Clinical application of instant 3D printed cast versus polymer orthosis in the treatment of colles fracture: a randomized controlled trial.

BACKGROUND: The shortcomings of plaster in water resistance, air permeability, skin comfort, fixed stability and weight of wearing are still to be solved. 3D printed cast can overcome the above shortcomings. At present, there is a relative lack of data on the clinical application of 3D printed cast, probably due to its complexity, relatively long operating time, and high price. We aimed to compare and evaluate the short-term effectiveness, safety and advantages of 3D printed wrist cast versus polymer orthosis in the treatment of Colles fracture. METHODS: Forty patients with Colles fracture in our hospital from June to December 2022 were selected and divided into an observation group (20 patients, treated with instant 3D printed cast) and a control group (20 cases, treated with polymer orthosis). Both groups treated with manual reduction and external fixation. The visual analogue scale (VAS), immobilization effectiveness and satisfaction scores, Disability of the Arm, Shoulder and Hand (DASH) score, complications and imaging data were collected and compared before immobilization and at 2, 6 and 12 weeks after the fracture. RESULTS: VAS at 2 weeks after the fracture was significantly lower in the observation group than in the control group ( P < 0.05). The immobilization effectiveness and satisfaction scores at 6 weeks after the fracture were significantly higher in the observation group than in the control group (all P < 0.05). The DASH scores at 2 and 6 weeks after the fracture were significantly lower in the observation group than in the control group (all P < 0.05). There wasn't rupture of the printed cast or orthosis in both groups. There were 2 cases of skin irritation in the control group, and no skin irritation occurred in the observation group. The palmar tilt angle and ulnar inclination angle at 2 weeks and 12 weeks after the fracture were significantly higher in the observation group than in the control group (all P < 0.05). CONCLUSIONS: Both instant 3D printed cast and polymer orthosis are effective in the treatment of Colles fracture. But instant 3D printed cast is better than polymer orthosis in areas of good clinical and imaging performance, and high patient satisfaction and comfort.

The efficacy of dynamic compression locking system vs. dynamic hip screw in the treatment of femoral neck fractures: a comparative study.

BACKGROUND: There is still a lack of consensus on which internal fixation method can better maintain the stability of femoral neck fractures (FNF), promote fracture healing, and reduce postoperative complications such as femoral head necrosis and nonunion. Therefore, the purpose of this study was to evaluate the clinical efficacy of the novel dynamic compression locking system (DCLS) versus dynamic hip screw (DHS) in the treatment of FNF. METHODS: Fifty cases of FNF from July 2018 to February 2020 were retrospectively analyzed. According to different treatment methods, they were divided into DCLS group (26 cases) and DHS group (24 cases). Baseline data, intraoperative and postoperative clinical data, reoperation rate, and Harris score were collected to evaluate the clinical efficacy. RESULTS: All patients were followed up for 24 months. All "fractures" were caused by fall. The baseline data of the two groups were comparable (P > 0.05). There weren't significant differences in the length of hospital stay and mobility after two years postoperatively between the two groups (P > 0.05). The operation time, blood loss, incision length, fluoroscopy times and the degree of femoral neck shortening after two years postoperatively in the DCLS group were significantly less than those in the DHS group (all P < 0.05). Harris score after two years postoperatively in the DCLS group was significantly higher than that in the DHS group (P < 0.05). Although the reoperation rate in the DHS group was slightly higher than that in the DCLS group, it wasn't statistical significance (P > 0.05). CONCLUSIONS: Compared with DHS, DCLS in the treatment of FNF had less surgical trauma, shorter incision length, shorter operation time, lower radiation dose and higher Harris scores. Although the reoperation rate in the DHS group was slightly higher than that in the DCLS group, it wasn't statistical difference. Further research is needed.

Biocatalytic Depletion of Tumorigenic Energy Sources Driven by Cascade Reactions for Efficient Antitumor Therapy.

