Dual-driven nanomotors enable tumor penetration and hypoxia alleviation for calcium overload-photo-immunotherapy against colorectal cancer.

The treatment efficacies of conventional medications against colorectal cancer (CRC) are restricted by a low penetrative, hypoxic, and immunosuppressive tumor microenvironment. To address these restrictions, we developed an innovative antitumor platform that employs calcium overload-phototherapy using mitochondrial N770-conjugated mesoporous silica nanoparticles loaded with CaO2 (CaO2-N770@MSNs). A loading level of 14.0 wt% for CaO2-N770@MSNs was measured, constituting an adequate therapeutic dosage. With the combination of oxygen generated from CaO2 and hyperthermia under near-infrared irradiation, CaO2-N770@MSNs penetrated through the dense mucus, accumulated in the colorectal tumor tissues, and inhibited tumor cell growth through endoplasmic reticulum stress and mitochondrial damage. The combination of calcium overload and phototherapy revealed high therapeutic efficacy against orthotopic colorectal tumors, alleviated the immunosuppressive microenvironment, elevated the abundance of beneficial microorganisms (e.g., Lactobacillaceae and Lachnospiraceae), and decreased harmful microorganisms (e.g., Bacteroidaceae and Muribaculaceae). Moreover, together with immune checkpoint blocker (αPD-L1), these nanoparticles showed an ability to eradicate both orthotopic and distant tumors, while potentiating systemic antitumor immunity. This treatment platform (CaO2-N770@MSNs plus αPD-L1) open a new horizon of synergistic treatment against hypoxic CRC with high killing power and safety.

Flat Silk Cocoon-Based Dressing: Daylight-Driven Rechargeable Antibacterial Membranes Accelerate Infected Wound Healing.

One of the leading causes of death globally, especially in underdeveloped countries, is bacterial infection. Recently, the prevalence of infections from antibiotic-resistant bacteria has been increasing, which makes the need for innovative antibacterial wound dressings urgent. It is reported that g-C3 N4 -based flat silk cocoons (FSCs) with rechargeable antibacterial activity can efficiently generate reactive oxygen species (ROS) under daylight irradiation. The photoactive FSCs store the ROS and then release them in the dark. The engineered FSCs exhibit integrated properties of good biocompatibility, strong mechanical characteristics, robust photoactivity with photostorability, and excellent bactericidal efficiency (99.9% contact killing). In a rat model of infected wounds, the photoactive FSCs induce faster healing and reduce bacterial infections. The successful application of these FSC materials as wound dressings may provide a versatile platform for exploring the use of green photoactive antibacterial materials for accelerated wound healing and prevention of infections.

Fabrication of Rechargeable Photoactive Silk Fibroin/Polyvinyl Alcohol Blend Nanofibrous Membranes for Killing Bacteria.

Antibacterial materials that prevent bacterial infections and mitigate bacterial virulence have attracted great scientific interest. In recent decades, bactericidal polymers have been presented as promising candidates to combat bacterial pathogens. However, the preparation of such materials has proven to be extremely challenging. Herein, photoactive silk fibroin/polyvinyl alcohol blended nanofibrous membranes grafted with 3,3',4,4'-benzophenone tetracarboxylic dianhydride (G-SF/PVA BNM) were fabricated by an electrospinning technique. The premise of this work is that the G-SF/PVA BNM can store photoactive activity under light irradiation and release reactive oxygen species for killing bacteria under dark conditions. The results showed that the resultant G-SF/PVA BNM exhibited the integrated properties of an ultrathin fiber diameter (298 nm), good mechanical properties, robust photoactive activity and photo-store capacity, and great photoinduced antibacterial activity against E. coli and S. aureus (99.999% bacterial reduction with 120 min). The successful construction of blended nanofibrous membranes gives a new possibility to the design of highly efficient antibacterial materials for public health protection.

Near-Infrared-Enpowered Nanomotor-Mediated Targeted Chemotherapy and Mitochondrial Phototherapy to Boost Systematic Antitumor Immunity.

