ObjectiveTo investigate the role of Krüppel-like factor 4 （KLF4） in type 1 diabetic nephropathy （DN） and to elucidate its underlying mechanisms. MethodsSixteen male Sprague-Dawley （SD） rats were selected and randomly divided into control group and model group， with 8 rats in each group. Rats in model group were intraperitoneally injected with a single dose of 55 mg/kg streptozotocin （STZ） to establish a diabetic nephropathy （DN） model， while those in control group were injected with an equal volume of sodium citrate buffer at the same time. After successful model establishment， the serum levels of blood urea nitrogen （BUN） and serum creatinine （SCR） were determined. Hematoxylin-eosin （HE） staining was performed on renal tissues to observe pathological changes， and immunofluorescence staining was conducted to detect the expression of KLF4 in renal tissues. Lipid peroxidation levels were evaluated by measuring malondialdehyde （MDA）， Fe²⁺， and lipid peroxidation products in rat kidneys. A high glucose （HG）-induced cell injury model was established in HK-2 cells， with mitochondrial membrane potential assessed using 5，5'，6，6'-tetrachloro-1，1'，3，3'- tetraethylbenzimidazolylcarbocyanine iodide （JC-1） staining. Lipid peroxidation levels （MDA， Fe²⁺， and lipid peroxides） were measured in HK-2 cells.KLF4-overexpressing HK-2 cells were then constructed， followed by repeated JC-1， MDA， Fe²⁺， and lipid peroxidation assays. Western blot was performed to evaluate the expression of ferroptosis-related proteins including glutathione peroxidase 4 （GPX4）， nuclear factor erythroid 2-related factor 2 （NRF2）， and Kelch-like ECH-associated protein 1 （Keap1）， in renal tissues， HK-2 cells， and KLF4-overexpressing HK-2 cells. ResultsCompared with the control group， DN rats exhibited elevated serum BUN and SCR levels， glomerular hypertrophy， renal interstitial fibrosis， and decreased KLF4 expression. Additionally， MDA， Fe²⁺， and lipid peroxidation levels increased， indicating enhanced ferroptosis in renal tissues， accompanied by reduced GPX4 and NRF2 expression and elevated Keap1 levels. Similarly， HG-treated HK-2 cells showed decreased KLF4 expression， increased MDA， Fe²⁺ and lipid peroxidation， elevated ferroptosis， and dysregulated GPX4/NRF2/Keap1 expression. However， KLF4 overexpression reversed these alterations induced by high glucose treatment. ConclusionIn the renal tissues of type 1 diabetic rats， the expression of KLF4 decreases the level of ferroptosis increases， and KLF4 overexpression could alleviate HG-induced HK-2 cell injury.

Objective To investigate the effect of4-amino-2-trifluoromethyl-phenyl retinate(ATPR)on acute liver injury induced by lipopolysaccharide(LPS)in C57BL/6 mice and its related mechanism.Methods Fifteen 6-week-old male C57BL/6 strain mice were randomly divided into normal group,model group and ATPR group,with 5 mice in each group.Mice in the ATPR group were intraperitoneally injected with ATPR(15 mg/kg·d),and normal group and model group were given solvent.After continuous administration for one week,model group and ATPR group were intraperitoneally injected with LPS(6 mg/kg),and all mice were sacrificed 6 hours later.The contents of Alanine aminotransferase(ALT)and Aspartate aminotransferase(AST)in serum of mice were detec-ted.The mRNA levels of Interleukin-6(IL-6)and Tumor necrosis factor-alpha(TNF-α)were detected by qPCR.Hematoxylin-eosin(H&E)staining was used to observe the histopathological changes of liver in mice.The ultra-structural changes of mouse hepatocytes were observed by Transmission electron microscope(TEM).The expres-sion levels of mitochondrial damage-related proteins FUNDC1 and OPA1 and autophagy related proteins LC3B,P62,Beclin1 and ATG5 were detected by Western blot.Results Compared with the normal group,the content of ALT and AST in serum and the mRNA levels of IL-6 and TNF-α in liver tissue increased in the model group,and the changes were reversed in the ATPR group.H&E staining showed that the hepatic lobule structure was normal in the normal group,the hepatic cords were arranged radially,there was no hyperemia and inflammatory cell infiltra-tion,and the hepatocyte boundary was clear.In the model group,the intercellular space of liver was enlarged,the arrangement of hepatic cords was disordered,and inflammatory cells infiltrated.In the ATPR group,the intercellu-lar space of liver and the structure of hepatic cords were restored,and the inflammatory cell infiltration was less.TEM showed that the damaged mitochondria and lipid droplet accumulation in the hepatocytes of mice in the model group were compared with that in the normal group,and the morphology and quantity of mitochondria and lipid droplet in the hepatocytes of mice in the ATPR group tended to be normal.Western blot showed that compared with the normal group,the expression of FUNDC1 protein in the liver tissues of mice in the model group increased,the expression of OPA1 protein decreased,the ratio of LC3B Ⅱ to LC3B Ⅰ decreased,the expression of P62 protein in-creased,the expression of Beclin1 and ATG5 protein decreased,and the above changes were reversed in the ATPR group.Conclusion ATPR alleviates acute liver injury induced by lipopolysaccharide in mice by promoting autoph-agy.