Glucose and lactate play important roles for tumor growth. How to simultaneously deprive tumors of glucose and lactate is a big challenge. We have developed a cascade catalytic system (denoted as FPGLC) based on fluorinated polymer (FP) with co-loading of glucose oxidase (GOx), lactate oxidase (LOx), and catalase (CAT). GOx and LOx deprive glucose and lactate, respectively, resulting in abundant hydrogen peroxide (H2 O2 ) generation. Meanwhile, CAT catalyzes H2 O2 into O2 , which not only promotes catalytic reactions of GOx and LOx for consuming more glucose and lactate, but also alleviates tumor hypoxia. Benefiting from the excellent cross-membrane and transmucosal penetration capacities of FP, FPGLC rapidly accumulated in tumors and subsequently mediated enhanced cascade catalytic therapy under the guidance of photoacoustic imaging. These results demonstrate that the dual depletion of glucose and lactate with O2 supply is a promising strategy for efficient antitumor starvation therapy.

Analysis of the effect of percutaneous vertebroplasty in the treatment of thoracolumbar Kümmell's disease with or without bone cement leakage.

BACKGROUND: Bone cement leakage is a major complication in the treatment of percutaneous vertebroplasty for Kümmell's disease, and the focus of close attention during the surgery. The purpose of this article was to investigate the clinical outcomes of Kümmell's disease treated by percutaneous vertebroplasty with or without bone cement leakage. METHODS: A total of 64 patients with Kümmell's disease from December 2016 to February 2018 treated by percutaneous vertebroplasty were included in the study. After the treatment, 32 cases were respectively divided into two groups according to X-ray examination of bone cement leakage: leakage group and non-leakage group. Preoperative course, age, sex, bone mineral density, damaged segment, anterior vertebral height, vertebral compression rate, Cobb angle, visual analogue scale and Oswestry dysfunction index were compared between the two groups. After surgery, the amount of bone cement injected, operation time, adjacent vertebral refracture rate, visual analogue scale, Oswestry dysfunction index, the recovery value of vertebral anterior height and the improvement value of Cobb angle were compared between the two groups. RESULTS: The course, age and Cobb angle of the leakage group were significantly greater than those of the non-leakage group (P< 0.05, respectively). The height of anterior vertebral margin and bone mineral density in the leakage group were significantly lower than those in the non-leakage group (P< 0.05, respectively). The two groups were followed up for at least 24 months. The amount of bone cement injected was significantly greater in the leakage group than in the non-leakage group (P=0.000). Visual analogue scale and Oswestry dysfunction index of the two groups on the second day after surgery and at the last follow-up were significantly lower than these before surgery (P< 0.05, respectively), but there was no significant difference between the two groups. In the leakage group, the recovery value of the anterior edge height of the injured vertebra and the improvement value of the Cobb angle on the second day after surgery and at the last follow-up were significantly improved compared with the non-leakage group (P< 0.05, respectively). CONCLUSION: Percutaneous vertebroplasty is an effective and minimally invasive treatment for Kümmell's disease. The leakage group had longer course, older age, more serious kyphotic deformity, vertebral compression and osteoporosis, and higher amount of bone cement injected than these of the non-leakage group. However, there were not significant differences in the rate of adjacent vertebral refractures, visual analogue scale and Oswestry dysfunction index between the two groups. Therefore, the bone cement leakage does not affect the surgical effect.

Fluorinated polymer emulsion systems: Construction and application in delivering genes and proteins.

Emulsions have shown great potential in the delivery of various types of cargoes such as nucleic acids and proteins. In this study, fluorinated polymer emulsions (PFx@PFD-n) were prepared using fluorinated polymers with different structures as surfactant in PFD emulsions under ultrasound. These polymer emulsions gave comparable DNA binding ability compared with corresponding polymers. Heparin competition experiment showed that polymer emulsions could compact DNA or protein to form more stable complexes. In vitro gene transfection results showed that the polymer emulsions could induce higher gene expression than corresponding polymers and polyethyleneimine (PEI), and the transfection efficiency was enhanced with the increase of PFD amount in polymer emulsions. Flow cytometry studies revealed that the emulsions could mediate more efficient cellular uptake with stronger serum tolerance. Moreover, the polymer emulsion could deliver considerable amount of OVA into Raw 264.7 cells at low mass ratio, showing its potential in immunotherapy. The activities of ß-galactosidase delivered by the emulsions could also be well maintained after entering cells. This study provides a strategy to construct cationic gene and cytosolic protein vectors with high efficiency and low toxicity.

