Objective·To investigate the reparative effects of photo-crosslinked gelatin methylacrylated(GelMA)hydrogel scaffolds loaded with tauroursodeoxycholic acid(TUDCA)on cartilage defects in rabbit knee joints.Methods·Photo-crosslinked GelMA hydrogel scaffolds loaded with TUDCA were prepared by the ultraviolet light irradiation method.The physicochemical properties of GelMA hydrogel scaffolds were characterized,and the cumulative release rate of TUDCA was determined.A rabbit knee cartilage defect model was established,and 18 rabbits were randomly assigned into three groups,with six rabbits in each group:the control group(no treatment was applied to the cartilage defect),the GelMA group(the cartilage defect was filled with GelMA hydrogel scaffold),and the GelMA+TUDCA group(the cartilage defect was filled with the GelMA hydrogel scaffold loaded with TUDCA).At 12 weeks postoperatively,the concentrations of two inflammatory factors in synovial fluid,tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β),were detected by enzyme-linked immunosorbent assay(ELISA).After euthanasia,knee cartilage samples were harvested for gross observation,safranin O-fast green staining,and toluidine blue staining.The repair of the cartilage defects was evaluated according to the International Cartilage Repair Society(ICRS)and Modified O'Driscoll Score(MODS)systems.Immunohistochemical staining was performed to detect type Ⅱ collagen(COL-Ⅱ)protein in the cartilage tissue,and Western blotting was used to assess the protein levels of aggrecan(ACAN)and COL-Ⅱ.Results·GelMA hydrogel scaffolds exhibited a more compact microstructure after ultraviolet light irradiation,along with an suitable mass swelling ratio and compressive modulus.The TUDCA-loaded photo-crosslinked GelMA hydrogel scaffolds demonstrated effective and sustained TUDCA release,achieving a cumulative release rate of 90.2%±2.5%within 28 d.ELISA results showed that compared to the control and GelMA groups,the concentrations of TNF-α and IL-1β in the synovial fluid of the GelMA+TUDCA group were significantly reduced(P<0.001).In the GelMA+TUDCA group,the cartilage defects were nearly fully repaired,with a smooth surface and good integration with the surrounding tissue.The number of newly formed chondrocytes increased,displaying orderly alignment,and the neocartilage exhibited excellent formation.Both ICRS and MODS scores were significantly higher in the GelMA+TUDCA group than those in the control and GelMA groups(P<0.001).Additionally,the expression levels of ACAN and COL-Ⅱ proteins were significantly elevated in the GelMA+TUDCA group compared to the control and GelMA groups(P<0.001).Conclusion·Photo-crosslinked GelMA hydrogel scaffolds loaded with TUDCA can effectively promote the repair of cartilage defects in rabbit knee joints.

In the field of oral medicine, 3D-printed individualized titanium mesh technology is gradually becoming an important means for the treatment of severe alveolar bone defect augmentation. This article provides a comprehensive analysis of the advantages of this technology, the evaluation of osteogenic effects, and the progress of research in clinical applications. In response to the current issue of variability in bone augmentation outcomes, this paper delves into multiple factors affecting bone augmentation effects, including individualized titanium mesh design (involving the thickness, pore size, pore shape, porosity, contour shape, selection of titanium alloy materials, and 3D printing technology), intraoperative procedures (the accuracy of placement during 3D-printed individualized titanium mesh surgery), and postoperative care (including the prevention of complications, formation of pseudoperiosteum, and stability of the titanium mesh). By integrating the clinical experience and research findings of our team, we propose a series of targeted optimization strategies, including designing, manufacturing, and clinically applying self-positioning individualized titanium meshs (positioning wings + individualized titanium meshs) to improve the positioning accuracy of the titanium mesh; propose individualized treatment processes and titanium mesh design schemes based on specific conditions of alveolar bone defects and soft tissue status; and emphasize the importance of long-term stable fixation of the titanium mesh to reduce the risk of postoperative mesh loosening and displacement. In addition, we appropriately summarize the evaluation methods for the bone augmentation effects of 3D-printed individualized titanium meshes, covering the following key indicators: (1) vertical bone augmentation and horizontal bone augmentation; (2) changes in bone contour morphology; (3) bone volume increase; (4) clinical indicators (surgical success rate, titanium mesh exposure, infection rate, and postoperative recovery); (5) aesthetic effect evaluation; (6) long-term stability; (7) radiological assessment; (8) patient satisfaction; and (9) precision of surgical operation, aiming to assist doctors in comprehensively assessing and in-depth analyzing the surgical outcomes to achieve the best therapeutic effects. The purpose of this article is to provide a reference for the optimization and clinical application of 3D-printed individualized titanium mesh technology and to lay a theoretical foundation for achieving the best osteogenic effects.

