Polydatin protects against articular cartilage degeneration by regulating autophagy mediated by the AMPK/mTOR signaling pathway.

BACKGROUND: Knee osteoarthritis (KOA) is one of the leading causes of disability. Polydatin has a potential effect on KOA treatment but the therapeutic mechanism is not clear. This study aims to investigate the therapeutic action of polydatin in KOA and its mechanism in activating autophagy via the AMP-activated protein kinase (AMPK)/mTOR signaling pathway. METHODS: After a KOA rat model was established by anterior cruciate ligament transection surgery, model rats were treated with polydatin 40 mg/kg for 30 days. Subsequently, cartilage tissues were collected, and hematoxylin-eosin (HE), Safranin-O, and TUNEL staining, and western blotting were performed to evaluate the pathological damage and autophagy-related protein expression. Then, human chondrocyte C28/I2 cells were stimulated with lipopolysaccharide (LPS), and the effects of polydatin on C28/I2 cell viability, apoptosis, and autophagy-related protein expression were detected by MTT, Flow Cytometry, and western blot. In addition, an AMPK inhibitor (Dorsomorphin 2HCl) was used to probe the cell proliferation and apoptosis of polydatin-administered C28/I2 cells. RESULTS: Polydatin ameliorated the pathological damage in rat cartilage tissues and inhibited cell apoptosis in KOA rats. Meanwhile, in C28/I2 cells, polydatin promoted viability and reduced apoptosis. In addition, the protein expression of collagen II, LC3II/LC3I, Beclin-1, and p-AMPK/AMPK were upregulated, and p62 and p-mTOR/mTOR were downregulated by polydatin treatment. Interestingly, relative results showed that the protective effect of polydatin in LPS-stimulated-C28/I2 cells was blocked by the AMPK/mTOR inhibitor, dorsomorphin 2HCl. CONCLUSION: Our research showed that polydatin reduced apoptosis and activated autophagy both in vivo and in vitro by the AMPK/mTOR signaling pathway to protect against KOA, which provided the basis for further investigation into the potential therapeutic impact of polydatin on KOA.

[Clinical outcomes of reverse shoulder arthroplasty for the treatment of failed fixation of proximal humeral fracrtures in the elderly patients].

OBJECTIVE: To evaluate the clinical outcomes of reverse total shoulder arthroplasty as a revision procedure for the failed fixation of proximal humeral fractures in the elderly patients. METHODS: A retrospective analysis was performed on 8 patients with failed internal fixation of proximal humeral fractures from May 2014 to March 2020, including 3 males and 5 females, aged from 65 to 75 years old. All 8 patients underwent reverse total shoulder arthroplasty, and the mean time between initial fixation and reverse total shoulder arthroplasty ranged from 8 to 16 months. Range of motion(ROM), University of California at Los Angeles(UCLA) shoulder score, visual analogue scale (VAS), self-rating anxiety scale(SAS), and Constant-Murley score of shoulder function were assessed pre-operatively and at the last follow-up. Complications relating to the surgery were recorded. RESULTS: All 8 patients successfully followed up. The mean follow-up after reverse total shoulder arhroplasty ranged from 16 to 28 months. The range of motion (forward flexion, external rotation, abduction and internal rotation) of the affected shoulder was significantly improved after surgery, and the post-operative VAS, SAS and UCLA scores were also significantly improved. For the Constant-Murley score of shoulder joint function, the total scores and the subscores of pain, daily activities, range of motion and strength test at the last follow-up were all significantly improved. Scapular glenoid notch was observed in patient, which was evaluated as grade 1 on imaging. All the other patients did not develop specific or non-specific complications. CONCLUSION: Reverse total shoulder arhroplasty is an appropriate treatment as a revision surgery for failed fixation of proximal humeral fractures. It has shown satisfactory clinical outcomes, accelerating the rehabilitation of shoulder function and improving the quality of life.

Durability of neutralization against Omicron subvariants after vaccination and breakthrough infection.

