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Background The previous acetabular surface manufacturing technology provides a suitable surface for bone ingrowth into cementless cups, but there were already some literatures reporting failure cases due to sintered titanium beads and titanium fiber mesh. Electron beam melting (EBM) technology has been used in manufacturing trabecular titanium acetabular cups with high porosity, pore size suitable for bone ingrowth, low elastic modulus and high friction coefficient. Objectives We study and evaluate the clinical and imaging outcomes of porous coated trabecular titanium cup manufactured with electron beam melting technique with a relatively large sample, in order to provide evidence-based basis for its clinical application. Methods Two hundred and thirty-six patients who underwent primary total hip arthroplasty using porous coated trabecular titanium cup from January 2019 to June 2021 in the Department of Joint Surgery of our hospital were selected. General date, imaging information, functional scores and complications were collected to evaluate the early clinical efficacy of the cup. Results All patients were followed up for 17–46 months, with an average of (26.2 ± 9.2) months. At the last follow-up, the preoperative HSS score increased from 43.7 ± 6.8 to 85.6 ± 9.3 points with statistical significance (P

Objective Henoch-Schonlein purpura nephritis has become a significant threat to children's health. Traditional combined therapy of glucocorticoids and cyclophosphamide leads to severe toxicity and complications. Therefore, identifying a feasible and effective strategy with low side-effects for the treatment of Henoch-Schonlein purpura nephritis is of great significance. Methods A randomized, controlled trial was carried out. A total of 279 children with Henoch-Schonlein purpura nephritis were recruited and randomly divided into three groups: control group (receiving the current standard therapy), TA group (receiving tacrolimus) and TA + tripterygium glycosides group (receiving tacrolimus + tripterygium treatment). The total duration of the trial was 6 months, and the duration of follow-up observation was 9 months. Results Various therapies showed similar therapeutic effects in the third and sixth months. The relief of Henoch-Schonlein purpura nephritis symptoms caused by TA + tripterygium glycosides was slower than the TA and control groups. The incidence of adverse reactions in the TA + tripterygium glycosides group was lower in the control and TA groups. The final treatment effect of the experimental groups was better than the control group. The recurrence rate in the TA + tripterygium glycosides group was also significantly lower. Conclusion Tacrolimus and tripterygium glycosides combined therapy had better effects and safety for long-term treatment of Henoch-Schonlein purpura nephritis.

Objective This study aimed to the evaluate the nephrotoxicity of CdSe/ZnS QDs in vitro and vivo, as well as investigate the underlying toxicity mechanisms. Results In vitro experiments showed that compared with control cells, CdSe/ZnS QDs treatment significantly inhibited cell viability and promoted cell apoptosis in dose-dependent manner in NRK cells. Notably, CdSe/ZnS QDs treatment increased the contents of MDA and ROS, and decreased the activities of SOD, CAT and GSH-Px; however, the co-treatment of NAC and QDs relieved the oxidative damage of NRK cells. Moreover, in vivo experiments also revealed that CdSe/ZnS QDs treatment obviously increased kidney weight coefficient, damaged the kidney function, as well as induced inflammatory response and inhibited the activation of NRF2/Keap1 pathway in kidney tissues of mice. Conclusions CdSe/ZnS QDs exhibited obvious nephrotoxicity by mediating oxidative damage and inflammatory response in vitro and in vivo via NRF2/Keap1 pathway. Methods The characterization of CdSe/ZnS QDs was analyzed by transmission electron microscope, emission spectrum scanning, and dynamic light scattering. Rat kidney cells (NRK) were exposed to different doses of CdSe/ZnS QDs with or without N-acetylcysteine (NAC, antioxidant). Then, cellular uptake of CdSe/ZnS QDs was detected, and in vitro cytotoxicity was evaluated by MTT assay and TUNEL assay.

