Objective To analyze serum calcium and phosphorus levels and its related factors of clinical type 2 diabetes mellitus (T2DM) with overt diabetic kidney disease (T2-dDKD).Methods Ninety cases of T2DM patients according to K/DOQI Recommendations in 2007 were selected as the study subjects.Based on the patients' 2 times mean urinary albumin/creatinine ratio (ACR),these people were divided into three groups,namely Normal albuminuria group (30 patients,ACR＜30 mg/gCr),Microalbuminuria group (30 patients,ACr =30-300 mg/gCr),Macroalbuminuria group (30 patients,ACR＞300 mg/gCr).Thirty cases of healthy at the same period were selected as the Control group.Serum calcium,phosphorus,hs-CRP,IL-6,HbA1c were detected.And glomerular filtration rate (eGFR) was calculated.Results The eGFR in Normal albuminuria group was more higher than other groups (P＜0.05),the eGFR of Microalbuminuria group was significantly lower than other groups (P＜0.05).Subgroups of T2DM with different albuminuria presence and severity,duration was also different between the groups,the more albumin in urine,the longer its duration.The contents of HbA1c in the groups of varying degrees of albuminuria increased as urinary albumin aggravation (HbA1c was (8.87±2.44) ％,(9.27±2.74)％,(11.04±2.86)％ respectively,P＜0.05),but there was not statistically significant between Microalbuminuria group ((9.27±2.74)％) and Normal albuminuria group ((8.87±2.44) ％).Compared with Control group,in subgroups of T2DM,serum calcium was decreased((2.22±0.19) mmol/L,(2.16±0.14) mmol/L,(2.13±0.18) mmol/L,and the Contorl group was (2.32±0.11)mmol/L,P＜0.05),and serum phosphorus ((1.16±0.31) mmol/L,(1.42±0.52) mmol/L,(1.98±0.58)mmol/L,and the Control group was (1.08±0.28) mmol/L),hs-CRP ((4.82±0.89) mmol/L,(8.46± 2.85)mmol/L,(13.09±3.49) mmol/L,and the Control group was (2.46±0.48) mmol/L),IL-6((10.32±4.19)pg/L,(14.78±4.34) pg/L,(16.67±6.62) pg/L,and the Control group was (7.03±2.15) pg/L) were increased(P＜0.05).In subgroups of T2DM,hs-CRP was significantly increased with the increase of the serum albumin((4.82±0.89) mmol/L,(8.46±2.85) mmol/L,(13.09±3.49) mmol/L,P＜0.05),there were no statistical significance about blood phosphorus among Macroalbuminuria group (1.98±0.58) mmol/L),control group((1.08±0.28) mmol/L),normal albuminuria group((1.16±0.31) mmol/L) and albumin urinary group (1.42±0.52) mmol/L).Serum phosphorus in Microalbuminuria group were positively correlated with hs-CRP,IL-6,HbA1c (r =0.431,0.384,0.517 respectively,P＜0.05).Serum phosphorus in Macroalbuminuria group were positively correlated with hs-CRP,IL-6,HbA1c (r=0.825,0.622,0.683 respectively,P＜0.01),but negatively with eGFR(r=0.600,P＜0.01).Conclusion Serum phosphorus metabolism is abnormal in patients with diabetic nephropathy,hs-CRP,IL-6,and HbA1c are the related factors influencing the progression of serum phosphorus in patients with diabetic nephropathy.

