BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

OBJECTIVE To explore the effect and potential mechanism of the compatibility of Astragali Radix-Puerariae Lobatae Radix on ferroptosis of liver cells in type 2 diabetes mellitus （T2DM） insulin resistance （IR） rats. METHODS Sixty male SD rats were randomly divided into control group （12 rats） and modeling group （48 rats）. The modeling group was fed with a high- fat diet for 4 consecutive weeks and then given a one-time tail vein injection of 1% streptozotocin to establish T2DM IR model. The model rats were randomly divided into model group， the compatibility of Astragali Radix-Puerariae Lobatae Radix group [QG group， 4.05 g/（kg·d）， intragastric administration]， ferroptosis inhibitor ferrostatin-1 group [Fer-1 group， 5 mg/kg by intraperitoneal injection， once every other day]， the compatibility of Astragali Radix-Puerariae Lobatae Radix+ferroptosis inducer erastin group [QG+erastin group， 4.05 g/（kg·d） by intragastric administration+erastin 10 mg/（kg·d）， intraperitoneal injection]. After 4 weeks of intervention， serum fasting blood glucose （FBG） and fasting insulin （FINS） were measured in each group of rats， and homeostasis model assessment of insulin resistance （HOMA-IR） and the natural logarithm of insulin action index（IAI） were calculated； the serum levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate transaminase （AST） and alanine transaminase （ALT）， Fe2+ and Fe content， glutathione （GSH）， malondialdehyde （MDA） and superoxide dismutase （SOD） levels， NADP+/NADPH ratio and reactive oxygen species （ROS） were determined. The pathological morphology of its liver tissue was observed； the protein expressions of glutathione peroxidase 4 （GPX4）， ferritin heavy chain 1 （FTH1）， long-chain acyl-CoA synthetase 3 （ACSL3）， ACSL4， ferritin mitochondrial （FTMT）， and cystine/glutamate anti-porter （xCT） in the liver tissue of rats were detected. RESULTS Compared with control group， the liver cells in the model group of rats showed disordered arrangement， swelling， deepened nuclear staining， and more infiltration of inflammatory cells， as well as a large number of hepatocyte vacuoles and steatosis； FBG （after medication）， the levels of TC， TG， LDL-C， AST， ALT， FINS， MDA and ROS， HOMA-IR， Fe2+ and Fe content， NADP+/NADPH ratio and protein expression of ACSL4 were significantly increased or up-regulated， while the levels of HDL-C， GSH and SOD， IAI， protein expressions of GPX4， FTH1， ACSL3， FTMT and xCT were significantly reduced or down-regulated （P＜0.01）. Compared with the model group， both QG group and Fer-1 group showed varying degrees of improvement in pathological damage of liver tissue and the levels of the above indicators， the differences in the changes of most indicators were statistically significant （P＜0.01 or P＜0.05）. Compared with QG group， the improvement of the above indexes of QG+erastin group had been reversed significantly （P＜0.01）. CONCLUSIONS The compatibility decoction of Astragali Radix-Puerariae Lobatae Radix can reduce the level of FBG in T2DM IR rats， and alleviate IR degree， ion overload and pathological damage of liver tissue. The above effects are related to the inhibition of ferroptosis.

China is a country with a high incidence of esophageal cancer.The pathological type is mainly squamous cell carcinoma.Squamous intraepithelial neoplasia is the most recognized precancerous lesion of esopha-geal squamous cell carcinoma,and its monitoring and intervention is an effective method to reduce the incidence of esophageal squamous cell carcinoma and improve the quality of life of patients.Understanding the etiology,clinical features,diagnosis and treatment of esophageal squamous cell carcinoma plays a crucial role in the prevention and early diagnosis and treatment of esophageal squamous cell carcinoma.At present,the clinical research related to esophageal squamous intraepithelial neoplasia is still insufficient,and there are some differences in clinical treat-ment.This review summarizes the risk factors,clinical features,diagnosis,prognosis and treatment of esophageal squamous intraepithelial neoplasia,hoping to provide ideas for the clinical management of esophageal squamous intraepithelial neoplasia.

