Research on hand, foot and mouth disease incidence forecasting using hybrid model in mainland China.

BACKGROUND: This study aimed to construct a more accurate model to forecast the incidence of hand, foot, and mouth disease (HFMD) in mainland China from January 2008 to December 2019 and to provide a reference for the surveillance and early warning of HFMD. METHODS: We collected data on the incidence of HFMD in mainland China between January 2008 and December 2019. The SARIMA, SARIMA-BPNN, and SARIMA-PSO-BPNN hybrid models were used to predict the incidence of HFMD. The prediction performance was compared using the mean absolute error(MAE), mean squared error(MSE), root mean square error (RMSE), mean absolute percentage error (MAPE), and correlation analysis. RESULTS: The incidence of HFMD in mainland China from January 2008 to December 2019 showed fluctuating downward trends with clear seasonality and periodicity. The optimal SARIMA model was SARIMA(1,0,1)(2,1,2)[12], with Akaike information criterion (AIC) and Bayesian Schwarz information criterion (BIC) values of this model were 638.72, 661.02, respectively. The optimal SARIMA-BPNN hybrid model was a 3-layer BPNN neural network with nodes of 1, 10, and 1 in the input, hidden, and output layers, and the R-squared, MAE, and RMSE values were 0.78, 3.30, and 4.15, respectively. For the optimal SARIMA-PSO-BPNN hybrid model, the number of particles is 10, the acceleration coefficients c1 and c2 are both 1, the inertia weight is 1, the probability of change is 0.95, and the values of R-squared, MAE, and RMSE are 0.86, 2.89, and 3.57, respectively. CONCLUSIONS: Compared with the SARIMA and SARIMA-BPNN hybrid models, the SARIMA-PSO-BPNN model can effectively forecast the change in observed HFMD incidence, which can serve as a reference for the prevention and control of HFMD.

The research on TBATS and ELM models for prediction of human brucellosis cases in mainland China: a time series study.

BACKGROUND: Human brucellosis is a serious public health concern in China. The objective of this study is to develop a suitable model for forecasting human brucellosis cases in mainland China. METHODS: Data on monthly human brucellosis cases from January 2012 to December 2021 in 31 provinces and municipalities in mainland China were obtained from the National Health Commission of the People's Republic of China website. The TBATS and ELM models were constructed. The MAE, MSE, MAPE, and RMSE were calculated to evaluate the prediction performance of the two models. RESULTS: The optimal TBATS model was TBATS (1, {0,0}, -, {< 12,4 >}) and the lowest AIC value was 1854.703. In the optimal TBATS model, {0,0} represents the ARIMA (0,0) model, {< 12,4 >} are the parameters of the seasonal periods and the corresponding number of Fourier terms, respectively, and the parameters of the Box-Cox transformation ω are 1. The optimal ELM model hidden layer number was 33 and the R-squared value was 0.89. The ELM model provided lower values of MAE, MSE, MAPE, and RMSE for both the fitting and forecasting performance. CONCLUSIONS: The results suggest that the forecasting performance of ELM model outperforms the TBATS model in predicting human brucellosis between January 2012 and December 2021 in mainland China. Forecasts of the ELM model can help provide early warnings and more effective prevention and control measures for human brucellosis in mainland China.

Effect and safety evaluation of tacrolimus and tripterygium glycosides combined therapy in treatment of Henoch-Schönlein purpura nephritis.

OBJECTIVE: Henoch-Schönlein 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-Schönlein purpura nephritis is of great significance. METHODS: A randomized, controlled trial was carried out. A total of 279 children with Henoch-Schönlein 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-Schönlein 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-Schönlein purpura nephritis.

Discovery of [1,2,4]triazolo[4,3-a]pyridines as potent Smoothened inhibitors targeting the Hedgehog pathway with improved antitumor activity in vivo.

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.

Nanoscale cationic micelles of amphiphilic copolymers based on star-shaped PLGA and PEI cross-linked PEG for protein delivery application.