Objective To study the presence of drug resistant mutations of protease and reverse transcriptase among human immunodeficiency virus (HIV)-1 strains isolated from treatment naive HIV/ acquired immune deficiency syndrome (AIDS) patients in Heilongjiang Province of China and to provide the baseline data for starting antiretroviral therapy in this area. Methods The protease and reverse transcriptase gene sequences were amplified by nested-polymerase chain reaction (PCR) and then sequenced. The results were compared to the subtype B consensus amino acid sequence and analyzed with Stanford HIV-db drug resistance sequence interpretation. Results The results showed that HIV strains from 49 patients were classified as subtype B'. No primary mutations associated with protease inhibitor were detected. Some secondary mutations associated with protease inhibitor were detected, which included V77I(91.5%), L63P(76.6%), I93L(74.5%), E35D(61.7%), R57K (19.1%), R41K(10.6%), A71V(8.5%), M36I(8.5%), L10I(6.4%), D60E(6.4%), L89M (4.2%) and G16E(2. 1%). Only one case had a primary mutation M184I that was associated with resistance to reverse transcriptase inhibitors. However, many secondary mutations associated with resistance to reverse transcriptase inhibitors were found, including I135L/T/R/V(81.8%), V106I(22.7%), V179D/E(11.4%), R211K(9.1%), L214F(4.5%), V189I(4.5%) and V108I(2. 3%).Conclusions The prevalence of genotypic anti-HIV drug resistance is very low in treatment naive HIV/AIDS patients in Heilongjiang Province. However, closely monitoring on drug resistance mutation is very important for preventing the development and prevalence of multi-drug resistant or cross drug resistant HIV.

BACKGROUND: In the intricate pathological milieu post-spinal cord injury (SCI), neural stem cells (NSCs) frequently differentiate into astrocytes rather than neurons, significantly limiting nerve repair. Hence, the utilization of biocompatible hydrogel scaffolds in conjunction with exogenous factors to foster the differentiation of NSCs into neurons has the potential for SCI repair. METHODS: In this study, we engineered a 3D-printed porous SilMA hydrogel scaffold (SM) supplemented with pH-/ temperature-responsive paclitaxel nanoparticles (PTX-NPs). We analyzed the biocompatibility of a specific concentration of PTX-NPs and its effect on NSC differentiation. We also established an SCI model to explore the ability of composite scaffolds for in vivo nerve repair. RESULTS: The physical adsorption of an optimal PTX-NPs dosage can simultaneously achieve pH/temperature-responsive release and commendable biocompatibility, primarily reflected in cell viability, morphology, and proliferation.An appropriate PTX-NPs concentration can steer NSC differentiation towards neurons over astrocytes, a phenomenon that is also efficacious in simulated injury settings. Immunoblotting analysis confirmed that PTX-NPs-induced NSC differentiation occurred via the MAPK/ERK signaling cascade. The repair of hemisected SCI in rats demonstrated that the composite scaffold augmented neuronal regeneration at the injury site, curtailed astrocyte and fibrotic scar production, and enhanced motor function recovery in rat hind limbs. CONCLUSION The scaffold’s porous architecture serves as a cellular and drug carrier, providing a favorable microenvironment for nerve regeneration. These findings corroborate that this strategy amplifies neuronal expression within the injury milieu, significantly aiding in SCI repair.

BACKGROUND: In the intricate pathological milieu post-spinal cord injury (SCI), neural stem cells (NSCs) frequently differentiate into astrocytes rather than neurons, significantly limiting nerve repair. Hence, the utilization of biocompatible hydrogel scaffolds in conjunction with exogenous factors to foster the differentiation of NSCs into neurons has the potential for SCI repair. METHODS: In this study, we engineered a 3D-printed porous SilMA hydrogel scaffold (SM) supplemented with pH-/ temperature-responsive paclitaxel nanoparticles (PTX-NPs). We analyzed the biocompatibility of a specific concentration of PTX-NPs and its effect on NSC differentiation. We also established an SCI model to explore the ability of composite scaffolds for in vivo nerve repair. RESULTS: The physical adsorption of an optimal PTX-NPs dosage can simultaneously achieve pH/temperature-responsive release and commendable biocompatibility, primarily reflected in cell viability, morphology, and proliferation.An appropriate PTX-NPs concentration can steer NSC differentiation towards neurons over astrocytes, a phenomenon that is also efficacious in simulated injury settings. Immunoblotting analysis confirmed that PTX-NPs-induced NSC differentiation occurred via the MAPK/ERK signaling cascade. The repair of hemisected SCI in rats demonstrated that the composite scaffold augmented neuronal regeneration at the injury site, curtailed astrocyte and fibrotic scar production, and enhanced motor function recovery in rat hind limbs. CONCLUSION The scaffold’s porous architecture serves as a cellular and drug carrier, providing a favorable microenvironment for nerve regeneration. These findings corroborate that this strategy amplifies neuronal expression within the injury milieu, significantly aiding in SCI repair.