Booster immunizations and breakthrough infections can elicit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant neutralizing activity. However, the durability of the neutralization response is unknown. We characterize the sensitivity of BA.1, BA.2, BA.2.75, BA.4/BA.5, BF.7, BQ.1.1, and XBB against neutralizing antibodies from vaccination, hybrid immunity, and breakthrough infections 4-6 months after vaccination and infection. We show that a two-dose CoronaVac or a third-dose ZF2001 booster elicits limited neutralization against Omicron subvariants 6 months after vaccination. Hybrid immunity as well as Delta, BA.1, and BA.2 breakthrough infections induce long-term persistence of the antibody response, and over 70% of sera neutralize BA.1, BA.2, BA.4/BA.5, and BF.7. However, BQ.1.1 and XBB, followed by BA.2.75, are more resistant to neutralization, with neutralizing titer reductions of ∼9- to 41-fold, ∼16- to 63-fold, and ∼4- to 25-fold, respectively. These data highlight additional vaccination in CoronaVac- or ZF2001-vaccinated individuals and provide insight into the durability of neutralization against Omicron subvariants.

Sub-nanometer-scale mapping of crystal orientation and depth-dependent structure of dislocation cores in SrTiO3.

Defects in crystals play a fundamental role in modulating mechanical, electrical, luminescent, and magnetic behaviors of materials. However, accurate measurement of defect structures is hindered by symmetry breaking and the corresponding complex modifications in atomic configuration and/or crystal tilt at the defects. Here, we report the deep-sub-angstrom resolution imaging of dislocation cores via multislice electron ptychography with adaptive propagator, which allows sub-nanometer scale mapping of crystal tilt in the vicinity of dislocation cores and simultaneous recovery of depth-dependent atomic structure of dislocations. The realization of deep-sub-angstrom resolution and depth-dependent imaging of defects shows great potential in revealing microstructures and properties of real materials and devices.

Epidemiological characteristics and prediction model construction of hemorrhagic fever with renal syndrome in Quzhou City, China, 2005-2022.

Background: Hemorrhagic fever with renal syndrome (HFRS) is one of the 10 major infectious diseases that jeopardize human health and is distributed in more than 30 countries around the world. China is the country with the highest number of reported HFRS cases worldwide, accounting for 90% of global cases. The incidence level of HFRS in Quzhou is at the forefront of Zhejiang Province, and there is no specific treatment for it yet. Therefore, it is crucial to grasp the epidemiological characteristics of HFRS in Quzhou and establish a prediction model for HFRS to lay the foundation for early warning of HFRS. Methods: Descriptive epidemiological methods were used to analyze the epidemic characteristics of HFRS, the incidence map was drawn by ArcGIS software, the Seasonal AutoRegressive Integrated Moving Average (SARIMA) and Prophet model were established by R software. Then, root mean square error (RMSE) and mean absolute error (MAE) were used to evaluate the fitting and prediction performances of the model. Results: A total of 843 HFRS cases were reported in Quzhou City from 2005 to 2022, with the highest annual incidence rate in 2007 (3.93/100,000) and the lowest in 2022 (1.05/100,000) (P trend<0.001). The incidence is distributed in a seasonal double-peak distribution, with the first peak from October to January and the second peak from May to July. The incidence rate in males (2.87/100,000) was significantly higher than in females (1.32/100,000). Farmers had the highest number of cases, accounting for 79.95% of the total number of cases. The incidence is high in the northwest of Quzhou City, with cases concentrated on cultivated land and artificial land. The RMSE and MAE values of the Prophet model are smaller than those of the SARIMA (1,0,1) (2,1,0)12 model. Conclusion: From 2005 to 2022, the incidence of HFRS in Quzhou City showed an overall downward trend, but the epidemic in high-incidence areas was still serious. In the future, the dynamics of HFRS outbreaks and host animal surveillance should be continuously strengthened in combination with the Prophet model. During the peak season, HFRS vaccination and health education are promoted with farmers as the key groups.

[Intervention strategy based on Caprini risk assessment model and its clinical effect in preventing deep vein thrombosis after total hip replacement].

