AIM:To investigate the effect of paeoniflorin on the inflammatory response of diabetic retinopathy rats by regulating phosphatidylinositol-3 kinase/protein kinase B(PI3K/Akt)signaling pathway.METHODS: A total of 70 SPF male SD rats were selected, and 12 rats were randomly selected as the control group(normal saline gavage). The remaining 58 rats were fed with high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin(STZ)to establish diabetic rat models. Rats with diabetic retinopathy were randomly divided into model group(normal saline), paeoniflorin low-dose group(100 mg/kg paeoniflorin), paeoniflorin high-dose group(200 mg/kg paeoniflorin)and metformin group(100 mg/kg metformin), with 12 rats in each group. The body mass of the rats in each group were compared. HE staining was used to observe the pathological changes of the rat retina. Automatic biochemical analyzer was used to detect the levels of fasting blood glucose, glycosylated hemoglobin, serum high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), total cholesterol and triglyceride in the rats. Enzyme-linked immunosorbent assay was used to detect the levels of serum superoxide dismutase(SOD), reactive oxygen species(ROS), malondialdehyde(MDA), glutathione peroxidase(GSH-PX), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6)and interleukin-1β(IL-1β)in the rats. Western blot was used to detect the expressions of Occludin, p-PI3K, tight junction protein-1(ZO-1), p-Akt and VE-Cadherin in the rat retina.RESULTS: The expression levels of Occludin, ZO-1 and VE-cadherin in low-dose and high-dose paeoniflora groups were higher than those in the model group, while the expression levels of TNF-α, IL-6, IL-1β, p-PI3K and p-Akt in serum were lower than those in the model group. The high-dose group of paeoniflorin was significantly better than the low-dose group of paeoniflorin(all P<0.05).CONCLUSION: Paeoniflorin may reduce inflammatory response in diabetic retinopathy rats by inhibiting PI3K/Akt signaling pathway.

AIM:To investigate the effect of paeoniflorin on the inflammatory response of diabetic retinopathy rats by regulating phosphatidylinositol-3 kinase/protein kinase B(PI3K/Akt)signaling pathway.METHODS: A total of 70 SPF male SD rats were selected, and 12 rats were randomly selected as the control group(normal saline gavage). The remaining 58 rats were fed with high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin(STZ)to establish diabetic rat models. Rats with diabetic retinopathy were randomly divided into model group(normal saline), paeoniflorin low-dose group(100 mg/kg paeoniflorin), paeoniflorin high-dose group(200 mg/kg paeoniflorin)and metformin group(100 mg/kg metformin), with 12 rats in each group. The body mass of the rats in each group were compared. HE staining was used to observe the pathological changes of the rat retina. Automatic biochemical analyzer was used to detect the levels of fasting blood glucose, glycosylated hemoglobin, serum high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), total cholesterol and triglyceride in the rats. Enzyme-linked immunosorbent assay was used to detect the levels of serum superoxide dismutase(SOD), reactive oxygen species(ROS), malondialdehyde(MDA), glutathione peroxidase(GSH-PX), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6)and interleukin-1β(IL-1β)in the rats. Western blot was used to detect the expressions of Occludin, p-PI3K, tight junction protein-1(ZO-1), p-Akt and VE-Cadherin in the rat retina.RESULTS: The expression levels of Occludin, ZO-1 and VE-cadherin in low-dose and high-dose paeoniflora groups were higher than those in the model group, while the expression levels of TNF-α, IL-6, IL-1β, p-PI3K and p-Akt in serum were lower than those in the model group. The high-dose group of paeoniflorin was significantly better than the low-dose group of paeoniflorin(all P<0.05).CONCLUSION: Paeoniflorin may reduce inflammatory response in diabetic retinopathy rats by inhibiting PI3K/Akt signaling pathway.