BACKGROUND: In the intricate pathological milieu post-spinal cord injury (SCI), neural stem cells (NSCs) frequently differentiate into astrocytes rather than neurons, significantly limiting nerve repair. Hence, the utilization of biocompatible hydrogel scaffolds in conjunction with exogenous factors to foster the differentiation of NSCs into neurons has the potential for SCI repair. METHODS: In this study, we engineered a 3D-printed porous SilMA hydrogel scaffold (SM) supplemented with pH-/ temperature-responsive paclitaxel nanoparticles (PTX-NPs). We analyzed the biocompatibility of a specific concentration of PTX-NPs and its effect on NSC differentiation. We also established an SCI model to explore the ability of composite scaffolds for in vivo nerve repair. RESULTS: The physical adsorption of an optimal PTX-NPs dosage can simultaneously achieve pH/temperature-responsive release and commendable biocompatibility, primarily reflected in cell viability, morphology, and proliferation.An appropriate PTX-NPs concentration can steer NSC differentiation towards neurons over astrocytes, a phenomenon that is also efficacious in simulated injury settings. Immunoblotting analysis confirmed that PTX-NPs-induced NSC differentiation occurred via the MAPK/ERK signaling cascade. The repair of hemisected SCI in rats demonstrated that the composite scaffold augmented neuronal regeneration at the injury site, curtailed astrocyte and fibrotic scar production, and enhanced motor function recovery in rat hind limbs. CONCLUSION The scaffold’s porous architecture serves as a cellular and drug carrier, providing a favorable microenvironment for nerve regeneration. These findings corroborate that this strategy amplifies neuronal expression within the injury milieu, significantly aiding in SCI repair.

BACKGROUND: In the intricate pathological milieu post-spinal cord injury (SCI), neural stem cells (NSCs) frequently differentiate into astrocytes rather than neurons, significantly limiting nerve repair. Hence, the utilization of biocompatible hydrogel scaffolds in conjunction with exogenous factors to foster the differentiation of NSCs into neurons has the potential for SCI repair. METHODS: In this study, we engineered a 3D-printed porous SilMA hydrogel scaffold (SM) supplemented with pH-/ temperature-responsive paclitaxel nanoparticles (PTX-NPs). We analyzed the biocompatibility of a specific concentration of PTX-NPs and its effect on NSC differentiation. We also established an SCI model to explore the ability of composite scaffolds for in vivo nerve repair. RESULTS: The physical adsorption of an optimal PTX-NPs dosage can simultaneously achieve pH/temperature-responsive release and commendable biocompatibility, primarily reflected in cell viability, morphology, and proliferation.An appropriate PTX-NPs concentration can steer NSC differentiation towards neurons over astrocytes, a phenomenon that is also efficacious in simulated injury settings. Immunoblotting analysis confirmed that PTX-NPs-induced NSC differentiation occurred via the MAPK/ERK signaling cascade. The repair of hemisected SCI in rats demonstrated that the composite scaffold augmented neuronal regeneration at the injury site, curtailed astrocyte and fibrotic scar production, and enhanced motor function recovery in rat hind limbs. CONCLUSION The scaffold’s porous architecture serves as a cellular and drug carrier, providing a favorable microenvironment for nerve regeneration. These findings corroborate that this strategy amplifies neuronal expression within the injury milieu, significantly aiding in SCI repair.

BACKGROUND: Degeneration of the annulus fibrosus (AF), an important structure of the intervertebral disc, is one of the main causes of degenerative disc disease. Fabrication of scaffolds replicating the stratified microstructure of the AF is critical for the successful regeneration of AF. METHODS: In this study, we cultured rabbit AF-derived stem cells (AFSCs) using fabricated electrospun fibrous poly-Llactic acid scaffolds with different diameters. We applied cyclic tensile strain (CTS) on the scaffolds to regulate the differentiation of AFSCs into specific cell types that resided at the inner, middle, and outer zones of the AF. RESULTS: We found that the morphologies of AFSCs on the smaller-fiber-diameter scaffolds were nearly round, whereas spindle-like cells morphologies were observed on large-diameter scaffolds. CTS enhanced these phenomena and made the cells slender. The expression levels of collagen-I in cells increased as a function of the fiber diameter, whereas collagen-II and aggrecan exhibited opposite trends. Moreover, the application of CTS upregulated the gene expressions of collagen-I, collagen-II, and aggrecan. CONCLUSION Overlaying the scaffolds with different CTS-stimulated cells could eventually lead to engineered AF tissues with hierarchical structures that approximated the native AF tissue. Thus, the proposed methodologies could be potentially applied for AF regeneration.

