OBJECTIVE: To evaluate the safety and effectiveness of anterior cervical discectomy and fusion (ACDF) by using zero-profile anchored cage (ZAC) in treatment of consecutive three-level cervical spondylosis, by comparing with plate-cage construct (PCC). METHODS: A clinical data of 65 patients with cervical spondylosis admitted between January 2020 and December 2022 and met the selection criteria was retrospectively analyzed. During consecutive three-level ACDF, 35 patients were fixed with ZAC (ZAC group) and 30 patients with PCC (PCC group). There was no significant difference in baseline data between the two groups ( P>0.05), including gender, age, body mass index, surgical segment, preoperative Japanese Orthopaedic Association (JOA) score, Neck Disability Index (NDI), visual analogue scale (VAS) score, prevertebral soft tissue thickness (PSTT), cervical lordosis, and surgical segmental angle. The operation time, intraoperative blood loss, hospital stay, clinical indicators (JOA score, NDI, VAS score), and radiological indicators (cervical lordosis, surgical segmental angle, implant subsidence, surgical segment fusion, and adjacent segment degeneration), and the postoperative complications [swelling of the neck (PSTT), dysphagia] were recorded and compared between the two groups. RESULTS: Patients in both groups were followed up 24-39 months. There was no significant difference in follow-up duration between the two groups ( P>0.05). The operation time and intraoperative blood loss were lower in ZAC group than in PCC group, and the length of hospital stay was longer, but there was no significant difference ( P>0.05). At each time point after operation, both groups showed significant improvements in JOA score, VAS score, and NDI compared with preoperative scores ( P<0.05), but there was no significant difference between the two groups at each time point after operation ( P>0.05). Both groups showed an increase in PSTT at 3 days and 3, 6 months after operation compared to preoperative levels ( P<0.05), but returned to preoperative levels at last follow-up ( P>0.05). The PSTT at 3 days and 3 months after operation were significantly lower in ZAC group than in PCC group ( P<0.05), and there was no significant difference between the two groups at 6 months and at last follow-up ( P>0.05). The incidences of dysphagia at 3 days and 3 months were significantly lower in ZAC group than in PCC group ( P<0.05), while no significant difference was observed at 6 months and last follow-up between the two groups ( P>0.05). There was no postoperative complication in both groups including hoarseness, esophageal injury, cough, or hematoma. Both groups showed improvement in cervical lordosis and surgical segmental angle compared to preoperative levels, with a trend of loss during follow-up. The cervical lordosis loss and surgical segmental angle loss were significantly more in the ZAC group than in PCC group ( P<0.05). The incidence of implante subsidence was significantly higher in ZAC group than in PCC group ( P<0.05). There was no significant difference between the ZAC group and PCC group in the incidences of surgical segment fusion and adjacent segment degeneration ( P>0.05). CONCLUSION In consecutive three-level ACDF, both ZAC and PCC can achieve satisfactory effectiveness. The former can reduce the incidence of postoperative dysphagia, while the latter can better maintain cervical curvature and reduce the incidence of implant subsidence.
Humans ; Spondylosis/surgery* ; Cervical Vertebrae/surgery* ; Spinal Fusion/instrumentation* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Diskectomy/instrumentation* ; Bone Plates ; Treatment Outcome ; Adult ; Aged ; Internal Fixators ; Operative Time ; Length of Stay

GPCRs are the largest membrane protein receptor superfamily in the human body, with more than 800 isoforms, and approximately 35% of Food and Drug Administration-approved and marketed drugs currently target GPCRs for the treatment of a wide range of diseases, for heart failure (beta-adrenergic receptors), peptic ulcer (histamine receptors), prostate cancer (gonadotropin receptors), hypertension (adrenergic and angiotensin receptors), pain (opioid receptors), and bronchial asthma (beta2-adrenergic receptors) examples. Although the number of GPCRs is enormous, the signaling proteins downstream of them are limited, heterotrimeric G proteins (GPs) are key proteins that signal GPCRs, translate extracellular stimuli into intracellular responses by coupling to GPCRs and initiate multiple signaling events via downstream cascades. Podocytes are an important component of the glomerular filtration barrier, and their damage is a central event in proteinuria formation and progressive glomerulosclerosis. This article reviews the regulation of GPs, their signaling and their role in podocyte injury to provide a theoretical basis for scientific research and clinical treatment of this disease.

