Personalized Porous Gelatin Methacryloyl Sustained-Release Nicotinamide Protects Against Noise-Induced Hearing Loss.

There are no Food and Drug Administration-approved drugs for treating noise-induced hearing loss (NIHL), reflecting the absence of clear specific therapeutic targets and effective delivery strategies. Noise trauma is demonstrated results in nicotinamide adenine dinucleotide (NAD+) downregulation and mitochondrial dysfunction in cochlear hair cells (HCs) and spiral ganglion neurons (SGNs) in mice, and NAD+ boosted by nicotinamide (NAM) supplementation maintains cochlear mitochondrial homeostasis and prevents neuroexcitatory toxic injury in vitro and ex vivo, also significantly ameliorated NIHL in vivo. To tackle the limited drug delivery efficiency due to sophisticated anatomical barriers and unique clearance pathway in ear, personalized NAM-encapsulated porous gelatin methacryloyl (PGMA@NAM) are developed based on anatomy topography of murine temporal bone by micro-computed tomography and reconstruction of round window (RW) niche, realizing hydrogel in situ implantation completely, NAM sustained-release and long-term auditory preservation in mice. This study strongly supports personalized PGMA@NAM as NIHL protection drug with effective inner ear delivery, providing new inspiration for drug-based treatment of NIHL.

Effects of 6-Hydroxykaempferol: A Potential Natural Product for Amelioration of Tendon Impairment.

Tendon impairment is a common injury associated with impairment of range of motion and pain. Currently, evidence has confirmed that natural herbs contribute to orthopedics and have shown excellent results in the clinical management of tendon impairment. Shujin Huoxue tablet (SHT) and its complex prescriptions are regularly used in tendon rupture therapy with positive results. This study aimed to discover the potential molecules that promote tendon healing. The Chinese traditional medicine system pharmacological database analysis platform (TCMSP) is the primary resource. The Traditional Chinese Medicine Integrated Database and Encyclopedia of Traditional Chinese Medicine database were used as secondary databases. The GeneCards database was used to search for reported tendinopathy-related genes by keywords. Functions of the targeted genes were analyzed using Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes. Protein-protein interaction information was extracted from the STRING database. Docking study, MTT assay, quantitative real-time PCR, and migration assays were performed to obtain a better understanding of the herbs according to cell function to test the basic pharmacological action in vitro. A total of 104 disease nodes, 496 target gene nodes, 35 ingredient nodes, and one drug node were extracted. According to the TCMSP database, 6-hydroxykaempferol, which reportedly promotes the proliferation of microvascular endothelial cells, is a molecule found in SHT. We found that it promoted the proliferation and migration of tendon fibroblasts and elevated tendon repair-related gene expression. Purified 6-hydroxykaempferol promoted the proliferation and migration of tendon fibroblasts and increased their mRNA expression in tendon proliferation.

Adherence to supplemental vitamin D intake and infant weight gain: a retrospective cohort study in rural southwestern China.

OBJECTIVES: We tested the hypothesis that vitamin D supplementation is associated with early body mass index (BMI) patterns. METHODS: Using retrospective longitudinal data of infants and toddlers in a 2-year follow-up study, we identified BMI-for-age Z score (BAZ) growth trajectories using latent class growth modeling (LCGM) analysis. Logistic regression models were adopted to investigate the impact of vitamin D supplementation on BAZ patterns. RESULTS: Five BAZ trajectories were derived using LCGM. Higher intake of vitamin D supplement was significantly associated with lower odds of rapid weight gain or mild undernutrition in the first 2 years (odds ratios: 0.60-0.83 for class 2: early rapid growth; 0.69-0.82 for class 3: early weight loss, late rapid growth; 0.83-0.89 for class 4: suboptimal growth). Adherence to 400 IU Vitamin D ≥ 1 year was significantly associated with less likelihood of being in class 3 (odds ratio 0.17). CONCLUSIONS: Among infants and toddlers aged 0 to 2 years, dietary supplementation of vitamin D is insufficient in rural areas of China. Insufficient vitamin D intake was found to be associated with suboptimal BAZ growth at early stages. Effective collaboration is needed between pediatricians and caregivers, to assure adherence to the nutritional guideline.