BACKGROUND: Degeneration of the annulus fibrosus (AF), an important structure of the intervertebral disc, is one of the main causes of degenerative disc disease. Fabrication of scaffolds replicating the stratified microstructure of the AF is critical for the successful regeneration of AF. METHODS: In this study, we cultured rabbit AF-derived stem cells (AFSCs) using fabricated electrospun fibrous poly-Llactic acid scaffolds with different diameters. We applied cyclic tensile strain (CTS) on the scaffolds to regulate the differentiation of AFSCs into specific cell types that resided at the inner, middle, and outer zones of the AF. RESULTS: We found that the morphologies of AFSCs on the smaller-fiber-diameter scaffolds were nearly round, whereas spindle-like cells morphologies were observed on large-diameter scaffolds. CTS enhanced these phenomena and made the cells slender. The expression levels of collagen-I in cells increased as a function of the fiber diameter, whereas collagen-II and aggrecan exhibited opposite trends. Moreover, the application of CTS upregulated the gene expressions of collagen-I, collagen-II, and aggrecan. CONCLUSION Overlaying the scaffolds with different CTS-stimulated cells could eventually lead to engineered AF tissues with hierarchical structures that approximated the native AF tissue. Thus, the proposed methodologies could be potentially applied for AF regeneration.

Objective:To investigate the therapeutic effect of comprehensive geriatric assessment(CGA) in elderly patients with chronic heart failure(CHF) complicated with sarcopenia, and to provide a theoretical reference for clinical application.Methods:This study was a prospective randomized controlled study. 110 elderly CHF patients with myopenia admitted to the Third People's Hospital of Hefei from January 2019 to February 2022 were selected. Using the random number table method, 56 cases were divided into an observation group and 54 cases into a control group. Before treatment, the control group of patients underwent a selective single assessment based on the hospital's requirements and the patient's actual situation, including a fall risk assessment, nutritional risk screening checklist assessment, and routine medication to improve cardiac function and prognosis; Before treatment, the patients in the observation group were assessed with CGA, including the assessment of physical function, mental and psychological status, multiple drug management, pain, Sleep disorder, and social environment. According to the assessment results, individual diagnosis and treatment plans were formulated, implemented, and dynamically adjusted. The two groups were treated for 12 weeks. The general information, treatment compliance, B-type brain natriuretic peptide (BNP) level, left ventricular Ejection fraction (LVEF), 6 min walking distance (6MWD), arm strength of upper limbs and 6 m walking speed, clinical efficacy and prognosis of the two groups were compared before and after treatment. The measurement data is represented by xˉ± s, group t-tests are used for inter group comparison, and paired t-tests are used for intra group comparison before and after treatment; Counting data is represented as an example (%), and inter group comparisons are made using χ 2 test, non parametric rank sum test was used for inter group comparison of hierarchical data. Results:There was no statistically significant difference in gender, age, course of CHF, smoking, alcohol consumption, number of comorbidities, cardiac function grading, and treatment compliance between the two groups of patients (all P>0.05), indicating comparability. Before treatment, there was no statistically significant difference in plasma BNP, LVEF, 6MWD, upper limb grip strength, and 6-meter walking speed between the two groups of patients (all P>0.05); After treatment, the BNP of both groups of patients was lower than before treatment and the observation group was lower than the control group. LVEF, 6MWD, upper limb grip strength, and 6-meter walking speed were all higher than before treatment and the observation group was higher than the control group [(343.45±34.95) ng/L vs (387.09±46.96) ng/L, (49.61±7.11)% vs (42.94±5.72)%, (348.92±37.73) m vs (297.74±43.48) m, (22.64±3.82) kg vs (19.48±3.88) kg, (0.97±0.10) m/s vs (0.83±0.12) m/s], The differences were statistically significant ( t-values were 5.51, -5.40, -6.60, -4.31, -6.60, all P<0.001). After 12 weeks of treatment, there was no statistically significant difference in clinical efficacy between the two groups of patients ( P=0.216), but the overall poor prognosis rate in the follow-up observation group was lower than that in the control group [7.14%(4/56) vs 22.22% (12/54)], and the difference was statistically significant (χ 2=5.03, P=0.025). Conclusions:Developing, implementing, and dynamically adjusting the individualized treatment plan involving CGA can improve the prognosis of elderly CHF patients with sarcopenia, help improve cardiac function, increase grip strength and somatic function, and reduce the risk of major adverse cardiovascular events ,all-cause mortality in elderly patients with CHF combined with sarcopeni and has certain clinical application value.

