Notum, a negative feedback regulator of the Wnt signaling, has emerged as a promising target for treating glucocorticoid-induced osteoporosis (GIOP). This study showcases an efficient strategy for discovering the anti-Notum constituents from herbal medicines (HMs) as novel anti-GIOP agents. Firstly, a rapid-responding near-infrared fluorogenic substrate for Notum was rationally engineered for high-throughput identifying the anti-Notum HMs. The results showed that Bu-Gu-Zhi (BGZ), a known anti-osteoporosis herb, potently inhibited Notum in a competitive-inhibition manner. To uncover the key anti-Notum constituents in BGZ, an efficient strategy was adapted via integrating biochemical, phytochemical, computational, and pharmacological assays. Among all identified BGZ constituents, three furanocoumarins were validated as strong Notum inhibitors, while 5-methoxypsoralen (5-MP) showed the most potent anti-Notum activity and favorable safety profiles. Mechanistically, 5-MP acted as a competitive inhibitor of Notum via creating strong hydrophobic interactions with Trp128 and Phe268 in the catalytic cavity of Notum. Cellular assays showed that 5-MP remarkably promoted osteoblast differentiation and activated Wnt signaling in dexamethasone (DXMS)-challenged MC3T3-E1 osteoblasts. In dexamethasone-induced osteoporotic mice, 5-MP strongly elevated bone mineral density (BMD) and improved cancellous and cortical bone thickness. Collectively, this study constructs a high-efficient platform for discovering key anti-Notum constituents from HMs, while 5-MP emerges as a promising anti-GIOP agent.

With the increasing emphasis on the bio-psycho-social medical model, significant progress has been made in patient-reported outcomes. Now, through a comprehensive analysis and synthesis of literature within the field, this study explores the advancements in the application of patient-reported outcomes in clinical research on lymphoma. The intention is to provide valuable references for future related studies.

Periodontitis is a chronic inflammatory and immune reactive disease induced by the subgingival biofilm.The therapeutic effect for susceptible patients is often unsatisfactory due to excessive inflammatory response and oxidative stress.Sinensetin(Sin)is a nature polymethoxylated flavonoid with anti-inflammatory and antioxidant activities.Our study aimed to explore the beneficial effect of Sin on periodontitis and the specific molecular mechanisms.We found that Sin attenuated oxidative stress and inflammatory levels of periodontal ligament cells(PDLCs)under inflammatory conditions.Administered Sin to rats with ligation-induced periodontitis models exhibited a protective effect against periodontitis in vivo.By molecular docking,we identified Bach1 as a strong binding target of Sin,and this binding was further verified by cellular thermal displacement assay and immunofluorescence assays.Chromatin immunoprecipitation-quantitative polymerase chain reaction results also revealed that Sin obstructed the binding of Bach1 to the HMOX1 promoter,subsequently upregulating the expression of the key antioxidant factor HO-1.Further functional experiments with Bach1 knocked down and overexpressed verified Bach1 as a key target for Sin to exert its antioxidant effects.Additionally,we demonstrated that Sin prompted the reduction of Bach1 by potentiating the ubiquitination degradation of Bach1,thereby inducing HO-1 expression and inhibiting oxidative stress.Overall,Sin could be a promising drug candidate for the treatment of periodontitis by targeting binding to Bach1.

For the transportation process of rescuing wounded personnel on naval vessels, a new type of shoulder type exoskeleton stretcher for individual soldier was designed in this paper. The three-dimensional model of the shoulder type exoskeleton stretcher for individual soldier was constructed using three dimensional modeling software. Finite element analysis technique was employed to conduct statics simulation, modal analysis, and transient dynamics analysis on the designed exoskeleton stretcher. The results show that the maximum stress of the exoskeleton stretcher for walking on flat ground is 265.55 MPa, which is lower than the allowable strength of the fabrication material. Furthermore, the overall deformation of the structure is small. Modal analysis reveals that the natural frequency range of the exoskeleton stretcher under different gait conditions is 1.96 Hz to 28.70 Hz, which differs significantly from the swing frequency of 1 Hz during walking. This indicates that the designed structure can effectively avoid resonance. The transient dynamics analysis results show that the maximum deformation and stress of exoskeleton stretcher remain within the safety range, which meets the expected performance requirements. In summary, the shoulder type exoskeleton stretcher for individual soldier designed in this study can solve the problem of requiring more than 2 people to carry for the existing stretcher, especially suitable for narrow spaces of naval vessels. The research results of this paper can provide a new solution for the rescue of wounded personnel on naval vessels.
Humans ; Stretchers ; Military Personnel ; Shoulder ; Exoskeleton Device ; Walking ; Gait ; Biomechanical Phenomena

