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Molecular clustering analysis has been developed to facilitate visual inspection in the process of structure-based virtual screening. However, traditional methods based on molecular fingerprints or molecular descriptors limit the accuracy of selecting active hit compounds, which may be attributed to the lack of representations of receptor structural and protein–ligand interaction during the clustering. Here, a novel deep clustering framework named ClusterX is proposed to learn molecular representations of protein–ligand complexes and cluster the ligands. In ClusterX, the graph was used to represent the protein–ligand complex, and the joint optimisation can be used efficiently for learning the cluster-friendly features. Experiments on the KLIFs database show that the model can distinguish well between the binding modes of different kinase inhibitors. To validate the effectiveness of the model, the clustering results on the virtual screening dataset further demonstrated that ClusterX achieved better or more competitive performance against traditional methods, such as SIFt and extended connectivity fingerprints. This framework may provide a unique tool for clustering analysis and prove to assist computational medicinal chemists in visual decision-making.

WD40 repeat and SOCS box containing 1 (WSB1) consists of seven WD40 repeat structural domains at the N-terminal end and one SOCS box structural domain at the C-terminal end. WSB1 promotes cancer progression by affecting the Von Hippel–Lindau tumor suppressor protein (pVHL) and upregulating hypoxia inducible factor-1α (HIF-1α) target gene expression. However, the crystal structure of WSB1 has not been reported, which is not beneficial to the research on WSB1 inhibitors. Therefore, we focused on specific small molecule inhibitors of WSB1. This study applied virtual screening and molecular dynamics simulations; finally, 20 compounds were obtained. Among them, compound G490-0341 showed the best stable structure and was a promising composite for further development of WSB1 inhibitors.

Backgrounds To compare the reduction effect of single loop and double loop in the treatment of acute acromioclavicular dislocation, postoperative complications and the effect of shoulder function recovery, so as to determine the best fixation method for acromioclavicular. Methods Patients with acute acromioclavicular dislocation treated with TightRope fixation in our hospital from January 2014 to May 2019 were reviewed. According to the different fixation methods, it can be divided into single loop group and double loop group. The difference and difference ratio of coracoclavicular spacing between the affected side and the healthy side at the 1st day, 3rd week, 6th week, 3rd month, 6th month, 1st year, 2nd year and the last follow-up were compared between the two groups, as well as the postoperative visual analog scale pain score (VAS), American Shoulder and Elbow Surgeon score(ASES) and constant-Murley score. Results On the 1st postoperative day, there was no significant difference in the reduction effect between the single loop group and the double loop group (P = 0.90,P = 0.93). 3 weeks after surgery, although the overall difference and difference rate of CCD between the two groups were different (P = 0.00,P = 0.00), there was no significant difference between type ⅲ and type ⅳ in terms of injury type (Type ⅲ P = 0.13,P = 0.16; Type ⅳ p = 0.22, p = 0.20;). Since 6 weeks after surgery, there were significant statistical differences in CCD difference rate between single loop group and double loop group. Conclusions Both single loop and double loop Tightrope can achieve satisfactory results in the treatment of fresh Rockwood ⅲ - ⅴ acromioclavicular dislocation. The single-loop group has the risk of postoperative reduction and loss.

CXC chemokine receptors 1 (CXCR1) and 2 (CXCR2) have been demonstrated to have critical roles in cancer metastasis. Because they share high homology sequences, it is still unclear how to design selective CXCR1 or CXCR2 antagonists. Based on a pharmacophore model we built, compound 2 bearing a 1,5-dihydro-4H-imidazol-4-one scaffold was identified as a selective CXCR2 antagonist with a low CXCR1 antagonism preference. Further optimization and structure-activity relationship studies led to compound C5 that overcame the disadvantages of compound 2 and performed with higher selectivity. It showed excellent oral bioavailability and in vitro anticancer metastasis activity. Further dynamic simulation of the molecular protein complex showed that the amino acid residue K320 of CXCR2 contributed most to the selectivity of C5. This study provides important clues for the design of new CXCR2 selective antagonists, and C5 can be a molecular tool for investigating the difference in the biological function of CXCR1 and CXCR2.

[Image: see text] CXC chemokine receptors 1 (CXCR1) and 2 (CXCR2) have been demonstrated to have critical roles in cancer metastasis. Because they share high homology sequences, it is still unclear how to design selective CXCR1 or CXCR2 antagonists. Based on a pharmacophore model we built, compound 2 bearing a 1,5-dihydro-4H-imidazol-4-one scaffold was identified as a selective CXCR2 antagonist with a low CXCR1 antagonism preference. Further optimization and structure–activity relationship studies led to compound C5 that overcame the disadvantages of compound 2 and performed with higher selectivity. It showed excellent oral bioavailability and in vitro anticancer metastasis activity. Further dynamic simulation of the molecular protein complex showed that the amino acid residue K320 of CXCR2 contributed most to the selectivity of C5. This study provides important clues for the design of new CXCR2 selective antagonists, and C5 can be a molecular tool for investigating the difference in the biological function of CXCR1 and CXCR2.