Objective·To investigate the reparative effects of photo-crosslinked gelatin methylacrylated(GelMA)hydrogel scaffolds loaded with tauroursodeoxycholic acid(TUDCA)on cartilage defects in rabbit knee joints.Methods·Photo-crosslinked GelMA hydrogel scaffolds loaded with TUDCA were prepared by the ultraviolet light irradiation method.The physicochemical properties of GelMA hydrogel scaffolds were characterized,and the cumulative release rate of TUDCA was determined.A rabbit knee cartilage defect model was established,and 18 rabbits were randomly assigned into three groups,with six rabbits in each group:the control group(no treatment was applied to the cartilage defect),the GelMA group(the cartilage defect was filled with GelMA hydrogel scaffold),and the GelMA+TUDCA group(the cartilage defect was filled with the GelMA hydrogel scaffold loaded with TUDCA).At 12 weeks postoperatively,the concentrations of two inflammatory factors in synovial fluid,tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β),were detected by enzyme-linked immunosorbent assay(ELISA).After euthanasia,knee cartilage samples were harvested for gross observation,safranin O-fast green staining,and toluidine blue staining.The repair of the cartilage defects was evaluated according to the International Cartilage Repair Society(ICRS)and Modified O'Driscoll Score(MODS)systems.Immunohistochemical staining was performed to detect type Ⅱ collagen(COL-Ⅱ)protein in the cartilage tissue,and Western blotting was used to assess the protein levels of aggrecan(ACAN)and COL-Ⅱ.Results·GelMA hydrogel scaffolds exhibited a more compact microstructure after ultraviolet light irradiation,along with an suitable mass swelling ratio and compressive modulus.The TUDCA-loaded photo-crosslinked GelMA hydrogel scaffolds demonstrated effective and sustained TUDCA release,achieving a cumulative release rate of 90.2%±2.5%within 28 d.ELISA results showed that compared to the control and GelMA groups,the concentrations of TNF-α and IL-1β in the synovial fluid of the GelMA+TUDCA group were significantly reduced(P<0.001).In the GelMA+TUDCA group,the cartilage defects were nearly fully repaired,with a smooth surface and good integration with the surrounding tissue.The number of newly formed chondrocytes increased,displaying orderly alignment,and the neocartilage exhibited excellent formation.Both ICRS and MODS scores were significantly higher in the GelMA+TUDCA group than those in the control and GelMA groups(P<0.001).Additionally,the expression levels of ACAN and COL-Ⅱ proteins were significantly elevated in the GelMA+TUDCA group compared to the control and GelMA groups(P<0.001).Conclusion·Photo-crosslinked GelMA hydrogel scaffolds loaded with TUDCA can effectively promote the repair of cartilage defects in rabbit knee joints.

