BACKGROUND:Currently,treatment method for knee osteoarthritis includes oral medicine,joint cavity drug injection,and physiotherapy,but the curative effect is limited.Existing studies have confirmed that silicon-based bioceramics can promote cartilage and subchondral bone repair and vascular regeneration.OBJECTIVE:To explore the effect of different concentrations of silicon-based bioceramics injected into the knee joint cavity in the treatment of knee osteoarthritis in rats.METHODS:Silicon-based bioceramics-calcium silicate was prepared.Twenty-five SD rats were randomly divided into five groups,with five rats in each group.The healthy group did not receive any intervention,and the modeling group,low-dose calcium silicate group,high-dose calcium silicate group,and saline group used anterior cruciate ligament transection to establish bilateral knee osteoarthritis models.Four weeks after modeling,0.05 mL of 50 and 100 mg/mL calcium silicate solution were injected into the knee joint cavity in the low-dose calcium silicate group and high-dose calcium silicate group,respectively,and 0.05 mL of saline was injected into the knee joint cavity in the saline group,once a week for 4 consecutive weeks.In the fifth week of administration,bilateral knee joint Micro-CT detection,knee joint cartilage hematoxylin-eosin staining,and modified Mankin score were performed.RESULTS AND CONCLUSION:(1)Micro-CT quantitative analysis showed that compared with the healthy group,the volume fraction and number of trabeculae of the medial tibial plateau in the modeling group decreased(P＜0.05),and the separation of trabeculae increased(P＜0.05).Compared with the modeling group,the volume fraction and number of trabeculae of the medial tibial plateau in the low-dose calcium silicate group and the saline group increased(P＜0.05),and the separation of trabeculae decreased(P＜0.05).(2)Hematoxylin-eosin staining showed that the cartilage surface of the healthy group and the low-dose calcium silicate group was relatively smooth and flat,the chondrocytes were evenly distributed,without clustered chondrocytes,the tide line was complete,and the staining was uniform;the cartilage surface of the high-dose calcium silicate group was slightly uneven,the middle and deep cells were disordered,with a small number of clustered chondrocytes,the tide line was discontinuous,and the staining was uneven;the cartilage surface of the saline group and the modeling group was obviously rough,the cells were disordered,with a large number of clustered chondrocytes,the tide line disappeared,and the staining was uneven.The modified Mankin score of the healthy group was lower than that of the high-dose calcium silicate group,the saline group,and the modeling group(P＜0.05).The modified Mankin score of the high-dose calcium silicate group and the low-dose calcium silicate group was lower than that of the saline group and the modeling group(P＜0.05).(3)The results show that calcium silicate knee joint injection has a certain effect in the treatment of knee osteoarthritis.Compared with 100 mg/mL calcium silicate solution,50 mg/mL calcium silicate solution can promote the recovery of subchondral bone and cartilage.

