BACKGROUND:Hydrolysis in vivo is the key mechanism of degradation in DL-polylactic acid (PDLLA). When it is combined with hydroxyapatite (HA), could the biodegradation and weight loss rate be improved? OBJECTIVE: To observe the changes in the interface and structure of HA/PDLLA composite after in vivo implantation into rabbit femoral defects.DESIGN: Randomized grouping and controlled observation.SETTING: Biomedical Materials and Engineering Research Center, Wuhan University of Technology.MATERIALS: Forty healthy adult Japan White Rabbits of 2.0-2.5 kg, either male or female were provided by the Animal Experimental Center of Hubei Province (No. SCXK. 2003-0005).METHODS: The experiment was conducted in Biomedical Materials and Engineering Research Center, Wuhan University of Technology from June 2005 to March 2006. ①The rabbits were randomly divided into two groups: HA/PDLLA group and PDLLA control group with 20 animals in each group. After anesthetized with ketamine and proazamine, the sample rods of HA/PDLLA and PDLLA were respectively implanted into the drilled bone cavities (φ5 mm × 8 mm) among condyles of femur sites of the rabbits, and the rod could be slightly higher than the surface of bone substance. The samples were covered by periosteum and skin, and then the skin and periosteum were repositioned. ②The complete implants and peripheral bone tissues were taken out respectively after 3, 6, 12 and 24 weeks implantation. The changes in the interface and structure of HA/PDLLA composite after in vivo implantation were observed by using scanning electron microscope (SEM, JSM-5610LV, Japan).MAIN OUTCOME MEASURES: Changes in the interface and structure of HA/PDLLA composite after in vivo implantation.RESULTS: Totally 40 rabbits were involved in the result analysis. After the materials were implanted, HA granules shed from the material surface, some fibroblasts grew into the tissue and a little new osteotylus was formed, indicating HA/PDLLA composite had capabilities of bone-formation and bone-connection. After 24 weeks implantation, the material was divided and wrapped by tissues, neogenetic bone tissue grew into the material, and the fracture healed well,indicating HA/PDLLA composite had good biocompatibility. As for biodegradable PDLLA polymer, hydrolysis in vivo is the most main mechanism of degradation; the degradation speed was decreased owing to being compounded with HA.CONCLUSION: HA/PDLLA composite has capabilities of bone-formation and bone-connection; the biocompatibility of the composite is improved accordingly on account of the decrease of the degradation speed. HA/PDLLA composite is suitable for clinical application as absorbable materials for internal fixation.

Objective To detect the relationship between the pathological degrees of chronic cholecystitis and coincident diseases. Method The pathological degree was divided into mild,moderate and severe degree according to the pathological changes in 442 cases of chronic cholecystitis,and the proliferation of mucosa cell was detected by SP immunohistochemical staining in 105 cases. Results The coincident calculus, polyp, adenoma in the mild chronic cholecystitis were 65.0%,17.1% and 0.5%, respectively. The coincident calculus, polyp, adenoma and malignant neoplasms in the moderate chronic cholecystitis were 70.1%, 19.4%, 3.7% and 2.2%. The coincident calculus, polyp, adenoma and malignant neoplasms in the severe chronic cholecystitis were 88.0%, 26.4%, 24.2% and 9.9%. The positive expression rates of PCNA in mild, moderate and severe chronic cholecystitis were 12.3%, 17.5% and 38.7%, respectively. The results showed that the pathological degree of chronic cholecystitis was obviously related to the coincidence of calculus, polyp, adenoma, malignant neoplasms. Conclusions Severe chronic cholecystitis is a high-risk lesion of gallbladder carcinoma,it should be removed surgically.

OBJECTIVE: To investigate a new way to yield plenty of high purity olfactory ensheathing cells (OECs) and its biocompatibility with appropriate scaffolds. METHODS: OECs were prepared from neonatal Wister rats and co-cultured with poly [LA-co-(Glc-alt-Lys)] (PLGL). Its contact angle, adherent rate, and activity rate were tested. RESULTS: The contact angle of poly (D, L-lactic acid) (PDLLA) (84.5 degree+/-1.5 degree) was significantly higher than that of PLGL (52.6 degree+/-0.8 degree), the adherent rate of PLGL (80%) was significantly higher than that of the PDLLA (57%), and the activity rate of PLGL (88%) was much higher than that of the PDLLA (76%). CONCLUSION PLGL possesses better hydrophilicity and biocompatibility than PDLLA, and it can provide a better cell growth circumstance which is helpful for the effective treatment of nerve injury.