To enhance the bioavailability of protein therapeutants and improve the stability of storage and delivery, a series of branched amphiphilic block copolymers consisting of cholic acid (CA) initiated poly(D,L-lactide-co-glycolide) (CA-PLGA) and water-soluble polyethyleneimine cross-linked polyethylene glycol (PEI-PEG) denoted as CA-PLGA-b-(PEI-PEG) were synthesized and characterized. CA-PLGA-b-(PEI-PEG) presented low cytotoxicity by MTT and cck-8 assay. The cationic CA-PLGA-b-(PEI-PEG) micelles (diameter about 100 nm and zeta potential 34-61 mV) were prepared through self-assembly method, and complexed with insulin via electrostatic interaction to obtain nanoscale micelle/insulin complexes. The micelle/insulin complexes-loaded CA-PLGA microspheres (MIC-MS, 10.4 ± 3.85 µm) were manufactured by employing a double emulsion (W1/O/W2) method. The in vitro insulin release behavior and in vivo hypoglycaemic effect of MIC-MS on streptozotocin (STZ) induced diabetic rats were compared with those of the insulin-loaded CA-PLGA microspheres (INS-MS, 7.8 ± 2.57 µm). The initial burst in vitro release of MIC-MS was markedly lower than that of INS-MS (P < 0.01), and the pharmacological availability of MIC-MS via subcutaneous administration was 148.9% relative to INS-MS. Therefore, the cationic CA-PLGA-b-(PEI-PEG) micelles can effectively increase the bioavailability of insulin in CA-PLGA microspheres and can be considered as a potential protein carrier.

Smoking and BMI mediate the causal effect of education on lower back pain: observational and Mendelian randomization analyses.

Objective: Low back pain (LBP) has been associated with education in previous observational studies, but the causality remains unclear. This study aims to assess the impact of education on LBP and to explore mediation by multiple lifestyle factors. Design: Univariable Mendelian randomization (MR) was performed to examine the overall effect of education on LBP. Subsequently, multivariable MR was conducted to assess both the direct effect of education on LBP and the influence of potential mediators. Indirect effects were estimated using either the coefficient product method or the difference method, and the proportion of mediation was calculated by dividing the indirect effect by the total effect. The observational study utilized data from the NHANES database collected between 1999 and 2004, and included 15,580 participants aged 20 years and above. Results: Increasing education by 4.2 years leads to a 48% reduction in the risk of LBP (OR=0.52; 95% CI: 0.46 to 0.59). Compared to individuals with less than a high school education, those with education beyond high school have a 28% lower risk of LBP (OR=0.72; 95% CI: 0.63 to 0.83). In the MR study, smoking accounts for 12.8% (95% CI: 1.04% to 20.8%) of the total effect, while BMI accounts for 5.9% (95% CI: 2.99% to 8.55%). The combined mediation effect of smoking and BMI is 27.6% (95% CI: 23.99% to 32.7%). In the NHANES study, only smoking exhibits a mediating effect, accounting for 34.3% (95% CI: 21.07% to 41.65%) of the effect, while BMI does not demonstrate a mediating role. Conclusions: Higher levels of education provide a protective effect against the risk of LBP. Additionally, implementing interventions to reduce smoking and promote weight loss among individuals with lower levels of education can also decrease this risk.

A Prospective Randomized Controlled Trial Assessing the Impact of Preoperative Combined with Postoperative Progressive Resistance Training on Muscle Strength, Gait, Balance and Function in Patients Undergoing Total Hip Arthroplasty.

Purpose: The aim of this study is to investigate the effects of a preoperative combined with postoperative moderate-intensity progressive resistance training (PRT) of the operative side in patients with hip osteoarthritis (HOA) who are undergoing total hip arthroplasty (THA). The study seeks to evaluate the impact of this combined intervention on muscle strength, gait, balance, and hip joint function in a controlled, measurable, and objective manner. Additionally, the study aims to compare the outcomes of this combined intervention with those of preoperative or postoperative muscle strength training conducted in isolation. Methods: A total of 90 patients with HOA scheduled for unilateral primary THA were randomly assigned to three groups: Pre group (preoperative PRT), Post group (postoperative PRT), and Pre& Post group (preoperative combined with postoperative PRT) focusing on hip flexion, extension, adduction, and abduction of operated side. Muscle strength, gait parameters, balance, and hip function were assessed at specific time points during a 12-month follow-up period. Results: All three groups showed significant improvements in muscle strength, with the Pre& Post group demonstrating the most pronounced and sustained gains. Gait velocity and cadence were significantly improved in the Pre& Post group at 1-month and 3-month postoperative follow-ups compared to the other groups. Similarly, the Pre& Post group exhibited superior balance performance at 3-month and 12-month postoperative follow-ups. The Harris Hip Score also showed better outcomes in the Pre& Post group at all follow-up intervals. Conclusion: Preoperative combined with postoperative moderate-intensity PRT in HOA patients undergoing THA led to superior improvements in muscle strength, gait, balance, and hip joint function compared to preoperative or postoperative PRT alone. This intervention shows significant promise in optimizing postoperative rehabilitation and enhancing patient outcomes following THA.

Prediction of global omicron pandemic using ARIMA, MLR, and Prophet models.

