Chondroitin sulfate-based universal nanoparticle delivers angiogenic inhibitor and paclitaxel to exhibit a combination of chemotherapy and anti-angiogenic therapy.

Blocking the tumor nutrient supply through angiogenic inhibitors is an effective treatment approach for malignant tumors. However, using angiogenic inhibitors alone may not be enough to achieve a significant tumor response. Therefore, we recently designed a universal drug delivery system combining chemotherapy and anti-angiogenic therapy to target tumor cells while minimizing drug-related side effects. This system (termed as PCCE) is composed of biomaterial chondroitin sulfate (CS), the anti-angiogenic peptide ES2, and paclitaxel (PTX), which collectively enhance antitumor properties. Interestingly, the PCCE system is conferred exceptional cell membrane permeability due to inherent characteristics of CS, including CD44 receptor-mediated endocytosis. The PCCE could respond to the acidic and high glutathione conditions, thereby releasing PTX and ES2. PCCE could effectively inhibit the proliferation, migration, and invasion of tumor cells and cause apoptosis, while PCCE can affect the endothelial cells tube formation and exert anti-angiogenic function. Consistently, more potent in vivo antitumor efficacy and non-toxic sides were demonstrated in B16F10 xenograft mouse models. PCCE can achieve excellent antitumor activity via modulating angiogenic and apoptosis-related factors. In summary, we have successfully developed an intelligent and responsive CS-based nanocarrier known as PCCE for delivering various antitumor drugs, offering a promising strategy for treating malignant tumors.

Fluorescent cellulose nanofibrils-based hydrogel incorporating MIL-125-NH2 for effective adsorption and detection of iodide ion.

To remove iodine ion (I-) from wastewater, a novel hydrogel, the fluorescent cellulose nanofibrils-based hydrogel (FCNH), was synthesized to enable both detection and adsorption of I-. The FCNH comprised cellulose nanofibrils (CNs), silver nanoclusters (AgNCs), and MIL-125-NH2. It exhibited an excellent adsorption capacity for I-, with a maximum adsorption capacity of 373.7 mg/g, fitting both the Langmuir and pseudo-second-order models. Additionally, FCNH displayed excellent regeneration properties, retaining 88.0 % of its initial adsorption capacity after six adsorption-desorption cycles. Functioning as a fluorescent sensor, the synthesized FCNH enabled the detection of I- through dynamic quenching, with linear ranges of 5 to 200 mg/L and 0.2 to 1.0 µg/L, and a determination limit of 0.11 µg/L. Analysis of the adsorption and detection mechanisms revealed that FCNH's outstanding performance arose from its 3D porous structure comprising CNs, AgNCs, and MIL-125-NH2. Economic analysis indicated that FCNH was inexpensive compared to commercially available activated carbon. Thus, FCNH demonstrated significant potential as an economical and reusable adsorbent for iodine ion removal.

Feasibility of Using Intraoperative Neurophysiological Monitoring for Detecting Bone Layer of Cervical Spine Surgery.

STUDY DESIGN: Intraoperative neurophysiological monitoring (IONM) as a guide to bone layer estimation was examined during posterior cervical spine lamina grinding. OBJECTIVE: To explore the feasibility of IONM to estimate bone layer thickness. SUMMARY OF BACKGROUND DATA: Cervical laminoplasty is a classic operation for cervical spondylosis. To increase safety and accuracy, surgery-assistant robots are currently being studied. It combines the advantages of various program awareness methods to form a feasible security strategy. In the field of spinal surgery, robots have been successfully used to help place pedicle screws. IONM is used to monitor intraoperative nerve conditions in spinal surgery. This study was designed to explore the feasibility of adding IONM to robot safety strategies. METHODS: Chinese miniature pig model was used. Electrodes were placed on the lamina, and the minimum stimulation threshold of DNEP for each lamina was measured (Intact lamina, IL). The laminae were ground to measure the DNEP threshold after incomplete grinding (Inner cortical bone preserved, ICP) and complete grinding (Inner cortical bone grinded, ICG). Subsequently, the lateral cervical mass screw canal drilling was performed, and the t-EMG threshold of the intact and perforated screw canals was measured and compared. RESULT: The threshold was significantly lower than that of the recommended threshold of DENP via percutaneous cervical laminae measurement. The DNEP threshold decreases with the process of laminae grinding. The DNEP threshold of the IL group was significantly higher than ICP and ICG group, while there was no significant difference between the ICP group and the ICG group. There was no significant relationship between the integrity of the cervical spine lateral mass screw path and t-EMG threshold. CONCLUSIONS: It is feasible to use DENP threshold to estimate lamina thickness. Cervical lateral mass screw canals by t-EMG showed no help to evaluate the integrity.

