[Latest Findings on Stimuli-Responsive Hydrogel Wound Dressings Applied in Diabetic Chronic Wound Repair].

Diabetic chronic wounds entail enormous psychological and economic burdens on diabetic patients. Traditional types of wound dressings lack diversity in their functions and do not have sufficient adaptability to the wound environment, which makes it difficult to meet the complicated needs arising during the healing process when they are used. Stimuli-responsive hydrogels respond specifically to the special environment of the wound area, for example, temperature, pH, glucose, etc., and achieve on-demand release by loading active substances, which effectively promotes diabetic wound healing. Herein, based on the research progress in stimulus-responsive wound dressings in recent years and the relevant work of our research team, we summarized and discussed hydrogel wound dressings responsive to temperature, pH, glucose, reactive oxygen species, enzymes, and multiple stimuli. Based on the special physiological environment of diabetic wounds, hydrogels with single or multiple stimuli-responsive properties can be designed so that they can release drugs on demand and improve the microenvironment of the wound, thus meeting the specific needs of different stages of wound healing. Although stimuli-responsive hydrogels currently show excellent therapeutic potential, there is still room for further development-cells or cytokines loaded in wound dressings usually act only at specific healing stages and the timing needs to be precisely controlled in order to avoid counterproductive effects on wound healing. In addition, the construction of sensor-therapeutic integrated devices for real-time monitoring of wound biochemical indicators so that drugs are release on demand and with precision to promote wound healing is also one of the topics that deserve more attention from researchers.

An Integrated Strategy for Rapid Hemostasis during Tumor Resection and Prevention of Postoperative Tumor Recurrence of Hepatocellular Carcinoma by Antibacterial Shape Memory Cryogel.

The inevitable bleeding during tumor resection greatly increases the risk of tumor recurrence caused by metastasis of cancer cells with blood, and hemostasis and prevention of post-operation tumor recurrence is still a challenge. However, a biomaterials approach for rapid hemostasis during tumor resection and simultaneous prevention of tumor recurrence is rarely reported. Here, zeolitic imidazolate framework (ZIF-8) nanoparticle-enhanced multinetwork cryogels are proposed which provide an integrated treatment regimen for rapid hemostasis through intraoperative blood trigger shape recovery and enhanced coagulation, and prevention of postoperative cancer recurrence via sonodynamic anticancer in a hepatocellular carcinoma model. A series of antibacterial shape memory multifunctional cryogels are synthesized based on glycidyl methacrylate-functionalized quaternized chitosan (QCSG), dopamine-modified hyaluronic acid (HA-DA), and hematoporphyrin monomethyl ether (HMME)-loaded dopamine-modified ZIF-8 (ZDH). Blood loss in different bleeding models confirms good hemostasis of ZIF-8 loading cryogels. Besides, in vitro tests confirm that QCSG/HA-DA/ZDH (QH/ZDH) cryogels significantly killed cancer cells by generating reactive oxygen species under ultrasound. Finally, significantly reduced tumor recurrence after the resection of ectopic hepatocellular carcinoma further confirms the good effect of QH/ZDH cryogels in preventing recurrence by a coordinated strategy of intraoperative hemostasis and postoperative sonodynamic therapy by pH-responsive HMME release, showing great potential in clinical application.

Injectable Antimicrobial Conductive Hydrogels for Wound Disinfection and Infectious Wound Healing.

As the abuse of antibiotics continues to increase, the emergence of antibiotic resistance and unknown drug-resistant bacterial infections pose a great threat on people worldwide. In this work, we aimed to develop a series of injectable antimicrobial conductive hydrogels based on glycidyl methacrylate functionalized quaternized chitosan (QCSG), gelatin methacrylate (GM), and graphene oxide (GO) for drug-resistant bacterial disinfection and infectious wound healing. The rheology, morphology, mechanical properties, and electrical and photothermal properties of the hydrogels were characterized. Furthermore, the good in vitro and in vivo intrinsic antibacterial, photothermal antibacterial, and antibiotics released antibacterial properties of this multiantibacterial hydrogel were verified. The good biocompatibility of these hydrogels was also investigated by cytocompatibility, hemocompatibility, and histocompatibility tests. In the drug-resistant Methicillin-resistant Staphylococcus aureus (MRSA) infected mouse full-thickness defect model, the wound closure rate, the length of dermal tissue gap, number of blood vessels and hair follicles in hematoxylin-eosin (HE) staining, the amount of collagen in Masson staining, and the related cytokines for the expression of inflammation (interleukin-6, IL-6) and regeneration of blood vessels (vascular endothelial growth factor, VEGF) in immunofluorescence were all further studied. All the results demonstrated the better wound healing effect of these multiantibacterial injectable conductive hydrogel in infectious skin tissue defect repair, indicating their great potential for infected wound healing.