In the field of dental aesthetics,digital aesthetic design plays a crucial role in helping dentists to predict treatment outcomes vis-ually,as well as in enhancing the consistency of knowledge and understanding of aesthetic goals between dentists and patients.It serves as the foundation for achieving ideal aesthetic effects.However,there is no clear standard for this digital process currently in China and abroad.Many dentists lack of systematic understanding of how to carry out digital aesthetic design for treatment.To establish standardized processes for dental aesthetic design and to improve the homogeneity of treatment outcomes,Chinese Society of Digital Dental Industry(CSD-DI)convened domestic experts in related field to compile this consensus.This article elaborates on the key aspects of digital aesthetic data collection,integration steps,and the digital aesthetic design process.It also formulates a decision tree for dental aesthetics at macro level and outlines corresponding workflows for various clinical scenarios,serving as a reference for clinicians.

As a threat to human health， steroid-induced osteonecrosis of femur head is a common refractory orthopedic disease mainly caused by glucocorticoids， with poor prognosis and unclear pathogenesis. Osteogenesis-associated signaling pathways play an important role in bone formation. Glucocorticoid-induced abnormal activation and transport of these signaling pathways lead to abnormal differentiation of bone marrow mesenchymal stem cells， dysfunction of bone metabolism， and osteogenesis disorders， which may be the main reasons for the occurrence and development of steroid-induced osteonecrosis of femur head. Bone formation and remodeling need the participation of bone marrow mesenchymal stem cells， which are stem cells characterized by continuous self-renewal and differentiation. The key to strengthening bone remodeling is to improve the osteogenic differentiation capacity， which is the key point to inhibit bone resorption and prevent bone marrow mesenchymal stem cells from differentiating into osteoclasts. Traditional Chinese medicine （TCM） has been used in the treatment of osteonecrosis in ancient times. It is recorded in the Treasury of Words on Materia Medica （《本草汇编》） that "The deficiency in the lower energizer cannot be tonified without Eucommiae Cortexz.The soreness in lower legs cannot be alleviated without Eucommiae Cortex...The pain in the waist and knee cannot be relieved without Eucommiae Cortex...Tonifying liver and invigorating kidney， Eucommiae Cortex is an essential medicine." This indicates that ancient physicians have already begun to use the liver-tonifying， kidney-invigorating， and sinew-bone-strengthening effects of Eucommiae Cortex for the treatment of osteonecrosis. As the national support for the development of TCM strengthens， increasing studies have been conducted on the TCM prevention and treatment of steroid-induced osteonecrosis of femur head. Studies have suggested that Chinese medicinal herbs can exert a positive effect on the differentiation of bone marrow mesenchymal stem cells by affecting targeted signaling molecules， and promote osteogenesis and bone defect repair， thus combating the occurrence and development of steroid-induced osteonecrosis of femur head. The regulation of osteogenic signaling pathway by Chinese medicines to prevent steroid-induced osteonecrosis of femoral head has become a hot research topic. This article reviews the studies about the prevention and treatment of steroid-induced osteonecrosis of femur head with the active components in Chinese medicinal herbs by regulating osteogenic signaling pathways. We then explore the mechanism of the active components in promoting the differentiation of bone marrow mesenchymal stem cells into osteoblasts and inhibiting their differentiation into osteoclasts to facilitate bone formation， aiming to provide a reference for the further study of treating steroid-induced osteonecrosis of femoral head with Chinese medicinal herbs.