OBJECTIVE: To analyze clinical effect of intervention strategies based on Caprini thrombosis risk assessment model for preventing deep vein thrombosis (DVT) after total hip replacement (THR). METHODS: From January 2018 to December 2021, 197 patients with THR were selected as retrospective cohort study subjects, including 114 males and 83 females, aged from 45 to 80 years with an average of (66.81±10.34) years old. Caprini thrombosis risk assessment model introduced in May 2019 was used as boundary and divided into two groups, 94 patients were performed routine intervention strategies(control group) and 103 patients were received intervention strategies based on Caprini thrombosis risk assessment model (observation group). Incidence of DVT, visual analogue scale (VAS), circumference difference of affected limb, serum D-dimer (D-D) level and Harris score of hip function between two groups were analyzed. RESULTS: One-hundred and ninty-seven patients were followed up from 1 to 3 months with an average of (2.57±0.31) months. Incidence of DVT was 1.94% in observation group and 11.70% in control group, and there was statistical difference between two groups (χ2=6.642, P=0.010). VAS scores between two groups decreased gradually (P<0.001). There was significant difference between two groups in VAS score on the 1st, 2nd, 3rd and 7th day after operation (P<0.05), but no difference between two groups on the 10th day after operation (P>0.05). Difference in circumference of the affected limb between two groups after operation was gradually reduced (P<0.001), and the difference in circumference of the affected limb between two groups was statistically significant on the 1st, 2nd, 3rd, 7th, and 10th day after operation(P<0.05). Levels of serum D-D between two groups were gradually decreased after operation(P<0.05), and differences in serum D-D levels between two groups on the 8th, 24th, 48th, and 72th hour after operation were statistically significant (P<0.05). Pain score and Harris total scores between two groups were significantly increased as tomes goes on(P<0.001), no difference in VAS at 3 months after discharge, and there were statistically significant differences in Harris scores between two groups immediately after discharge, 1 month and 3 months after discharge (P<0.001). CONCLUSION: Intervention strategy based on Caprini thrombosis risk assessment model could reduce incidence of DVT in patients with THR, improve postoperative pain and swelling of the affected limb, and promote recovery of hip joint function.

Introduction of Two-Dose Mumps-Containing Vaccine into Routine Immunization Schedule in Quzhou, China, Using Cox-Proportional Hazard Model.

Mumps is a vaccine-preventable disease caused by the mumps virus, but the incidence of mumps has increased among the children who were vaccinated with one-dose measles-mumps-rubella (MMR) in recent years. In this study, we analyzed the influence of different doses of mumps-containing vaccine (MuCV) against mumps using Cox-proportional hazard model. We collected 909 mumps cases of children who were born from 2006 to 2010 and vaccinated with different doses of MuCV in Quzhou during 2006-2018, which were all clinically diagnosed. Kaplan-Meier survival methods and Cox-proportional hazard model were used to estimate the hazard probabilities. Kaplan-Meier curves showed that the cumulative hazard of male and female has no difference; lower hazards were detected among those who were vaccinated with two-dose MuCV, born in 2006, and infected after supplementary immunization activities (SIA). Cox-proportional hazard regression suggested that onset after SIA, born in 2006, and vaccinated with two-dose MuCV were protective factors against infection even after adjusting for potential confounding effects. Our study showed that it was necessary to revise the diagnostic criteria of mumps and identify RT-PCR as the standard for mumps diagnosis in China. We suggested that routine immunization schedule should introduce two doses of MMR and prevaccination screening should be performed before booster immunization in vaccinated populations.

Persistence of Antibody and Cellular Immune Responses in Coronavirus Disease 2019 Patients Over Nine Months After Infection.