Clinical observation of two bone cement distribution modes of percutaneous vertebroplasty in the treatment of thoracolumbar Kümmell's disease.

BACKGROUND: In recent years, percutaneous vertebroplasty (PVP) has provided a new option for the treatment of Kümmell's disease (KD). This retrospective study aimed to investigate the differences in clinical characteristics, clinical efficacy, and related complications between two types of bone cement distribution patterns in the PVP treatment of KD. METHODS: A total of 63 patients with KD from January 2016 to February 2018 who received PVP treatment were examined at least 24 months. According to X-ray distribution modes of bone cement after PVP treatment, they were divided into 2 groups: blocky group (30 cases) and spongy group (33 cases). Clinical features and disease severity preoperatively, and clinical efficacy and related complications postoperatively were statistically compared between the two groups. RESULTS: The two groups were followed for at least 24 months. The duration of disease, age, Cobb angle, and vertebral compression rate preoperatively were significantly higher in the blocky group than in the spongy group (P < 0.05, respectively). The height of vertebral anterior margin and BMD were significantly lower in the blocky group than in the spongy group (P < 0.05, respectively). The amount of bone cement injected was significantly greater in the blocky group than in the spongy group (P = 0.000). VAS and ODI of the two groups were significantly reduced at the first day, the first year, and the last follow-up postoperatively (all P = 0.000) and were maintained at the last follow-up. VAS and ODI postoperatively decreased significantly in the spongy group compared with the blocky group (P = 0.000). The correction degrees of kyphosis and vertebral compression postoperatively in the two groups were significantly corrected, but gradually decreased over time (P < 0.05), and these correction degrees were significantly higher in the blocky group than in the spongy group, and the postoperative losses were also more serious. CONCLUSIONS: The disease was more serious in the blocky group than in the spongy group. The amount of bone cement, correction degrees of postoperative kyphosis and vertebral compression were significantly higher in the blocky group than in the spongy group, but its postoperative losses of the correction degrees of kyphosis and vertebral compression were also more serious. However, for pain relief and functional recovery, the spongy group was superior to the blocky group. Therefore, the spongy distribution pattern should be formed during the injection of bone cement to obtain better therapeutic effect.

Comparison of the clinical outcomes of percutaneous vertebroplasty vs. kyphoplasty for the treatment of osteoporotic Kümmell's disease:a prospective cohort study.

BACKGROUND: Percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) are widely used in the treatment of Kümmell's disease. The purpose of this article is to investigate the clinical efficacy of PVP and PKP for Kümmell's disease. METHODS: The clinical data that 56 cases of Kümmell's disease treated with either PVP (28 cases) or PKP (28 cases) from December 2015 to December 2017 were prospectively analyzed. Gender, age, course of disease, injury segment, bone mineral density (BMD), visual analogue scale (VAS), Oswestry disability index (ODI), imaging measurement indexes before surgery between the two groups showed no significant difference (all P > 0.05). The bone cement leakage rate, bone cement injection amount, operation time, VAS, ODI, the rate of vertebral compression, correction rate of kyphosis and refracture rate of adjacent vertebra in 2 years were compared between the two groups to calculate clinical efficacy. RESULTS: The two groups were followed up for 24-48 months. There was no significant difference in the follow-up time, amount of bone cement injected, incidence of bone cement leakage and refracture rate of adjacent vertebrae between the two groups (all P > 0.05). The operation time, intraoperative blood loss and fluoroscopy times of the PVP group were significantly lower than those of the PKP group (all P = 0.000). VAS score and ODI of the two groups were significantly lower at 1 day, 1 year and 2 years after surgery than before surgery (all P < 0.05), but there was not statistically significant difference between the two groups at each time point after surgery (all P > 0.05). The rate of vertebral compression and kyphosis correction in the two groups were significantly corrected (P < 0.05, respectively) and decreased significantly with time (all P < 0.05), But there was not significant difference between the two groups at any time point (all P > 0.05). CONCLUSION: Both PVP and PKP can achieve similar effects in the treatment of Kümmell's disease. Because the cost, operation time, blood loss, radiation exposure and surgical procedure of PVP are less than those of PKP, PVP has more clinical priority value.