Objective:To evaluate the anterior expansion of sacral foramen and decompression of sacral plexus via the lateral-rectus approach (LRA) in the surgical treatment of sacral fractures complicated with sacral plexus injury.Methods:From January 2013 to June 2018, 11 patients were treated at Department of Orthopaedics, The Third Hospital Affiliated to Southern Medical University for obsolete sacral fractures complicated with sacral plexus injury. They were 8 males and 3 females, aged from 17 to 54 years (average, 38 years). According to the Denis classification, all the sacral fractures belonged to Denis Zone Ⅱ. According to British Medical Research Council (BMRC) grading system, the nerve injury was complete damage in 2 cases and partial damage in 9. The mean time from injury to surgery was 6 months (range, from 0.7 to 12.0 months). After the sacroiliac joint was exposed via the LRA, the lumbosacral trunk was exposed and released between iliac vessels and the iliopsoas. Next, the S1 foramen was expanded and the S1 nerve root was released after separation of the median sacral artery and the internal iliac artery. Reduction and fixation of the sacroiliac joint was carried out for patients with unstable sacral fracture. X-ray and CT examinations of the pelvis were performed to evaluate fracture healing and neurological function recovery postoperatively.Results:Of this cohort of 11 cases, operation succeeded in 10 but failed in one whose sacral fracture was found to have completely healed with the S1 foramina totally occluded. The surgical time averaged 110 min (range, from 70 to 220 min) and the blood loss 1, 100 mL (range, from 450 to 2, 800 mL). Postoperative X-ray and CT examinations showed that the sacral foramens were expanded significantly without any complications. The follow-up time averaged 18 months (range, from 12 months to 4 years). By the BMRC grading system at the last follow-up, the neural function was completely recovered in 5 cases, partially recovered in 4 cases and not recovered in one.Conclusion:Significant anterior expansion of sacral foramen and decompression of sacral plexus via the LRA is a viable and effective alternative for treatment of sacral fractures complicated with sacral plexus injury.

Objective:Numerous studies have shown that neuroplasticity plays an important role in the pathogenesis of depression. This study aimed to investigate the relationship between the brain derived neurotrophic factor (BDNF) (Val66Met, rs6265) genotype and gray matter volume (GMV) in the first episode and treatment-naive patients with major depressive disorder (MDD) and healthy subjects.Methods:This study included 41 first episode and treatment-naive MDD patients (MDD group) and 44 sex and age matched healthy controls (HC group). All participants were arranged to take magnetic resonance imaging (MRI) scan. Meanwhile, BDNF rs6265 polymorphism was detected. Voxel-based morphometry (VBM) method was then performed to test the impact of the diagnosis (MDD vs. HC) and BDNF genotype (Met allele vs. Val/Val homozygous) on GMV. Results:There was no statistically significant difference on BDNF rs 6265 sites alleles frequency and genotype between MDD and HC groups (MDD χ 2=0.004, P>0.05; HC χ2=0.048, P>0.05). Gray matter volume in the left precuneus ( F=3.702, P<0.001), right middle temporal gyrus ( F=4.020, P<0.001) and cerebellum vermis_4_5 ( F=3.836, P<0.001) was larger in MDD patients than in the control group. BDNF genotype had effects on left fusiform gyrus ( F=-4.152, P<0.001). BDNF genotype-diagnosis interaction was found to be associated with left anterior cingulate cortex ( F=-4.775, P<0.001) and right anterior cingulate ( F=-3.795, P<0.001). For participants with Val/Val homozygous, compared to HC group, the volume of left anterior cingulate was reduced in MDD patients ( F=-3.729, P<0.001). For participants with the Met allele, compared to healthy controls, MDD patients showed significantly increased GMV in the left middle frontal gyrus ( F=4.317, P<0.001), right inferior occipital gyrus ( F=4.744, P<0.001), right supramarginal gyrus ( F=3.838, P<0.001), and left median cingulate gyrus( F=4.041, P<0.001). Separately in MDD patients and the control group, the GMV did not differ between the Val/Val homozygous group and the Met allele group. Conclusion:BDNF rs6265 alleles could be related to brain structural abnormalities in MDD patients, and could further explain the pathological mechanism of MDD.

Objective:Numerous studies have shown that neuroplasticity plays an important role in the pathogenesis of depression. This study aimed to investigate the relationship between the brain derived neurotrophic factor (BDNF) (Val66Met, rs6265) genotype and gray matter volume (GMV) in the first episode and treatment-naive patients with major depressive disorder (MDD) and healthy subjects.Methods:This study included 41 first episode and treatment-naive MDD patients (MDD group) and 44 sex and age matched healthy controls (HC group). All participants were arranged to take magnetic resonance imaging (MRI) scan. Meanwhile, BDNF rs6265 polymorphism was detected. Voxel-based morphometry (VBM) method was then performed to test the impact of the diagnosis (MDD vs. HC) and BDNF genotype (Met allele vs. Val/Val homozygous) on GMV. Results:There was no statistically significant difference on BDNF rs 6265 sites alleles frequency and genotype between MDD and HC groups (MDD χ 2=0.004, P>0.05; HC χ2=0.048, P>0.05). Gray matter volume in the left precuneus ( F=3.702, P<0.001), right middle temporal gyrus ( F=4.020, P<0.001) and cerebellum vermis_4_5 ( F=3.836, P<0.001) was larger in MDD patients than in the control group. BDNF genotype had effects on left fusiform gyrus ( F=-4.152, P<0.001). BDNF genotype-diagnosis interaction was found to be associated with left anterior cingulate cortex ( F=-4.775, P<0.001) and right anterior cingulate ( F=-3.795, P<0.001). For participants with Val/Val homozygous, compared to HC group, the volume of left anterior cingulate was reduced in MDD patients ( F=-3.729, P<0.001). For participants with the Met allele, compared to healthy controls, MDD patients showed significantly increased GMV in the left middle frontal gyrus ( F=4.317, P<0.001), right inferior occipital gyrus ( F=4.744, P<0.001), right supramarginal gyrus ( F=3.838, P<0.001), and left median cingulate gyrus( F=4.041, P<0.001). Separately in MDD patients and the control group, the GMV did not differ between the Val/Val homozygous group and the Met allele group. Conclusion:BDNF rs6265 alleles could be related to brain structural abnormalities in MDD patients, and could further explain the pathological mechanism of MDD.