Comparative analysis of paraspinal muscle imbalance between idiopathic scoliosis and congenital scoliosis from the transcriptome aspect.

Background: Previous studies have analyzed paraspinal muscle imbalance in idiopathic scoliosis (IS) with methods including imaging, histology and electromyography. However, whether paraspinal muscle imbalance is the cause or the consequence of spinal deformities in IS remains unclear. Comparison of paraspinal muscle imbalance between IS and congenital scoliosis (CS) may shed some light on the causality of paraspinal muscle imbalance and IS. This study aimed to elucidate the generality and individuality of paraspinal muscle imbalance between IS and CS from gene expression. Methods: Five pairs of surgical-treated IS and CS patients were matched. Bilateral paraspinal muscles at the apex were collected for transcriptome sequencing. Differentially expressed genes (DEGs) between the convexity and concavity in both IS and CS were identified. Comparison of DEGs between IS and CS was conducted to discriminate IS-specific DEGs from DEGs shared by both IS and CS. Bioinformatics analysis was performed. The top 10 hub genes in the protein-protein interaction (PPI) network of IS-specific DEGs were validated by quantitative PCR (qPCR) in 10 pairs of IS and CS patients. Results: A total of 370 DEGs were identified in IS, whereas 380 DEGs were identified in CS. Comparison of DEGs between IS and CS identified 59 DEGs shared by IS and CS, along with 311 DEGs specific for IS. These IS-specific DEGs were enriched in response to external stimulus and signaling receptor binding in GO terms and calcium signaling pathway in KEGG pathways. The top 10 hub genes in the PPI network of IS-specific DEGs include BDKRB1, PRH1-TAS2R14, CNR2, NPY4R, HTR1E, CXCL3, ICAM1, ALB, ADIPOQ, and GCGR. Among these hub genes, the asymmetrical expression of PRH1-TAS2R14 and ADIPOQ in IS but not CS were validated by qPCR. Conclusions: Transcriptomic differences in bilateral paraspinal muscles between the convexity and concavity in IS share few similarities with those in CS.

Hidden blood loss in three different endoscopic spinal procedures for lumbar disc herniation.

Purpose: This study compared hidden blood loss (HBL) among three different endoscopic spinal procedures and investigated its risk factors. Patients and methods: This single-centre retrospective analysis collected data from consecutive hospitalized patients with single-segment lumbar disc herniation (LDH) undergoing unilateral biportal endoscopic discectomy (UBE), percutaneous endoscopic transforaminal discectomy (PETD), or percutaneous endoscopic interlaminar discectomy (PEID) from December 2020 to October 2022. HBL was calculated using Nadler's and Gross's formulas. The authors used Pearson's or Spearman's correlation analysis to explore the relationship between patient characteristics and HBL. Multivariate linear regression analysis was used to identify independent risk factors for HBL. Results: In total, 122 consecutive patients (68 females and 54 males) were enroled in this study. The average HBL was 381.87±218.01 ml in the UBE group, 252.05±118.44 ml in the PETD group and 229.63±143.9 ml in the PEID group (P<0.05). Pearson's or Spearman's correlation analysis showed that operative time, preoperative haemoglobin, preoperative haematocrit, and preoperative Albumin (ALB) were correlated with HBL in the UBE group, while sex, age, operative time, postoperative ALB, and patients' blood volume (PBV) were related to HBL in the PETD group (P<0.05). Operative time and preoperative activated partial thromboplastin time were related to HBL in the PEID group (P<0.05). Multiple linear regression analysis showed a positive correlation between HBL and operative time in all three groups (P<0.001, P<0.001, P<0.05). Conclusion: HBL was higher in the UBE group than in the PETD and PEID groups, and operative time may be a common risk factor for the three groups.