Perilla frutescens (L.) Britt. is a characteristic oil crop rich in polyunsaturated fatty acids, particularly α-linolenic acid, which has important development and utilization value. The Dof transcription factor is one of the plant-specific transcription factor families, which is widely involved in important biological processes such as plant growth, development, and metabolic regulation. In order to explore the key Dof transcription factors involved in the oil biosynthesis and systematically analyze their regulatory mechanisms of P. frutescens seeds, a total of 56 PfDof gene family members were identified from the genome and transcriptome data of P. frutescens and classified into four subfamilies according to sequence characteristics. All PfDofs contained highly conserved C₂-C₂ zinc finger domains, with gene duplication being the primary mechanism driving their evolution and expansion. Genes within the same subgroup exhibited similar gene structures and conserved motifs. The 56 PfDofs were predicted as unstable hydrophilic proteins, with α-helixes and random coils as their predominant structural components. The RNA-seq results revealed that 11 PfDofs exhibited differential expression during different developmental stages of P. frutescens seeds. RT-qPCR was performed to further validate the expression patterns of these 11 members across various tissue samples (root, stem, leaf, and flower) of P. frutescens and at different developmental stages of its seeds. The results showed that PfDof29 exhibited the highest expression level in seeds, which was consistent with the transcriptome data. Subcellular localization studies demonstrated that PfDof29 was localized to the nucleus and had a transcriptional activation activity. Overexpression of PfDof29 in Nicotiana tabacum resulted in a significant increase in total oil content of tobacco leaves, accompanied by reductions in starch and soluble sugar content, while the protein content remained unchanged. Additionally, the metabolic balance between saturated and unsaturated fatty acids in the transgenic tobacco leaves was altered, with a significant increase in α-linolenic acid content. The expression levels of the fatty acid desaturase genes NtFAD2, NtFAD3, and NtFAD8 were significantly upregulated. A yeast one-hybrid assay revealed that PfDof29 could directly bind to the promoter region of PfFAD8, thereby regulating its expression. This study provides an initial understanding of the regulatory mechanisms of PfDof transcription factors in the synthesis and accumulation of oil in P. frutescens. These findings offer new insights into the enhancement of oil content and quality of P. frutescens seeds.
Transcription Factors/physiology* ; Perilla frutescens/metabolism* ; Plant Proteins/metabolism* ; Gene Expression Regulation, Plant ; alpha-Linolenic Acid/biosynthesis* ; Lipids/biosynthesis* ; Seeds/genetics*

Objective:To analyze the potential clinical biological factors influencing the major pathological response (MPR) to neoadjuvant immunochemotherapy in patients with resectable head and neck squamous cell carcinoma (HNSCC).Methods:This retrospective study enrolled patients with resectable HNSCC who underwent neoadjuvant immunochemotherapy at Sun Yat-sen University Cancer Center from June 1, 2019 to December 31, 2021. Binary logistic regression was used to analyze the correlation between clinical characteristics, inflammatory markers and MPR, and a nomogram model was constructed. The calibration curve and decision curve analysis were used to verify the predictive ability and accuracy of the nomogram model.Results:A total of 173 patients were included in the study, with 141 males and 32 females, aged from 22 to 83 years. After pathological assessment, the patients were divided into two groups: MPR group (108 cases) and non MPR group (65 cases). Logistics regression analysis indicated that the patients with HPV+oropharyngeal cancer, partial response or complete response by imaging assessment, low pre-treatment platelet/lymphocyte ratio, low pre-treatment C reactive protein/albumin ratio and lower pre-and post-treatment C reactive protein/albumin ratio difference were more likely to have MPR (all P<0.05). Nomogram model was constructed based on the above factors, with a C-index of 0.826 (95% CI: 0.760-0.892), and the calibration curve and decision curve analysis confirmed the prediction accuracy of the model. Conclusion:This study shows that many factors are related to MPR of patients with resectable HNSCC receiving neoadjuvant immunochemotherapy and the constructed nomogram model helps to develop personalized treatment strategies for the patients.