Dynamic compression locking system versus multiple cannulated compression screw for the treatment of femoral neck fractures: a comparative study.

BACKGROUND: Femoral neck fractures are one of the problems in clinical treatment. The prognosis is uncertain. Currently, No internal fixation method is superior to other internal fixation methods in the treatment of femoral neck fractures. Therefore, the internal fixation system needs to be further explored. The aim of this study was to compare clinical outcomes of femoral neck dynamic compression locking system (DCLS) and multiple cannulated compression screws(MCCS) in the treatment of femoral neck fractures. METHODS: A prospective analysis of 54 cases of femoral neck fractures treated with either a DCLS (n = 28) or MCCS (n = 26) was conducted between December 2015 and November 2017 in authors' hospitals. The perioperative and postoperative parameters of the two groups were recorded and evaluated. RESULTS: Fifty-four patients were followed up for 24-47 months. The etiology was caused by a fall. There was no significant difference in follow-up time, operation time, incision length, surgical blood loss, the incidence of perioperative and postoperative healing complications, and mobility in the two groups (all P > 0.05). The Harris score, fracture healing time, femoral neck shortening, partial weight-bearing time and complete weight-bearing time were significantly better in the DCLS group than in the MCCS group (all P < 0.05). The fracture healing rate in the DCLS group was higher than that in the MCCS group. CONCLUSIONS: The DCLS and MCCS might be equally effective in terms of operation time, incision length, surgical blood loss, the incidence of perioperative and postoperative healing complications, and mobility in the treatment of femoral neck fractures. However, the DCLS is superior to the MCCS in Harris score, fracture healing time, femoral neck shortening, weight-bearing time and fracture healing rate. So, DCLS deserves further study.

Bioinspired pyrimidine-containing cationic polymers as effective nanocarriers for DNA and protein delivery.

Cationic polymers have shown great potential in the delivery of nucleic acids and proteins. In this study, a series of pyrimidine-based cationic polymers were synthesized via the Michael addition reaction from pyrimidine-based linkages and low molecular weight polyethyleneimine (PEI). The structure-activity relationship (SAR) of these materials in DNA and protein delivery was investigated. These materials could condense both DNA and protein into nanoparticles with proper sizes and zeta-potentials. In vitro experiments indicated that such polymers were efficient in transporting DNA and proteins into cells. Furthermore, the bioactivity of the genes and proteins encapsulated in these polymers were maintained during the delivery processes. Among the polymers, U-PEI600 synthesized from a uracil-containing linker and PEI 600 Da mediated comparable gene expression to PEI 25 kDa. Moreover, the activities of ß-galactosidase delivered by U-PEI600 were well maintained after entering the cells. Evaluation using an immune response assay showed that the U-PEI600/OVA polyplex could stimulate greater production of immune factors with low cytotoxicity. Our study provides a strategy for the construction of cationic polymeric gene and cytosolic protein vectors with high efficiency and low toxicity.

Amino Acid-Linked Low Molecular Weight Polyethylenimine for Improved Gene Delivery and Biocompatibility.

The construction of efficient and low toxic non-viral gene delivery vectors is of great significance for gene therapy. Herein, two novel polycations were constructed via Michael addition from low molecular weight polyethylenimine (PEI) 600 Da and amino acid-containing linkages. Lysine and histidine were introduced for the purpose of improved DNA binding and pH buffering capacity, respectively. The ester bonds afforded the polymer biodegradability, which was confirmed by the gel permeation chromatography (GPC) measurement. The polymers could well condense DNA into nanoparticles and protect DNA from degradation by nuclease. Compared with PEI 25 kDa, these polymers showed higher transfection efficiency, lower toxicity, and better serum tolerance. Study of this mechanism revealed that the polyplexes enter the cells mainly through caveolae-mediated endocytosis pathway; this, together with their biodegradability, facilitates the internalization of polyplexes and the release of DNA. The results reveal that the amino acid-linked low molecular weight PEI polymers could serve as promising candidates for non-viral gene delivery.