Objective:To investigate the expression of SHIP1 in the patients with acute myeloid leukemia and its effect on the apoptosis of human leukemia cells.Methods:The expression of SHIP1 in the bone marrow of patients with acute myeloid leukemia was detected by Westem blot.U937 cells was transfected with SHIP1 expression vector (pEGFP-SHIP1 group) and empty vector control (pEGFP group) respectively,U937 cells without transfection were used as the control group.Flow cytometry was used to detect the apoptosis of the cells,the expression of SHIP1,Bcl-2,Bax,Akt,p-Akt were detected by western blot.Results:The expression of SHIP1 in the bone marrow of patients with acute myeloid leukemia was significantly lower than that of the normal human bone marrow SHIP 1 (P＜0.01).The SHIP1 and Bax expressions as well as the apoptotic rate ofpEGFP-SHIP1 group were significantly higher than those of the control group(P＜0.01),while the Bcl-2 and p-Akt expressions were significantly lower than those in the control group(P＜0.01).Conclusions:SH-P1 expression was down regulated in the bone marrow of patients with acute myeloid leukemia.SHIP1 could promote the apoptosis of human leukemia cells via Akt signaling pathway.

Objective: To explore sarcoplasmic reticulum ryanodine receptor2 (RyR 2) expression and calcium releasing function in chronic heart failure (CHF) rabbits and to study the impact of long term valsartan treatment in relevant animals. Methods: HF model was established by volume overloading with pressure overloading in experimental rabbits. 27 rabbits were divided into 3 groups: Sham group, HF group and HF+valsartan group. n=9 in each group and the animals were treated for 7 weeks. Left ventricular structure, hemodynamic parameters, expression and functional changes of myocardiocyte sarcoplasmic reticulum RyR 2 were observed and compared among different groups. Results: Compared with Sham group, HF group had increased left ventricular mess index (LVMI), left ventricular end diastolic pressure (LVEDP) and decreased left ventricular shortening fraction, LVEF, all P<0.05. Compared with HF group, HF+valsartan group showed decreased LVMI, LVEDP and increased left ventricular shortening fraction, LVEF, all P<0.05. Sarcoplasmic reticulum RyR 2 expression and calcium releasing function were lower in HF group than Sham group, P<0.05; while they were both higher in HF+valsartan group than HF group, P<0.05. Conclusion: Long term application of valsartan could improve the cardiac function which might be related to increased myocardial sarcoplasmic reticulum RyR 2 expression and calcium releasing function in experimental CHF rabbits.

Objective: To explore the changes of protein expression and activity of calcium/calmodulin-dependent protein kinase-II (CaMK-II) in myocardium nucleus and sarcoplasmic reticulum in experimental rabbits with heart failure (HF).
Methods: A total of 16 rabbits were divided into 2 groups: Sham group and HF group, the HF model was established by volume overload plus pressure overload.n=8 in each group and all animals were treated for 7 weeks. Left ventricular structure, hemodynamic parameters and protein expression and activity of CaMK-II in myocardium nucleus and sarcoplasmic reticulum were examined and compared between 2 groups.
Results: Compared with Sham group, HF group presented increased left ventricular mass index (LVMI) (1.32 ± 0.06) g/kg vs (3.61 ± 0.09) g/kg, LVEDP (-1.50 ± 0.50) mmHg vs (23.00 ± 2.37) mmHg, allP<0.05; while decreased left ventricular shorten fraction (37.83 ± 3.58) % vs (17.38 ± 3.13) % and LVEF (71.92 ± 4.56) % vs (38.50 ± 6.07) %, allP<0.05. The protein expression and activity of CaMK-II were both higher in HF group than Sham group, allP<0.05.
Conclusion: Increased protein expression and activity of CaMK-II in myocardium nucleus and sarcoplasmic reticulum might be one of the mechanisms for HF occurrence in experimental rabbits.