BACKGROUND:Currently,treatment method for knee osteoarthritis includes oral medicine,joint cavity drug injection,and physiotherapy,but the curative effect is limited.Existing studies have confirmed that silicon-based bioceramics can promote cartilage and subchondral bone repair and vascular regeneration.OBJECTIVE:To explore the effect of different concentrations of silicon-based bioceramics injected into the knee joint cavity in the treatment of knee osteoarthritis in rats.METHODS:Silicon-based bioceramics-calcium silicate was prepared.Twenty-five SD rats were randomly divided into five groups,with five rats in each group.The healthy group did not receive any intervention,and the modeling group,low-dose calcium silicate group,high-dose calcium silicate group,and saline group used anterior cruciate ligament transection to establish bilateral knee osteoarthritis models.Four weeks after modeling,0.05 mL of 50 and 100 mg/mL calcium silicate solution were injected into the knee joint cavity in the low-dose calcium silicate group and high-dose calcium silicate group,respectively,and 0.05 mL of saline was injected into the knee joint cavity in the saline group,once a week for 4 consecutive weeks.In the fifth week of administration,bilateral knee joint Micro-CT detection,knee joint cartilage hematoxylin-eosin staining,and modified Mankin score were performed.RESULTS AND CONCLUSION:(1)Micro-CT quantitative analysis showed that compared with the healthy group,the volume fraction and number of trabeculae of the medial tibial plateau in the modeling group decreased(P＜0.05),and the separation of trabeculae increased(P＜0.05).Compared with the modeling group,the volume fraction and number of trabeculae of the medial tibial plateau in the low-dose calcium silicate group and the saline group increased(P＜0.05),and the separation of trabeculae decreased(P＜0.05).(2)Hematoxylin-eosin staining showed that the cartilage surface of the healthy group and the low-dose calcium silicate group was relatively smooth and flat,the chondrocytes were evenly distributed,without clustered chondrocytes,the tide line was complete,and the staining was uniform;the cartilage surface of the high-dose calcium silicate group was slightly uneven,the middle and deep cells were disordered,with a small number of clustered chondrocytes,the tide line was discontinuous,and the staining was uneven;the cartilage surface of the saline group and the modeling group was obviously rough,the cells were disordered,with a large number of clustered chondrocytes,the tide line disappeared,and the staining was uneven.The modified Mankin score of the healthy group was lower than that of the high-dose calcium silicate group,the saline group,and the modeling group(P＜0.05).The modified Mankin score of the high-dose calcium silicate group and the low-dose calcium silicate group was lower than that of the saline group and the modeling group(P＜0.05).(3)The results show that calcium silicate knee joint injection has a certain effect in the treatment of knee osteoarthritis.Compared with 100 mg/mL calcium silicate solution,50 mg/mL calcium silicate solution can promote the recovery of subchondral bone and cartilage.

Objective Through the analysis of the clinical characteristics of post-interventional complications of ventilator-associ-ated pneumonia(VAP)in patients with hypertension and acute large vessel occlusive cerebral infarction(AIS-LVO),we aim to develop and validate a risk prediction model.Methods We conducted a retrospective analysis of clinical data from 107 patients hospitalized for hypertension with AIS-LVO at Dongguan Hospital of Guangzhou University of Traditional Chinese Medicine between July 2020 and Au-gust 2023.Patients were categorized into two groups based on their hospitalization:the VAP group,consisting of 64 patients who devel-oped VAP,and the non-VAP group,comprising 43 patients who did not experience VAP.Least absolute shrinkage and selection opera-tor regression(LASSO)analysis was employed to identify potential predictors.Subsequently,a nomogram model was constructed using multifactorial Logistic regression analysis.The model's discriminative ability,calibration,and clinical utility were assessed using the area(AUC)under the receiver operating characteristic(ROC)curve,calibration curves,and decision curve analysis(DCA).Results In 107 patients with hypertension and AIS-LVO who underwent interventional surgery,the incidence of VAP was 59.8％.The results revealed statistically significant differences between the two groups in terms of age,presence of atrial fibrillation,admission national institutes of health stroke scale(NIHSS)score,admission glasgow coma scale(GCS)score,impaired consciousness,swallowing dysfunction,opera-tive time,postoperative 24-hour systemic inflammatory response index(SIRI),duration of mechanical ventilation,length of ICU stay,and the presence of an indwelling gastrostomy tube(P＜0.05).Additionally,the incidence of poor functional outcomes was 57.8％in the VAP group compared to 14.0％in the non-VAP group,indicating a worse prognosis for patients in the VAP group.The variables i-dentified through LASSO regression screening were included in a multifactorial Logistic regression analysis.This analysis revealed that the SIRI and the duration of mechanical ventilation were independent risk factors for the development of VAP following intervention in patients with hypertension and AIS-LVO(P＜0.05).Conversely,the admission GCS score was identified as a protective factor(P＜0.05).These three indicators were utilized to construct a prognostic nomogram model.The model's internal validity was assessed using the Boot-strap method with 1000 resamples,and the calibration curves were found to be in close agreement with the ideal fitted line,exhibiting a mean absolute error of 0.029,indicating good curve accuracy.The Logistic regression model's goodness of fit was evaluated using the Hos-mer and Lemeshow test,which yielded a x2 value of 5.38 and a P-value of 0.716,suggesting a good fit.The AUC of the model was 0.812(95％confidence interval 0.730-0.894),and the DCA indicated that the model has favorable clinical applicability.Conclusion A prediction model based on admission GCS score,postoperative 24-hour SIRI,and duration of mechanical ventilation demonstrates a robust predictive value for the incidence of VAP following intervention in patients with hypertension and acute ischemic stroke with AIS-LVO.