Objective:To explore the relationships between sarcopenia and the clinical efficacy and prognosis of elderly patients with esophageal cancer who were treated by radical radiotherapy.Methods:The clinicopathological data of 134 elderly patients with esophageal cancer who received radical radiotherapy in Department of Radiotherapy, Affiliated Hospital of Yangzhou University from January 2013 to December 2018 were retrospectively analyzed. The muscle cross-sectional area at the level of the third lumbar vertebra was measured by using computed tomography (CT) images. These patients were divided into sarcopenia group ( n=56) and non-sarcopenia group ( n=78) according to the skeletal muscle index before radiotherapy. The efficacy and incidence of adverse reactions of the two groups were compared. Kaplan-Meier method was used to plot the survival curve, and Cox regression model was used to analyze prognostic factors. Results:There was a significant difference in the objective response rate between the sarcopenia and non-sarcopenia group at 1 month after radiotherapy [53.57% (30/56) vs. 71.79% (56/78) , χ2=4.71, P=0.030]. There was no significant difference in the disease control rate between the two groups [94.64% (53/56) vs. 91.03% (71/78) , χ2=0.21, P=0.651]. There was a significant difference in the total incidence of adverse reactions between the sarcopenia and non-sarcopenia group [67.86% (38/56) vs. 47.44% (37/78) , χ2=5.52, P=0.019]. By the end of the follow-up, the 1-, 3- and 5-year overall survival (OS) rates of 134 elderly patients with esophageal cancer who received radical radiotherapy were 91.0%, 73.1% and 55.2% respectively. The median OS of patients in the sarcopenia and non-sarcopenia group were 14 months and 26 months respectively, with a statistically significant difference ( χ2=9.84, P=0.002) . The median progression-free survival (PFS) of the two groups were 7 months and 18 months respectively, with a statistically significant difference ( χ2=9.91, P=0.002) . Univariate analysis showed that cT stage ( HR=2.45, 95% CI: 1.26-4.74, P=0.008) , cN stage ( HR=1.63, 95% CI: 1.06-2.50, P=0.027) , cTNM stage ( HR=2.04, 95% CI: 1.28-3.27, P=0.003) , body mass index (BMI) ( HR=2.23, 95% CI: 1.01-4.90, P=0.046) , pre-radiotherapy sarcopenia ( HR=2.45, 95% CI: 1.27-4.72, P=0.007) and chemotherapy ( HR=0.30, 95% CI: 0.11-0.83, P=0.020) were prognostic factors for OS; cT stage ( HR=2.27, 95% CI: 1.18-4.39, P=0.015) , cN stage ( HR=1.61, 95% CI: 1.04-2.47, P=0.030) , cTNM stage ( HR=1.90, 95% CI: 1.19-3.02, P=0.007) , BMI ( HR=1.98, 95% CI: 1.06-3.79, P=0.032) , pre-radiotherapy sarcopenia ( HR=1.79, 95% CI: 1.06-3.04, P=0.031) and adverse reactions ( HR=0.60, 95% CI: 0.38-0.97, P=0.037) were prognostic factors for PFS. Multivariate analysis showed that pre-radiotherapy sarcopenia ( HR=1.91, 95% CI: 1.22-3.00, P=0.005) was an independent prognostic factor for OS; BMI ( HR=1.80, 95% CI: 1.03-3.15, P=0.039) and pre-radiotherapy sarcopenia ( HR=2.00, 95% CI: 1.27-3.14, P=0.003) were independent prognostic factors for PFS. Conclusion:Sarcopenia before radiotherapy can be a useful predictor for prognosis in elderly patients with esophageal cancer who received radical radiotherapy, and patients with sarcopenia benefit less from treatment.