Animals ; Animals, Newborn ; Biocompatible Materials ; Cells, Cultured ; Lactic Acid ; chemical synthesis ; pharmacology ; Nerve Regeneration ; Olfactory Bulb ; cytology ; Polyglycolic Acid ; chemical synthesis ; pharmacology ; Polylactic Acid-Polyglycolic Acid Copolymer ; Rats ; Rats, Wistar ; Spinal Cord Injuries ; physiopathology ; Tissue Engineering ; methods ; Tissue Scaffolds ; chemistry

OBJECTIVE To investigate the efficacy and adverse reaction of CD 19-targeted chimeric antigen receptor T cells （CAR-T）in the treatment of relapsed/refractory diffuse large B -cell lymphoma （R/R DLBCL ），so as to provide an evidence -based basis for more reasonable and efficient application of CAR -T. METHODS Retrieved from PubMed ，Embase，Cochrane， ClinicalTrials.gov，CNKI，Wanfang，VIP database ，the literature about CD 19 targeted CAR -T in the treatment of R/R DLBCL that were published from the inception to April 2022 were screened . Taking objective remission rate （ORR），complete remission rate （CRR）and incidence of adverse reactions as outcome indicators ，subgroup analysis was performed according to the costimulatory factor of CAR -T and the different types of research . R 4.1.2 software was used for meta -analysis，sensitivity analysis and publication bias analysis . RESULTS A total of 11 pieces of literature were screened ，involving 1 466 patients. The ORR of CD -19 targeted CAR -T cells in the treatment of R/R DLBCL was 72.1%（95% CI：62.3%-81.9%），the CRR was 50.8%（95% CI：41.1%- 60.5%），the incidence of cytokine release syndrome （CRS）was 77.5%（95% CI：65.6%-89.4%），the incidence of neurotoxicity was 41.4%（95% CI：26.8%-56.1%）. Results of subgroup analysis showed that the incidence of ORR ，CRR，CRS and neurotoxicity in costimulatory factor CD 28 subgroup were higher than those in 4-1BB subgroup . The incidence of ORR ，CRR，CRS and neurotoxicity in the observational experimental subgroup were higher than those in the intervention experimental subgroup . CONCLUSIONS CD19 targeted CAR -T has high ORR and CRR for R/R DLBCL ，as well as higher incidence of adverse reactions. Co-stimulatory factor CD 28 has higher ORR ，CRR， CRS incidence and neurotoxicity incidence than 4-1BB.

Background Aluminum can induce irreversible structural and synaptic functional damage, and the associated mechanism may be related to the neurite damage regulated by glycogen synthase kinase-3β (GSK-3β)/collapsin response mediator protein 2 (CRMP2). Objective This experiment is conducted to investigate the effect of aluminum-maltolate [Al(mal)₃] on primary hippocampal neuron neurites in mice, and reveal the role of GSK-3β-CRMP2 in this process. Methods The hippocampus of newborn ICR mice (≤ 24 h old) was used for primary neuronal cultures. On the 5th day in vitro (DIV5), neuron purity detection were performed by confocal laser scanning microscopy. On DIV7, the neurons were transfected with lentiviral vector-mediated mNeonGreen. On DIV10, the neurons with mNeonGreen fluorescence in good growth state were treated with Al(mal)₃. The stage I experimental groups were blank control group, maltol group, 10 µmol·L⁻¹ Al group, 20 µmol·L⁻¹ Al group, and 40 µmol·L⁻¹ Al group. Then 20 µmol·L⁻¹ Al was used to establish a model of neurite injury and for the intervention. The stage II experimental groups were blank control group, dimethyl sulfoxide (DMSO) group, Al (20 µmol·L⁻¹) group, SB (GSK-3β inhibitor, 1 µmol·L⁻¹), and SB (1 µmol·L⁻¹)+Al (20 µmol·L⁻¹) group. CCK-8 method was used to detect the viability of neurons. The primary hippocampal neurons of mice were scanned with high content analysis system at 0 h and 48 h after Al or SB treatment, and the density and length of neurites were analyzed. Western blotting was used to detect the expression and phosphorylation levels of CRMP2 and GSK-3β in primary hippocampal neurons of mice. Results The immunofluorescence results showed that the purity of primary neurons was more than 90%. Compared with the blank control group in stage I, the cell viability rates of the 10, 20, and 40 µmol·L⁻¹ Al groups were decreased after 48h of Al(mal)₃ treatment (P<0.05), while the