Chondroitin sulfate-modified antiangiogenic peptide conjugate induces cell apoptosis via the mitochondria-mediated pathway to perform antitumor activity.

Tumor growth and metastasis heavily rely on angiogenesis, crucial for solid tumor development. Inhibiting angiogenesis associated with tumors emerges as a potent therapeutic approach. Our previous work synthesized the chondroitin sulfate-modified antiangiogenic peptide CS-ES2-AF (CS-EA), which exhibited better antiangiogenic activity, longer half-life, and more robust targeting. In this work, we further evaluated the stability in vitro, cellular uptake mechanism, cell apoptosis mechanism, antitumor activity in vivo, and safety of CS-EA. The stability of CS-EA was consistently superior to that of EA at different temperatures and in different pH ranges. Furthermore, CS-EA mainly entered EAhy926 cells through the clathrin-mediated endocytosis pathway. CS-EA inhibited endothelial cell proliferation, and induced cell apoptosis through downregulating the Bcl-2, reducing mitochondria membrane potential, upregulating cytochrome c, Caspase 3, and reactive oxygen species levels. CS-EA showed better antitumor activity in the B16 xenografted tumor model, with a tumor inhibition rate 1.92 times higher than EA. Simultaneously, it was observed that CS-EA did not cause any harmful effects on the vital organs of the mice. These findings indicate that CS-EA holds significant promise for the treatment of tumors.

High-Level Biosynthesis of Chlorogenic Acid from Mixed Carbon Sources of Xylose and Glucose through a Rationally Refactored Pathway Network.

Chlorogenic acid (CGA) has incredible potential for various pharmaceutical, nutraceutical, and agricultural applications. However, the traditional extraction approach from plants is time-consuming, further limiting its production. Herein, we design and construct the de novo biosynthesis pathway of CGA using modular coculture engineering in Escherichia coli, which is composed of MG09 and BD07 strains. To accomplish this, the phenylalanine-deficient MG09 strain was engineered to utilize xylose preferentially and to overproduce precursor caffeic acid, while the tyrosine-deficient BD07 strain was constructed to consume glucose exclusively to enhance another precursor quinic acid availability for the biosynthesis of CGA. Further pathway modularization and balancing in the context of syntrophic cocultures resulted in additional production improvement. The coculture strategy avoids metabolic flux competition in the biosynthesis of two CGA precursors, caffeic acid and quinic acid, and allows for production improvement by balancing module proportions. Finally, the optimized coculture based on the aforementioned efforts produced 131.31 ± 7.89 mg/L CGA. Overall, the modular coculture engineering strategy in this study provides a reference for constructing microbial cell factories that can efficiently biomanufacture complex natural products.

Advances in the variations and biomedical applications of stimuli-responsive nanodrug delivery systems.