Emissive Metallacycle-Crosslinked Supramolecular Networks with Tunable Crosslinking Densities for Bacterial Imaging and Killing.

The chemical structures and topologies of the crosslinks in supramolecular networks play a crucial role in their properties and functions. Herein, the preparation of a type of poly(N-isopropylacrylamide) (PNIPAAM)-based supramolecular networks crosslinked by emissive hexagonal metallacycles is presented. The topological connections in these networks greatly affect their properties, as evidenced by their differences in absorption, emission, lower critical solution temperature, and modulus along with the variation of crosslinking densities. The integration of PNIPAAM and metallacycles in the networks benefits them improved bioavailability, making them serve as reagents for bacterial imaging and killing. This study provides a strategy to prepare cavity-crosslinked polymer networks for antibacterial applications.

Adhesive Hemostatic Conducting Injectable Composite Hydrogels with Sustained Drug Release and Photothermal Antibacterial Activity to Promote Full-Thickness Skin Regeneration During Wound Healing.

Developing injectable nanocomposite conductive hydrogel dressings with multifunctions including adhesiveness, antibacterial, and radical scavenging ability and good mechanical property to enhance full-thickness skin wound regeneration is highly desirable in clinical application. Herein, a series of adhesive hemostatic antioxidant conductive photothermal antibacterial hydrogels based on hyaluronic acid-graft-dopamine and reduced graphene oxide (rGO) using a H2 O2 /HPR (horseradish peroxidase) system are prepared for wound dressing. These hydrogels exhibit high swelling, degradability, tunable rheological property, and similar or superior mechanical properties to human skin. The polydopamine endowed antioxidant activity, tissue adhesiveness and hemostatic ability, self-healing ability, conductivity, and NIR irradiation enhanced in vivo antibacterial behavior of the hydrogels are investigated. Moreover, drug release and zone of inhibition tests confirm sustained drug release capacity of the hydrogels. Furthermore, the hydrogel dressings significantly enhance vascularization by upregulating growth factor expression of CD31 and improve the granulation tissue thickness and collagen deposition, all of which promote wound closure and contribute to a better therapeutic effect than the commercial Tegaderm films group in a mouse full-thickness wounds model. In summary, these adhesive hemostatic antioxidative conductive hydrogels with sustained drug release property to promote complete skin regeneration are an excellent wound dressing for full-thickness skin repair.

[Only overlapping stents therapy for intracranial vertebral artery dissection aneurysms].

OBJECTIVE: To evaluate the feasibility, safety, clinical, and angiographic follow-up of only overlapping stents therapy for intracranial vertebral artery dissection aneurysms (VADA). METHODS: Eight consecutive patients (6 men, 2 women; mean age 46.8 years ranging from 34 to 62 years) with intracranial VADA admitted to Department of Neurology, Chinese People's Liberation Army General Hospital from June 2008 to June 2014 were retrospectively reviewed. All patients were diagnosed intracranial VADA by MRI or digital subtraction angiography (DSA). All patients were treated by only overlapping stents therapy under general anesthesia. In the endovascular treatment process 2 to 3 Solitaire, Neuroform or Wingspan self-expandable stents were overlapping implanted in the segment of the aneurysms. All patients received routine antiplatelet therapy before and after endovascular treatment. RESULTS: The operative procedures were succeeded in all patients. Eight patients were implanted 18 stents (2 patients, 3 stents; 6 patients, 2 stents). The stents were located accurately and implanted smoothly, none perioperative complications occurred. All patients lived and worked normally and had no recurrent symptoms on follow-up of 6 to 48 months. All patients performed DSA reexamination on follow-up. The aneurysm blocked in 2 patients, the size lessened in 2 patients, and the size had no change in 3 patients. CONCLUSIONS: Only overlapping stents therapy for treating intracranial VADA is feasible and has good operation safety. Preliminary follow-up results show that it can reduce the probability of thrombosis or hemorrhage and can improve the patients' life quality.