Efficacy and experience of arthroscopic lateral patella retinaculum releasing through/outside synovial membrane for the treatment of lateral patellar compression syndrome.

BACKGROUND: Arthroscopic closure release includes arthroscopic lateral patella retinaculum releasing (LPRR) either outside synovial membrane (OSM) or through synovial membrane (TSM). At present, there is no research to compare the clinical efficacy of the above two methods for the treatment of lateral patellar compression syndrome (LPCS). So, the goal of this study was to investigate the method and overcome of arthroscopic LPRR either OSM or TSM for the treatment of LPCS. METHODS: From September 2014 to December 2017, 125 patients of LPCS underwent arthroscopic LPRR either OSM or TSM combined with joint debridement. In the OSM group, knee joint was cleaned first. The surface of lateral patella retinaculum (LPR) was created the chamber for arthroscopic operation to release LPR. Synovial membrane was retained. In the TSM group, knee joint was cleaned first. Then synovial membrane, joint capsule and LPR, and superficial fascia were gradually incised from the joint cavity to subcutaneous tissue. The synovial membrane was cut open. Before and after surgery, Lysholm score, patella medial shift, Kujala score, VAS score and surgical complications were collected for evaluating clinical overcomes. RESULTS: All patients were followed up for 1.5-5 years. All patients had significant reduction in knee pain and improved function after 1 month and 1 year. The Lysholm score, the distance of patella medial shift, Kujala score, and VAS score in the OSM group and the TSM group were significantly improved in the final follow-up compared with before surgery (All P < 0.001), but these observed targets before surgery and at the last follow-up were compared between the OSM group and the TSM group with no statistical differences. However, the number of occurrences of joint hematoma and adhesion was significantly higher in the TSM group than the OSM group (P = 0.024). CONCLUSIONS: Arthroscopic closing LPRR for the treatment of LPCS can effectively improve the function and symptoms of patellofemoral joint with the advantages of small trauma, rapid recovery and less complications. But, the number of occurrences of hemarthrosis and joint adhesion were significantly higher in the TSM group than in the OSM group. TRIAL REGISTRATION: The trial registration number (IRCT): IRCT20200205046378N1 and date of registration: February 10, 2020 (retrospectively registered).

Cationic Heteropolymers with Various Functional Groups as Efficient and Biocompatible Nonviral Gene Vectors.

With the rise and development of gene therapy, it is of great significance to develop highly efficient and biocompatible polymeric gene carriers. In this work, a series of heteropolymers from ring-opening polymerization of diepoxide compounds and various functional primary amines were synthesized. The feed dosage of amines was adjusted to obtain the polymers with different functional group contents, and the structure-activity relationships of these polymers as nonviral gene vectors were examined in detail. Results revealed that, although the amine with the fluorinated chain seemed to be less reactive in the polymerization, the relative content of each component in the target product was consistent with the feed dosage. Compared to the "golden standard" polyethylenimine (PEI) 25 kDa, these heteropolymers showed much lower cytotoxicity and higher gene transfection efficiency, especially in serum-containing medium, and up to 78 times of efficiency than PEI was obtained. Meanwhile, they exhibited much better serum resistance than PEI, compared with the transfection efficiency in serum-free experiments, and even higher efficiency could be achieved with serum in HeLa cells. Mechanism study results suggest that the content of fluorinated chain and histamine might distinctly influence their transfection. The fluorinated chains could enhance the serum tolerance and cellular uptake efficiency (with serum), while the imidazole group in the histamine chain would improve the endosome/lysosome escape.

ROS-responsive fluorinated polycations as non-viral gene vectors.