[Electro-acupuncture promotes repair of rotator cuff injury in rats].

OBJECTIVE: To observe the therapeutic effect of electro-acupuncture on tendon healing and functional recovery of rotator cuff injury in rats and explore the therapeutic mechanism of electro-acupuncture. METHODS: Ninety SD rats were randomly divided into electro-acupuncture group, model group and blank control group, and models of rotator cuff injury were established in the former two groups.The rats in electro-acupuncture group was treated with electro-acupuncture after the operation, and those in the other two groups received no treatment.The right forefoot thermal withdrawal latency (TWL), the contents of IL-1ß, IL-6 and TNF-α in the synovial fluid and the maximum tension load of supraspinatus tendon were measured at 2, 4 and 8 weeks after the operation. RESULTS: TWL in the model group was significantly lower than that in the blank control group and electro-acupuncture group at 2, 4 and 8 weeks after the operation (P < 0.05).At all these time points, the contents of IL-1ß, IL-6 and TNF-α in the synovial fluid were significantly higher in the model group than in the blank control group and electro-acupuncture group (P < 0.05).At 2 weeks, the maximum load in electro-acupuncture group and model group were significantly lower than that in the blank control group (P < 0.05).At 4 and 8 weeks after the operation, the maximum pull load was significantly greater in electro-acupuncture group than in the model group (P < 0.05). CONCLUSIONS: Electro-acupuncture treatment not only effectively reduces the expression of inflammatory factors to relieve pain, but also promotes the repair of damaged tissue to improve the biomechanical properties of rotator cuff in the rat models.

Decreased Synovial Fluid Biomarkers Levels Are Associated with Rehabilitation of Function and Pain in Rotator Cuff Tear Patients Following Electroacupuncture Therapy.

BACKGROUND The aim of this study was to assess inflammatory cytokines levels in synovial fluid (SF) before and after electroacupuncture (EA) treatment and to explore whether these biomarkers are associated with function of rotator cuff tear (RCT) patients. MATERIAL AND METHODS We recruited 54 patients with RCT and separated them into an EA group and a control group. The SF biomarker levels were detected at baseline and at 6-week and 6-month follow-up. The symptomatic severity was evaluated by visual analog scale (VAS), Constant-Murley score, and American Shoulder and Elbow Surgeons score (ASES). We also investigated the correlation between symptomatic severity and biomarker levels in SF of the shoulder joint. RESULTS The reductions in VAS and improved functional score (ASES and Constant-Murley score) were significantly different between the 2 groups, and SF biomarker concentrations were significantly lower in the EA group. IL-1ß levels were significantly negatively correlated with Constant-Murley score (r=-0.73, P=0.04) and ASES score (r=-0.59, P<0.001) and positively correlated with VAS scores (r=0.81, P=0.004). IL-6 levels were significantly negatively correlated with Constant-Murley score (r=-0.67, P=0.03) and positively correlated with VAS score (r=0.7, P=0.01). MMP-1 levels were significantly negatively correlated with ASES score (r=-0.57, P<0.001). CONCLUSIONS The biomarkers in SF were directly associated with shoulder pain and shoulder function in rotator cuff tear. EA, as a safe and effective conservative therapy, obviously decreased the level of inflammatory cytokines in RCT patients, accompanied by a reduction in shoulder pain and improved function.

Effects of Amifostine Pre-treatment on MIRNA, LNCRNA, and MRNA Profiles in the Hypothalamus of Mice Exposed to 60Co Gamma Radiation.