Di-tert-butyl peroxide-mediated atom-transfer radical addition of 2-chlorodithiane to aryl alkynes under mild conditions.

Atom transfer radical addition (ATRA) of 2-chlorodithiane onto aryl alkynes through the use of di-tert-butyl peroxide as an oxidant at room temperature directly affords a variety of synthetically valuable ß-chloro-(Z)-vinyl dithianes in good yields with high regioselectivities and without the assistance of any transition metals. It provides an operationally simple pathway to access vinyl dithianes with controlled formation of a new C(sp(2) )C bond and a C(sp(2) )Cl bond.

[Image anatomic characteristics and clinical diagnosis and treatment of cerebral venous sinus stenosis].

OBJECTIVE: To explore the imaging anatomic features of symptomatic cerebral venous sinus stenosis, and evaluate the efficacy and feasibility of different treatment methods. METHODS: From August 2001 to September 2004, 173 patients (transverse sinus stenosis 150, middle of the superior sagittal sinus stenosis 18, proximal part of sigmoid sinus stenosis 3, straight sinus stenosis 2; combined with sinus diverticulum 14, combined with Labbe's vein stenosis 3) were confirmed venous sinus stenosis by digital subtraction angiography (DSA). Among these patients, 121 were treated by stent implantation and the other 52 with mild symptoms by anticoagulation and/or thrombolysis treatment. RESULT: The treatment procedures were succeeded in all patients. 2 patients developed temporal and occipital hemorrhage during the procedure of artery thrombolysis, and 1 patient developed epidural hematoma in the transverse sinus area.All the 3 patients had a satisfactory prognosis through symptomatic treatment.There was no recurrence for all the patients during the follow-up period ranging from 1 to 9 years.9 patients who had recurring dizziness were confirmed no stent stenosis or thrombosis by DSA. The sites of stenosis in 168 patients (97%) were in the connect area of sigmoid and transverse sinuses or in the middle segment of superior sagittal sinus, where arachnoid granulations were focused on according to the anatomic characteristics. CONCLUSIONS: There is significant correlation between the cerebral venous sinuses stenosis and the abnormal growth of arachnoid granulations in the sinuses; the neurologic deficits caused by venous sinus stenosis can be relieved and eliminated by anticoagulation, thrombolysis, or stent implantation. Favorable medium-long term outcome is showed in the study population.

[Short term effect of multiple stents parallel placement and reconstruction technique for the treatment of giant fusiform vertebrobasilar dissecting aneurysms].

OBJECTIVE: To investigate the feasibility,safety and follow-up results of multiple stents parallel placement and reconstruction technique for treating giant vertebrobasilar dissecting aneurysms. METHODS: Five consecutive patients with giant fusiform vertebrobasilar dissecting aneurysms in Department of Neurology,Chinese People's Liberation Army General Hospital were retrospectively reviewed from April 2011 to October 2013. All patients were diagnosed vertebrobasilar dissecting aneurysms by MRI and digital subtraction angiography (DSA), the aneurysm size ranged 8.2-15.0 mm. All patients were treated by multiple stents parallel placement and reconstruction technique under general anesthesia. In the endovascular treatment process, 2-3 Solitaire or Neuroform self-expandable stents were parallel implanted in the maximum extension segment of the aneurysms to reconstruct the cavity of the aneurysm and solved the problem that the diameter of the intracranial stent is less than the diameter of the aneurysms. Multiple stents parallel placement can keep the stents stable in the cavity. The parallel stent can close the dissection as well as strengthen the aneurysm walls to alleviate the vessel pulsative compression of the brain stem. Furthermore, one of the parallel stents was selected for the main blood flow channel. Based on the main channel, telescope technique was used to completely covering the dissection. It can not only prevent the progress of dissection to normal regions, but also be helpful for blood flow channel reconstruction to reduce the hemodynamic disorders. All Patients received routine antiplatelet therapy before and after endovascular treatment. RESULTS: The operative procedures were succeeded in all patients. Five patients were implanted 18 stents (3 stents in 3 patients; 4 stents in 1 patient; 5 stents in 1 patient; parallel 3 stents in 2 patients; parallel 2 stents in 3 patients). The signs and symptoms of brain stem and posterior group of cranial nerves improved significantly. All patients lived and worked normally and had no recurrent symptoms on follow-up of 6-24 months. All patients performed DSA reexamination at 6-12 months postoperation. The aneurysm size lessened in 2 patients and had no change in 3 patients. CONCLUSIONS: Multiple stents parallel placement and reconstruction technique for treating giant fusiform vertebrobasilar dissecting aneurysms is feasible and have good operation safety. It may control the dilatation of the aneurysm and reduce the probability of thrombosis or hemorrhage. It can improve the patients' clinical symptoms and quality of life in short term follow-up. The long term result need for further follow-up.