Polycation carriers hold great potential in gene therapy. However, they usually suffer from obvious cytotoxicity and unsatisfactory transfection efficiency. In this report, a series of fluorobenzene substituted and thioacetal contained polycations (TAEA-S-xF) were prepared to explore novel alternatives for safe and efficient non-viral polymeric gene vectors. The reactive oxygen species (ROS)-responsive property of thioacetal moieties together with the fluorine effect were hope to bring the vector better performance in gene delivery process. These materials could efficiently condense DNA into nanoparticles with proper size and surface potential. The structure-activity relationship of these materials was systematically investigated, and the In vitro transfection results revealed that the amount of fluorine atoms on the linkage plays important role to ensure the transfection efficiency and serum tolerance. The ROS-responsive behavior was verified by NMR, gel electrophoresis experiment and dynamic light scattering (DLS) assay. Cytotoxicity assay results also suggest that these ROS-degradable polycations show good biocompatibility in response to higher ROS level in cancer cells. Among these fluorinated polymers, the one with the most fluorine atoms showed the best transfection efficiency, which was up to 54 times higher than polyethyleneimine (PEI) 25 kDa. Mechanism studies reveal that its better performance may come from good cellular uptake and endosome escape ability.

Low molecular weight PEI-based fluorinated polymers for efficient gene delivery.

Fluorinated biomaterials have been reported to have promising features as non-viral gene carriers. In this study, a series of fluorinated polymeric gene carriers were synthesized via Michael addition from low molecular weight polyethyleneimine (PEI) and fluorobenzoic acids (FBAs)-based linking compounds with different numbers of fluorine atoms. The structure-activity relationship (SAR) of these materials was systematically investigated. SAR studies showed that fluorine could screen the positive charge of these polymers. However, this shielding effect of fluorine would endow fluorinated polymers with good balance between DNA condensation and release. In vitro transfection results suggested that these fluorinated polymers could mediate efficient gene delivery. Flow cytometry and confocal microscopy studies demonstrated that more efficient cell uptake could be achieved by fluorinated materials with more fluorine atoms. Cytotoxicity assays showed that these fluorinated materials exhibited very low cytotoxicity even at high mass ratios. This study demonstrates that FBA-based fluorinated biopolymers have the potential for practical application.

The clinical application of a novel method of internal fixation for femoral neck fractures-dynamic locking compression system.

BACKGROUND: Femoral neck fractures are the commonly encountered injury in orthopedic practice and result in significant morbidity and mortality. Currently, how to treat femoral neck fractures safely and effectively is still a challenge. The objective of this study is to evaluate the efficiency of dynamic compression locking system for femoral neck fractures. METHODS: This is a retrospective study conducted from May 2015 to October 2016. The study included 36 patients suffering from femoral neck fractures who underwent closed reduction and were fixed using dynamic compression locking system. All surgeries were performed by the same surgeon. The study was conducted by telephone and on-site follow-up. The Garden classification and anatomical site classification were categorized for all patients. We assessed radiographic outcomes of union, femoral neck shortening, screw back-out, and femoral head avascular necrosis. We also evaluated functional outcome using the Harris hip score. Other outcomes included the length of surgery, duration of hospital stay, injury to surgery time, intraoperative hemorrhage, time to clinical bone union, and other fracture complications. RESULTS: All patients were followed up 12 to 29 months with an average of 21.58 ± 5.41 months. All cases were caused by falls including 17 males and 19 females with an average age of 65.33 ± 9.30 years old ranging from 53 to 82 years old. Among them, injury to surgery time ranged between 1 and 4 days with an average of 2.58 ± 1.05 days. Duration of hospital stay was 8 to 21 days with an average of 15.33 ± 3.71 days. Intraoperative hemorrhage was 40 to 80 ml with an average of 61.67 ± 12.31 ml. Operation time was from 35 to 80 min with average of 50.25 ± 11.77 min. According to Garden classification, 9 cases (25%) were type II and 27 cases (75%) were type III. According to the anatomical site classification, 8 cases (22.2%) were subcapital femoral neck fractures, 19 cases (52.8%) trans-cervical, and 9 cases (25%) basi-cervical. At present, the follow-up has not found the fracture complications of femoral head avascular necrosis, fracture nonunion, and re-fracture. All patients achieved solid bone union. The mean time of clinical bone union was 3 to 4 months. Among all patients, there were only 3 cases of femoral neck shortening < 5 mm and 1 case of screw back-out = 4 mm. For Harris scoring, average Harris scale at the end of the follow-up was 93.42 ± 3.95 ranging from 85 to 98. There were 32 cases of excellent function scores on the Harris scale and 4 cases of good function scores on the Harris scale. Therefore, the excellent and good rate of Harris hip scores was 100%. CONCLUSIONS: Femoral neck dynamic compression locking system for femoral neck fractures in elderly patients can provide effective stability and reduce complications and revision rates.