BACKGROUND: The duration of humoral and T and B cell response after the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear. METHODS: We performed a cross-sectional study to assess the virus-specific antibody and memory T and B cell responses in coronavirus disease 2019 (COVID-19) patients up to 343 days after infection. Neutralizing antibodies and antibodies against the receptor-binding domain, spike, and nucleoprotein of SARS-CoV-2 were measured. Virus-specific memory T and B cell responses were analyzed. RESULTS: We enrolled 59 patients with COVID-19, including 38 moderate, 16 mild, and 5 asymptomatic patients; 31 (52.5%) were men and 28 (47.5%) were women. The median age was 41 years (interquartile range, 30-55). The median day from symptom onset to enrollment was 317 days (range 257 to 343 days). We found that approximately 90% of patients still have detectable immunoglobulin (Ig)G antibodies against spike and nucleocapsid proteins and neutralizing antibodies against pseudovirus, whereas ~60% of patients had detectable IgG antibodies against receptor-binding domain and surrogate virus-neutralizing antibodies. The SARS-CoV-2-specific IgG+ memory B cell and interferon-γ-secreting T cell responses were detectable in more than 70% of patients. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2-specific immune memory response persists in most patients approximately 1 year after infection, which provides a promising sign for prevention from reinfection and vaccination strategy.

TNF-α released from retinal Müller cells aggravates retinal pigment epithelium cell apoptosis by upregulating mitophagy during diabetic retinopathy.

Retinal pigment epithelium (RPE) cell damage, including mitophagy-associated cell apoptosis, accelerates the pathogenesis of diabetic retinopathy (DR), a common complication of diabetes that causes blindness. Müller cells interact with RPE cells via pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α). Herein, we investigated the role of the RPE cell epidermal growth factor receptor (EGFR)/p38 mitogen-activated protein kinase (p38)/nuclear factor kappa B (NF-κB) pathway in Müller cell-derived TNF-α-induced mitophagy-associated apoptosis during DR. Our results showed that TNF-α released from Müller cells activated the EGFR/p38/NF-κB/p62 pathway to increase mitophagy and apoptosis in RPE cells under high glucose (HG) conditions. Additionally, blockade of the TNF-α/EGFR axis alleviates blood-retina barrier breakdown in diabetic mice. Our data further illustrate the effects of the Müller cell inflammatory response on RPE cell survival, implying potential molecular targets for DR treatment.

Mid-term results of bilateral synchronous total hip arthroplasty for bony ankylosis in patients with ankylosing spondylitis.

BACKGROUND: Total hip arthroplasty (THA) for bony ankylosis is technically challenging in patients with ankylosing spondylitis (AS). This study aimed to determine the mid-term results of bilateral synchronous THA for bony ankylosis in patients with AS. METHODS: Nineteen cases of bony ankylosis in patients with AS who received bilateral synchronous THA were included in this study (17 males and 2 females, mean age 49.2 years). Disease duration was 5-38 years (mean 18 years and 6 months). All patients received cementless THA. Intraoperative blood loss, visual analog scale (VAS) score, and complications were assessed. Harris hip scores evaluated the clinical effect. RESULTS: Patients were followed up for 62-98 months (mean 82.5 months). VAS score decreased from 7.42 ± 0.92 to 2.42 ± 0.83, Harris hip score improved from 21.8 ± 7.2 to 80.3 ± 6.5, and the flexion-extension range of the hip improved from 0 to 142.3 ± 6.2°. One patient with septum bronchiale had a fracture intraoperatively and was treated with wire strapping. One patient had a traction injury of the femoral nerve postoperatively and recovered 1 year after the operation. Loosening and subsidence were not observed in all patients. Heterotopic bone formation was noted in 3 patients. No complications such as joint dislocation, acute infection, and deep vein thrombosis were found. CONCLUSION: Bilateral synchronous THA was effective for bony ankylosis of the hip in patients with AS because it improved patients' quality of life and had satisfactory mid-term outcomes.

Chondroprotective Effect of Wufu Decoction on Tumor Necrosis Factor-α-Induced Chondrocytes via the Extracellular Signal Regulated Kinase 1/2 Signaling Pathway.