cell viability rate of the maltol group had no significant change. There was no significant difference in cell viability rate among the DMSO group, the SB group, and the control group after 48h of SB treatment, and the viability rate of neurons in the SB+Al group was higher than that in the Al group (P<0.05) in stage II. The 48 h/0 h ratios of average number and length of neurites in the control group were 90.13%±11.70% and 113.24%±8.34%, respectively. The 48 h/0 h ratios in the Al group were 56.47%±16.36% and 62.06%±6.75%, respectively, which were lower than those in the control group (P<0.05). The 48 h/0 h ratios of average number of neurites in the SB group (99.03%±21.83%) was not significantly different from that in the control group, but the 48 h/0 h ratio of average length of neurites in the SB group (128.72%±15.39%) was higher than that in the control group (P<0.05). The 48 h/0 h ratios of average number (72.59%±10.89%) and length of neurites (93.84%±14.65%) in the SB+Al group were significantly increased compared with those in the Al group (P<0.05). Western blotting results showed that: There was no significant difference in GSK-3β protein level among all groups; compared with the control group (1.00±0.18), the protein level of p-GSK-3β in the Al group (0.45±0.05) was significantly decreased, and that in the SB group (1.32±0.23) was significantly increased; the protein level of p-GSK-3β in the SB+Al group (0.80±0.05) was significantly higher than that in the Al group (P<0.05). Compared with the control group (1.00±0.07), the CRMP2 protein level in the Al group (0.66±0.11) was significantly decreased (P<0.05), while that in the SB group (1.01±0.02) was not significantly changed. Compared with the control group (1.00±0.13), the p-CRMP2 protein level in the Al group (1.50±2.18) was significantly increased, and that in the SB group (0.62±0.09) was significantly decreased (P<0.05); the protein level of p-CRMP2 in the SB+Al group (1.28±0.24) was lower than that in the Al group (P<0.05). Conclusion Aluminum may activate GSK-3β, increase CRMP2 phosphorylation level, and damage neurite growth.

OBJECTIVE：To investigate the effects of dihydroartemisinin （DHA）on the metabolism of amino acid metabolites in human hepatocellular carcinoma cells Huh 7 and BEL- 7402，and to provide theoretic basis for clarifying the mechanism of DHA regulating the metabolism of hepatocellular carcinoma cells. METHODS ：CCK-8 method was taken to detect the effect of different concentrations of DHA （12.5，25，50，100 µmol/L）treating for 24，48，72 h on the two kinds of cells. Two kinds of cells were divided into control group and administration group （DHA，25 µmol/L），and then cultured with drug-free or drug-containing medium for 24 h，operated in parallel for three times. After derivatization of cell samples in each group ，GC-MS method was used to detect the content of amino acid metabolites ，combined with SIMCA-P software analysis and compound library comparison ，the differential metabolites in two kinds of cells were screened out. The pathway enrichment analysis of differential metabolism was conducted with Metaboanalyst 4.0 software. RESULTS ：Compared with control group ，the contents of glutamine ，glutathione， phenylalanine，fumaric acid and taurine were trending down in Huh 7 or BEL- 7402 cells. There were 28 and 29 differential metabolites obtained from the above two kinds of cells ，and 10 of them were common differential metabolites ，including glutamine，glutathione，taurine，fumaric acid ，phenylalanine，etc. The differential metabolites were enriched in 8 and 6 pathways respectively. The common enrichment pathways were amino acid-tRNA biosynthesis ，aspartate-alanine-glutamate metabolism ， nitrogen metabolism ，phenylalanine metabolism and pentose phosphate pathway ，etc. CONCLUSIONS ：DHA can significantly reduce the activities of Huh 7 cells and BEL- 7402 cells，and the contents of glutamine ，glutamic acid ，glutathione and phenylalanine，etc. It may regulate the growth of the two kinds of cells by influencing the mechanism of aspartic acid- alanine-glutamate metabolic pathway ，etc.