BACKGROUND:The most prominent transcription factor activated by tumor stem cells in osteosarcoma is EZH2,and silencing of EZH2 has been reported to inhibit osteosarcoma cell growth.Studies have confirmed that bovine serum albumin-chitosan nanoparticles are a drug delivery vector with excellent biocompatibility and biodegradability,and the albumin carrier can provide tumor-targeted drug delivery function. OBJECTIVE:To investigate the effect and mechanism of bovine serum albumin-chitosan nanoparticles loaded with EPZ6438(EZH2 inhibitor)for the treatment of osteosarcoma. METHODS:(1)Bovine serum albumin-chitosan nanoparticles loaded with and without EPZ6438 were prepared.The drug encapsulation rate and drug release rate of serum albumin-chitosan nanoparticles loaded with EPZ6438 were detected.(2)MG-63 cells were divided into four groups and added with PBS(control group),serum albumin-chitosan nanoparticle extract solution(blank nanoparticle group),EPZ6438 solution(free drug group),and serum albumin-chitosan nanoparticle extract loaded with EPZ6438(drug-loaded nanoparticle group),respectively.After 3 days of culture,cell apoptosis was detected by flow cytometry and the expression of caspase-3 mRNA was detected by RT-PCR.(3)Twelve nude mice were selected and the subcutaneous tumor-bearing mouse model was established by injecting MG-63 cell suspension under the armpit.After successful modeling,the mice were randomly divided into four groups for intervention.Normal saline(control group),serum albumin-chitosan nanoparticle solution(blank nanoparticle group),EPZ6438 solution(free drug group)and serum albumin-chitosan nanoparticle solution loaded with EPZ6438(drug-loaded nanoparticle group)were injected into tumor tissues,with three animals in each group.After 7 days of injection,the tumor volume and frozen sections of tumor tissue were observed by TUNEL staining. RESULTS AND CONCLUSION:(1)The drug encapsulation rate of the nanoparticles was about 8.8%,and the nanoparticles had a good drug release effect in pure water.The drug release amount was(34.72±1.93)μg at 24 hours,(48.58±1.10)μg at 72 hours,(49.18±1.24)μg at 120 hours,and(50.25±1.13)μg at 168 hours.The drug release reached the plateau at 120 hours,and the release rate was about 97.9%.(2)After 3 days of cell culture with MG-63,the apoptotic rate in the control group and blank nanoparticle group was lower than that in the free drug group and drug-loaded nanoparticle group(P<0.001),and the expression of caspase 3 mRNA was lower than that in the free drug group and drug-loaded nanoparticle group(P<0.000 1).(3)After 7 days of injection,the tumor volume of nude mice in the drug-loaded nanoparticle group was smaller than that in the other three groups(P<0.05),and the percentage of TUNEL-positive cells in tumor tissue was higher than that in the other three groups(P<0.000 1).(4)The results verify that serum albumin-chitosan nanoparticles loaded with EPZ6438 can inhibit the growth of osteosarcoma by inducing apoptosis of tumor cells.