Chemotherapy is an important cancer treatment modality, but the clinical utility of chemotherapeutics is limited by their toxic side effects, inadequate distribution and insufficient intracellular concentrations. Nanodrug delivery systems (NDDSs) have shown significant advantages in cancer diagnosis and treatment. Variable NDDSs that respond to endogenous and exogenous triggers have attracted much research interest. Here, we summarized nanomaterials commonly used for tumor therapy, such as peptides, liposomes, and carbon nanotubes, as well as the responses of NDDSs to pH, enzymes, magnetic fields, light, and multiple stimuli. Specifically, well-designed NDDSs can change in size or morphology or rupture when induced by one or more stimuli. The varying responses of NDDSs to stimulation contribute to the molecular design and development of novel NDDSs, providing new ideas for improving drug penetration and accumulation, inhibiting tumor resistance and metastasis, and enhancing immunotherapy.

Isolation, purification, and antiosteoporosis activity of donkey bone collagen from discarded bone and its antioxidant peptides.

Oxidative stress plays a crucial role in the development of osteoporosis. In this study, it was observed that donkey bone collagen (DC) at a concentration of 500 µg/mL scavenged 17.89 % of 1,1-Diphenyl-2-picrylhydrazyl (DPPH) free radicals, indicating its antioxidant properties. Additionally, when an oxidative damage osteoblast model was created using H2O2, 100 µg/mL DC demonstrated the ability to enhance cell survival by 27.31 %. Furthermore, 50 µg/mL DC increased the intracellular differentiation marker alkaline phosphatase (ALP) level by 62.65 %. Additionally, the study revealed that DC significantly increased the expression of osteoporosis-related factors in serum and effectively restored the abnormal structure of spongy bone in mice osteoporosis model. Peptides (GGWFL, ANLGPA, and GWFK) isolated from DC through gastrointestinal digestion and subsequent enzymatic purification in vitro demonstrated the ability to safeguard osteoblasts from H2O2-induced damage by reducing intracellular reactive oxygen species (ROS). This protection resulted in enhanced cell survival and promoted osteoblast differentiation. This investigation underscores that DC can shield oxidative damage osteoblast model from oxidative stress, ameliorate osteoporosis, and enhance bone density in mice osteoporosis model. These findings suggest various DC applications in the food and medicine industries.

Key processes in tumor metastasis and therapeutic strategies with nanocarriers: a review.

Cancer metastasis is the leading cause of cancer-related death. Metastasis occurs at all stages of tumor development, with unexplored changes occurring at the primary site and distant colonization sites. The growing understanding of the metastatic process of tumor cells has contributed to the emergence of better treatment options and strategies. This review summarizes a range of features related to tumor cell metastasis and nanobased drug delivery systems for inhibiting tumor metastasis. The mechanisms of tumor metastasis in the ideal order of metastatic progression were summarized. We focus on the prominent role of nanocarriers in the treatment of tumor metastasis, summarizing the latest applications of nanocarriers in combination with drugs to target important components and processes of tumor metastasis and providing ideas for more effective nanodrug delivery systems.

Percutaneous uniportal full-endoscopic surgery for treating symptomatic lumbar facet joint cysts under local anesthesia combined with monitored anesthesia care: a preliminary report of eight cases with at least 1 year follow-up.

Background: Lumbar facet joint cysts (FJCs) are a relatively rare clinical pathology that can result in radiculopathy or neurogenic claudication. Various treatments such as percutaneous aspiration and surgery have been reported to have good clinical outcomes. However, few clinical studies have aimed to treat symptomatic lumbar FJCs by using uniportal full-endoscopic (UFE) surgery. This study aimed to investigate the preliminary clinical outcomes of UFE surgery for the treatment of lumbar FJCs under local anesthesia combined with monitored anesthesia care (MAC). Methods: Eight patients (five males and three females) with symptomatic lumbar FJCs who underwent UFE surgery under local and MAC anesthesia were enrolled in this study between January 2018 and April 2022. The clinical characteristics, radiological features, operative information, visual analog scale (VAS) score, Oswestry disability index (ODI), and overall outcome rating based on the modified MacNab criteria were retrospectively analyzed. Results: Of the eight patients, four underwent a transforaminal approach and four underwent an interlaminar approach. Postoperatively, the mean VAS score for leg pain decreased from 6.1 before surgery to 0.6 after surgery, and the ODI decreased from 74.5% to 14.7%. All patients were followed up for more than 1 year, and the good-to-excellent rate based on the modified MacNab criteria remained 100% at the last follow-up. No complications occurred during the follow-up period. Conclusion: Lumbar FJCs can cause severe radiating leg pain and/or neurogenic claudication due to the dural sac compression and nerve roots. As an alternative treatment, UFE decompression under local and MAC anesthesia may provide effective clinical outcomes for symptomatic lumbar FJCs.