Supramolecular hydrogels for wound repair and hemostasis.

The unique network characteristics and stimuli responsiveness of supramolecular hydrogels have rendered them highly advantageous in the field of wound dressings, showcasing unprecedented potential. However, there are few reports on a comprehensive review of supramolecular hydrogel dressings for wound repair and hemostasis. This review first introduces the major cross-linking methods for supramolecular hydrogels, which includes hydrogen bonding, electrostatic interactions, hydrophobic interactions, host-guest interactions, metal ligand coordination and some other interactions. Then, we review the advanced materials reported in recent years and then summarize the basic principles of each cross-linking method. Next, we classify the network structures of supramolecular hydrogels before outlining their forming process and propose their potential future directions. Furthermore, we also discuss the raw materials, structural design principles, and material characteristics used to achieve the advanced functions of supramolecular hydrogels, such as antibacterial function, tissue adhesion, substance delivery, anti-inflammatory and antioxidant functions, cell behavior regulation, angiogenesis promotion, hemostasis and other innovative functions in recent years. Finally, the existing problems as well as future development directions of the cross-linking strategy, network design, and functions in wound repair and hemostasis of supramolecular hydrogels are discussed. This review is proposed to stimulate further exploration of supramolecular hydrogels on wound repair and hemostasis by researchers in the future.

ROS-responsive hydrogels with spatiotemporally sequential delivery of antibacterial and anti-inflammatory drugs for the repair of MRSA-infected wounds.

For the treatment of MRSA-infected wounds, the spatiotemporally sequential delivery of antibacterial and anti-inflammatory drugs is a promising strategy. In this study, ROS-responsive HA-PBA/PVA (HPA) hydrogel was prepared by phenylborate ester bond cross-linking between hyaluronic acid-grafted 3-amino phenylboronic acid (HA-PBA) and polyvinyl alcohol (PVA) to achieve spatiotemporally controlled release of two kinds of drug to treat MRSA-infected wound. The hydrophilic antibiotic moxifloxacin (M) was directly loaded in the hydrogel. And hydrophobic curcumin (Cur) with anti-inflammatory function was first mixed with Pluronic F127 (PF) to form Cur-encapsulated PF micelles (Cur-PF), and then loaded into the HPA hydrogel. Due to the different hydrophilic and hydrophobic nature of moxifloxacin and Cur and their different existing forms in the HPA hydrogel, the final HPA/M&Cur-PF hydrogel can achieve different spatiotemporally sequential delivery of the two drugs. In addition, the swelling, degradation, self-healing, antibacterial, anti-inflammatory, antioxidant property, and biocompatibility of hydrogels were tested. Finally, in the MRSA-infected mouse skin wound, the hydrogel-treated group showed faster wound closure, less inflammation and more collagen deposition. Immunofluorescence experiments further confirmed that the hydrogel promoted better repair by reducing inflammation (TNF-α) and promoting vascular (VEGF) regeneration. In conclusion, this HPA/M&Cur-PF hydrogel that can spatiotemporally sequential deliver antibacterial and anti-inflammatory drugs showed great potential for the repair of MRSA-infected skin wounds.

Efficacy and safety of intercostal nerve anastomosis in immediate subpectoral prosthetic breast reconstruction after nipple-areola-sparing mastectomy: a randomized, controlled, open-label clinical study.