Peripheral nerve injury (PNI) is an important clinical complication, which brings long-term physical and psychological pain and economic burden to patients. There is no satisfactory treatment plan for PNI. Although microsurgery technology has been greatly developed, some peripheral nerve defects or ruptures caused by external forces can be repaired by surgery or nerve transplantation. However, due to the weak ability of nerve cell regeneration and surgical operations may cause damage to the injured nerves, the patient's functional recovery may not be able to achieve the desired effect. Therefore, it is urgent to find a safe and effective method to treat PNI. Mesenchymal stem cells have special differentiation potential and can differentiate into a variety of cell types in vitro and in vivo, and have received widespread attention from researchers. In this paper, the research progress of mesenchymal stem cells in nerve injury repair was summarized, and the characteristics, functions of mesenchymal stem cells and the mechanism of action in peripheral nerve injury repair were reviewed.

Objective To study the clinical efficacy and safety of icotinib hydrochloride tablets combined with whole brain radiotherapy (WBRT) in non-small cell lung cancer (NSCLC) brain metastasis.Methods Fifty-three patients with NSCLC brain metastasis who were unable to tolerate chemotherapy or chemotherapy failed were selected in Baotou Central Hospital from October 2010 to April 2015.The patients were divided into the observation group (n =27) and the control group (n =26) using random number table method.Two patients were dropped out,one in the control group and one in the observation group.The patients in the control group were given WBRT (30 Gy/15 Fx).On this basis,the patients in the observation group were given icotinib hydrochloride tablets 125 mg,3 times a day.The patients were followed up for 18 months after the end of WBRT.The adverse reactions,clinical efficacy and the median survival times of the two groups were compared.Results The objective response rate of the observation group was 88.5％,which was higher than that of the control group (64.0％),and the difference was statistically significant (x2 =4.238,P =0.040).The incidence rates of skin rash and liver function damage in the observation group were 76.9％ and 15.4％,which were higher than those in the control group (0,x2=31.638,P ＜ 0.001;x2 =4.173,P =0.041).However,most of them were degree Ⅰ-Ⅱ,and they were tolerable.There were no significant differences in the incidence of myelosuppression and gastrointestinal reactions between the two groups (26.9％ vs.20.0％,x2 =0.339,P=0.560;34.6％ vs.28.0％,x2 =0.259,P=0.611).The median survival time in the observation group (9.0 months) was longer than that in the control group (7.0 months).The one year survival rate of the observation group was 33.3％,which was higher than that of the control group (23.1％),but the difference was not significant (x2 =0.676,P =0.411).Conclusion Icotinib hydrochloride tablets combined with WBRT in the treatment of brain metastasis with NSCLC can significantly improve the curative effects of brain metastasis,and it has a survival advantage,with tolerable adverse reactions.

Objective: To explore the night sleep quality of shift nurses and the current situation of their daytime tiredness, sleepiness, and to provide evidence for nursing administrators and managers to allocate human resources reasonably and prevent adverse events. Methods: The cross-sectional method was utilized to conduct a questionnaire survey among shift nurses in a tertiary teaching hospital in Shandong Province from March to May inclusive, 2017. Results: There was a total of 233 valid questionnaires returned. The prevalence of sleep disorder, daytime tiredness and sleepiness was 45.92%, 16.31% and 13.30%, respectively. The differences of the nurses' sleep quality at night between different ages, marriages, educational backgrounds and professional titles were statistically significant (P<0.05) , while the differences of daytime burnout and sleep state between different shift systems were statistically significant (P<0.01) . Night sleep quality was positively correlated with daytime tiredness and sleepiness (P<0.05) . The results of multiple linear regression analysis showed that age, marriage, educational background and professional title had an impact on nurses' sleep quality at night (P<0.05) . Shift system had an impact on nurses' daytime burnout and sleep apnea (P<0.01) . Conclusion There was a high prevalence of night sleep disorder, daytime tiredness and sleepiness among the shift nurses. Nursing administrators and managers should pay more attention to the night sleep quality of nurses who aged over 30 years old, married, without a bachelor degree and those with a lower professional rank. Furthermore, the current situation of daytime tiredness and sleepiness among two-shift only nurses was worrisome.