[Review for treatment effect and signaling pathway regulation of kidney-tonifying traditional Chinese medicine on osteoporosis].

The treatment effect and signaling pathway regulation effects of kidney-tonifying traditional Chinese medicine on osteoporosis have been widely studied, but there is no systematic summary currently. This review comprehensively collected and analyzed the traditional Chinese medicines on the treatment and signaling pathway regulation of osteoporosis in recent ten years, such as Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus, Eucommiae Cortex, Psoraleae Fructus and Dipsaci Radix. Based on the existing findings, the following conclusions were obtained: ①kidney-tonifying traditional Chinese medicine treated osteoporosis mainly through BMP-Smads, Wnt/ß-catenin, MAPK, PI3K/AKT signaling pathway to promote osteoblast bone formation and through OPG/RANKL/ RANK, estrogen, CTSK signaling pathway to inhibit osteoclasts of bone resorption. Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus and Psoraleae Fructus up-regulated the expression of key proteins and genes of BMP-Smads and Wnt/ß-catenin signaling pathways to promote bone formation. Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus, Eucommiae Cortex, Psoraleae Fructus and Dipsaci Radix inhibited the bone resorption by mediating the OPG/RANKL/RANK signaling pathway. ②Kidney-tonifying traditional Chinese medicine prevented and treated osteoporosis through a variety of ways: icariin in Epimedii Folium, naringin in Drynariae Rhizoma, osthole in Cnidii Fructus and psoralen in Psoraleae Fructus can regulate BMP-Smads, Wnt/ß-catenin signaling pathway to promote bone formation, but also activate OPG/RANKL/RANK, CTSK and other signaling pathways to inhibit bone resorption. ③The crosstalk of the signaling pathways and the animal experiments of the traditional Chinese medicine on the prevention and treatment of osteoporosis as well as their multi-target mechanism and comprehensive regulation need further clarification.

A reduction-responsive liposomal nanocarrier with self-reporting ability for efficient gene delivery.

In the past few decades, although various reduction-responsive nanocarriers have been designed and explored for gene delivery, it is difficult to directly detect or monitor the reduction capability of these carriers, especially under intracellular conditions. Taking advantage of the generated fluorescence signal in the reduction process of the naphthalimide-sulfonamide (NS) group, we developed a novel liposomal nanocarrier, FNSL, which showed reduction-sensitive property and self-reporting character. As a new reduction-responsive site in a gene delivery system, the NS group in FNSL is capable of responding to glutathione (GSH) and simultaneously emitting green fluorescence at 500 nm in both extra- and intracellular circumstances. Hence, it will be very convenient to assess the reducibility of this carrier and monitor the stimuli-responsive gene release via fluorescence signal. FNSL has high affinity for DNA and can condense it into nanoparticles with a proper nano-size and zeta potential. Compared with the non-reducible FNAL, FNSL showed enhanced gene release capability, higher transfection efficiency (TE), and lower cytotoxicity. Furthermore, treatment of FNSL-mediated transfection with slightly exogenous GSH greatly improved the TE of FNSL in HepG2 cells, and its TE was even higher than that of Lipofectamine 2000. These results demonstrate that FNSL possesses great potential for efficient and low-toxicity gene delivery, and this study on a bioreducible liposome with self-reporting ability would be a guide for further research on the development of biodegradable gene carriers.

Synthesis and Properties of Low-Molecular-Weight PEI-Based Lipopolymers for Delivery of DNA.