Purpose: This aims to investigate the efficacy and safety of intercostal nerve anastomosis among breast cancer patients who undergo immediate subpectoral prosthetic breast reconstruction after nipple-areola-sparing mastectomy. Methods: From 2022 to 2023, female patients between the ages of 20 and 60 diagnosed with stage I-IIIA breast cancer, who required and were willing to undergo immediate subpectoral prosthetic breast reconstruction after nipple-areola-sparing mastectomy, were screened and assigned to take the operation with (treatment group) or without (control group) intercostal nerve anastomosis (the nerves with appropriate length and thickness were selected from the 2nd-4th intercostal nerves, which were then dissociated and anastomosed to the posterior areola tissue). A radial incision at the surface projection of the tumor location was used. The patients' breast local sensation was assessed using Semmes-Weinstein monofilaments before the operation as well as at 10 days, 3 months, and 6 months postoperatively. Furthermore, the patients' quality of life was evaluated 6 months postoperatively using the EORTC QLQ-C30 questionnaire. Adverse events, operation duration, drainage volume, and the duration of drainage tube carrying time were also monitored and recorded. Results: Compared to the pre-operative period, a significant decrease in local sensation was observed 10 days after surgery in both groups. However, the control group showed a significant reduction in sensation at 3 and 6 months postoperatively, while the treatment group showed noticeable recovery. A statistically significant difference (P < 0.001) in local sensation between the pre-operative and post-operative periods was observed at the final follow-up in the two groups. By the time of 3 and 6 months postoperatively, a significant difference was seen in the local sensation between the two groups. Intercostal nerve anastomosis was found to significantly improve the patients' quality of life, including emotional (P = 0.01), physical (P = 0.04), and social functioning (P = 0.02) and pain (P = 0.04). There were no significant differences in general characteristics (such as age, BMI, and subtypes). Although intercostal nerve anastomosis increased the duration of operation by around 20 min (P < 0.001), it did not affect the volume or duration of postoperative drainage tube usage between the two groups. Conclusion: This study indicated that intercostal nerve anastomosis improved the local sensation and quality of life of patients who underwent immediate subpectoral prosthetic breast reconstruction after nipple-areola-sparing mastectomy. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=42487, identifier ChiCTR1900026340.

Physical dynamic double-network hydrogels as dressings to facilitate tissue repair.

Double-network hydrogels can be tuned to have high mechanical strength, stability, elasticity and bioresponsive properties, which can be combined to create self-healing, adhesive and antibacterial wound dressings. Compared with single-network hydrogel, double-network hydrogel shows stronger mechanical properties and better stability. In comparison with chemical bonds, the cross-linking in double networks makes them more flexible than single-network hydrogels and capable of self-healing following mechanical damage. Here, we present the stepwise synthesis of physical double-network hydrogels where hydrogen bonds and coordination reactions provide self-healing, pH-responsive, tissue-adhesive, antioxidant, photothermal and antibacterial properties, and can be removed on demand. We then explain how to carry out physical, chemical and biological characterizations of the hydrogels for use as wound dressings, yet the double-network hydrogels could also be used in different applications such as tissue engineering scaffolds, cell/drug delivery systems, hemostatic agents or in flexible wearable devices for monitoring physiological and pathological parameters. We also outline how to use the double-network hydrogels in vivo as wound dressings or hemostatic agents. The synthesis of the ureido-pyrimidinone-modified gelatin, catechol-modified polymers and the hydrogels requires 84 h, 48 h and 1 h, respectively, whereas the in vivo assays require 3.5 weeks. The procedure is suitable for users with expertise in biomedical polymer materials.

Conductive hydrogels for tissue repair.

