AIM:To investigate the role of minocycline on glutamate uptake in the periventricular zone and its putative mechanism after hypoxic exposure in neonatal rats.METHODS: A model of hypoxic-ischemic brain damage (HIBD) was developed by putting postnatal 1 d rat pups in 5%O2 for 3.5 h.The glutamate level in periventricular zone was measured by liquid chromatography coupled with tandem mass spectrometry assay ( LC-MS/MS) after hypoxic exposure for 4 h and 1 d.The dynamic changes of glutamate transporters EAAT1, and EAAT2 during developmental period in periventricular zone were determined by Western blot.Moreover, the expression of EAAT1, EAAT2, Iba-1, IL-1β, TNF-αand TGF-β1 was also detected by Western blot after hypoxic exposure for 4 h and 1 d in that region.The effects of mino-cycline on all parameters mentioned above were tested after minocycline treatment at the same time points and in the same region.RESULTS:After hypoxic exposure, glutamate level was increased, but it was decreased after minocycline treat-ment.EAAT1 and EAAT2 kept a low expression level at the first postnatal week, but a predominant elevation was found at the end of the second postnatal week.The expression of EAAT1, EAAT2, Iba-1, IL-1βand TGF-β1 was increased at 1 d after hypoxic exposure.EAAT1 and TNF-αexpression was significantly up-regulated, while EAAT2 was down-regulated af-ter minocycline treatment.CONCLUSION: Minocycline inhibits the increase in the glutamate level after hypoxia in periventricular region of the neonatal rats.The mechanism may relate to the selective regulation of glutamate transporters, rather than the inhibition of neuroinflammation in periventricular zone.

Objective:To preliminarily explore the effects of tumor treating fields (TTF) arrays on the dose distribution in the treatment of Glioblastoma (GBM) using combined radiotherapy and concurrent TTF.Methods:EDR2 and MatriXX plate ionization chamber were employed to measure the absorbed doses of tissues at different depths (< 1 mm, 3 mm, 5 mm, 1 cm, 1.5 cm, 3 cm, 5 cm, 10 cm, and 15 cm) in the case that TTF arrays and latex-free foam were attached and not attached on the surface. Then the absorbed doses were calculated, compared, and analyzed. For the volumetric arc therapy (VMAT) of 10 GBM patients, deep dose verification was performed using the Sun Nuclear ArcCheck 3D dose verification system and the D99%, Dmean, and D1% of tumors and OARs were assessed. Results:The surface dose increased by 173% in the case that TTF arrays and latex-free foam were attached to the surface compared with the case of the surface with nothing attached. The surface dose increased by 61.7% due to the attachment of low-density latex-free foam. The dose deviation gradually decreased with an increase in the depth and stabilized (about 4%) at a depth of greater than 1.5 cm. As indicated by the VMAT verification result, the D99%, Dmean, and D1% of PTV and CTV decreased by 1.1%-1.2% and the Dmean and D1% of OARs (i.e., brainstem, pituitary gland, optic chiasma, optic nerve, eyeball, and eye crystal) decreased by 0.7%-1.5% in the case that TTF array and latex-free foam were attached on the surface compared with the case the surface with nothing attached. Conclusions:The combined radiotherapy and concurrent TTF in the GBM treatment will lead to a slight reduction of the absorbed doses of targets and OARs but a significant increase in the absorbed doses of the scalp. Therefore, it is recommended that the scalp doses should be reduced as far as possible in the design of the radiation treatment plan to reduce the adverse reactions on the scalp of GBM patients.

BACKGROUND:Intervertebral disc degeneration is an important cause of low back pain.At present,there are many modeling methods for disc degeneration in China and abroad,but there is not a model for low back pain due to disc degeneration. OBJECTIVE:To compare the effect of mechanical puncture combined with tumor necrosis factor α and complete Freund's adjuvant with a conventional disc mechanical puncture alone. METHODS:A total of 18 male adult Sprague-Dawley rats were randomly divided into 3 groups,with 6 animals in each group.No treatment was given in the blank group.Animal models of intervertebral disc degeneration were made in the L4-5 segments of rats in the control using conventional mechanical puncture.In the experimental group,on the basis of mechanical puncture,tumor necrosis factor α+complete Freund's adjuvant was injected into the L4-5 intervertebral discs using a microinjector to establish a model of disc degeneration induced by mechanical puncture combined with inflammatory factors.Four weeks after surgery,the pain threshold of rats was measured by the hot plate method for assessing the perception of heat injury in rats with intervertebral disc degeneration.MRI examination was performed to observe the disc degeneration in each group.ELISA was used to detect the levels of serum tumor necrosis factor α,interleukin 1β,interleukin 6 and prostaglandin E2.Hematoxylin-eosin and Safranin O-fast green staining were used to observe the morphological changes of the disc. RESULTS AND CONCLUSION:In terms of pain,the behavioral pain threshold of the experimental group was continuously decreased,and the levels of serum inflammatory factors were significantly higher compared with the control group.In terms of morphology,the MRI results showed that the L4-5 nucleus pulposus signal completely disappeared in the experimental group.Histopathological results showed that in the control group,the nucleus pulposus was intact,more notochord cells were visible,and some fiber rings were ruptured,while in the experimental group,there are fewer notochord cells and the structure of the nucleus pulposus and fibrous ring is disturbed,with the boundary disappearing.To conclude,mechanical puncture combined with tumor necrosis factor alpha and complete Freund's adjuvant can successfully establish a discogenic low back pain model in rats.This operation is simple and economical to achieve obvious disc degeneration and low back pain,with greatly shortened molding cycle.This model can be used as a reference for studying discogenic low back pain models.