BACKGROUND:The angle of screw placement in anterior cervical discectomy and fusion plays a crucial role in determining the stability of the internal fixation system. OBJECTIVE:To predict the impact of different screw placement angles on the stress experienced by the internal fixation system in anterior cervical discectomy and fusion utilizing finite element analysis,with the ultimate goal of identifying the optimal screw placement angle. METHODS:A three-dimensional reconstruction method was employed to establish a mechanical model of the cervical spine,enabling the simulation of three distinct working conditions:scoliosis,uprightness,and forward flexion.In SolidWorks 2017,the anterior cervical plate and screw models were built according to different placement angles of the screws,with a as the inward offset,b as the ideal position,c as the outward offset,d as the downward offset,and e as the upward offset.The stress distribution of internal fixation system at different screw placement angles was observed,and the stress and displacement were recorded. RESULTS AND CONCLUSION:(1)By constructing a finite element model of the entire cervical spine and incorporating an anterior titanium plate,it was found that the biomechanical changes in the spine did not significantly differ based on the various angles of screw insertion on the titanium plate under the same working conditions.(2)However,microscopic analysis revealed that the outward offset(c)screw position exhibited the most effective resistance against side bending,while the downward offset(d)screw demonstrated optimal load-bearing capacity in the upright condition.Additionally,the outward deviation(c)screw displayed superior anti-bending effects in the reverse buckling condition.(3)The fixation effect of the internal fixation device remained relatively stable across different motion conditions.Although there was a 10％variation in the internal fixation effect under the three working conditions when the screw was placed inward,outward,downward,or upward,the displacement changes were minimal.These findings suggest that the requirements of load bearing,bending resistance,and flexion resistance could be simultaneously met without a specific optimal screw location in clinical practice.(4)The placement direction of titanium plate screw in anterior cervical disc-resection and fusion has little effect on the mechanical stability of the cervical spine.The screw angles in different directions have little influence on the stability of the internal fixation device in the lateral,upright,and forward flexion movements of the cervical spine.There is no need to pursue the direction of screw placement in clinical operations.

The development of animal early embryos commences with the reprogramming of terminally differentiated gametes into totipotent zygotes following fertilization. During the initial stages of embryonic development, the transcriptional levels of zygotic genome remain silent and maternal gene products dominate the regulation of development. As embryonic development progresses, the maternal gene products undergo phased degradation while the zygotic genome gradually activates transcription, marking the transition from the maternal regulation to the zygotic genome regulation in early embryonic development, which is also referred to as the maternal-zygotic transition (MZT). Zygotic genome activation (ZGA) is a critical turning process in this transition, and its accurate occurrence is crucial for early embryonic development and cell fate decisions. However, the regulatory factors and molecular mechanisms of ZGA remain poorly understood. Studies have shown that ZGA varies greatly among different species and may be affected by a variety of regulatory factors such as DNA methylation, histone modification, non-coding RNA, chromatin remodeling and ZGA related factors. Here, we review the research progress of the above regulatory factors affecting ZGA, which can provide valuable insights for further investigations into the ZGA related mechanisms of early embryos.

Tranexamic acid is widely used in joint orthopedic surgery.At the same time,it has high safety and few adverse drug reactions.It can effectively improve intraoperative bleeding and promote early functional recovery of patients.This article reviews the mode of administration,safe dose,administration time and adverse drug reactions of tranexamic acid in the perioperative period of joint replacement and arthroscopic surgery,in order to provide reference for the clinical application of tranexamic acid.

Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.

Objective:To evaluate the clinical effect of autologous fat graft in the correction of varying degrees of nasolabial fold drop.Methods:From September 2018 to September 2021, 96 patients mean age of 41 years, with range from 36 to 50 years with nasolabial fold drop admitted in our hospital were treated with autologous fat graft, the improvement of nasolabial fold drop was evaluated by the change of severity (wrinkle severity rating scale, WSRS) to observe the clinical effect and complications of autologous fat graft.Results:Among 96 patients, 75 cases were accepted once treatment, the other 21 cases were accepted twice treatment. The patients were followed up for 12 months, 58 cases (60.4%) of patients had significant improvement, 30 cases (31.3%) of patients had moderate improvement, and 8 cases (8.3%) of patients had slight improvement. There were no complications except mild bruising in early postoperative period in some patients.Conclusions:Autologous fat graft in the correction of varying degrees of nasolabial fold drop is safe and effective, which could be popularized in clinical practice.