Conductive hydrogels (CHs) combine the biomimetic properties of hydrogels with the physiological and electrochemical properties of conductive materials, and have attracted extensive attention in the past few years. In addition, CHs have high conductivity and electrochemical redox properties and can be used to detect electrical signals generated in biological systems and conduct electrical stimulation to regulate the activities and functions of cells including cell migration, cell proliferation, and cell differentiation. These properties give CHs unique advantages in tissue repair. However, the current review of CHs is mostly focused on their applications as biosensors. Therefore, this article reviewed the new progress of CHs in tissue repair including nerve tissue regeneration, muscle tissue regeneration, skin tissue regeneration and bone tissue regeneration in the past five years. We first introduced the design and synthesis of different types of CHs such as carbon-based CHs, conductive polymer-based CHs, metal-based CHs, ionic CHs, and composite CHs, and the types and mechanisms of tissue repair promoted by CHs including anti-bacterial, antioxidant and anti-inflammatory properties, stimulus response and intelligent delivery, real-time monitoring, and promoted cell proliferation and tissue repair related pathway activation, which provides a useful reference for further preparation of bio-safer and more efficient CHs used in tissue regeneration.

[Hydrochemical Characteristics and Formation Causes of Ground Karst Water Systems in Gudui Spring Catchment].

As one of the famous karst springs in Shanxi Province, the Gudui spring is the only medium-low temperature hot spring, with a long history of development and a rich cultural accumulation. The karst groundwater in the Gudui spring catchment was taken as the research object. Through systematic sample collection and isotope analysis, hydrochemistry (Durov map, ion ratio, Gibbs map, and hydrogen and oxygen isotope) methods were comprehensively used to analyze groundwater hydrochemistry and groundwater system runoff characteristics. The87Sr/86Sr value of karst groundwater in the Gudui spring catchment was 0.709 to 0.717, and the Mg/(Mg+Ca) value was 0.27 to 0.74. By analyzing the Sr isotope composition and Mg/(Mg+Ca) and 1/Sr variation characteristics, it was concluded that the karst groundwater in the Gudui spring catchment was a mixture of deep hot water and shallow cold water. The karst water subsystem of Nanliang spring presented the characteristics of carbonate stratum runoff. The karst water subsystem of Fuling Mountain Gaoxian Haitou spring and the deep circulation subsystem of Houma Basin exhibited the runoff characteristics of carbonate rock and igneous rock strata. The karst water subsystem of Taiershan Jiuyuanshan Gudui spring presented the runoff characteristics of carbonate rock and ancient silicoaluminate strata. The δ18O value in karst groundwater of Guodui spring area ranged from -11.46‰ to -7.81‰, and the average value was -10.08‰. The range of the δD value was -83.7‰ to -60.8‰, and the average value was -73.6‰. This showed that karst groundwater in the spring area was the result of mixing of various types of water. Through comparative analysis of hydrogen and oxygen isotopes of 2014 and 2021 sampling points at the same location, it was concluded that the change in water samples at the Guduiquan resulted from the gradual accumulation of water supplied by Sanquan Reservoir. The change in Sanquan Reservoir was due to the influence of Yellow River diversion. The karst groundwater in the spring area were characterized by large calcium ion, magnesium ion, and sodium ion values; a small potassium ion value; a large sulfate value; and a small chloride value. The hydrochemical types of karst groundwater in Gudui spring catchment could be divided into SO4-Na, SO4-Ca, HCO3-Na, HCO3-Mg, HCO3-Ca, and Cl-Na. The hydrochemical types of karst groundwater showed evident hydrochemical composition zoning from HCO3-Ca·Mg→HCO3·SO4-Ca·Mg→SO4·HCO3-Na·Ca→SO4·Cl-Na·Ca. According to the comprehensive analysis of hydrochemical isotope and hydrogeological conditions, the karst water subsystem of Nanliang spring was primarily recharged by rainfall infiltration in the exposed limestone area and river infiltration, and its karst groundwater was recharged by runoff from south to north to the karst water subsystem of Fuling Mountain Gaoxian Haitou spring and the deep circulation subsystem of Houma Basin. The karst water subsystem of Taier Jiuyuan Mountain Gudui spring received rainfall infiltration supplement and upstream runoff supplement from the exposed limestone area. Its karst groundwater flowed from north to south and received the supply of Sanquan Reservoir from Yellow River water in the natural discharge area of Gudui spring.

Antibacterial conductive self-healing hydrogel wound dressing with dual dynamic bonds promotes infected wound healing.