Phototherapy is an important strategy to inhibit tumor growth and activate antitumor immunity. However, the effect of photothermal/photodynamic therapy (PTT/PDT) is restricted by limited tumor penetration depth and unsatisfactory potentiation of antitumor immunity. Here, a near-infrared (NIR)-driven nanomotor is constructed with a mesoporous silicon nanoparticle (MSN) as the core, end-capped with Antheraea pernyi silk fibroin (ApSF) comprising arginine-glycine-aspartate (RGD) tripeptides. Upon NIR irradiation, the resulting ApSF-coated MSNs (DIMs) loading with photosensitizers (ICG derivatives, IDs) and chemotherapeutic drugs (doxorubicin, Dox) can efficiently penetrate into the internal tumor tissues and achieve effective phototherapy. Combined with chemotherapy, a triple-modal treatment (PTT, PDT, and chemotherapy) approach is developed to induce the immunogenic cell death of tumor cells and to accelerate the release of damage-associated molecular patterns. In vivo results suggest that DIMs can promote the maturation of dendritic cells and surge the number of infiltrated immune cells. Meanwhile, DIMs can polarize macrophages from M2 to M1 phenotypes and reduce the percentages of immunosuppressive Tregs, which reverse the immunosuppressive tumor microenvironment and activate systemic antitumor immunity. By achieving synergistic effects on the tumor inhibition and the antitumor immunity activation, DIMs show great promise as new nanoplatforms to treat metastatic breast cancer.

Coordination with zirconium: A facile approach to improve the mechanical properties and thermostability of gelatin hydrogel.

The poor mechanical property and thermostability restricted applications of gelatin hydrogel. Herein, a facile and inexpensive approach of immerging cooling induced gelatin hydrogels into Zr(SO4)2 dilute solution was applied to overcome these shortages. After this treatment, the micropores in hydrogel decreased to tens of microns while the water content slightly decreased. XPS results revealed that the coordination bonds formed between amino or carboxyl groups of gelatins and Zr4+. After immerging in 0.06 M Zr4+ solution, mechanical tests showed that the elastic modulus, compressive modulus and compressive strength of hydrogel were about 400, 1192 and 476 kPa, respectively, which were approximate 100, 11 and 5 times larger than those of pure gelatin. The DSC data indicated that the thermoreversible temperature of triple helix structure in gelatin was improved from about 30 °C to 55 °C. More importantly, the rheological temperature sweep test revealed that hydrogels with 0.06 M Zr4+ treatment can maintain the hydrogel state without melting even at 80 °C. CCK-8 tests and Calcein-AM/PI double-stain experiments demonstrated Zr4+ coordination was non-cytotoxic. These promising data indicated this nontoxic method was efficient and had potential to fabricate gelatin related materials for further application.

Multi-responsive nanotheranostics with enhanced tumor penetration and oxygen self-producing capacities for multimodal synergistic cancer therapy.

Incorporation of multiple functions into one nanoplatform can improve cancer diagnostic efficacy and enhance anti-cancer outcomes. Here, we constructed doxorubicin (DOX)-loaded silk fibroin-based nanoparticles (NPs) with surface functionalization by photosensitizer (N770). The obtained nanotheranostics (N770-DOX@NPs) had desirable particle size (157 nm) and negative surface charge (-25 mV). These NPs presented excellent oxygen-generating capacity and responded to a quadruple of stimuli (acidic solution, reactive oxygen species, glutathione, and hyperthermia). Surface functionalization of DOX@NPs with N770 could endow them with active internalization by cancerous cell lines, but not by normal cells. Furthermore, the intracellular NPs were found to be preferentially retained in mitochondria, which were also efficient for near-infrared (NIR) fluorescence imaging, photothermal imaging, and photoacoustic imaging. Meanwhile, DOX could spontaneously accumulate in the nucleus. Importantly, a mouse test group treated with N770-DOX@NPs plus NIR irradiation achieved the best tumor retardation effect among all treatment groups based on tumor-bearing mouse models and a patient-derived xenograft model, demonstrating the unprecedented therapeutic effects of trimodal imaging-guided mitochondrial phototherapy (photothermal therapy and photodynamic therapy) and chemotherapy. Therefore, the present study brings new insight into the exploitation of an easy-to-use, versatile, and robust nanoplatform for programmable targeting, imaging, and applying synergistic therapy to tumors.

Retrospective study of therapeutic effect of Tongbi paste vs Fufangzhuifeng paste for shoulder periarthritis.