Objective Through the analysis of the clinical characteristics of post-interventional complications of ventilator-associ-ated pneumonia(VAP)in patients with hypertension and acute large vessel occlusive cerebral infarction(AIS-LVO),we aim to develop and validate a risk prediction model.Methods We conducted a retrospective analysis of clinical data from 107 patients hospitalized for hypertension with AIS-LVO at Dongguan Hospital of Guangzhou University of Traditional Chinese Medicine between July 2020 and Au-gust 2023.Patients were categorized into two groups based on their hospitalization:the VAP group,consisting of 64 patients who devel-oped VAP,and the non-VAP group,comprising 43 patients who did not experience VAP.Least absolute shrinkage and selection opera-tor regression(LASSO)analysis was employed to identify potential predictors.Subsequently,a nomogram model was constructed using multifactorial Logistic regression analysis.The model's discriminative ability,calibration,and clinical utility were assessed using the area(AUC)under the receiver operating characteristic(ROC)curve,calibration curves,and decision curve analysis(DCA).Results In 107 patients with hypertension and AIS-LVO who underwent interventional surgery,the incidence of VAP was 59.8％.The results revealed statistically significant differences between the two groups in terms of age,presence of atrial fibrillation,admission national institutes of health stroke scale(NIHSS)score,admission glasgow coma scale(GCS)score,impaired consciousness,swallowing dysfunction,opera-tive time,postoperative 24-hour systemic inflammatory response index(SIRI),duration of mechanical ventilation,length of ICU stay,and the presence of an indwelling gastrostomy tube(P＜0.05).Additionally,the incidence of poor functional outcomes was 57.8％in the VAP group compared to 14.0％in the non-VAP group,indicating a worse prognosis for patients in the VAP group.The variables i-dentified through LASSO regression screening were included in a multifactorial Logistic regression analysis.This analysis revealed that the SIRI and the duration of mechanical ventilation were independent risk factors for the development of VAP following intervention in patients with hypertension and AIS-LVO(P＜0.05).Conversely,the admission GCS score was identified as a protective factor(P＜0.05).These three indicators were utilized to construct a prognostic nomogram model.The model's internal validity was assessed using the Boot-strap method with 1000 resamples,and the calibration curves were found to be in close agreement with the ideal fitted line,exhibiting a mean absolute error of 0.029,indicating good curve accuracy.The Logistic regression model's goodness of fit was evaluated using the Hos-mer and Lemeshow test,which yielded a x2 value of 5.38 and a P-value of 0.716,suggesting a good fit.The AUC of the model was 0.812(95％confidence interval 0.730-0.894),and the DCA indicated that the model has favorable clinical applicability.Conclusion A prediction model based on admission GCS score,postoperative 24-hour SIRI,and duration of mechanical ventilation demonstrates a robust predictive value for the incidence of VAP following intervention in patients with hypertension and acute ischemic stroke with AIS-LVO.