In clinical applications, there is a lack of wound dressings that combine efficient resistance to drug-resistant bacteria with good self-healing properties. In this study, a series of adhesive self-healing conductive antibacterial hydrogel dressings based on oxidized sodium alginate-grafted dopamine/carboxymethyl chitosan/Fe3+ (OSD/CMC/Fe hydrogel)/polydopamine-encapsulated poly(thiophene-3-acetic acid) (OSD/CMC/Fe/PA hydrogel) were prepared for the repair of infected wound. The Schiff base and Fe3+ coordination bonds of the hydrogel structure are dynamic bonds that can be repaired automatically after the hydrogel network is disrupted. Macroscopically, the hydrogel exhibits self-healing properties, allowing the hydrogel dressing to adapt to complex wound surfaces. The OSD/CMC/Fe/PA hydrogel showed good conductivity and photothermal antibacterial properties under near-infrared (NIR) light irradiation. In addition, the hydrogels exhibit tunable rheological properties, suitable mechanical properties, antioxidant properties, tissue adhesion properties and hemostatic properties. Furthermore, all hydrogel dressings improved wound healing in the infected full-thickness defect skin wound repair test in mice. The wound size repaired by OSD/CMC/Fe/PA3 hydrogel + NIR was much smaller (12%) than the control group treated with Tegaderm™ film after 14 days. In conclusion, the hydrogels have high antibacterial efficiency, suitable conductivity, great self-healing properties, good biocompatibility, hemostasis and antioxidant properties, making them promising candidates for wound healing dressings for the treatment of infected skin wounds.

The efficacy and safety of using pyrotinib combined with capecitabine as neoadjuvant therapy in elderly patients with HER2-positive breast cancer: a single-arm prospective clinical trial.

Background: Pyrotinib combined with capecitabine has been approved for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer in China. To date, the management of early-stage or locally advanced HER2-positive breast cancer in the clinic remains challenging. We conducted this trial to investigate the efficacy and safety of pyrotinib combined with capecitabine as neoadjuvant therapy (NAT) in elderly patients with HER2-positive breast cancer. Due to the stimulation of blood vessels by chemotherapy drugs, the elasticity of blood vessels in the elderly decreases, and then chemotherapy infusion is more likely to lead to phlebitis. Both pyrotinib and capecitabine can be taken to facilitate home treatment for elderly patients with HER2-positive breast cancer (BC). Methods: From January 2020 to March 2021, patients aged between 70 and 81 years old with stage IIA-IIIB HER2-positive breast cancer were screened, enrolled, and assigned to receive six cycles of pyrotinib (320-400 mg, orally, once daily) plus capecitabine (1,250 mg/m2, orally, twice daily) on days 1-14 in every 21-day cycle. The primary endpoint was the objective response rate (ORR). Adverse events (AEs) were assessed in every neoadjuvant cycle. Surgery was performed after the last cycle, and the total pathological complete response (tpCR) was evaluated postoperatively. Results: Of the 23 patients enrolled, the ORR was 100% (23/23; 95% confidence intervals: 85 to 100). All patients underwent surgery with a tpCR rate of 43.5% (10/23; 95% confidence intervals: 23 to 66). The most common AE was diarrhea, occurring in 19 of 23 patients (82.6%); most of these patients sustained mild diarrhea (Grade 1 or Grade 2) and only three had moderate diarrhea (Grade 3). The incidences of other AEs, including weakness, loss of appetite, leukopenia, nausea, vomiting, hand-foot syndrome, etc., were low and the symptoms were mild. No severe AEs (Grade 4 or 5) were observed throughout the treatment. Conclusion: In our study, pyrotinib combined with capecitabine as neoadjuvant therapy in elderly women with HER2-positive breast cancer is safe and showed efficacy in this population, which may be widely used as a protocol for clinical neoadjuvant therapy.

Renal microvascular injury in chronic aristolochic acid nephropathy and protective effects of Cozaar.