Globally, since the outbreak of the Omicron variant in November 2021, the number of confirmed cases of COVID-19 has continued to increase, posing a tremendous challenge to the prevention and control of this infectious disease in many countries. The global daily confirmed cases of COVID-19 between November 1, 2021, and February 17, 2022, were used as a database for modeling, and the ARIMA, MLR, and Prophet models were developed and compared. The prediction performance was evaluated using mean absolute error (MAE), mean absolute percentage error (MAPE), and root mean square error (RMSE). The study showed that ARIMA (7, 1, 0) was the optimum model, and the MAE, MAPE, and RMSE values were lower than those of the MLR and Prophet models in terms of fitting performance and forecasting performance. The ARIMA model had superior prediction performance compared to the MLR and Prophet models. In real-world research, an appropriate prediction model should be selected based on the characteristics of the data and the sample size, which is essential for obtaining more accurate predictions of infectious disease incidence.

The research of SARIMA model for prediction of hepatitis B in mainland China.

ABSTRACT: Hepatitis B virus infection is a major global public health concern. This study explored the epidemic characteristics and tendency of hepatitis B in 31 provinces of mainland China, constructed a SARIMA model for prediction, and provided corresponding preventive measures.Monthly hepatitis B case data from mainland China from 2013 to 2020 were obtained from the website of the National Health Commission of the People's Republic of China. Monthly data from 2013 to 2020 were used to build the SARIMA model and data from 2021 were used to test the model.Between 2013 and 2020, 9,177,313 hepatitis B cases were reported in mainland China. SARIMA(1,0,0)(0,1,1)12 was the optimal model and its residual was white noise. It was used to predict the number of hepatitis B cases from January to December 2021, and the predicted values for 2021 were within the 95% confidence interval.This study suggests that the SARIMA model simulated well based on epidemiological trends of hepatitis B in mainland China. The SARIMA model is a feasible tool for monitoring hepatitis B virus infections in mainland China.

The research of ARIMA, GM(1,1), and LSTM models for prediction of TB cases in China.

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.

The significance of the hemalexin C1q, RBP, and urinary NAG levels in the diagnosis and prognosis of children with purpura nephritis.

PURPOSE: To investigate the significance of the hemalexin C1q, retinal-binding-protein (RBP), and urinary N-acety1-ß-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.

CdSe/ZnS quantum dots exhibited nephrotoxicity through mediating oxidative damage and inflammatory response.

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.

Computational studies of potent covalent inhibitors on wild type or T790M/L858R mutant epidermal growth factor receptor.

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.

Discovery of Dihydropyrrol-2-ones as Novel G0/G1-Phase Arresting Agents Inducing Apoptosis.

A series of dihydropyrrol-2-ones (DHPs) were designed and synthesized via an efficient multicomponent reaction at room temperature for evaluation of their bioactivities against four human cancer lines (MCF-7, RKO, HeLa, and A549) in vitro. Preliminary structure-activity relationship studies showed that R4 = 3-MeO-4-OH-Ph is a crucial group for increasing cytotoxicities against RKO cells and the influences of R1-R3 depend on their combination. It was found that DHPs 5a, 5q, and 5s showed the best antiproliferative activities against A549, RKO, and all four studied cell lines, respectively (IC50 = 1.9, 0.8, and 0.9-2.4 µM). They can be used as new lead compounds for developing potentially selective or broad spectrum anticancer agents. 5q proves as a potent G0/G1-phase arresting agent inducing cell apoptosis by increasing/decreasing the levels of p53 and p21/cyclin D1.

[Treatment of old calcaneal fractures with calcaneus V-shape osteotomy for the subtalar joint preservation].