OBJECTIVE: To compare the therapeutic effects of Tongbi and Fufangzhuifeng pastes in shoulder periarthritis. METHODS: The retrospective study was conducted at the Chongqing Traditional Chinese Medicine Hospital, China, and comprised data of shoulder periarthritis patients who were treated from December 2018 to June 2019. Group A had data of patients treated with Tongbi paste and group B had data of patients treated with Fufangzhuifeng paste. The groups were compared for effect on pain, shoulder flexion, abduction and extension. Data was analysed using SPSS 22. RESULTS: Of the 81 patients, 43(53%) were in group A; 18(42%) males and 25(58%) females with an overall mean age of 54.26±12.38 years (range: 28-79 years) who were suffering from shoulder periarthritis for a mean duration of 5.08±3.07 months (range: 0.25-13 months). There were 38(47%) patients in group B; 23(60.5%) females and 15(39.5%) males with an overall mean age of 53.08±11.08 years (range: 33-76 years) who were suffering from shoulder periarthritis for a mean duration of 4.96±2.77 months (range: 1-12 months). Mean pain, shoulder flexion, abduction and extension scores after two weeks of treatment were significantly better for group A compared to group B (p<0.001), but after three weeks of treatment, intergroup differences were different but not significant (p>0.05). CONCLUSION: Tongbi and Fufangzhuifeng pastes were found to have a positive effect in the treatment of shoulder periarthritis, with the former providing faster relief.

Retrospective study of effect of whole-body vibration training on balance and walking function in stroke patients.

BACKGROUND: Dysfunction in stroke patients has been a problem that we committed to solve and explore. Physical therapy has some effect to regain strength, balance, and coordination. However, it is not a complete cure, so we are trying to find more effective treatments. AIM: To observe the effect of whole-body vibration training (WVT) on the recovery of balance and walking function in stroke patients, which could provide us some useful evidence for planning rehabilitation. METHODS: The clinical data of 130 stroke participants who underwent conventional rehabilitation treatment in our hospital from January 2019 to August 2020 were retrospectively analyzed. The participants were divided into whole-body vibration training (WVT) group and non-WVT (NWVT) group according to whether they were given WVT. In the WVT group, routine rehabilitation therapy was combined with WVT by the Galileo Med L Plus vibration trainer at a frequency of 20 Hz and a vibration amplitude of 0+ACY-plusmn+ADs-5.2 mm, and in the NWVT group, routine rehabilitation therapy only was provided. The treatment course of the two groups was 4 wk. Before and after treatment, the Berg balance scale (BBS), 3 m timed up-and-go test (TUGT), the maximum walking speed test (MWS), and upper limb functional reaching (FR) test were performed. RESULTS: After 4 wk training, in both groups, the BBS score and the FR distance respectively increased to a certain amount (WVT = 46.08 ± 3.41 vs NWVT = 40.22 ± 3.75; WVT = 20.48 ± 2.23 vs NWVT = 16.60 ± 2.82), with P < 0.05. Furthermore, in the WVT group, both BBS score and FR distance (BBS: 18.32 ± 2.18; FR: 10.00 ± 0.92) increased more than that in the NWVT group (BBS: 13.29 ± 1.66; FR: 6.16 ± 0.95), with P < 0.05. Meanwhile, in both groups, the TUGT and the MWS were improved after training (WVT = 32.64 ± 3.81 vs NWVT = 39.56 ± 3.68; WVT = 12.73 ± 2.26 vs NWVT = 15.04 ± 2.27, respectively), with P < 0.05. The change in the WVT group (TUGT: 17.49 ± 1.88; MWS: 6.79 ± 0.81) was greater than that in the NWVT group (TUGT: 10.76 ± 1.42; MWS: 4.84 ± 0.58), with P < 0.05. CONCLUSION: The WVT could effectively improve the balance and walking function in stroke patients, which may be good for improving their quality of life.

The efficacy and safety of fire needle for the treatment of lumbar disc herniation: A protocol for systematic review and meta-analysis.