Multiple myeloma (MM) is a highly malignant hematologic cancer that occurs when an atypical plasma cell develops in the bone marrow and reproduces quickly. Despite varies of new drugs have been developed or under clinic trial, MM is still essentially incurable, while XPO1 inhibition has emerged as a promising therapeutic strategy in the treatment of MM. Using the second-generation XPO1 inhibitor KPT-8602 as the lead compound, structure-based optimization provided D4 with high anti-proliferation efficacy (IC

The balance of osteoblasts and marrow adipocytes from bone marrow mesenchymal stem cells (BM-MSCs) maintains bone health. Under aging or other pathological stimuli, BM-MSCs will preferentially differentiate into marrow adipocytes and reduce osteoblasts, leading to osteoporosis. Long non-coding RNA differentiation antagonizing non-protein coding RNA (DANCR) participates in the osteogenic differentiation of human BM-MSCs, but the mechanism by which DANCR regulates the osteogenic differentiation of human BM-MSCs has not been fully explained. We observed that DANCR and prospero homeobox 1 (PROX1) were downregulated during osteogenic differentiation of human BM-MSCs, while miR-1301-3p had an opposite trend. DANCR overexpression decreased the levels of alkaline phosphatase, RUNX2, osteocalcin, Osterix in BM-MSCs after osteogenic induction, but DANCR silencing had the opposite result. Moreover, DANCR sponged miR-1301-3p to regulate PROX1 expression. miR-1301-3p overexpression reversed the suppressive role of DANCR elevation on the osteogenic differentiation of human BM-MSCs. Also, PROX1 elevation abolished the promoting role of miR-1301-3p overexpression on the osteogenic differentiation of human BM-MSCs. In conclusion, DANCR suppressed the osteogenic differentiation of human BM-MSCs through the miR-1301-3p/PROX1 axis, offering a novel mechanism by which DANCR is responsible for the osteogenic differentiation of human BM-MSCs.

To investigate the clinical effect of modified Judet quadricepsplasty (MJ) combined with patella traction designed by ourselves in the treatment of knee joint rigidity after a femoral fracture. We retrospectively reviewed the clinical data of 21 patients with stiff knee joint after a femoral fracture treated by modified Judet quadricepsplasty combined with patella traction designed by the author from May 2014 to January 2017. The age at revision surgery was 20–57 (36 ± 12) years. The time between fracture fixation to quadricepsplasty was five to 23 (15 ± 5) months, and the follow-up was 11–32 (18 ± 6) months. Pre-operative, intra-operative, post-operative and final follow-up range of motion (ROM), the total traction time, and complications were assessed. The knee joint function was evaluated according to Judet’s classification scheme. Knee ROM was 5–60 (36 ± 13) ° pre-operatively, and 30–80 (53 ± 13) ° after MJ (an increase of 0–30 (17 ± 10)) (p < 0.05). The duration of patellar traction was ten to 14 (11 ± 2) days. Knee ROM after traction device removal was 90–100 (92 ± 3) °, an increase of 10–65 (39–14) ° compared with the ROM after arthrolysis (p < 0.05). The follow-up duration was 11–32 (18 ± 6) months. Knee ROM at final follow-up was 80–130 (104 ± 12) °, an increase of 40–100 (68 ± 16) 8° compared with pre-operatively (p < 0.05), and of − 10–40 (12 ± 13) ° compared with the ROM after traction removal (p < 0.05). Knee function was excellent in 14 cases (67%), good in 6 (28%), and fair in one (5%). The MJ plus patellar traction lengthens the contracted quadriceps femoris, thus restoring knee function within a short period of time.

Objective To investigate the effect of tranexamic acid (TXA) on hidden bleeding in older intertrochanteric fracture patients treated with intramedullary nails. Method Between January 2016 and January 2017, 100 cases of intertrochanteric fractures eligible for the study were treated with proximal femoral nail antirotation (PFNA) in our hospital. All patients were divided into two groups of 50 patients each: the TXA group and a blank control group. In the TXA group, all patients received TXA at a dose of 10 mg/kg−1 intravenously, 10 min preoperatively and 5 h postoperatively. The control group did not receive TXA. We recorded the volume of intraoperative blood loss and postoperative drainage, and the need for postoperative blood transfusion and transfusion volume for all patients. Blood routine examination was performed on the day of surgery and 2 days postoperatively. We calculated the total blood loss and hidden blood loss in the two groups separately according to the Gross equation. All patients underwent deep vein ultrasound of the lower limbs preoperatively and 1 week postoperatively to detect thrombosis. Results Compared with controls, patients in the TXA group had lower: overt bleeding (50.59 ml; p = .012), total blood loss (181.58 ml; p = .005), hidden blood loss (130.64 ml; p = .037), volume of blood transfusion (110.0 ml; p = .019), and 20% lower transfusion rate compared with the control group. Patients receiving short-nail fixation had significantly lower hidden blood loss compared with patients receiving long-nail fixation (p Conclusion TXA significantly reduced hidden blood loss in older intertrochanteric fracture patients treated with intramedullary nails without an increased risk of thrombosis in lower limb deep veins.

Rationale: Primary iliopsoas abscess (IPA), an uncommon clinical entity, often has no specific clinical features, and advanced imaging techniques are often required for diagnosis. Patient Concerns: We successfully treated 3 patients with primary IPA complicated by rapid development of septic shock within 2 months. Diagnosis: All patients were in shock at the time of admission and were diagnosed with primary IPA by history, clinical examination and imaging findings. Interventions: All patients were treated by surgical drainage and sensitive antibiotics based on culture results. Outcomes: The patients eventually recovered and were discharged within 2 months. Lessons: An IPA may not be diagnosed in a timely manner because it has no specific symptoms or signs. Therefore, special attention must be given to patients with sudden onset of abdominal pain, hip pain, or high fever without an obvious cause, a primary IPA should be highly suspected in such patients.