Acute gastrointestinal dysfunction is a common and important complication of sepsis. As no exiting formal definition and classification of gastrointestinal dysfunction, most of the treatment strategies for gastrointestinal dysfunction are not based on clinical evidence, but on their own clinical experience. Experts of traditional Chinese medicine, integrated traditional Chinese and Western medicine and Western medicine from various disciplines in Shanghai are organized by the Shanghai Society of Integrated Traditional Chinese and Western Medicine and the Emergency Department Branch of Shanghai Physicians Association. After repeated discussion, literature search and formulation of the outline, we developed consensus on gastrointestinal dysfunction secondary to sepsis with integrating Traditional Chinese Medicine and Western medicine by consulting extensively on clinical experts in the fields of emergency medicine, gastroenterology, general surgery, infectious medicine and traditional Chinese medicine, and holding several expert forums and consultation meetings. This clinical expert consensus focused on acute gastrointestinal injury (AGI) classification and inducer of sepsis. In this consensus, the common symptoms, diagnosis, classifications, treatment strategies and suggestions of acute gastrointestinal injury or dysfunction secondary to sepsis were explored from the aspect of both Traditional Chinese Medicine and Western medicine.

With the emergence of DNA nanotechnology in the 1980s, self-assembled DNA nanostructures have attracted considerable attention worldwide due to their inherent biocompatibility, unsurpassed programmability, and versatile functions. Especially promising nanostructures are tetrahedral framework nucleic acids (tFNAs), first proposed by Turberfield with the use of a one-step annealing approach. Benefiting from their various merits, such as simple synthesis, high reproducibility, structural stability, cellular internalization, tissue permeability, and editable functionality, tFNAs have been widely applied in the biomedical field as three-dimensional DNA nanomaterials. Surprisingly, tFNAs exhibit positive effects on cellular biological behaviors and tissue regeneration, which may be used to treat inflammatory and degenerative diseases. According to their intended application and carrying capacity, tFNAs could carry functional nucleic acids or therapeutic molecules through extended sequences, sticky-end hybridization, intercalation, and encapsulation based on the Watson and Crick principle. Additionally, dynamic tFNAs also have potential applications in controlled and targeted therapies. This review summarized the latest progress in pure/modified/dynamic tFNAs and demonstrated their regenerative medicine applications. These applications include promoting the regeneration of the bone, cartilage, nerve, skin, vasculature, or muscle and treating diseases such as bone defects, neurological disorders, joint-related inflammatory diseases, periodontitis, and immune diseases.
Nucleic Acids/chemistry* ; Regenerative Medicine ; Consensus ; Reproducibility of Results ; DNA/chemistry*

The study aims to improve the level of fine management of medical equipments, give full play to the functions and roles for better patient service, and explore methods for evaluating the benefits of medical equipment that can take into account and reflect the needs of multiple parties. Based on objectives and key results(OKR) methods and concepts, a benefit evaluation system was developed with the goal of giving full play to the functions and roles of medical equipments, with corresponding evaluation indexes and supervision and evaluation mechanisms formulated as well. This index system could take into account the needs and concerns of hospitals, the departments in use, the management authorities and patients at large, while contributing to process supervision and continuous improvement. In the OKR practice of large medical equipments(CT, MR) from 2018 to 2019, they had performed significantly better in inspections, inspection positive coincident rates, clinical service capabilities, maintenance assurance levels, patient satisfaction, scientific research and academics among others. The use of a medical equipment benefit evaluation system based on OKR concepts and methods can provide effective evaluation indicators for the operation and management of medical equipments. In addition, the system can maintain internal improvement momentum leveraging process supervision and continuous improvement methods, in order to assure the elevation of fine management level of medical equipments of modern hospitals, thus offering better medical services for patients at large.