Objective: To identify the social ecological factors of individual, family, and physical environments for affecting the development of fundamental motor skills (FMS) among overweight and obese children, so as to provide a basis for the future intervention design and policy making. Methods: From March to April 2022, one public primary school was recruited from each of the 4 main urban areas in Shijiazhuang, and a total of 425 children in schools were recruited for data collection including individual, family, physical environmental factors, by using a stratified cluster random sampling approach. Test of Gross Motor Development-Third Edition (TGMD-3) was used to evaluate children s FMS. Hierarchical linear regression model was employed to analysis the associations between the 18 factors for individual, family, and physical environments, and the FMS of overweight and obese children. Results: Individual level including the child s age, gender and sleep duration, and family level including high family economic level, parental support for physical activity, and the physical activity environment surrounding the family and community were consistent predictors of movement skills ( B =0.422, -1.972, 0.014, 0.045, 1.042, 0.827, 1.898), ball skills ( B =0.858, 3.953, 0.013, 0.092, 2.141, 1.173, 1.954), and composite skills ( B =1.305, 1.915, 0.028, 0.142, 3.091, 1.962, 3.879) among overweight and obese children ( P <0.05). Furthermore, child s body mass index (BMI), moderate to vigorous physical activity, perceived motor competence, pleasure of exercise,as well as BMI and physical activity levels of their primary caregiver, were associated with different types of FMS ( P <0.05). Individual, family, and physical environmental factors had moderate to high predictive explanatory power for FMS among overweight and obese children ( 2=0.69, 0.75, 0.93, P <0.01). Conclusions The factors influencing the development of FMS in overweight and obese children are multifaceted, with individual, family, and physical environment factors all playing significant roles.Corresponding measures should be actively taken to improve FMS in overweight and obese children.

Objective: To investigate the effects of lactoprotein iron chelates on rats with iron deficiency anaemia (IDA), so as to provide insights into developing and utilizing novel iron supplements. Methods: Seventy weaning female SPF-graded rats of the SD strain were randomly divided into the control group (A), model group (B), ferrous sulfate group (C), lactoferrin group (D), lactoferrin iron chelate group (E), Casein oligopeptide iron chelate group (F) and whey protein oligopeptide iron chelate group (G), with 10 rats in each group. The rats in group A were fed with normal diet, and the others were fed with poor iron diet for IDA modeling. The corresponding interventions were given by intragastric administration once a day. The iron ion concentrations of group C, E, F and G were 2.0 mg/kg, and the protein and oligopeptide concentrations of group D, E, F and G were 2 000 mg/kg. Body weight and hemoglobin of rats were measured weekly during 21-day intervention. At the end, peripheral blood samples were collected, and blood routine, iron metabolism and liver function indicators were determined. Results: After the intervention, among blood routine indicators, the rats in group C, E, F and G showed elevated hemoglobin, red blood cell, mean corpuscular volume and hematocrit, and decreased free protoporphyrin and mean corpuscular hemoglobin concentration when compared with the rats in group B (all P<0.05); among iron metabolism indicators, the rats in group C, E and G showed elevated serum ferritin, the rats in group C, E, F and G showed elevated serum iron, the rats in group C, D, E, F and G showed decreased unsaturated iron binding capacity and total iron binding capacity when compared with the rats in group B (all P<0.05); among liver function indicators, the rats in group E and G showed decreased alanine transaminase when compared with the rats in group B (both P<0.05). Conclusions Lactoprotein alone could not completely improve IDA in rats compared with traditional iron supplement (ferrous sulfate). Lactoprotein iron chelate, especially whey protein oligopeptide iron chelate, could significantly improve IDA, iron reserve and liver function damage in rats.