Consecutive Case Series of Uniportal Full-endoscopic Unilateral Laminotomy for Bilateral Decompression in Lumbar Spinal Stenosis: Relationship between Decompression Range and Functional Outcomes.

OBJECTIVE: Uniportal full-endoscopic unilateral laminotomy for bilateral decompression (UFE-ULBD) has been used to treat lumbar spinal stenosis (LSS) with satisfactory outcomes. However, a limited number of studies have investigated the relationship between decompression range and clinical outcomes. This study aimed to investigate the efficacy of UFE-ULBD for single-segment LSS and to explore the relationship between the decompression range and functional outcomes. METHODS: Single-segment LSS patients who had undergone UFE-ULBD using an interlaminar approach between November 2021 and February 2023 were retrospectively analyzed. Patient demographics, visual analogue scale (VAS) scores for leg and back pain, Oswestry disability index (ODI) scores, modified MacNab grades, and radiological outcomes, including the decompression ratio of the disc-flava ligament space and osseous lateral recess, the enlargement ratio of superior articular process interval, lamina interval dural sac cross-sectional area (DSCA), were collected. The independent sample t-tests, paired sample t-tests, chi-square tests, Fisher's exact tests, and Pearson's and Spearman's correlation analyses were used. RESULTS: Forty patients (23 males, and 17 females) were retrospectively enrolled in this study. The mean follow-up period was 12 months. At the last follow-up, VAS scores for leg pain and back pain decreased from 6.0 ± 0.8 to 1.0 ± 1.9 (p < 0.001), and from 6.0 ± 0.8 to 1.2 ± 1.8 (p < 0.001) respectively; ODI score decreased from 71.7 ± 6.2 to 24.3 ± 21.3 (p < 0.001). According to the modified MacNab criteria, the results were excellent in 28 (70%), good in 5 (12.5%), fair in 6 (15%), and poor in 1 (2.5%), with an excellent-good rate of 82.5%. The postoperative DSCA enlarged from 57.69 ± 21.86 to 150.75 ± 39.33 mm2 (p < 0.001), with an enlargement ratio of 189.43 ± 107.83%. No difference in clinical or radiological parameters was detected between patients with excellent, good, fair, or poor outcomes based on the modified MacNab criteria. CONCLUSION: UFE-ULBD can provide satisfactory clinical and radiological outcomes in single-segment LSS patients. With sufficient exposure to the dural sac boundary, the functional outcome was not related to the radiological decompression range in LSS patients who had undergone UFE-ULBD.

CD44 targeting nanodrug based on chondroitin sulfate for melanoma therapy by inducing mitochondrial apoptosis pathways.

Neovascularization is crucial to the occurrence and progression of tumors, and the development of antiangiogenic drugs has essential theoretical value and clinical significance. However, antiangiogenesis therapy alone cannot meet the needs of tumor therapy. Meanwhile, polysaccharides are ideal drug carriers with promising applications in drug modification and delivery. In this research, we developed a novel redox and acid sensitive nanodrug (CDDP-CS-Cys-EA, CCEA) composed of chondroitin sulfate (CS), antiangiogenic peptide (endostatin2-alft1, EA) and chemotherapeutic drug (cisplatin, CDDP). CCEA exhibited redox and acid responsiveness, better blood hemocompatibility (hemolysis rate < 5 %), the ability to target tumors (CD44-mediated endocytosis), and strong antiangiogenesis and antitumor characteristics in vitro. Moreover, CCEA showed excellent antitumor activity and low toxicity in B16 xenograft mice. It also has been confirmed that CCEA induced tumor cell apoptosis through promoting the expression of Bax, suppressing the expression of Bcl-2, decreasing mitochondrial membrane potential, releasing cytochrome C (Cyto C), and enhancing the activities of Caspase 9 and Caspase 3. The results of this paper provided a theoretical basis and insight for the development of antitumor drugs.