Objective To investigate the interventional effects of Icariin(IC A)combined with prednisone acetate tablets(PAT)in rats with steroid-resistant nephrotic syndrome(SRNS)model.Methods Male SD rats were used to construct the SRNS model with 2 injections of adriamycin(ADR),and were randomly divided into the model group,PAT group,ICA group,and the combined group,with 10 rats in each group after successful modeling;another 10 rats were taken as the blank group.The blank and model groups were given 0.9％NaCl;the PAT group was given 6.3 mg·kg-1·d-1 PAT;the ICA group was given 50 mg·kg-1·d-1 ICA;and the combined group was given 6.3 mg·kg-1·d-1 PAT+50 mg·kg-1·d-1 ICA.The volume of gavage of the five groups of rats was 1 mL·100 g-1,and the drug was administered once a day for 6 weeks.The renal function and blood lipid level of rats in each group were compared;the expression of calcium/calmodulin dependent protein kinase Ⅱ α(CaMK Ⅱα),cofilin-1 and F-actin were detected by Western blotting.Results Urinary protein quantification values at 8 weeks in blank,model,PAT,ICA and combined groups were(6.66±1.48),(178.38±8.96),(161.56±5.49),(157.13±8.32)and(96.90±5.05)mg·24 hi-1;serum creatinine levels were(30.90±1.79),(41.10±2.77),(34.90±2.03),(35.10±2.18)and(31.90±2.47)μmol·L-1;triglycerides levels were(0.87±0.14),(2.30±0.41),(1.94±0.44),(1.17±0.59)and(0.89±0.30)mmol·L-1;total cholesterol levels were(1.54±0.08),(2.53±0.22),(2.14±0.59),(2.27±0.31)and(1.93±0.32)mmol·L-1;the relative expression levels of CaMK Ⅱ α proteins were 0.88±0.09,0.65±0.06,0.71±0.08,0.76±0.07 and 0.88±0.08;the p-Cofilin-1/Cofilin-1 ratios were 0.56±0.27,2.52±0.04,0.75±0.02,0.91±0.20 and 0.53±0.05;the relative expression levels of F-actin protein were 0.93±0.01,0.64±0.01,0.75±0.02,0.80±0.01 and 0.85±0.00,respectively.The differences of the above indexes in the model group were statistically significant compared with those in the blank group and the combined group(all P＜0.05).Conclusion ICA combined with PAT can improve renal function,lipid levels,improve renal histopathological structure,and promote skeletal protein remodeling in SRNS rats by regulating CaMK Ⅱ α/Cofilin-1/F-actin pathway.

Renal fibrosis is a common pathological manifestation of all chronic kidney diseases.Ferroptosis is closely related to the pathogenesis of renal fibrosis and can influence the onset of renal fibrosis,and it is the most critical step in the development of renal fibrosis.The paper describes the relationship between ferroptosis and renal fibrosis,discusses the research progress of ferroptosis on renal fibrosis,and further summarizes,analyzes,and describes the effective and highly targeted natural active ingredients of traditional Chinese medicines against ferroptosis,and concludes that the reversal of renal fibrosis is achieved through the regulation of the key targets of ferroptosis,with a view to providing a broad new direction for its prospects in the field of renal fibrotic disease prevention and treatment;and to provide a scientific guide for clinical treatment and basis for clinical treatment.

Objective To study the common basis and association between sickness behaviour and occurrence of classical symptoms of kidney yang deficiency of rats with adriamycin nephropathy.Methods The SD rats were given adriamycin by tail-vein injection for 2 times(4.0 and 3.5 mg·kg-1,one week apart)to construct the model of nephrotic syndrome with Chinese medicine symptom of kidney yang deficiency.After successful modeling,the model rats were randomly divided into adriamycin group(ADR group),corticosterone group(CORT group)and hydrocortisone group(HYD group),with 12 rats per group;another 12 normal rats were taken as normal group.In the HYD group,25 mg·kg-1·d-1 HYD was administered for 14 d to establish kidney yang deficiency model with simple hypothalamus-pituitary-adrenal cortex(HPA)axis inhibition.CORT group was adding 25 μg·mL-1 corticosterone to the water for 6 weeks,and the others drinking water supplied.The levels of urinary 17-hydroxy steroid were measured by enzyme linked immunosorbent assay.Glucocorticoid receptor(GR)and nuclear factor-kappa B(NF-κB)protein expression levels in kidney and hypothalamus were detected by Western blotting.Results In the normal,ADR,CORT and HYD groups,the urinary 17-hydroxysteroid levels were(19.14±1.94),(10.07±1.62),(20.30±1.55)and(14.23±2.37)μg·L-1;the relative expression levels of GR protein in hypothalamic were 0.63±0.05,0.11±0.05,0.85±0.08 and 0.35±0.06;the relative expression levels of NF-κB protein in hypothalamic were 0.06±0.03,0.96±0.03,0.59±0.01 and 0.23±0.04;the relative expression levels of GR protein in kidney tissue were 0.94±0.06,0.06±0.02,0.40±0.02 and 0.09±0.08;the relative expression levels of NF-κB protein in kidney tissue were 0.07±0.05,0.81±0.12,0.72±0.07 and 0.49±0.08,respectively.Compared with the ADR and HYD groups,the above indexes in the normal group were statistically significant(P＜0.05,P＜0.01).And compared with the ADR group,the relative expression levels of NF-κB protein in renal tissue with CORT group were not statistically significant(P＞0.05),but the other indexes in CORT group were statistically significant(all P＜0.01).Conclusion HPA axis dysfunction with GR damaged and activated inflammatory levels are the common basis for the combination of typical symptoms of kidney yang deficiency and sickness behaviour which characterised by"deficiency and cold syndrome".