Objective To investigate the clinical efficacy of bone filling mesh bag combined with pedicle anchoring for the treatment of Stage Ⅲ reducible Kummell disease.Method The 35 paients with Stage Ⅲ reducible Kummell disease were treated with bone filling mesh bag combined with pedicle anchoring from January 2018 to December 2022.The operation Time,intraoperative blood lose,bone cement injection volume and surgical complications were recorded.The VAS score,ODI value,kyphosis Cobb angle and midline height of the injured vertebral were compared at preoperative,postoperative 1 day and last follow-up.Results All patients were followed up for 12-24 months[(15±3.5)months].Operation time was 35-63 min[(45±5.8)min],intraoperative blood loss was 10-35 ml[(20±5)ml],bone cement injection volume was 4.5-7.8 ml[(5.5±1.8)ml].There were 4 cases of bone cement leakage,there were 1 case of intervertebral leakage,2 cases of lateral leakage,1 case of anterior leakage and no patient with intracanal leakage.All bone cement leakage did not lead to clinical symptoms,bone cement poisoning and pulmonary embolism.No cement mass slip.All patients were followed up for 12 to 24 months[(15±3.5)months].VAS scores and Oswestry Disability Index(ODI)values were significantly lower on the first day after surgery than before surgery,with statistical significance(P＜0.05).The 3-month follow-up was slightly higher than that on the first day after surgery,and the difference was not statistically significant(P＞0.05).The midline height and Cobb Angle of the injured vertebra were measured by imaging.The height of the injured vertebra recovered significantly on the first day after operation,and the Cobb Angle decreased significantly,the difference was statistically significant(P＜0.05).The midline height of the injured vertebrae decreased and the Cobb Angle increased slightly at 3 months after the operation,but the difference was not statistically significant(P＞0.05).Conclusion In the the treatment of Stage Ⅲ reducible Kummell disease,Bone filling mesh bag combined with Pedicle anchoring have good clinical efficacy,which can significantly reduce the pain of patients,relieve clinical symptoms,improve spinal function,improve quality of life,and reduce the incidence of bone cement leakage and slippage.

Objective:To study the protective effect of alendronate combined with Lactobacillus rhamnosus on bone loss in ovariectomized mice.Methods:Fifty female C57BL/6 mice were divided into 5 equal groups ( n=10). Ovariotomy was performed in groups A, B, C and D while a sham operation was performed in group E. Group A was subjected to combined administration of alendronate and Lactobacillus rhamnosus, group B to administration of alendronate, group C to administration of Lactobacillus rhamnosus, and groups D and E to administration of physiological saline only. At 3 months after operation, all the mice were sacrificed to harvest their femurs. Micro CT scanning was performed to detect the bone mineral density (BMD), trabecular relative volume, bone surface area/bone volume, and trabecular thickness and number of trabecular bone. Three-point bending test was used to detect the maximum load, stiffness, ultimate load, Young＇s modulus, and fracture energy. Osteocalcin and alkaline phosphatase levels were measured using blood samples from the mice eyeballs. The 2 groups were compared in terms of all the above indexes. Results:The BMD [(669.87±67.87) mg/cm 3], maximum load [(14.35±0.75) N] and fracture energy [(1,497.43±38.29) J/m 2] in group A were significantly higher than those in group B [(520.07±9.01) mg/cm 3, (11.94±0.82) N and(1,277.61±35.12) J/m 2] and group C [(388.15±25.61) mg/cm 3, (11.10±0.93) N and (1,115.27±63.24) J/m 2] (all P<0.05). The osteocalcin level in group A [(22.25±1.78) ng/mL] was significantly higher than that in group B [(19.08±1.45) ng/mL] and group D [(19.33±1.66) ng/mL] (both P<0.05). The alkaline phosphatase level in group A [(83.21±9.69) ng/mL] was significantly lower than that in group C [(113.16±14.44) ng/mL] and group D [(137.96±14.01) g/mL] (both P<0.05). Conclusion:Alendronate combined with Lactobacillus rhamnosus may play a synergistic role in prevention of bone loss in ovariectomized mice, because combined administration of the two is more effective than administration of either of the two.