Objective To investigate the effect of Lumbricus protein on the phenotypic transformation of corporal cavernosum smooth muscle cells(CCSMC)and erectile function in diabetic erectile dysfunction(DMED)rats.Methods Sixty male SD rats with normal erectile function were randomly divided into a blank group,a model group,a Sildelafil group(5 mg·kg-1),and a Lumbricus protein low-,medium-,and high-dose group(45,90,and 180 mg·kg-1),with 10 rats in each group.The diabetic rat model was established by intraperitoneal injection of Streptozotocin(STZ,50 mg·kg-1)combined with high-fat feed feeding;after 8 weeks,the DMED rat model was prepared by neck injection of Apomorphine(APO,100 μg·kg-1).After successful modeling,the rats were administered with a dose of Apomorphine by gavage once a day for 4 weeks.The blood glucose levels and body mass of rats in each group were measured before modeling,on the third day of modeling,and after 4 weeks of drug administration.The intracavernous pressure(ICP)and carotid artery pressure(MAP)were measured by multi-channel physiological recorder,and the ICP/MAP ratio was calculated.The expressions of contractile markers α-smooth muscle actin(α-SMA),smooth muscle myosin heavy chain(SMMHC)and synthetic markers Collagen I and osteopontin(OPN)in corpus cavernosum were detected by immunohistochemistry.The mRNA expression levels of α-SMA,SMMHC and Collagen I in corpus cavernosum were detected by RT-PCR.The protein expression levels of α-SMA,Desmin,Collagen I and OPN in corpus cavernosum were detected by Western Blot.Results Compared with the blank group,the blood glucose levels of the rats in the model group were significantly increased on the third day of modeling and after 4 weeks of administration(P＜0.01),and the body mass was significantly decreased after 4 weeks of administration(P＜0.01).ICP and ICP/MAP ratio were significantly decreased(P＜0.01).The protein expression levels of α-SMA,SMMHC and Desmin in penile corpus cavernosum were significantly decreased(P＜0.01),and the protein expression levels of Collagen I and OPN were significantly increased(P＜0.01).The mRNA expression levels of α-SMA and SMMHC in corpus cavernosum were significantly decreased(P＜0.01),and the mRNA expression level of Collagen I was significantly increased(P＜0.01).Compared with the model group,there was no significant change in blood glucose and body mass of rats in the administration group(P＞0.05).ICP and ICP/MAP ratio were significantly increased(P＜0.01).The expression levels of α-SMA,SMMHC and Desmin in corpus cavernosum were significantly increased(P＜0.01),while the expression levels of Collagen I and OPN were significantly decreased(P＜0.01).The mRNA expression levels of α-SMA and SMMHC in corpus cavernosum were significantly increased(P＜0.01),and the mRNA expression level of Collagen I was significantly decreased(P＜0.01).Conclusion Lumbricus protein can improve the erectile function of DMED rats,and its mechanism may be related to the inhibition of CCSMC from'contractile'to'synthetic(proliferative)'transformation.

【Objective】 To analyze the clinical characteristics of serum vitamin K2 in children and its correlation with bone mineral density, so as to provide reference for the prevention of insufficient bone strength in children. 【Methods】 A total of 4 145 children who underwent serum vitamin K2 testing and physical examination at pediatric outpatient clinics of several municipal and county hospitals in Chongqing from January 2020 to March 2023 were retrospectively selected into this study for serum vitamin K2-related analysis.Further 844 school-age children who completed serum 25-(OH)D and lumbar bone densitometry measurements were screened to analyze the correlation between vitamin K2level and bone mineral density 【Results】 The overall serum vitamin K2 deficiency rate was 61.6% (2 553/4 145), and the difference in serum vitamin K2 deficiency rate between different age groups was statistically significant (χ²=39.364, P<0.05).The vitamin K2 level of children was significantly influenced by season and maternal education level (χ²=45.310,9.990, P<0.05).There were significant differences in age (Z=3.416), gender (χ²=9.218) and serum vitamin K2 deficiency rate (χ²=5.826) between normal bone mass development group and insufficient bone mass development group (P<0.05).Multivariate Logistic regression analysis suggested that vitamin K2 deficiency was an independent risk factor for insufficient bone mass development in school-age children (OR=1.37,95%CI:1.03 - 1.83, P=0.030). 【Conclusions】 There is a higher serum vitamin K2 deficiency rate among children, especially infants and school-age children.Decreased bone mineral density in school-age children may be associated with serum vitamin K2 deficiency.