Objective To determine the value of the apparent diffusion coefficient (ADC) of magnetic resonance diffusion-weighted imaging (MRDWI) combined with squamous cell carcinoma antigen (SCC) and carcinoembryonic antigen (CEA) in the evaluation of the efficacy and prognosis of concurrent chemoradiotherapy for cervical carcinoma.Methods A total of 80 patients with cervical squamous cell carcinoma confirmed by histology or cytology in our hospital from 2013 to 2016 were included in this study.Of the 80 patients, 39 were FIGO stage ⅡB, 7 were stage ⅢA, 26 were stage ⅢB, and 8 were stage ⅠVA.MRDWI examination and SCC and CEA measurements were first performed for the patients following group assignment, and the patients were then given extrapelvic radiotherapy (45-50 Gy)+platinum-based chemotherapy plus brachytherapy (20-25 Gy) based on their conditions.MRDWI, SCC, and CEA examinations were performed again after treatment to determine the changes in ADC, SCC, and CEA.In addition, ADC, SCC, and CEA were examined in the middle stage of treatment for 40 patients.Data were analyzed using the paired t-test or ANOVA.Results The overall response rate of the 80 patients after concurrent chemoradiotherapy was 100%.No disease progression was identified in any of the patients until the end of treatment, and the overall survival time of the patients was all above 6 months.Serum SCC and CEA were reduced after treatment (P=0.000,0.000), whereas the ADC value was increased after treatment (P=0.000).The increase in ACD following the decreases in SCC and CEA after treatment (P=0.000, 0.000) was indicative of increased efficacy of the concurrent chemotherapy and radiotherapy.Conclusions MRDWI combined with SCC and CEA is highly reliable for the evaluation of efficacy and prognosis of concurrent chemoradiotherapy for cervical cancer.

Objective To investigate the expressions of B7-H1 and Bcl-2 proteins in epithelial ovarian cancer,and to explore the association of the expressions of B7-H1 and Bcl-2 with clinicopathological features.Methods The expressions of B7-H1 and Bcl-2 proteins were detected by immunohistochemistry in 80 cases of epithelial ovarian cancer tissues and 20 normal ovary tissues.The association of the expressions of B7-H1 and Bcl-2 with the clinicopathological features was analyzed.Results The positive expression rates of B7-H1 and Bcl-2 in epithelial ovarian cancer tissues were 77.5％ (62/80) and 58.8％ (47/80),both higher than 15.0％ (3/20) and 10.0％ (2/20) in normal ovary tissues with significant difference (x2 =27.473,P ＜ 0.05 ; x2 =15.216,P ＜ 0.05).Both of Bcl-2 and B7-H1 expressions in epithelial ovarian cancer tissues were negatively correlated with the differentiation degree of epithelial ovarian cancer (x2 =9.367,P ＜ 0.01 ; x2 =11.702,P ＜ 0.01).The Bcl-2 expression in epithelial ovarian cancer tissues was positively correlated with the FIGO stage (x2 =7.766,P ＜ 0.01).The expression of B7-H1 was positively correlated with the expression of Bcl-2 in epithelial ovarian cancer (r =0.400,P ＜0.01).Conclusion The expressions of B7-H1 and Bcl-2 are up-regulated in epithelial ovarian cancer and they correlate to each other positively.The expressions of B7-H1 and Bcl-2 are correlated with the invasion and metastasis of epithelial ovarian cancer.The detection of B7-H1 combined with Bcl-2 may have an important clinical significance in the diagnosis and treatment for patients with epithelial ovarian cancer.