Unilateral bi-portal endoscopy for unilateral L5 nerve injury due to post-traumatic epidural hematoma at T12/L1 level: A case report and literature review.

INTRODUCTION AND IMPORTANCE: Spinal epidural hematoma (SEH) is an uncommon condition that can result in severe neurological problems and needs to be treated as soon as possible. The incidence of traumatic SEH is 0.5 %-1.7 %, but increases to 9 % in patients with rheumatic diseases. Surgical treatment options include open surgery and minimally invasive surgery. We reported a post-traumatic SEH at T12/L1 level combined with L5 nerve injury and treated by UBE technique. To our knowledge, there was no reported cases like this. CASE PRESENTATION: A 38-year-old man with left leg weakness and severe back pain after fell down while cycling. Physical examination suggested left hip abduction was 2/5 strength, left dorsiflexion of hallux dorsal extension was 0/5 strength and the left ankle dorsiflexion was 2/5 strength. Magnetic resonance images (MRI) of lumbar spine showed a two-leveled hematoma extending from T12 to L1. After 1 year of surgery, the patient's symptoms had largely disappeared and he was able to perform daily activities independently. CLINICAL DISCUSSION: An epidural hematoma at the L1 level is can cause symptoms of the L5 nerve root alone, which may be due to anatomical reasons. Complete removal of the epidural hematoma is necessary to restore the function of the nerve. We report a case of successful removal of an epidural hematoma using the UBE technique with good postoperative results. CONCLUSIONS: The single nerve injury can occur with a thoracolumbar segmental hematoma, and UBE technology could be used to remove epidural hematoma.

Proteomic Comparison of Paraspinal Muscle Imbalance Between Idiopathic Scoliosis and Congenital Scoliosis.

OBJECTIVE: This study aims to compare the proteomic profiles of paraspinal muscle imbalance between idiopathic scoliosis (IS) and congenital scoliosis (CS). METHODS: Bilateral paraspinal muscles of 5 pairs of matched IS and CS patients were collected. Proteome patterns of paraspinal muscles were established. Differentially expressed proteins (DEPs) in paraspinal muscles between the convexity and the concavity were screened out. DEPs shared by both IS and CS and IS-specific DEPs were identified. Bioinformatic analyses of DEPs were performed. RESULTS: Among 105 DEPs identified in IS, 30 displayed predominant expression on the convexity, whereas other 75 exhibited predominant expression on the concavity. DEPs in IS were mainly enriched in calcium ion binding and DNA binding in gene ontology (GO) term and glycolysis/gluconeogenesis and purine metabolism in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Among 48 DEPs identified in CS, 25 were predominantly expressed on the convexity and 23 on the concavity. DEPs in CS were mainly enriched in receptor activity and immune response in GO term and glycolysis/gluconeogenesis and cellular senescence in KEGG pathway. Comparison of DEPs between IS and CS identified only 8 proteins shared by both types of scoliosis. Among the 97 IS-specific DEPs, 28 were predominantly expressed on the convexity and 69 on the concavity. IS-specific genes were enriched in calcium ion binding and protein glycosylation in GO term and glycolysis/gluconeogenesis and hypertrophic cardiomyopathy in KEGG pathway. CONCLUSION: IS and CS exhibit proteomic imbalance in bilateral paraspinal muscles but share few similarities. Paraspinal muscle imbalance in IS might not be the consequence of spinal deformities.