Polysaccharides are the main active ingredients in traditional Chinese medicine and ideal raw materials for new drug development with diverse structures,rich activity and low toxicity.Research has shown that traditional Chinese medicine polysaccharides(TCMP)exhibit outstanding associated activities in anti-tumor,immunomodulatory,anti-fibrotic,and Alzheimer's disease prevention,with clear mechanisms and targeting properties.In this review,we discuss research progress of the mechanisms and discovery of target molecules of TCMP in various areas,including anticancer,immunomodulation,gut microbiota regulation,anti-fibrosis,and Alzheimer's disease prevention.By analyzing relevant literature,it has been observed that TCMP exhibits various complex mechanisms of action,highlighting significant targeting properties in immunomodulation,anticancer effects and disrupts angiogenesis activities.At the same time,this review summarizes and analyzes the current shortcomings and challenges in the research on TCMP and proposes future directions,aiming to provide new ideas and strategies for understanding the basis of active substances in traditional Chinese medicine and the development of original new drugs based on polysaccharides.

Objective This study aims to investigate the structure and anti-angiogenic activity of homogeneous polysaccharides in Honeysuckle flowers,constructing the theoretical basis for its widespread application.Methods Homogeneous Honeysuckle polysaccharide LF-02-2 was obtained through water extraction,alcohol precipitation,anion exchange chromatography,and gel permeation chromatography.The structure of LF-02-2 was deduced through molecular weight determination,monosaccharide composition analysis,sugar residue linkage analysis,partial acid hydrolysis,and sugar aldonic acid reduction combined with NMR data.Additionally,in vitro tube formation experiments using human microvascular endothelial cells(HMEC-1)were conducted to assess its anti-angiogenic activity.Results Structural analysis of LF-02-2 revealed a homogeneous polysaccharide with a weight-average molecular weight of 74.1 kDa.The monosaccharide composition included rhamnose(Rha),galactose(Gal),galacturonic acid(GalA),and arabinose(Ara)in molar ratios of 10.43:14.94:6.66:67.97.The main chain consisted of 1,4-linked α-Galp A,1,2-linked α-Rhap,and 1,2,4-linked α-Rhap.Branches were connected to O-4 of 1,2,4-linked α-Rhap and included β-Galp with terminal connections and 1,4,6-linked β-Galp and α-Araf with terminal and 1,5-linked connections.Tube formation experiments demonstrated that LF-02-2 significantly inhibited tube formation in human microvascular endothelial cells(HMEC).Conclusion LF-02-2,an RG-I pectic polysaccharide from Honeysuckle flowers,exhibited significant anti-angiogenic activity,suggesting its potential for development as an anti-angiogenic drug.