Abstract: Objective To construct a shuttle vector pHT315-AaCPR100A with two spore-producing-dependent promoters and the target gene AaCPR100A in Escherichia coli-Bacillus thuringiensis. Methods The forward promoter of Cry3A, named Pro-1 (+), was amplified by PCR using pSVP27A plasmid as the template, and the target gene AaCPR100A was amplified using Aedes aegypti RNA reverse conversion cDNA as the template. The plasmid pHT315 was linearized by digestion with Hind Ⅲ and Sal Ⅰ. The forward promoter and the target gene were inserted into the linearized vector pHT315 successively by in-fusion cloning according to the transcription direction. The synthesized plasmid containing the Cry3A reverse promoter sequence was used as the template, and the Pro-1 (-) reverse promoter was amplified by PCR. The intermediate vector containing the forward promoter and the target gene was linearized by EcoR I restriction enzyme, and the reverse promoter was inserted downstream of the target gene by in-fusion cloning in the direction of transcription. Results By agarose gel electrophoresis, the forward promoter, target gene AaCPR100A and reverse promoter bands were clear and of good quality, which could be used for in-fusion cloning experiments. The two spore-producing-dependent promoters and target gene fragments were connected by In-fusion cloning. The recombinant vector pHT315-AaCPR100A was verified by PCR. The forward promoter, target gene fragment and reverse promoter were successfully amplified in the recombinant vector. Nucleotide sequencing verified that the sequencing results of the bidirectional promoter sequence and the target gene sequence were basically consistent with the sequence alignment results, which met the requirements of the construction of vector elements and proved that the recombinant vector was successfully constructed. Conclusions Based on the above results, this study proves that the recombinant shuttle vector with two spore-producing-dependent promoters can be successfully constructed by in-fusion cloning technology, laying the foundation for the construction of engineered Bacillus thuringiensis expressing dsRNA of AaCPR100A.

[This corrects the article DOI: 10.1016/j.apsb.2019.01.003.].

Background: Recent studies have found that there are significant associations between body iron status and the development of diabetes. In the present study, we aimed to analyze the association among iron overload (IO), insulin resistance (IR), and diabetes in Chinese adults, and to explore the sex difference. Methods: Men and women (age >19 years) who participated in the Chinese Health and Nutrition Survey and did not have diabetes at baseline were followed between 2009 and 2015 (n=5,779). Over a mean of 6 years, 75 participants were diagnosed with incident diabetes. Logistic regression was used to assess the risk factors associated with IO. Cox proportional hazard regression was used to estimate the risk of incident diabetes and to determine whether the risk differed among subgroups. Causal mediation analysis (CMA) was used to explore the mechanism linking IO and diabetes. Results: According to sex-stratified multivariable-adjusted Cox proportional hazards regression, IO increased the risk of incident diabetes. Women with IO had a higher risk of diabetes than men. Subgroup analysis with respect to age showed that the association between IO and diabetes was stronger in older women and younger men (P<0.001). CMA showed that liver injury (alanine transaminase) and lipid metabolism abnormalities (triglyceride, apolipoprotein B) contributed to the association between IO and diabetes. Conclusion IO is associated with diabetes and this association is sex-specific. IO may indirectly induce IR via liver injury and lipid metabolism abnormalities, resulting in diabetes.

Photothermal therapy has been intensively investigated for treating cancer in recent years. However, the long-term therapeutic outcome remains unsatisfying due to the frequently occurred metastasis and recurrence. To address this challenge, immunotherapy has been combined with photothermal therapy to activate anti-tumor immunity and relieve the immunosuppressive microenvironment within tumor sites. Here, we engineered silica-based core‒shell nanoparticles (JQ-1@PSNs-R), in which silica cores were coated with the photothermal agent polydopamine, and a bromodomain-containing protein 4 (BRD4) inhibitor JQ-1 was loaded in the polydopamine layer to combine photothermal and immune therapy for tumor elimination. Importantly, to improve the therapeutic effect, we increased the surface roughness of the nanoparticles by hydrofluoric acid (HF) etching during the fabrication process, and found that the internalization of JQ-1@PSNs-R was significantly improved, leading to a strengthened photothermal killing effect as well as the increased intracellular delivery of JQ-1. In the animal studies, the multifunctional nanoparticles with rough surfaces effectively eradicated melanoma via photothermal therapy, successfully activated tumor-specific immune responses against residual tumor cells, and further prevented tumor metastasis and recurrence. Our results indicated that JQ-1@PSNs-R could serve as an innovative and effective strategy for combined cancer therapy.