There is increasing evidence that the expression of non-coding RNA and mRNA (messenger RNA) is significantly altered following high-dose ionizing radiation (IR), and their expression may play a critical role in cellular responses to IR. However, the role of non-coding RNA and mRNA in radiation protection, especially in the nervous system, remains unknown. In this study, microarray profiles were used to determine microRNA (miRNA), long non-coding RNA (lncRNA), and mRNA expression in the hypothalamus of mice that were pretreated with amifostine and subsequently exposed to high-dose IR. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. We found that fewer miRNAs, lncRNAs, and mRNAs were induced by amifostine pre-treatment in exposed mice, which exhibited antagonistic effects compared to IR, indicating that amifostine attenuated the IR-induced effects on RNA profiles. GO and KEGG pathway analyses showed changes in a variety of signaling pathways involved in inflammatory responses during radioprotection following amifostine pre-treatment in exposed mice. Taken together, our study revealed that amifostine treatment altered or attenuated miRNA, lncRNA, and mRNA expression in the hypothalamus of exposed mice. These data provide a resource to further elucidate the mechanisms underlying amifostine-mediated radioprotection in the hypothalamus.

[Research progress on mechanism of acupuncture and moxibustion promoting fracture healing].

Acupuncture has a significant effect on promoting fracture healing. It can dredge meridians and collaterals, regulate qi and blood, eliminate swelling and remove stasis. However, its mechanism is still not fully elucidated. With the development of research, it has been found in recent years that the mechanism of acupuncture and moxibustion promoting fracture healing involves regulating the expression level of cell growth factor, activating Wnt/ß-Catenin and other signal pathways, improving local blood circulation, affecting the content of mineral elements in bone, regulating the endocrine system, promoting the differentiation and proliferation of bone cells, promoting the proliferation and activation of osteoblasts and influencing the apoptosis of bone cells And so on. The mechanism of acupuncture and moxibustion promoting fracture healing is very complex, which is still at the level of animal experiments and cells.

[Effect of electroacupuncture on rehabilitation of knee joint movement after anterior cruciate ligament reconstruction].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the rehabilitation of knee joint function after anterior cruciate ligament (ACL) reconstruction. METHODS: A total of 140 patients with ACL reconstruction were randomly divided into an observation group (58 cases recruited, 12 cases dropped out) and a control group (65 cases recruited, 5 cases dropped out). The patients in the control group were treated with routine rehabilitation treatment. The patients in the observation group, on the basis of the treatment in the control group, were treated with EA at Fengshi (GB 31), Futu (ST 32), Zusanli (ST 36), Shangjuxu (ST 37), Fenglong (ST 40), Xuanzhong (GB 39), Diji (SP 8) and Sanyinjiao (SP 6) on the affected side (2 Hz/100 Hz of dilatational wave, 2-5 mA). Each EA treatment lasted 20-30 min, twice a day for 7 days. The swelling degree (d), pain visual analogue scale (VAS), knee joint range of motion (ROM), scores of International Knee Documentation Committee (IKDC) subjective short form and scores of Lysholm were observed in the two groups 1 day, 1 month, 3 months, 6 months and 1 year after operation. RESULTS: One month and 3 months after operation, the swelling degree (d) and VAS scores in the observation group were lower than those in the control group (P<0.05); 6 months and 1 year after operation, there was no significant difference between the two groups on the swelling degree (d) and VAS scores (P>0.05). One month, 3 months, 6 months and 1 year after operation, the ROM of the knee joint in the observation group was higher than that in the control group (P<0.05), the IKDC score and Lysholm score were higher than those in the control group (P<0.05). Within one year, there were no relaxations, fractures and other related complications in the two groups. The pivot shift test, anterior drawer test and the Lachman test were all negative. CONCLUSION: EA combined with routine rehabilitation training could obviously reduce the pain of knee joint, improve the swelling degree, increase the ROM of knee joint, promote the functional recovery in patients with ACL reconstruction, which are superior to rehabilitation training alone.

Transcriptional activation of miR-320a by ATF2, ELK1 and YY1 induces cancer cell apoptosis under ionizing radiation conditions.