BACKGROUND:Hydrogel microparticles,due to their porous and injectable properties,have demonstrated unique advantages in biomedical fields,such as the delivery of cells and bioactive factors/drugs,the construction of tissue repair scaffolds.They have broad application prospects. OBJECTIVE:To review the latest research progress and discuss the key problems and challenges in the research of bone tissue engineering based on hydrogel microparticles. METHODS:The relevant articles in PubMed and CNKI were searched by computer.The English key words were"hydrogels,microparticles,microspheres,microcarriers,bone,bone defect,bone repair,bone healing,bone tissue engineering"while the Chinese key words were"hydrogels,microparticles,microspheres,bone tissue engineering,bone defect,bone repair,bone regeneration".The retrieval period was from 2002 to 2022,and 127 articles were finally included for review. RESULTS AND CONCLUSION:(1)At present,various hydrogel microparticles have been developed for use in bone tissue engineering strategies,for example,hydrogel microparticles carrying cells or bioactive factors/drugs,hydrogel microparticles as biological scaffolds,stimulus-responsive hydrogel microparticles,biomineralized hydrogel microparticles,hydrogel microparticles combined with other biological materials.(2)Bone tissue engineering repair strategies based on hydrogel microparticles mainly regulate bone repair by promoting stem cell recruitment and osteogenic differentiation,regulating the local inflammatory microenvironment and promoting angiogenesis at the site of injury.However,the present studies did not deeply explore the effect of bone tissue engineering based on hydrogel microparticles on the recruitment and differentiation of endogenous stem cells and the regulation of the inflammatory microenvironment by the physical and chemical properties of hydrogel microparticles.The long-term in vivo adverse reactions of hydrogel microparticles have not been explored yet,and it is difficult to mass-produce them,thus future research needs to strengthen the mechanism exploration and technical route,so as to provide a reasonable reference for the development of hydrogel microparticles that can be used for clinical transformation.

Objective:To investigate the level of death anxiety and its related factors in patients with newly diagnosed cancer at different stages.Methods:A total of 266 cancer patients in a tertiary oncology hospital were se-lected and investigated at admission(Tl),discharge(T2),and 1 month after discharge(T3).They were assessed with the self-compiled general information questionnaire,Templer's Death Anxiety Scale(T-DAS),Acceptance and Action Questionnaire Second Edition(AAQ-Ⅱ.),and the Chinese version of the Meaning in Life Questionnaire(C-MLQ).The Kruskal-Wallis H test and generalized estimating equation were used to analyze the level of death anxi-ety and its influencing factors in cancer patients at different time points.Results:The Kruskal-Wallis H test showed that the total T-DAS scores and the difference in the scores of the four dimensions were statistically significant at three time points(Ps＜0.01),with the highest T1 score and the lowest T3 score.The results of generalized estima-ting equation showed that male gender(β=1.25),junior high school education(β=2.59),worker(β=1.46),farmer(β=1.67),respiratory(β=1.74),digestive system tumor(β=2.51),and AAQ-Ⅱ score(β=0.23)posi-tively predicted death anxiety in patients with cancer.Head and neck(β=-1.73),breast tumors(β=-1.84),stage Ⅰ(β=-2.58)and stage Ⅱ tumors(β=-2.11),and C-MLQ score(β=-0.15)negatively predicted death anxiety in patients with cancer.Conclusion:Death anxiety in patients with newly diagnosed cancer is highest on ad-mission and gradually relieves after discharge.

Although oxymatrine (OMT) has been shown to directly inhibit the replication of hepatitis B virus (HBV), limited research has been done with this drug. In the present study, the antiviral effect of OMT was investigated in an immunocompetent mouse model of chronic HBV infection. The infection was achieved by tail vein injection of a large volume of DNA solution. OMT (2.2, 6.7 and 20 mg/kg) was administered by daily intraperitoneal injection for 6 weeks. The efficacy of OMT was evaluated by the levels of HBV DNA, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B core antigen (HBcAg). The immunoregulatory activity of OMT was evaluated by serum ELISA and flow cytometry. Results shows that OMT at 20 mg/kg inhibited HBV replication, and it was more efficient than entecavir (ETV) in the elimination of serum HBsAg and intrahepatic HBcAg. In addition, OMT accelerated the production of interferon-(IFN-) in a dose-dependent manner in CD4T cells. Our findings demonstrate the beneficial effects of OMT on the enhancement of immunological function and in the control of HBV antigens. The findings suggest this drug to be a good antiviral therapeutic candidate for the treatment of HBV infection.