BACKGROUND: A very large acceleration in clinical studies on the efficacy of fire needle to treat lumbar disc herniation (LDH) are increasing, while studies on the assessment of its efficacy are still lacking. Therefore, this study will demonstrate the efficacy of fire needle in the treatment of LDH combining with the meta-analysis. METHODS: The studies on randomized controlled trials (RCTs) will be searched at the databases of China National Knowledge Infrastructure (CNKI), WANFANG database (Chinese Medicine Premier), Chinese Scientific Journal Database (VIP), Chinese Biomedical Literature database (CBM), PubMed, EMBASE, and Cochrane Library from their inception to May 1, 2020. RESULTS: This authentic and multi-dimensional study will shed light on the referable information for the treatment of LDH with fire needle. CONCLUSION: This study will evaluate the efficacy of fire needle in the treatment of LDH. REGISTRATION: PROSPERO (registration number CRD42020158596).

Retrospective Study of Rehabilitation Exercise Combined with Extracorporeal Shock Wave Therapy for Knee Osteoarthritis.

BACKGROUND The aim of this study was to investigate the effect of rehabilitation exercise combined with extracorporeal shock wave therapy (ESWT) on knee osteoarthritis (KOA). MATERIAL AND METHODS The clinical data of 217 patients with KOA who underwent ESWT in our hospital from December 2017 to January 2020 were retrospectively analyzed. The patients were divided into a rehabilitation exercise (RE) group and a non-rehabilitation exercise (NRE) group according to whether they were given RE. The treatment course of the 2 groups was 5 weeks. Pain Visual Analog Scale (VSA), Western Ontario and McMaster Universities knee osteoarthritis index visualized scale (WOMAC), Lequesne index scores, Range of motion (ROM) score, and Japanese Orthopaedic Association (JOA) scores were used to evaluate the treatment effect of the 2 groups of patients. RESULTS After 5 weeks of treatment, the VSA scores (p<0.001), WOMAC scores (P<0.001) and Lequesne index scores (P<0.001) of the RE group and NRE group were significantly lower than those before treatment, while ROM score (P<0.001) and JOA score (p=0.006) were significantly increased. Compared with the NRE group, the VAS score (3.14±0.64 vs. 4.78±0.85, P=0.002), WOMAC score (20.37±4.06 vs. 27.82±4.57, P<0.001) and Lequesne index score (6.13±1.83 vs. 7.35±2.21, P=0.019) in the RE group were significantly lower than those in the NHE group; however, the ROM score (89.13±9.83 vs. 79.15±6.25, P=0.021) and JOA score (79.53±7.59 vs. 67.85±8.27, P=0.016) were significantly higher than those in the NRE group. CONCLUSIONS RE combined with ESWT has a positive effect on KOA, which may more significantly relieve the patient's clinical symptoms and improve joint function and quality of life.

Pluronic F127-Modified Electrospun Fibrous Meshes for Synergistic Combination Chemotherapy of Colon Cancer.

Colon cancer ranks as the third most common malignancy in the world. Combination chemotherapy, resorting to electrospun fibrous technology, has been considered as a promising strategy to exert synergistic effects in colon cancer treatment. Herein, we manufactured various pluronic F127 (PF127)-modified electrospun fibrous meshes with different weight ratios of camptothecin (CPT) and curcumin (CUR). The fluorescence characterization of the obtained PF127-CPT-meshes, PF127-CUR-meshes, and PF127-CPT/CUR-meshes (2:1) showed that CPT and CUR were evenly distributed within individual fibers of these meshes. Drug release experiments revealed that both types of drugs could be released from fibrous meshes simultaneously and sustainably. Importantly, these meshes exhibited strong in vitro anti-colon cancer activities, compared with the control meshes without drugs. Moreover, the combination index values of the PF127-CPT/CUR-meshes (CPT/CUR weight ratio = 5:1, 3:1, or 2:1) were <0.5 after incubation for respective 24 and 36 h, indicating the synergistic anti-colon cancer effects of CPT and CUR in fibrous meshes. Collectively, these results demonstrate that PF127-CPT/CUR-meshes can be developed as an efficient implantable system for effective synergistic treatment of colon cancer.

Scalable fabrication of bimetal modified polyacrylonitrile (PAN) nanofibrous membranes for photocatalytic degradation of dyes.