BACKGROUND: To investigate the renal microvascular injury in chronic aristolochic acid nephropathy (AAN) and the protective effects of Cozaar. METHODS: Male Sprague-Dawley rats were randomized into three groups. Rats in the model group received Caulis Aristolochiae manshuriensis (CAM) decoction by gavage (10 mL/kg/day); those in the Cozaar group were gavaged with CAM and Cozaar (33.3 mg/kg/day); and those in the control group only received an equal daily volume of saline solution by gavage. Kidney tissues were observed under a light and electron microscope. CD34, caspase-3, and bone morphogenetic protein-7 (BMP-7) were determined by immunohistochemistry, and expressions of angiopoietin (Ang) 1 and 2, Tie-2, BMP-7, and vascular endothelial growth factor (VEGF) mRNA were monitored via real-time polymerase chain reaction (PCR). RESULTS: (1) The kidney tissue injury in the chronic AAN model group was apparent, compared to the normal structure in the normal control group, and the Cozaar group showed relieved injury. (2) The expression of caspase-3 in the model group was elevated, while expressions of BMP-7 and CD34 were decreased (p < 0.05). Cozaar lessened caspase-3 expression (p < 0.05) and promoted BMP-7 and CD34 expressions (p < 0.05). (3) Real-time PCR demonstrated a downregulation of Ang-1, Tie-2, BMP-7, and VEGF mRNA (p < 0.05) and an upregulation of Ang-2 mRNA (p < 0.01) in the renocortex, while Cozaar upregulated the expression of Ang-1, Tie-2, BMP-7, and VEGF mRNA (p < 0.05). CONCLUSION: Renal microvascular injury was observed in chronic AAN, which was hypothetically correlated with a lack in the expressions of Ang-1, BMP-7, Tie-2, and VEGF and an excess in caspase-3 and Ang-2. Cozaar can significantly ameliorate the renal microvascular injury and protect renal function.

Antibacterial biomaterials for skin wound dressing.

Bacterial infection and the ever-increasing bacterial resistance have imposed severe threat to human health. And bacterial contamination could significantly menace the wound healing process. Considering the sophisticated wound healing process, novel strategies for skin tissue engineering are focused on the integration of bioactive ingredients, antibacterial agents included, into biomaterials with different morphologies to improve cell behaviors and promote wound healing. However, a comprehensive review on anti-bacterial wound dressing to enhance wound healing has not been reported. In this review, various antibacterial biomaterials as wound dressings will be discussed. Different kinds of antibacterial agents, including antibiotics, nanoparticles (metal and metallic oxides, light-induced antibacterial agents), cationic organic agents, and others, and their recent advances are summarized. Biomaterial selection and fabrication of biomaterials with different structures and forms, including films, hydrogel, electrospun nanofibers, sponge, foam and three-dimension (3D) printed scaffold for skin regeneration, are elaborated discussed. Current challenges and the future perspectives are presented in this multidisciplinary field. We envision that this review will provide a general insight to the elegant design and further refinement of wound dressing.

Mussel-inspired adhesive antioxidant antibacterial hemostatic composite hydrogel wound dressing via photo-polymerization for infected skin wound healing.

With the increasing prevalence of drug-resistant bacterial infections and the slow healing of chronically infected wounds, the development of new antibacterial and accelerated wound healing dressings has become a serious challenge. In order to solve this problem, we developed photo-crosslinked multifunctional antibacterial adhesive anti-oxidant hemostatic hydrogel dressings based on polyethylene glycol monomethyl ether modified glycidyl methacrylate functionalized chitosan (CSG-PEG), methacrylamide dopamine (DMA) and zinc ion for disinfection of drug-resistant bacteria and promoting wound healing. The mechanical properties, rheological properties and morphology of hydrogels were characterized, and the biocompatibility of these hydrogels was studied through cell compatibility and blood compatibility tests. These hydrogels were tested for the in vitro blood-clotting ability of whole blood and showed good hemostatic ability in the mouse liver hemorrhage model and the mouse-tail amputation model. In addition, it has been confirmed that the multifunctional hydrogels have good inherent antibacterial properties against Methicillin-resistant Staphylococcus aureus (MRSA). In the full-thickness skin defect model infected with MRSA, the wound closure ratio, thickness of granulation tissue, number of collagen deposition, regeneration of blood vessels and hair follicles were measured. The inflammation-related cytokines (CD68) and angiogenesis-related cytokines (CD31) expressed during skin regeneration were studied. All results indicate that these multifunctional antibacterial adhesive hemostatic hydrogels have better healing effects than commercially available Tegaderm™ Film, revealing that they have become promising alternative in the healing of infected wounds.