Background Aluminum can cause synaptic plasticity damage in the hippocampus, probably due to blocked interneuronal signal transmission. MicroRNA-29a (miR-29a) can target phosphatase and tensin homolog deleted on chromosome ten (PTEN) expression and participate in the generation of neuronal networks, and may be involved in the effect of aluminum on the electrical activity of neuronal networks. Objective To study the role and mechanism of miR-29a-targeted PTEN in aluminum-induced neuronal network injury in primary hippocampal neurons of ICR mice treated with maltol aluminum [Al(mal)₃] in vitro. Methods Primary hippocampal neurons of ICR mice born within 24 h were cultured in vitro. The purity of neurons was determined by labeling neuron-specific microtubule-associated protein 2 (MAP2) by immunofluorescence staining on day six of the culture; neurons were treated with different concentrations of Al(mal)₃, and divided into a control group, and 10, 20, and 40 μmol·L⁻¹ Al(mal)₃ groups, and neuronal cell viability was detected by CCK-8 method. Al(mal)₃ at 20 μmol·L⁻¹ was selected for subsequent experiments to establish a neuronal network injury model for intervention. The lentivirus infection method was used to transfect miR-29a into neurons, which were divided into mNG, mNG+20 μmol·L⁻¹ Al(mal)₃, miR-29a, and miR-29a+20 μmol·L⁻¹ Al(mal)₃ groups, and micro-electrode array (MEA) was used to analyze the firing of neuronal network. The expressions of miR-29a and PTEN mRNA in each group were detected by real-time PCR (RT-PCR), and the expression of PTEN protein in each group was detected by Western blotting. Results The purity of primary mouse hippocampal neurons was greater than 90%, and the viability of the neurons was above 80% in all groups. At 48 h of the designed Al(mal)₃ treatments, the changes in spike frequency, burst frequency, network burst frequency, and synchrony index of neurons cultivated on MEA plates in the control group were 207.56%±38.70%, 73.19%±46.43%, 75.42%±33.04%, and 117.13%±15.54%, respectively; the Al(mal)₃ groups’ neuronal network electrical activity showed a decreasing trend. Compared with the control group, the spike frequency, burst frequency, network burst frequency, and synchrony index of the 20 and 40 μmol·L⁻¹ Al(mal)₃ groups significantly decreased (The changes were 171.70%±28.08%, 49.20%±23.23%, 50.20%±18.18%, and 85.45%±20.30%; 150.68%±26.15%, 43.43%±15.54%, 52.05%±26.31%, and 26.80%±8.29%, respectively, P < 0.05). Compared with the control group (1.00), the miR-29a relative expression levels were significantly decreased in the 20 μmol·L⁻¹ Al(mal)₃ group (0.74±0.09) and the 40 μmol·L⁻¹ Al(mal)₃ group (0.62±0.12) (P < 0.05); the relative expression levels of PTEN mRNA were significantly increased in the 20 μmol·L⁻¹ Al(mal)₃ group (1.32±0.12) and the 40 μmol·L⁻¹ Al(mal)₃ group (1.48±0.11) (P < 0.05); the PTEN protein relative expression levels (1.29±0.12 and 1.82±0.10, respectively) were also significantly increased (P < 0.05). By overexpressing miR-29a in mouse primary hippocampal neurons, the spike frequency, burst frequency, and network burst frequency were significantly higher in the miR-29a group compared with the mNG group (The changes were 252.80%±62.03%, 171.65%±56.30%, and 197.75%±27.12%, respectively, P<0.05). The mNG+20 μmol·L⁻¹ Al(mal)₃ group showed a significant decrease in all indicators of neuronal network electrical activity (The changes were 123.28%±47.31%, 66.62%±31.53%, 70.60%±12.48%, and 52.86%±20.26%, respectively, P < 0.05). Compared with the mNG+20 μmol·L⁻¹ Al(mal)₃ group, the electrical activity indicators of neuronal network were significantly higher in the miR-29a+20 μmol·L⁻¹ Al(mal)₃ group (The changes were 161.41%±42.13%, 101.16%±30.63%, 127.02%±29.58%, and 109.73%±15.61%, respectively, P < 0.05). Compared with the mNG group (1.00), the neuronal PTEN mRNA relative expression (0.67±0.11) and the PTEN protein expression (0.75±0.08) were decreased in the miR-29a group (P < 0.05); the PTEN mRNA relative expression (1.32±0.12) and the PTEN protein relative expression (1.46±0.15) in the mNG+20 μmol·L⁻¹ Al(mal)₃ group were increased (P < 0.05). Compared with the mNG+20 μmol·L⁻¹ Al(mal)₃ group, the PTEN mRNA relative expression (0.93±0.06) and the PTEN protein relative expression (0.92±0.09) were decreased in the miR-29a+20 μmol·L⁻¹ Al(mal)₃ group (P < 0.05). Conclusion Aluminum significantly inhibits the electrical activity of hippocampal neuronal networks, and miRNA-29a may be involved in the aluminum-induced impairment of hippocampal neuronal network electrical activity by regulating PTEN expression.