OBJECTIVE: To observe the clinical effect of calcaneus V-shape osteotomy for the subtalar joint preservation in the treatment of old calcaneal fractures. METHODS: A retrospective study was conducted on 18 patients (18 feet) with old calcaneal fractures treated by calcaneus V-shape osteotomy from March 2014 to November 2017. Included 13 males and 5 females, aged from 23 to 48 years old with an average of (34.3±4.5) years and the course of disease was from 2 to 9 months with an average of (4.5±4.1) months. According to the classification of Sanders, 14 cases of type II and 4 cases of type III. The postoperative complications were observed. The changes of Böhler angle, Gissane angle, heel height and the tilt angle of talus were compared between before operation and 12 months after operation. Maryland foot score was used to evaluate the curative effect. RESULTS: Fourteen patients were followed up, 4 patients were loss to follow-up. And the follow-up time was 13 to 35 months, with an average of (21.2±4.1) months. The fracture healing time was 10 to 12 weeks with an average of (12.4±2.1) weeks. One patient had skin necrosis of incision after operation, and no complications such as nonunion of fracture and loosening or rupture of internal fixation were found. The tilt angle of talus, Böhler angle, Gissane angle, heel height at 12 months after operation were (11.4±5.1)°, (24.7±4.3)°, (124±3.1)°, (46.1±2. 8) mm, respectively, while before operation were (9.1±2.9)°, (6.8±3.1)°, (93.4±11.7)°, (34.5±5.3) mm, there were significant difference between before and after operation. Maryland score was significantly increased from 59.21±7.21 preoperatively to 86.34 ±4.14 postoperatively 12 months(t=43.1, P<0.05), and 8 cases got excellent results, 4 good, 1 fair, 1 poor. CONCLUSIONS: Calcaneus V-shape osteotomy for subtalar joint preservation is one of the effective methods in the treatment of old calcaneal fractures, which has the advantages of preserving subtalar joint, correcting calcaneal deformity, inproving foot appearance, alleviating foot pain and raising foot function.

[Four kinds of operative methods for subtalar arthrodesis in treating old calcaneal fracture].

OBJECTIVE: To explore clinical efficacy of four surgical methods for subtalar joint fusion and internal fixation in treating old calcaneal fractures. METHODS: From March 2014 to November 2017, 25 patients (26 feet) with old calcaneal fractures treated with four surgical methods of subtalar arthrodesis were retrospectively analyzed, including subtalar joint fusion in situ for 2 patients (2 feet), subtalar articular strut bone graft fusion for 6 patients (6 feet), subtalar joint fusion with calcaneus V-shaped osteotomy for 6 patients(6 feet), and subtalar bone graft fusion with calcaneus cuneiform osteotomy for 11 patients (11 feet). They aged from 23 to 70 years old with an average of (36.7±5.8) years old, and the courses of disease ranged from 3 to 35 months with an average of (9.5±5.1) months. Postoperative complications were observed, talar tilt angle, calcaneus Böhler angle, Gissane angle, and the heel height were compared before and after surgery at 12 months. VAS score and American Orthopaedic Foot and Ankle Society(AOFAS) score were employed to evaluate clinical efficacy at 12 months after surgery. RESULTS: Twenty-one patients (21 feet) were followed up for 13 to 34 months with an average of (20.1±3.7) months, four patients(5 feet) were lost to follow-up. Two patients were underwent surgical incision rupture, 1 patient occurred fracture nonunion, and no complications such as fracture nonunion, loosening or fracture of internal fixation occurred in the other patients. There were significant differences between preoperative and postoperative in talar tilt angle[(5.3±2.4)° vs (11.2±4.6)°, t=7.24, P<0.05], calcaneus Böhler angle[(5.4±2.7)° vs(25.5±5.3)°, t=11.2, P<0.05], Gissane angle[(89.4±9.6)° vs (122.0±5.2)°, t=8.13, P<0.05], and heel height[(28.5±5.1) mm vs(47.1±3.7) mm, t=6.45, P<0.05]. VAS score was decreased from 5.2±1.0 before operation to 1.6±0.7 at 12 months after operation(t=5.12, P<0.05); AOFAS score was improved from 52.4±6.4 to 86.2±5.2 at 12 months after operation(t=6.41, P<0.05); 14 feet got excellent results, 4 good , 2 moderate and 1 poor. CONCLUSIONS: Subtalar joint fusion in situ, subtalar articular strut bone graft fusion, subtalar joint fusion with calcaneus V-shaped osteotomy, and subtalar bone graft fusion with calcaneus cuneiform osteotomy are effective operation methods for old calcaneal fractures, which have advantages of relieving pain, correcting deformity of calcaneal, improving foot function. Reasonable selection and treatment is the key to ensure the efficacy.

[Bone and soft tissue combined with surgery for the treatment soft flatfoot combined with painful navicular bone].