Rapid enzymatic degradation and fragmentation during DNA administration can result in limited gene expression, and consequently, poor efficacy. It is necessary to use novel vectors for DNA delivery. Herein, we aimed to design useful carriers for enhancing transfection efficiency (TE). These lipopolymers were prepared through Michael addition reactions from low-molecular-weight (LMW) polyethyleneimine (PEI) and linkers with three kinds of steroids. Agarose gel electrophoresis assay results displayed that the three lipopolymers could condense plasmid DNA well, and the formed polyplexes had appropriate sizes around 200⁻300 nm, and zeta potentials of about +25⁻40 mV. The results of in vitro experiments using HeLa, HEK293, and MCF-7 cells showed that these lipopolymers present higher TE than 25-kDa PEI, both in the absence and presence of 10% serum. Flow cytometry and confocal microscopy studies also demonstrated that these lipopolymer/DNA complexes present higher cellular uptake and intracellular distribution. The measurement of critical micelle concentration (CMC) revealed that these lipopolymers could form micelles, which are suited for drug delivery. All results suggest that the three materials may serve as hopeful candidates for gene and drug delivery in future in vivo applications.

Biodegradable Gene Carriers Containing Rigid Aromatic Linkage with Enhanced DNA Binding and Cell Uptake.

The linking and modification of low molecular weight cationic polymers (oligomers) has become an attracted strategy to construct non-viral gene carriers with good transfection efficiency and much reduced cytotoxicity. In this study, PEI 600 Da was linked by biodegradable bridges containing rigid aromatic rings. The introduction of aromatic rings enhanced the DNA-binding ability of the target polymers and also improved the stability of the formed polymer/DNA complexes. The biodegradable property and resulted DNA release were verified by enzyme stimulated gel electrophoresis experiment. These materials have lower molecular weights compared to PEI 25 kDa, but exhibited higher transfection efficiency, especially in the presence of serum. Flow cytometry and confocal laser scanning microscopy results indicate that the polymers with aromatic rings could induce higher cellular uptake. This strategy for the construction of non-viral gene vectors may be applied as an efficient and promising method for gene delivery.

Efficacy and safety of chemotherapy with or without targeted therapy in biliary tract cancer: A meta-analysis of 7 randomized controlled trials.

The systematic treatment based on gemcitabine plus cisplatin is recommended as the current standard chemotherapy for unresectable or metastatic biliary tract cancers. However, the exact benefits from the recognized regime are still dismal. We thus elicit this study in an attempt to analyze whether targeted therapy coupled with various chemotherapy could produce improvement of survival benefits. The clinical trials were searched electronically from databases till July 2016 published in English and Chinese. Nine hundred and sixty-four patients from 7 trials were identified in our analysis. The overall analysis achieved a significantly higher overall response rate (ORR) among the patients treated with targeted drugs plus chemotherapy than chemotherapy alone (OR=1.87; 95% CI: 1.37-2.57; P=0.000), but failed in the overall progression-free survival (PFS) [mean difference (MD)=0.63; 95% CI:-0.45-1.72; P=0.26] and overall survival (OS) (MD=-0.67; 95% CI:-2.54-1.20; P=0.49). In the sub analysis, better ORR was obtained with the addition of EGFR (OR=1.75; 95% CI: 1.20-2.56; P=0.004) and VEGFR (OR=2.5; 95% CI: 1.28-4.87; P=0.007) targeted therapy. Furthermore, the sub analysis of EGFR target showed an significant improvement on PFS (MD=1.36; 95% CI: 0.29-2.43; P=0.01). No significant differences were observed in the incidences of neutropenia (OR=1.37; 95% CI: 0.89-2.12), thrombocytopenia (OR=1.40; 95% CI: 0.83-2.39), anemia (OR=1.21; 95% CI: 0.62-2.38), peripheral neuropathy (OR=1.52; 95% CI: 0.81-2.88), increased AST/ALT (OR=1.40; 95% CI: 0.82-2.39) as well as fatigue (OR=1.65; 95% CI: 0.96-2.84) in either of the treatment groups. In conclusion, better ORR associated with chemotherapy combined with targeted therapy (both targeting EGFR and VEGF) is found in the present meta-analysis without the cost of increased unacceptable toxicities, but regretfully not for the OS. The sub-analysis of targeting EGFR instead of VEGF obtains a superior PFS. Otherwise, there is no statistically significant difference in the overall PFS between the combination regime and chemotherapy alone. Given the paucity of favorable data, we need further studies to characterize optimal targeted agents to confirm the potential value to biliary tract cancer.