OBJECTIVE: Wufu Decoction (WFD) is a herbal formulation composed of five traditional Chinese herbs that is used clinically for arthritis treatment in China. The current study investigated the chondroprotective effects and the underlying mechanism of WFD for osteoarthritis (OA) therapy. METHODS: The chondroprotective effects of WFD were investigated based on vitro study. Following the successful isolation of chondrocytes from rat cartilage tissues and the identification of collagen II expression with immunofluorescence staining, chondrocytes were co-incubated with tumor necrosis factor-α (TNF-α) to induce an inflammation model; WFD was also administered. After the treatment, cell viability was determined by MTT assay, cell apoptosis was assessed by DAPI staining, the concentration of inflammation cytokines interleukin (IL)-1ß and IL-6 were detected with ELISA assay, the expression of collagen II, MEK1/2-ERK1/2 signaling pathway proteins was detected using western blotting, and mRNA expression of MMP-1, MMP-9 and MMP-13 were determined with quantitative real-time polymerase chain reaction. RESULTS: Wufu Decoction significantly restored the cell viability suppressed by TNF-α and inhibited the cell apoptosis induced by TNF-α in chondrocytes. The high concentrations of IL-1ß and IL-6 in TNF-α-induced model cells were significantly decreased in WFD-treated chondrocytes, and the immunofluorescence staining and western blot results showed that the inhibited expression of collagen II in the TNF-α-induced model group was significantly increased in WFD-treated chondrocytes. The protein expressions of MEK1/2, p-ERK1/2, and P53 were significantly reduced in the WFD-treated group compared with those in the model group, and the mRNA expressions of MMP-1, MMP-9, and MMP-13 were also significantly reduced with WFD treatment. CONCLUSION: The present study indicated that WFD exerted a chondroprotective effect in TNF-α-induced chondrocytes via the regulation of the ERK1/2 signaling pathway, suggesting that WFD has therapeutic potential for OA therapy.

Relationships between traditional larval indices and meteorological factors with the adult density of Aedes albopictus captured by BG-mosquito trap.

OBJECTIVES: Larval indices have been used for Ae. albopictus surveillance for many years, while there is limited use in assessing dengue transmission risk and adult mosquito emergence. This study is aimed to explore the relationships between larval indices and the Ae. albopictus density captured by BG-mosquito trap (BG-trap) method, with considering the meteorological factors. METHODS: Data on larval density, adult mosquito density and meteorology factors were collected in an entomological survey carried out in Quzhou City, Zhejiang Province of China in 2018. The Spearman's rank correlation and Pearson correlation were used for the analysis on the correlation of density indices. Generalized additive models were established to analyze the influencing factors of mosquito density. RESULTS: Breteau index (BI), House index (HI) and Container index (CI) were highly correlated with each other (r>0.7, p<0.05). The Ae. albopictus density was significantly correlated with CI (rs = 0.260, p<0.05), CI pre one week (rs = 0.259, p<0.05), and CI pre three weeks (rs = 0.329, p<0.05). BI was correlated with female Ae. albopictus density pre 4 weeks (r = -0.299, p<0.05). Female Ae. albopictus density was correlated with CI pre 3 weeks (rs = 0.303, p<0.05). The influencing factors of BI were average wind speed pre 1 week, average temperature and female Ae. albopictus density pre 4 weeks. The influencing factors of CI were average humidity pre 3 weeks and average temperature. The influencing factors of HI were average temperature and precipitation pre 4 weeks. The influencing factor of Ae. albopictus density and female Ae. albopictus density was temperature. CONCLUSIONS: The adult Ae. albopictus density had low correlation with certain larval indices. Some of the meteorology factors played significant roles in the density of adult Ae. albopictus and larva with or without a time lag.

MiR-126 targets IL-17A to enhance proliferation and inhibit apoptosis in high-glucose-induced human retinal endothelial cells.