Does Progesterone Affect Perioperative Blood Loss during Posterior Spinal Fusion Surgeries in Female Patients with Adolescent Idiopathic Scoliosis? A Retrospective Study.

OBJECTIVE: Menstruation is considered a contraindication for elective surgery for higher operative blood loss. Progesterone is often used to postpone menstruation to avoid surgery during menstruation. This study aimed to explore whether using progesterone to postpone menstruation affects perioperative blood loss and complications in female patients with adolescent idiopathic scoliosis (AIS) who underwent posterior spinal fusion (PSF) surgery. METHODS: A retrospective study was performed for female patients diagnosed with AIS who underwent PSF surgery between March 2013 and January 2021. Patients scheduled to undergo PSF surgery from 2 days before menstruation to 3 days after menstruation were treated with progesterone preoperatively. The patients were divided into two groups according to progesterone use (progesterone injection group; control group). Demographic and surgical data including intraoperative blood loss (IBL), normalized blood loss (NBL), total blood loss (TBL), transfusion rate, perioperative complications, postoperative drainage time, postoperative hospital stay, and preoperative coagulation function data were collected. RESULTS: A total of 206 patients were included in the study. Among them, the progesterone injection group included 41 patients, with an average age of 14.8 years. While the control group included 165 patients, with an average age of 14.9 years. The two groups were matched for age, height, weight, operation time, Risser sign, correction rate, mean curve Cobb angle, bending Cobb angle, number of internal fixations, and number of fused levels (all P > 0.05). Regarding coagulation function, no significant differences were found in thrombin time, activated partial thromboplastin time, fibrinogen, prothrombin time, and platelet count between the two groups (all P > 0.05). IBL, NBL, and TBL were higher in progesterone injection group; however, the difference was nonsignificant (all P > 0.05). Transfusion rate, perioperative complications, postoperative drainage time, and postoperative hospital stay were not statistically different between groups (all P > 0.05). CONCLUSION: Intramuscular injection of progesterone to avoid menstruation during PSF surgery did not affect perioperative blood loss and complications in AIS patients. It may be a safe method for AIS patients to avoid menstrual problems affecting the operation time and receive PSF surgery as scheduled.

Review: Application of chitosan and its derivatives in medical materials.

Chitin is a natural polymeric polysaccharide extracted from marine crustaceans, and chitosan is obtained by removing part of the acetyl group (usually more than 60 %) in chitin's structure. Chitosan has attracted wide attention from researchers worldwide due to its good biodegradability, biocompatibility, hypoallergenic and biological activities (antibacterial, immune and antitumor activities). However, research has shown that chitosan does not melt or dissolve in water, alkaline solutions and general organic solvents, which greatly limits its application range. Therefore, researchers have carried out extensive and in-depth chemical modification of chitosan and prepared a variety of chitosan derivatives, which have expanded the application field of chitosan. Among them, the most extensive research has been conducted in the pharmaceutical field. This paper summarizes the application of chitosan and chitosan derivatives in medical materials over the past five years.

Glycol-Split Heparin-Linked Prodrug Nanoparticles Target the Mitochondrion Apparatus for Cancer Metastasis Treatment.

The progression and metastasis of solid tumors rely strongly on neovascularization. However, angiogenesis inhibitors alone cannot meet the needs of tumor therapy. This study prepared a new drug conjugate (PTX-GSHP-CYS-ES2, PGCE) by combining polysaccharides (heparin without anticoagulant activity, GSHP), chemotherapeutic drugs (paclitaxel, PTX), and antiangiogenic drugs (ES2). Furthermore, a tumor-targeted prodrug nanoparticle delivery system is established. The nanoparticles appear to accumulate in the mitochondrial of tumor cells and achieve ES2 and PTX release under high glutathione and acidic environment. It has been confirmed that PGCE inhibited the expression of multiple metastasis-related proteins by targeting the tumor cell mitochondrial apparatus and disrupting their structure. Furthermore, PGCE nanoparticles inhibit migration, invasion, and angiogenesis in B16F10 tumor-bearing mice and suppress tumor growth and metastasis in vitro. Further in vitro and in vivo experiments show that PGCE has strong antitumor growth and metastatic effects and exhibits efficient anti-angiogenesis properties. This multi-targeted nanoparticle system potentially enhances the antitumor and anti-metastatic effects of combination chemotherapy and antiangiogenic drugs.

