±0.8)d,which was longer than (0.8 ±0.3)d of the non -hyponatremia group (t =2.984,P =0.003).The hospital mortality rate of the hyponatremia group was 12.3%,which was higher than 3.1% of the non -hyponatremia group(χ2 =7.189,P =0.007).The 90 -day mortality rate of the hyponatremia group was 29.2%, which was higher than 15.1% of the non -hyponatremia group(χ2 =7.017,P =0.008).When the serum sodium cut-off value was 128.8mmol/L by drawing ROC curve,the mortality rate in patients with lower than this value was 26.3%,while the mortality rate in patients with higher than the value was 3.7%.Conclusion Hyponatremia is related with the severity and prognosis of acute exacerbation of chronic obstructive pulmonary disease.It is most important to prevent and correct hyponatremia at early disease stage.