Background and objective Tuberculosis (Tuberculosis, TB) is a public health problem in China, which not only endangers the population’s health but also affects economic and social development. It requires an accurate prediction analysis to help to make policymakers with early warning and provide effective precautionary measures. In this study, ARIMA, GM(1,1), and LSTM models were constructed and compared, respectively. The results showed that the LSTM was the optimal model, which can be achieved satisfactory performance for TB cases predictions in mainland China. Methods The data of tuberculosis cases in mainland China were extracted from the National Health Commission of the People’s Republic of China website. According to the TB data characteristics and the sample requirements, we created the ARIMA, GM(1,1), and LSTM models, which can make predictions for the prevalence trend of TB. The mean absolute error (MAE), root mean square error (RMSE), and mean absolute percentage error (MAPE) were applied to evaluate the effects of model fitting predicting accuracy. Results There were 3,021,995 tuberculosis cases in mainland China from January 2018 to December 2020. And the overall TB cases in mainland China take on a downtrend trend. We established ARIMA, GM(1,1), and LSTM models, respectively. The optimal ARIMA model is the ARIMA (0,1,0) × (0,1,0)12. The equation for GM(1,1) model was X(k+1) = -10057053.55e(-0.01k) + 10153178.55 the Mean square deviation ratio C value was 0.49, and the Small probability of error P was 0.94. LSTM model consists of an input layer, a hidden layer and an output layer, the parameters of epochs, learning rating are 60, 0.01, respectively. The MAE, RMSE, and MAPE values of LSTM model were smaller than that of GM(1,1) and ARIMA models. Conclusions Our findings showed that the LSTM model was the optimal model, which has a higher accuracy performance than that of ARIMA and GM (1,1) models. Its prediction results can act as a predictive tool for TB prevention measures in mainland China.

Acute lymphoblastic leukemia (ALL) is characterized by abnormal lymphoblasts accumulation in the bone marrow and blood. Despite great efforts have been made in exploring novel therapeutic method, the prognosis of children with ALL is still unsatisfied. Glucocorticoid (GC) resistance is a great obstacle for the clinical treatment of ALL. Therefore, it is essential to investigate the molecular mechanism underlying the GC resistance. According to previous reports, long noncoding RNAs (lncRNAs) are involved in drug resistance of various human cancers. LncRNA HOXA cluster antisense RNA2 (HOXA-AS2) has been reported in several human malignancies due to its oncogenic property. However, the molecular mechanism of HOXA-AS2 involved in the GC resistance of ALL still needs to be further clarified. At first, we found that lncRNA HOXA-AS2 was highly expressed both in prednisone insensitive ALL cell lines and patient samples. Gain or loss-of-function assays revealed that HOXA-AS2 enhanced GC resistance via promoting cell proliferation and inhibiting cell apoptosis. Furthermore, we validated that HOXA-AS2 upregulated HOXA3, thereby activating EGFR/Ras/Raf/MEK/ERK signaling pathway. Our findings showed that HOXA-AS2 may be a potential therapeutic target for ALL patients with poor GC resistance.

Purpose: To investigate the significance of the hemalexin C1q, retinal-binding-protein (RBP), and urinary N-acety1-β-D-glucosaminidase (NAG) levels in the diagnosis and prognosis of children with purpura nephritis. Methods: A total of 130 children with purpura nephritis admitted to our hospital from January 2017 to December 2019 were recruited as the study cohort, including 43 children with purpura nephritis as the observation group, 51 children with purpura nephritis as the control group, and 36 healthy children undergoing physical examinations at the same time period as the healthy group. The basic data of the three groups of children were compared, and the hemalexin C1q, RBP, and urinary NAG levels were observed. The children were divided into a good prognosis group and a poor prognosis group according to the observation group’s follow-up data. The significance of the hemalexin C1q, RBP, and urinary NAG levels for the diagnosis and prognosis of children with purpura nephritis was investigated by comparing the hemalexin C1q, RBP, and urinary NAG levels in these two groups. Results: The hemalexin C1q, RBP, and urinary NAG levels in the observation group, the control group, and the healthy group were significantly reduced, and the differences were statistically significant (P < 0.05). The hemalexin C1q, RBP, and urinary NAG levels of the children in the good prognosis group were significantly lower than they were in the poor prognosis group (P < 0.05). Conclusion: The hemalexin C1q, RBP, and urinary NAG levels in the diagnosis and prognosis of children with purpura nephritis have a definite value and can be used as effective predictors for the prognosis of children with purpura nephritis.