MicroRNAs (miRNAs or miRs) play important roles in numerous cellular processes, including development, proliferation, tumorigenesis and apoptosis. It has been reported that miRNA expression is induced by ionizing radiation (IR) in cancer cells. However, the underlying molecular mechanisms are not yet fully understood. In this study, endogenous miR­320a and its primary precursor (pri­miR­320a) were assayed by reverse transcription­quantitative PCR (RT­qPCR). Luciferase activities were measured using a dual­luciferase reporter assay system. Western blot analysis was used to determine the protein expressions of upstream and downstream genes of miR­320a. Cell apoptosis was evaluated by Annexin V apoptosis assay and cell proliferation was measured using the trypan blue exclusion method. The results revealed that miR­320a expression increased linearly with the IR dose and treatment duration. Three transcription factors, activating transcription factor 2 (ATF2), ETS transcription factor (ELK1) and YY1 transcription factor (YY1), were activated by p38 mitogen­activated protein kinase (MAPK) and mitogen­activated protein kinase 8 (JNK) and by upregulated miR­320a expression under IR conditions. In addition, it was identified that X­linked inhibitor of apoptosis (XIAP) was an miR­320a target gene during the IR response. By targeting XIAP, miR­320a induced apoptosis and inhibited the proliferation of the cancer cells. On the whole, the results of this study demonstrated that miRNA­320a, regulated by the p38 MAPK/JNK pathway, enhanced the radiosensitivity of cancer cells by inhibiting XIAP and this may thus prove to be a potential therapeutic approach with which to overcome radioresistance in cancer treatment.

Doctors' compliance with national guidelines and clinical pathway on the treatment of tuberculosis inpatients in Hubei, China.

RATIONALE, AIMS AND OBJECTIVES: The Ministry of Health in China has enacted a revised National Tuberculosis Control Program (NTP) guidelines and clinical pathway (CP) on new smear-positive pulmonary tuberculosis (TB) inpatients to improve the quality of TB care and asked doctors' compliance to them on the treatment of TB inpatients. However, it remains unknown whether doctors adhere to them well. So this study focuses on evaluating the doctors' compliance with them in one representative TB hospital for medical quality improvement. METHODS: A hospital-based retrospective study involving all medical records of newly diagnosed smear-positive pulmonary TB inpatients from July 2011 to July 2013. Analysis indicators including adequate drug regimens rate, adequate drug dosages rate and adequate length of hospital stay rate were chosen to assess doctors' compliance with NTP guidelines and CP on the treatment of new smear-positive pulmonary TB inpatients. The optimal value of these indicators is 100%. RESULTS: Of the 334 inpatients selected, the rate of adequate drug regimens prescribed is 26.95% (90/334), and the rate of adequate drug dosages is 0% (0/90). For the dosage of single drug, the rates of adequate dosage of isoniazid, rifampicin, pyrazinamide and ethambutol are 24.44% (22/90), 85.56% (77/90), 70% (63/90) and 13.33% (12/90). Moreover, 75.56% (68/90) of isoniazid was prescribed too high and 83.34% (75/90) of ethambutol was prescribed too low. The rate of adequate length of hospital stay provided is 28.44% (95/334). CONCLUSION: Doctors' compliance with NTP guidelines and CP on new smear-positive pulmonary TB inpatients is depressed and needs improvement.

Stimulation of osteogenic differentiation in stromal cells of giant cell tumour of bone by zoledronic acid.

Therapeutic effects of zoledronic acid (ZOL) on giant cell tumour of bone (GCT) have been proven. Apoptosis induction was considered to be one of the mechanisms of ZOL tumour inhibition. In this study, we presented the possibility of an osteogenic differentiation stimulation mechanism of ZOL and further investigated dosage and time effects. We treated stromal cells of GCT (GCTSC) with ZOL for 48 hours at different concentrations (0 µM, 0.01 µM, 0.1 µM, 1 µM, 5 µM, 30 µM) and assessed apoptotic and osteogenic differentiation markers with immunohistochemical techniques and real-time quantitative RT-PCR. Our results suggested that ZOL enhanced mRNA expression of Cbfa-1, osterix and osteocalcin genes with a maximum effect at 1 µM in GCTSC. Time course experiments indicated a time dependent osteogenic differentiation effect. In conclusion, ZOL may be considered as an adjuvant in the treatment of GCT not only by inducing apoptosis but also by stimulating osteogenic differentiation of remaining tumor stromal cells after surgery.