Background::The calcineurin inhibitor (CNI)-based immune maintenance regimen that is commonly used after renal transplantation has greatly improved early graft survival after transplantation; however, the long-term prognosis of grafts has not been significantly improved. The nephrotoxicity of CNI drugs is one of the main risk factors for the poor long-term prognosis of grafts. Sirolimus (SRL) has been employed as an immunosuppressant in clinical practice for over 20 years and has been found to have no nephrotoxic effects on grafts. Presently, the regimen and timing of SRL application after renal transplantation vary, and clinical data are scarce. Multicenter prospective randomized controlled studies are particularly rare. This study aims to investigate the effects of early conversion to a low-dose CNI combined with SRL on the long-term prognosis of renal transplantation.Methods::Patients who receive four weeks of a standard regimen with CNI + mycophenolic acid (MPA) + glucocorticoid after renal transplantation in multiple transplant centers across China will be included in this study. At week 5, after the operation, patients in the experimental group will receive an additional administration of SRL, a reduction in the CNI drug doses, withdrawal of MPA medication, and maintenance of glucocorticoids. In addition, patients in the control group will receive the maintained standard of care. The patients’ vital signs, routine blood tests, routine urine tests, blood biochemistry, serum creatinine, BK virus (BKV)/cytomegalovirus (CMV), and trough concentrations of CNI drugs and SRL at the baseline and weeks 12, 24, 36, 48, 72, and 104 after conversion will be recorded. Patient survival, graft survival, and estimated glomerular filtration rate will be calculated, and concomitant medications and adverse events will also be recorded.Conclusion::The study data will be utilized to evaluate the efficacy and safety of early conversion to low-dose CNIs combined with SRL in renal transplant patients.Trial registration::Chinese Clinical Trial Registry, ChiCTR1800017277.

Nanomaterial-based drug sustainable release systems have been tentatively applied to bone regeneration. They, however, still face disadvantages of high toxicity, low biocompatibility, and low drug-load capacity. In view of the low toxicity and high biocompatibility of polymer nanomaterials and the excellent load capacity of hollow nanomaterials with high specific surface area, we evaluated the hollow polydopamine nanoparticles (HPDA NPs), in order to find an optimal system to effectively deliver the osteogenic drugs to improve treatment of bone defect. Data demonstrated that the HPDA NPs synthesized herein could efficiently load four types of osteogenic drugs and the drugs can effectively release from the HPDA NPs for a relatively longer time in vitro and in vivo with low toxicity and high biocompatibility. Results of qRT-PCR, ALP, and alizarin red S staining showed that drugs released from the HPDA NPs could promote osteogenic differentiation and proliferation of rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. Image data from micro-CT and H&E staining showed that all four osteogenic drugs released from the HPDA NPs effectively promoted bone regeneration in the defect of tooth extraction fossa in vivo, especially tacrolimus. These results suggest that the HPDA NPs, the biodegradable hollow polymer nanoparticles with high drug load rate and sustainable release ability, have good prospect to treat the bone defect in future clinical practice.
Animals ; Bone Regeneration ; Indoles ; Nanoparticles ; Osteogenesis ; Pharmaceutical Preparations ; Polymers ; Rats