Diabetic retinopathy (DR) is a common complication of diabetes mellitus (DM), which results in vision loss. This study explored the role of miR-126 in high-glucose-induced human retinal endothelial cells (HRECs) and its underlying molecular mechanisms. The results showed that the expression levels of miR-126 and interleukin-17A (IL-17A) in high-glucose-induced HRECs were downregulated and upregulated, respectively. Functionally, overexpression of miR-126 promoted proliferation and suppressed apoptosis in high-glucose-induced HRECs, while IL-17A reversed the effects induced by miR-126. However, overexpression of IL-17A inhibited the proliferation and induced apoptosis, while knockdown of IL-17A accelerated the proliferation and repressed apoptosis. In addition, miR-126 repressed the expression of IL-17A, Bax, and caspase-3, while promoting the expression of survivin and phosphorylation of PI3K and AKT; restoration of IL-17A rescued these effects. Furthermore, IL-17A was identified as a target of miR-126. This indicates that miR-126 enhances proliferation and inhibits apoptosis in high-glucose-induced HRECs by activating the PI3K-AKT pathway, increasing survivin levels, and decreasing Bax and caspase-3 expression by targeting IL-17A, suggesting that miR-126 could be a novel target for preventing DR.

[High strength wire under arthroscopy combined with outside anchor nail in treating Meyers McKeever II, III avulsion fracture of anterior cruciate ligament tibial check point].

OBJECTIVE: To explore clinical effect of high strength wire under arthroscopy combined with outside anchor nail in treating Meyers McKeever II, III anterior cruciate ligament tibial check point. METHODS: From March 2014 to June 2016, 21 patients with Meyers McKeever II, III avulsion fracture of anterior cruciate ligament tibial check point were treated by high strength wire under arthroscopy combined outside anchor nail. There were 13 males and 8 females aged from 18 to 48 years old with an average of (26.40±5.42) years old. There were 9 cases injured on the left side, and 12 cases on the right side. The courses of disease included sports injuries of 12 cases, falling down injuries of 6 cases, and accident injuries of 3 cases. According to Meyers-McKeever classification, 16 patients were type II and 5 patients were type III. All fractures were fresh, closed and simple injury. The time from injury to operation ranged from 2 to 15 days with an average of (6.20±2.63) d. Lysholm score, IKDC score and the changes of knee mobility were observed and compared before operation and 6 months after operation. RESULTS: Twenty-one patients were followed up for 12 to 24 months with an average of (14.30±3.01) months. Operation time ranged from 40 to 65 min with an average of (45.10±4.82) min, Blood loss ranged from 5 to 15 ml with an average of (10.05±2.75) ml. Lysholm score was improved from 50.29±6.67 before operation to 92.48±2.18 at 6 months after operation. IKDC scores was increased from 47.19±4.57 before operation to 90.71±2.22 at 6 months after operation. Knee joint activity was respectively (83.05±5.33)° and (132.05±7.15)° before operation and 6 months after operation. CONCLUSIONS: High strength wire under arthroscopy combined outside anchor nail in treating Meyers McKeever II, III ACL tibial check point has the advantages of less trauma, firm fixation, and satisfactory clinical effect.

[Reverse total shoulder arthroplasty for the treatment of old fracture of proximal humerus in elderly patients].

OBJECTIVE: To investigate clinical results of reverse total shoulder arthroplasty in treating old fracture of proximal humerus in elderly patients. METHODS: From January 2012 to December 2017, 12 elderly patients with old proximal humeral fractures were treated with reverse total shoulder arthroplasty. There were 5 males and 7 females with an average age of 70.2 years old (ranged from 63 to 81 years old) and an average course of 12.3 months (ranged from 9 to 18 months). VAS score was used to evaluate the degree of pain relief of shoulder joint, Constant-Murley score was used to evaluate the improvement of shoulder joint function and observe the complications during and after operation. RESULTS: All the 12 patients were followed up with an average duration of 22.3 months (ranged from 15 to 56 months). At the latest follow-up, the VAS score was 1.9±1.4, and Constant-Murley score was 83.4±8.4. Among them, shoulder joint flexion was (92.5±7.7)°, abduction was (90.4±14.3)°, external rotation was(31.9±10.0)°, and internal rotation was(58.9±13.1)°. There was statistical significance before and after treatment(P<0.05). There were 2 cases with glenoid notch. The imaging findings were grade I and grade II respectively. No loosening was found during follow-up. No infection, acromial fracture, prosthesis loosening, axillary nerve injury and other complications occurred. CONCLUSIONS: Reverse total shoulder arthroplasty in treating old proximal humeral fractures in elderly patients can achieve satisfactory results, however, indications and complications should be noted.