OBJECTIVE: To explore short-term clinical effects of bone and soft tissue combined with surgery for the treatment of soft flatfoot accompanied with painful navicular bone. METHODS: From May 2015 to August 2017, 16 patients (16 feet) with navicular bone soft flatfoot accompanied with painful navicular bone were treated with bone and soft tissues operation (gastrocnemius release, medial displacement calcaneal osteotomy, and excision of accessory navicular with reconstruction of posterior tibial tendon). Among them, there were 9 males (9 feet) and 7 females (7 feet), aged from 22 to 48 years old with an average of (32.0±3.4) years old. The duration of diseases ranged from 6 months to 5 years with an average of (2.4±1.7) years. The postoperative complications were observed, talocalcaneal angle, the first metatarsal horn of the talus, arch height, angle of inclination and calcaneal valgus before and after operation at 12 months were compared. VAS score and AOFAS score after operation at 12 months were applied to evaluate pain relief and function. RESULTS: All patients were followed up for an average of (18.4±3.5) months(13~25 months). The incisions of patients were healed at grade A without wound infection, nonunion or delayed union, internal fixation fracture or loosening and other complications. Medial pain of foot was disappeared and motor ability was restored at 12 months after operation. Arch height, angle of inclination and the first metatarsal horn of the talus of lateral X-ray before operation and after operation at 12 months on weight-bearing foot were(21.51±1.20)°vs(31.01±1.62)°, (10.71±1.52)°vs(22.12±2.11)°, (15.61±1.41)°vs(5.10±1.20)°; talocalcaneal angle, the first metatarsal horn of the talus of AP X-ray before operation and after operation at 12 months on weight-bearing foot were (36.12±2.21) ° vs (22.12±2.61)°, (13.41±1.51)°vs(4.30±0.91)°; calcaneal valgus of axial X-ray before operation and after operation at 12 months on weight-bearing foot were (10.80±1.21)°vs(3.92±1.81)°; there were statistical difference in imaging indicators between preoperation and 12 months after operation. VAS score was significantly decreased from (6.21±2.31) before operation to (1.82±0.56) at 12 months after operation (t=2.64, P<0.05). AOFAS score was obviously increased from (51.2±5.6)before operation to (87.1±4.7)at 12 months after operation (t=3.43, P<0.05). CONCLUSIONS: Bone and soft tissue operation (namely, gastrocnemius release, medial displacement calcaneal osteotomy, and excision of accessory navicular with reconstruction of posterior tibial tendon) could obviously relieve foot pain, improve foot appearance and function in patients with navicular bone soft flatfoot complicated with painful navicular bone, and has certain clinical efficacy.

TCF7L2 activated HOXA-AS2 decreased the glucocorticoid sensitivity in acute lymphoblastic leukemia through regulating HOXA3/EGFR/Ras/Raf/MEK/ERK pathway.

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.

[Synthesis of amphiphilic block copolymer of PLGA-b-(PEI-co-PEG) and characterization of the self-assembled cationic micelles].

OBJECTIVE: To synthesize a biodegradable and minimally cytotoxic amphiphilic block copolymer of PLGA-b-(PEI-co- PEG) and study its micellization behavior. METHODS: PLGA was synthesized by ring-opening polymerization. The cross-linked copolymer of PEI-co-PEG was synthesized from the low-molecular-weight polyethyleneimine (PEI, 1800 D) and hydrophilic poly(ethylene glycol) (PEG, 2000 D). PLGA-b-(PEI-co-PEG) was synthesized by dehydration condensation reaction of PLGA and water soluble PEI-co-PEG. The biodegradability of PEI-co-PEG was evaluated according to the molecular weight change after incubation at 37 ℃ for different time. The cytotoxicity of PLGA- b-(PEI-co-PEG) and PEI-co-PEG in MCF-7 cells was determined by MTT assay. The cationic PLGA-b-(PEI-co-PEG) micelles were prepared by standard dialysis method. The particle size and Zeta potential of the micelles were measured by a Malvern laser particle size analyzer. Micelle/insulin complexes were prepared by simple mixing method and their morphology were characterized by transmission electron microscopy (TEM). The fluorescence quenching method was used to determine the stability of the micelle/insulin complexes at different salt concentrations. RESULTS: Amphiphilic block copolymer of PLGA-b-(PEI-co-PEG) was successfully synthesized. The half-life of PEI-co-PEG degradation in PBS at 37 ℃ was about 48 h. The 50% cell inhibiting concentration (IC50) of PLGA-b-(PEIco- PEG) and PEI-co-PEG in MCF-7 cells were 1375.7 µg/mL and 425.1 µg/mL, respectively. The micelles of PLGA-b-(PEI-co- PEG) (particle size: 99.5±2.61 nm, Zeta potential: 52.9±2.38 mV) were complexed with insulin via electrostatic interaction and formed nanoscale micelle/insulin complexes. The dissociation rate of micelle/insulin complexes in 150 mmol/L NaCl solution was 27.6%. CONCLUSIONS: The synthesized PEI-co-PEG shows good degradability in vitro. The cytotoxicity of PLGA-b-(PEI-co- PEG) is significantly lower than PEI-co-PEG, and PLGA-b-(PEI-co-PEG) micelle/insulin complexes have good salt- resistant stability in physiological condition.