Objective : To investigate the clinicopathological features and survival rate of oral squamous cell carcinoma patients in China. Methods: The clinicopathological characteristics, stage, treatment modality, and 5-year disease-specific survival (DSS) rate of 1 915 OCSCC patients who received initial treatment at the Sun Yat-sen University Cancer Center from 1990 to 2013 were collected and analyzed. The clinicopathological characteristics, stage, treatment modality, and 5-year disease-specific survival (DSS) rate of OCSCC patients treated during the successive decades of 1990-1999, 2000-2009, and 2010-2013 were analyzed retrospectively to show the trends over time. Results : The average age of all OCSCC patients who received initial treatment at this cancer center from 1990 to 2013 was 54.8 years (SD, 12.6 years). The sex ratio was approximately 2:1. The oral tongue was the site most prone for OCSCC, accounting for 63.6% of all cases. The proportions of early-stage (Ⅰ-Ⅱ) and advanced-stage (Ⅲ-Ⅳ) cases were approximate. Regarding the treatment modality, surgery-based treatment accounted for 80.4%. Survival analysis showed that the 5-year DSS rate of all cases was 57%. Survival decreased with age. The survival of females, nonsmokers, and nondrinkers was higher than that of males, smokers, and drinkers. The 5-year DSS rates of patients with squamous cell carcinoma of the lips, oral tongue, and other sites of the oral cavity were 81%, 63%, and 42%, respectively. The 5-year DSS rates of patients who received surgery-based treatment and nonsurgical treatment were 66% and 19%, respectively. The analysis of trends over time showed that in the period of 1990-1999 and 2010-2013, the age and sex ratio were relatively stable. The proportion of patients with squamous cell carcinoma of the lips and oral tongue gradually decreased, while the proportion of those with squamous cell carcinoma of the other sites of the oral cavity gradually increased. The proportion of surgery-based treatment increased from 77.7% to 91.3%. The 5-year DSS rate gradually increased from 53% in 1990-1999 to 64% in 2010-2013. The 5-year DSS rate of female patients increased significantly from 55% to 78%. However, the 5-year DSS rate of male patients was relatively stable. The 5-year DSS rate of patients who received surgery-based treatment gradually increased from 62% to 69%. Conclusion The 5-year DSS rate has steadily improved for OCSCC patients at this cancer center from 1990-2013, especially in female patients. The 5-year DSS rate of patients with squamous cell carcinoma of the oral tongue has reached the rate in developed countries worldwide. The proportion and survival rate of patients who received surgery-based treatment gradually increased. The survival rate of patients with squamous cell carcinoma of the other sites of the oral cavity was significantly lower than that of patients with squamous cell carcinoma of the lips and oral tongue, suggesting that more effort should be put into the treatment of patients with squamous cell carcinoma of the other sites of the oral cavity to improve the survival rate in the future.

Objective To explore the clinical effect of training assisted by a lower limb rehabilitation robot on the bladder and intestinal function of paraplegic spinal cord injury survivors. Methods Thirty-eight paraplegic patients with spinal cord injury were divided according to their admission order into an experimental group ( n=19) and a control group (n=19). Both groups were given conventional rehabilitation training, while the experimental group was additionally provided with robot-assisted lower limb training in three stages:adaptation, training and con-solidation. It lasted 30 minutes daily, 5 days per week for 12 weeks. Before and after the training, an urodynamics examination system was used to evaluate the maximum urine flow, bladder capacity, residual urine volume, bladder pressure and detrusor pressure. Colon transit time, mean rectal pressure and intestinal function were measured using the colon transit test, a mean rectal pressure test, and the Functional Independence Measure ( FIM) scale respective-ly. Results The average bladder volume, maximum urine flow rate, average urine flow rate, detrusor pressure, bladder compliance, average rectal pressure and intestinal FIM score of the robot training group after training were all significantly better than before the training, as were the average residual urine volume and colon transit time. After the training, the average bladder volume, maximum urine flow rate, average urine flow rate, detrusor pressure, bladder compliance and average rectal pressure of the robot training group were all significantly higher than those of the control group, while the average residual urine volume and colon transit time were significantly smaller. Then, 32％ of the patients in the experimental group achieved no less than 6 points for their average FIM score, significantly higher than in the control group. Conclusion Robot-assisted lower limb training combined with comprehensive rehabilitation training can effectively improve the bladder and intestinal function of paraplegic patients after a spinal cord injury.