Retrosynthetic planning with experience-guided Monte Carlo tree search.

In retrosynthetic planning, the huge number of possible routes to synthesize a complex molecule using simple building blocks leads to a combinatorial explosion of possibilities. Even experienced chemists often have difficulty to select the most promising transformations. The current approaches rely on human-defined or machine-trained score functions which have limited chemical knowledge or use expensive estimation methods for guiding. Here we propose an experience-guided Monte Carlo tree search (EG-MCTS) to deal with this problem. Instead of rollout, we build an experience guidance network to learn knowledge from synthetic experiences during the search. Experiments on benchmark USPTO datasets show that, EG-MCTS gains significant improvement over state-of-the-art approaches both in efficiency and effectiveness. In a comparative experiment with the literature, our computer-generated routes mostly matched the reported routes. Routes designed for real drug compounds exhibit the effectiveness of EG-MCTS on assisting chemists performing retrosynthetic analysis.

Clinical Statistical Analysis with Comparison between Pelvic and Non-pelvic Chondrosarcoma.

OBJECTIVES: Chondrosarcomas are rare tumors with a variable biological characteristic. Their treatment clinically and surgically is controversial. Analysis of the clinical statistics and prognostic factors of pelvic chondrosarcoma provides a reference for clinical diagnosis and treatment. METHODS: A total of 73 cases of chondrosarcoma were collected, including 24 pelvic samples, from 2008 to 2017 from the hospital database and divided into two groups: pelvic chondrosarcoma and non-pelvic chondrosarcoma. The clinical characteristics and prognostic factors of pelvic chondrosarcoma were analyzed using different statistical methods. RESULTS: Among the 24 pelvic chondrosarcoma patients, the ratio of male to female was 1.4:1, and the median age was 43.5 years. According to the classification proposed by Enneking, there were five grade I, 14 grade II, and five grade III. Histological grading of chondrosarcoma was grade I in one case, II in 15 cases, and III in eight cases. The histological type was 17 conventional, three dedifferentiated, two secondary, one myxoid, and one mesenchymal. The overall survival rates for 24 cases at three, five, and 10 years were 82.2±8.1%, 77.3±8.9%, and 52.4±12.1%, respectively. The local recurrence rate of pelvic chondrosarcoma after surgical resection (83.3%) was significantly higher than that of other sites (34.7%), and the difference was statistically significant (p < 0.001). The final proportion of amputation rate (50.0%) was also higher than other parts (20.4%), with a statistically significant difference (p = 0.010). The total survival of the two groups was not significantly different (p = 0.216). CONCLUSIONS: Chondrosarcoma of bone generally has an excellent prognosis when optimally diagnosed and treated by an experienced team of specialists. Pelvic chondrosarcoma has a higher local recurrence rate than the other sites and tends to result in amputation. Early local recurrence after surgery indicates a poor prognosis.

Comparison of chondrosarcoma cases: current clinical situations among institutions.

OBJECTIVE: Chondrosarcoma is a rare tumor that has a variable biological characteristic, and its treatment is controversial. We performed a comparison review of different regional institutions series to assess the clinical outcome of patients. METHODS: A retrospective review of 33 chondrosarcomas (Grades I, II, and III) patient data since 2013, compared with 15 author's total 868 patients published literature results to find more about clinical and statistical advantages and similarities with author institute cases. Here is the mentioning of clinical information, surgery type categorized, adjuvants types, genders, follow-up years, recurrence, affected areas, death rates, successful outcome, and survival rates using statistical methods. RESULTS: The overall survival rate was 94%, successful outcome 85% in 4.3±1.2 years follow-up. Observed wide resection, distilled water as adjuvant, chemo and radiotherapy significantly shows excellent results over our compared chondrosarcoma literature data. We have also marked that females and humerus bone are more affected by chondrosarcoma among those literature data. CONCLUSIONS: Low-grade chondrosarcoma of the skeleton can be treated with wide resection. Using distilled water give good oncological outcome and a very low rate of post-surgical complications for chondrosarcoma all grades recurrence.

Circular RNA circANKIB1 promotes the progression of osteosarcoma by regulating miR-217/PAX3 axis.

BACKGROUND: Circular RNAs (circRNAs) have been discovered to exert essential roles in human cancers, including osteosarcoma (OS). The aim of this study was to investigate the exact roles and regulatory mechanism of circRNA ankyrin repeat and IBR domain containing 1 (circANKIB1) in OS. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression levels of circANKIB1, microRNA-217 (miR-217) and paired box 3 (PAX3). Cell proliferation was assessed by colony formation assay. Cell cycle distribution and apoptosis rate were determined by flow cytometry analysis. Wound healing assay and transwell assay were employed to evaluate cell migration and invasion abilities. Western blot assay was used to analyze the protein levels of PAX3, E-cadherin and Vimentin. Targeting relationship between miR-217 and circANKIB1 or PAX3 was predicted by Circular RNA Interactome or TargetScan and demonstrated by dual-luciferase reporter assay. The mice xenograft model was established to confirm the role of circANKIB1 in vivo. RESULTS: CircANKIB1 and PAX3 were high-expressed, whereas miR-217 was low-expressed in OS tissues and cells. Knockdown of circANKIB1 inhibited the progression of OS by reducing cell proliferation, migration, invasion, and tumor growth (in vivo), and inducing apoptosis. MiR-217 was a direct target of circANKIB1, and its inhibition reversed the inhibitory effect of circANKIB1 knockdown on the progression of OS cells. Moreover, PAX3 was a direct target of miR-217, and miR-217 exerted the anti-tumor role in OS cells by targeting PAX3. Furthermore, circANKIB1 positively regulated PAX3 expression by sponging miR-217. CONCLUSION: Knockdown of circANKIB1 suppressed OS progression by upregulating miR-217 and downregulating PAX3, which might provide a novel insight into the pathogenesis of OS.

The necessity of treating asymptomatic bacteriuria with antibiotics in the perioperative period of joint arthroplasty: a metaanalysis

Background/aim: Oral antibiotics are usually used to treat asymptomatic bacteriuria during the perioperative period of joint replacement. However, there is no unified conclusion as to whether asymptomatic bacteriuria causes infection around joint prostheses, and the efficacy of antibiotics is unknown. Materials and methods: We systematically searched PubMed, CNKI, Ovid, Cochrane Library, EMBASE, manual research, and references of relevant articles up to January 1, 2020, to identify and compare observational studies. The Cochrane systematic review method was used, and Review Manager 5.3 software was used for analysis. Results: Nine articles were included in the analysis, involving 29,844 cases of joint arthroplasty and 2366 cases of asymptomatic bacteriuria. Periprosthetic joint infection had a significantly higher incidence in the asymptomatic bacteriuria group than in the nonasymptomatic bacteriuria group (Odds Ratio: OR = 3.15, 95% CI: 1.23­8.02, P = 0.02). Seven of the nine articles reported the use of antibiotics for treating perioperative asymptomatic bacteriuria and there was no significant difference in the incidence of periprosthetic joint infection between the two groups (OR = 1.64, 95% CI: 0.84­3.23, P = 0.15). Conclusion: The occurrence of asymptomatic bacteriuria in the perioperative period of joint arthroplasty is a risk factor for periprosthetic joint infection, and the use of antibiotics for asymptomatic bacteriuria does not change the rate of incidence.