Objective:To investigate the effects of oligodeoxynucleotide (ODN) MT01 on the morphology, proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs).Methods:The BMSCs of SD rat were isolated and cultured by direct adherence method . The extracted cells were identified by cell morphology of different generations, the expression of surface markers detected by flow cytometry and osteogenic differentiation potential. ODN MT01 group was set up in a gradient of concentrations (0.5, 1.0, 2.0, 4.0 μg/ml) and PBS group as control. Each group of experiments was repeated three times. The morphological changes of cell nucleus and cytoskeleton were fluorescent stained by DAPI and FITC-phalloidin, respectively. The proliferation activities of the BMSCs in different group were analyzed by CCK-8 assay at 1, 4 and 7 d. The degrees of osteogenic differentiation of BMSCs in different group were assessed via alkaline phosphatase (ALP) staining, ALP activity assay and alizarin red S staining respectively on the 7th and 21st days after cultured in osteogenic induction medium. Statistical differences between two groups and among groups were analyzed by t-test and one-way ANOVA, respectively. Differences were regarded as statistically significant when a P value of less than 0.05. Results:Flow cytometry showed that the BMSCs were positive for CD29 (99.8%) and CD44 (96.1%) while negative for CD11b (1.03%) and CD45 (1.74%). ALP staining and alizarin red S staining were positive at different stages of osteogenesis induction confirmed that BMSCs was able to differentiate into the osteoblast. The nucleus and cytoskeleton staining showed that BMSCs were shrunk and the extensibility was reduced when the concentration of ODN MT01 was 4.0 μg/ml. CCK-8 assay showed that the absorbance value of control group was 0.446±0.018, 1.0 μg/ml ODN MT01 was 0.505±0.019, 2.0 μg/ml ODN MT01 was 0.528±0.014 after cultured for 4 days. Compared with the control group, the difference is statistically significant ( t=2.954, 4.083, P=0.033, 0.008). The absorbance value of control group was 0.514±0.027, 1.0 μg/ml ODN MT01 was 0.607±0.007, and 2.0 μg/ml ODN MT01 was 0.636±0.023 after cultured for 7 days. Compared with the control group, the difference was statistically significant ( t=4.664, 6.091, P=0.009, 0.008). The proliferation ability of BMSCs was significantly higher than that of the control group. However, 4.0 μg/ml ODN MT01 (0.427±0.013) had an inhibitory effect on the proliferation ability of BMSCs ( t=4.332, P=0.0149). The blue mass and mineralized nodule improved significantly with the increase of ODN MT01 concentration during the induction of osteogenic differentiation of BMSCs. After cultured for 4 days, the result of ALP activity assay was similar to ALP staining. The activity value of ODN MT01 in the control group was 1.207±0.023, 0.5 μg/ml ODN MT01 was 1.747±0.095, 1.0 μg/ml ODN MT01 was 2.200±0.136, 2.0 μg/ml ODN MT01 was 3.560±0.088, 4.0 μg/ml ODN MT01 was 3.490±0.144. Compared with the control group, the difference was statistically significant ( t=4.313, 7.934, 18.800, 18.240; P=0.005, 0.001, <0.001, <0.001). But there was no difference between 2.0 and 4.0 μg/ml groups ( t=0.562, P=0.590). Conclusions:ODN MT01 with concentration of 2.0 μg/ml could significantly stimulate the proliferation and osteogenic differentiation of BMSCs without affecting the morphology of BMSCs.