Objective To evaluate the effect of hydrogen-rich saline on Toll-like receptor 4 (TLR4) /nuclear factor kappa B (NF-κB) signaling pathway in the sciatic nerve of rats with diabetic neuropathic pain (DNP).Methods Pathogen-free male Sprague-Dawley rats, aged 8 weeks, weighing 180-210 g, were used in the study.DPN model was established by intraperitoneal injection of 1％ streptozocin (STZ) 65 mg/kg.Twenty-four diabetic rats were randomly divided into 2 groups (n =12 each) using a random number table: DPN group and hydrogen-rich saline group (HRS group).Another 12 normal rats were randomly selected and served as control group (group C).At 14 days after STZ injection, hydrogenrich saline 5 ml/kg was injected intraperitoneally once a day for 14 consecutive days in group HRS, while the equal volume of normal saline was given in C and DNP groups.Mechanical paw withdrawal threshold to yon Frey stimuli (MWT) and thermal paw withdrawal latency (TWL) were measured at 2 days before STZ injection (T0) , and 7, 14, 21 and 28 days after STZ injection (T1-4).The motor nerve conduction velocity (MNCV) of the right hindlimb was measured after pain threshold was measured at T4.After measurement of neurological function was completed, the expression of TLR4 and NF-κB was detected in the sciatic nerve (by Western blot) , the tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) contents in sciatic nerves were measured by enzyme-linked immunosorbent assay, and the neuronal apoptosis was detected by TUNEL.The apoptosis index was calculated.Results Compared with group C, the MWT was significantly decreased at T1-4, TWL was shortened at T2-4, and MNCV was decreased at T4, the expression of TLR4 and NF-κB, contents of TNF-α and IL-6, and apoptosis index were increased in HRS and DNP groups (P＜0.05).Compared with group DNP, the MWT was significantly increased, and TWL was prolonged at T3,4 MNCV was increased T4, and the expression of TLR4 and NF-κB, contents of TNF-α and IL-6, and apoptosis index were decreased in group HRS (P＜ 0.05).Conclusion Hydrogen-rich saline can mitigate DNP through blocking TLR4/NF-κB signaling pathway in the sciatic nerve of rats.

Objective To evaluate the effect of hydrogen?rich saline on nuclear factor erythroid 2?related factor 2 ( Nrf2)∕antioxidant response element ( ARE) pathway in the peripheral nerve in a rat model of diabetic neuropathic pain ( DNP ) . Methods Thirty?six healthy male Sprague?Dawley rats, aged 8 weeks, weighing 180-200 g, were randomly divided into 3 groups ( n=12 each) using a random number table: control group ( C group) , DNP group and hydrogen?rich saline group ( HRS group) . Diabetes melli?tus was produced by intraperitoneal 1% streptozocin ( STZ) 65 mg∕kg and confirmed by fasting blood glucose concentration>16?67 mmol∕L. Hydrogen?rich saline 5 ml∕kg was injected intraperitoneally once a day for 14 consecutive days starting from 14 days after STZ injection in group HRS, and the equal volume of normal saline was given in C and DNP groups. The mechanical paw withdrawal threshold ( MWT) and thermal paw withdrawal latency ( TWL) were measured at 2 days before STZ injection ( T0 ) , and 7, 14, 21 and 28 days after STZ injection ( T1?4 ) . After measurement of the pain threshold at T4 , the motor nerve conduction velocity ( MNCV) of the right hindlimb and distal motor latency were measured. The expression of Nrf2 in nucleoprotein and HO?1 and NQO1 in total protein was detected in the sciatic nerve by Western blot. Re?sults Compared with group C, the MWT was significantly decreased, and the TWL was shortened at T1?4 , and the expression of Nrf2 in nucleoprotein and HO?1 and NQO1 in total protein was up?regulated in DNP and HRS groups (P<0?05). Compared with group DNP, the MWT was significantly increased, and the TWL was prolonged at T3 and T4 , and the expression of Nrf2 in nucleoprotein and HO?1 and NQO1 in total protein was up?regulated in group HRS ( P<0?05) . Conclusion The mechanism by which hydrogen?rich saline mitigates DNP is related to activated Nrf2∕ARE pathway in the peripheral nerve of rats.