In this paper, we designed and synthesized two analog compounds M1 and T1 that have a Michael acceptor warhead. Although only slightly diversity existed in the structures of M1 and T1, their inhibitory activities against wild type epidermal growth factor receptor (EGFRWT) and T790M/L858R mutant epidermal growth factor receptor (EGFRT790M/L858R) were significant different. Thus, multiple computational approaches were applied to investigate the interactions between the compounds with EGFRWT and EGFRT790M/L858R in order to explore the effect of different compounds. The molecular docking and MD simulations were performed to study the intermolecular interactions between compounds and EGFR. The binding free energy revealed that M1-EGFRWT and M1-EGFRT790M/L858R complexes have stronger binding affinity compared with the corresponding T1-EGFRWT and T1-EGFRT790M/L858R complexes, respectively. And the binding free energy decompositions for each residue analysis indicated that the van der Waals interactions are the major contributor to enhance the compounds to bind with EGFR. In addition, covalent binding complexes of M1-EGFRWT and M1-EGFRT790M/L858R were constructed and studied. Moreover, quantum mechanics method was applied to investigate the reaction mechanism of covalent binding of the compound and EGFR. The results will provide the details of structural and energetic information to develop potent covalent EGFR inhibitors in the future.

In this study, folic acid-conjugated lipid nanoparticles were successfully prepared to enhance the active targeting of capsaicin (CAP) in ovarian cancers. The particles were nanosized and exhibited a controlled release of drug in the physiological conditions. The folic acid (FA)-conjugated system exhibited a remarkably higher uptake of nanoparticles in the cancer cells compared to that of non-targeted system. The folate-conjugated CAP-loaded lipid nanoparticles (CFLN) upon interacting with cancer cells were internalized via receptor-mediated endocytosis mechanism and resulted in higher concentration in the cancer cells. Consistently, CFLN showed a remarkably higher toxic effect compared to that of non-targeted nanoparticle system. CFLN showed significantly higher cancer cell apoptosis with nearly 39% of cells in apoptosis chamber (early and late) compared to only ∼21% and ∼11% for CAP-loaded lipid nanoparticles (CLN) and CAP. The loading of drug in the lipid nanoparticle system extended the drug retention in the blood circulation and allowed the active targeting to specific cancer cells. The prolonged circulation of drug attributed to the antifouling property of polyethylene glycol molecule in the structure. Overall, study highlights that using targeting moiety could enhance the therapeutic response of nanomedicines in the treatment of solid tumors.

Triple-negative breast cancer (TNBC), a subset of breast cancers, have poorer survival than other breast cancer types. Recent studies have demonstrated that the abnormal Hedgehog (Hh) pathway is activated in TNBC and that these treatment-resistant cancers are sensitive to inhibition of the Hh pathway. Smoothened (Smo) protein is a vital constituent in Hh signaling and an attractive drug target. Vismodegib (VIS) is one of the most widely studied Smo inhibitors. But the clinical application of Smo inhibitors is limited to adult patients with BCC and AML, with many side effects. Therefore, it's necessary to develop novel Smo inhibitor with better profiles. Twenty [1,2,4]triazolo[4,3-a]pyridines were designed, synthesized and screened as Smo inhibitors. Four of these novel compounds showed directly bound to Smo protein with stronger binding affinity than VIS. The new compounds showed broad anti-proliferative activity against cancer cell lines in vitro, especially triple-negative breast cancer cells. Mechanistic studies demonstrated that TPB15 markedly induced cell cycle arrest and apoptosis in MDA-MB-468 cells. TPB15 blocked Smo translocation into the cilia and reduced Smo protein and mRNA expression. Furthermore, the expression of the downstream regulatory factor glioma-associated oncogene 1 (Gli1) was significantly inhibited. Finally, TPB15 demonstrated greater anti-tumor activity in our animal models than VIS with lower toxicity. Hence, these results support further optimization of this novel scaffold to develop improved Smo antagonists.