Objective:To evaluate the biomechanical performance of our self-designed anatomical plate for posterolateral tibial plateau in comparison with conventional plates for treatment of posterolateral tibial plateau fractures.Methods:A novel anatomic plate for posterolateral tibial plateau was designed according to the data measured in the superior fibular capitulum and 3D CT segmentation. Twenty-four knee joints were obtained from 12 freshly frozen adult cadavers to make models of posterolateral tibial plateau fracture. The models were divided into 3 groups( n=8). In group A, fixation was simulated via the supra-fibular-head approach after autogenous iliac bone-graft by our self-designed anatomic plate for posterolateral tibial plateau; in group B, fixation was simulated via the posterior tibial approach after autogenous iliac bone-graft by a small T-plate; in group C, fixation was simulated via the supra-fibular-head approach after autogenous iliac bone-graft by a normal L-plate. Biomechanical tests were carried out in the 3 groups to measure the vertical displacements of split bone fragment under the vertical compression loads of 500 N, 1,000 N and 1,500 N and the maximum compression upon failure of internal fixation (compressed displacemen t=3 mm). Results:At the vertical compression loads of 500 N, 1,000 N and 1,500 N, the vertical displacements of split bone fragment showed significant differences among the 3 groups ( P<0.05); there was a significant difference between group C and groups A and B, respectively ( P<0.05), but an insignificant difference between group A and group B ( P>0.05) though group A performed slightly better. In terms of the maximum compression upon failure of internal fixation, significant differences existed among the 3 groups ( P<0.05); there was a significant difference between group C and groups A and B, respectively ( P< 0.05), but an insignificant difference between group A and group B ( P>0.05). Conclusions:Our self-designed anatomic plate for posterolateral tibial plateau can firmly fixate the fracture fragments of posterolateral condyle.

Objective:To explore the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed/refractory acute myeloid leukemia (AML).Methods:The clinical data of 35 patients with relapsed/refractory AML treated with allo-HSCT in the Affiliated Cancer Hospital of Zhengzhou University from June 2011 to October 2018 was retrospectively analyzed. The overall survival (OS), disease-free survival (DFS), graft versus host disease (GVHD) incidence, transplantation related mortality and recurrence rate were calculated, and the risk factors affecting prognosis were analyzed.Results:Hematopoietic reconstitution was obtained in all patients after transplantation. The 100 d incidence of grade Ⅱ-Ⅳ acute GVHD was (22.9±7.7)%, and the 3-year incidence of chronic GVHD was (49.5±10.60)%. The median follow-up time after transplantation was 14.1 months (4.2-89.4 months). In all cases, 18 cases survived (including 16 cases of DFS), and 17 cases died. Fourteen cases relapsed, and the median recurrence time was 4.7 months (2.9-32.4 months). The 3-year OS rate and DFS rate were (44.4±9.3)% and (43.0±9.5)%, respectively. Univariate analysis showed that the non-remission disease before transplantation, poor genetic risk grade before transplantation and recurrence after transplantation were the risk factors for OS (all P < 0.05). The 3-year OS rates in complete remission before transplantation group and non-remission before transplantation group were (63.2±12.0)% and (15.7±12.8)% ( P = 0.025), the 3-year DFS rates were (62.2±12.3)% and (15.3±12.7)% ( P = 0.028), and the 3-year recurrence rates were (28.2±10.7)% and (80.6±15.7)% ( P = 0.057). The 3-year recurrence rate in genetic high-risk group was higher than that in middle-risk group and low-risk group [100.0%, (45.0±12.1)% and (14.3±13.2)%, P = 0.045]. The 3-year tansplantation related mortality was (18.7±7.7)%. Conclusions:Allo-HSCT is an effective method for salvage treatment of relapsed/refractory AML, and recurrence is the main factor affecting survival. Reducing tumor load before transplantation is very important for reducing recurrence and improving curative effect.