Fabricating nanostructured fibrous membranes as photocatalyst would facilitate the effective treatment of dyeing effluents. However, creating such photocatalytic nanofibrous membranes has proven tremendously challenging. In this work, we report a scalable strategy to prepare copper-iron bimetal modified polyacrylonitrile (PAN) nanofibrous membranes by electrospinning technology. The resultant PAN membranes exhibit an ultra-fine fiber diameter (600 nm), large surface area (5.34 m2 g-1) and excellent photocatalytic capacity for reactive blue 19, reactive red 195 and acid orange 7 (＞99.99%) within 60 min. The successful synthesis of such intriguing materials could provide a versatile platform for further exploring nano-sized photocatalyst fibrous membranes for degradation of dyes.

Scalable fabrication of sulfated silk fibroin nanofibrous membranes for efficient lipase adsorption and recovery.

Fabricating adsorptive materials for fast and high efficient adsorption of enzymes is critical to match the great demands for separation and recovery of enzymes used as biocatalysts. However, it has proven extremely challenging. Here, we report a cost-effective strategy to construct the sulfated group surface-functionalized silk fibroin nanofibrous membranes (SS-SFNM) under mild conditions for positively charged Candida rugosa lipase adsorption. The naturally abundant silk is thus reconstructed into nanofibrous membranes with tunable surface functions. Thereby, the resultant SS-SFNM exhibited excellent adsorption performance towards lipase, including a superior adsorption capacity of 148 mg g-1, fast adsorption equilibrium within 3 h and good reversibility. The fabrication of such fascinating silk-based materials may provide new chance into the design and development of multi-functional membranes for various separated applications.

A reverse micelle strategy for fabricating magnetic lipase-immobilized nanoparticles with robust enzymatic activity.

Enzyme-immobilized nanoparticles that are both catalysis effective and recyclable would have wide applications ranging from bioengineering and food industry to environmental fields; however, creating such materials has proven extremely challenging. Herein, we present a scalable methodology to create Candida rugosa lipase-immobilized magnetic nanoparticles (L-MNPs) by the combination of nonionic reverse micelle method and Fe3O4 nanoparticles. Our approach causes the naturally abundant and sustainable Candida rugose lipase to ordered-assemble into nanoparticles with high catalytic activity and durability. The resultant L-MNPs exhibit the integrated properties of high porosity, large surface area, fractal dimension, robust enzymatic activity, good durability, and high magnetic saturation (59 emu g-1), which can effectively catalyze pentyl valerate esterification and be easily separated by an external magnet in 60 second. The fabrication of such fascinating L-MNPs may provide new insights for developing functional enzyme-immobilized materials towards various applications.

HIF-1α as a Regulator of BMP2-Induced Chondrogenic Differentiation, Osteogenic Differentiation, and Endochondral Ossification in Stem Cells.

BACKGROUND/AIMS: Joint cartilage defects are difficult to treat due to the limited self-repair capacities of cartilage. Cartilage tissue engineering based on stem cells and gene enhancement is a potential alternative for cartilage repair. Bone morphogenetic protein 2 (BMP2) has been shown to induce chondrogenic differentiation in mesenchymal stem cells (MSCs); however, maintaining the phenotypes of MSCs during cartilage repair since differentiation occurs along the endochondral ossification pathway. In this study, hypoxia inducible factor, or (HIF)-1α, was determined to be a regulator of BMP2-induced chondrogenic differentiation, osteogenic differentiation, and endochondral bone formation. METHODS: BMP2 was used to induce chondrogenic and osteogenic differentiation in stem cells and fetal limb development. After HIF-1α was added to the inducing system, any changes in the differentiation markers were assessed. RESULTS: HIF-1α was found to potentiate BMP2-induced Sox9 and the expression of chondrogenesis by downstream markers, and inhibit Runx2 and the expression of osteogenesis by downstream markers in vitro. In subcutaneous stem cell implantation studies, HIF-1α was shown to potentiate BMP2-induced cartilage formation and inhibit endochondral ossification during ectopic bone/cartilage formation. In the fetal limb culture, HIF-1α and BMP2 synergistically promoted the expansion of the proliferating chondrocyte zone and inhibited chondrocyte hypertrophy and endochondral ossification. CONCLUSION: The results of this study indicated that, when combined with BMP2, HIF-1α induced MSC differentiation could become a new method of maintaining cartilage phenotypes during cartilage tissue engineering.

The use of pneumatic tourniquet in total knee arthroplasty: a meta-analysis.