Objective This study aims to elucidate the structure-activity domain of LBP1C-2 targeting Kvβ.2 through an exploration of the structure-activity relationship.This study may also provide the scientific basis for the development of drug candidate with anti-early-onset dementia activity.Methods After partial acid hydrolysis,various structural fragments were obtained and subjected to monosaccharide composition and molecular weight analysis.Potential target proteins were selected using a protein chip,followed by validation of the targeting specificity of each structural fragment using surface plasmon resonance(SPR)technology.Results Through high-throughput screening using the HuProtTM human protein array,potential target protein Kvβ.2 was identified for LBP1C-2.SPR experiments revealed a strong binding affinity between LBP1C-2 and Kvβ.2 protein,with a binding constant(KD)of 1.9×10-7 M.The various structural fragments of LBP1C-2 exhibited different binding strengths with the target protein Kvβ.2.Among them,the segment LBP1C-2-1I(18.1 k Da)with a molar ratio of rhamose to galecturonic acid of 1:1 showed a binding strength to Kvβ.2 similar to that of the polysaccharide LBP1C-2,with a KD of approximately 3.3×10-7 M.Structural analysis indicates that the structure of LBP1C-2-1I contains 1,2-linked Rha and 1,4-linked GalA which are alternatively linked.The acid-hydrolyzed extracellular portion corresponding to this segment,LBP1C-2-1O may also bind to Kvβ.2.However,compared to other segments,it demonstrated a higher tendency to dissociate from the protein.Knockdown of the KCNAB2 gene(Kvβ.2)in BV2 cells inhibited the uptake of Aβ in BV2 cells,suggesting that protein Kvβ.2 may be a functional protein in the development of Alzheimer's disease.Conclusion LBP1C-2-1I has been identified as the primary active domain through which LBP1C-2 targets Kvβ.2.This suggests that the active domain of LBP1C-2 predominantly resides on the main chain rather than the side chain.This study provides crucial insights for a deeper understanding of the anti-early-onset dementia activity of LBP1C-2 and lays an experimental foundation for the design and development of targeted drugs for anti-early-onset dementia based on Lycium barbarum polysaccharides.

Objective To elucidate the structural basis of polysaccharides with hypoglycemic activity in mulberry leaves,and provide a theoretical basis for the development and utilization of mulberry leaves.Methods The crude polysaccharides from mulberry leaves were extracted by hot water.The components of SY02,SY02-3,SY02-3A and SY02-3B were obtained by ion-exchange chromatography and gel permeation chromatography.We determined the physicochemical properties of homogeneous polysaccharide.The structure of mulberry leaf polysaccharide was identified by monosaccharide composition analysis,sugar residue linkage analysis and nuclear magnetic analysis.Palimitate(PA)induced INS-1 cell apoptosis model was used to determine the protective effect of mulberry leaf polysaccharide on INS-1E cell apoptosis,and Caspase3/7 activity kit was used to detect mulberry leaf polysaccharide on the key protein of INS-1E cell apoptosis Cleaved by Western blot method effect of Caspase 3 expression.Results The crude polysaccharide SY was extracted from mulberry leaves by hot water,which was separated by ion exchange resin column and purified by gel column to obtain SY02-3.After purification,we obtained homogeneous polysaccharide SY02-3A and proteoglycan SY02-3B,with molecular weights of 3.7×104 Da and 1.03×104 Da.The results of monosaccharide composition analysis showed that SY02-3A contained rhamnose,galacturonic acid,galactose,xylose and arabinose.The molar ratio of SY02-3A was 23.97:33.85:11.73:5.04:25.41,and the yield was 0.32%.SY02-3B is composed of rhamnose,galacturonic acid,glucose,galactose and arabinose.The molar ratio of SY02-3B is 19.83:10.34:45.42:9.01:2.23:13.17 with a yield of 2.00%.SY02-3B contains 14 amino acids,among which the content of aspartate,glutamic acid,alanine and glycine is relatively high.We also found that SY02-3 protects palmitic acid-induced INS-1E cell apoptosis,which may be associated with reduced Caspase 3 activity and down-regulated cleaved Caspase 3 protein expression.Conclusion Mulberry leaf polysaccharide SY02-3,which contains acid peptidoglycan(SY02-3A)and proteoglycan(SY02-3B)in mulberry leaves,has the effect of inhibiting PA-induced apoptosis of INS-1E cells.