Optimization of protein removal process of Lonicera japonica polysaccharide and its immunomodulatory mechanism in cyclophosphamide-induced mice by metabolomics and network pharmacology.

In this study, TCA-n-butanol was chosen as the best deproteinization method for Lonicera japonica polysaccharide (LJP) by comparing the polysaccharide retention rate and the protein clearance rate of five different methods. The response surface methodology (RSM) based on the Box-Behnken design (BBD) was used to optimize the deproteinization conditions as follows: TCA: n-butanol = 1: 5.1, polysaccharide solution: (TCA-n-butanol) = 1: 2.8, and shook for 33 min. LJP could promote the thymus and spleen indexes of cyclophosphamide (CTX)-induced immune-deficient mice. Besides, the contents of cytokine interleukin-2 (IL-2) and hemolysin in mice serum were augmented after treatment with LJP. Based on serum metabolomics analysis, a total of 14 metabolites (VIP >1.0, FC >2 or FC <0.5, and p value < .05) were selected as the potential biological biomarkers related to the LJP for treating CTX-induced mice. After the pathway enrichment analysis, these metabolites were mainly involved in the relevant pathways of arginine biosynthesis, Citrate cycle, and other metabolic pathways. Network pharmacology further showed that there were 57 key targeting proteins in the intersection of the potential biological biomarkers and immunodeficiency-related targeting proteins according to protein-protein interactions analysis (PPI). The biological function analysis indicated that the potential biological processes were mainly associated with tricarboxylic acid (TCA) cycle, phospholipid metabolic process, metabolic process, and so on. In conclusion, serum metabolomics combined with network pharmacology could be helpful to clarify the immunomodulatory mechanism of LJP and provide a literature basis for further clinical research on the therapeutic mechanism of LJP.

Improved Principal Component Analysis (IPCA): A Novel Method for Quantitative Calibration Transfer between Different Near-Infrared Spectrometers.

Given the labor-consuming nature of model establishment, model transfer has become a considerable topic in the study of near-infrared (NIR) spectroscopy. Recently, many new algorithms have been proposed for the model transfer of spectra collected by the same types of instruments under different situations. However, in a practical scenario, we need to deal with model transfer between different types of instruments. To expand model applicability, we must develop a method that could transfer spectra acquired from different types of NIR spectrometers with different wavenumbers or absorbance. Therefore, in our study, we propose a new methodology based on improved principal component analysis (IPCA) for calibration transfer between different types of spectrometers. We adopted three datasets for method evaluation, including public pharmaceutical tablets (dataset 1), corn data (dataset 2), and the spectra of eight batches of samples acquired from the plasma ethanol precipitation process collected by FT-NIR and MicroNIR spectrometers (dataset 3). In the calibration transfer for public datasets, IPCA displayed comparable results with the classical calibration transfer method using piecewise direct standardization (PDS), indicating its obvious ability to transfer spectra collected from the same types of instruments. However, in the calibration transfer for dataset 3, our proposed IPCA method achieved a successful bi-transfer between the spectra acquired from the benchtop and micro-instruments with/without wavelength region selection. Furthermore, our proposed method enabled improvements in prediction ability rather than the degradation of the models built with original micro spectra. Therefore, our proposed method has no limitations on the spectrum for model transfer between different types of NIR instruments, thus allowing a wide application range, which could provide a supporting technology for the practical application of NIR spectroscopy.