BACKGROUND: Pneumatic tourniquet use in total knee arthroplasty (TKA) is always a controversial issue. The aim of the present study is to assess the effectiveness and safety of its use in patients receiving primary unilateral TKA, and to explore the most safe and effective protocols. MATERIALS AND METHODS: This review was based on cochrane methodology for conducting meta-analysis. Only randomized controlled trials (RCTs) were eligible for this study. The participants were adults who had undergone primary unilateral TKA. The Review Manager Database (RevMan version 5.0, The Cochrane Collaboration 2008) was used to analyze the dates of the selected studies. RESULTS: Thirteen RCTs involving 859 patients were included in this analysis. The use of tourniquet could significantly reduce operation time (mean difference -5.01 min, P = 0.003), intraoperative blood loss (mean difference -201.85 ml, P < 0.00001) and total blood loss volumes (mean difference -125.03 ml, P = 0.61). But postoperative (mean difference 45.99 ml, P = 0.68) were slightly increased in that situation. With respect to surgical complications, a tendency of increasing risk ratio was observed for tourniquet group. CONCLUSIONS: Our results indicate that tourniquet application could reduce surgical time, intraoperative blood loss and total blood loss, but increases postoperative total blood loss. With respect to postoperative complications, DVT and surgical site infection rates are relatively augmented in the tourniquet group.

[Co-expression of BMP2 and Sox9 promotes chondrogenic differentiation of mesenchymal stem cells in vitro].

OBJECTIVE: To investigate the effect of co-expression of bone morphogenetic protein 2 (BMP2) and Sox9 on chondrogenic differentiation of mesenchymal stem cells (MSCs) in vitro and provide experimental evidence for tissue engineering of cartilage. METHODS: Mouse embryonic bone marrow MSC C3H10T1/2 cells were infected with recombinant adenovirus expressing BMP2, Sox9 and green fluorescent protein (GFP) for 3-14 days, with cells infected with the adenovirus carrying GFP gene as the control. The mRNA expression of the markers of chondrogenic differentiation, including collagen type II (Col2a1), aggrecan (ACAN), and collagen type X (Col10a1), were determined by real-time PCR. Alcian blue staining was used for quantitative analysis of sulfated glycosaminoglycan in the cellular matrix. The expression of Col2a1 protein was assayed by immunohistochemical staining and Western blot analysis. RESULTS: Adenovirus-mediated BMP2 expression induced chondrogenic differentiation of C3H10T1/2 cells. Overexpression of Sox9 effectively enhanced BMP2-induced expression of the chondrogenic markers Col2a1, aggrecan and Col10a1 mRNAs, and promoted the synthesis of sulfated glycosaminoglycan and Col2a1 protein in C3H10T1/2 cells. CONCLUSION: Co-expression of BMP2 and Sox9 can promote chondrogenic differentiation of MSCs in vitro, which provides a new strategy for tissue engineering of cartilage.

Sox9 potentiates BMP2-induced chondrogenic differentiation and inhibits BMP2-induced osteogenic differentiation.

Bone morphogenetic protein 2 (BMP2) is one of the key chondrogenic growth factors involved in the cartilage regeneration. However, it also exhibits osteogenic abilities and triggers endochondral ossification. Effective chondrogenesis and inhibition of BMP2-induced osteogenesis and endochondral ossification can be achieved by directing the mesenchymal stem cells (MSCs) towards chondrocyte lineage with chodrogenic factors, such as Sox9. Here we investigated the effects of Sox9 on BMP2-induced chondrogenic and osteogenic differentiation of MSCs. We found exogenous overexpression of Sox9 enhanced the BMP2-induced chondrogenic differentiation of MSCs in vitro. Also, it inhibited early and late osteogenic differentiation of MSCs in vitro. Subcutaneous stem cell implantation demonstrated Sox9 potentiated BMP2-induced cartilage formation and inhibited endochondral ossification. Mouse limb cultures indicated that BMP2 and Sox9 acted synergistically to stimulate chondrocytes proliferation, and Sox9 inhibited BMP2-induced chondrocytes hypertrophy and ossification. This study strongly suggests that Sox9 potentiates BMP2-induced MSCs chondrogenic differentiation and cartilage formation, and inhibits BMP2-induced MSCs osteogenic differentiation and endochondral ossification. Thus, exogenous overexpression of Sox9 in BMP2-induced mesenchymal stem cells differentiation may be a new strategy for cartilage tissue engineering.