Chikungunya Fever Outbreak, Zhejiang Province, China, 2017.

We report a disease outbreak caused by chikungunya virus in Zhejiang Province, China, in August 2017. Phylogenic analysis indicated that this virus belonged to the Indian Ocean clade of the East/Central/South African genotype and was imported by a traveler returning from Bangladesh.

Xiao Yao San against Corticosterone-Induced Stress Injury via Upregulating Glucocorticoid Receptor Reaction Element Transcriptional Activity.

Previous studies have revealed that uncontrollable stress can impair the synaptic plasticity and firing property of hippocampal neurons, which influenced various hippocampal-dependent tasks including memory, cognition, behavior, and mood. In this work, we had investigated the effects and mechanisms of the Chinese herbal medicine Xiao Yao San (XYS) against corticosterone-induced stress injury in primary hippocampal neurons (PHN) cells. We found that XYS and RU38486 could increase cell viabilities and decrease cell apoptosis by MTT, immunofluorescence, and flow cytometry assays. In addition, we observed that XYS notably inhibited the nuclear translocation of GR and upregulated the mRNA and protein expressions levels of Caveolin-1, GR, BDNF, TrkB, and FKBP4. However, XYS downregulated the FKBP51 expressions. Furthermore, the results of the electrophoretic mobility shift assay (EMSA) and double luciferase reporter gene detection indicated that FKBP4 promotes the transcriptional activity of GR reaction element (GRE) by binding with GR, and FKBP51 processed the opposite action. The in vivo experiment also proved the functions of XYS. These results suggested that XYS showed an efficient neuroprotection against corticosterone-induced stress injury in PHN cells by upregulating GRE transcriptional activity, which should be developed as a potential candidate for treating stress injury in the future.

Evaluation of a Novel HA/ZrO2-Based Porous Bioceramic Artificial Vertebral Body Combined with a rhBMP-2/Chitosan Slow-Release Hydrogel.

A new HA/ZrO2-based porous bioceramic artificial vertebral body (AVB), carried a recombinant human bone morphogenetic protein-2 (rhBMP-2)/chitosan slow-release hydrogel was prepared to repair vertebral bone defect in beagles. An ionic cross-linking was used to prepare the chitosan hydrogel (CS gel) as the rhBMP-2 slow-release carrier. The vertebral body defects were implanted with the rhBMP-2-loaded AVB in group A, or a non-drug-loaded AVB in group B, or autologous iliac in group C. The encapsulation rate of rhBMP-2 in rhBMP-2-loaded CS gel was 91.88±1.53%, with a drug load of 39.84±2.34 ng/mg. At 6, 12, 24 weeks postoperatively, radiography showed that the bone calluses gradually increased with time in group A, where the artificial vertebral body had completely fused with host-bone at 24 weeks after surgery. In group C, an apparent bone remodeling was occurred in the early stages, and the graft-bone and host-bone had also fused completely at 24 weeks postoperatively. In group B, fusion occurred less than in groups A and C. At 24 weeks after surgery, micro-computed tomography (Micro-CT) revealed that the volume of newly-formed bone in group A was significantly more than in group B (p<0.05). At 24 weeks after surgery, ultra-compressive strengths of the operated segments were 14.03±1.66 MPa in group A, 8.62±1.24 MPa in group B, and 13.78±1.43 MPa in group C. Groups A and C were both significantly higher than group B (p < 0.05). At 24 weeks postoperatively, the hard tissue sections showed that the AVB of group A had tightly fused with host bone, and that pores of the AVB had been filled with abundant nearly mature bone, and that the new bone structured similarly to a trabecular framework, which was similar to that in group C. In contrast, implant fusion of the AVB in group B was not as apparent as group A. In conclusion, the novel HA/ZrO2-based porous bioceramic AVB carried the rhBMP-2-loaded CS gel can promote the repair of bony defect, and induce bone tissue to grow into the pores, which may replace iliac bone grafts as commonly applied in clinical practice.